A Relative Bioavailability and Food-Effect Study of GSK3640254 Tablet and Capsule Formulations in Healthy Participants
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: GSK3640254 Tablet; GSK3640254 Capsule
Intervention description: GSK3640254 tablets will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.; GSK3640254 capsules will contain mesylate salt with a unit dose of 100 mg (2x100 mg) and will be administered orally.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Eligible participants will be randomly assigned to 1 of 2 treatment sequences (AB or BA) in Part 1 and 1 of 3 treatment sequences (CDE, DEC, or ECD) in Part 2.
Masking: None (Open Label)
Masking description: This is an open label study.
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Healthy participants; GSK3640254; Human immunodeficiency virus; Relative Bioavailability

Summary:

      This is an open-label, 2 part, single-dose and crossover study conducted to assess the
      relative bioavailability of a tablet compared to a capsule of GSK3640254 and to assess the
      effect of food on the GSK3640254 tablet in healthy participants. This study will also
      evaluate the effect of food (fasted, moderate fat meal, and high fat meal) on the
      pharmacokinetics of the GSK3640254 mesylate tablet formulation. In Part 1, participants will
      be randomly assigned to 1 of 2 treatment sequences (AB or BA) in two sequential treatment
      periods; and in Part 2, participants will be randomly assigned to 1 of 3 treatment sequences
      (CDE, DEC, or ECD) in three sequential treatment periods. Participants will be randomized to
      receive a single dose of GSK3640254 200 milligram (mg) capsules under moderate fat conditions
      and GSK3640254 200 mg tablets under moderate fat, fasted and high fat conditions in each
      treatment period. Approximately 30 participants will be enrolled.
    

Eligibility criteria:

        Inclusion Criteria

          -  Participants must be 18 to 55 years of age inclusive, at the time of signing the
             informed consent.

          -  Participants who are 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 (history and ECG).

          -  Body weight >=50.0 kilogram (kg) (110 pounds [lbs]) for men and >=45.0 kg (99 lbs) for
             women and body mass index within the range 18.5 to 31.0 kg per square meter (kg/m^2)
             (inclusive).

          -  Contraceptive use by men or women should be consistent with local regulations
             regarding the methods of contraception for those participating in clinical studies.
             Male participants: Males shall not engage in intercourse while confined in the clinic.
             There is no need for an extended period of double barrier use or prolonged abstinence
             after study discharge. Female participants: 1. A female participant is eligible to
             participate if she is not pregnant or breastfeeding, and at least 1 of the following
             conditions applies: a. not a woman of childbearing potential (WOCBP); or Is a WOCBP
             and using a nonhormonal contraceptive method that is highly effective, with a failure
             rate of <1 percent (%), for 28 days before intervention, during the intervention
             period, and for at least 28 days after the last dose of study intervention. The
             investigator should evaluate the effectiveness of the contraceptive method in
             relationship to the first dose of study intervention. 2. A WOCBP must have a negative
             highly sensitive serum pregnancy test at Screening and Day -1. 3. Additional
             requirements for pregnancy testing during and after study intervention.

          -  The investigator is responsible for review of medical history, menstrual history, and
             recent sexual activity to decrease the risk for inclusion of a woman with an early
             undetected pregnancy.

          -  Capable of giving signed informed consent, which includes compliance with the
             requirements and restrictions.

        Exclusion Criteria

          -  Current or chronic history of liver disease or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).

          -  A pre-existing condition interfering with normal gastrointestinal (GI) anatomy or
             motility (example [e.g.], gastroesophageal reflux disease, gastric ulcers, gastritis),
             hepatic and/or renal function, that could interfere with the absorption, metabolism,
             and/or excretion of the study intervention or render the participant unable to take
             oral study intervention.

          -  Prior cholecystectomy surgery (prior appendectomy is acceptable).

          -  Any history of significant underlying psychiatric disorder, including, but not limited
             to, schizophrenia, bipolar disorder with or without psychotic symptoms, other
             psychotic disorders, or schizotypal (personality) disorder.

          -  Any history of major depressive disorder with or without suicidal features, or anxiety
             disorders that required medical intervention (pharmacologic or not) such as
             hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient
             treatment. Participants with other conditions such as adjustment disorder or dysthymia
             that have required shorter term medical therapy (<6 months) without inpatient
             treatment and are currently well-controlled clinically or resolved may be considered
             for entry after discussion and agreement with the Medical Monitor.

          -  Any pre-existing physical or other psychiatric condition (including alcohol or drug
             abuse), which, in the opinion of the investigator (with or without psychiatric
             evaluation), could interfere with the participant's ability to comply with the dosing
             schedule and protocol evaluations or which might compromise the safety of the
             participant.

          -  Medical history of cardiac arrhythmias, prior myocardial infarction in the past 3
             months, or cardiac disease or a family or personal history of long QT syndrome.

          -  Presence of hepatitis B surface antigen at Screening or within 3 months prior to
             starting study intervention.

          -  Positive hepatitis C antibody test result at Screening or within 3 months prior to
             starting study intervention and positive on reflex to hepatitis C ribonucleic acid
             (RNA).

          -  Positive Human immunodeficiency virus (HIV)-1 and -2 antigen/antibody immunoassay at
             Screening.

          -  ALT >1.5 times upper limit of normal (ULN). A single repeat of ALT is allowed within a
             single Screening period to determine eligibility.

          -  Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin
             is fractionated and direct bilirubin <35%). A single repeat of any laboratory
             abnormality is allowed within a single Screening period to determine eligibility.

          -  Any acute laboratory abnormality at Screening which, in the opinion of the
             investigator, should preclude participation in the study of an investigational
             compound.

          -  Any Grade 2 to 4 laboratory abnormality at Screening, with the exception of creatine
             phosphokinase (CPK) and lipid abnormalities (e.g., total cholesterol, triglycerides),
             and ALT (described above), will exclude a participant from the study unless the
             investigator can provide a compelling explanation for the laboratory result(s) and has
             the assent of the sponsor. A single repeat of any laboratory abnormality is allowed
             within a single Screening period to determine eligibility.

          -  A positive test result for drugs of abuse (including marijuana), alcohol, or cotinine
             (indicating active current smoking) at Screening or before the first dose of study
             intervention.

          -  Unable to refrain from the use of prescription or nonprescription drugs including
             vitamins, herbal and dietary supplements (including Saint 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 intervention and for the duration of the
             study.

          -  Treatment with any vaccine within 30 days prior to receiving study intervention.

          -  Unwillingness to abstain from excessive consumption of any food or drink containing
             grapefruit and grapefruit juice, Seville oranges, blood oranges, or pomelos or their
             fruit juices within 7 days prior to the first dose of study intervention(s) 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 study
             intervention (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.

          -  Any positive (abnormal) response confirmed by the investigator on a screening
             clinician- or qualified designee-administered Columbia Suicide Severity Rating Scale
             (C-SSRS).

          -  Any significant arrhythmia or ECG finding (e.g., prior myocardial infarction in the
             past 3 months, symptomatic bradycardia, non-sustained or sustained atrial arrhythmias,
             non-sustained or sustained ventricular tachycardia, second-degree atrioventricular
             block Mobitz Type II, third-degree atrioventricular block, complete heart block, or
             conduction abnormality) which, in the opinion of the investigator or Medical Monitor,
             will interfere with the safety for the individual participant.

          -  Exclusion criteria for Screening ECG (a single repeat is allowed for eligibility
             determination): Heart rate: <50 or >100 beats per minute and QTcF interval: >450
             millisecond.

          -  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 grams of alcohol: a
             half pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL)
             measure of spirits.

          -  Unable to refrain from 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.