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A Two-part Study to Compare a Tablet and Capsule Formulation of GSK2838232 With and Without Food, and to Assess the Safety and Drug Levels of Repeated Once-daily Doses of GSK2838232 Without Ritonavir

Primary Purpose

Infection, Human Immunodeficiency Virus, HIV Infections

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

GSK2838232 100 mg tablet

GSK2838232 50 mg capsule

Ritonavir 100 mg tablets

Placebo for GSK2838232 tablets

About this trial

This is an interventional treatment trial for Infection, Human Immunodeficiency Virus focused on measuring GSK2838232, safety, food effect, capsule, healthy, PK, tablet

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Between 18 and 55 years of age inclusive, at the time of signing the informed consent.
Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, and outside the reference range for the population being studied, may be included only if the Investigator in consultation with the medical monitor, if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
A creatinine clearance (CLcr) > 80 milliliter per minute (mL/min) as determined by Cockcroft-Gault equation: CLcr = (140 minus age) multiplied by weight divided by (72 multiplied by serum creatinine) (times 0.85 if female) where age is in years, weight in kilogram (kg), and serum creatinine is in units of milligram per deciliter (mg/dL).
Body weight >=50.0 kg (110 pounds [lbs.]) for men and >=45.0 kg (99 lbs) for women and body mass index (BMI) within the range 18.5 to 31.0 kg/meter (m)^2 (inclusive).
Males or females.
A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin [hCG] test), not lactating, and of non-reproductive potential which is defined as:

Reproductive potential:

There is no definitive drug-drug interaction (DDI) information with GSK2838232 and an interaction with oral contraceptives is possible, so other (barrier, inter-uterine device etc.) methods of contraception will be required. Females of reproductive potential may only be enrolled if they are using two forms of complementary contraception, which must include at least one barrier method. They will be counseled on safer sex practices. Fertile females, who have an established, long-term lifestyle of sexual abstinence, or only same sex partners, require no other means of birth control.

Non-reproductive potential:

Pre-menopausal females with one of the following: Documented tubal ligation; documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; hysterectomy; documented Bilateral Oophorectomy.
Postmenopausal defined as 12 months of spontaneous amenorrhea in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT) must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.
- Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until one week after the last dose of study medication.
Vasectomy with documentation of azoospermia.
Male condom plus partner use of one of the contraceptive options below: Contraceptive subdermal implant with a <1 percent rate of failure per year; intrauterine device or intrauterine system with a <1 percent rate of failure per year; oral contraceptive, either combined or progestogen alone or injectable progestogen; contraceptive vaginal ring; percutaneous contraceptive patches.
- Capable of giving signed informed consent.

Exclusion Criteria:

ALT >1.5 times upper limit of normal (ULN)
Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent).
Current or chronic history of liver disease, or known hepatic or biliary abnormalities.
Subjects who have asthma or a history of asthma.
Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
Unable to refrain from the use of prescription or non-prescription drugs, 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, unless in the opinion of the Investigator and GlaxoSmithKline medical monitor, the medication will not interfere with the study procedures or compromise participant safety.
History of regular alcohol consumption (within 6 months prior to screening or unable to refrain from alcohol use from 5 days prior to admission through the last blood sample collected) defined as:
• For United States sites: an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 gram of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
Regular use of tobacco- or nicotine- containing products within 6 months prior to screening. Unable to refrain from smoking from the Screening Visit through the last blood sample collected. As confirmed by a urine cotinine test.
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.
Presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C virus (HCV) test result at screening or within 3 months prior to first dose of study treatment.
Screening or Baseline cardiac troponin I greater than the 99 percent cutoff (>0.045 nanogram [ng]/mL by the Dimension Vista cTnI assay) for a given assay.
A positive pre-study drug/alcohol screen.
A positive test for human immunodeficiency virus (HIV) antibody.
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days.
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
Exclusion Criteria for 24-hour Screening Holter:
- Any symptomatic arrhythmia (except isolated extra systoles).
- Sustained cardiac arrhythmias (such as atrial fibrillation or flutter, supraventricular tachycardia (>= 10 consecutive beats), complete heart block).
- Non-sustained or sustained ventricular tachycardia (defined as >=3 consecutive ventricular ectopic beats).
- Any conduction abnormality (including but not specific to left or right incomplete or complete bundle branch block, atrioventricular (AV) block [2nd degree or higher], Wolff Parkinson White (WPW) syndrome etc.).
- Sinus Pauses >3 seconds.
- 300 or more supraventricular ectopic beats in 24 hours.
- 250 or more ventricular ectopic beats in 24 hours.
Any clinically significant abnormal echocardiogram finding.
Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination):
- Heart rate <45 or >100 beats per minute (bpm) for males; <50 or >100 bpm for females
- PR interval <120 or >220 milliseconds (msec)
- QRS duration <70 or >120 msec
- QTc interval (Fridericia's) >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, AV block [2nd degree or higher], WPW syndrome).
- Sinus Pauses >3 seconds.
- Any significant arrhythmia which, in the opinion of the Investigator or GSK medical monitor, will interfere with the safety for the individual subject.
- Non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats).

