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

Effects of GSK3640254 on the Single-Dose Pharmacokinetics of Probe Substrates (Caffeine, Metoprolol, Montelukast, Flurbiprofen, Omeprazole, Midazolam, Digoxin, and Pravastatin) in Healthy Subjects

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04425902

Enrollment

Registered

2020-06-11

Start date

2020-12-16

Completion date

2021-03-10

Last updated

2024-01-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

HIV Infections

Keywords

GSK3640254, Human immunodeficiency virus (HIV) infections, Drug interaction, Pharmacokinetics, Probe substrate

Brief summary

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

Interventions

DRUGGSK3640254 200 mg

GSK3640254 will be available as oral tablets at unit dose strength of 100 mg.

DRUGCaffeine 200 mg

Caffeine will be available as oral tablets at unit dose strength of 200 mg.

DRUGMetoprolol 100 mg

Metoprolol will be available as oral tablets at unit dose strength of 100 mg.

DRUGMontelukast 10 mg

Montelukast will be available as oral tablets at unit dose strength of 10 mg.

DRUGFlurbiprofen 100 mg

Flurbiprofen will be available as oral tablets at unit dose strength of 100 mg.

DRUGOmeprazole 40 mg

Omeprazole will be available as oral capsules at unit dose strength of 40 mg.

DRUGMidazolam 5 mg (2.5 mL)

Midazolam will be available as syrup for oral administration at unit dose strength of 2 milligram per milliliter (mg/mL).

DRUGDigoxin 0.25 mg

Digoxin will be available as oral tablet at unit dose strength of 0.25 mg.

DRUGPravastatin 40 mg

Pravastatin will be available as oral tablet at unit dose strength of 40 mg.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Masking description

This is a single-group, single-arm study that has no masking.

Intervention model description

This is a single-sequence, one-way drug interaction study.

Eligibility

Sex/Gender

ALL

Age

18 Years to 50 Years

Healthy volunteers

Yes

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. *

Design outcomes

Primary

Measure	Time frame	Description
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Time t (AUC[0-t]) for 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	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.
AUC From Time Zero Extrapolated to Infinity (AUC[0-infinity]) for 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	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.
Maximum Observed Plasma Concentration (Cmax) for 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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine.
Time to Cmax (Tmax) for 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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine.
Apparent Terminal Phase Half-life (t1/2) for 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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine.
AUC(0-t) for Metoprolol	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	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.
AUC(0-infinity) for Metoprolol	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	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.
Cmax for Metoprolol	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol.
Tmax for Metoprolol	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol.
t1/2 for Metoprolol	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol.
AUC(0-t) for Montelukast	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	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.
AUC(0-infinity) for Montelukast	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	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.
Cmax for Montelukast	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast.
Tmax for Montelukast	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast.
t1/2 for Montelukast	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast.
AUC(0-t) for Flurbiprofen	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	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.
AUC(0-infinity) for Flurbiprofen	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	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.
Cmax for Flurbiprofen	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen.
Tmax for Flurbiprofen	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen.
t1/2 for Flurbiprofen	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen.
AUC(0-t) for Omeprazole	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	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.
AUC(0-infinity) for Omeprazole	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	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.
Cmax for Omeprazole	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole.
Tmax for Omeprazole	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole.
t1/2 for Omeprazole	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole.
AUC(0-t) for Midazolam	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	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.
AUC(0-infinity) for Midazolam	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	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.
Cmax for Midazolam	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam.
Tmax for Midazolam	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam.
t1/2 for Midazolam	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam.
AUC(0-t) for Digoxin	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	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.
AUC(0-infinity) for Digoxin	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	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.
Cmax for Digoxin	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin.
Tmax for Digoxin	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin.
t1/2 for Digoxin	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin.
AUC(0-t) for Pravastatin	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	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.
AUC(0-infinity) for Pravastatin	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	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.
Cmax for Pravastatin	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin.
Tmax for Pravastatin	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin.
t1/2 for Pravastatin	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin.

