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

NCT ID: NCT03231943

Last Updated: 2021-06-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-19
• Study Completion Date: 2018-09-09

Brief Summary

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

Conditions

Infection, Human Immunodeficiency Virus; HIV Infections

Study Design

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

Study Groups

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.

Group Type: EXPERIMENTAL

GSK3640254

Intervention Type: DRUG

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

Intervention Type: DRUG

Placebo capsule matching to the study treatment will be given via oral route during each dosing day with approximately 240 mL of water.

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.

Group Type: EXPERIMENTAL

GSK3640254

Intervention Type: DRUG

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.

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo capsule matching to the study treatment will be given via oral route during each dosing day with approximately 240 mL of water.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.
• 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.

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

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

ViiV Healthcare

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

GSK Investigational Site

Cambridge, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: BACKGROUND

PMID: 33200887 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-001367-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

207187

Identifier Type: -

Identifier Source: org_study_id