Infection, Human Immunodeficiency VirusPhase 1NCT03231943

GSK3640254 First Time in Human (FTIH) Study in Healthy Volunteers

A Phase 1 study testing GSK3640254 in people with Infection, Human Immunodeficiency Virus and HIV Infections, run by ViiV Healthcare 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

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Infection, Human Immunodeficiency Virus, HIV Infections
What is being tested?: GSK3640254
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 78 participants
Where: 1 siteUnited Kingdom
Study dates: 19 Sep 2017to 9 Sep 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

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

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Subjects must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
Subjects who are overtly healthy as determined by medical evaluation including medical history and psychiatric history, physical examination, laboratory tests, and 24 hour Holter monitoring.
Body weight >=50.0 kilogram (kg) (110 pounds) for men and 45.0kg (99 pounds) for women and body mass index (BMI) within the range 18.5-32.0 kg per meter square (kg/m^2) (inclusive).
Male or female subjects. A male subject must agree to use contraception during the treatment period and for at least 14 weeks following the last dose, corresponding to the time needed to eliminate study treatment for potential genotoxic and teratogenic study treatments plus an additional 90 days (spermatogenesis cycle). In addition, male subjects must refrain from donating sperm during this period. A female subject is eligible to participate if she is not a woman of childbearing potential (WOCBP).
Capable of giving signed informed consent.

Who cannot join

Alanine transaminase (ALT) >1.5 into upper limit of normal (ULN).
Bilirubin >1.5 into ULN (isolated bilirubin >1.5 into ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities.
Pre-existing clinically relevant, in the opinion of the primary investigator (PI), gastro-intestinal pathology or diagnosis - example irritable bowel syndrome, inflammatory bowel disease, and/or significant Baseline signs and symptoms.
Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
Any known or suspected pre-existing psychiatric condition.

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Any other clinical condition (including but not limited to active substance use) or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study; unable to comply with dosing requirements; or unable to comply with study visits; or a condition that could affect the absorption, distribution, metabolism or excretion of the drug.
Unable to refrain from the use of prescription or non-prescription drugs (with the exception of paracetamol), including vitamins, herbal and dietary supplements (including 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 and for the duration of the study, unless in the opinion of the Investigator and ViiV Healthcare Sponsor and medical monitor, the medication will not interfere with the study medications, procedures, or compromise subject safety.
Unwillingness to abstain from ingestion of any food or drink containing grapefruit and grapefruit juice, Seville oranges, blood oranges, or pomelos within 7 days prior to the first dose of study treatment(s) or until the end of the study.
Participation in another concurrent clinical study or prior clinical study (with the exception of imaging trials) 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).
Where participation in the study would result in donation of blood or blood products in excess of 500 milliliter (mL) within 56 days.
Presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study treatment.
A positive pre-study drug/alcohol screen.
A positive test for a diagnostic HIV-1 polymerase chain reaction (PCR).
Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
Exclusion criteria for screening ECG: Heart rate <45 or >100 beats per minute (bpm) for males and <50 or >100 bpm for females; PR interval <120 or >220 millisecond (msec); QRS duration <70 or >120 msec; the Fridericia's QT correction formula (QTcF) interval >450 msec.
Evidence of previous myocardial infarction (does not include ST segment changes associated with re-polarization).
Any conduction abnormality (including but not specific to left or right complete bundle branch block, Atrioventricular block [2nd degree or higher], Wolff-Parkinson-White [WPW] syndrome).
Sinus Pauses >3 seconds.
Any significant arrhythmia which, in the opinion of the Investigator or GlaxoSmithKline/ViiV medical monitor, will interfere with the safety for the individual subject.
Non-sustained or sustained ventricular tachycardia (3 consecutive ventricular ectopic beats).
History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 units. One unit is equivalent to 8 gram of alcohol: a half-pint approximately 240 mL of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
Regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or medical monitor, contraindicates their participation.

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

GSK Investigational Site
Cambridge, CB2 2GG

Other trials in United Kingdom

About this study

Official title: A Double-Blind (Sponsor Unblinded), Randomized, Placebo-Controlled, Single and Repeated Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK3640254 in Healthy Participants

Human immuno deficiency virus 1 (HIV-1) infections continues to be a serious health threat throughout the world and development of medicines with new mechanism of action have an important role to play. GSK3640254 is a maturation inhibitor (MI) and can be effective in HIV-1 treatment. This randomized, 2-part, single and repeat increasing dose study will collect information on safety, tolerability and drug levels in the body of in healthy subjects for GSK3640254. The information collected in this study will help in further clinical development of GSK3640254, including a Phase IIA Proof of Concept (PoC) study in HIV-infected subjects. Approximately 16 healthy subjects will be randomized to receive single oral dose of GSK3640254 and placebo in Part 1 and approximately 56 healthy subjects will be randomized to receive repeat oral dose of GSK3640254 or placebo in Part 2. All doses will be given immediately after a moderate fat meal. Maximum duration of study participation will be approximately 12 weeks.

Conditions: Infection, Human Immunodeficiency Virus, HIV Infections
Being tested: GSK3640254, Placebo
Keywords: FTIH, Healthy, Tolerability, Dose-escalation, HIV-1, Safety, PK, GSK3640254, Maturation inhibitor
Medical subject headings: Infections, Acquired Immunodeficiency Syndrome, HIV Infections

What participants receive

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

GSK3640254Drug
GSK3640254 is a capsule available in 1 milligram (mg), 10 mg and 100 mg dosing strength. GSK3640254 capsule will be given via oral route during each dosing day with approximately 240 mL of water.
PlaceboDrug
Placebo capsule matching to the study treatment will be given via oral route during each dosing day with approximately 240 mL of water.

