Evaluation of Pharmacokinetic Interaction Between GSK3640... | NCT04425902

Label	Type	Description	Intervention Names
Probe Substrates/GSK3640254 200 mg/Probe Substrates+GSK3640254	Experimental	All participants will receive a single dose of treatment A: Probe substrates (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; followed by treatment B- GSK3640254 200 mg on Days 11 to 20; further followed by treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.	Drug: GSK3640254 200 mg Drug: Caffeine 200 mg Drug: Metoprolol 100 mg Drug: Montelukast 10 mg Drug: Flurbiprofen 100 mg Drug: Omeprazole 40 mg Drug: Midazolam 5 mg (2.5 mL) Drug: Digoxin 0.25 mg Drug: Pravastatin 40 mg

Name	Type	Description	Arm Group Labels	Other Names
GSK3640254 200 mg	Drug	GSK3640254 will be available as oral tablets at unit dose strength of 100 mg.	Probe Substrates/GSK3640254 200 mg/Probe Substrates+GSK3640254

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Time t (AUC[0-t]) for Caffeine	Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine. Area under the plasma concentration-time curve from time zero to time t, to be calculated using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.	Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3
AUC From Time Zero Extrapolated to Infinity (AUC[0-infinity]) for Caffeine	Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.	Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3
Maximum Observed Plasma Concentration (Cmax) for Caffeine	Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine.	Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3
Time to Cmax (Tmax) for Caffeine	Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine.	Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3
Apparent Terminal Phase Half-life (t1/2) for Caffeine	Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine.

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE was defined as any untoward medical occurrence that, at any dose, results in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and other situations according to medical or scientific judgement.

Eligibility Module

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.

Name	Affiliation	Role
GSK Clinical Trials	ViiV Healthcare	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Las Vegas	Nevada	89113	United States

PubMed Identifier	Type	Citation	Retractions
36822839	Background	Zhang Y, Johnson M, Joshi S, Yazdani P, Zhan J, Wen B, Bainbridge V, Gartland M, Lataillade M. Open-label, drug-drug interaction study between the HIV-1 maturation inhibitor GSK3640254 and a metabolic probe cocktail in healthy participants. Br J Clin Pharmacol. 2023 Jul;89(7):2236-2245. doi: 10.1111/bcp.15699. Epub 2023 Mar 13.

ID	Title	Description
FG000	All Treated Participants	All treated participants received a single dose of treatment A: Probe substrates (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; followed by treatment B- GSK3640254 200 mg once daily from Days 11 to 20; further followed by treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Apr 12, 2021	Feb 18, 2022

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Time t (AUC[0-t]) for Caffeine

Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine. Area under the plasma concentration-time curve from time zero to time t, to be calculated using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

The Pharmacokinetic (PK) Parameter Population included all participants who underwent plasma PK sampling and had evaluable PK parameters estimated. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hour*nanograms per milliliter (h*ng/mL)

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG00020 OG00119

Title

Denominators

Categories

Title	Measurements
	OG00037970± 31.1 OG00142230± 32.4

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Ratio of geometric least square mean	1.11			2-Sided	90	0.94	1.32			A mixed-effect model with treatment as a fixed effect and measurements within participant as repeated measures was performed on the natural ln-transformed parameter.		Other

Primary

AUC From Time Zero Extrapolated to Infinity (AUC[0-infinity]) for Caffeine

Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Primary

Maximum Observed Plasma Concentration (Cmax) for Caffeine

Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanograms per milliliter (ng/mL)

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts

Primary

Time to Cmax (Tmax) for Caffeine

Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Median

Full Range

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

Apparent Terminal Phase Half-life (t1/2) for Caffeine

Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

AUC(0-t) for Metoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Primary

AUC(0-infinity) for Metoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Primary

Cmax for Metoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

Tmax for Metoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Median

Full Range

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

t1/2 for Metoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

AUC(0-t) for Montelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Primary

AUC(0-infinity) for Montelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Primary

Cmax for Montelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanograms per milliliter (ng/mL)

