Celiac DiseasePhase 1NCT04604795

Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GSK3915393 in Healthy Participants and to Evaluate the Interaction Between GSK3915393 and Grapefruit Juice and Itraconazole

A Phase 1 study testing GSK3915393 Capsules, GSK3915393 Solution for Infusion and Itraconazole in people with Celiac Disease and Coeliac Disease, run by GlaxoSmithKline at 1 site in United Kingdom.

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 is a 3-part first time into human study (FTIH) study for GSK3915393. Parts A and B of the study will evaluate the safety, tolerability and pharmacokinetics (PK) of single ascending and repeat oral doses of GSK3915393 in healthy adult participants. Read more about this study

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Celiac Disease, Coeliac Disease
What is being tested?: GSK3915393 Capsules, GSK3915393 Solution for Infusion and Itraconazole
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 65 participants
Where: 1 siteUnited Kingdom
Study dates: 4 Nov 2020to 29 Jun 2021
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 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Between 18 and 50 years of age inclusive, at the time of signing the informed consent.
Healthy participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
Negative coronavirus disease of 2019 (COVID-19) test on admission.
Body weight >=40 kilograms (kg) and body mass index (BMI) within the range 18.5-29.9 kilograms per square meter (kg/m^2) (inclusive).
Male or females: No restrictions for male participants. A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: Is a woman of non-childbearing potential (WONCBP) OR Is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method from 30 days prior to first dose until follow up visit. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated in relationship to the first dose of study intervention). A WOCBP must have a negative highly sensitive pregnancy test (serum) at screening and on admission to the clinical unit. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
Capable of giving signed informed consent.

Who cannot join

History or current evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal (Irritable bowel syndrome [IBS], Gastroesophageal reflux disease [GERD], nausea, vomiting or dysphagia), endocrine, hematological, neurological, or psychiatric disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
Current evidence of active infection.
Participants with signs/symptoms suggestive of COVID-19 (i.e. fever, cough, etc) within the past 14 days prior to screening and admission to clinical unit.
Participants with known COVID-19 positive contacts in the past 14 days prior to screening and admission to clinical unit.
Any history of suicidal behavior within the past 6 months or any history of attempted suicide in a participant's lifetime.
Alanine transaminase (ALT) >1.5 times upper limit of normal (ULN).

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Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
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 gastrointestinal (GI) surgery (with exception of appendectomy).
Average QT interval corrected using Fridericia's formula (QTcF) >450 milliseconds (msec) at screening.
Any clinically relevant abnormality on the screening medical assessment, laboratory examination, or electrocardiogram.
History of QTc prolongation, symptomatic cardiac arrhythmias or cardiac arrest.
For Part C only, history of liver toxicity resulting from drug administration.
For Part C only, history of intolerance to itraconazole.
History of sensitivity to any of the study medication, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GlaxoSmithKline Medical Monitor, contraindicates their participation.
Use of any immunosuppressive medications within 6 months prior to entry.
Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, probiotics, antacids, herbal and dietary supplements (including Saint [St] John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half- lives (whichever is longer) prior to the first dose of study medication for each dosing, unless in the opinion of the Investigator and GlaxoSmithKline Medical Monitor the medication will not interfere with the study procedures or compromise participant safety. (Paracetamol is acceptable at a dose of no more than 500 milligrams [mg] at a time and no more than 2 grams [g] per day).
Participants who have received a COVID-19 vaccine within 7 days of admission (or readmission) to the clinical unit or who are demonstrating signs/symptoms attributed to a COVID-19 vaccination that occurred greater than 7 days earlier.
Recent donation of blood or blood products such that participation in the study would result in loss of blood in excess of 500 milliliter (mL) within 56 days.
The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Exposure to more than 4 investigational medicinal products within 12 months prior to the first dosing day.
Unwillingness or inability to follow the procedures outlined in the protocol or any other type of medical research within 30 days of randomization.
Presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to first dose of study treatment.
Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment.
A positive pre-study drug/alcohol screen.
Positive human immunodeficiency virus (HIV) antibody test.
History of drug abuse (as defined by the current version of the Diagnostic and Statistical Manual [DSM]) within 2 years before dosing, or a positive drug screen reflecting consumption of illicit drugs.
Regular alcohol consumption within 6 months prior to screening: An average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 g of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
Urinary cotinine levels indicative of smoking or use of tobacco or nicotine-containing products (e.g. nicotine patches or vaporizing devices) at screening or on admission to the unit.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

GSK Investigational Site
London, NW10 7EW

Other trials in United Kingdom

About this study

Official title: A Randomized, Placebo Controlled, Double Blind, Single and Repeat Dose Escalation Phase 1 Study to Evaluate Safety, Tolerability, and Pharmacokinetics of GSK3915393 in Healthy Participants and Open Label Assessment of Coadministration of GSK3915393 With Grapefruit Juice and Itraconazole on the Pharmacokinetics of GSK3915393

Conditions: Celiac Disease, Coeliac Disease
Being tested: GSK3915393 Capsules, GSK3915393 Solution for Infusion, Placebo capsules, Itraconazole, Water
Keywords: Celiac disease, Itraconazole, Grape fruit juice, GSK3915393, Healthy Participants, Pharmacokinetics, First time into human
Medical subject headings: Celiac Disease

What participants receive

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

GSK3915393 CapsulesDrug
GSK3915393 capsules will be given orally.
GSK3915393 Solution for InfusionDrug
GSK3915393 solution for infusion will be administered intravenously.
Placebo capsulesDrug
Placebo matching GSK3915393 capsules will be given orally.
ItraconazoleDrug
Participants will be administered with GSK3915393 along with ITZ orally
WaterOther
Participants will be administered with GSK3915393 along with water orally
Grape fruit juiceOther
Participants will be administered with GSK3915393 along with GFJ orally

Study groups in NCT04604795
Study group	Role	What they receive
Part A:GSK3915393 DLs 1,3,4,intravenous (IV) microdose and placebo (Sequence A)	Experimental	In Part A, participants will receive dose levels (DLs) 1, 3, 4, IV microdose of GSK3915393, and placebo in a pre-determined sequence (Sequence A). There will be a washout period of at least 7 days between each dose. Oral dose levels will be determined based on safety, tolerability and PK data. Receives: Drug: GSK3915393 Capsules; Drug: GSK3915393 Solution for Infusion; Drug: Placebo capsules
Part A:GSK3915393 DLs 1,2,4,IV microdose and placebo (Sequence B)	Experimental	In Part A, participants will receive dose levels 1, 2, 4, IV microdose of GSK3915393 and placebo in a pre-determined sequence (Sequence B). There will be a washout period of at least 7 days between each dose. Oral dose levels will be determined based on safety, tolerability and PK data. Receives: Drug: GSK3915393 Capsules; Drug: GSK3915393 Solution for Infusion; Drug: Placebo capsules
Part A:GSK3915393 DLs 1,2,3,IV microdose and placebo (Sequence C)	Experimental	In Part A, participants will receive dose levels 1, 2, 3, IV microdose of GSK3915393 and placebo in a pre-determined sequence (Sequence C). There will be a washout period of at least 7 days between each dose. Oral dose levels will be determined based on safety, tolerability and PK data. Receives: Drug: GSK3915393 Capsules; Drug: GSK3915393 Solution for Infusion; Drug: Placebo capsules
Part A:GSK3915393 DLs 2,3,4,IV microdose and placebo (Sequence D)	Experimental	In Part A, participants will receive dose levels 2, 3, 4, IV microdose of GSK3915393 and placebo in a pre-determined sequence (Sequence D). There will be a washout period of at least 7 days between each dose. Oral dose levels will be determined based on safety, tolerability and PK data. Receives: Drug: GSK3915393 Capsules; Drug: GSK3915393 Solution for Infusion; Drug: Placebo capsules
Part B: Cohort 1: Participants receiving GSK3915393 DL X	Experimental	Participants will receive GSK3915393 dose level X twice daily during Part B of the study. Dose levels will be determined based on safety, tolerability and PK data from Part A. Receives: Drug: GSK3915393 Capsules
Part B: Cohort 1: Participants receiving placebo	Placebo comparator	Participants will receive placebo matching GSK3915393 dose level X during Part B of the study. Receives: Drug: Placebo capsules
Part B: Cohort 2: Participants receiving GSK3915393 DL Y	Experimental	Participants will receive GSK3915393 dose level Y twice daily during Part B of the study. Dose levels will be determined based on safety, tolerability and PK data from Part A and Part B. Receives: Drug: GSK3915393 Capsules
Part B: Cohort 2: Participants receiving placebo	Placebo comparator	Participants will receive placebo matching GSK3915393 dose level Y twice daily during Part B of the study Receives: Drug: Placebo capsules
Part B: Cohort 3: Participants receiving GSK3915393 DL Z	Experimental	Participants will receive GSK3915393 dose level Z twice daily during Part B of the study. Dose levels will be determined based on safety, tolerability and PK data from Part A and Part B. Receives: Drug: GSK3915393 Capsules
Part B: Cohort 3: Participants receiving placebo	Placebo comparator	Participants will receive placebo matching GSK3915393 dose level Z twice daily during Part B of the study. Receives: Drug: Placebo capsules
Part C: GSK3915393 IV/GSK3915393 IV+ITZ/GSK3915393+water/GSK3915393+GFJ/GSK3915393+ITZ (Sequence A)	Experimental	Participants will receive GSK3915393 IV microdose in period 1 followed by combination of GSK3915393 IV microdose and itraconazole (ITZ) in period 2. Participants will then receive oral GSK3915393 plus water in period 3, oral GSK3915393 plus grape fruit juice (GFJ) in period 4 and oral GSK3915393 plus ITZ in period 5. Receives: Drug: GSK3915393 Capsules; Drug: GSK3915393 Solution for Infusion; Drug: Itraconazole; Other: Water; Other: Grape fruit juice
Part C: GSK3915393 IV/GSK3915393 IV+ITZ/GSK3915393+GFJ/GSK3915393+water/GSK3915393+ITZ (Sequence B)	Experimental	Participants will receive GSK3915393 IV microdose in period 1 followed by combination of GSK3915393 IV microdose and ITZ in period 2. Participants will then receive oral GSK3915393 plus GFJ in period 3, oral GSK3915393 plus water in period 4 and oral GSK3915393 plus ITZ in period 5. Receives: Drug: GSK3915393 Capsules; Drug: GSK3915393 Solution for Infusion; Drug: Itraconazole; Other: Water; Other: Grape fruit juice