Secondary

Measure	Time frame	Description
Treatment B: Change From Baseline in Hematocrit	Baseline (Day 10) and Day 20	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment C: Change From Baseline in Hematocrit	Baseline (Day 20), Days 22 and 25	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment A: Change From Baseline in Hemoglobin	Baseline (Day -1) and Day 10	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment B: Change From Baseline in Hemoglobin	Baseline (Day 10) and Day 20	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment C: Change From Baseline in Hemoglobin	Baseline (Day 20), Days 22 and 25	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment A: Change From Baseline in Erythrocytes	Baseline (Day -1) and Day 10	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment B: Change From Baseline in Erythrocytes	Baseline (Day 10) and Day 20	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment C: Change From Baseline in Erythrocytes	Baseline (Day 20), Days 22 and 25	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment A: Change From Baseline in Erythrocytes Mean Corpuscular Volume	Baseline (Day -1) and Day 10	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment B: Change From Baseline in Erythrocytes Mean Corpuscular Volume	Baseline (Day 10) and Day 20	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Volume	Baseline (Day 20), Days 22 and 25	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment A: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin	Baseline (Day -1) and Day 10	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment B: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin	Baseline (Day 10) and Day 20	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin	Baseline (Day 20), Days 22 and 25	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day -1) and Day 10	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.
Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 10) and Day 20	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.
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 20), Days 22 and 25	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.
Treatment A: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin	Baseline (Day -1) and Day 10	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment B: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin	Baseline (Day 10) and Day 20	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment C: Tmax for GSK3640254	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	Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254.
Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin	Baseline (Day 20), Days 22 and 25	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment A: Change From Baseline in Albumin, Globulin, Protein	Baseline (Day -1) and Day 10	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment B: Change From Baseline in Albumin, Globulin, Protein	Baseline (Day 10) and Day 20	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment C: Change From Baseline in Albumin, Globulin, Protein	Baseline (Day 20), Days 22 and 25	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment A: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Baseline (Day -1) and Day 10	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment B: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Baseline (Day 10) and Day 20	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Baseline (Day 20), Days 22 and 25	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment A: Change From Baseline in Amylase, Lipase	Baseline (Day -1) and Day 10	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment B: Change From Baseline in Amylase, Lipase	Baseline (Day 10) and Day 20	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment C: Change From Baseline in Amylase, Lipase	Baseline (Day 20), Days 22 and 25	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)	Baseline (Day 1, Pre-Dose) and Day 10	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.
Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Baseline (Day 11, Pre-Dose) and Day 20	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.
Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Baseline (Day 21, Pre-Dose), Days 22 and 25	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.
Treatment C: t1/2 for GSK3640254	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	Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254.
Treatment A: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF	Baseline (Day 1, Pre-dose) and Day 10	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment B: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF	Baseline (Day 11, Pre-Dose) and Day 20	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.
Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF	Baseline (Day 21, Pre-Dose), Days 22 and 25	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.
Treatment A: Absolute Values of Oral Temperature	Baseline (Day 1, Pre-dose) and Day 10	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.
Treatment B: Absolute Values of Oral Temperature	Baseline (Day 11, Pre-Dose) and Day 20	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.
Treatment C: Absolute Values of Oral Temperature	Baseline (Day 21, Pre-Dose), Days 22 and 25	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.
Treatment A: Absolute Values of Pulse Rate	Baseline (Day 1, Pre-dose) and Day 10	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.
Treatment B: Absolute Values of Pulse Rate	Baseline (Day 11, Pre-Dose) and Day 20	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.
Treatment C: Absolute Values of Pulse Rate	Baseline (Day 21, Pre-Dose), Days 22 and 25	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.
Treatment A: Absolute Values of Respiratory Rate	Baseline (Day 1, Pre-dose) and Day 2	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.
Treatment B: Absolute Values of Respiratory Rate	Baseline (Day 11, Pre-Dose) and Day 20	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.
Treatment C: Absolute Values of Respiratory Rate	Baseline (Day 21, Pre-Dose), Days 22 and 25	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.
Treatment A: Absolute Values of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	Baseline (Day 1, Pre-dose) and Day 10	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.
Treatment B: Absolute Values of SBP and DBP	Baseline (Day 11, Pre-Dose) and Day 20	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.
Treatment C: Absolute Values of SBP and DBP	Baseline (Day 21, Pre-Dose), Days 22 and 25	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.
Treatment A: Change From Baseline in Oral Temperature	Baseline (Day 1, Pre-dose) and Day 10	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment B: Change From Baseline in Oral Temperature	Baseline (Day 11, Pre-Dose) and Day 20	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment C: Change From Baseline in Oral Temperature	Baseline (Day 21, Pre-Dose), Days 22 and 25	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment A: Change From Baseline in Pulse Rate	Baseline (Day 1, Pre-dose) and Day 10	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment B: Change From Baseline in Pulse Rate	Baseline (Day 11, Pre-Dose) and Day 20	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment C: Change From Baseline in Pulse Rate	Baseline (Day 21, Pre-Dose), Days 22 and 25	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment A: Change From Baseline in Respiratory Rate	Baseline (Day 1, Pre-dose) and Day 2	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment B: Change From Baseline in Respiratory Rate	Baseline (Day 11, Pre-Dose) and Day 20	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment C: Change From Baseline in Respiratory Rate	Baseline (Day 21, Pre-Dose), Days 22 and 25	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment A: Change From Baseline in SBP and DBP	Baseline (Day 1, Pre-dose) and Day 10	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment B: Change From Baseline in SBP and DBP	Baseline (Day 11, Pre-Dose) and Day 20	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment C: Change From Baseline in SBP and DBP	Baseline (Day 21, Pre-Dose), Days 22 and 25	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment C: AUC(0-t) for GSK3640254	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	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.
Treatment C: AUC From Time Zero to the End of the Dosing Interval at Steady State (AUC[0-tau]) for GSK3640254	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	Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254.
AUC(0-t) for Alpha-hydroxymetoprolol	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	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.
AUC(0-infinity) for Alpha-hydroxymetoprolol	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	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.
Cmax for Alpha-hydroxymetoprolol	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol. Alpha-hydroxymetoprolol is a metabolite of metoprolol.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	Up to Day 26	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.
t1/2 for Alpha-hydroxymetoprolol	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol. Alpha-hydroxymetoprolol is a metabolite of metoprolol.
AUC(0-t) for 36-hydroxymontelukast	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	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.
AUC(0-infinity) for 36-hydroxymontelukast	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	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.
Cmax for 36-hydroxymontelukast	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukast. 36-hydroxymontelukast is a metabolite of montelukast.
Tmax for 36-hydroxymontelukast	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukast. 36-hydroxymontelukast is a metabolite of montelukast.
t1/2 for 36-hydroxymontelukast	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukast. 36-hydroxymontelukast is a metabolite of montelukast.
AUC(0-t) for 5-hydroxyomeprazole	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	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.
AUC(0-infinity) for 5-hydroxyomeprazole	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	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.
Cmax for 5-hydroxyomeprazole	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole. 5-hydroxyomeprazole is a metabolite of omeprazole.
Tmax for 5-hydroxyomeprazole	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole. 5-hydroxyomeprazole is a metabolite of omeprazole.
t1/2 for 5-hydroxyomeprazole	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole. 5-hydroxyomeprazole is a metabolite of omeprazole.
AUC(0-t) for 1-hydroxymidazolam	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	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.
AUC(0-infinity) for 1-hydroxymidazolam	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	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.
Cmax for 1-hydroxymidazolam	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of 1-hydroxymidazolam. 1-hydroxymidazolam is a metabolite of midazolam.
Tmax for 1-hydroxymidazolam	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of 1-hydroxymidazolam. 1-hydroxymidazolam is a metabolite of midazolam.
t1/2 for 1-hydroxymidazolam	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of 1-hydroxymidazolam. 1-hydroxymidazolam is a metabolite of midazolam.
Ratio of Cmax of Alpha-hydroxymetoprolol to Metoprolol	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	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.
Ratio of AUC(0-infinity) of Alpha-hydroxymetoprolol to Metoprolol	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	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.
Ratio of Cmax of 36-hydroxymontelukast to Montelukast	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	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.
Ratio of AUC(0-infinity) of 36-hydroxymontelukast to Montelukast	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	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.
Ratio of Cmax of 5-hydroxyomeprazole to Omeprazole	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	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.
Ratio of AUC(0-infinity) of 5-hydroxyomeprazole to Omeprazole	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	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.
Ratio of Cmax of 1-hydroxymidazolam to Midazolam	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	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.
Ratio of AUC(0-infinity) of 1-hydroxymidazolam to Midazolam	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	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.
Tmax for Alpha-hydroxymetoprolol	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	Blood samples were collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol. Alpha-hydroxymetoprolol is a metabolite of metoprolol.
Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day -1) and Day 10	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.
Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day 10) and Day 20	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.
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day 20), Days 22 and 25	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.
Treatment A: Absolute Values of Hematocrit	Baseline (Day -1) and Day 10	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.
Treatment B: Absolute Values of Hematocrit	Baseline (Day 10) and Day 20	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.
Treatment C: Absolute Values of Hematocrit	Baseline (Day 20), Days 22 and 25	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.
Treatment A: Absolute Values of Hemoglobin	Baseline (Day -1) and Day 10	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.
Treatment B: Absolute Values of Hemoglobin	Baseline (Day 10) and Day 20	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.
Treatment C: Absolute Values of Hemoglobin	Baseline (Day 20), Days 22 and 25	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.
Treatment A: Absolute Values of Erythrocytes	Baseline (Day -1) and Day 10	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.
Treatment B: Absolute Values of Erythrocytes	Baseline (Day 10) and Day 20	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.
Treatment C: Absolute Values of Erythrocytes	Baseline (Day 20), Days 22 and 25	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.
Treatment A: Absolute Values of Erythrocytes Mean Corpuscular Volume	Baseline (Day -1) and Day 10	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.
Treatment B: Absolute Values of Erythrocytes Mean Corpuscular Volume	Baseline (Day 10) and Day 20	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.
Treatment C: Cmax for GSK3640254	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	Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254.
Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Volume	Baseline (Day 20), Days 22 and 25	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.
Treatment A: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin	Baseline (Day -1) and Day 10	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.
Treatment B: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin	Baseline (Day 10) and Day 20	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.
Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin	Baseline (Day 20), Days 22 and 25	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.
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day -1) and Day 10	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.
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 10) and Day 20	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.
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 20), Days 22 and 25	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.
Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Baseline (Day -1) and Day 10	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.
Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Baseline (Day 10) and Day 20	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.
Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Baseline (Day 20), Days 22 and 25	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.
Treatment A: Absolute Values of Albumin, Globulin, Protein	Baseline (Day -1) and Day 10	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.
Treatment B: Absolute Values of Albumin, Globulin, Protein	Baseline (Day 10) and Day 20	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.
Treatment C: Absolute Values of Albumin, Globulin, Protein	Baseline (Day 20), Days 22 and 25	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.
Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase	Baseline (Day -1) and Day 10	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.
Treatment C: Plasma Concentration at the End of the Dosing Interval (Ctau) for GSK3640254	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	Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254.
Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Baseline (Day 10) and Day 20	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.
Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Baseline (Day 20), Days 22 and 25	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.
Treatment A: Absolute Values of Amylase, Lipase	Baseline (Day -1) and Day 10	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.
Treatment B: Absolute Values of Amylase, Lipase	Baseline (Day 10) and Day 20	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.
Treatment C: Absolute Values of Amylase, Lipase	Baseline (Day 20), Days 22 and 25	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.
Treatment A: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day -1) and Day 10	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.
Treatment B: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day 10) and Day 20	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.
Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day 20), Days 22 and 25	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.
Treatment A: Change From Baseline in Hematocrit	Baseline (Day -1) and Day 10	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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

