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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Infection, Human Immunodeficiency Virus
• Intervention / Treatment: Drug: GSK3640254; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Cambridge, United Kingdom, CB2 2GG
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Subjects in cohort 1-2: Part 1; 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.	Drug: GSK3640254; 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.; Drug: Placebo; Placebo capsule matching to the study treatment will be given via oral route during each dosing day with approximately 240 mL of water.
EXPERIMENTAL: GSK3640254 receivers (cohort 3-6 and expansion): Part 2; 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.	Drug: GSK3640254; 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.
PLACEBO_COMPARATOR: Subjects receiving placebo (cohort 3-6): Part 2; 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.	Drug: Placebo; Placebo capsule matching to the study treatment will be given via oral route during each dosing day with approximately 240 mL of water.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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).	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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

Collaborators and Investigators

• Sponsor: ViiV Healthcare
• Collaborators: GlaxoSmithKline

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 19, 2017
• Primary Completion (ACTUAL): September 9, 2018
• Study Completion (ACTUAL): September 9, 2018

Study Registration Dates

• First Submitted: July 24, 2017
• First Submitted That Met QC Criteria: July 24, 2017
• First Posted (ACTUAL): July 27, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 10, 2021
• Last Update Submitted That Met QC Criteria: May 28, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Safety; HIV-1; Healthy; PK; Tolerability; Dose-escalation; FTIH; GSK3640254; Maturation inhibitor
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Slow Virus Diseases; HIV Infections; Infections; Communicable Diseases; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: 207187; 2017-001367-21 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study is available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No