Irritable Bowel SyndromePhase 1NCT03154086

A Phase 1, First Time in Human (FTIH) Study to Evaluate GSK3352589, a REarranged During Transfection (RET) Growth Factor Receptor Tyrosine Kinase Inhibitor, in Healthy Volunteers

A Phase 1 study testing GSK3352589 in people with Irritable Bowel Syndrome, run by GlaxoSmithKline at 1 site in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This FTIH study is designed to assess the safety, tolerability and pharmacokinetic (PK) of escalating single and repeat oral doses of GSK3352589 in normal healthy volunteers. This is a randomized, double-blind (sponsor unblinded), placebo controlled, dose escalation study that will have two parts; Part A and Part B. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Irritable Bowel Syndrome
What is being tested?: GSK3352589
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 68 participants
Where: 1 siteAustralia
Study dates: 17 May 2017to 5 Mar 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Between 18 and 55 years of age inclusive, at the time of signing the informed consent.
Healthy as determined by the investigator based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. - History of regular bowel habits
Male or Female of non-childbearing potential.
Capable of giving signed informed consent which includes compliance with the requirements and restrictions.

Who cannot join

ALT and bilirubin >1.5 x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Previous Diagnosis of IBS
Estimated Glomerular Filtration Rate <60 millilter per minute per 1.73 square meter (mL/min/1.73m^2)
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
History of Gastroesophageal reflux disease (GERD), dyspepsia, Gastrointestinal (GI) bleeding, diverticulitis, diverticular stricture or other intestinal strictures, GI surgery that could affect motility
Unwillingness or inability to follow the procedures outlined in the protocol

Trial locations and contacts

1 site in 1 country.

Australia1 site

GSK Investigational Site
Adelaide, South Australia, 5000

Other trials in Australia

About this study

Official title: A Phase I, First Time in Human, Two Part, Randomized, Placebo-Controlled, Double-Blind (Sponsor Unblind), Single and Repeat Dose Escalating Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK3352589, a REarranged During Transfection (RET) Growth Factor Receptor Tyrosine Kinase Inhibitor, in Normal Healthy Volunteers

Conditions: Irritable Bowel Syndrome
Being tested: GSK3352589, Matching Placebo
Keywords: REarranged during Transfection
Medical subject headings: Irritable Bowel Syndrome, Multiple Endocrine Neoplasia Type 2a

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

GSK3352589Drug
It will be available in the dose of 1, 5, 25 and 100 mg tablet for oral administration.
Matching PlaceboDrug
It will be available across all strengths to match active drug in the form of tablet for oral administration.

