GSK3739937 First-Time-In-Human (FTIH) Study in Healthy Volunteers
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: GSK3739937 (PIB); Placebo; GSK3739937 (Tablet)
Intervention description: GSK3739937 will be administered as oral suspension.; Placebo will be given orally during each dosing day.; GSK3739937 Tablet will be administered via oral route.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Part 1 is a single ascending dose study, Part 2 is multiple ascending dose study while Part 3 is a 3-period crossover design.
Masking: Double (Participant, Investigator)
Masking description: This will be a double-blind study with participants and the site-staff blinded and sponsor unblended. Part 3 of the study will be open-label.
Enrollment: 91.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Acquired Immunodeficiency Syndrome; First-time-in-human; Pharmacokinetics; Safety; Tolerability

Summary:

      This study is a Phase 1, double-blind (sponsor-unblinded), randomized, placebo-controlled,
      single- and repeat-dose escalation study including a weekly oral dose (MAD) cohort and a
      relative bioavailability (RBA) and food effect (FE) cohort to investigate the safety,
      tolerability and PK of VH3739937 in healthy participants. This is a three part study. Part 1
      and Part 2 is designed to gain information on the safety, tolerability, and pharmacokinetic
      (PK) properties of GSK3739937 when administered as powder-in-a-bottle (PiB). Part 3 will
      evaluate the RBA of the GSK3739937 PiB and GSK3739937 Tablet and the safety, tolerability and
      PK parameters of the tablet formulation when administered under fasting and fed conditions.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant must be 18 to 55 years of age inclusive, at the time of signing the
             informed consent.

          -  Participants who are overtly 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).

          -  Participants who are negative on two consecutive tests for severe acute respiratory
             syndrome coronavirus-2 (SARs-CoV-2), performed at Screening and on admission and
             (re-)admission to the Phase I unit, using an approved molecular test polymerase chain
             reaction (PCR).

          -  Participants who are able to understand and comply with protocol requirements and
             timetables, instructions, and protocol-stated restrictions.

          -  Body weight >=50.0 kilograms (kg) (110 pound [lbs]) for men and >=45.0 kg (99 lbs) for
             women and body mass index within the range 18.5 to 32.0 kilogram per square meter
             (kg/m^2).

          -  Male participants are eligible to participate if they agree to use contraceptive
             methods

          -  A female participant is eligible to participate if she is not pregnant or
             breastfeeding, and is not a woman of childbearing potential (WOCBP). - Capable of
             giving signed informed consent

        Exclusion Criteria:

          -  Signs and symptoms which in the opinion of the investigator are suggestive of
             coronavirus disease 2019 (COVID-19) (i.e. fever, cough etc) within 14 days of
             inpatient admission.

          -  Contact with known COVID-19 positive persons in the 14 days prior to inpatient
             admission.

          -  History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal,
             endocrine, hematological, or neurological disorders capable of significantly altering
             the absorption, distribution, metabolism, or elimination of drugs; constituting a risk
             when taking the study intervention or interfering with the interpretation of data.

          -  Pre-existing clinically relevant, in the opinion of the principal investigator (PI),
             gastro-intestinal pathology or diagnosis - e.g. irritable bowel syndrome, inflammatory
             bowel disease, and/or significant baseline signs and symptoms.

          -  Medical history of cardiac arrhythmias or cardiac disease or a family and personal
             history of long QT syndrome.

          -  Any known or suspected pre-existing psychiatric condition

          -  Any positive (abnormal) response confirmed by the investigator or clinician (or
             qualified designee) administered Columbia Suicide Severity Rating Scale (CSSRS) at
             screening .

          -  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 participant
             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.

          -  Estimated glomerular filtration rate (eGFR) <90 milliliters/minute (mL/min) or serum
             creatinine >1.1 x upper limit of normal (ULN).

          -  Hemoglobin <12.5 grams/deciliter (g/dL) for men and <11 g/dL for women.

          -  ALT or AST >1.1x ULN.

          -  Bilirubin >1.1 x ULN (isolated bilirubin >1.1 x ULN is acceptable if bilirubin is
             fractionated and direct bilirubin <35%).

          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities
             (with the exception of Gilbert's syndrome or asymptomatic gallstones)

          -  Any significant arrhythmia or ECG finding (e.g., prior myocardial infarction in the
             past 3 months (does not include ST segment changes associated with repolarization),
             symptomatic bradycardia, non-sustained or sustained atrial arrhythmias, non-sustained
             or sustained ventricular tachycardia (>=3 consecutive ventricular ectopic beats),
             second-degree atrioventricular (AV) block Mobitz Type II, third-degree
             atrioventricular block, complete heart block, or conduction abnormality (including but
             not specific to left or right complete bundle branch; AV block [2nd degree or higher];
             Wolff-Parkinson-White [WPW] syndrome), Sinus Pauses > 3 seconds, which, in the opinion
             of the investigator or ViiV Healthcare (VH)/ GlaxoSmithKline (GSK) Medical Monitor,
             will interfere with the safety for the individual participant.

          -  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.

          -  Past or intended use of over-the-counter or prescription medication [including
             cytochrome p450 enzyme inducers or inhibitors, vitamins, herbal and dietary
             supplements ] within 7 days (or 14 days if the drug is a potential enzyme inducer) or
             5 half-lives (whichever is longer) prior to dosing and for the duration of the study,
             unless in the opinion of the Investigator and Sponsor, the medication will not
             interfere with the study medications, procedures, or compromise participant 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 treatments or until the end of the study.

          -  Participation in the study would result in loss of blood or blood products in excess
             of 500 mL within 56 days

          -  Exposure to more than 4 new chemical entities within 12 months prior to the first
             dosing day

          -  Current enrolment or past participation within the last 30 days, 5 half-lives or twice
             the duration of the biological effect of the investigational product (whichever is
             longer) before signing of consent in this or any other clinical study involving an
             investigational study intervention or any other type of medical research

          -  Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior
             to first dose of study intervention

          -  Positive Hepatitis C antibody test result at screening or within 3 months prior to
             first dose of study intervention.

          -  Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3
             months prior to first dose of study intervention

          -  Positive pre-study drug/alcohol screen

          -  Positive HIV antibody/antigen test

          -  Regular use of known drugs of abuse

          -  Regular alcohol consumption within 6 months prior to the study defined as: An average
             weekly intake of >14 units for males or >7 units for females.

          -  Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or
             nicotine-containing products (e.g. nicotine patches or vaporizing devices) within 6
             months prior to screening and at admission.

          -  Sensitivity to any of the study interventions, or components thereof, or drug or other
             allergy that, in the opinion of the investigator or medical monitor, contraindicates
             participation in the study.