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

Tmax for Montelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Median

Full Range

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

t1/2 for Montelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

AUC(0-t) for Flurbiprofen

Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Primary

AUC(0-infinity) for Flurbiprofen

Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Primary

Cmax for Flurbiprofen

Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

Tmax for Flurbiprofen

Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Median

Full Range

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

t1/2 for Flurbiprofen

Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

AUC(0-t) for Omeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Primary

AUC(0-infinity) for Omeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Primary

Cmax for Omeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

Tmax for Omeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Median

Full Range

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

t1/2 for Omeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

AUC(0-t) for Midazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Primary

AUC(0-infinity) for Midazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Primary

Cmax for Midazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

Tmax for Midazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Median

Full Range

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

t1/2 for Midazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

AUC(0-t) for Digoxin

Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours*picogram per milliliter (h*pg/mL)

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Primary

AUC(0-infinity) for Digoxin

Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*pg/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Primary

Cmax for Digoxin

Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Picogram per milliliter (pg/mL)

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

Tmax for Digoxin

Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Median

Full Range

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

t1/2 for Digoxin

Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

AUC(0-t) for Pravastatin

Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Primary

AUC(0-infinity) for Pravastatin

Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Primary

Cmax for Pravastatin

Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

Tmax for Pravastatin

Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Median

Full Range

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Primary

t1/2 for Pravastatin

Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Secondary

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE was defined as any untoward medical occurrence that, at any dose, results in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and other situations according to medical or scientific judgement.

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Count of Participants

Participants

Up to Day 26

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.
OG002	Treatment C: Probe Substrates + GSK3640254 200 mg

Secondary

Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils

Blood samples were collected to analyze the hematology parameters: platelet count, leukocyte count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A.

Safety Population.

Posted

Mean

Standard Deviation

10^9 cells per liter

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils

Blood samples were collected to analyze the hematology parameters: platelet count, leukocyte count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B.

Safety Population.

Posted

Mean

Standard Deviation

10^9 cells per liter

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils

Blood samples were collected to analyze the hematology parameters: platelet count, leukocyte count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C.

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

10^9 cells per liter

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Absolute Values of Hematocrit

Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A.

Safety Population.

Posted

Mean

Standard Deviation

Proportion of red blood cells in blood

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Absolute Values of Hematocrit

Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B.

Safety Population.

Posted

Mean

Standard Deviation

Proportion of red blood cells in blood

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Absolute Values of Hematocrit

Blood samples were collected to analyze the hematology parameter: hematocrit. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C.

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Proportion of red blood cells in blood

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Absolute Values of Hemoglobin

Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A.

Safety Population.

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Absolute Values of Hemoglobin

Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B.

Safety Population.

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Absolute Values of Hemoglobin

Blood samples were collected to analyze the hematology parameter: hemoglobin. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C.

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Absolute Values of Erythrocytes

Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A.

Safety Population.

Posted

Mean

Standard Deviation

10^12 cells per liter

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Absolute Values of Erythrocytes

Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B.

Safety Population.

Posted

Mean

Standard Deviation

10^12 cells per liter

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Absolute Values of Erythrocytes

Blood samples were collected to analyze the hematology parameter: erythrocytes. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C.

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

10^12 cells per liter

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Absolute Values of Erythrocytes Mean Corpuscular Volume

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A.

Safety Population.

Posted

Mean

Standard Deviation

Femtoliter

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Absolute Values of Erythrocytes Mean Corpuscular Volume

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B.

Safety Population.

Posted

Mean

Standard Deviation

Femtoliter

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Volume

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular volume. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C.

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Femtoliter

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A.

Safety Population.

Posted

Mean

Standard Deviation

Picograms

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B.

Safety Population.

Posted

Mean

Standard Deviation

Picograms

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin

Blood samples were collected to analyze the hematology parameter: erythrocytes mean corpuscular hemoglobin. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C.

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Picograms

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea

Blood samples were collected to analyze the chemistry parameters: glucose, carbon dioxide, cholesterol, triglycerides, anion gap, calcium, chloride, phosphate, potassium, sodium, urea. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A.

Safety Population.

Posted

Mean

Standard Deviation

Millimoles per liter

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea

Blood samples were collected to analyze the chemistry parameters: glucose, carbon dioxide, cholesterol, triglycerides, anion gap, calcium, chloride, phosphate, potassium, sodium, and urea. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B.

Safety Population.