Study groups in NCT03154086
Study group	Role	What they receive
Part A: Cohort 1: Placebo/GSK3352589 5mg/15mg/50mg	Experimental	Subjects will receive single oral dose of placebo tablet in Period 1 followed by GSK3352589 5 milligrams (mg) tablet in Period 2 followed by GSK3352589 15 mg tablet in Period 3 followed by GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Receives: Drug: GSK3352589; Drug: Matching Placebo
Part A:Cohort 1:GSK3352589 2mg/ Placebo/GSK3352589 15mg/50mg	Experimental	Subjects will receive single oral dose of GSK3352589 2 mg tablet in Period 1 followed by Placebo tablet in Period 2 followed by GSK3352589 15 mg tablet in Period 3 followed by GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Receives: Drug: GSK3352589; Drug: Matching Placebo
Part A:Cohort 1: GSK3352589 2mg/5mg/Placebo/GSK3352589 50mg	Experimental	Subjects will receive single oral dose of GSK3352589 2 mg tablet in Period 1 followed by GSK3352589 5 mg tablet in Period 2 followed by Placebo tablet in Period 3 followed by GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Receives: Drug: GSK3352589; Drug: Matching Placebo
Part A:Cohort 1: GSK3352589 2mg/5mg/15mg/Placebo	Experimental	Subjects will receive single oral dose of GSK3352589 2 mg tablet in Period 1 followed by GSK3352589 5 mg tablet in Period 2 followed by GSK3352589 15 mg tablet in Period 3 followed by Placebo tablet in Period 4 of Cohort 1 in Part A of the study. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Receives: Drug: GSK3352589; Drug: Matching Placebo
Part A:Cohort 2: GSK3352589 25mg Fasted/GSK3352589 25mg Fed	Experimental	Subjects will receive single oral dose of GSK3352589 25 mg tablet in Period 1 (fasted state) and Period 2 (fed state). Subjects will return for their next scheduled dosing Period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Receives: Drug: GSK3352589
Part A: Cohort 2: Placebo Fasted/Placebo Fed	Experimental	Subjects will receive single oral dose of placebo tablet matching GSK3352589 25 mg in Period 1 (fasted state) and Period 2 (fed state). Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Receives: Drug: Matching Placebo
Part A:Cohort 3: GSK3352589 150 mg/Placebo	Experimental	Subjects will receive single oral dose of GSK3352589 150 mg tablet in Period 1 followed by placebo tablet matching GSK3352589 150 mg in Period 2 in Cohort 3 of Part A. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Receives: Drug: GSK3352589; Drug: Matching Placebo
Part A:Cohort 3: Placebo/GSK3352589 400 mg	Experimental	Subjects will receive single oral dose of placebo tablet matching GSK3352589 400 mg in Period 1 followed by single oral dose of GSK3352589 400 mg tablet in Period 2 in Cohort 3 of Part A. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Receives: Drug: GSK3352589; Drug: Matching Placebo
Part A:Cohort 3: GSK3352589 150mg/GSK3352589 400mg	Experimental	Subjects will receive single oral dose of GSK3352589 150 mg tablet in Period 1 followed by GSK3352589 400 mg tablet in Period 2 in Cohort 3 of Part A. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period. Receives: Drug: GSK3352589
Part B: GSK3352589	Experimental	Subjects will receive repeat oral doses of GSK3352589 of 5 mg, 15 mg, 50 mg, 100 mg or 200 mg twice daily administered for 14 days. Receives: Drug: GSK3352589
Part B: Placebo	Placebo comparator	Subjects will receive repeat oral doses of placebo twice a day tablet administered for 14 days. Receives: Drug: Matching Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment.
Measured: Up to 64 days in Cohort 1
Part A: Number of Participants With SAEs and Non-SAEs in Cohort 2
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment.
Measured: Up to 30 days in Cohort 2
Part A: Number of Participants With SAEs and Non-SAEs in Cohort 3
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment.
Measured: Up to 30 days in Cohort 3
Part B: Number of Participants With SAEs and Non-SAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment.
Measured: Up to 25 days
Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 1
A complete physical examination will include, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented.
Measured: Up to 64 days in Cohort 1
Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 2
A complete physical examination included, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented.
Measured: Up to 30 days in Cohort 2
Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 3
A complete physical examination included, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented.
Measured: Up to 30 days in Cohort 3
Part B: Number of Participants With Abnormal Findings After Physical Examination
A complete physical examination included, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented.
Measured: Up to 25 days
Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3
Triplicate 12-lead ECGs were obtained at indicated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT corrected (QTc) intervals. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Baseline is defined as the last available, non-missing mean value of triplicate assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). The number of participants with abnormal clinically significant (CS) and not clinically significant (NCS) findings for ECG parameters have been presented.
Measured: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2
Part A: Number of Participants With Abnormal ECG Findings in Cohort 2
Triplicate 12-lead ECGs were obtained at indicated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Baseline is defined as the last available, non-missing mean value of triplicate assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). The number of participants with abnormal CS and NCS findings for ECG parameters have been presented.
Measured: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2
Part B: Number of Participants With Abnormal ECG Findings
Triplicate 12-lead ECGs were obtained at indicated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Baseline is defined as the last available, non-missing mean value of triplicate assessment prior to the first administration of study drug. The number of participants with abnormal CS and NCS findings for ECG parameters have been presented.
Measured: Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 7 (Pre-dose, 4 Hours Post-dose), Day 14 (Pre-dose, 4 Hours Post-dose), Follow-up (Day 25)
Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3
Blood pressure of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
Part A: Change From Baseline in SBP and DBP in Cohort 2
Blood pressure of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
Part B: Change From Baseline in SBP and DBP
Blood pressure of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 (Pre-dose, 4 Hours Post-dose), Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14 (Pre-dose, 4 Hours Post-dose), Day 15, Follow-up (Day 25)
Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3
Pulse rate of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
Part A: Change From Baseline in Pulse Rate in Cohort 2
Pulse rate of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
Part B: Change From Baseline in Pulse Rate
Pulse rate of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 (Pre-dose, 4 Hours Post-dose), Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14 (Pre-dose, 4 Hours Post-dose), Day 15, Follow-up (Day 25)
Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3
Body temperature of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
Part A: Change From Baseline in Body Temperature in Cohort 2
Body temperature of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
Part B: Change From Baseline in Body Temperature
Body temperature of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 (Pre-dose, 4 Hours Post-dose), Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14 (Pre-dose, 4 Hours Post-dose), Day 15, Follow-up (Day 25)
Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1
The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid).
Measured: Up to 64 days in Cohort 1
Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2
The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid).
Measured: Up to 30 days in Cohort 2
Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3
The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid).
Measured: Up to 30 days in Cohort 3
Part B: Average BSFS at Indicated Time Points
The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid).
Measured: Day -1, Days 1-3, Days 4-7, Days 1-7, Days 8-14
Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3
Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1) and Day 3
Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2
Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1) and Day 3
Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes
Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Part A: Change From Baseline in Erythrocytes in Cohort 1 and 3
Blood samples were collected for analysis of hematology parameters including Erythrocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1) and Day 3
Part A: Change From Baseline in Erythrocytes in Cohort 2
Blood samples were collected for analysis of hematology parameters including Erythrocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1) and Day 3
Part B: Change From Baseline in Erythrocytes
Blood samples were collected for analysis of hematology parameters including Erythrocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Part A: Change From Baseline in Hemoglobin in Cohort 1 and 3