What is being measured

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

Part A: Number of Participants With All Non-serious Adverse Events (AEs) and Serious AEs (SAEs) Following Administration of Oral Dose
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any serious adverse event that, at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per investigator's medical or scientific judgment.
Measured: Up to 70 days
Part A: Number of Participants With Treatment-related AEs Following Administration of Oral Dose
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants with treatment related AEs were presented.
Measured: Up to 70 days
Part B: Number of Participants With All Non-serious AEs and SAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any serious adverse event that, at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per investigator's medical or scientific judgment.
Measured: Up to 28 days
Part B: Number of Participants With Treatment-related AEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants with treatment related AEs are presented.
Measured: Up to 28 days
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Blood samples were collected for analysis of chemistry parameters. PCI ranges were >=2*Upper limit of normal (ULN) units per liter (U/L)(Alanine Aminotransferase [ALT]), >=2*ULN (U/L) (Aspartate Aminotransferase ([AST]), >=2*ULN (Alkaline Phosphatase [ALP]) (U/L), >=1.5*ULN (micromoles per liter) (bilirubin), <2 or >2.75 millimoles/liter (L) (mmol/L)(calcium), <3 or >11 mmol/L (glucose), <3 or >5.5 mmol/L (potassium), <130 or >150 mmol/L (sodium),<50 or >85 grams/liter (protein). Participants were counted in worst case category that their value changes to (low, within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100 percentage (%).
Measured: Up to 70 days
Part A: Number of Participants With Worst Case Chemistry Results-creatinine by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Blood samples were collected for analysis of creatinine. Participants were counted under increase of PCI if they had change from Baseline > 44.2 micromoles per Liter for any post Baseline assessment. Participants who did not meet this PCI criteria are counted as within (w/in) range.
Measured: Up to 70 days
Part A: Number of Participants With Worst Case Chemistry Results-urea by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Blood samples were collected for analysis of chemistry parameters. PCI range for Urea: High >10.5 mmol/L. Participants were counted in worst case category that their value changes to (within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category.
Measured: Up to 70 days
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Blood samples were collected for analysis of hematology parameters. PCI ranges were >1*10^9 cell per liter (cells/L) (eosinophils), <0.2 or >0.54 proportion of red blood cells in blood (hematocrit), <80 or >180 grams per liter(g/L) (hemoglobin), <3 or >20 x10^9 cells/L (leukocytes), <0.8*10^9 cells/L (lymphocytes), <1.5 or >16*10^9 cells/L (neutrophils) and <100 or >550*10^9 cells/L (platelets). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example [e.g.], High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' \& 'To High', so the percentages may not add to 100%.
Measured: Up to 70 days
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Vital signs included diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse rate (PR), body temperature, respiratory rate (RR) and were measured after resting for at least 5 minutes in semi-supine position. PCI ranges were, SBP (millimeters of mercury[mmHg]): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), heart rate (beats per minute): <40 (low) or >110 (high), respiration rate (breaths per minute):<=8 (low) or >20 (high) and body temperature (degrees Celsius) <=35.5 (low) or >38.0 (high). Participants were counted in worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To W/in Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100%.
Measured: Up to 70 days
Part A: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings Following Administration of Oral Dose
Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Abnormal findings were categorized as clinically significant and not clinically significant. 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. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
Measured: Up to 70 days
Part A: Number of Participants With Abnormal Physical Examination Findings Following Administration of Oral Dose
A full physical examination was performed which included, at a minimum, assessments of the Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems.
Measured: Up to 70 days
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Blood samples were collected for analysis of chemistry parameters. PCI ranges were >=2*ULN (U/L)(ALT), >=2*ULN (U/L) (AST), >=2*ULN (ALP) (U/L), >=1.5*ULN (micromoles per liter) (bilirubin), <2 or >2.75 millimoles/liter (L) (mmol/L)(calcium), <3 or >11 mmol/L (glucose), <3 or >5.5 mmol/L (potassium), <130 or >150 mmol/L (sodium),<50 or >85 grams/liter (protein). Participants were counted in worst case category that their value changes to (low, within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100 percentage (%).
Measured: Up to 28 days
Part B: Number of Participants With Worst Case Chemistry Results-urea by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Blood samples were collected for analysis of chemistry parameters. PCI range for Urea: High >10.5 mmol/L. Participants were counted in worst case category that their value changes to (within [w/in] range or NC, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category.
Measured: Up to 28 days
Part B: Number of Participants With Worst Case Chemistry Results-creatinine by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose
Blood samples were collected for analysis of creatinine. Participants were counted under increase of PCI if they had change from Baseline > 44.2 micromoles per Liter for any post Baseline assessment. Participants who did not meet this PCI criteria are counted as w/in range. Participants whose laboratory value became within range, were recorded in 'To within Range' category.
Measured: Up to 28 days
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Blood samples were collected for analysis of hematology parameters. PCI ranges were 1*10^9 cell per liter (cells/L) (eosinophils), <0.2 or >0.54 proportion of red blood cells in blood (hematocrit), <80 or >180 grams per liter(g/L) (hemoglobin), <3 or >20 x10^9 cells/L (leukocytes), <0.8*10^9 cells/L (lymphocytes), <1.5 or >16*10^9 cells/L (neutrophils) and <100 or >550*10^9 cells/L (platelets). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example [e.g.], High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' \& 'To High', so the percentages may not add to 100%.
Measured: Up to 28 days
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Vital signs included DBP, SBP, PR, body temperature, RR and were measured after resting for at least 5 minutes in semi-supine position. PCI ranges were, SBP (mmHg): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), heart rate (beats per minute): <40 (low) or >110 (high), respiration rate (breaths per minute):<=8 (low) or >20 (high) and body temperature (degrees Celsius) <=35.5 (low) or >38.0 (high). Participants were counted in worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To W/in Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100%.
Measured: Up to 28 days
Part B: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings Following Repeat Oral Dose of GSK3915393
Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Abnormal findings were categorized as clinically significant and not clinically significant. 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. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
Measured: Up to 28 days
Part B: Number of Participants With Abnormal Physical Examination Findings Following Administration of Repeat Oral Dose of GSK3915393
A full physical examination was performed which included, at a minimum, assessments of the Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems.
Measured: Up to 28 days
Part C: Maximum Observed Plasma Drug Concentration (Cmax) Following IV Dose of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 10 hours post-dose
Part C: Cmax of GSK3915393 Following IV Dose of GSK3915393+ITZ
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, and 60 hours post-dose
Part C: Cmax Following Oral Dose of GSK3915393 in Combination With Water, GFJ and ITZ
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. For Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, concentrations after 24 hours post-dose were expected to be non-quantifiable. Cmax was derived based on collected assessments (up to 24 hours for Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, up to 60 hours for Part C: GSK3915393 20 mg+ ITZ). Only the quantifiable concentration time points were to be considered for assessment of pharmacokinetic parameters.
Measured: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48 and 60 hours post-dose
Part C: Time to Maximum Observed Plasma Drug Concentration (Tmax) Following IV Dose of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 10 hours post-dose
Part C: Tmax of GSK3915393 Following IV Dose of GSK3915393+ITZ
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, and 60 hours post-dose
Part C: Tmax of GSK3915393 Following Oral Dose of GSK3915393 in Combination With Water, GFJ and ITZ
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. For Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, concentrations after 24 hours post-dose were expected to be non-quantifiable. Tmax was derived based on collected assessments (up to 24 hours for Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, up to 60 hours for Part C: GSK3915393 20 mg+ ITZ). Only the quantifiable concentration time points were to be considered for assessment of pharmacokinetic parameters.
Measured: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48 and 60 hours post-dose
Part C: Area Under Curve up to the Last Measurable Concentration (AUCLST[0-10]) Following IV Dose of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 10 hours post-dose
Part C: AUCLST(0-24) of GSK3915393 Following IV Dose of GSK3915393+ITZ
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, and 24 hours post-dose
Part C: AUCLST(0-24) of GSK3915393 Following Oral Dose of GSK3915393 in Combination With Water, GFJ and ITZ
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours post-dose
Part C: AUC From Time Zero to Infinity (AUC[0-inf]) Following IV Dose of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 10 hours post-dose
Part C: AUC(0-inf) of GSK3915393 Following IV Dose of GSK3915393+ITZ
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, and 60 hours post-dose
Part C: AUC(0-inf) of GSK3915393 Following Oral Dose of GSK3915393 in Combination With Water, GFJ and ITZ
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. For Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, concentrations after 24 hours post-dose were expected to be non-quantifiable. AUC(0-inf) was derived based on collected assessments (up to 24 hours for Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, up to 60 hours for Part C: GSK3915393 20 mg+ ITZ). Only the quantifiable concentration time points were to be considered for assessment of pharmacokinetic parameters.
Measured: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48 and 60 hours post-dose
Part C: Apparent Terminal Half-life (t1/2) of GSK3915393 Following IV Dose of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 10 hours post-dose
Part C: t1/2 of GSK3915393 Following IV Dose of GSK3915393+ITZ
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, and 60 hours post-dose
Part C: t1/2 of GSK3915393 Following Oral Dose of GSK3915393 in Combination With Water, GFJ and ITZ
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. For Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, concentrations after 24 hours post-dose were expected to be non-quantifiable. t1/2 was derived based on collected assessments (up to 24 hours for Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, up to 60 hours for Part C: GSK3915393 20 mg+ ITZ). Only the quantifiable concentration time points were to be considered for assessment of pharmacokinetic parameters.
Measured: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48 and 60 hours post-dose