Posted

Mean

Standard Deviation

Millimoles per liter

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea

Blood samples were collected to analyze the chemistry parameters: glucose, carbon dioxide, cholesterol, triglycerides, anion gap, calcium, chloride, phosphate, potassium, sodium and urea. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C.

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Millimoles per liter

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin

Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A.

Safety Population.

Posted

Mean

Standard Deviation

Micromoles per liter

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin

Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B.

Safety Population.

Posted

Mean

Standard Deviation

Micromoles per liter

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin

Blood samples were collected to analyze the chemistry parameters: urate, creatinine, bilirubin and direct bilirubin. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C.

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Micromoles per liter

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Absolute Values of Albumin, Globulin, Protein

Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A.

Safety Population.

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Absolute Values of Albumin, Globulin, Protein

Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B.

Safety Population.

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Absolute Values of Albumin, Globulin, Protein

Blood samples were collected to analyze the chemistry parameters: albumin, globulin and protein. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C.

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase

Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST and gamma-glutamyl transferase. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A.

Safety Population.

Posted

Mean

Standard Deviation

International units per liter

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase

Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST, and gamma-glutamyl transferase. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B.

Safety Population.

Posted

Mean

Standard Deviation

International units per liter

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase

Blood samples were collected to analyze the chemistry parameters: creatine kinase, lactate dehydrogenase, ALT, ALP, AST, gamma-glutamyl transferase. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C.

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

International units per liter

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Absolute Values of Amylase, Lipase

Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A.

Safety Population.

Posted

Mean

Standard Deviation

Units per liter

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Absolute Values of Amylase, Lipase

Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B.

Safety Population.

Posted

Mean

Standard Deviation

Units per liter

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Absolute Values of Amylase, Lipase

Blood samples were collected to analyze the chemistry parameters: amylase and lipase. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C.

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Units per liter

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils

Safety Population.

Posted

Mean

Standard Deviation

10^9 cells per liter

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils

Blood samples were collected to analyze the hematology parameters: platelet count, leukocyte count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Safety Population.

Posted

Mean

Standard Deviation

10^9 cells per liter

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils

Blood samples were collected to analyze the hematology parameters: platelet count, leukocyte count, neutrophils, lymphocytes, monocytes, eosinophils and basophils. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

10^9 cells per liter

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Change From Baseline in Hematocrit

Safety Population.

Posted

Mean

Standard Deviation

Proportion of red blood cells in blood

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Change From Baseline in Hematocrit

Safety Population.

Posted

Mean

Standard Deviation

Proportion of red blood cells in blood

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Change From Baseline in Hematocrit

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Proportion of red blood cells in blood

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Change From Baseline in Hemoglobin

Safety Population.

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Change From Baseline in Hemoglobin

Safety Population.

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Change From Baseline in Hemoglobin

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Change From Baseline in Erythrocytes

Safety Population.

Posted

Mean

Standard Deviation

10^12 cells per liter

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Change From Baseline in Erythrocytes

Safety Population.

Posted

Mean

Standard Deviation

10^12 cells per liter

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Change From Baseline in Erythrocytes

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

10^12 cells per liter

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Change From Baseline in Erythrocytes Mean Corpuscular Volume

Safety Population.

Posted

Mean

Standard Deviation

Femtoliter

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Change From Baseline in Erythrocytes Mean Corpuscular Volume

Safety Population.

Posted

Mean

Standard Deviation

Femtoliter

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Volume

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Femtoliter

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin

Safety Population.

Posted

Mean

Standard Deviation

Picograms

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin

Safety Population.

Posted

Mean

Standard Deviation

Picograms

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Picograms

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea

Blood samples were collected to analyze the chemistry parameters: glucose, carbon dioxide, cholesterol, triglycerides, anion gap, calcium, chloride, phosphate, potassium, sodium, and urea. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day -1), before the dose of Treatment A. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Safety Population.

Posted

Mean

Standard Deviation

Millimoles per liter

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea

Blood samples were collected to analyze the chemistry parameters: glucose, carbon dioxide, cholesterol, triglycerides, anion gap, calcium, chloride, phosphate, potassium, sodium, and urea. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 10), before the first dose of Treatment B. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Safety Population.