Blood samples were collected for analysis of hematology parameters including hemoglobin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1) and Day 3
Part A: Change From Baseline in Hemoglobin in Cohort 2
Blood samples were collected for analysis of hematology parameters including hemoglobin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1) and Day 3
Part B: Change From Baseline in Hemoglobin
Blood samples were collected for analysis of hematology parameters including hemoglobin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Part A: Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) in Cohort 1 and Cohort 3
Blood samples were collected for analysis of hematology parameters including Erythrocyte MCV. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1) and Day 3
Part A: Change From Baseline in Erythrocyte MCV in Cohort 2
Blood samples were collected for analysis of hematology parameters including Erythrocyte MCV. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1) and Day 3
Part B: Change From Baseline in Erythrocyte MCV
Blood samples were collected for analysis of hematology parameters including Erythrocyte MCV. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Part A: Change From Baseline in Erythorocyte Mean Corpuscular Hemoglobin (MCH) in Cohort 1 and 3
Blood samples were collected for analysis of hematology parameters including Erythorocyte MCH. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1) and Day 3
Part A: Change From Baseline in Erythrocyte MCH in Cohort 2
Blood samples were collected for analysis of hematology parameters including Erythorocyte MCH. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1) and Day 3
Part B: Change From Baseline in Erythrocyte MCH
Blood samples were collected for analysis of hematology parameters including Erythorocyte MCH. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Part A: Change From Baseline in Hematocrit in Cohort 1 and 3
Blood samples were collected for analysis of hematology parameters including Hematocrit. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1) and Day 3
Part A: Change From Baseline in Hematocrit in Cohort 2
Blood samples were collected for analysis of hematology parameters including Hematocrit. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1) and Day 3
Part B: Change From Baseline in Hematocrit
Blood samples were collected for analysis of hematology parameters including Hematocrit. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3
Blood samples were collected for analysis of clinical chemistry parameters including ALT, AST and Alk Phos. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1) and Day 3
Part A: Change From Baseline in ALT, AST and Alk Phos in Cohort 2
Blood samples were collected for analysis of clinical chemistry parameters including ALT, AST and Alk Phos. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1) and Day 3
Part B: Change From Baseline in ALT, AST and Alk Phos
Blood samples were collected for analysis of hematology parameters including ALT, AST and Alk Phos. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3
Blood samples were collected for analysis of clinical chemistry parameters including bilirubin, creatinine, direct bilirubin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1) and Day 3
Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 2
Blood samples were collected for analysis of clinical chemistry parameters including bilirubin, creatinine, and direct bilirubin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1) and Day 3
Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin
Blood samples were collected for analysis of hematology parameters including bilirubin, creatinine, and direct bilirubin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3
Blood samples were collected for analysis of clinical chemistry parameters including Calcium, Glucose, Potassium, Sodium, Urea. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1) and Day 3
Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2
Blood samples were collected for analysis of clinical chemistry parameters including Calcium, Glucose, Potassium, Sodium, Urea. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1) and Day 3
Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea
Blood samples were collected for analysis of hematology parameters including Calcium, Glucose, Potassium, Sodium, Urea. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3
Blood samples were collected for analysis of clinical chemistry parameters including albumin, and total protein. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1) and Day 3
Part A: Change From Baseline in Albumin and Total Protein in Cohort 2
Blood samples were collected for analysis of clinical chemistry parameters including albumin and total protein. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1) and Day 3
Part B: Change From Baseline in Albumin, Total Protein
Blood samples were collected for analysis of hematology parameters including albumin and total protein. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3
Urine samples were collected from participants for analysis of specific gravity of urine. Urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, potential of hydrogen (pH), protein, specific gravity and Urobilinogen were analyzed by dipstick method. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period
1 (or the first available Dosing Period if Dosing Period 1 is unavailable).
Measured: Baseline (Day-1) and Day 3
Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2
Urine samples were collected from participants for analysis of specific gravity of urine. Urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, potential of hydrogen (pH), protein, specific gravity and Urobilinogen were analyzed by dipstick method. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period
1 (or the first available Dosing Period if Dosing Period 1 is unavailable).
Measured: Baseline (Day -1) and Day 3
Part B: Number of Participants With Abnormal Findings for Urine Parameters
Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Non-zero Concentration (AUC [0-t]) Following Single Dose Administration of GSK3352589
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-t) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods. The PK Parameter population comprised of all randomized participants who received at least one dose of active treatment and who had GSK3352589 Pharmacokinetic parameter estimates from any portion of the study.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK3352589
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-infinity) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Part A: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of GSK3352589
Blood samples were collected from participants for pharmacokinetic analysis including Cmax following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Part A: Time to Reach Cmax (Tmax) Following Single Dose Administration of GSK3352589
Blood samples were collected from participants for pharmacokinetic analysis including Tmax following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Part A: Terminal Elimination Half-life (t1/2) Following Single Dose Administration of GSK3352589
Blood samples were collected from participants for pharmacokinetic analysis including t1/2 following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Part A: Cmax Following Single Dose Administration of GSK3352589-Food Effect
Blood samples were collected from participants for pharmacokinetic analysis following administration of GSK3352589 in fasted and fed condition to assess the effect of food on pharmacokinetics of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Part A: AUC (0-t) Following Single Dose Administration of GSK3352589- Food Effect
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-t) following administration of GSK3352589 in fasted and fed condition to assess the effect of food on pharmacokinetics of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Part A: AUC (0-infinity) Following Single Dose Administration of GSK3352589- Food Effect
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-infinity) following administration of GSK3352589 in fasted and fed condition to assess the effect of food on pharmacokinetics of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Part B: AUC (0-t) Following Repeat Dose Administration of GSK3352589
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-t) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14
Part B: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours Post-dose (AUC [0-24]) Following Repeat Dose Administration of GSK3352589
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-24) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14
Part B: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK3352589
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-tau) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14
Part B: Cmax Following Repeat Dose Administration of GSK3352589
Blood samples were collected from participants for pharmacokinetic analysis including Cmax following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14
Part B: Tmax Following Repeat Dose Administration of GSK3352589
Blood samples were collected from participants for pharmacokinetic analysis including Tmax following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods.
Measured: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