Study groups in NCT03231943
Study group	Role	What they receive
Subjects in cohort 1-2: Part 1	Experimental	Eligible subjects will participate in cohort 1 or 2 and each of these two cohorts will contain up to four escalating doses of GSK3640254. In each cohort, 6 subjects will be randomized to receive single oral dose of GSK3640254 and 2 subjects will be randomized to receive placebo. Hence, each subject in cohort 1 and 2 will receive up to 3 escalating doses of GSK3640254 and one placebo in crossover manner. Receives: Drug: GSK3640254; Drug: Placebo
GSK3640254 receivers (cohort 3-6 and expansion): Part 2	Experimental	Eligible subjects will participate in one of the 4 cohorts (3,4,5,6). In each cohort, 6 subjects will be randomized to receive a once-daily oral dose of GSK3640254 for 14 days. After the safety data of cohort 3-6 is available, 18 eligible subjects will be randomized to receive once daily oral dose of GSK3640254 for 14 days in expansion cohort. Receives: Drug: GSK3640254
Subjects receiving placebo (cohort 3-6): Part 2	Placebo comparator	Eligible subjects will participate in one of the 4 cohorts (3,4,5,6). In each cohort, 2 subjects will be randomized to receive a once-daily oral dose of placebo for 14 days. After the safety data of cohort 3-6 is available, 6 eligible subjects will be randomized to receive once daily oral dose of placebo for 14 days in expansion cohort. Receives: Drug: Placebo

What is being measured

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

Part 1:Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE. Results are presented treatment wise.
Measured: Up to Day 15
Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets.
Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Part 1: Change From Baseline in Hematology Parameters: Erythrocytes.
Blood samples were collected to analyze the hematology parameters: erythrocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.Results are presented treatment wise.
Measured: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Part 1: Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Volume (Erythrocyte MCV).
Blood samples were collected to analyze the hematology parameters: erythrocyte MCV. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin (Erythrocyte MCH)
Blood samples were collected to analyze the hematology parameter: Erythrocyte MCH. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.Results are presented treatment wise.
Measured: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Part 1: Change From Baseline in Hematology Parameter: Hematocrit
Blood samples were collected to analyze the hematology parameter: hematocrit. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Part 1: Change From Baseline in Hematology Parameter: Percentage of Reticulocytes
Blood samples were collected to analyze the hematology parameter: percentage of reticulocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Part 1: Change From Baseline in Hematology Parameter: Hemoglobin (Hb)
Blood samples were collected to analyze the hematology parameter: Hb. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Part 1: Change From Baseline in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP)
Blood samples were collected to analyze the chemistry parameter: ALT, AST, and ALP. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Part 1: Change From Baseline in Clinical Chemistry Parameters : Bicarbonate, Calcium, Chloride, Magnesium, Phosphate, Potassium, Sodium, Urea
Blood samples were collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, urea. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Part 1: Change From Baseline in Cholesterol, Glucose, High Density Lipoprotein (HDL) Cholesterol, Low Density Cholesterol (LDL) Cholesterol, Triglycerides
Blood samples were collected to analyze the chemistry parameter: cholesterol, glucose, HDL cholesterol, LDL cholesterol, triglycerides. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -2) and Day 1 (96 hours) and Follow up (Day 15)
Part 1: Change From Baseline in Chemistry Parameter: Glucose
Blood samples were collected to analyze the chemistry parameter: glucose . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -2) and Day 1 (96 hours) and Follow up (Day 15)
Part 1: Change From Baseline in Clinical Chemistry Parameter: Bilirubin, Creatinine, Direct Bilirubin
Blood samples were collected to analyze the chemistry parameter: bilirubin, creatinine, direct bilirubin . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Part 1: Change From Baseline in Clinical Chemistry Parameter: Protein
Blood samples were collected to analyze the chemistry parameter: Protein. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Part 1: Number of Participants With Abnormal Urinalysis
Urine samples were collected at given time points to analyze the abnormal findings for potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.
Measured: Up to Day 15
Part 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
SBP and DBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -1), 1,2,4.5,6,12,24,48,72,96 hours post dose and Follow up (Day 15)
Part 1: Change From Baseline in Vital Signs: Pulse Rate
Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -1), 1,2,4.5,6,12,24,48,72,96 hours post dose and Follow up (Day 15)
Part 1: Change From Baseline in Vital Signs: Temperature
Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -1), 1,2,4.5,6,12,24,48,72,96 hours post dose and Follow up (Day 15)
Part 1: Change From Baseline in Vital Sign: Respiratory Rate
Respiratory rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -1), 1,2,4.5,6,12,24,48,72,96 hours post dose and Follow up (Day 15)
Part 1: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
12-lead ECGs were measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS).
Measured: Baseline (Day 1 predose), 1,2,4,6,12,24,48,72,96 hours post dose and Follow up (Day 15)
Part 2: Number of Participants AEs and SAEs
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE. Results are presented treatment wise.
Measured: Up to Day 28
Part 2: Change From Baseline in Abnormal Hematology Findings: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets.
Blood samples were collected at indicated time points to analyze the hematology parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -2), Pre dose on Days 2,4,6,8,10,12,14 Day 14 : 48 and 96 hours post dose, Follow up (Day 28)
Part 2: Change From Baseline in Hematology Parameter: Erythrocytes
Blood samples were collected at indicated time points to analyze the hematology parameters: Erythrocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -2), Pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)
Part 2: Change From Baseline in Hematology Parameter: Erythrocytes MCV
Blood samples were collected at indicated time points to analyze the hematology parameters: Erythrocyte MCV. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)
Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin (Erythrocyte MCH)
Blood samples were collected at indicated time points to analyze the hematology parameter: Erythrocyte MCH. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)
Part 2: Change From Baseline in Hematology Parameter: Hematocrit
Blood samples were collected at indicated time points to analyze the hematology parameter: hematocrit. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)
Part 2: Change From Baseline in Hematology Parameter: Percentage of Reticulocytes
Blood samples were collected to analyze the hematology parameter: percentage of reticulocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)
Part 2: Change From Baseline in Hematology Parameter: Hb
Blood samples were collected at indicated time points to analyze the hematology parameter: Hb. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)
Part 2: Change From Baseline in Chemistry Parameter: ALT, AST,ALP
Blood samples were collected to analyze the chemistry parameter: ALT, AST,ALP. Day -2was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day14: 48 and 96 hours post dose, Follow up (Day 28)
Part 1: Change From Baseline in Bicarbonate, Calcium, Chloride, Cholesterol, Magnesium, Phosphate, Potassium, Sodium, Urea
Blood samples were collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, urea. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)
Part 2: Change From Baseline in Cholesterol, HDL Cholesterol, LDL Cholesterol, Triglycerides
Blood samples were collected at indicated time points to analyze the chemistry parameter: cholesterol, HDL cholesterol, LDL cholesterol, triglycerides. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -2), Day 8 (pre dose), Day 14 (48 hours) post dose and Follow up (Day 28)
Part 2: Change From Baseline in Chemistry Parameter: Glucose
Blood samples were collected at indicated time points to analyze the chemistry parameter: glucose . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -2), Day 8 (predose), Day 14 (48 hours) post dose and Follow up (Day 28)
Part 2: Change From Baseline in Chemistry Parameter: Bilirubin, Creatinine, Direct Bilirubin
Blood samples were collected to analyze the chemistry parameter: bilirubin, creatinine, direct bilirubin . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)
Part 2: Change From Baseline in Chemistry Parameter: Protein
Blood samples were collected to analyze the chemistry parameter: Protein. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)
Part 2: Number of Participants With Abnormal Urinalysis
Urine samples were collected analyze the abnormal findings for potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.
Measured: Up to Day 28
Part 2: Change From Baseline in Vital Signs: SBP and DBP
SBP and DBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -1), pre dose on Days 1,2,4,6,8,10,12,and 14 (pre dose and 72 hours) and Follow up (Day 28)
Part 2: Change From Baseline in Vital Sign: Pulse Rate
Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Measured: Baseline (Day -1), pre dose on Days 1,2,4,6,8,10,12, and 14 (pre dose and 72 hours) and Follow up (Day 28)
Part 2: Change From Baseline in Vital Sign: Temperature
Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -1), pre dose on Days 1,2,4,6,8,10,12, and 14 (pre dose and 72 hours) and Follow up (Day 28)
Part 2: Change From Baseline in Vital Sign: Respiratory Rate
Respiratory rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Measured: Baseline (Day -1), pre dose on Days 1,2,4,6,8,10,12 and 14 (pre dose and 72 hours) and Follow up (Day 28)
Part 2: Number of Participants With Abnormal ECG Findings
12-lead ECG were obtained at given time points. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS).Results are presented treatment wise.
Measured: Day 1 (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5, 5.5, 6, 8, 12, 24 hours); Pre-dose on Days 3, 4, 6, 8, 10, 12; Day 14: Pre-dose, 1, 2, 4.5, 5, 6, 12, 24, 48, 72 and 96 hours post-dose and follow up (Day 28)

