A Study to Compare the Relative Bioavailability of Two Different Formulations of GSK3640254
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: GSK3640254 bis-hydrochloride salt capsule; GSK3640254 Mesylate Salt Capsule
Intervention description: Administered orally (as single dose) on morning of Day 1, as 2 capsules of 100 mg following a moderate calorie and fat meal during Period 1 and Period 2, at the specified sequence, as per study.; Administered orally (as single dose) on morning of Day 1, as 2 capsules of , 100 mg following a moderate calorie and fat meal during Period 1 and Period 2, at the specified sequence, as per study.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Subjects will receive GSK3640254 bis-hydrochloride salt capsule followed by mesylate salt capsule or vice versa in two treatment periods.
Masking: None (Open Label)
Masking description: This is an open-label study.
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: 2-period; Pharmacokinetics; FTIH; GSK3640254; healthy subject; bioavailability

Summary:

      This is a first time in human (FTIH), 2-period study, to assess the relative bioavailability
      of a mesylate salt capsule of GSK3640254, compared to a bis- hydrochloride salt capsule of
      GSK3640254, in healthy subjects, administered following a moderate calorie and fat meal. The
      subjects will be randomized to 2 sequences, Regimen AB or Regimen BA. For Regimen AB: The
      Regimen A, which will include oral administration of GSK3640254 bis-hydrochloride Capsule 200
      milligram (mg) (reference), which will be administered, in Period 1 and Regimen B will
      include GSK3640254 Mesylate salt capsule (test), 200 mg, which will be administered in Period
      2. For the regimen BA, the regimen B, will be administered, in Period 1 and regimen A, in
      Period 2. Each of the regimens will be given orally as 2 capsules in the morning, as per
      randomization sequence. There will be a minimum washout of 7 days between each dose of study
      treatment. A total, of 14 subjects, are planned to be enrolled in the study. The maximum
      duration of the study from screening to follow-up is approximately 7 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject 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, physical examination, laboratory tests, and cardiac monitoring.

          -  Body weight >= 50 kilogram (kg) for men and >= 45 kg for women, and body mass index
             (BMI) within the range 19.0 to 32.0 kg per meter square (kg/m^2) (inclusive).

          -  Male or female subjects, where 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 and the
             female subjects who is eligible to participate if she is not a woman of childbearing
             potential (WOCBP).

          -  Capable of giving signed informed consent

        Exclusion Criteria:

          -  History of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal
             (GI), endocrine, hematological, or neurological disorders capable of significantly
             altering the absorption, metabolism, or elimination of drugs; constituting a risk when
             taking the study treatment; or interfering with the interpretation of data.

          -  History of clinically significant psychiatric disorders as judged by the investigator.
             Psychiatric disorder requiring pharmacologic treatment in the last 5 years.

          -  Any positive (abnormal) response confirmed by the investigator on a screening
             clinician (or qualified designee) administered Columbia Suicide Severity Rating Scale
             (CSSRS).

          -  History or current evidence of febrile seizures, epilepsy, convulsions, significant
             head injury, or other significant neurologic conditions.

          -  History of GI surgery (with exception of appendectomy).

          -  History of Cholecystectomy

          -  Any history of GI ulceration (esophageal, stomach, duodenal).

          -  Any history of GI symptoms requiring treatment in the last 3 months

          -  History of unexplained vaginal bleeding, endometrial hyperplasia with atypia or
             endometrial carcinoma

          -  Presence or history of clinically significant allergy requiring treatment, as judged
             by the investigator. Hayfever, is allowed unless it is active.

          -  ALT >1.5x upper limit of normal (ULN).

          -  Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is
             fractionated and direct bilirubin <35% of total).

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome).

          -  Medical history of cardiac arrhythmias or cardiac disease or a family or personal
             history of long QT syndrome.

          -  ECG, screening details where heart rate (<40 or >100 beats per minute [bpm]), PR
             interval (<120 or >220 millisecond [msec]), QRS duration (<70 or >120 msec), QT
             interval by Fridericia's correction formula (QTcF) interval (>450 msec) for male
             subjects and heart rate of <50 or >100 bpm for female subjects.

          -  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 (AV) block [2nd degree or higher], Wolf
             Parkinson- White [WPW] syndrome).

          -  Sinus Pauses >3 seconds

          -  Any significant arrhythmia which, in the opinion of the Investigator OR
             GlaxoSmithKline (GSK)/ViiV Medical monitor, will interfere with the safety for the
             individual subject.

          -  Non-sustained or sustained ventricular tachycardia (with consecutive ventricular
             ectopic beats).

          -  Prior or concomitant therapy, where past or intended use of over-the-counter or
             prescription medication, including herbal medications within 7 days (or 14 days if the
             drug is a potential enzyme inducer), or 5 half-lives (whichever is longer) prior to
             dosing (paracetamol/acetaminophen [up to 2 grams per day], and 2.5%, hydrocortisone
             [for ECG lead contact dermatitis] is permitted any time during the study).

          -  Prior or concurrent clinical study experience where, participation in the study would
             result in loss of blood or blood products in excess of 500 mL within a 56 day period;
             therefore donation or loss of greater than 400 mL of blood within the previous 3
             months.

          -  Current enrollment or past participation within the last 3 months before signing of
             consent in this or any other clinical study involving an investigational study
             treatment or any other type of medical research.

          -  Subjects, who have previously been enrolled in this study.

          -  Presence of Hepatitis B surface antigen (HBsAg) at screening or positive Hepatitis C
             antibody test result at screening or within 3 months prior to first dose.

          -  Confirmed positive pre-study drug/alcohol screen.

          -  Positive human immunodeficiency virus (HIV) antibody test.

          -  Regular use of known drugs of abuse, or history of drug or alcohol abuse in the past 5
             years.

          -  Regular alcohol consumption within 6 months prior to the study defined as an average
             weekly intake of >21 units for males or >14 units for females. One unit is equivalent
             to 8 gram of alcohol: a half-pint (approximately 240 mL) of beer or 1 (25 mL) measure
             of spirits. One glass (125 mL) of wine is equivalent to 1.5 to 2 units, depending on
             type)

          -  Current use or history of regular use of tobacco- or nicotine-containing products
             within 6 months prior to screening. A confirmed carbon monoxide breath test reading of
             greater than 10 parts per million.

          -  Sensitivity to any of the study treatments, or components thereof, or drug or other
             allergy that, in the opinion of the investigator or medical monitor, contraindicates
             participation in the study.

          -  Subjects who do not have suitable veins for multiple venepunctures/cannulation as
             assessed by the investigator at screening.

          -  Subjects who do not have the ability to swallow size 00 capsules.

          -  Subjects who are study site employees, or immediate family members of a study site or
             sponsor employee.