Countries

United States

Participant flow

Recruitment details

This study was conducted in the United States.

Pre-assignment details

A total of 20 participants were enrolled and received study treatment.

Participants by arm

Arm	Count
All Treated Participants 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; 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.	20
Total	20

Arm

Count

All Treated Participants

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; 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.

Total

Withdrawals & dropouts

Period	Reason	FG000
Treatment Period 2 (Days 11 to 20)	Adverse Event	1

Baseline characteristics

Characteristic	All Treated Participants
Age, Continuous	36.4 Years STANDARD_DEVIATION 9.65
Race/Ethnicity, Customized Black or African American	9 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	2 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	9 Participants
Sex: Female, Male Female	7 Participants
Sex: Female, Male Male	13 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 20	0 / 20	0 / 19
other Total, other adverse events	1 / 20	5 / 20	5 / 19
serious Total, serious adverse events	0 / 20	0 / 20	0 / 19

Outcome results

Primary

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

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

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	Apparent Terminal Phase Half-life (t1/2) for Caffeine	5.380 Hours	Geometric Coefficient of Variation 21.2
Treatment C: Probe Substrates + GSK3640254 200 mg	Apparent Terminal Phase Half-life (t1/2) for Caffeine	6.085 Hours	Geometric Coefficient of Variation 17.4

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.

Time frame: 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

Population: 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.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Time t (AUC[0-t]) for Caffeine	37970 Hournanograms per milliliter (hng/mL)	Geometric Coefficient of Variation 31.1
Treatment C: Probe Substrates + GSK3640254 200 mg	Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Time t (AUC[0-t]) for Caffeine	42230 Hournanograms per milliliter (hng/mL)	Geometric Coefficient of Variation 32.4

90% CI: [0.94, 1.32]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-infinity) for Digoxin	19180 h*pg/mL	Geometric Coefficient of Variation 21.5
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-infinity) for Digoxin	20090 h*pg/mL	Geometric Coefficient of Variation 27.1

90% CI: [0.92, 1.19]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-infinity) for Flurbiprofen	66700 h*ng/mL	Geometric Coefficient of Variation 28.1
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-infinity) for Flurbiprofen	68660 h*ng/mL	Geometric Coefficient of Variation 26.7

90% CI: [0.89, 1.19]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-infinity) for Metoprolol	659.1 h*ng/mL	Geometric Coefficient of Variation 134.4
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-infinity) for Metoprolol	813.1 h*ng/mL	Geometric Coefficient of Variation 135.3

90% CI: [0.71, 2.14]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-infinity) for Midazolam	70.08 h*ng/mL	Geometric Coefficient of Variation 31.4
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-infinity) for Midazolam	65.46 h*ng/mL	Geometric Coefficient of Variation 31.2

90% CI: [0.79, 1.1]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-infinity) for Montelukast	2859 h*ng/mL	Geometric Coefficient of Variation 20.6
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-infinity) for Montelukast	3109 h*ng/mL	Geometric Coefficient of Variation 18.6

90% CI: [0.98, 1.21]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-infinity) for Omeprazole	1127 h*ng/mL	Geometric Coefficient of Variation 98.6
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-infinity) for Omeprazole	1093 h*ng/mL	Geometric Coefficient of Variation 75.5

90% CI: [0.54, 1.73]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-infinity) for Pravastatin	72.09 h*ng/mL	Geometric Coefficient of Variation 62.9
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-infinity) for Pravastatin	43.70 h*ng/mL	Geometric Coefficient of Variation 47.5

90% CI: [0.45, 0.82]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-t) for Digoxin	16690 Hourspicogram per milliliter (hpg/mL)	Geometric Coefficient of Variation 21.7
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-t) for Digoxin	17840 Hourspicogram per milliliter (hpg/mL)	Geometric Coefficient of Variation 26.9

90% CI: [0.94, 1.22]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-t) for Flurbiprofen	64930 h*ng/mL	Geometric Coefficient of Variation 28.9
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-t) for Flurbiprofen	66170 h*ng/mL	Geometric Coefficient of Variation 27.6

90% CI: [0.88, 1.18]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-t) for Metoprolol	655.0 h*ng/mL	Geometric Coefficient of Variation 135.2
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-t) for Metoprolol	807.3 h*ng/mL	Geometric Coefficient of Variation 136.4

90% CI: [0.71, 2.14]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-t) for Midazolam	67.11 h*ng/mL	Geometric Coefficient of Variation 31.3
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-t) for Midazolam	62.95 h*ng/mL	Geometric Coefficient of Variation 31

90% CI: [0.8, 1.11]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-t) for Montelukast	2724 h*ng/mL	Geometric Coefficient of Variation 19.9
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-t) for Montelukast	2940 h*ng/mL	Geometric Coefficient of Variation 18.4

90% CI: [0.97, 1.2]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-t) for Omeprazole	728.1 h*ng/mL	Geometric Coefficient of Variation 114.7
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-t) for Omeprazole	817.9 h*ng/mL	Geometric Coefficient of Variation 82.1

90% CI: [0.72, 1.75]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-t) for Pravastatin	69.92 h*ng/mL	Geometric Coefficient of Variation 63.9
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-t) for Pravastatin	51.03 h*ng/mL	Geometric Coefficient of Variation 75.5

90% CI: [0.52, 1.03]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC From Time Zero Extrapolated to Infinity (AUC[0-infinity]) for Caffeine	39720 h*ng/mL	Geometric Coefficient of Variation 30.6
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC From Time Zero Extrapolated to Infinity (AUC[0-infinity]) for Caffeine	44440 h*ng/mL	Geometric Coefficient of Variation 30.6