Secondary outcomes (28)

Part 1: Area Under the Plasma Concentration Time Curve (AUC) From Zero to 24 Hour (AUC[0-24]) of GSK3640254
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12,24 hours post-dose
Part 1: AUC From Zero to Time of Last Sample Taken (AUC[0-Tlast]) of GSK3640254
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose
Part 1: AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3640254
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose
Part 1: Apparent Terminal Phase Half-life (T1/2) of GSK3640254
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Most of the concentrations were below limit of quantification (BLQ) at this dose group this value and/ or %AUC extrapolated was >20% for all participants so this value should be used with caution. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose
Part 1: Apparent Oral Clearance (CL/F) of GSK3640254
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose
Part 1: Maximum Observed Concentration (Cmax), Concentration of GSK3640254 at 24 Hours (C24) and Last Quantifiable Concentration (Clast) of GSK3640254
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin.
Measured: Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose
Part 1: Time of Occurrence of Cmax (Tmax), Lag Time (Tlag), and Time to Reach Clast (Tlast) of GSK3640254
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose
Part 2: AUC(0-24) of GSK3640254: Day 1
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12 and 24 hours post-dose on Day 1
Part 2: Cmax, C24 of GSK3640254 on Day 1
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12 hours post-dose on Day 1
Part 2: Tmax, Tlag of GSK3640254 on Day 1
Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin.
Measured: Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12 hours post-dose on Day 1
Part 2: Tmax GSK3640254 on Day 14
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose
Part 2: Cmax of GSK3640254 on Day 14
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose
Part 2: AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]): Day 14
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours after Day 14 dose
Part 2: Plasma Trough Concentration (Ctau) of GSK3640254: Day 14
Blood samples were collected at indicated timepoints and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. The PK parameter name for Part 2 (Day 14) trough concentration was changed using Phoenix WinNonlin 8 from Ct to Ctrough. Day 15 Ctrough values were used for dose proportionality and time to steady-state assessments.
Measured: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose
Part 2: T1/2 of GSK3640254: Day 14
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose
Part 2: CL/F of GSK3640254: Day 14
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin.
Measured: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose
Part 1: Dose Proportionality (AUC[0-inf]) Following Single Dose of GSK3640254 on Day 1
Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post dose
Part 1: Dose Proportionality (AUC0-24) Following Single Dose of GSK3640254 on Day 1
Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours post dose
Part 1: Dose Proportionality for Cmax Following Single Dose of GSK3640254 on Day 1
Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post dose
Part 2: Dose Proportionality (AUC0-tau) Following Repeated Dose of GSK3640254 on Day 14
Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose
Part 2: Dose Proportionality (Ctrough) Following Repeated Dose of GSK3640254 on Day 14
Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose
Part 2: Dose Proportionality (Cmax) Following Repeated Dose of GSK3640254 on Day 14
Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose
Part 2: Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]) From Day 1 to Day 14
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. The accumulation ratio was estimated by calculating the ratio of the geometric least squares (GLS) means of PK parameters between Day 14 and Day 1, and the corresponding 90% CI for each dose. Ratio and 90% confidence interval is presented. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose
Part 2: Accumulation Ratio of Cmax (R [CMAX]) From Day 1 to Day 14
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. The accumulation ratio was estimated by calculating the ratio of the geometric least squares (GLS) means of PK parameters between Day 14 and Day 1, and the corresponding 90% CI for each dose. Ratio and 90% confidence interval is presented. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose
Part 2: Accumulation Ratio of C(Tau) (R[CTAU]) From Day 2 to Day 15
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. The accumulation ratio was estimated by calculating the ratio of the geometric least squares (GLS) means of PK parameters between Day 15 and Day 2, and the corresponding 90% CI for each dose. Ratio and 90% confidence interval is presented. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 15 dose
Part 2: Pre-dose Concentration of GSK3640254 on Day 2 to Day 14
Blood samples were collected at indicated time points and PK analysis was performed. PK parameters were determined by non-compartmental methods with Phoenix WinNonlin. results are presented treatment wise.
Measured: Pre-dose on Days 2,3,4,6,8,10,12 and 14
Part 2: Dose Proportionality (Cmax) Following Repeated Dose of GSK3640254 at Day 1
Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post dose
Part 2: Dose Proportionality (AUC0-24) Following Repeated Dose of GSK3640254 at Day 1
Blood samples were collected at indicated time points and PK analysis was performed. Dose proportionality was assessed using the power model. Results are presented treatment wise.
Measured: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post dose