17 May 20175 Mar 2018

First posted15 May 2017
Study start17 May 2017
Primary completion5 Mar 2018
Study completion5 Mar 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Irritable Bowel SyndromeStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 68 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03154086
Sponsor's protocol ID: 207440
Status last verified: Jun 2019
First submitted: 12 May 2017
Last updated: 9 Aug 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Reedy BA, O'Connor-Semmes R, Hacquoil K, Gorycki P, Verticelli A, Molga A. First-in-Human Study for a Selective Rearranged During Transfection Tyrosine Kinase Inhibitor, GSK3352589, to Investigate the Safety, Tolerability, and Pharmacokinetics in Healthy Volunteers. Clin Pharmacol Drug Dev. 2021 Apr;10(4):334-345. doi: 10.1002/cpdd.911. Epub 2021 Feb 19.
PubMed 33606922

Want to know more?

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Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 9 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I, First Time in Human, Two Part, Randomized, Placebo-Controlled, Double-Blind (Sponsor Unblind), Single and Repeat Dose Escalating Study to Evaluate the Safety, Tolerability and Pharmacokinetics of GSK3352589, a REarranged During Transfection (RET) Growth Factor Receptor Tyrosine Kinase Inhibitor, in Normal Healthy Volunteers
ClinicalTrials.gov ID: NCT03154086
Acronym / sponsor ID: 207440
Conditions: Irritable Bowel Syndrome
Keywords: REarranged during Transfection
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 68 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 17 May 2017 (actual)
Primary completion: 5 Mar 2018 (actual)
Study completion: 5 Mar 2018 (actual)
First posted: 15 May 2017 (actual)
Results: Posted 9 Aug 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 11

Arm	Type	Receives
Part A: Cohort 1: Placebo/GSK3352589 5mg/15mg/50mg	Experimental	Drug: GSK3352589, Drug: Matching PlaceboSubjects will receive single oral dose of placebo tablet in Period 1 followed by GSK3352589 5 milligrams (mg) tablet in Period 2 followed by GSK3352589 15 mg tablet in Period 3 followed by GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.
Part A:Cohort 1:GSK3352589 2mg/ Placebo/GSK3352589 15mg/50mg	Experimental	Drug: GSK3352589, Drug: Matching PlaceboSubjects will receive single oral dose of GSK3352589 2 mg tablet in Period 1 followed by Placebo tablet in Period 2 followed by GSK3352589 15 mg tablet in Period 3 followed by GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.
Part A:Cohort 1: GSK3352589 2mg/5mg/Placebo/GSK3352589 50mg	Experimental	Drug: GSK3352589, Drug: Matching PlaceboSubjects will receive single oral dose of GSK3352589 2 mg tablet in Period 1 followed by GSK3352589 5 mg tablet in Period 2 followed by Placebo tablet in Period 3 followed by GSK3352589 50 mg tablet in Period 4 of Cohort 1 in Part A of the study. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.
Part A:Cohort 1: GSK3352589 2mg/5mg/15mg/Placebo	Experimental	Drug: GSK3352589, Drug: Matching PlaceboSubjects will receive single oral dose of GSK3352589 2 mg tablet in Period 1 followed by GSK3352589 5 mg tablet in Period 2 followed by GSK3352589 15 mg tablet in Period 3 followed by Placebo tablet in Period 4 of Cohort 1 in Part A of the study. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.
Part A:Cohort 2: GSK3352589 25mg Fasted/GSK3352589 25mg Fed	Experimental	Drug: GSK3352589Subjects will receive single oral dose of GSK3352589 25 mg tablet in Period 1 (fasted state) and Period 2 (fed state). Subjects will return for their next scheduled dosing Period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.
Part A: Cohort 2: Placebo Fasted/Placebo Fed	Experimental	Drug: Matching PlaceboSubjects will receive single oral dose of placebo tablet matching GSK3352589 25 mg in Period 1 (fasted state) and Period 2 (fed state). Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.
Part A:Cohort 3: GSK3352589 150 mg/Placebo	Experimental	Drug: GSK3352589, Drug: Matching PlaceboSubjects will receive single oral dose of GSK3352589 150 mg tablet in Period 1 followed by placebo tablet matching GSK3352589 150 mg in Period 2 in Cohort 3 of Part A. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.
Part A:Cohort 3: Placebo/GSK3352589 400 mg	Experimental	Drug: GSK3352589, Drug: Matching PlaceboSubjects will receive single oral dose of placebo tablet matching GSK3352589 400 mg in Period 1 followed by single oral dose of GSK3352589 400 mg tablet in Period 2 in Cohort 3 of Part A. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.
Part A:Cohort 3: GSK3352589 150mg/GSK3352589 400mg	Experimental	Drug: GSK3352589Subjects will receive single oral dose of GSK3352589 150 mg tablet in Period 1 followed by GSK3352589 400 mg tablet in Period 2 in Cohort 3 of Part A. Subjects will return for their next scheduled dosing period approximately 14 days (wash out period) after administration of the study drug during the prior dosing period.
Part B: GSK3352589	Experimental	Drug: GSK3352589Subjects will receive repeat oral doses of GSK3352589 of 5 mg, 15 mg, 50 mg, 100 mg or 200 mg twice daily administered for 14 days.
Part B: Placebo	Placebo comparator	Drug: Matching PlaceboSubjects will receive repeat oral doses of placebo twice a day tablet administered for 14 days.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (4 listed)

Between 18 and 55 years of age inclusive, at the time of signing the informed consent.
Healthy as determined by the investigator based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. - History of regular bowel habits
Male or Female of non-childbearing potential.
Capable of giving signed informed consent which includes compliance with the requirements and restrictions.