Secondary outcomes (51)

Part A: Cmax Following Single Oral Dose of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dose
Part A: Cmax Following Single IV Dose of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose
Part A: Tmax Following Single Oral Dose of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dose
Part A: Tmax Following IV Dose of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose
Part A: AUCLST(0-24) Following Single Oral Dose of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, and 24 hours post-dose
Part A: AUCLST(0-6) Following Single IV Dose of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose
Part A: AUC(0-inf) Following Single Oral Dose of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dose
Part A: AUC(0-inf) Following Single IV Dose of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose
Part A: t1/2 Following Single IV Dose of GSK3915393 100 mcg IV
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose
Part A: Clearance (CL) Following Single IV Dose of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose
Part A: Volume of Distribution (Vd) Following Single IV Dose of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose
Part A: Absolute Bioavailability (F) Following Single Oral Dose of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. Absolute bioavailability is the amount of drug from a formulation that reaches the systemic circulation relative to an IV dose. It was expressed as ratio was calculated as (AUC[0-inf] for oral divided by oral dose) divided by (AUC[0-inf] for IV/dose given as IV).
Measured: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dose
Part A: Fraction of Drug Escaping Hepatic Metabolism (FH) Following Single Oral Dose of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. FH was expressed as ratio and was calculated as: 1 minus hepatic extraction ratio. Hepatic extraction ratio=hepatic blood clearance (milliliters per minute)/hepatic blood flow (milliliters per minute).
Measured: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dose
Part A: Product of Fraction of Drug Absorbed and Fraction of Drug Escaping Gut Metabolism (FA*FG) Following Oral Dose of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. Product of FA*FG was calculated as: (absolute bioavailability [F] divided by fraction of drug escaping hepatic metabolism [FH]).
Measured: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dose
Part A: Number of Participants With All Non-serious AEs and SAEs Following Administration Administration of IV Dose of GSK3915393
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any serious adverse event that, at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per investigator's medical or scientific judgment.
Measured: Up to 21 days
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Blood samples were collected for analysis of chemistry parameters. PCI ranges were >=2*ULN (U/L)(ALT), >=2*ULN (U/L) (AST), >=2*ULN (ALP) (U/L), >=1.5*ULN (micromoles per liter) (bilirubin), <2 or >2.75 millimoles/liter (L) (mmol/L)(calcium), <3 or >11 mmol/L (glucose), <3 or >5.5 mmol/L (potassium), <130 or >150 mmol/L (sodium),<50 or >85 grams/liter (protein). Participants were counted in worst case category that their value changes to (low, within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100 percentage (%).
Measured: Up to 21 days
Part A: Number of Participants With Worst Case Chemistry Results-creatinine by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Blood samples were collected for analysis of creatinine. Participants were counted under increase of PCI if they had change from Baseline >44.2 micromoles per Liter for any post Baseline assessment. Participants who did not meet this PCI criteria are counted as w/in range.
Measured: Up to 21 days
Part A: Number of Participants With Worst Case Chemistry Results-urea by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Blood samples were collected for analysis of chemistry parameters. PCI range for Urea: High >10.5 mmol/L. Participants were counted in worst case category that their value changes to (within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category.
Measured: Up to 21 days
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Blood samples were collected for analysis of hematology parameters. PCI ranges were >1*10^9 cell per liter (cells/L) (eosinophils), <0.2 or >0.54 proportion of red blood cells in blood (hematocrit), <80 or >180 grams per liter(g/L) (hemoglobin), <3 or >20 x10^9 cells/L (leukocytes), <0.8*10^9 cells/L (lymphocytes), <1.5 or >16*10^9 cells/L (neutrophils) and <100 or >550*10^9 cells/L (platelets). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example [e.g.], High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' \& 'To High', so the percentages may not add to 100%.
Measured: Up to 21 days
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following IV Dose of GSK3915393
Vital signs included DBP, SBP, PR, body temperature, RR and were measured after resting for at least 5 minutes in semi-supine position. PCI ranges were, SBP (mmHg): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), heart rate (beats per minute): <40 (low) or >110 (high), respiration rate (breaths per minute):<=8 (low) or >20 (high) and body temperature (degrees Celsius) <=35.5 (low) or >38.0 (high). Participants were counted in worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To W/in Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100%.
Measured: Up to 21 days
Part A: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings Following Administration of IV Dose of GSK3915393
Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Abnormal findings were categorized as clinically significant and not clinically significant. 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. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
Measured: Up to 21 days
Part A: Number of Participants With Abnormal Physical Examination Findings Following Administration of IV Dose of GSK3915393
A full physical examination was performed which included, at a minimum, assessments of the Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems.
Measured: Up to 21 days
Part B: Cmax(0-10) Following Dosing of GSK3915393 on Days 1 and 14
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Days 1 and 14: Pre-dose, 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, and 10 hours post-dose
Part B: Cmax(10-24) Following Repeat Dose 20 mg and 80 mg of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Days 1 and 14: 10 hours, 10 hours 20 minutes, 10 hours 40 minutes, 12, 12.5 ,13, 14, 16, and 24 hours post-dose
Part B: Cmax(10-24) Following Dose 160 mg (QD) of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Days 1 and 14: 10, 24 hours post-dose
Part B: Tmax(0-10) Following Dosing of GSK3915393 on Days 1 and 14
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Days 1 and 14: Pre-dose, 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, and 10 hours post-dose
Part B: Tmax(10-24) Following Repeat Dose 20 mg BID and 80 mg BID of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Days 1 and 14: 10 hours, 10 hours 20 minutes, 10 hours 40 minutes, 12, 12.5 ,13, 14, 16, and 24 hours post-dose
Part B: Tmax(10-24) Following Dose 160 mg (QD) of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Days 1 and 14: 10, 24 hours post-dose
Part B: AUCLST(0-10) Following Dosing of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Days 1 and 14: Pre-dose, 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, and 10 hours post-dose
Part B: AUCLST(0-24) Following Repeat Dose 20 mg BID and 80 mg BID of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Days 1 and 14: Pre-dose, 20 minutes, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 10 hours 20 minutes, 10 hours 40 minutes, 12, 12.5 ,13, 14, 16, and 24 hours post-dose
Part B: AUCLST(0-24) Following Dose of GSK3915393 160 mg (QD)
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Days 1 and 14: Pre-dose, 20 minutes, 40 minutess, 1, 1.5, 2, 3 ,4, 6, 10 and 24 hours post-dose
Part B: AUC(10-24) Following Repeat Dose 20 mg BID and 80 mg BID of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Days 1 and 14: 10 hours, 10 hours 20 minutes, 10 hours 40 minutes, 12, 12.5 ,13, 14, 16, and 24 hours post-dose
Part B: AUC(10-24) Following Repeat Dose of GSK3915393 160 mg (QD)
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Days 1 and 14: 10 and 24 hours post-dose
Part B: Cmax(0-10) Following First Dosing of GSK3915393 on Days 3, 5 and 7 (for Food-effect Assessment)
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Days 3, 5 and 7: Pre-dose, 20, 40 minutes, 1, 1.5, 2, 3, 4, 6 and 10 hours post-dose
Part B: Tmax(0-10) Following First Dosing of GSK3915393 on Days 3, 5 and 7 (for Food-effect Assessment)
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Days 3, 5 and 7: Pre-dose, 20, 40 minutes, 1, 1.5, 2, 3, 4, 6 and 10 hours post-dose
Part B: AUCLST(0-10) Following First Dosing of GSK3915393 on Days 3, 5 and 7 (for Food-effect Assessment)
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Days 3, 5 and 7: Pre-dose, 20, 40 minutes, 1, 1.5 ,2, 3, 4, 6 and 10 hours post-dose
Part B: Trough Concentration (Ctau) Following Dose of 20 mg BID and 80 mg BID of GSK3915393 on Day 14
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Day 14: Pre-dose, 20, 40 minutes, 1, 1.5 ,2, 3, 4, 6, 10, 10 hour 20 minutes, 10 hours 40 minutes, 12, 12.5, 13, 14, 16 and 24 hours post-dose
Part B: Trough Concentration (Ctau) Following Dose of 160 mg of GSK3915393 on Day 14
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Measured: Day 14: Pre-dose, 20, 40 minutes, 1, 1.5 ,2, 3, 4, 6, 10, and 24 hours post-dose
Part C: Number of Participants With All Non-serious AEs and SAEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any serious adverse event that, at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per investigator's medical or scientific judgment.
Measured: Up to 72 days
Part C: Number of Participants With Treatment-related AEs Following Dose of GSK3915393
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants with treatment related AEs are presented.
Measured: Up to 72 days
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Blood samples were collected for analysis of chemistry parameters. PCI ranges were >=2*ULN (U/L)(ALT), >=2*ULN (U/L) (AST), >=2*ULN (ALP) (U/L), >=1.5*ULN (micromoles per liter) (bilirubin), <2 or >2.75 millimoles/liter (L) (mmol/L)(calcium), <3 or >11 mmol/L (glucose), <3 or >5.5 mmol/L (potassium), <130 or >150 mmol/L (sodium),<50 or >85 grams/liter (protein). Participants were counted in worst case category that their value changes to (low, within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100 percentage (%).
Measured: Up to 72 days
Part C: Number of Participants With Worst Case Chemistry Results: Creatinine by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Blood samples were collected for analysis of creatinine. Participants were counted under increase of PCI if they had change from Baseline > 44.2 micromoles per Liter for any post Baseline assessment. Participants who did not meet this PCI criteria are counted as w/in range. Participants whose laboratory value became within range, were recorded in 'To within Range' category.
Measured: Up to 72 days
Part C: Number of Participants With Worst Case Chemistry Results: Urea by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Blood samples were collected for analysis of chemistry parameters. PCI range for Urea: High >10.5 mmol/L. Participants were counted in worst case category that their value changes to ( within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category.
Measured: Up to 72 days
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Blood samples were collected for analysis of hematology parameters. PCI ranges were 1*10^9 cell per liter (cells/L) (eosinophils), <0.2 or >0.54 proportion of red blood cells in blood (hematocrit), <80 or >180 grams per liter(g/L) (hemoglobin), <3 or >20 x10^9 cells/L (leukocytes), <0.8*10^9 cells/L (lymphocytes), <1.5 or >16*10^9 cells/L (neutrophils) and <100 or >550*10^9 cells/L (platelets). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example [e.g.], High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' \& 'To High', so the percentages may not add to 100%.
Measured: Up to 72 days
Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Dose Administration of GSK3915393
Vital signs included DBP, SBP, PR, body temperature, RR and were measured after resting for at least 5 minutes in semi-supine position. PCI ranges were, SBP (mmHg): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), heart rate (beats per minute): <40 (low) or >110 (high), respiration rate (breaths per minute):<=8 (low) or >20 (high) and body temperature (degrees Celsius) <=35.5 (low) or >38.0 (high). Participants were counted in worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To W/in Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100%.
Measured: Up to 72 days
Part C: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings Following Administration of GSK3915393
Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Abnormal findings were categorized as clinically significant and not clinically significant. 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. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
Measured: Up to 72 days
Part C: Number of Participants With Abnormal Physical Examination Findings Following Administration of GSK3915393
A full physical examination was performed which included, at a minimum, assessments of the Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems.
Measured: Up to 72 days
Part C: Fraction of Drug Escaping Hepatic Metabolism (FH) Following IV Dose of GSK3915393
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. FH was expressed as ratio and was calculated as: 1 minus hepatic extraction ratio. Hepatic extraction ratio=hepatic blood clearance (milliliters per minute)/hepatic blood flow (milliliters per minute)
Measured: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hour 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24, 36, 48, and 60 hours post-dose
Part C: FH Following IV Administration of GSK3915393+ITZ
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. FH was expressed as ratio and was calculated as: 1 minus Hepatic extraction ratio. Hepatic extraction ratio=hepatic blood clearance (milliliters per minute)/hepatic blood flow (milliliters per minute)
Measured: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hour 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, and 60 hours post-dose
Part C: Fraction of Drug Escaping Gut Metabolism (FG) Following Oral Administration of GSK3915393+Water
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. FG was expressed as ratio and calculated as: AUC of GSK3915393+water divided by AUC of GSK3915393+GFJ.
Measured: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours post-dose
Part C: Fraction of Drug Absorbed (FA) Following Oral Administration of GSK3915393+Water
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. FA was expressed as ratio was calculated as absolute bioavailability (F) divided by the product of fraction of drug escaping hepatic metabolism (FH) and fraction of drug escaping gut metabolism (FG).
Measured: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours post-dose

Timeline

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

4 Nov 202029 Jun 2021

First posted27 Oct 2020
Study start4 Nov 2020
Primary completion29 Jun 2021
Study completion29 Jun 2021

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.
Other trials for Celiac DiseaseStudies 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
Model description: This is a 3-part study. Parts A and C will have a 5 period crossover design Part B will be conducted as a parallel group dose escalation study.
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 65 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04604795
Sponsor's protocol ID: 213585
Status last verified: Jun 2022
First submitted: 6 Oct 2020
Last updated: 9 May 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: IPD for this study will be made available via the Clinical Study Data Request site.