Timeline

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

19 Sep 20179 Sep 2018

First posted27 Jul 2017
Study start19 Sep 2017
Primary completion9 Sep 2018
Study completion9 Sep 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Infection, Human Immunodeficiency VirusStudies of the same condition, open and under way.
More trials run by ViiV HealthcareThe 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: Sequential
Model description: This is a dose-escalation study and dose will be escalated based on the safety data of the initial dose.
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 78 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03231943
Sponsor's protocol ID: 207187
Other IDs: 2017-001367-21, 2017
Status last verified: May 2021
First submitted: 24 Jul 2017
Last updated: 10 Jun 2021
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 is available via the Clinical Study Data Request site.

Publications

Joshi SR, Fernando D, Igwe S, McKenzie L, Krishnatry AS, Halliday F, Zhan J, Greene TJ, Xu J, Ferron-Brady G, Lataillade M, Min S. Phase I evaluation of the safety, tolerability, and pharmacokinetics of GSK3640254, a next-generation HIV-1 maturation inhibitor. Pharmacol Res Perspect. 2020 Dec;8(6):e00671. doi: 10.1002/prp2.671.
PubMed 33200887

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The sponsor has not listed a contact. The official record may have more details.

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

Questions to ask the study team

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

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Study at a glance

From the registry record, last updated by the sponsor on 10 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Double-Blind (Sponsor Unblinded), Randomized, Placebo-Controlled, Single and Repeated Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK3640254 in Healthy Participants
ClinicalTrials.gov ID: NCT03231943
Acronym / sponsor ID: 207187
Conditions: Infection, Human Immunodeficiency Virus, HIV Infections
Keywords: FTIH, Healthy, Tolerability, Dose-escalation, HIV-1, Safety, PK, GSK3640254
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 78 participants (actual)
Lead sponsor: ViiV HealthcareIndustry (pharma, biotech, devices)
Collaborators: GlaxoSmithKline
Study start: 19 Sep 2017 (actual)
Primary completion: 9 Sep 2018 (actual)
Study completion: 9 Sep 2018 (actual)
First posted: 27 Jul 2017 (actual)
Results: Posted 18 Oct 2019

Clinical summary

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Sequential
Masking: Double blind (participant, investigator)
Number of arms: 3
Model description: This is a dose-escalation study and dose will be escalated based on the safety data of the initial dose.

Arm	Type	Receives
Subjects in cohort 1-2: Part 1	Experimental	Drug: GSK3640254, Drug: PlaceboEligible subjects will participate in cohort 1 or 2 and each of these two cohorts will contain up to four escalating doses of GSK3640254. In each cohort, 6 subjects will be randomized to receive single oral dose of GSK3640254 and 2 subjects will be randomized to receive placebo. Hence, each subject in cohort 1 and 2 will receive up to 3 escalating doses of GSK3640254 and one placebo in crossover manner.
GSK3640254 receivers (cohort 3-6 and expansion): Part 2	Experimental	Drug: GSK3640254Eligible subjects will participate in one of the 4 cohorts (3,4,5,6). In each cohort, 6 subjects will be randomized to receive a once-daily oral dose of GSK3640254 for 14 days. After the safety data of cohort 3-6 is available, 18 eligible subjects will be randomized to receive once daily oral dose of GSK3640254 for 14 days in expansion cohort.
Subjects receiving placebo (cohort 3-6): Part 2	Placebo comparator	Drug: PlaceboEligible subjects will participate in one of the 4 cohorts (3,4,5,6). In each cohort, 2 subjects will be randomized to receive a once-daily oral dose of placebo for 14 days. After the safety data of cohort 3-6 is available, 6 eligible subjects will be randomized to receive once daily oral dose of placebo for 14 days in expansion cohort.

Who may qualify

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

Key inclusion criteria (5 listed)

Subjects must be 18 to 55 years of age inclusive, at the time of signing the informed consent.
Subjects who are overtly healthy as determined by medical evaluation including medical history and psychiatric history, physical examination, laboratory tests, and 24 hour Holter monitoring.
Body weight >=50.0 kilogram (kg) (110 pounds) for men and 45.0kg (99 pounds) for women and body mass index (BMI) within the range 18.5-32.0 kg per meter square (kg/m^2) (inclusive).
Male or female subjects. A male subject must agree to use contraception during the treatment period and for at least 14 weeks following the last dose, corresponding to the time needed to eliminate study treatment for potential genotoxic and teratogenic study treatments plus an additional 90 days (spermatogenesis cycle). In addition, male subjects must refrain from donating sperm during this period. A female subject is eligible to participate if she is not a woman of childbearing potential (WOCBP).
Capable of giving signed informed consent.