90% CI: [0.95, 1.32]

Primary

Cmax for Digoxin

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

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	Cmax for Digoxin	1026 Picogram per milliliter (pg/mL)	Geometric Coefficient of Variation 48.3
Treatment C: Probe Substrates + GSK3640254 200 mg	Cmax for Digoxin	1282 Picogram per milliliter (pg/mL)	Geometric Coefficient of Variation 56.5

90% CI: [0.96, 1.63]

Primary

Cmax for Flurbiprofen

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

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	Cmax for Flurbiprofen	10220 ng/mL	Geometric Coefficient of Variation 24.7
Treatment C: Probe Substrates + GSK3640254 200 mg	Cmax for Flurbiprofen	10710 ng/mL	Geometric Coefficient of Variation 19.8

90% CI: [0.93, 1.18]

Primary

Cmax for Metoprolol

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

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	Cmax for Metoprolol	127.4 ng/mL	Geometric Coefficient of Variation 90
Treatment C: Probe Substrates + GSK3640254 200 mg	Cmax for Metoprolol	141.1 ng/mL	Geometric Coefficient of Variation 94.4

90% CI: [0.72, 1.69]

Primary

Cmax for Midazolam

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

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	Cmax for Midazolam	15.44 ng/mL	Geometric Coefficient of Variation 39.5
Treatment C: Probe Substrates + GSK3640254 200 mg	Cmax for Midazolam	13.95 ng/mL	Geometric Coefficient of Variation 42.3

90% CI: [0.73, 1.12]

Primary

Cmax for Montelukast

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

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	Cmax for Montelukast	379.8 Nanograms per milliliter (ng/mL)	Geometric Coefficient of Variation 25.2
Treatment C: Probe Substrates + GSK3640254 200 mg	Cmax for Montelukast	393.5 Nanograms per milliliter (ng/mL)	Geometric Coefficient of Variation 19.5

90% CI: [0.92, 1.17]

Primary

Cmax for Omeprazole

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

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	Cmax for Omeprazole	224.4 ng/mL	Geometric Coefficient of Variation 121.6
Treatment C: Probe Substrates + GSK3640254 200 mg	Cmax for Omeprazole	256.6 ng/mL	Geometric Coefficient of Variation 72

90% CI: [0.73, 1.78]

Primary

Cmax for Pravastatin

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

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	Cmax for Pravastatin	19.45 ng/mL	Geometric Coefficient of Variation 79.8
Treatment C: Probe Substrates + GSK3640254 200 mg	Cmax for Pravastatin	15.19 ng/mL	Geometric Coefficient of Variation 76.9

90% CI: [0.54, 1.14]

Primary

Maximum Observed Plasma Concentration (Cmax) for Caffeine

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

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	Maximum Observed Plasma Concentration (Cmax) for Caffeine	4340 Nanograms per milliliter (ng/mL)	Geometric Coefficient of Variation 22.1
Treatment C: Probe Substrates + GSK3640254 200 mg	Maximum Observed Plasma Concentration (Cmax) for Caffeine	4110 Nanograms per milliliter (ng/mL)	Geometric Coefficient of Variation 25.9

90% CI: [0.83, 1.08]

Primary

t1/2 for Digoxin

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

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	t1/2 for Digoxin	40.279 Hours	Geometric Coefficient of Variation 14.3
Treatment C: Probe Substrates + GSK3640254 200 mg	t1/2 for Digoxin	38.784 Hours	Geometric Coefficient of Variation 12

Primary

t1/2 for Flurbiprofen

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

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	t1/2 for Flurbiprofen	6.123 Hours	Geometric Coefficient of Variation 31
Treatment C: Probe Substrates + GSK3640254 200 mg	t1/2 for Flurbiprofen	6.088 Hours	Geometric Coefficient of Variation 30.4

Primary

t1/2 for Metoprolol

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

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	t1/2 for Metoprolol	4.872 Hours	Geometric Coefficient of Variation 65.6
Treatment C: Probe Substrates + GSK3640254 200 mg	t1/2 for Metoprolol	5.342 Hours	Geometric Coefficient of Variation 59.6

Primary

t1/2 for Midazolam

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

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	t1/2 for Midazolam	5.756 Hours	Geometric Coefficient of Variation 13.2
Treatment C: Probe Substrates + GSK3640254 200 mg	t1/2 for Midazolam	5.222 Hours	Geometric Coefficient of Variation 20.6

Primary

t1/2 for Montelukast

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

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	t1/2 for Montelukast	5.035 Hours	Geometric Coefficient of Variation 10.2
Treatment C: Probe Substrates + GSK3640254 200 mg	t1/2 for Montelukast	5.135 Hours	Geometric Coefficient of Variation 7.4

Primary

t1/2 for Omeprazole

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

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	t1/2 for Omeprazole	1.439 Hours	Geometric Coefficient of Variation 32
Treatment C: Probe Substrates + GSK3640254 200 mg	t1/2 for Omeprazole	1.219 Hours	Geometric Coefficient of Variation 28.1

Primary

t1/2 for Pravastatin

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

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	t1/2 for Pravastatin	3.189 Hours	Geometric Coefficient of Variation 43.4
Treatment C: Probe Substrates + GSK3640254 200 mg	t1/2 for Pravastatin	3.156 Hours	Geometric Coefficient of Variation 47.2

Primary

Time to Cmax (Tmax) for Caffeine

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

Time frame: 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

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

Arm	Measure	Value (MEDIAN)
Treatment A: Probe Substrates	Time to Cmax (Tmax) for Caffeine	2.000 Hours
Treatment C: Probe Substrates + GSK3640254 200 mg	Time to Cmax (Tmax) for Caffeine	3.000 Hours

Primary

Tmax for Digoxin

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

Time frame: 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

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

Arm	Measure	Value (MEDIAN)
Treatment A: Probe Substrates	Tmax for Digoxin	3.000 Hours
Treatment C: Probe Substrates + GSK3640254 200 mg	Tmax for Digoxin	2.000 Hours

Primary

Tmax for Flurbiprofen

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

Time frame: 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

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

Arm	Measure	Value (MEDIAN)
Treatment A: Probe Substrates	Tmax for Flurbiprofen	3.000 Hours
Treatment C: Probe Substrates + GSK3640254 200 mg	Tmax for Flurbiprofen	4.000 Hours

Primary

Tmax for Metoprolol

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

Time frame: 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

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

Arm	Measure	Value (MEDIAN)
Treatment A: Probe Substrates	Tmax for Metoprolol	2.000 Hours
Treatment C: Probe Substrates + GSK3640254 200 mg	Tmax for Metoprolol	3.000 Hours

Primary

Tmax for Midazolam

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

Time frame: 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

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

Arm	Measure	Value (MEDIAN)
Treatment A: Probe Substrates	Tmax for Midazolam	1.000 Hours
Treatment C: Probe Substrates + GSK3640254 200 mg	Tmax for Midazolam	1.000 Hours

Primary

Tmax for Montelukast

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

Time frame: 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

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

Arm	Measure	Value (MEDIAN)
Treatment A: Probe Substrates	Tmax for Montelukast	5.000 Hours
Treatment C: Probe Substrates + GSK3640254 200 mg	Tmax for Montelukast	6.000 Hours