Sites / Locations

GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Placebo Comparator

Arm Label

Treatment sequence ABC: Part 1

Treatment sequence BAC: Part 1

GSK2838232 tablet without RTV: Part 2

Placebo without RTV: Part 2

Arm Description

A single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation will be administered under fed conditions (treatment A) in period 1 in Part 1A. A single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation will be administered under fed conditions (treatment B) in period 2 in Part 1A. Both these treatments in Part 1A will be administered with RTV in fed state with a washout of 10 days. A single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation (with RTV) will be administered under fasted conditions (treatment C) in period 3 in Part 1B. There will be a wash out of 15 days between Part 1A and Part 1B.

A single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation will be administered under fed conditions (treatment B) in period 1 in Part 1A. A single dose of GSK2838232 200 mg (as 4 x 50 mg) capsule formulation will be administered under fed conditions (treatment A) in period 2 in Part 1A. A single dose of GSK2838232 200 mg (as 2 x 100 mg) tablet formulation (with RTV) will be administered under fasted conditions (treatment C) in period 3 in Part 1B. There will be a wash out of 15 days between Part 1A and Part 1B.

In Part 2, subjects will receive non-RTV boosted GSK2838232 500 mg, given as single daily doses for 11 days. The dose will not exceed 500 mg (as 5 x 100 mg tablets) once daily (QD).

In Part 2, subjects will receive a Placebo given as single daily doses for 11 days.

Outcomes

Primary Outcome Measures

Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet and capsule formulation in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods. Pharmacokinetic Population comprised of all participants in the Safety Population who had at least 1 non-missing pharmacokinetic assessment (Non-quantifiable [NQ] values were considered as non-missing values).

Part 1: Maximum Observed Concentration (Cmax) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State

Part 1: AUC (0-infinity) Following Administration of GSK2838232 Tablet in Fasted and Fed State

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as tablet formulation in fed and fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Part 1: Cmax Following Administration of GSK2838232 Tablet in Fasted and Fed State

Part 1: Time of Occurrence of Cmax (Tmax) Following Administration of GSK2838232 Tablet in Fasted and Fed State

Part 2: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/ birth defect, is associated with liver injury or impaired liver function or any other situations as per medical or scientific judgment. Safety Population comprised of all participants who received at least 1 dose of the study treatment (including placebo) with at least 1 post-Baseline safety assessment. Number of participants with SAEs and common non-SAEs (>=5%) are presented.

Part 2: Number of Participants With Worst Case Hematology Results to Potential Clinical Importance (PCI) Criteria

Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. PCI ranges were < 0.075 or >0.54 proportion of red blood cells in blood for hematocrit, <25 or >180 grams per liter (g/L) for hemoglobin, < 3 or >20 cells per liter (cells/L) for leukocytes, 0.8 x10^9 cells/L for lymphocytes, 1.5 x10^9 cells/L for neutrophils, and <100 or >550 cells/L for platelets. Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (example given [e.g.], High to High), or whose value became within range, were recorded in the "To within Range or No Change" category.