Key exclusion criteria (24 listed)

Alanine transaminase (ALT) >1.5 into upper limit of normal (ULN).
Bilirubin >1.5 into ULN (isolated bilirubin >1.5 into ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities.
Pre-existing clinically relevant, in the opinion of the primary investigator (PI), gastro-intestinal pathology or diagnosis - example irritable bowel syndrome, inflammatory bowel disease, and/or significant Baseline signs and symptoms.
Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.

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
GSK3640254GSK3640254 is a capsule available in 1 milligram (mg), 10 mg and 100 mg dosing strength. GSK3640254 capsule will be given via oral route during each dosing day with approximately 240 mL of water.	Drug	GSK3640254 receivers (cohort 3-6 and expansion): Part 2, Subjects in cohort 1-2: Part 1
PlaceboPlacebo capsule matching to the study treatment will be given via oral route during each dosing day with approximately 240 mL of water.	Drug	Subjects in cohort 1-2: Part 1, Subjects receiving placebo (cohort 3-6): Part 2

Primary outcome

Part 1:Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
Time frame: Up to Day 15
An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE. Results are presented treatment wise.
Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets.
Time frame: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Hematology Parameters: Erythrocytes.
Time frame: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Blood samples were collected to analyze the hematology parameters: erythrocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.Results are presented treatment wise.
Part 1: Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Volume (Erythrocyte MCV).
Time frame: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Blood samples were collected to analyze the hematology parameters: erythrocyte MCV. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part 1: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin (Erythrocyte MCH)
Time frame: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Blood samples were collected to analyze the hematology parameter: Erythrocyte MCH. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.Results are presented treatment wise.
Part 1: Change From Baseline in Hematology Parameter: Hematocrit
Time frame: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Blood samples were collected to analyze the hematology parameter: hematocrit. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Hematology Parameter: Percentage of Reticulocytes
Time frame: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Blood samples were collected to analyze the hematology parameter: percentage of reticulocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Hematology Parameter: Hemoglobin (Hb)
Time frame: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Blood samples were collected to analyze the hematology parameter: Hb. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphate (ALP)
Time frame: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Blood samples were collected to analyze the chemistry parameter: ALT, AST, and ALP. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Clinical Chemistry Parameters : Bicarbonate, Calcium, Chloride, Magnesium, Phosphate, Potassium, Sodium, Urea
Time frame: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Blood samples were collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, urea. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Cholesterol, Glucose, High Density Lipoprotein (HDL) Cholesterol, Low Density Cholesterol (LDL) Cholesterol, Triglycerides
Time frame: Baseline (Day -2) and Day 1 (96 hours) and Follow up (Day 15)
Blood samples were collected to analyze the chemistry parameter: cholesterol, glucose, HDL cholesterol, LDL cholesterol, triglycerides. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Chemistry Parameter: Glucose
Time frame: Baseline (Day -2) and Day 1 (96 hours) and Follow up (Day 15)
Blood samples were collected to analyze the chemistry parameter: glucose . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Clinical Chemistry Parameter: Bilirubin, Creatinine, Direct Bilirubin
Time frame: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Blood samples were collected to analyze the chemistry parameter: bilirubin, creatinine, direct bilirubin . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Clinical Chemistry Parameter: Protein
Time frame: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15)
Blood samples were collected to analyze the chemistry parameter: Protein. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part 1: Number of Participants With Abnormal Urinalysis
Time frame: Up to Day 15
Urine samples were collected at given time points to analyze the abnormal findings for potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.
Part 1: Change From Baseline in Vital Signs: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Time frame: Baseline (Day -1), 1,2,4.5,6,12,24,48,72,96 hours post dose and Follow up (Day 15)
SBP and DBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Vital Signs: Pulse Rate
Time frame: Baseline (Day -1), 1,2,4.5,6,12,24,48,72,96 hours post dose and Follow up (Day 15)
Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Vital Signs: Temperature
Time frame: Baseline (Day -1), 1,2,4.5,6,12,24,48,72,96 hours post dose and Follow up (Day 15)
Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Vital Sign: Respiratory Rate
Time frame: Baseline (Day -1), 1,2,4.5,6,12,24,48,72,96 hours post dose and Follow up (Day 15)
Respiratory rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Time frame: Baseline (Day 1 predose), 1,2,4,6,12,24,48,72,96 hours post dose and Follow up (Day 15)
12-lead ECGs were measured in a semi-supine position using an automated ECG machine after approximately 5 minutes of rest for the participant. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS).
Part 2: Number of Participants AEs and SAEs
Time frame: Up to Day 28
An AE is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE. Results are presented treatment wise.
Part 2: Change From Baseline in Abnormal Hematology Findings: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets.
Time frame: Baseline (Day -2), Pre dose on Days 2,4,6,8,10,12,14 Day 14 : 48 and 96 hours post dose, Follow up (Day 28)
Blood samples were collected at indicated time points to analyze the hematology parameters: basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 2: Change From Baseline in Hematology Parameter: Erythrocytes
Time frame: Baseline (Day -2), Pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)
Blood samples were collected at indicated time points to analyze the hematology parameters: Erythrocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part 2: Change From Baseline in Hematology Parameter: Erythrocytes MCV
Time frame: Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)
Blood samples were collected at indicated time points to analyze the hematology parameters: Erythrocyte MCV. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part 2: Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin (Erythrocyte MCH)
Time frame: Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)
Blood samples were collected at indicated time points to analyze the hematology parameter: Erythrocyte MCH. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part 2: Change From Baseline in Hematology Parameter: Hematocrit
Time frame: Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)
Blood samples were collected at indicated time points to analyze the hematology parameter: hematocrit. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 2: Change From Baseline in Hematology Parameter: Percentage of Reticulocytes
Time frame: Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)
Blood samples were collected to analyze the hematology parameter: percentage of reticulocytes. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 2: Change From Baseline in Hematology Parameter: Hb
Time frame: Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)
Blood samples were collected at indicated time points to analyze the hematology parameter: Hb. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part 2: Change From Baseline in Chemistry Parameter: ALT, AST,ALP
Time frame: Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day14: 48 and 96 hours post dose, Follow up (Day 28)
Blood samples were collected to analyze the chemistry parameter: ALT, AST,ALP. Day -2was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 1: Change From Baseline in Bicarbonate, Calcium, Chloride, Cholesterol, Magnesium, Phosphate, Potassium, Sodium, Urea
Time frame: Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)
Blood samples were collected to analyze the chemistry parameter: bicarbonate, calcium, chloride, magnesium, phosphate, potassium, sodium, urea. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part 2: Change From Baseline in Cholesterol, HDL Cholesterol, LDL Cholesterol, Triglycerides
Time frame: Baseline (Day -2), Day 8 (pre dose), Day 14 (48 hours) post dose and Follow up (Day 28)
Blood samples were collected at indicated time points to analyze the chemistry parameter: cholesterol, HDL cholesterol, LDL cholesterol, triglycerides. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 2: Change From Baseline in Chemistry Parameter: Glucose
Time frame: Baseline (Day -2), Day 8 (predose), Day 14 (48 hours) post dose and Follow up (Day 28)
Blood samples were collected at indicated time points to analyze the chemistry parameter: glucose . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 2: Change From Baseline in Chemistry Parameter: Bilirubin, Creatinine, Direct Bilirubin
Time frame: Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)
Blood samples were collected to analyze the chemistry parameter: bilirubin, creatinine, direct bilirubin . Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 2: Change From Baseline in Chemistry Parameter: Protein
Time frame: Baseline (Day -2), pre dose on Days 2,4,6,8,10,12,14 Day 14: 48 and 96 hours post dose, Follow up (Day 28)
Blood samples were collected to analyze the chemistry parameter: Protein. Day -2 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 2: Number of Participants With Abnormal Urinalysis
Time frame: Up to Day 28
Urine samples were collected analyze the abnormal findings for potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by dipstick.
Part 2: Change From Baseline in Vital Signs: SBP and DBP
Time frame: Baseline (Day -1), pre dose on Days 1,2,4,6,8,10,12,and 14 (pre dose and 72 hours) and Follow up (Day 28)
SBP and DBP were measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 2: Change From Baseline in Vital Sign: Pulse Rate
Time frame: Baseline (Day -1), pre dose on Days 1,2,4,6,8,10,12, and 14 (pre dose and 72 hours) and Follow up (Day 28)
Pulse rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value.
Part 2: Change From Baseline in Vital Sign: Temperature
Time frame: Baseline (Day -1), pre dose on Days 1,2,4,6,8,10,12, and 14 (pre dose and 72 hours) and Follow up (Day 28)
Temperature was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 2: Change From Baseline in Vital Sign: Respiratory Rate
Time frame: Baseline (Day -1), pre dose on Days 1,2,4,6,8,10,12 and 14 (pre dose and 72 hours) and Follow up (Day 28)
Respiratory rate was measured in semi-supine position after 5 minutes rest for the participants at indicated time points. Day -1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the specified time point value. Results are presented treatment wise.
Part 2: Number of Participants With Abnormal ECG Findings
Time frame: Day 1 (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5, 5.5, 6, 8, 12, 24 hours); Pre-dose on Days 3, 4, 6, 8, 10, 12; Day 14: Pre-dose, 1, 2, 4.5, 5, 6, 12, 24, 48, 72 and 96 hours post-dose and follow up (Day 28)
12-lead ECG were obtained at given time points. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS).Results are presented treatment wise.