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See locations

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Study at a glance

From the registry record, last updated by the sponsor on 9 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Placebo Controlled, Double Blind, Single and Repeat Dose Escalation Phase 1 Study to Evaluate Safety, Tolerability, and Pharmacokinetics of GSK3915393 in Healthy Participants and Open Label Assessment of Coadministration of GSK3915393 With Grapefruit Juice and Itraconazole on the Pharmacokinetics of GSK3915393
ClinicalTrials.gov ID: NCT04604795
Acronym / sponsor ID: 213585
Conditions: Celiac Disease, Coeliac Disease
Keywords: Celiac disease, Itraconazole, Grape fruit juice, GSK3915393, Healthy Participants, Pharmacokinetics, First time into human
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 65 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 4 Nov 2020 (actual)
Primary completion: 29 Jun 2021 (actual)
Study completion: 29 Jun 2021 (actual)
First posted: 27 Oct 2020 (actual)
Results: Posted 9 May 2023

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: 12
Model description: This is a 3-part study. Parts A and C will have a 5 period crossover design Part B will be conducted as a parallel group dose escalation study.

Arm	Type	Receives
Part A:GSK3915393 DLs 1,3,4,intravenous (IV) microdose and placebo (Sequence A)	Experimental	Drug: GSK3915393 Capsules, Drug: GSK3915393 Solution for Infusion, Drug: Placebo capsulesIn Part A, participants will receive dose levels (DLs) 1, 3, 4, IV microdose of GSK3915393, and placebo in a pre-determined sequence (Sequence A). There will be a washout period of at least 7 days between each dose. Oral dose levels will be determined based on safety, tolerability and PK data.
Part A:GSK3915393 DLs 1,2,4,IV microdose and placebo (Sequence B)	Experimental	Drug: GSK3915393 Capsules, Drug: GSK3915393 Solution for Infusion, Drug: Placebo capsulesIn Part A, participants will receive dose levels 1, 2, 4, IV microdose of GSK3915393 and placebo in a pre-determined sequence (Sequence B). There will be a washout period of at least 7 days between each dose. Oral dose levels will be determined based on safety, tolerability and PK data.
Part A:GSK3915393 DLs 1,2,3,IV microdose and placebo (Sequence C)	Experimental	Drug: GSK3915393 Capsules, Drug: GSK3915393 Solution for Infusion, Drug: Placebo capsulesIn Part A, participants will receive dose levels 1, 2, 3, IV microdose of GSK3915393 and placebo in a pre-determined sequence (Sequence C). There will be a washout period of at least 7 days between each dose. Oral dose levels will be determined based on safety, tolerability and PK data.
Part A:GSK3915393 DLs 2,3,4,IV microdose and placebo (Sequence D)	Experimental	Drug: GSK3915393 Capsules, Drug: GSK3915393 Solution for Infusion, Drug: Placebo capsulesIn Part A, participants will receive dose levels 2, 3, 4, IV microdose of GSK3915393 and placebo in a pre-determined sequence (Sequence D). There will be a washout period of at least 7 days between each dose. Oral dose levels will be determined based on safety, tolerability and PK data.
Part B: Cohort 1: Participants receiving GSK3915393 DL X	Experimental	Drug: GSK3915393 CapsulesParticipants will receive GSK3915393 dose level X twice daily during Part B of the study. Dose levels will be determined based on safety, tolerability and PK data from Part A.
Part B: Cohort 1: Participants receiving placebo	Placebo comparator	Drug: Placebo capsulesParticipants will receive placebo matching GSK3915393 dose level X during Part B of the study.
Part B: Cohort 2: Participants receiving GSK3915393 DL Y	Experimental	Drug: GSK3915393 CapsulesParticipants will receive GSK3915393 dose level Y twice daily during Part B of the study. Dose levels will be determined based on safety, tolerability and PK data from Part A and Part B.
Part B: Cohort 2: Participants receiving placebo	Placebo comparator	Drug: Placebo capsulesParticipants will receive placebo matching GSK3915393 dose level Y twice daily during Part B of the study
Part B: Cohort 3: Participants receiving GSK3915393 DL Z	Experimental	Drug: GSK3915393 CapsulesParticipants will receive GSK3915393 dose level Z twice daily during Part B of the study. Dose levels will be determined based on safety, tolerability and PK data from Part A and Part B.
Part B: Cohort 3: Participants receiving placebo	Placebo comparator	Drug: Placebo capsulesParticipants will receive placebo matching GSK3915393 dose level Z twice daily during Part B of the study.
Part C: GSK3915393 IV/GSK3915393 IV+ITZ/GSK3915393+water/GSK3915393+GFJ/GSK3915393+ITZ (Sequence A)	Experimental	Drug: GSK3915393 Capsules, Drug: GSK3915393 Solution for Infusion, Drug: Itraconazole, Other: Water, Other: Grape fruit juiceParticipants will receive GSK3915393 IV microdose in period 1 followed by combination of GSK3915393 IV microdose and itraconazole (ITZ) in period 2. Participants will then receive oral GSK3915393 plus water in period 3, oral GSK3915393 plus grape fruit juice (GFJ) in period 4 and oral GSK3915393 plus ITZ in period 5.
Part C: GSK3915393 IV/GSK3915393 IV+ITZ/GSK3915393+GFJ/GSK3915393+water/GSK3915393+ITZ (Sequence B)	Experimental	Drug: GSK3915393 Capsules, Drug: GSK3915393 Solution for Infusion, Drug: Itraconazole, Other: Water, Other: Grape fruit juiceParticipants will receive GSK3915393 IV microdose in period 1 followed by combination of GSK3915393 IV microdose and ITZ in period 2. Participants will then receive oral GSK3915393 plus GFJ in period 3, oral GSK3915393 plus water in period 4 and oral GSK3915393 plus ITZ in period 5.

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (6 listed)

Between 18 and 50 years of age inclusive, at the time of signing the informed consent.
Healthy participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
Negative coronavirus disease of 2019 (COVID-19) test on admission.
Body weight >=40 kilograms (kg) and body mass index (BMI) within the range 18.5-29.9 kilograms per square meter (kg/m^2) (inclusive).
Male or females: No restrictions for male participants. A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: Is a woman of non-childbearing potential (WONCBP) OR Is a woman of childbearing potential (WOCBP) and using an acceptable contraceptive method from 30 days prior to first dose until follow up visit. The investigator should evaluate the potential for contraceptive method failure (e.g., noncompliance, recently initiated in relationship to the first dose of study intervention). A WOCBP must have a negative highly sensitive pregnancy test (serum) at screening and on admission to the clinical unit. The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.

Key exclusion criteria (30 listed)

History or current evidence of cardiovascular, respiratory, hepatic, renal, gastrointestinal (Irritable bowel syndrome [IBS], Gastroesophageal reflux disease [GERD], nausea, vomiting or dysphagia), endocrine, hematological, neurological, or psychiatric disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
Current evidence of active infection.
Participants with signs/symptoms suggestive of COVID-19 (i.e. fever, cough, etc) within the past 14 days prior to screening and admission to clinical unit.
Participants with known COVID-19 positive contacts in the past 14 days prior to screening and admission to clinical unit.
Any history of suicidal behavior within the past 6 months or any history of attempted suicide in a participant's lifetime.

