Effect of Therapeutic and Supratherapeutic Oral Doses of GSK3640254 on Cardiac Conduction Compared to Placebo and a Single Oral Dose of Moxifloxacin

This study will aim to evaluate the effect of therapeutic and supratherapeutic oral doses of GSK3640254 on cardiac conduction compared to placebo and a single oral dose of Moxifloxacin in healthy adult participants. The study has 2 parts: Part 1 will determine the supratherapeutic dose for Part 2, which will be the main corrected QT interval (QTc) study. Part 1 will evaluate once daily (QD) dosing of GSK3640254 or placebo and Part 2 will investigate the safety, tolerability and Pharmacokinetics (PK) of GSK3640254 doses on cardiac conduction as compared to placebo and a single oral dose of Moxifloxacin in healthy adult participants. Moxifloxacin will be included as a positive control.


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 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 kilograms 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 or female participants:

  1. 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.
  2. Female participants:

  (i) A female participant is eligible to participate if she is not pregnant, planning to become pregnant within the next 6 months, or breastfeeding, and at least 1 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. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.

(ii) A WOCBP must have a negative highly sensitive serum pregnancy test at Screening and Check-in.

* Capable of giving signed informed, which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in this protocol.

Exclusion criteria:

* Participants with 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 (for example \[e.g.\], gastro-esophageal 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 (prior appendectomy is acceptable).
* Clinically significant illness, including viral syndromes, within 3 weeks of dosing.
* A participant with known or suspected active Coronavirus Disease-2019 (COVID-19) infection OR contact with an individual with known COVID-19, within 14 days of study enrollment (World Health Organization \[WHO\] definitions).
* 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 (more than \[\>\]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/GlaxoSmithKline (VH/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 indicative of an increased risk of a cardiac arrhythmia or cardiac disease, including the following:

  1. History of symptomatic cardiac arrhythmias or palpitations associated with pre-syncope or syncope, or history of unexplained syncope.
  2. History of cardiac arrest.
  3. 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 HR less than 50 bpm based on vital signs or ECG), presyncope or syncopal episodes, or additional risk factors for torsades de pointes (e.g., heart failure).
  4. History of clinically relevant structural cardiac disease including hypertrophic obstructive cardiomyopathy.
  5. History of hypokalemia.
* History of heart disease (e.g., coronary heart disease, angina).
* 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.
* Positive Human Immunodeficiency virus (HIV)-1 and -2 antigen/antibody immunoassay at Screening.
* Alanine aminotransferase (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 (including hypokalemia, hypercalcemia, or hypomagnesemia) 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 (previously described), 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.
* Urine drug screen positive (showing presence of): amphetamines, barbiturates, cocaine, Methylenedioxymethamphetamine (MDMA), cannabinoids, methamphetamines, phencyclidine, or non-prescribed opiates, oxycodone, benzodiazepines, methadone, or tricyclic antidepressants at screening or before dosing of study intervention.
* Unable to refrain from the use of prescription or nonprescription drugs including vitamins, herbal and dietary supplements (including Saint \[St\] 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 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 this or another clinical study.
* Prior intolerance to Moxifloxacin.
* Prior participation in this clinical study (participants may not participate in both Part 1 and Part 2 of the 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).
* A sustained supine systolic blood pressure \>150 millimeters of mercury (mm Hg) or \<90 mm Hg or a supine diastolic blood pressure \>95 mm Hg or \<50 mm Hg at Screening or Check-in (Day -2). Blood pressure may be retested once in the supine position. The blood pressure abnormality is considered sustained if either the systolic or the diastolic pressure values are outside the stated limits after 2 assessments, in which case the participant may not be randomized.
* A resting HR of \<50 bpm or \>100 bpm when vital signs are measured at Screening or Check-in (Day -2). A HR from 100 to 110 bpm can be rechecked by ECG or vital signs within up to 2 hours to verify eligibility.
* An uninterpretable ECG or any significant arrhythmia or ECG finding (e.g., prior myocardial infarction in the past 3 months, significant pathological Q-waves (defined as Q-wave \>40 ms or depth greater than 0.4-0.5 millivolts \[mV\], symptomatic bradycardia, non-sustained or sustained atrial arrhythmias, ventricular pre-excitation, non-sustained or sustained ventricular tachycardia, any degree of atrioventricular block, complete left bundle branch block, or conduction abnormality) which, in the opinion of the investigator or VH/GSK Medical Monitor, will interfere with the safety of the individual participant.
* Exclusion criteria for Screening ECG (a single repeat is allowed for eligibility determination):

  (i) HR: \<50 or \>100 bpm (ii) QTcF interval1: \>450 ms (iii) QRS interval: \>110 ms (iv) PR interval: \>200 ms
* Screening Holter (24 hours) with any of the following:

  (i) Sinus bradycardia less than or equal to (\<=)35 bpm or junctional arrhythmia \>60 bpm for 10 seconds or longer.

(ii) Non-sustained ventricular tachycardia or more than 30 ventricular premature depolarizations during an hour.

(iii) Atrial arrhythmia \>100 bpm for 3 seconds or longer or more than 40 atrial premature depolarizations during an hour.

* History of alcoholism and/or drug/chemical abuse or regular alcohol consumption within 6 months of screening, 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 and for the duration of the study.
* 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.