GSK3640254 First Time in Human (FTIH) Study in Healthy Volunteers
Condition: Infection, Human Immunodeficiency Virus; HIV Infections
MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome
Intervention: GSK3640254; Placebo
Intervention description: 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 capsule matching to the study treatment will be given via oral route during each dosing day with approximately 240 mL of water.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: This is a dose-escalation study and dose will be escalated based on the safety data of the initial dose.
Masking: Double (Participant, Investigator)
Masking description: This will be a double-blind study with subjects and the site-staff blinded and sponsor unblinded.
Enrollment: 78.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: FTIH; Healthy; Tolerability; Dose-escalation; HIV-1; Safety; PK; GSK3640254; Maturation inhibitor

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.
    

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.

          -  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.