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
GSK3915393 CapsulesGSK3915393 capsules will be given orally.	Drug	Part A:GSK3915393 DLs 1,2,3,IV microdose and placebo (Sequence C), Part A:GSK3915393 DLs 1,2,4,IV microdose and placebo (Sequence B), Part A:GSK3915393 DLs 1,3,4,intravenous (IV) microdose and placebo (Sequence A), Part A:GSK3915393 DLs 2,3,4,IV microdose and placebo (Sequence D), Part B: Cohort 1: Participants receiving GSK3915393 DL X, Part B: Cohort 2: Participants receiving GSK3915393 DL Y, Part B: Cohort 3: Participants receiving GSK3915393 DL Z, Part C: GSK3915393 IV/GSK3915393 IV+ITZ/GSK3915393+GFJ/GSK3915393+water/GSK3915393+ITZ (Sequence B), Part C: GSK3915393 IV/GSK3915393 IV+ITZ/GSK3915393+water/GSK3915393+GFJ/GSK3915393+ITZ (Sequence A)
GSK3915393 Solution for InfusionGSK3915393 solution for infusion will be administered intravenously.	Drug	Part A:GSK3915393 DLs 1,2,3,IV microdose and placebo (Sequence C), Part A:GSK3915393 DLs 1,2,4,IV microdose and placebo (Sequence B), Part A:GSK3915393 DLs 1,3,4,intravenous (IV) microdose and placebo (Sequence A), Part A:GSK3915393 DLs 2,3,4,IV microdose and placebo (Sequence D), Part C: GSK3915393 IV/GSK3915393 IV+ITZ/GSK3915393+GFJ/GSK3915393+water/GSK3915393+ITZ (Sequence B), Part C: GSK3915393 IV/GSK3915393 IV+ITZ/GSK3915393+water/GSK3915393+GFJ/GSK3915393+ITZ (Sequence A)
Placebo capsulesPlacebo matching GSK3915393 capsules will be given orally.	Drug	Part A:GSK3915393 DLs 1,2,3,IV microdose and placebo (Sequence C), Part A:GSK3915393 DLs 1,2,4,IV microdose and placebo (Sequence B), Part A:GSK3915393 DLs 1,3,4,intravenous (IV) microdose and placebo (Sequence A), Part A:GSK3915393 DLs 2,3,4,IV microdose and placebo (Sequence D), Part B: Cohort 1: Participants receiving placebo, Part B: Cohort 2: Participants receiving placebo, Part B: Cohort 3: Participants receiving placebo
ItraconazoleParticipants will be administered with GSK3915393 along with ITZ orally	Drug	Part C: GSK3915393 IV/GSK3915393 IV+ITZ/GSK3915393+GFJ/GSK3915393+water/GSK3915393+ITZ (Sequence B), Part C: GSK3915393 IV/GSK3915393 IV+ITZ/GSK3915393+water/GSK3915393+GFJ/GSK3915393+ITZ (Sequence A)
WaterParticipants will be administered with GSK3915393 along with water orally	Other	Part C: GSK3915393 IV/GSK3915393 IV+ITZ/GSK3915393+GFJ/GSK3915393+water/GSK3915393+ITZ (Sequence B), Part C: GSK3915393 IV/GSK3915393 IV+ITZ/GSK3915393+water/GSK3915393+GFJ/GSK3915393+ITZ (Sequence A)
Grape fruit juiceParticipants will be administered with GSK3915393 along with GFJ orally	Other	Part C: GSK3915393 IV/GSK3915393 IV+ITZ/GSK3915393+GFJ/GSK3915393+water/GSK3915393+ITZ (Sequence B), Part C: GSK3915393 IV/GSK3915393 IV+ITZ/GSK3915393+water/GSK3915393+GFJ/GSK3915393+ITZ (Sequence A)

Primary outcome

Part A: Number of Participants With All Non-serious Adverse Events (AEs) and Serious AEs (SAEs) Following Administration of Oral Dose
Time frame: Up to 70 days
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any serious adverse event that, at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per investigator's medical or scientific judgment.
Part A: Number of Participants With Treatment-related AEs Following Administration of Oral Dose
Time frame: Up to 70 days
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants with treatment related AEs were presented.
Part B: Number of Participants With All Non-serious AEs and SAEs
Time frame: Up to 28 days
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any serious adverse event that, at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, other situations as per investigator's medical or scientific judgment.
Part B: Number of Participants With Treatment-related AEs
Time frame: Up to 28 days
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. Number of participants with treatment related AEs are presented.
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Time frame: Up to 70 days
Blood samples were collected for analysis of chemistry parameters. PCI ranges were >=2*Upper limit of normal (ULN) units per liter (U/L)(Alanine Aminotransferase [ALT]), >=2*ULN (U/L) (Aspartate Aminotransferase ([AST]), >=2*ULN (Alkaline Phosphatase [ALP]) (U/L), >=1.5*ULN (micromoles per liter) (bilirubin), <2 or >2.75 millimoles/liter (L) (mmol/L)(calcium), <3 or >11 mmol/L (glucose), <3 or >5.5 mmol/L (potassium), <130 or >150 mmol/L (sodium),<50 or >85 grams/liter (protein). Participants were counted in worst case category that their value changes to (low, within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100 percentage (%).
Part A: Number of Participants With Worst Case Chemistry Results-creatinine by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Time frame: Up to 70 days
Blood samples were collected for analysis of creatinine. Participants were counted under increase of PCI if they had change from Baseline > 44.2 micromoles per Liter for any post Baseline assessment. Participants who did not meet this PCI criteria are counted as within (w/in) range.
Part A: Number of Participants With Worst Case Chemistry Results-urea by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Time frame: Up to 70 days
Blood samples were collected for analysis of chemistry parameters. PCI range for Urea: High >10.5 mmol/L. Participants were counted in worst case category that their value changes to (within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category.
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Time frame: Up to 70 days
Blood samples were collected for analysis of hematology parameters. PCI ranges were >1*10^9 cell per liter (cells/L) (eosinophils), <0.2 or >0.54 proportion of red blood cells in blood (hematocrit), <80 or >180 grams per liter(g/L) (hemoglobin), <3 or >20 x10^9 cells/L (leukocytes), <0.8*10^9 cells/L (lymphocytes), <1.5 or >16*10^9 cells/L (neutrophils) and <100 or >550*10^9 cells/L (platelets). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example [e.g.], High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' \& 'To High', so the percentages may not add to 100%.
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Oral Dose
Time frame: Up to 70 days
Vital signs included diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse rate (PR), body temperature, respiratory rate (RR) and were measured after resting for at least 5 minutes in semi-supine position. PCI ranges were, SBP (millimeters of mercury[mmHg]): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), heart rate (beats per minute): <40 (low) or >110 (high), respiration rate (breaths per minute):<=8 (low) or >20 (high) and body temperature (degrees Celsius) <=35.5 (low) or >38.0 (high). Participants were counted in worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To W/in Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100%.
Part A: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings Following Administration of Oral Dose
Time frame: Up to 70 days
Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Abnormal findings were categorized as clinically significant and not clinically significant. 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. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
Part A: Number of Participants With Abnormal Physical Examination Findings Following Administration of Oral Dose
Time frame: Up to 70 days
A full physical examination was performed which included, at a minimum, assessments of the Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems.
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Time frame: Up to 28 days
Blood samples were collected for analysis of chemistry parameters. PCI ranges were >=2*ULN (U/L)(ALT), >=2*ULN (U/L) (AST), >=2*ULN (ALP) (U/L), >=1.5*ULN (micromoles per liter) (bilirubin), <2 or >2.75 millimoles/liter (L) (mmol/L)(calcium), <3 or >11 mmol/L (glucose), <3 or >5.5 mmol/L (potassium), <130 or >150 mmol/L (sodium),<50 or >85 grams/liter (protein). Participants were counted in worst case category that their value changes to (low, within [w/in] range or no change [NC], or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100 percentage (%).