Primary

Tmax for Omeprazole

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

Time frame: 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

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

Arm	Measure	Value (MEDIAN)
Treatment A: Probe Substrates	Tmax for Omeprazole	6.000 Hours
Treatment C: Probe Substrates + GSK3640254 200 mg	Tmax for Omeprazole	6.000 Hours

Primary

Tmax for Pravastatin

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

Time frame: 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

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

Arm	Measure	Value (MEDIAN)
Treatment A: Probe Substrates	Tmax for Pravastatin	1.500 Hours
Treatment C: Probe Substrates + GSK3640254 200 mg	Tmax for Pravastatin	3.000 Hours

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-infinity) for 1-hydroxymidazolam	31.86 h*ng/mL	Geometric Coefficient of Variation 32.5
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-infinity) for 1-hydroxymidazolam	28.99 h*ng/mL	Geometric Coefficient of Variation 36.6

90% CI: [0.76, 1.09]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-infinity) for 36-hydroxymontelukast	252.5 h*ng/mL	Geometric Coefficient of Variation 48.2
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-infinity) for 36-hydroxymontelukast	249.3 h*ng/mL	Geometric Coefficient of Variation 58.7

90% CI: [0.75, 1.29]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-infinity) for 5-hydroxyomeprazole	767.4 h*ng/mL	Geometric Coefficient of Variation 30.9
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-infinity) for 5-hydroxyomeprazole	762.0 h*ng/mL	Geometric Coefficient of Variation 25.6

90% CI: [0.83, 1.19]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-infinity) for Alpha-hydroxymetoprolol	682.8 h*ng/mL	Geometric Coefficient of Variation 34.1
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-infinity) for Alpha-hydroxymetoprolol	632.8 h*ng/mL	Geometric Coefficient of Variation 50.7

90% CI: [0.74, 1.16]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-t) for 1-hydroxymidazolam	31.07 h*ng/mL	Geometric Coefficient of Variation 33
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-t) for 1-hydroxymidazolam	28.07 h*ng/mL	Geometric Coefficient of Variation 37

90% CI: [0.75, 1.09]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-t) for 36-hydroxymontelukast	234.2 h*ng/mL	Geometric Coefficient of Variation 47.2
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-t) for 36-hydroxymontelukast	230.9 h*ng/mL	Geometric Coefficient of Variation 59.1

90% CI: [0.75, 1.29]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-t) for 5-hydroxyomeprazole	713.5 h*ng/mL	Geometric Coefficient of Variation 38
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-t) for 5-hydroxyomeprazole	785.1 h*ng/mL	Geometric Coefficient of Variation 24.7

90% CI: [0.93, 1.3]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	AUC(0-t) for Alpha-hydroxymetoprolol	531.3 h*ng/mL	Geometric Coefficient of Variation 159.4
Treatment C: Probe Substrates + GSK3640254 200 mg	AUC(0-t) for Alpha-hydroxymetoprolol	487.9 h*ng/mL	Geometric Coefficient of Variation 174.4

90% CI: [0.49, 1.71]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	Cmax for 1-hydroxymidazolam	7.933 ng/mL	Geometric Coefficient of Variation 53.8
Treatment C: Probe Substrates + GSK3640254 200 mg	Cmax for 1-hydroxymidazolam	6.722 ng/mL	Geometric Coefficient of Variation 48.1

90% CI: [0.65, 1.1]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	Cmax for 36-hydroxymontelukast	24.62 ng/mL	Geometric Coefficient of Variation 45.7
Treatment C: Probe Substrates + GSK3640254 200 mg	Cmax for 36-hydroxymontelukast	23.22 ng/mL	Geometric Coefficient of Variation 55

90% CI: [0.73, 1.22]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	Cmax for 5-hydroxyomeprazole	181.1 ng/mL	Geometric Coefficient of Variation 63.1
Treatment C: Probe Substrates + GSK3640254 200 mg	Cmax for 5-hydroxyomeprazole	203.3 ng/mL	Geometric Coefficient of Variation 28.6

90% CI: [0.88, 1.44]

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	Cmax for Alpha-hydroxymetoprolol	45.70 ng/mL	Geometric Coefficient of Variation 199.8
Treatment C: Probe Substrates + GSK3640254 200 mg	Cmax for Alpha-hydroxymetoprolol	39.21 ng/mL	Geometric Coefficient of Variation 212.6

90% CI: [0.43, 1.72]

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.

Time frame: Up to Day 26

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

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Treatment A: Probe Substrates	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	AEs	1 Participants
Treatment A: Probe Substrates	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	SAEs	0 Participants
Treatment C: Probe Substrates + GSK3640254 200 mg	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	AEs	5 Participants
Treatment C: Probe Substrates + GSK3640254 200 mg	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	SAEs	0 Participants
Treatment C: Probe Substrates + GSK3640254 200 mg	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	AEs	5 Participants
Treatment C: Probe Substrates + GSK3640254 200 mg	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	SAEs	0 Participants

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.

Time frame: 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

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

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Ratio of AUC(0-infinity) of 1-hydroxymidazolam to Midazolam	0.4677 Ratio	Standard Deviation 0.19853
Treatment C: Probe Substrates + GSK3640254 200 mg	Ratio of AUC(0-infinity) of 1-hydroxymidazolam to Midazolam	0.4618 Ratio	Standard Deviation 0.20637

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.

Time frame: 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

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

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Ratio of AUC(0-infinity) of 36-hydroxymontelukast to Montelukast	0.09182 Ratio	Standard Deviation 0.033472
Treatment C: Probe Substrates + GSK3640254 200 mg	Ratio of AUC(0-infinity) of 36-hydroxymontelukast to Montelukast	0.08562 Ratio	Standard Deviation 0.036555

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.

Time frame: 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

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

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Ratio of AUC(0-infinity) of 5-hydroxyomeprazole to Omeprazole	1.151 Ratio	Standard Deviation 0.66463
Treatment C: Probe Substrates + GSK3640254 200 mg	Ratio of AUC(0-infinity) of 5-hydroxyomeprazole to Omeprazole	1.077 Ratio	Standard Deviation 0.59178

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.

Time frame: 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

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

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Ratio of AUC(0-infinity) of Alpha-hydroxymetoprolol to Metoprolol	1.733 Ratio	Standard Deviation 1.6208
Treatment C: Probe Substrates + GSK3640254 200 mg	Ratio of AUC(0-infinity) of Alpha-hydroxymetoprolol to Metoprolol	1.449 Ratio	Standard Deviation 1.6511

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.

Time frame: 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

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

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Ratio of Cmax of 1-hydroxymidazolam to Midazolam	0.5286 Ratio	Standard Deviation 0.23819
Treatment C: Probe Substrates + GSK3640254 200 mg	Ratio of Cmax of 1-hydroxymidazolam to Midazolam	0.4955 Ratio	Standard Deviation 0.20616

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.

Time frame: 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

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

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Ratio of Cmax of 36-hydroxymontelukast to Montelukast	0.06766 Ratio	Standard Deviation 0.025068
Treatment C: Probe Substrates + GSK3640254 200 mg	Ratio of Cmax of 36-hydroxymontelukast to Montelukast	0.06308 Ratio	Standard Deviation 0.025951

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.

