Evaluation of Pharmacokinetic Interaction Between GSK3640254 and Caffeine, Metoprolol, Montelukast, Flurbiprofen, Omeprazole, Midazolam, Digoxin, and Pravastatin in Healthy Adults

This is an open-label, single sequence study that is being conducted to investigate the potential drug-drug interaction (DDI) when GSK3640254 is co-administered with a cocktail of cytochrome P450 (CYP) enzymes and transporter probe substrates in healthy participants. This study will aid in understanding these interactions and resulting changes in exposure (if any) when drugs that are metabolized via these pathways are given in combination with GSK3640254. The study will consist of a Screening period and 3 sequential treatment regimens. Participants will be administered a single dose of probe substrate drugs (caffeine 200 milligram (mg), metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg and pravastatin 40 mg) on Day 1. Participants will then receive GSK3640254 200 mg once daily on Days 11 to 20 followed by co-administration of probe substrate drugs with GSK3640254 on Day 21.


Eligibility Criteria:
Inclusion Criteria:

* Participant must be 18 to 50 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 (including cardiopulmonary examination), laboratory tests, and cardiac monitoring (history and ECG).
* Body weight more than or equal to (\>=) 50.0 kilograms (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 kilogram 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 should 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.
* A female participant is eligible to participate if she is not pregnant or breastfeeding and at least one of the following conditions applies:
* Is not a woman of childbearing potential (WOCBP) or
* Is a WOCBP and using a non-hormonal contraceptive method that is highly effective, with a failure rate of less than (\<) 1 percent (%) for 28 days before intervention, during the intervention period, and for at least 28 days after the last dose of study intervention.
* A WOCBP must have a negative highly sensitive serum pregnancy test at Screening and check-in (Day-1).
* Capable of giving signed informed consent, which includes compliance with the requirements and restrictions, listed in the informed consent form (ICF) and in the protocol.

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 (e.g., gastro-esophageal reflux disease, gastric ulcers, gastritis) or 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.
* 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 ViiV Healthcare (VH)/GlaxoSmithKline (GSK) 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.
* History of asthma, bronchospasm, or sleep apnea.
* History of chronic musculoskeletal pain (myalgias).
* History of rhabdomyolysis.
* History of a bleeding disorder.
* History of Raynaud's disease.
* History indicative of an increased risk of a cardiac arrhythmia or cardiac disease, including the following:
* History of cardiac arrhythmias or palpitations associated with presyncope or syncope, or history of unexplained syncope.
* History of clinically relevant cardiac disease including symptomatic or asymptomatic arrhythmias (including but not limited to ventricular fibrillation, ventricular tachycardia, any degree of atrioventricular block, Brugada syndrome, Wolff-Parkinson-White syndrome, and sinus bradycardia, defined as heart rate less than 50 beats per minute (bpm) based on vital signs or ECG), presyncope or syncopal episodes, or additional risk factors for torsades de pointes (e.g., heart failure).
* History of clinically relevant structural cardiac disease including hypertrophic obstructive cardiomyopathy.
* History of hypokalemia.
* History of heart disease (e.g., coronary heart disease).
* 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 HIV-1 and 2 antigen/antibody immunoassay at Screening.
* ALT\>=1.5 × upper limit of normal (ULN). A single repeat of ALT is allowed within a single screening period to determine eligibility.
* Bilirubin \>=5 × ULN (isolated bilirubin \>=5 × 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 lipid abnormalities (e.g., total cholesterol, triglycerides), and ALT, 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 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 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 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).
* Prior exposure to GSK3640254 in another clinical study.
* Where participation in the study would result in donation of blood or blood products in excess of 500 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).
* SBP \<100 mm Hg. Up to 2 repeats are allowed for confirmation.
* 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, any degree of atrioventricular block, or conduction abnormality) which 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 bpm, PR interval- \>200 milliseconds and QTcF- \>450 milliseconds.
* 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 (g) 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.
* History of aspirin allergy.
* A participant with known or suspected active coronavirus disease of 2019 (COVID-19) infection OR contact with an individual with known COVID-19, within 14 days of study enrollment.