28 secondary outcomes

Part 1: Area Under the Plasma Concentration Time Curve (AUC) From Zero to 24 Hour (AUC[0-24]) of GSK3640254
Time frame: Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12,24 hours post-dose
Part 1: AUC From Zero to Time of Last Sample Taken (AUC[0-Tlast]) of GSK3640254
Time frame: Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose
Part 1: AUC From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-inf]) of GSK3640254
Time frame: Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose
Part 1: Apparent Terminal Phase Half-life (T1/2) of GSK3640254
Time frame: Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose
Part 1: Apparent Oral Clearance (CL/F) of GSK3640254
Time frame: Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose
Part 1: Maximum Observed Concentration (Cmax), Concentration of GSK3640254 at 24 Hours (C24) and Last Quantifiable Concentration (Clast) of GSK3640254
Time frame: Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose
Part 1: Time of Occurrence of Cmax (Tmax), Lag Time (Tlag), and Time to Reach Clast (Tlast) of GSK3640254
Time frame: Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12, 24, 48, 72 and 96 hours post-dose
Part 2: AUC(0-24) of GSK3640254: Day 1
Time frame: Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12 and 24 hours post-dose on Day 1
Part 2: Cmax, C24 of GSK3640254 on Day 1
Time frame: Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12 hours post-dose on Day 1
Part 2: Tmax, Tlag of GSK3640254 on Day 1
Time frame: Pre-dose and 0.5,1,1.5,2,2.5,3,3.5,4,4.5,5,6,8,12 hours post-dose on Day 1
Part 2: Tmax GSK3640254 on Day 14
Time frame: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose
Part 2: Cmax of GSK3640254 on Day 14
Time frame: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose
Part 2: AUC From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]): Day 14
Time frame: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours after Day 14 dose
Part 2: Plasma Trough Concentration (Ctau) of GSK3640254: Day 14
Time frame: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose
Part 2: T1/2 of GSK3640254: Day 14
Time frame: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose
Part 2: CL/F of GSK3640254: Day 14
Time frame: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose
Part 1: Dose Proportionality (AUC[0-inf]) Following Single Dose of GSK3640254 on Day 1
Time frame: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post dose
Part 1: Dose Proportionality (AUC0-24) Following Single Dose of GSK3640254 on Day 1
Time frame: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24 hours post dose
Part 1: Dose Proportionality for Cmax Following Single Dose of GSK3640254 on Day 1
Time frame: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post dose
Part 2: Dose Proportionality (AUC0-tau) Following Repeated Dose of GSK3640254 on Day 14
Time frame: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose
Part 2: Dose Proportionality (Ctrough) Following Repeated Dose of GSK3640254 on Day 14
Time frame: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose
Part 2: Dose Proportionality (Cmax) Following Repeated Dose of GSK3640254 on Day 14
Time frame: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose
Part 2: Accumulation Ratio of AUC(0-tau) (R [AUC{0-TAU}]) From Day 1 to Day 14
Time frame: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose
Part 2: Accumulation Ratio of Cmax (R [CMAX]) From Day 1 to Day 14
Time frame: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 14 dose
Part 2: Accumulation Ratio of C(Tau) (R[CTAU]) From Day 2 to Day 15
Time frame: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours after Day 15 dose
Part 2: Pre-dose Concentration of GSK3640254 on Day 2 to Day 14
Time frame: Pre-dose on Days 2,3,4,6,8,10,12 and 14
Part 2: Dose Proportionality (Cmax) Following Repeated Dose of GSK3640254 at Day 1
Time frame: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post dose
Part 2: Dose Proportionality (AUC0-24) Following Repeated Dose of GSK3640254 at Day 1
Time frame: Pre-dose and 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72 and 96 hours post dose

