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

NCT ID: NCT03234036

Last Updated: 2020-10-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-02
• Study Completion Date: 2017-11-10

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.

Conditions

Infection, Human Immunodeficiency Virus; HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Treatment sequence ABC: Part 1

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.

Group Type: EXPERIMENTAL

GSK2838232 100 mg tablet

Intervention Type: DRUG

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.

GSK2838232 50 mg capsule

Intervention Type: DRUG

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.

Ritonavir 100 mg tablets

Intervention Type: DRUG

It is a white film-coated ovaloid tablets.

Treatment sequence BAC: Part 1

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.

Group Type: EXPERIMENTAL

GSK2838232 100 mg tablet

Intervention Type: DRUG

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.

GSK2838232 50 mg capsule

Intervention Type: DRUG

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.

Ritonavir 100 mg tablets

Intervention Type: DRUG

It is a white film-coated ovaloid tablets.

GSK2838232 tablet without RTV: Part 2

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).

Group Type: EXPERIMENTAL

GSK2838232 100 mg tablet

Intervention Type: DRUG

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.

Placebo without RTV: Part 2

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

Group Type: PLACEBO_COMPARATOR

Placebo for GSK2838232 tablets

Intervention Type: DRUG

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.

Interventions

GSK2838232 100 mg tablet

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

GSK2838232 50 mg capsule

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

Ritonavir 100 mg tablets

It is a white film-coated ovaloid tablets.

Intervention Type: DRUG

Placebo for GSK2838232 tablets

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.

Intervention Type: DRUG

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.

Exclusion Criteria

• 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.

• 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.

• 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.

• 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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Baltimore, Maryland, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 32558338 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

205820

Identifier Type: -

Identifier Source: org_study_id