Posted

Mean

Standard Deviation

Millimoles per liter

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea

Blood samples were collected to analyze the chemistry parameters: glucose, carbon dioxide, cholesterol, triglycerides, anion gap, calcium, chloride, phosphate, potassium, sodium and urea. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 20), before the dose of Treatment C. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Millimoles per liter

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Secondary

Treatment A: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin

Safety Population.

Posted

Mean

Standard Deviation

Micromoles per liter

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin

Safety Population.

Posted

Mean

Standard Deviation

Micromoles per liter

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Micromoles per liter

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Change From Baseline in Albumin, Globulin, Protein

Safety Population.

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Change From Baseline in Albumin, Globulin, Protein

Safety Population.

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Change From Baseline in Albumin, Globulin, Protein

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Grams per liter

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase

Safety Population.

Posted

Mean

Standard Deviation

International units per liter

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase

Safety Population.

Posted

Mean

Standard Deviation

International units per liter

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

International units per liter

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Change From Baseline in Amylase, Lipase

Safety Population.

Posted

Mean

Standard Deviation

Units per liter

Baseline (Day -1) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Change From Baseline in Amylase, Lipase

Safety Population.

Posted

Mean

Standard Deviation

Units per liter

Baseline (Day 10) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Change From Baseline in Amylase, Lipase

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Units per liter

Baseline (Day 20), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)

Twelve-lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 1, Pre-Dose), before the dose in Treatment A.

Safety Population.

Posted

Mean

Standard Deviation

Milliseconds

Baseline (Day 1, Pre-Dose) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval

Twelve-lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 11, Pre-Dose), before the first dose in Treatment B.

Safety Population.

Posted

Mean

Standard Deviation

Milliseconds

Baseline (Day 11, Pre-Dose) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval

Twelve-lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 21, Pre-Dose), before the first dose in Treatment C.

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Milliseconds

Baseline (Day 21, Pre-Dose), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF

Safety Population.

Posted

Mean

Standard Deviation

Milliseconds

Baseline (Day 1, Pre-dose) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF

Twelve-lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 11, Pre-Dose), before the first dose in Treatment B. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Safety Population.

Posted

Mean

Standard Deviation

Milliseconds

Baseline (Day 11, Pre-Dose) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF

Twelve-lead ECGs were obtained to measure PR Interval, QRS Duration, QT Interval and QTcF Interval. Twelve-lead ECGs were performed with the participant in a supine position after a rest of at least 10 minutes. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 21, Pre-Dose), before the first dose in Treatment C. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Milliseconds

Baseline (Day 21, Pre-Dose), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Secondary

Treatment A: Absolute Values of Oral Temperature

Oral temperature was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 1, Pre-Dose), before the dose in Treatment A.

Safety Population.

Posted

Mean

Standard Deviation

Degrees Celsius

Baseline (Day 1, Pre-dose) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Absolute Values of Oral Temperature

Oral temperature was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 11, Pre-Dose), before the first dose in Treatment B.

Safety Population.

Posted

Mean

Standard Deviation

Degrees Celsius

Baseline (Day 11, Pre-Dose) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Absolute Values of Oral Temperature

Oral temperature was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 21, Pre-Dose), before the first dose in Treatment C.

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Degrees Celsius

Baseline (Day 21, Pre-Dose), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Absolute Values of Pulse Rate

Pulse rate was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 1, Pre-Dose), before the dose in Treatment A.

Safety Population.

Posted

Mean

Standard Deviation

Beats per minute

Baseline (Day 1, Pre-dose) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Absolute Values of Pulse Rate

Pulse rate was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 11, Pre-Dose), before the first dose in Treatment B.

Safety Population.

Posted

Mean

Standard Deviation

Beats per minute

Baseline (Day 11, Pre-Dose) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Absolute Values of Pulse Rate

Pulse rate was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 21, Pre-Dose), before the first dose in Treatment C.

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Beats per minute

Baseline (Day 21, Pre-Dose), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Absolute Values of Respiratory Rate

Respiratory rate was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 1, Pre-Dose), before the dose in Treatment A.

Safety Population.