Time frame: 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

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

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Ratio of Cmax of 5-hydroxyomeprazole to Omeprazole	0.9461 Ratio	Standard Deviation 0.56833
Treatment C: Probe Substrates + GSK3640254 200 mg	Ratio of Cmax of 5-hydroxyomeprazole to Omeprazole	0.8810 Ratio	Standard Deviation 0.49954

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.

Time frame: 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

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

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Ratio of Cmax of Alpha-hydroxymetoprolol to Metoprolol	0.7869 Ratio	Standard Deviation 0.76896
Treatment C: Probe Substrates + GSK3640254 200 mg	Ratio of Cmax of Alpha-hydroxymetoprolol to Metoprolol	0.7066 Ratio	Standard Deviation 0.93732

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	t1/2 for 1-hydroxymidazolam	3.632 Hours	Geometric Coefficient of Variation 15.6
Treatment C: Probe Substrates + GSK3640254 200 mg	t1/2 for 1-hydroxymidazolam	3.717 Hours	Geometric Coefficient of Variation 21

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	t1/2 for 36-hydroxymontelukast	5.310 Hours	Geometric Coefficient of Variation 14.3
Treatment C: Probe Substrates + GSK3640254 200 mg	t1/2 for 36-hydroxymontelukast	5.644 Hours	Geometric Coefficient of Variation 15.1

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	t1/2 for 5-hydroxyomeprazole	1.580 Hours	Geometric Coefficient of Variation 15.4
Treatment C: Probe Substrates + GSK3640254 200 mg	t1/2 for 5-hydroxyomeprazole	1.569 Hours	Geometric Coefficient of Variation 13.5

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	t1/2 for Alpha-hydroxymetoprolol	8.040 Hours	Geometric Coefficient of Variation 31.4
Treatment C: Probe Substrates + GSK3640254 200 mg	t1/2 for Alpha-hydroxymetoprolol	8.339 Hours	Geometric Coefficient of Variation 23

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.

Time frame: 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

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

Arm	Measure	Value (MEDIAN)
Treatment A: Probe Substrates	Tmax for 1-hydroxymidazolam	1.000 Hours
Treatment C: Probe Substrates + GSK3640254 200 mg	Tmax for 1-hydroxymidazolam	1.000 Hours

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.

Time frame: 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

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

Arm	Measure	Value (MEDIAN)
Treatment A: Probe Substrates	Tmax for 36-hydroxymontelukast	6.000 Hours
Treatment C: Probe Substrates + GSK3640254 200 mg	Tmax for 36-hydroxymontelukast	6.000 Hours

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.

Time frame: 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

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

Arm	Measure	Value (MEDIAN)
Treatment A: Probe Substrates	Tmax for 5-hydroxyomeprazole	6.000 Hours
Treatment C: Probe Substrates + GSK3640254 200 mg	Tmax for 5-hydroxyomeprazole	6.000 Hours

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.

Time frame: 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

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

Arm	Measure	Value (MEDIAN)
Treatment A: Probe Substrates	Tmax for Alpha-hydroxymetoprolol	3.033 Hours
Treatment C: Probe Substrates + GSK3640254 200 mg	Tmax for Alpha-hydroxymetoprolol	4.000 Hours

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.

Time frame: Baseline (Day 1, Pre-Dose) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)	Day 10: QTcF Interval	405.8 Milliseconds	Standard Deviation 16.25
Treatment A: Probe Substrates	Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)	Baseline (Day 1, Pre-dose): PR Interval	154.8 Milliseconds	Standard Deviation 20.92
Treatment A: Probe Substrates	Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)	Day 10: PR Interval	158.2 Milliseconds	Standard Deviation 22.67
Treatment A: Probe Substrates	Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)	Baseline (Day 1, Pre-dose): QRS Duration	92.5 Milliseconds	Standard Deviation 8.34
Treatment A: Probe Substrates	Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)	Day 10: QRS Duration	95.0 Milliseconds	Standard Deviation 10.11
Treatment A: Probe Substrates	Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)	Baseline (Day 1, Pre-dose): QT Interval	391.2 Milliseconds	Standard Deviation 22.41
Treatment A: Probe Substrates	Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)	Day 10: QT Interval	398.3 Milliseconds	Standard Deviation 22.19
Treatment A: Probe Substrates	Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)	Baseline (Day 1, Pre-dose): QTcF Interval	401.0 Milliseconds	Standard Deviation 16.48

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.

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Absolute Values of Albumin, Globulin, Protein	Baseline (Day -1): Albumin	42.9 Grams per liter	Standard Deviation 2.95
Treatment A: Probe Substrates	Treatment A: Absolute Values of Albumin, Globulin, Protein	Day 10: Albumin	42.2 Grams per liter	Standard Deviation 3.14
Treatment A: Probe Substrates	Treatment A: Absolute Values of Albumin, Globulin, Protein	Baseline (Day -1): Globulin	27.4 Grams per liter	Standard Deviation 3.14
Treatment A: Probe Substrates	Treatment A: Absolute Values of Albumin, Globulin, Protein	Day 10: Globulin	25.9 Grams per liter	Standard Deviation 3.04
Treatment A: Probe Substrates	Treatment A: Absolute Values of Albumin, Globulin, Protein	Baseline (Day -1): Protein	70.3 Grams per liter	Standard Deviation 4.52
Treatment A: Probe Substrates	Treatment A: Absolute Values of Albumin, Globulin, Protein	Day 10: Protein	68.1 Grams per liter	Standard Deviation 3.77

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.

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Absolute Values of Amylase, Lipase	Baseline (Day -1): Lipase	29.4 Units per liter	Standard Deviation 14.73
Treatment A: Probe Substrates	Treatment A: Absolute Values of Amylase, Lipase	Day 10: Lipase	31.6 Units per liter	Standard Deviation 11.99
Treatment A: Probe Substrates	Treatment A: Absolute Values of Amylase, Lipase	Baseline (Day -1): Amylase	59.5 Units per liter	Standard Deviation 22.37
Treatment A: Probe Substrates	Treatment A: Absolute Values of Amylase, Lipase	Day 10: Amylase	56.9 Units per liter	Standard Deviation 20.93

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.

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase	Baseline (Day -1): AST	14.6 International units per liter	Standard Deviation 3.89
Treatment A: Probe Substrates	Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase	Day 10: AST	15.6 International units per liter	Standard Deviation 5.32
Treatment A: Probe Substrates	Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase	Baseline (Day -1): Gamma-glutamyl transferase	19.1 International units per liter	Standard Deviation 7.16
Treatment A: Probe Substrates	Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase	Baseline (Day -1): Creatine kinase	103.7 International units per liter	Standard Deviation 79.68
Treatment A: Probe Substrates	Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase	Day 10: Creatine kinase	66.9 International units per liter	Standard Deviation 34.67
Treatment A: Probe Substrates	Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase	Baseline (Day -1): Lactate dehydrogenase	131.3 International units per liter	Standard Deviation 19.59
Treatment A: Probe Substrates	Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase	Day 10: Lactate dehydrogenase	114.8 International units per liter	Standard Deviation 16.87
Treatment A: Probe Substrates	Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase	Baseline (Day -1): ALT	15.6 International units per liter	Standard Deviation 7.66
Treatment A: Probe Substrates	Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase	Day 10: ALT	20.1 International units per liter	Standard Deviation 14.66
Treatment A: Probe Substrates	Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase	Baseline (Day -1): ALP	62.7 International units per liter	Standard Deviation 18.46
Treatment A: Probe Substrates	Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase	Day 10: ALP	60.8 International units per liter	Standard Deviation 18.03
Treatment A: Probe Substrates	Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase	Day 10: Gamma-glutamyl transferase	18.9 International units per liter	Standard Deviation 8.1

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.