Part 2: Number of Participants With Worst Case Clinical Chemistry Results to PCI Criteria

Blood samples were collected from participants for analysis of following clinical chemistry parameters; glucose, alanine aminotransferase (ALT), albumin, alkaline phosphatase, aspartate aminotransferase (AST), bilirubin, calcium, potassium and sodium. PCI ranges were <30 g/L for albumin, <2 or >2.75 millimoles per liter (mmol/L) for calcium, <3 or >9 mmol/L for glucose, >=2 times Upper limit of Normal (ULN) units per liter (U/L) for ALT, >=2 times ULN U/L for alkaline phosphatase, >=2 times ULN U/L for AST, >=1.5 times ULN micromoles per liter (µmol/L) for bilirubin, <3 or >5.5 mmol/L for potassium, and <130 or >150 mmol/L for sodium. Participants were counted in the worst case category that their value changes to (low, within range or no change,or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category.

Part 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria

Urine samples were collected from participants for analysis of following urinalysis parameters; specific gravity, potential of hydrogen (pH), presence of glucose, protein, occult blood, ketones in urine analyzed by dipstick method. The dipstick test gives results in a semi-quantitative manner. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The reference range is 1.002-1.030. Urine pH is an acid-base measurement. Normal urine has a slightly acid pH (5.0 - 6.0). Participants were counted in the worst case category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the "To Normal or No Change" category.

Part 2: Blood Pressure at Indicated Time Points

Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in supine position after 10 minutes rest for the participants at indicated time points.

Part 2: Change From Baseline in Blood Pressure

SBP and DBP were measured in supine position after 10 minutes rest for participants at indicated time points. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.

Part 2: Pulse Rate at Indicated Time Points

Pulse rate of participants was measured in supine position after 10 minutes rest at indicated time points.

Part 2: Change From Baseline in Pulse Rate

Pulse rate was measured in supine position after 10 minutes rest at indicated time points. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.

Part 2: Number of Participants With Abnormal Electrocardiogram (ECG) Findings

Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Part 2: Change From Baseline in Mean Heart Rate Values as ECG Parameter

Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.

Part 2: Change From Baseline in PR Interval, QRS, QT Interval, and QTcF Interval as ECG Parameters

Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates measures PR, QRS, QT and QTcF intervals. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.

Part 2: Area Under the Plasma Drug Concentration Time Curve From Pre-dose to the End of the Dosing Interval at Steady State (AUC[0-tau]) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Part 2: Cmax Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State

Part 2: Observed Concentration at the End of the Dosing Interval (Ctau) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State

Part 2: Tmax Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State

Part 2: Lag-time (Tlag) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 1

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as a non-boosted once-daily dosing tablet in fed state. Tlag is a time delay between drug administration and first observed concentration. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Part 2: AUC(0-infinity) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11

Part 2: Apparent Terminal Phase Half-life (T1/2) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11

Part 2: Time of Last Quantifiable Concentration (Tlast) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11

Secondary Outcome Measures

Part 1: Number of Participants With SAEs and Non-SAEs

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/ birth defect, is associated with liver injury or impaired liver function or any other situations as per medical or scientific judgment. Number of participants with SAEs and common non-SAEs (>=5%) are presented.

Part 1: Number of Participants With Worst Case Hematology Results to PCI Criteria

Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. PCI ranges were >0.54 as proportion of red blood cells in blood for hematocrit, >180 g/L for hemoglobin, < 3 or >20 cells/L for leukocytes, 0.8 x10^9 cells/L for lymphocytes, 1.5 x10^9 cells/L for neutrophils, and <100 or >550 cells/L for platelets. Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category.

Part 1: Number of Participants With Worst Case Clinical Chemistry Results to PCI Criteria

Blood samples were collected from participants for analysis of following clinical chemistry parameters; glucose, ALT, albumin, alkaline phosphatase, AST, bilirubin, calcium, potassium and sodium. PCI ranges were <30 g/L for albumin, <2 or 2.75 mmol/L for calcium, <3 or >9 mmol/L for glucose, >=2 times ULN U/L for ALT, >=2 times ULN U/L for alkaline phosphatase, >=2 times ULN U/L for AST, >=1.5 times ULN µmol/L for bilirubin, <3 or >5.5 mmol/L for potassium, and <130 or >150 mmol/L for sodium. Participants were counted in the worst case category that their value changes to (low, within range or no change,or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category.

Part 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria

Urine samples were collected from participants for analysis of following urinalysis parameters; specific gravity, pH, presence of glucose, protein, occult blood, ketones in urine analyzed by dipstick method. The dipstick test gives results in a semi-quantitative manner. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The reference range is 1.002-1.030. Urine pH is an acid-base measurement. Normal urine has a slightly acid pH (5.0 - 6.0). Participants were counted in the worst case category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became normal, were recorded in the "To Normal or No Change" category.