Posted

Mean

Standard Deviation

Breaths per minute

Baseline (Day 1, Pre-dose) and Day 2

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Absolute Values of Respiratory Rate

Respiratory rate was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 11, Pre-Dose), before the first dose in Treatment B.

Safety Population.

Posted

Mean

Standard Deviation

Breaths per minute

Baseline (Day 11, Pre-Dose) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Absolute Values of Respiratory Rate

Respiratory rate was measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 21, Pre-Dose), before the first dose in Treatment C.

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Breaths per minute

Baseline (Day 21, Pre-Dose), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Absolute Values of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

SBP and DBP were measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment A was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 1, Pre-Dose), before the dose in Treatment A.

Safety Population.

Posted

Mean

Standard Deviation

Millimeters of mercury

Baseline (Day 1, Pre-dose) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Absolute Values of SBP and DBP

SBP and DBP were measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment B was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 11, Pre-Dose), before the first dose in Treatment B.

Safety Population.

Posted

Mean

Standard Deviation

Millimeters of mercury

Baseline (Day 11, Pre-Dose) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Absolute Values of SBP and DBP

SBP and DBP were measured in the supine position after at least 5 minutes of rest for the participant in a quiet setting without distractions. Baseline for treatment C was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits (Day 21, Pre-Dose), before the first dose in Treatment C.

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Millimeters of mercury

Baseline (Day 21, Pre-Dose), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Change From Baseline in Oral Temperature

Safety Population.

Posted

Mean

Standard Deviation

Degrees Celsius

Baseline (Day 1, Pre-dose) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Change From Baseline in Oral Temperature

Safety Population.

Posted

Mean

Standard Deviation

Degrees Celsius

Baseline (Day 11, Pre-Dose) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Change From Baseline in Oral Temperature

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Degrees Celsius

Baseline (Day 21, Pre-Dose), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Change From Baseline in Pulse Rate

Safety Population.

Posted

Mean

Standard Deviation

Beats per minute

Baseline (Day 1, Pre-dose) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Change From Baseline in Pulse Rate

Safety Population.

Posted

Mean

Standard Deviation

Beats per minute

Baseline (Day 11, Pre-Dose) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Change From Baseline in Pulse Rate

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Beats per minute

Baseline (Day 21, Pre-Dose), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Change From Baseline in Respiratory Rate

Safety Population.

Posted

Mean

Standard Deviation

Breaths per minute

Baseline (Day 1, Pre-dose) and Day 2

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Change From Baseline in Respiratory Rate

Safety Population.

Posted

Mean

Standard Deviation

Breaths per minute

Baseline (Day 11, Pre-Dose) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Change From Baseline in Respiratory Rate

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Breaths per minute

Baseline (Day 21, Pre-Dose), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment A: Change From Baseline in SBP and DBP

Safety Population.

Posted

Mean

Standard Deviation

Millimeters of mercury

Baseline (Day 1, Pre-dose) and Day 10

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.

Units	Counts
Participants	OG000

Secondary

Treatment B: Change From Baseline in SBP and DBP

Safety Population.

Posted

Mean

Standard Deviation

Millimeters of mercury

Baseline (Day 11, Pre-Dose) and Day 20

ID	Title	Description
OG000	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.

Units	Counts
Participants	OG000

Secondary

Treatment C: Change From Baseline in SBP and DBP

Safety Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Millimeters of mercury

Baseline (Day 21, Pre-Dose), Days 22 and 25

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment C: AUC(0-t) for GSK3640254

Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose in treatment period 3

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment C: AUC From Time Zero to the End of the Dosing Interval at Steady State (AUC[0-tau]) for GSK3640254

Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose in treatment period 3

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment C: Cmax for GSK3640254

Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose in treatment period 3

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment C: Plasma Concentration at the End of the Dosing Interval (Ctau) for GSK3640254

Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose in treatment period 3

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment C: Tmax for GSK3640254

Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Median

Full Range

Hours

Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose in treatment period 3

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

Treatment C: t1/2 for GSK3640254

Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours

Pre-dose and at 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 12, 24, 48, 72, 96, and 120 hours post-dose in treatment period 3

ID	Title	Description
OG000	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants	OG000