Key exclusion criteria (6 listed)

ALT and bilirubin >1.5 x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Previous Diagnosis of IBS
Estimated Glomerular Filtration Rate <60 millilter per minute per 1.73 square meter (mL/min/1.73m^2)
Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
History of Gastroesophageal reflux disease (GERD), dyspepsia, Gastrointestinal (GI) bleeding, diverticulitis, diverticular stricture or other intestinal strictures, GI surgery that could affect motility

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GSK3352589It will be available in the dose of 1, 5, 25 and 100 mg tablet for oral administration.	Drug	Part A: Cohort 1: Placebo/GSK3352589 5mg/15mg/50mg, Part A:Cohort 1: GSK3352589 2mg/5mg/15mg/Placebo, Part A:Cohort 1: GSK3352589 2mg/5mg/Placebo/GSK3352589 50mg, Part A:Cohort 1:GSK3352589 2mg/ Placebo/GSK3352589 15mg/50mg, Part A:Cohort 2: GSK3352589 25mg Fasted/GSK3352589 25mg Fed, Part A:Cohort 3: GSK3352589 150 mg/Placebo, Part A:Cohort 3: GSK3352589 150mg/GSK3352589 400mg, Part A:Cohort 3: Placebo/GSK3352589 400 mg, Part B: GSK3352589
Matching PlaceboIt will be available across all strengths to match active drug in the form of tablet for oral administration.	Drug	Part A: Cohort 1: Placebo/GSK3352589 5mg/15mg/50mg, Part A: Cohort 2: Placebo Fasted/Placebo Fed, Part A:Cohort 1: GSK3352589 2mg/5mg/15mg/Placebo, Part A:Cohort 1: GSK3352589 2mg/5mg/Placebo/GSK3352589 50mg, Part A:Cohort 1:GSK3352589 2mg/ Placebo/GSK3352589 15mg/50mg, Part A:Cohort 3: GSK3352589 150 mg/Placebo, Part A:Cohort 3: Placebo/GSK3352589 400 mg, Part B: Placebo