Part 1: Blood Pressure at Indicated Time Points

SBP and DBP of participants were measured in supine position after 10 minutes rest at indicated time points.

Part 1: Change From Baseline in Blood Pressure

SBP and DBP were measured in supine position after 10 minutes rest for the participant at indicated time points. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.

Part 1: Pulse Rate at Indicated Time Points

Pulse rate was measured in supine position after 10 minutes rest for the participant at indicated time points.

Part 1: Change From Baseline in Pulse Rate

Pulse rate was measured in supine position after 10 minutes rest for the participant at indicated time points. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.

Part 1: Number of Participants With Abnormal ECG Findings

Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTcF intervals. CS and NCS abnormal ECG findings have been presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Part 1: Change From Baseline in Mean Heart Rate Values as ECG Parameter

Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.

Part 1: Change From Baseline in PR Interval, QRS, QT Interval, and QTcF Interval as ECG Parameters

Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates measures PR, QRS, QT and QTcF intervals. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.

Part 1: Tlag Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Tlag is a time delay between drug administration and first observed concentration. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Part 1: Tmax Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Part 1: T1/2 Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Part 1: Tlast Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Part 1: Plasma Drug Concentration at 24 Hours (C24) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Part 1: AUC(0-t) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Part 2: Slope of Pre-dose Concentration of GSK2838232 Administered as Non-boosted Once-daily Doses of a Tablet Formulation to Assess Achievement of Steady State

Blood sample were collected at indicated time points to assess pre-dose concentration of GSK2838232 when administered as non-boosted once-daily doses of a tablet formulation for 11 days in Part 2. Slope and 90 percent confidence interval have been presented.

Part 2: Accumulation Ratio Calculated From AUC(0-tau) Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation

Blood sample were collected at indicated time points to calculate accumulation ratio from AUC(0-tau) following administration of GSK2838232 as non-boosted once-daily doses of a tablet formulation. Accumulation ratio of GSK2838232 was evaluated by Day 11, AUC (0-tau) divided by Day 1, AUC (0-tau).

Part 2: Accumulation Ratio Calculated From Cmax Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation

Blood sample were collected at indicated time points to calculate accumulation ratio from Cmax following administration of GSK2838232 as non-boosted once-daily doses of a tablet formulation. Accumulation ratio of GSK2838232 was evaluated by Day 11, Cmax divided by Day 1, Cmax.

Part 2: Accumulation Ratio Calculated From Ctau Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation

Blood sample were collected at indicated time points to calculate accumulation ratio from Ctau following administration of GSK2838232 as non-boosted once-daily doses of a tablet formulation. Accumulation ratio of GSK2838232 was evaluated by Day 11, Ctau divided by Day 1, Ctau.

Full Information

NCT ID

NCT03234036

First Posted

July 26, 2017

Last Updated

October 6, 2020

Sponsor

GlaxoSmithKline

1. Study Identification

Unique Protocol Identification Number

NCT03234036

Brief Title

A Two-part Study to Compare a Tablet and Capsule Formulation of GSK2838232 With and Without Food, and to Assess the Safety and Drug Levels of Repeated Once-daily Doses of GSK2838232 Without Ritonavir

Official Title

A Two Part Study to Assess i) the Relative Bioavailability and Food Effect of a Novel Tablet Formulation of Boosted-GSK2838232 Compared to Capsule and ii) the Safety and Pharmacokinetics of Repeated Once-Daily Doses of Non-boosted GSK2838232

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Completed

Study Start Date

August 2, 2017 (Actual)

Primary Completion Date

November 10, 2017 (Actual)

Study Completion Date

November 10, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

This study will be conducted in two Parts to confirm the acceptability/selection of a tablet formulation for future clinical development of GSK2838232. Part 1 of the study will assess single ritonavir (RTV)-boosted doses of a new tablet formulation given with food (containing approximately 30% fat) against the reference capsule formulation also given with food and then will assess the impact of fasted conditions on the tablet performance. In Part 2, non-boosted GSK2838232 will be given as once-daily tablet doses for 11 days in a separate group of subjects, assuming the tablet performance is considered acceptable from Part 1. Approximately 16 healthy subjects will be enrolled to provide at least 12 evaluable subjects through the three study periods in Part 1. 10 healthy subjects will be enrolled to provide at least 8 evaluable subjects through the single study period in Part 2. The maximum duration of study participation will be approximately 9 to 10 weeks for Part 1; and 8 to 9 weeks for Part 2.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Infection, Human Immunodeficiency Virus, HIV Infections