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Absolute Values of Erythrocytes	Baseline (Day -1)	4.836 10^12 cells per liter	Standard Deviation 0.4125
Treatment A: Probe Substrates	Treatment A: Absolute Values of Erythrocytes	Day 10	4.664 10^12 cells per liter	Standard Deviation 0.4459

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.

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin	Baseline (Day -1)	29.37 Picograms	Standard Deviation 1.546
Treatment A: Probe Substrates	Treatment A: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin	Day 10	29.57 Picograms	Standard Deviation 1.667

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.

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Absolute Values of Erythrocytes Mean Corpuscular Volume	Baseline (Day -1)	86.71 Femtoliter	Standard Deviation 3.748
Treatment A: Probe Substrates	Treatment A: Absolute Values of Erythrocytes Mean Corpuscular Volume	Day 10	88.02 Femtoliter	Standard Deviation 3.938

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.

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day -1): Cholesterol	4.4570 Millimoles per liter	Standard Deviation 1.00121
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day -1): Glucose	5.0348 Millimoles per liter	Standard Deviation 0.37437
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 10: Glucose	4.8211 Millimoles per liter	Standard Deviation 0.44125
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day -1): Carbon Dioxide	104.1 Millimoles per liter	Standard Deviation 2.04
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 10: Carbon Dioxide	25.4 Millimoles per liter	Standard Deviation 2.11
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 10: Cholesterol	3.8118 Millimoles per liter	Standard Deviation 0.85065
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day -1): Triglycerides	1.2232 Millimoles per liter	Standard Deviation 0.51018
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 10: Triglycerides	1.1814 Millimoles per liter	Standard Deviation 0.82178
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day -1): Anion Gap	7.9 Millimoles per liter	Standard Deviation 1.8
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 10: Anion Gap	13.8 Millimoles per liter	Standard Deviation 1.71
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day -1): Calcium	2.3765 Millimoles per liter	Standard Deviation 0.09976
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 10: Calcium	2.3141 Millimoles per liter	Standard Deviation 0.10267
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day -1): Chloride	25.8 Millimoles per liter	Standard Deviation 2.1
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 10: Chloride	103.7 Millimoles per liter	Standard Deviation 1.81
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day -1): Phosphate	1.1075 Millimoles per liter	Standard Deviation 0.16734
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 10: Phosphate	1.1754 Millimoles per liter	Standard Deviation 0.16141
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day -1): Potassium	4.48 Millimoles per liter	Standard Deviation 0.339
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 10: Potassium	4.43 Millimoles per liter	Standard Deviation 0.256
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day -1): Sodium	137.7 Millimoles per liter	Standard Deviation 2
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 10: Sodium	138.4 Millimoles per liter	Standard Deviation 1.93
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day -1): Urea	4.8195 Millimoles per liter	Standard Deviation 0.78983
Treatment A: Probe Substrates	Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 10: Urea	5.9458 Millimoles per liter	Standard Deviation 1.43309

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.

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Absolute Values of Hematocrit	Baseline (Day -1)	0.4188 Proportion of red blood cells in blood	Standard Deviation 0.03442
Treatment A: Probe Substrates	Treatment A: Absolute Values of Hematocrit	Day 10	0.4098 Proportion of red blood cells in blood	Standard Deviation 0.03577

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.

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Absolute Values of Hemoglobin	Baseline (Day -1)	141.9 Grams per liter	Standard Deviation 13.27
Treatment A: Probe Substrates	Treatment A: Absolute Values of Hemoglobin	Day 10	137.7 Grams per liter	Standard Deviation 13.07

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.

Time frame: Baseline (Day 1, Pre-dose) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Absolute Values of Oral Temperature	Baseline (Day 1, Pre-dose)	36.38 Degrees Celsius	Standard Deviation 0.293
Treatment A: Probe Substrates	Treatment A: Absolute Values of Oral Temperature	Day 10	36.26 Degrees Celsius	Standard Deviation 0.252

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.

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 10: Lymphocytes	1.8965 10^9 cells per liter	Standard Deviation 0.33426
Treatment A: Probe Substrates	Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day -1): Platelet count	258.6 10^9 cells per liter	Standard Deviation 59.14
Treatment A: Probe Substrates	Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 10: Platelet count	265.9 10^9 cells per liter	Standard Deviation 60.21
Treatment A: Probe Substrates	Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day -1): Leukocyte count	5.64 10^9 cells per liter	Standard Deviation 1.338
Treatment A: Probe Substrates	Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 10: Leukocyte count	6.30 10^9 cells per liter	Standard Deviation 1.343
Treatment A: Probe Substrates	Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day -1): Neutrophils	3.1504 10^9 cells per liter	Standard Deviation 1.25074
Treatment A: Probe Substrates	Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 10: Neutrophils	3.7430 10^9 cells per liter	Standard Deviation 1.27763
Treatment A: Probe Substrates	Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day -1): Lymphocytes	1.8217 10^9 cells per liter	Standard Deviation 0.39628
Treatment A: Probe Substrates	Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day -1): Monocytes	0.4890 10^9 cells per liter	Standard Deviation 0.15889
Treatment A: Probe Substrates	Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 10: Monocytes	0.4515 10^9 cells per liter	Standard Deviation 0.12708
Treatment A: Probe Substrates	Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day -1): Eosinophils	0.1461 10^9 cells per liter	Standard Deviation 0.15067
Treatment A: Probe Substrates	Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 10: Eosinophils	0.1610 10^9 cells per liter	Standard Deviation 0.15071
Treatment A: Probe Substrates	Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day -1): Basophils	0.0331 10^9 cells per liter	Standard Deviation 0.01657
Treatment A: Probe Substrates	Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 10: Basophils	0.0440 10^9 cells per liter	Standard Deviation 0.01569

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.

Time frame: Baseline (Day 1, Pre-dose) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Absolute Values of Pulse Rate	Baseline (Day 1, Pre-dose)	64.5 Beats per minute	Standard Deviation 8.97
Treatment A: Probe Substrates	Treatment A: Absolute Values of Pulse Rate	Day 10	65.0 Beats per minute	Standard Deviation 8.19

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.

Time frame: Baseline (Day 1, Pre-dose) and Day 2

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Absolute Values of Respiratory Rate	Baseline (Day 1, Pre-dose)	16.1 Breaths per minute	Standard Deviation 1.37
Treatment A: Probe Substrates	Treatment A: Absolute Values of Respiratory Rate	Day 2	15.8 Breaths per minute	Standard Deviation 2.33

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.