Secondary

AUC(0-t) for Alpha-hydroxymetoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol. Alpha-hydroxymetoprolol is a metabolite of metoprolol. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Secondary

AUC(0-infinity) for Alpha-hydroxymetoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol. Alpha-hydroxymetoprolol is a metabolite of metoprolol. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Secondary

Cmax for Alpha-hydroxymetoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol. Alpha-hydroxymetoprolol is a metabolite of metoprolol.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts

Secondary

Tmax for Alpha-hydroxymetoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol. Alpha-hydroxymetoprolol is a metabolite of metoprolol.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Median

Full Range

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts

Secondary

t1/2 for Alpha-hydroxymetoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol. Alpha-hydroxymetoprolol is a metabolite of metoprolol.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts

Secondary

AUC(0-t) for 36-hydroxymontelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukas. 36-hydroxymontelukast is a metabolite of montelukast. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Secondary

AUC(0-infinity) for 36-hydroxymontelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukast. 36-hydroxymontelukast is a metabolite of montelukast. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Secondary

Cmax for 36-hydroxymontelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukast. 36-hydroxymontelukast is a metabolite of montelukast.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts

Secondary

Tmax for 36-hydroxymontelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukast. 36-hydroxymontelukast is a metabolite of montelukast.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Median

Full Range

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts

Secondary

t1/2 for 36-hydroxymontelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukast. 36-hydroxymontelukast is a metabolite of montelukast.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts

Secondary

AUC(0-t) for 5-hydroxyomeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole. 5-hydroxyomeprazole is a metabolite of omeprazole. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Secondary

AUC(0-infinity) for 5-hydroxyomeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole. 5-hydroxyomeprazole is a metabolite of omeprazole. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Secondary

Cmax for 5-hydroxyomeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole. 5-hydroxyomeprazole is a metabolite of omeprazole.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts

Secondary

Tmax for 5-hydroxyomeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole. 5-hydroxyomeprazole is a metabolite of omeprazole.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Median

Full Range

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts

Secondary

t1/2 for 5-hydroxyomeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole. 5-hydroxyomeprazole is a metabolite of omeprazole.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts

Secondary

AUC(0-t) for 1-hydroxymidazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 1-hydroxymidazolam. 1-hydroxymidazolam is a metabolite of midazolam. The AUC(0-t) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Secondary

AUC(0-infinity) for 1-hydroxymidazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 1-hydroxymidazolam. 1-hydroxymidazolam is a metabolite of midazolam. The AUC(0-infinity) was determined using the linear trapezoidal rule for each incremental trapezoid and the log trapezoidal rule for each decremental trapezoid.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Secondary

Cmax for 1-hydroxymidazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 1-hydroxymidazolam. 1-hydroxymidazolam is a metabolite of midazolam.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts

Secondary

Tmax for 1-hydroxymidazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 1-hydroxymidazolam. 1-hydroxymidazolam is a metabolite of midazolam.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Median

Full Range

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts
Participants

Secondary

t1/2 for 1-hydroxymidazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of 1-hydroxymidazolam. 1-hydroxymidazolam is a metabolite of midazolam.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units	Counts

Secondary

Ratio of Cmax of Alpha-hydroxymetoprolol to Metoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of parent drug (metoprolol) and its metabolite (alpha-hydroxymetoprolol). Ratio of Cmax of metabolite to parent drug has been presented.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Ratio

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units

Secondary

Ratio of AUC(0-infinity) of Alpha-hydroxymetoprolol to Metoprolol

Blood samples were collected at the indicated time points for pharmacokinetic analysis of parent drug (metoprolol) and its metabolite (alpha-hydroxymetoprolol). Ratio of AUC(0-infinity) of metabolite to parent drug has been presented.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Ratio

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Secondary

Ratio of Cmax of 36-hydroxymontelukast to Montelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of parent drug (montelukast) and its metabolite (36-hydroxymontelukast). Ratio of Cmax of metabolite to parent drug has been presented.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Ratio

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units

Secondary

Ratio of AUC(0-infinity) of 36-hydroxymontelukast to Montelukast

Blood samples were collected at the indicated time points for pharmacokinetic analysis of parent drug (montelukast) and its metabolite (36-hydroxymontelukast). Ratio of AUC(0-infinity) of metabolite to parent drug has been presented.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Ratio