Keywords

GSK2838232, safety, food effect, capsule, healthy, PK, tablet

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Crossover Assignment

Model Description

The randomization number will determine the allocation of treatment sequences (ABC or BAC) for Part 1, and of treatment (GSK2838232 without RTV or placebo) for Part 2. Allocation to treatment for Part 1A or Part 1B (with Part 2 being fixed) will be according to a predetermined random order.

Masking

ParticipantInvestigator

Masking Description

Part 1 of the study will be open label and thus not be blinded. Part 2 of the study will be single blinded because of the unavailability of matching placebo tablets. The Principal Investigator and the subject will be completely blinded to specific treatment assignment.

Allocation

Randomized

Enrollment

26 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment sequence ABC: Part 1

Arm Type

Experimental

Arm Description

Arm Title

Treatment sequence BAC: Part 1

Arm Type

Experimental

Arm Description

Arm Title

GSK2838232 tablet without RTV: Part 2

Arm Type

Experimental

Arm Description

In Part 2, subjects will receive non-RTV boosted GSK2838232 500 mg, given as single daily doses for 11 days. The dose will not exceed 500 mg (as 5 x 100 mg tablets) once daily (QD).

Arm Title

Placebo without RTV: Part 2

Arm Type

Placebo Comparator

Arm Description

In Part 2, subjects will receive a Placebo given as single daily doses for 11 days.

Intervention Type

Drug

Intervention Name(s)

GSK2838232 100 mg tablet

Intervention Description

It is a white to slightly colored tablet. It will be supplied as prefilled tablets in bulk for dispensing to subjects at the site according to the treatment code.

Intervention Type

Drug

Intervention Name(s)

GSK2838232 50 mg capsule

Intervention Description

It is a pink unmarked capsule. It will be supplied as prefilled capsules in bulk for dispensing to subjects at the site according to the treatment code.

Intervention Type

Drug

Intervention Name(s)

Ritonavir 100 mg tablets

Intervention Description

It is a white film-coated ovaloid tablets.

Intervention Type

Drug

Intervention Name(s)

Placebo for GSK2838232 tablets

Intervention Description

It is a white to slightly colored tablet. The placebo tablets supplied will not be identical to GSK2838232 tablets. It will be administered by site staff via an opaque card or paper tube.

Primary Outcome Measure Information:

Title

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1 and 2 of Part 1

Title

Part 1: Maximum Observed Concentration (Cmax) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1 and 2 of Part 1

Title

Part 1: AUC (0-infinity) Following Administration of GSK2838232 Tablet in Fasted and Fed State

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1

Title

Part 1: Cmax Following Administration of GSK2838232 Tablet in Fasted and Fed State

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1

Title

Part 1: Time of Occurrence of Cmax (Tmax) Following Administration of GSK2838232 Tablet in Fasted and Fed State

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1

Title

Part 2: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs

Description

Time Frame

Up to 25 days

Title

Part 2: Number of Participants With Worst Case Hematology Results to Potential Clinical Importance (PCI) Criteria

Description

Time Frame

Up to 25 days

Title

Part 2: Number of Participants With Worst Case Clinical Chemistry Results to PCI Criteria

Description

Time Frame

Up to 25 days

Title

Part 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria

Description

Time Frame

Up to 25 days

Title

Part 2: Blood Pressure at Indicated Time Points

Description

Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured in supine position after 10 minutes rest for the participants at indicated time points.

Time Frame

Day -1; Pre-dose, 1, 4 hours on Day 1; 24 hours (Day 2); 48 hours (Day 3); 72 hours (Day 4), Days 5, 6, 7, 8, 9, 10; Pre-dose, 1, 4 , 24, 48, 72 hours on Day 11; Follow-up (Day 25)

Title

Part 2: Change From Baseline in Blood Pressure

Description

Time Frame

Baseline (Day -1) and 1, 4 hours on Day 1; 24 hours (Day 2); 48 hours (Day 3); 72 hours (Day 4), Days 5, 6, 7, 8, 9, 10; Pre-dose, 1, 4 , 24, 48, 72 hours on Day 11; Follow-up (Day 25)

Title

Part 2: Pulse Rate at Indicated Time Points

Description

Pulse rate of participants was measured in supine position after 10 minutes rest at indicated time points.