Part B: Number of Participants With Worst Case Chemistry Results-urea by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose of GSK3915393
Time frame: Up to 28 days
Blood samples were collected for analysis of chemistry parameters. PCI range for Urea: High >10.5 mmol/L. Participants were counted in worst case category that their value changes to (within [w/in] range or NC, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To within Range No Change' category.
Part B: Number of Participants With Worst Case Chemistry Results-creatinine by PCI Criteria Post-Baseline Relative to Baseline Following Administration of Repeat Oral Dose
Time frame: Up to 28 days
Blood samples were collected for analysis of creatinine. Participants were counted under increase of PCI if they had change from Baseline > 44.2 micromoles per Liter for any post Baseline assessment. Participants who did not meet this PCI criteria are counted as w/in range. Participants whose laboratory value became within range, were recorded in 'To within Range' category.
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Time frame: Up to 28 days
Blood samples were collected for analysis of hematology parameters. PCI ranges were 1*10^9 cell per liter (cells/L) (eosinophils), <0.2 or >0.54 proportion of red blood cells in blood (hematocrit), <80 or >180 grams per liter(g/L) (hemoglobin), <3 or >20 x10^9 cells/L (leukocytes), <0.8*10^9 cells/L (lymphocytes), <1.5 or >16*10^9 cells/L (neutrophils) and <100 or >550*10^9 cells/L (platelets). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (for example [e.g.], High to High), or whose value became within range, were recorded in "To within Range or No Change" category. Participants were counted twice if participant has values that changed 'To Low' \& 'To High', so the percentages may not add to 100%.
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following Repeat Oral Dose of GSK3915393
Time frame: Up to 28 days
Vital signs included DBP, SBP, PR, body temperature, RR and were measured after resting for at least 5 minutes in semi-supine position. PCI ranges were, SBP (mmHg): <85 (low) or >160 (high), DBP (mmHg): <45 (low) or >100 (high), heart rate (beats per minute): <40 (low) or >110 (high), respiration rate (breaths per minute):<=8 (low) or >20 (high) and body temperature (degrees Celsius) <=35.5 (low) or >38.0 (high). Participants were counted in worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, are recorded in 'To W/in Range No Change' category. Participants were counted twice if participant had values that changed 'To Low' and 'To High', so percentages may not add to 100%.
Part B: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings Following Repeat Oral Dose of GSK3915393
Time frame: Up to 28 days
Twelve lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured QTc, PR, QRS intervals. Abnormal findings were categorized as clinically significant and not clinically significant. 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. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
Part B: Number of Participants With Abnormal Physical Examination Findings Following Administration of Repeat Oral Dose of GSK3915393
Time frame: Up to 28 days
A full physical examination was performed which included, at a minimum, assessments of the Skin, Cardiovascular, Respiratory, Gastrointestinal and Neurological systems.
Part C: Maximum Observed Plasma Drug Concentration (Cmax) Following IV Dose of GSK3915393
Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 10 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Part C: Cmax of GSK3915393 Following IV Dose of GSK3915393+ITZ
Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, and 60 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Part C: Cmax Following Oral Dose of GSK3915393 in Combination With Water, GFJ and ITZ
Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48 and 60 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. For Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, concentrations after 24 hours post-dose were expected to be non-quantifiable. Cmax was derived based on collected assessments (up to 24 hours for Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, up to 60 hours for Part C: GSK3915393 20 mg+ ITZ). Only the quantifiable concentration time points were to be considered for assessment of pharmacokinetic parameters.
Part C: Time to Maximum Observed Plasma Drug Concentration (Tmax) Following IV Dose of GSK3915393
Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 10 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Part C: Tmax of GSK3915393 Following IV Dose of GSK3915393+ITZ
Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, and 60 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Part C: Tmax of GSK3915393 Following Oral Dose of GSK3915393 in Combination With Water, GFJ and ITZ
Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48 and 60 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. For Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, concentrations after 24 hours post-dose were expected to be non-quantifiable. Tmax was derived based on collected assessments (up to 24 hours for Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, up to 60 hours for Part C: GSK3915393 20 mg+ ITZ). Only the quantifiable concentration time points were to be considered for assessment of pharmacokinetic parameters.
Part C: Area Under Curve up to the Last Measurable Concentration (AUCLST[0-10]) Following IV Dose of GSK3915393
Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 10 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Part C: AUCLST(0-24) of GSK3915393 Following IV Dose of GSK3915393+ITZ
Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, and 24 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Part C: AUCLST(0-24) of GSK3915393 Following Oral Dose of GSK3915393 in Combination With Water, GFJ and ITZ
Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14 and 24 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Part C: AUC From Time Zero to Infinity (AUC[0-inf]) Following IV Dose of GSK3915393
Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 10 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Part C: AUC(0-inf) of GSK3915393 Following IV Dose of GSK3915393+ITZ
Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, and 60 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Part C: AUC(0-inf) of GSK3915393 Following Oral Dose of GSK3915393 in Combination With Water, GFJ and ITZ
Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48 and 60 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. For Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, concentrations after 24 hours post-dose were expected to be non-quantifiable. AUC(0-inf) was derived based on collected assessments (up to 24 hours for Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, up to 60 hours for Part C: GSK3915393 20 mg+ ITZ). Only the quantifiable concentration time points were to be considered for assessment of pharmacokinetic parameters.
Part C: Apparent Terminal Half-life (t1/2) of GSK3915393 Following IV Dose of GSK3915393
Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, and 10 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Part C: t1/2 of GSK3915393 Following IV Dose of GSK3915393+ITZ
Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 10, 12, 24, 36, 48, and 60 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393.
Part C: t1/2 of GSK3915393 Following Oral Dose of GSK3915393 in Combination With Water, GFJ and ITZ
Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48 and 60 hours post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3915393. For Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, concentrations after 24 hours post-dose were expected to be non-quantifiable. t1/2 was derived based on collected assessments (up to 24 hours for Part C: GSK3915393 20 mg+ Water and Part C: GSK3915393 20 mg+ GFJ, up to 60 hours for Part C: GSK3915393 20 mg+ ITZ). Only the quantifiable concentration time points were to be considered for assessment of pharmacokinetic parameters.