Results and safety

Results posted to the registry on 18 Oct 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1: Placebo Followed by GSK3640254 10mg/100mg/400mg	2	2
Part 1: GSK3640254 1mg/ Placebo /100 mg/400 mg	2	2
Part 1: GSK3640254 1mg/10mg/Placebo /400mg	2	2
Part 1: GSK3640254 1mg/10mg/100mg/Placebo	2	2
Part 1: Placebo/ GSK3640254 30mg/200 mg/700 mg	2	2
Part1:GSK3640254 3mg/Placebo/200mg/700mg	2	2
Part 1:GSK3640254 3mg/30mg/Placebo/GSK3640254 700mg	2	2
Part 1:GSK3640254 3mg/30mg/GSK3640254 200mg/Placebo	2	2
Part 2: Repeated Dose GSK3640254 50 mg	0	0
Part 2: Repeated Dose GSK3640254 100mg	0	0
Part 2: GSK3640254 200mg + Expansion	0	0
Part 2: Repeated Dose GSK3640254 320mg	0	0
Part 2: Repeated Dose Placebo	0	0

Primary outcome: Part 1:Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)

Time frame: Up to Day 15. Count of participants. Unit: Participants

Measure	Part 1: GSK3640254 1 mg n = 6	Part 1: GSK3640254 3 mg n = 6	Part 1: GSK3640254 10 mg n = 6	Part 1: GSK3640254 30mg n = 6	Part 1: GSK3640254 100 mg n = 6	Part 1: GSK3640254 200 mg n = 6	Part 1: GSK3640254 400 mg n = 6	Part 1: GSK3640254 700 mg n = 6	Part 1: Single Dose Placebo n = 16
AE	3	2	4	3	3	4	4	1	7
SAE	0	0	0	0	0	0	0	0	0

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

Primary outcome: Part 1: Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets.

Time frame: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15). Mean (Standard Deviation). Unit: 10^9 cells /Liter

Measure	Part 1: GSK3640254 1 mg n = 6	Part 1: GSK3640254 3 mg n = 6	Part 1: GSK3640254 10 mg n = 6	Part 1: GSK3640254 30mg n = 6	Part 1: GSK3640254 100 mg n = 6	Part 1: GSK3640254 200 mg n = 6	Part 1: GSK3640254 400 mg n = 6	Part 1: GSK3640254 700 mg n = 6	Part 1: Single Dose Placebo n = 16
Basophils, 24 hours, n=6,6,6,6,6,6,5,6,16	-0.002 (0.0075)	-0.002 (0.0147)	0.005 (0.0084)	-0.002 (0.0075)	-0.007 (0.0103)	0.002 (0.0098)	-0.002 (0.0148)	-0.007 (0.0121)	0.001 (0.0106)
Basophils, 48 hours, n=6,6,5,6,6,6,6,6,16	-0.002 (0.0098)	0.012 (0.0117)	0.010 (0.0187)	-0.007 (0.0103)	-0.005 (0.00550)	0.007 (0.0082)	0.000 (0.0167)	0.000 (0.0110)	0.005 (0.0115)
Basophils, 96 hours, n=6,6,6,6,6,6,6,6,15	0.003 (0.0103)	0.000 (0.0155)	-0.003 (0.0103)	-0.002 (0.0147)	-0.005 (0.0152)	0.002 (0.0098)	-0.007 (0.0052)	-0.002 (0.0147)	0.004 (0.0118)
Basophils, Day 15,n=6,6,6,6,6,6,6,6,16	0.002 (0.0133)	0.012 (0.0117)	0.000 (0.0110)	0.002 (0.0098)	-0.007 (0.0082)	0.010 (0.0063)	-0.005 (0.0207)	-0.005 (0.0084)	0.007 (0.0178)
Eosinophils, 24 hours, n=6,6,6,6,6,6,5,6,16	-0.022 (0.1876)	0.012 (0.0376)	0.005 (0.0650)	0.015 (0.0489)	0.008 (0.0508)	-0.017 (0.0186)	-0.032 (0.0642)	0.023 (0.0266)	0.005 (0.0648)
Eosinophils, 48 hour, 6,6,5,6,6,6,6,6,16

Primary outcome: Part 1: Change From Baseline in Hematology Parameters: Erythrocytes.