Time Frame

Day -1; Pre-dose, 1, 4 hours on Day 1; 24 hours (Day 2); 48 hours (Day 3); 72 hours (Day 4), Days 5, 6, 7, 8, 9, 10; Pre-dose, 1, 4 , 24, 48, 72 hours on Day 11; Follow-up (Day 25)

Title

Part 2: Change From Baseline in Pulse Rate

Description

Time Frame

Baseline (Day -1) and 1, 4 hours on Day 1; 24 hours (Day 2); 48 hours (Day 3); 72 hours (Day 4), Days 5, 6, 7, 8, 9, 10; Pre-dose, 1, 4 , 24, 48, 72 hours on Day 11; Follow-up (Day 25)

Title

Part 2: Number of Participants With Abnormal Electrocardiogram (ECG) Findings

Description

Time Frame

Day -1; 1, 4, 12 hours on Day 1; Days 2, 3, 5, 8; 1, 4, 12, 24 Hours on Day 11; Follow-up (Day 25)

Title

Part 2: Change From Baseline in Mean Heart Rate Values as ECG Parameter

Description

Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.

Time Frame

Baseline (Day -1) and 1, 4, 12 hours on Day 1; Days 2, 3 5, 8; Pre-dose, 1, 4, 12, 24 hours Day 11; Follow-up (Day 25)

Title

Part 2: Change From Baseline in PR Interval, QRS, QT Interval, and QTcF Interval as ECG Parameters

Description

Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates measures PR, QRS, QT and QTcF intervals. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.

Time Frame

Baseline (Day -1) and 1, 4, 12 hours on Day 1; Days 2, 3 5, 8; Pre-dose, 1, 4, 12, 24 hours Day 11; Follow-up (Day 25)

Title

Description

Time Frame

Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Title

Part 2: Cmax Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State

Description

Time Frame

Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Title

Part 2: Observed Concentration at the End of the Dosing Interval (Ctau) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State

Description

Time Frame

Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Title

Part 2: Tmax Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State

Description

Time Frame

Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Title

Part 2: Lag-time (Tlag) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 1

Description

Time Frame

Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1 in Part 2

Title

Part 2: AUC(0-infinity) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Title

Part 2: Apparent Terminal Phase Half-life (T1/2) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Title

Part 2: Time of Last Quantifiable Concentration (Tlast) Following Administration of Non-boosted Once-daily Doses of GSK2838232 Tablet in Fed State on Day 11

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Secondary Outcome Measure Information:

Title

Part 1: Number of Participants With SAEs and Non-SAEs

Description

Time Frame

Up to 60 days

Title

Part 1: Number of Participants With Worst Case Hematology Results to PCI Criteria

Description

Blood samples were collected from participants for analysis of following hematology parameters; hematocrit, hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. PCI ranges were >0.54 as proportion of red blood cells in blood for hematocrit, >180 g/L for hemoglobin, < 3 or >20 cells/L for leukocytes, 0.8 x10^9 cells/L for lymphocytes, 1.5 x10^9 cells/L for neutrophils, and <100 or >550 cells/L for platelets. Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category.

Time Frame

Up to 60 days

Title

Part 1: Number of Participants With Worst Case Clinical Chemistry Results to PCI Criteria

Description

Time Frame

Up to 60 days

Title

Part 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria

Description

Time Frame

Up to 60 days

Title

Part 1: Blood Pressure at Indicated Time Points

Description

SBP and DBP of participants were measured in supine position after 10 minutes rest at indicated time points.

Time Frame

Day -2; Day -1; Pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72 Hours on Day 1

Title

Part 1: Change From Baseline in Blood Pressure

Description

Time Frame

Baseline (Day -1) and 1, 2, 4, 6, 8, 12, 24, 48, 72 Hours on Day 1

Title

Part 1: Pulse Rate at Indicated Time Points

Description

Pulse rate was measured in supine position after 10 minutes rest for the participant at indicated time points.