Primary outcome

Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1
Time frame: Up to 64 days in Cohort 1
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment.
Part A: Number of Participants With SAEs and Non-SAEs in Cohort 2
Time frame: Up to 30 days in Cohort 2
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment.
Part A: Number of Participants With SAEs and Non-SAEs in Cohort 3
Time frame: Up to 30 days in Cohort 3
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment.
Part B: Number of Participants With SAEs and Non-SAEs
Time frame: Up to 25 days
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations as per medical or scientific judgment.
Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 1
Time frame: Up to 64 days in Cohort 1
A complete physical examination will include, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented.
Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 2
Time frame: Up to 30 days in Cohort 2
A complete physical examination included, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented.
Part A: Number of Participants With Abnormal Findings After Physical Examination in Cohort 3
Time frame: Up to 30 days in Cohort 3
A complete physical examination included, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented.
Part B: Number of Participants With Abnormal Findings After Physical Examination
Time frame: Up to 25 days
A complete physical examination included, at a minimum, assessments of the skin, cardiovascular, respiratory, gastrointestinal and neurological systems. Brief symptom directed physical examination included, at a minimum, assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). Number of participants with clinically significant abnormal physical examination findings have been presented.
Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings in Cohort 1 and Cohort 3
Time frame: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2
Triplicate 12-lead ECGs were obtained at indicated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT corrected (QTc) intervals. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Baseline is defined as the last available, non-missing mean value of triplicate assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). The number of participants with abnormal clinically significant (CS) and not clinically significant (NCS) findings for ECG parameters have been presented.
Part A: Number of Participants With Abnormal ECG Findings in Cohort 2
Time frame: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2
Triplicate 12-lead ECGs were obtained at indicated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Baseline is defined as the last available, non-missing mean value of triplicate assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). The number of participants with abnormal CS and NCS findings for ECG parameters have been presented.
Part B: Number of Participants With Abnormal ECG Findings
Time frame: Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 7 (Pre-dose, 4 Hours Post-dose), Day 14 (Pre-dose, 4 Hours Post-dose), Follow-up (Day 25)
Triplicate 12-lead ECGs were obtained at indicated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Baseline is defined as the last available, non-missing mean value of triplicate assessment prior to the first administration of study drug. The number of participants with abnormal CS and NCS findings for ECG parameters have been presented.
Part A: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) in Cohort 1 and Cohort 3
Time frame: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
Blood pressure of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in SBP and DBP in Cohort 2
Time frame: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
Blood pressure of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part B: Change From Baseline in SBP and DBP
Time frame: Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 (Pre-dose, 4 Hours Post-dose), Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14 (Pre-dose, 4 Hours Post-dose), Day 15, Follow-up (Day 25)
Blood pressure of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Pulse Rate in Cohort 1 and Cohort 3
Time frame: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
Pulse rate of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Pulse Rate in Cohort 2
Time frame: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
Pulse rate of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part B: Change From Baseline in Pulse Rate
Time frame: Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 (Pre-dose, 4 Hours Post-dose), Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14 (Pre-dose, 4 Hours Post-dose), Day 15, Follow-up (Day 25)
Pulse rate of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Body Temperature in Cohort 1 and Cohort 3
Time frame: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
Body temperature of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Body Temperature in Cohort 2
Time frame: Baseline (Pre-dose on Day 1), Day 1 (1, 4, 12 Hours Post-dose), Day 2 and Day 3
Body temperature of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part B: Change From Baseline in Body Temperature
Time frame: Baseline (Pre-dose on Day 1), Day 1 (4 Hours Post-dose), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 (Pre-dose, 4 Hours Post-dose), Day 8, Day 9, Day 10, Day 11, Day 12, Day 13, Day 14 (Pre-dose, 4 Hours Post-dose), Day 15, Follow-up (Day 25)
Body temperature of participants was measured at indicated time points in a supine position after 5 minutes rest. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Number of Participants With Different Stool Types Assessed Using Bristol Stool Form Scale (BSFS) in Cohort 1
Time frame: Up to 64 days in Cohort 1
The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid).
Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 2
Time frame: Up to 30 days in Cohort 2
The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid).
Part A: Number of Participants With Different Stool Types Assessed Using BSFS in Cohort 3
Time frame: Up to 30 days in Cohort 3
The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid).
Part B: Average BSFS at Indicated Time Points
Time frame: Day -1, Days 1-3, Days 4-7, Days 1-7, Days 8-14
The BSFS describes 7 types of stool as following; Type 1-Separate hard lumps (hard to pass), Type 2-Sausage-shaped but lumpy, Type 3-Like a sausage but cracks on surface, Type 4-Like a sausage or snake, smooth and soft, Type 5- Soft blobs with clear cut edges, Type-6 Fluffy pieces with ragged edges, a mushy stool, and Type 7-Watery, no solid pieces (entirely liquid). BSFS was used by the participants during the study to capture the quality of stool using a 7-point scale ranging from Type 1=separate hard lumps like nuts (difficult to pass) to 7= watery, no solid pieces (entirely liquid).
Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 1 and Cohort 3
Time frame: Baseline (Day -1) and Day 3
Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes in Cohort 2
Time frame: Baseline (Day -1) and Day 3
Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part B: Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, and Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Erythrocytes in Cohort 1 and 3
Time frame: Baseline (Day -1) and Day 3
Blood samples were collected for analysis of hematology parameters including Erythrocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Erythrocytes in Cohort 2
Time frame: Baseline (Day -1) and Day 3
Blood samples were collected for analysis of hematology parameters including Erythrocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part B: Change From Baseline in Erythrocytes
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Blood samples were collected for analysis of hematology parameters including Erythrocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Hemoglobin in Cohort 1 and 3
Time frame: Baseline (Day -1) and Day 3
Blood samples were collected for analysis of hematology parameters including hemoglobin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Hemoglobin in Cohort 2
Time frame: Baseline (Day -1) and Day 3
Blood samples were collected for analysis of hematology parameters including hemoglobin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part B: Change From Baseline in Hemoglobin
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Blood samples were collected for analysis of hematology parameters including hemoglobin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Erythrocyte Mean Corpuscular Volume (MCV) in Cohort 1 and Cohort 3
Time frame: Baseline (Day -1) and Day 3
Blood samples were collected for analysis of hematology parameters including Erythrocyte MCV. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Erythrocyte MCV in Cohort 2
Time frame: Baseline (Day -1) and Day 3
Blood samples were collected for analysis of hematology parameters including Erythrocyte MCV. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part B: Change From Baseline in Erythrocyte MCV
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Blood samples were collected for analysis of hematology parameters including Erythrocyte MCV. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Erythorocyte Mean Corpuscular Hemoglobin (MCH) in Cohort 1 and 3
Time frame: Baseline (Day -1) and Day 3
Blood samples were collected for analysis of hematology parameters including Erythorocyte MCH. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Erythrocyte MCH in Cohort 2
Time frame: Baseline (Day -1) and Day 3