51 secondary outcomes

Part A: Cmax Following Single Oral Dose of GSK3915393
Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dose
Part A: Cmax Following Single IV Dose of GSK3915393
Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose
Part A: Tmax Following Single Oral Dose of GSK3915393
Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dose
Part A: Tmax Following IV Dose of GSK3915393
Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose
Part A: AUCLST(0-24) Following Single Oral Dose of GSK3915393
Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, and 24 hours post-dose
Part A: AUCLST(0-6) Following Single IV Dose of GSK3915393
Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose
Part A: AUC(0-inf) Following Single Oral Dose of GSK3915393
Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dose
Part A: AUC(0-inf) Following Single IV Dose of GSK3915393
Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose
Part A: t1/2 Following Single IV Dose of GSK3915393 100 mcg IV
Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose
Part A: Clearance (CL) Following Single IV Dose of GSK3915393
Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose
Part A: Volume of Distribution (Vd) Following Single IV Dose of GSK3915393
Time frame: Pre-dose and at 20, 40 minutes, 1, 1 hour 5 minutes, 1 hour 10 minutes, 1 hours 20 minutes, 1 hour 40 minutes, 2, 2.5, 3, 3.5, 4, 5 and 6 hours post-dose
Part A: Absolute Bioavailability (F) Following Single Oral Dose of GSK3915393
Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dose
Part A: Fraction of Drug Escaping Hepatic Metabolism (FH) Following Single Oral Dose of GSK3915393
Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dose
Part A: Product of Fraction of Drug Absorbed and Fraction of Drug Escaping Gut Metabolism (FA*FG) Following Oral Dose of GSK3915393
Time frame: Pre-dose and at 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 12, 14, 24 and 36 hours post-dose
Part A: Number of Participants With All Non-serious AEs and SAEs Following Administration Administration of IV Dose of GSK3915393
Time frame: Up to 21 days
Part A: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Time frame: Up to 21 days
Part A: Number of Participants With Worst Case Chemistry Results-creatinine by PCI Criteria Post-Baseline Relative to Baseline Following Administration Administration of IV Dose of GSK3915393
Time frame: Up to 21 days
Part A: Number of Participants With Worst Case Chemistry Results-urea by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Time frame: Up to 21 days
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline Following Administration of IV Dose of GSK3915393
Time frame: Up to 21 days
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline Following IV Dose of GSK3915393
Time frame: Up to 21 days
Part A: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings Following Administration of IV Dose of GSK3915393
Time frame: Up to 21 days
Part A: Number of Participants With Abnormal Physical Examination Findings Following Administration of IV Dose of GSK3915393
Time frame: Up to 21 days
Part B: Cmax(0-10) Following Dosing of GSK3915393 on Days 1 and 14
Time frame: Days 1 and 14: Pre-dose, 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, and 10 hours post-dose
Part B: Cmax(10-24) Following Repeat Dose 20 mg and 80 mg of GSK3915393
Time frame: Days 1 and 14: 10 hours, 10 hours 20 minutes, 10 hours 40 minutes, 12, 12.5 ,13, 14, 16, and 24 hours post-dose
Part B: Cmax(10-24) Following Dose 160 mg (QD) of GSK3915393
Time frame: Days 1 and 14: 10, 24 hours post-dose
Part B: Tmax(0-10) Following Dosing of GSK3915393 on Days 1 and 14
Time frame: Days 1 and 14: Pre-dose, 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, and 10 hours post-dose
Part B: Tmax(10-24) Following Repeat Dose 20 mg BID and 80 mg BID of GSK3915393
Time frame: Days 1 and 14: 10 hours, 10 hours 20 minutes, 10 hours 40 minutes, 12, 12.5 ,13, 14, 16, and 24 hours post-dose
Part B: Tmax(10-24) Following Dose 160 mg (QD) of GSK3915393
Time frame: Days 1 and 14: 10, 24 hours post-dose
Part B: AUCLST(0-10) Following Dosing of GSK3915393
Time frame: Days 1 and 14: Pre-dose, 20, 40 minutes, 1, 1.5, 2, 3, 4, 6, and 10 hours post-dose
Part B: AUCLST(0-24) Following Repeat Dose 20 mg BID and 80 mg BID of GSK3915393
Time frame: Days 1 and 14: Pre-dose, 20 minutes, 40 minutes, 1, 1.5, 2, 3, 4, 6, 10, 10 hours 20 minutes, 10 hours 40 minutes, 12, 12.5 ,13, 14, 16, and 24 hours post-dose
Part B: AUCLST(0-24) Following Dose of GSK3915393 160 mg (QD)
Time frame: Days 1 and 14: Pre-dose, 20 minutes, 40 minutess, 1, 1.5, 2, 3 ,4, 6, 10 and 24 hours post-dose
Part B: AUC(10-24) Following Repeat Dose 20 mg BID and 80 mg BID of GSK3915393
Time frame: Days 1 and 14: 10 hours, 10 hours 20 minutes, 10 hours 40 minutes, 12, 12.5 ,13, 14, 16, and 24 hours post-dose
Part B: AUC(10-24) Following Repeat Dose of GSK3915393 160 mg (QD)
Time frame: Days 1 and 14: 10 and 24 hours post-dose
Part B: Cmax(0-10) Following First Dosing of GSK3915393 on Days 3, 5 and 7 (for Food-effect Assessment)
Time frame: Days 3, 5 and 7: Pre-dose, 20, 40 minutes, 1, 1.5, 2, 3, 4, 6 and 10 hours post-dose
Part B: Tmax(0-10) Following First Dosing of GSK3915393 on Days 3, 5 and 7 (for Food-effect Assessment)
Time frame: Days 3, 5 and 7: Pre-dose, 20, 40 minutes, 1, 1.5, 2, 3, 4, 6 and 10 hours post-dose
Part B: AUCLST(0-10) Following First Dosing of GSK3915393 on Days 3, 5 and 7 (for Food-effect Assessment)
Time frame: Days 3, 5 and 7: Pre-dose, 20, 40 minutes, 1, 1.5 ,2, 3, 4, 6 and 10 hours post-dose
Part B: Trough Concentration (Ctau) Following Dose of 20 mg BID and 80 mg BID of GSK3915393 on Day 14
Time frame: Day 14: Pre-dose, 20, 40 minutes, 1, 1.5 ,2, 3, 4, 6, 10, 10 hour 20 minutes, 10 hours 40 minutes, 12, 12.5, 13, 14, 16 and 24 hours post-dose
Part B: Trough Concentration (Ctau) Following Dose of 160 mg of GSK3915393 on Day 14
Time frame: Day 14: Pre-dose, 20, 40 minutes, 1, 1.5 ,2, 3, 4, 6, 10, and 24 hours post-dose
Part C: Number of Participants With All Non-serious AEs and SAEs
Time frame: Up to 72 days
Part C: Number of Participants With Treatment-related AEs Following Dose of GSK3915393
Time frame: Up to 72 days