Time Frame

Day -2; Day -1; Pre-dose, 1, 2, 4, 6, 8, 12, 24, 48, 72 Hours on Day 1

Title

Part 1: Change From Baseline in Pulse Rate

Description

Time Frame

Baseline (Day -1) and 1, 2, 4, 6, 8, 12, 24, 48, 72 Hours on Day 1

Title

Part 1: Number of Participants With Abnormal ECG Findings

Description

Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTcF intervals. CS and NCS abnormal ECG findings have been presented. CS abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Time Frame

Day -2, Day -1; 1, 2, 4, 6, 8, , 12, 24, 48, 72 hours on Day 1

Title

Part 1: Change From Baseline in Mean Heart Rate Values as ECG Parameter

Description

Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates the heart rate. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.

Time Frame

Baseline (Day -1) and 1, 2, 4, 6, 8, 12, 24, 48, 72 hours on Day 1

Title

Part 1: Change From Baseline in PR Interval, QRS, QT Interval, and QTcF Interval as ECG Parameters

Description

Single and triplicate 12-lead ECG's were obtained at least 5 minutes apart in the supine position after 10 minutes of rest at indicated time points using an ECG machine that automatically calculates measures PR, QRS, QT and QTcF intervals. Baseline was defined as the latest pre-dose assessment, including those from unscheduled visits. Change from Baseline was defined as any visit value minus Baseline value.

Time Frame

Baseline (Day -1) and 1, 2, 4, 6, 8, 12, 24, 48, 72 hours on Day 1

Title

Part 1: Tlag Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State

Description

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1

Title

Part 1: Tmax Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State

Description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1

Title

Part 1: T1/2 Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State

Description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1

Title

Part 1: Tlast Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State

Description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1

Title

Part 1: Plasma Drug Concentration at 24 Hours (C24) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State

Description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1

Title

Part 1: AUC(0-t) Following Administration of GSK2838232 Tablet and Capsule Formulation in Fed State and Tablet Formulation in Fasted State

Description

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2838232 given as capsule and tablet formulation in fed state as well as tablet formulation in fasted state. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time Frame

Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 120 hours post-dose in treatment periods 1, 2 and 3 of Part 1

Title

Part 2: Slope of Pre-dose Concentration of GSK2838232 Administered as Non-boosted Once-daily Doses of a Tablet Formulation to Assess Achievement of Steady State

Description

Time Frame

Pre-dose on Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10 and Day 11 in Part 2

Title

Part 2: Accumulation Ratio Calculated From AUC(0-tau) Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation

Description

Time Frame

Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Title

Part 2: Accumulation Ratio Calculated From Cmax Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation

Description

Time Frame

Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

Title

Part 2: Accumulation Ratio Calculated From Ctau Following Administration of GSK2838232 as Non-boosted Once-daily Doses of a Tablet Formulation

Description

Time Frame

Pre-dose, 0.5,1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12 and 24 hours post-dose on Day 1; Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, 72, 96 and 120 hours post-dose on Day 11 in Part 2