Time frame: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15). Mean (Standard Deviation). Unit: 10^12 cells/Liter

Measure	Part 1: GSK3640254 1 mg n = 6	Part 1: GSK3640254 3 mg n = 6	Part 1: GSK3640254 10 mg n = 6	Part 1: GSK3640254 30mg n = 6	Part 1: GSK3640254 100 mg n = 6	Part 1: GSK3640254 200 mg n = 6	Part 1: GSK3640254 400 mg n = 6	Part 1: GSK3640254 700 mg n = 6	Part 1: Single Dose Placebo n = 16
24 hours, n=6,6,6,6,6,6,5,6,16	0.118 (0.2576)	0.338 (0.1150)	-0.005 (0.1747)	0.147 (0.2925)	0.212 (0.2335)	0.198 (0.0933)	0.084 (0.1928)	0.302 (0.1447)	0.197 (0.2148)
48 hours, n=6,6,5,6,6,6,6,6,16	0.162 (0.2899)	0.142 (0.1607)	-0.024 (0.2501)	0.108 (0.3252)	0.152 (0.1528)	0.288 (0.1082)	0.087 (0.2295)	0.180 (0.2440)	0.171 (0.2112)
96 hours, n=6,6,6,6,6,6,6,6,15	0.155 (0.2290)	0.202 (0.1683)	0.083 (0.2499)	0.178 (0.2320)	-0.035 (0.2672)	0.112 (0.0674)	0.062 (0.2528)	0.237 (0.2530)	0.189 (0.1834)
Follow Up (Day 15), n=6,6,6,6,6,6,6,6,16	0.027 (0.1876)	0.145 (0.2041)	-0.060 (0.3138)	0.023 (0.3370)	-0.205 (0.1639)	0.053 (0.1549)	-0.295 (0.2001)	0.007 (0.2067)	0.032 (0.2691)

Population analysed: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Primary outcome: Part 1: Change From Baseline in Hematology Parameters: Erythrocytes Mean Corpuscular Volume (Erythrocyte MCV).

Time frame: Baseline (Day -2), 24 hours, 48 hours, 96 hours and Follow up (Day 15). Mean (Standard Deviation). Unit: Femtoliter

Measure	Part 1: GSK3640254 1 mg n = 6	Part 1: GSK3640254 3 mg n = 6	Part 1: GSK3640254 10 mg n = 6	Part 1: GSK3640254 30mg n = 6	Part 1: GSK3640254 100 mg n = 6	Part 1: GSK3640254 200 mg n = 6	Part 1: GSK3640254 400 mg n = 6	Part 1: GSK3640254 700 mg n = 6	Part 1: Single Dose Placebo n = 16
24 hour, n=6,6,6,6,6,6,5,6,16	-0.50 (1.390)	-0.03 (0.497)	0.17 (0.689)	0.70 (0.494)	-1.07 (0.575)	-0.28 (1.192)	-0.64 (0.754)	-0.25 (0.853)	0.05 (0.797)
48 hour, n=6,6,5,6,6,6,6,6,16	-0.42 (0.966)	0.35 (1.231)	0.06 (0.673)	0.13 (0.659)	-0.57 (0.843)	0.10 (1.135)	-1.18 (0.703)	-0.18 (0.725)	0.24 (0.932)
96 hour,n=6,6,6,6,6,6,6,6,15	1.75 (0.619)	0.43 (0.950)	0.02 (0.979)	-0.22 (1.030)	-0.85 (1.214)	0.28 (1.177)	-0.15 (0.616)	-0.13 (0.388)	0.20 (1.196)
Follow up (Day 15), n=6,6,6,6,6,6,6,6,16	0.15 (1.263)	1.83 (0.505)	0.53 (0.850)	-0.20 (1.241)	-0.15 (1.253)	0.42 (1.339)	-0.10 (1.567)	-0.28 (0.840)	0.14 (1.153)

Population analysed: Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

28 secondary outcomes are reported in the full results.

Adverse events

Time frame: On-treatment and post-treatment non-serious adverse events and serious adverse events were collected up to Day 15 for Part 1 and Day 28 for Part 2 of the study.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1:GSK3640254 1 mg	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part 1:GSK3640254 3 mg	0 of 6 (0%)	2 of 6 (33.3%)	0 of 6
Part 1:GSK3640254 10 mg	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6
Part 1:GSK3640254 30 mg	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part 1:GSK3640254 100 mg	0 of 6 (0%)	3 of 6 (50%)	0 of 6
Part 1:GSK3640254 200 mg	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6
Part 1:GSK3640254 400 mg	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6
Part 1:GSK3640254 700 mg	0 of 6 (0%)	1 of 6 (16.7%)	0 of 6
Part 1: Single Dose Placebo	0 of 16 (0%)	7 of 16 (43.8%)	0 of 16
Part 2: Repeated Dose GSK3640254 50 mg	0 of 6 (0%)	4 of 6 (66.7%)	0 of 6
Part 2: Repeated Dose GSK3640254 100 mg	0 of 6 (0%)	5 of 6 (83.3%)	0 of 6
Part 2: Repeated Dose GSK3640254 200mg +Expansion	0 of 25 (0%)	19 of 25 (76%)	0 of 25
Part 2: Repeated Dose GSK3640254 320 mg	0 of 7 (0%)	6 of 7 (85.7%)	0 of 7
Part 2: Repeated Dose Placebo	0 of 14 (0%)	10 of 14 (71.4%)	0 of 14

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 33200887Joshi SR, Fernando D, Igwe S, McKenzie L, Krishnatry AS, Halliday F, Zhan J, Greene TJ, Xu J, Ferron-Brady G, Lataillade M, Min S. Phase I evaluation of the safety, tolerability, and pharmacokinetics of GSK3640254, a next-generation HIV-1 maturation inhibitor. Pharmacol Res Perspect. 2020 Dec;8(6):e00671. doi: 10.1002/prp2.671.
Individual participant dataSharing planned: Yes. IPD for this study is 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

ViiV Healthcare

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 GSK3640254 in people with Infection, Human Immunodeficiency Virus and HIV Infections, run by ViiV Healthcare 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 5 inclusion and 24 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 10 Jun 2021. 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 18 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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

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

What does the primary outcome measure?

Part 1:Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) (time frame: Up to Day 15). The study lists 40 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 NCT03231943, which also lists 1 linked publication.

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

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

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2021; AzTrials last refreshed its copy on 7 Nov 2026.