Blood samples were collected for analysis of hematology parameters including Erythorocyte MCH. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part B: Change From Baseline in Erythrocyte MCH
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Blood samples were collected for analysis of hematology parameters including Erythorocyte MCH. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Hematocrit in Cohort 1 and 3
Time frame: Baseline (Day -1) and Day 3
Blood samples were collected for analysis of hematology parameters including Hematocrit. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Hematocrit in Cohort 2
Time frame: Baseline (Day -1) and Day 3
Blood samples were collected for analysis of hematology parameters including Hematocrit. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part B: Change From Baseline in Hematocrit
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Blood samples were collected for analysis of hematology parameters including Hematocrit. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Alanine Aminotransferase (ALT),Aspartate Aminotransferase (AST), Alkaline Phosphatase (Alk Phos) in Cohort 1 and 3
Time frame: Baseline (Day -1) and Day 3
Blood samples were collected for analysis of clinical chemistry parameters including ALT, AST and Alk Phos. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in ALT, AST and Alk Phos in Cohort 2
Time frame: Baseline (Day -1) and Day 3
Blood samples were collected for analysis of clinical chemistry parameters including ALT, AST and Alk Phos. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part B: Change From Baseline in ALT, AST and Alk Phos
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Blood samples were collected for analysis of hematology parameters including ALT, AST and Alk Phos. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 1 and 3
Time frame: Baseline (Day -1) and Day 3
Blood samples were collected for analysis of clinical chemistry parameters including bilirubin, creatinine, direct bilirubin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin in Cohort 2
Time frame: Baseline (Day -1) and Day 3
Blood samples were collected for analysis of clinical chemistry parameters including bilirubin, creatinine, and direct bilirubin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part B: Change From Baseline in Bilirubin, Creatinine, Direct Bilirubin
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Blood samples were collected for analysis of hematology parameters including bilirubin, creatinine, and direct bilirubin. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 1 and 3
Time frame: Baseline (Day -1) and Day 3
Blood samples were collected for analysis of clinical chemistry parameters including Calcium, Glucose, Potassium, Sodium, Urea. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea in Cohort 2
Time frame: Baseline (Day -1) and Day 3
Blood samples were collected for analysis of clinical chemistry parameters including Calcium, Glucose, Potassium, Sodium, Urea. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part B: Change From Baseline in Calcium, Glucose, Potassium, Sodium, Urea
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Blood samples were collected for analysis of hematology parameters including Calcium, Glucose, Potassium, Sodium, Urea. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Albumin and Total Protein in Cohort 1 and 3
Time frame: Baseline (Day -1) and Day 3
Blood samples were collected for analysis of clinical chemistry parameters including albumin, and total protein. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Change From Baseline in Albumin and Total Protein in Cohort 2
Time frame: Baseline (Day -1) and Day 3
Blood samples were collected for analysis of clinical chemistry parameters including albumin and total protein. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable). Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part B: Change From Baseline in Albumin, Total Protein
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Blood samples were collected for analysis of hematology parameters including albumin and total protein. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 1 and Cohort 3
Time frame: Baseline (Day-1) and Day 3
Urine samples were collected from participants for analysis of specific gravity of urine. Urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, potential of hydrogen (pH), protein, specific gravity and Urobilinogen were analyzed by dipstick method. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable).
Part A: Number of Participants With Abnormal Findings for Urine Parameters in Cohort 2
Time frame: Baseline (Day -1) and Day 3
Urine samples were collected from participants for analysis of specific gravity of urine. Urine parameters including bilirubin, glucose, ketones, leukocyte esterase, nitrite, occult blood, potential of hydrogen (pH), protein, specific gravity and Urobilinogen were analyzed by dipstick method. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug in Dosing Period 1 (or the first available Dosing Period if Dosing Period 1 is unavailable).
Part B: Number of Participants With Abnormal Findings for Urine Parameters
Time frame: Baseline (Day -2), Day 7, Day 15 and Follow-up (Day 25)
Blood samples were collected for analysis of hematology parameters including Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelets, Leukocytes. Baseline is defined as the last available, non-missing assessment prior to the first administration of study drug. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Non-zero Concentration (AUC [0-t]) Following Single Dose Administration of GSK3352589
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-t) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods. The PK Parameter population comprised of all randomized participants who received at least one dose of active treatment and who had GSK3352589 Pharmacokinetic parameter estimates from any portion of the study.
Part A: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK3352589
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-infinity) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Part A: Maximum Observed Plasma Concentration (Cmax) Following Single Dose Administration of GSK3352589
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Blood samples were collected from participants for pharmacokinetic analysis including Cmax following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Part A: Time to Reach Cmax (Tmax) Following Single Dose Administration of GSK3352589
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Blood samples were collected from participants for pharmacokinetic analysis including Tmax following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Part A: Terminal Elimination Half-life (t1/2) Following Single Dose Administration of GSK3352589
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Blood samples were collected from participants for pharmacokinetic analysis including t1/2 following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Part A: Cmax Following Single Dose Administration of GSK3352589-Food Effect
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Blood samples were collected from participants for pharmacokinetic analysis following administration of GSK3352589 in fasted and fed condition to assess the effect of food on pharmacokinetics of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Part A: AUC (0-t) Following Single Dose Administration of GSK3352589- Food Effect
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-t) following administration of GSK3352589 in fasted and fed condition to assess the effect of food on pharmacokinetics of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Part A: AUC (0-infinity) Following Single Dose Administration of GSK3352589- Food Effect
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 12, 16, 24, 36, 48 Hours Post-dose
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-infinity) following administration of GSK3352589 in fasted and fed condition to assess the effect of food on pharmacokinetics of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part A was conducted by non-compartmental methods.
Part B: AUC (0-t) Following Repeat Dose Administration of GSK3352589
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-t) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods.
Part B: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours Post-dose (AUC [0-24]) Following Repeat Dose Administration of GSK3352589
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-24) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods.
Part B: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK3352589
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14
Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-tau) following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods.
Part B: Cmax Following Repeat Dose Administration of GSK3352589
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14
Blood samples were collected from participants for pharmacokinetic analysis including Cmax following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods.
Part B: Tmax Following Repeat Dose Administration of GSK3352589
Time frame: Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 1; Pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 8, 10, 11, 12, 14, 16, 24 Hours Post-dose on Day 14
Blood samples were collected from participants for pharmacokinetic analysis including Tmax following administration of GSK3352589. Pharmacokinetic analysis of GSK3352589 in Part B was conducted by non-compartmental methods.