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Secondary

Ratio of Cmax of 5-hydroxyomeprazole to Omeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of parent drug (omeprazole) and its metabolite (5-hydroxyomeprazole). Ratio of Cmax of metabolite to parent drug has been presented.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Ratio

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units

Secondary

Ratio of AUC(0-infinity) of 5-hydroxyomeprazole to Omeprazole

Blood samples were collected at the indicated time points for pharmacokinetic analysis of parent drug (omeprazole) and its metabolite (5-hydroxyomeprazole). Ratio of AUC(0-infinity) of metabolite to parent drug has been presented.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Ratio

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Secondary

Ratio of Cmax of 1-hydroxymidazolam to Midazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of parent drug (midazolam) and its metabolite (1-hydroxymidazolam). Ratio of Cmax of metabolite to parent drug has been presented.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Ratio

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Units

Secondary

Ratio of AUC(0-infinity) of 1-hydroxymidazolam to Midazolam

Blood samples were collected at the indicated time points for pharmacokinetic analysis of parent drug (midazolam) and its metabolite (1-hydroxymidazolam). Ratio of AUC(0-infinity) of metabolite to parent drug has been presented.

PK Parameter Population. Only those participants with data available at the specified time points were analyzed.

Posted

Mean

Standard Deviation

Ratio

Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3

ID	Title	Description
OG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.
OG001	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Dizziness	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected20 at risk EG0013 affected20 at risk EG0020 affected19 at risk
Headache	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0001 affected20 at risk EG0011 affected20 at risk EG0021 affected19 at risk
Taste disorder	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected20 at risk EG0010 affected20 at risk EG0021 affected19 at risk
Nausea	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk EG0021 affected19 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected20 at risk EG0010 affected20 at risk EG0021 affected19 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk EG0020 affected19 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected20 at risk EG0010 affected20 at risk EG0021 affected19 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk EG0020 affected19 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk EG0020 affected19 at risk
Rash papular	Skin and subcutaneous tissue disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk EG0020 affected19 at risk
Dry throat	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk EG0020 affected19 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 affected20 at risk EG0011 affected20 at risk EG0020 affected19 at risk

ID	Term
D015658	HIV Infections
D000163	Acquired Immunodeficiency Syndrome
D007239	Infections

ID	Term
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D015229	Sexually Transmitted Diseases, Viral
D012749	Sexually Transmitted Diseases
D016180	Lentivirus Infections
D012192	Retroviridae Infections
D012327	RNA Virus Infections
D014777	Virus Diseases
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D007153	Immunologic Deficiency Syndromes
D007154	Immune System Diseases
D012897	Slow Virus Diseases

ID	Term
D014970	Xanthines
D000470	Alkaloids
D006571	Heterocyclic Compounds
D011688	Purinones
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D050198	Phenoxypropanolamines
D011412	Propanolamines
D000605	Amino Alcohols
D000438	Alcohols
D009930	Organic Chemicals
D020005	Propanols
D000588	Amines
D011422	Propionates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D001713	Biphenyl Compounds
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D053799	2-Pyridinylmethylsulfinylbenzimidazoles
D013454	Sulfoxides
D013457	Sulfur Compounds
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring
D001562	Benzimidazoles
D001569	Benzodiazepines
D001552	Benzazepines
D004071	Digitalis Glycosides
D002298	Cardenolides
D002301	Cardiac Glycosides
D002297	Cardanolides
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D006027	Glycosides
D002241	Carbohydrates
D009281	Naphthalenes
D011084	Polycyclic Aromatic Hydrocarbons

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Treatment A: Probe Substrates	All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 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.	20	20	1	20
EG001	Treatment B: GSK3640254 200 mg	All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.	20	20	5	20
EG002	Treatment C: Probe Substrates + GSK3640254 200 mg	All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.	19	19	5	19

ID	Term
C000723722	GSK3640254
D002110	Caffeine
D008790	Metoprolol
C093875	montelukast
D005480	Flurbiprofen
D009853	Omeprazole
D008874	Midazolam
D004077	Digoxin
D017035	Pravastatin