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Between 18 and 55 years of age inclusive, at the time of signing the informed consent. Healthy as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, and outside the reference range for the population being studied, may be included only if the Investigator in consultation with the medical monitor, if required, agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. A creatinine clearance (CLcr) > 80 milliliter per minute (mL/min) as determined by Cockcroft-Gault equation: CLcr = (140 minus age) multiplied by weight divided by (72 multiplied by serum creatinine) (times 0.85 if female) where age is in years, weight in kilogram (kg), and serum creatinine is in units of milligram per deciliter (mg/dL). Body weight >=50.0 kg (110 pounds [lbs.]) for men and >=45.0 kg (99 lbs) for women and body mass index (BMI) within the range 18.5 to 31.0 kg/meter (m)^2 (inclusive). Males or females. A female subject is eligible to participate if she is not pregnant (as confirmed by a negative serum human chorionic gonadotrophin [hCG] test), not lactating, and of non-reproductive potential which is defined as: Reproductive potential: There is no definitive drug-drug interaction (DDI) information with GSK2838232 and an interaction with oral contraceptives is possible, so other (barrier, inter-uterine device etc.) methods of contraception will be required. Females of reproductive potential may only be enrolled if they are using two forms of complementary contraception, which must include at least one barrier method. They will be counseled on safer sex practices. Fertile females, who have an established, long-term lifestyle of sexual abstinence, or only same sex partners, require no other means of birth control. Non-reproductive potential: Pre-menopausal females with one of the following: Documented tubal ligation; documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; hysterectomy; documented Bilateral Oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) and estradiol levels consistent with menopause. Females on hormone replacement therapy (HRT) must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment. Male subjects with female partners of child bearing potential must comply with the following contraception requirements from the time of first dose of study medication until one week after the last dose of study medication. Vasectomy with documentation of azoospermia. Male condom plus partner use of one of the contraceptive options below: Contraceptive subdermal implant with a <1 percent rate of failure per year; intrauterine device or intrauterine system with a <1 percent rate of failure per year; oral contraceptive, either combined or progestogen alone or injectable progestogen; contraceptive vaginal ring; percutaneous contraceptive patches. Capable of giving signed informed consent. Exclusion Criteria: ALT >1.5 times upper limit of normal (ULN) Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent). Current or chronic history of liver disease, or known hepatic or biliary abnormalities. Subjects who have asthma or a history of asthma. Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome. Unable to refrain from the use of prescription or non-prescription drugs, 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, unless in the opinion of the Investigator and GlaxoSmithKline medical monitor, the medication will not interfere with the study procedures or compromise participant safety. History of regular alcohol consumption (within 6 months prior to screening or unable to refrain from alcohol use from 5 days prior to admission through the last blood sample collected) defined as: • For United States sites: an average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 gram of alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits. Regular use of tobacco- or nicotine- containing products within 6 months prior to screening. Unable to refrain from smoking from the Screening Visit through the last blood sample collected. As confirmed by a urine cotinine test. 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. Presence of hepatitis B surface antigen (HBsAg), or positive hepatitis C virus (HCV) test result at screening or within 3 months prior to first dose of study treatment. Screening or Baseline cardiac troponin I greater than the 99 percent cutoff (>0.045 nanogram [ng]/mL by the Dimension Vista cTnI assay) for a given assay. A positive pre-study drug/alcohol screen. A positive test for human immunodeficiency virus (HIV) antibody. Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). Exposure to more than four new chemical entities within 12 months prior to the first dosing day. Exclusion Criteria for 24-hour Screening Holter: Any symptomatic arrhythmia (except isolated extra systoles). Sustained cardiac arrhythmias (such as atrial fibrillation or flutter, supraventricular tachycardia (>= 10 consecutive beats), complete heart block). Non-sustained or sustained ventricular tachycardia (defined as >=3 consecutive ventricular ectopic beats). Any conduction abnormality (including but not specific to left or right incomplete or complete bundle branch block, atrioventricular (AV) block [2nd degree or higher], Wolff Parkinson White (WPW) syndrome etc.). Sinus Pauses >3 seconds. 300 or more supraventricular ectopic beats in 24 hours. 250 or more ventricular ectopic beats in 24 hours. Any clinically significant abnormal echocardiogram finding. Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination): Heart rate <45 or >100 beats per minute (bpm) for males; <50 or >100 bpm for females PR interval <120 or >220 milliseconds (msec) QRS duration <70 or >120 msec QTc interval (Fridericia's) >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, AV block [2nd degree or higher], WPW syndrome). Sinus Pauses >3 seconds. Any significant arrhythmia which, in the opinion of the Investigator or GSK medical monitor, will interfere with the safety for the individual subject. Non-sustained or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

GSK Clinical Trials

Organizational Affiliation

GlaxoSmithKline

Official's Role

Study Director

Facility Information:

Facility Name

GSK Investigational Site

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21225

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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 URL

https://www.clinicalstudydatarequest.com/Posting.aspx?ID=20589

Citations:

PubMed Identifier

32558338

Citation

Johnson M, Jewell RC, Gan J, Dumont E, Burns O, Johns BA. A Phase 1 Study to Assess the Relative Bioavailability, Food Effect, and Safety of a Tablet Formulation of GSK2838232, a Novel HIV Maturation Inhibitor in Healthy Participants After Single and Repeated Doses. Clin Pharmacol Drug Dev. 2020 Nov;9(8):972-977. doi: 10.1002/cpdd.820. Epub 2020 Jun 18.

Results Reference

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Learn more about this trial

A Two-part Study to Compare a Tablet and Capsule Formulation of GSK2838232 With and Without Food, and to Assess the Safety and Drug Levels of Repeated Once-daily Doses of GSK2838232 Without Ritonavir

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