Results and safety

Results posted to the registry on 9 May 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
PartA: Placebo/GSK3915393 60mg/100mcg IV/160mg	3	3
Part A: GSK3915393 15mg/Placebo/100mcg IV/160mg	3	3
Part A: GSK3915393 15mg/60mg/100mcg IV/Placebo	3	3
Part A: GSK3915393 15mg/60mg/100mcg IV/160mg	3	3
Part B: Placebo	0	0
Part B: GSK3915393 20 mg (BID)	0	0
Part B: GSK3915393 80 mg (BID)	0	0
Part B: GSK3915393 160 mg (QD)	0	0
PartC:GSK3915393 100mcg IV/100mcgIV+ITZ/20mg+GFJ/20+WTR/20+ITZ	0	0
Part C:GSK3915393 100mg IV/100mcgIV+ITZ/20mg+WTR/20+GFJ/20+ITZ	0	0

Primary outcome: Part A: Number of Participants With All Non-serious Adverse Events (AEs) and Serious AEs (SAEs) Following Administration of Oral Dose

Time frame: Up to 70 days. Count of participants. Unit: Participants

Measure	Part A: Placebo n = 9	Part A: GSK3915393 15 mg n = 9	Part A: GSK3915393 60 mg n = 9	Part A: GSK3915393 160 mg n = 9
All non-serious AEs	1	2	3	1
SAEs	0	0	0	0

Population analysed: Safety Population comprised of all randomized participants who received at least one dose of study treatment.

Primary outcome: Part A: Number of Participants With Treatment-related AEs Following Administration of Oral Dose

Time frame: Up to 70 days. Count of participants. Unit: Participants

Measure	Part A: Placebo n = 9	Part A: GSK3915393 15 mg n = 9	Part A: GSK3915393 60 mg n = 9	Part A: GSK3915393 160 mg n = 9
Value	0	0	0	0

Population analysed: Safety Population.

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

Time frame: Up to 28 days. Count of participants. Unit: Participants

Measure	Part B: Placebo n = 10	Part B: GSK3915393 20 mg (BID) n = 10	Part B: GSK3915393 80 mg (BID) n = 9	Part B: GSK3915393 160 mg (QD) n = 9
All non-serious AEs	3	5	1	5
SAEs	0	0	0	0

Population analysed: Safety Population.

Primary outcome: Part B: Number of Participants With Treatment-related AEs

Time frame: Up to 28 days. Count of participants. Unit: Participants

Measure	Part B: Placebo n = 10	Part B: GSK3915393 20 mg (BID) n = 10	Part B: GSK3915393 80 mg (BID) n = 9	Part B: GSK3915393 160 mg (QD) n = 9
Value	1	0	0	0

Population analysed: Safety Population.

51 secondary outcomes are reported in the full results.

Adverse events

Time frame: All-cause mortality, all non-serious and SAEs were collected up to Day 70 in Part A, up to Day 28 in Part B and up to Day 72 in Part C. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part A: Placebo	0 of 9 (0%)	1 of 9 (11.1%)	0 of 9
Part A: GSK3915393 15 mg	0 of 9 (0%)	2 of 9 (22.2%)	0 of 9
Part A: GSK3915393 60 mg	0 of 9 (0%)	3 of 9 (33.3%)	0 of 9
Part A: GSK3915393 160 mg	0 of 9 (0%)	1 of 9 (11.1%)	0 of 9
Part A: GSK3915393 100 mcg IV	0 of 12 (0%)	4 of 12 (33.3%)	0 of 12
Part B: Placebo	0 of 10 (0%)	3 of 10 (30%)	0 of 10
Part B: GSK3915393 20 mg (BID)	0 of 10 (0%)	5 of 10 (50%)	0 of 10
Part B: GSK3915393 80 mg (BID)	0 of 9 (0%)	1 of 9 (11.1%)	0 of 9
Part B: GSK3915393 160 mg (QD)	0 of 9 (0%)	5 of 9 (55.6%)	0 of 9
Part C: GSK3915393 100 mcg IV	0 of 12 (0%)	5 of 12 (41.7%)	0 of 12
Part C: GSK3915393 100 mcg+ITZ	0 of 11 (0%)	2 of 11 (18.2%)	0 of 11
Part C: GSK3915393 20 mg+ Water	0 of 11 (0%)	3 of 11 (27.3%)	0 of 11
Part C: GSK3915393 20 mg+ GFJ	0 of 12 (0%)	2 of 12 (16.7%)	0 of 12
Part C: GSK3915393 20 mg+ ITZ	0 of 10 (0%)	2 of 10 (20%)	0 of 10

Limitations and caveats (from the sponsor): Cardiac telemetry traces were examined after the study had completed. For all the participants with an adverse event of ventricular tachycardia reported following repeat dosing of 160 mg QD (part B), the tracings revealed narrow QRS complex beats that "march" through the presumed wide complex beats at a fixed rate, identical to the heart rate prior to and immediately following the event. These findings support a diagnosis of artifact and are not consistent with ventricular tachycardia.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.

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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 GSK3915393 Capsules, GSK3915393 Solution for Infusion and Itraconazole in people with Celiac Disease and Coeliac Disease, run by GlaxoSmithKline at 1 site in United Kingdom.

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 6 inclusion and 30 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 May 2023. 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 United Kingdom. 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 May 2023). 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 All Non-serious Adverse Events (AEs) and Serious AEs (SAEs) Following Administration of Oral Dose (time frame: Up to 70 days). The study lists 33 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 NCT04604795.

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 May 2023.