Results and safety

Results posted to the registry on 9 Aug 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part A: Cohort 1: Placebo/GSK3352589 5mg/15mg/50mg	2	2
Part A:Cohort 1:GSK3352589 2mg/Placebo/GSK3352589 15mg/50mg	2	2
Part A:Cohort 1: GSK3352589 2mg/ 5mg/Placebo/ GSK3352589 50mg	2	2
Part A:Cohort 1:GSK3352589 2mg/5mg/15mg/Placebo	2	2
Part A:Cohort 2:GSK3352589 25 mg Fasted/GSK3352589 25 mg Fed	0	0
Part A: Cohort 2: Placebo Fasted/Placebo Fed	0	0
Part A:Cohort 3: GSK3352589 150 mg/Placebo	0	0
Part A:Cohort 3: Placebo /GSK3352589 400 mg	0	0
Part A:Cohort 3: GSK3352589 150 mg/GSK3352589 400 mg	0	0
Part B: Placebo BID	0	0
Part B: GSK3352589 5 mg BID	0	0
Part B: GSK3352589 15 mg BID	0	0
Part B: GSK3352589 50 mg BID	0	0
Part B: GSK3352589 100 mg BID	0	0
Part B: GSK3352589 200 mg BID	0	0

Primary outcome: Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1

Time frame: Up to 64 days in Cohort 1. Count of participants. Unit: Participants

Measure	Part A: Cohort 1: Placebo n = 8	Part A: Cohort 1: GSK3352589 2 mg n = 6	Part A: Cohort 1: GSK3352589 5 mg n = 6	Part A: Cohort 1: GSK3352589 15 mg n = 6	Part A: Cohort 1: GSK3352589 50 mg n = 5
Any SAE	0	1	0	0	0
Any non-SAE	3	5	3	2	2

Population analysed: Safety Population comprised of all randomized participants who received at least one dose of study medication and was based on the actual treatment received, if this differed from that to which the participant was randomized.

Primary outcome: Part A: Number of Participants With SAEs and Non-SAEs in Cohort 2

Time frame: Up to 30 days in Cohort 2. Count of participants. Unit: Participants

Measure	Part A: Cohort 2: Fasted Placebo n = 2	Part A: Cohort 2: Fed Placebo n = 2	Part A: Cohort 2: GSK3352589 Fasted 25 mg n = 6	Part A: Cohort 2: GSK3352589 Fed 25 mg n = 6
Any SAE	0	0	0	0
Any non-SAE	1	0	3	1

Population analysed: Safety population

Primary outcome: Part A: Number of Participants With SAEs and Non-SAEs in Cohort 3

Time frame: Up to 30 days in Cohort 3. Count of participants. Unit: Participants

Measure	Part A: Cohort 3: Placebo n = 4	Part A: Cohort 3: GSK3352589 150 mg n = 6	Part A: Cohort 3: GSK3352589 400 mg n = 5
Any SAE	0	0	0
Any non-SAE	2	3	1

Population analysed: Safety population

Primary outcome: Part B: Number of Participants With SAEs and Non-SAEs

Time frame: Up to 25 days. Count of participants. Unit: Participants

Measure	Part B: Placebo BID n = 10	Part B: GSK3352589 5 mg BID n = 6	Part B: GSK3352589 15 mg BID n = 6	Part B: GSK3352589 50 mg BID n = 6	Part B: GSK3352589 100 mg BID n = 6	Part B: GSK3352589 200 mg BID n = 6
Any SAE	0	0	0	0	0	0
Any non-SAE	9	5	6	2	5	5

Population analysed: Safety population

Adverse events

Time frame: Serious adverse events (SAEs) and non-SAEs were collected up to 64 days in Cohort 1, up to 30 days in Cohort 2, up to 30 days in Cohort 3 each in Part A of the study and up to 25 days in Part B of the study.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A: Cohort 1: Placebo	0 of 8 (0%)	3 of 8 (37.5%)	0 of 8
Part A: Cohort 1: GSK3352589 2 mg	1 of 6 (16.7%)	5 of 6 (83.3%)	0 of 6
Part A: Cohort 1: GSK3352589 5 mg	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part A: Cohort 1: GSK3352589 15 mg	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Part A: Cohort 1: GSK3352589 50 mg	0 of 5 (0%)	2 of 5 (40%)	0 of 5
Part A: Cohort 2: Fasted Placebo	0 of 2 (0%)	1 of 2 (50%)	0 of 2
Part A: Cohort 2: Fed Placebo	0 of 2 (0%)	0 of 2 (0%)	0 of 2
Part A: Cohort 2: GSK3352589 Fed 25 mg	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part A: Cohort 2: GSK3352589 Fasted 25 mg	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Part A: Cohort 3: Placebo	0 of 4 (0%)	2 of 4 (50%)	0 of 4
Part A: Cohort 3: GSK3352589 150 mg	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part A: Cohort 3: GSK3352589 400 mg	0 of 5 (0%)	1 of 5 (20%)	0 of 5
Part B: Placebo BID	0 of 10 (0%)	9 of 10 (90%)	0 of 10
Part B: GSK3352589 5 mg BID	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
Part B: GSK3352589 15 mg BID	0 of 6 (0%)	6 of 6 (100%)	0 of 6
Part B: GSK3352589 50 mg BID	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Part B: GSK3352589 100 mg BID	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
Part B: GSK3352589 200 mg BID	0 of 6 (0%)

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33606922Reedy BA, O'Connor-Semmes R, Hacquoil K, Gorycki P, Verticelli A, Molga A. First-in-Human Study for a Selective Rearranged During Transfection Tyrosine Kinase Inhibitor, GSK3352589, to Investigate the Safety, Tolerability, and Pharmacokinetics in Healthy Volunteers. Clin Pharmacol Drug Dev. 2021 Apr;10(4):334-345. doi: 10.1002/cpdd.911. Epub 2021 Feb 19.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

GSK Clinical Trials study director

GlaxoSmithKline

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK3352589 in people with Irritable Bowel Syndrome, run by GlaxoSmithKline at 1 site in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part A: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs in Cohort 1 (time frame: Up to 64 days in Cohort 1). The study lists 70 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03154086, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2019.