Time frame: Baseline (Day 1, Pre-dose) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Absolute Values of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	Baseline (Day 1, Pre-dose): DBP	65.1 Millimeters of mercury	Standard Deviation 6.73
Treatment A: Probe Substrates	Treatment A: Absolute Values of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	Baseline (Day 1, Pre-dose): SBP	111.0 Millimeters of mercury	Standard Deviation 9.03
Treatment A: Probe Substrates	Treatment A: Absolute Values of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	Day 10: SBP	107.7 Millimeters of mercury	Standard Deviation 9.32
Treatment A: Probe Substrates	Treatment A: Absolute Values of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)	Day 10: DBP	59.7 Millimeters of mercury	Standard Deviation 6.24

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.

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Baseline (Day -1): Urate	347.3632 Micromoles per liter	Standard Deviation 69.50981
Treatment A: Probe Substrates	Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 10: Urate	365.5046 Micromoles per liter	Standard Deviation 75.74195
Treatment A: Probe Substrates	Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Baseline (Day -1): Creatinine	84.9524 Micromoles per liter	Standard Deviation 19.89935
Treatment A: Probe Substrates	Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 10: Creatinine	86.4110 Micromoles per liter	Standard Deviation 21.46247
Treatment A: Probe Substrates	Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Baseline (Day -1): Bilirubin	9.8325 Micromoles per liter	Standard Deviation 3.13227
Treatment A: Probe Substrates	Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 10: Bilirubin	8.0028 Micromoles per liter	Standard Deviation 3.01005
Treatment A: Probe Substrates	Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Baseline (Day -1): Direct bilirubin	2.0520 Micromoles per liter	Standard Deviation 0.70177
Treatment A: Probe Substrates	Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 10: Direct bilirubin	1.7015 Micromoles per liter	Standard Deviation 0.63856

Secondary

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

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Albumin, Globulin, Protein	Albumin	-0.7 Grams per liter	Standard Deviation 1.75
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Albumin, Globulin, Protein	Globulin	-1.5 Grams per liter	Standard Deviation 1.61
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Albumin, Globulin, Protein	Protein	-2.2 Grams per liter	Standard Deviation 2.57

Secondary

Treatment A: Change From Baseline in Amylase, Lipase

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Amylase, Lipase	Lipase	2.2 Units per liter	Standard Deviation 6.81
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Amylase, Lipase	Amylase	-2.6 Units per liter	Standard Deviation 7.86

Secondary

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

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Creatine kinase	-36.9 International units per liter	Standard Deviation 59.38
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Lactate dehydrogenase	-16.5 International units per liter	Standard Deviation 15.5
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	ALT	4.5 International units per liter	Standard Deviation 11.51
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	ALP	-1.9 International units per liter	Standard Deviation 6.39
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	AST	1.0 International units per liter	Standard Deviation 4.52
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Gamma-glutamyl transferase	-0.2 International units per liter	Standard Deviation 3.86

Secondary

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

Time frame: Baseline (Day 1, Pre-dose) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF	PR Interval	3.4 Milliseconds	Standard Deviation 9.28
Treatment A: Probe Substrates	Treatment A: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF	QRS Duration	2.5 Milliseconds	Standard Deviation 4.37
Treatment A: Probe Substrates	Treatment A: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF	QT Interval	7.1 Milliseconds	Standard Deviation 12.81
Treatment A: Probe Substrates	Treatment A: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF	QTcF Interval	4.8 Milliseconds	Standard Deviation 9.27

Secondary

Treatment A: Change From Baseline in Erythrocytes

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Erythrocytes	-0.172 10^12 cells per liter	Standard Deviation 0.2219

Secondary

Treatment A: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin	0.20 Picograms	Standard Deviation 0.352

Secondary

Treatment A: Change From Baseline in Erythrocytes Mean Corpuscular Volume

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Erythrocytes Mean Corpuscular Volume	1.31 Femtoliter	Standard Deviation 1.539

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.

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Glucose	-0.2137 Millimoles per liter	Standard Deviation 0.29663
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Carbon Dioxide	-78.7 Millimoles per liter	Standard Deviation 3.12
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Cholesterol	-0.6452 Millimoles per liter	Standard Deviation 0.47501
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Triglycerides	-0.0418 Millimoles per liter	Standard Deviation 0.59458
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Anion Gap	5.9 Millimoles per liter	Standard Deviation 2.21
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Calcium	-0.0624 Millimoles per liter	Standard Deviation 0.04889
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Chloride	78.0 Millimoles per liter	Standard Deviation 2.98
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Phosphate	0.0678 Millimoles per liter	Standard Deviation 0.10522
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Potassium	-0.05 Millimoles per liter	Standard Deviation 0.402
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Sodium	0.7 Millimoles per liter	Standard Deviation 2.16
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Urea	1.1263 Millimoles per liter	Standard Deviation 0.97483

Secondary

Treatment A: Change From Baseline in Hematocrit

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Hematocrit	-0.0090 Proportion of red blood cells in blood	Standard Deviation 0.02082

Secondary

Treatment A: Change From Baseline in Hemoglobin

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Hemoglobin	-4.2 Grams per liter	Standard Deviation 6.34

Secondary

Treatment A: Change From Baseline in Oral Temperature

Time frame: Baseline (Day 1, Pre-dose) and Day 10

Population: Safety Population.

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Oral Temperature	-0.12 Degrees Celsius	Standard Deviation 0.314

Secondary

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

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Platelet count	7.3 10^9 cells per liter	Standard Deviation 20.01
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Leukocyte count	0.66 10^9 cells per liter	Standard Deviation 0.844
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Neutrophils	0.5926 10^9 cells per liter	Standard Deviation 0.68577
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Lymphocytes	0.0748 10^9 cells per liter	Standard Deviation 0.25872
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Monocytes	-0.0375 10^9 cells per liter	Standard Deviation 0.09379
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Eosinophils	0.0150 10^9 cells per liter	Standard Deviation 0.07023
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Basophils	0.0110 10^9 cells per liter	Standard Deviation 0.02138

Secondary

Treatment A: Change From Baseline in Pulse Rate

Time frame: Baseline (Day 1, Pre-dose) and Day 10

Population: Safety Population.

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Pulse Rate	0.5 Beats per minute	Standard Deviation 6.27

Secondary

Treatment A: Change From Baseline in Respiratory Rate

Time frame: Baseline (Day 1, Pre-dose) and Day 2

Population: Safety Population.

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Respiratory Rate	-0.3 Breaths per minute	Standard Deviation 2.62

Secondary

Treatment A: Change From Baseline in SBP and DBP

Time frame: Baseline (Day 1, Pre-dose) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Change From Baseline in SBP and DBP	SBP	-3.3 Millimeters of mercury	Standard Deviation 9.67
Treatment A: Probe Substrates	Treatment A: Change From Baseline in SBP and DBP	DBP	-5.4 Millimeters of mercury	Standard Deviation 5.96

Secondary

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

Time frame: Baseline (Day -1) and Day 10

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin	Urate	18.1414 Micromoles per liter	Standard Deviation 39.28786
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin	Creatinine	1.4586 Micromoles per liter	Standard Deviation 5.65145
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin	Bilirubin	-1.8297 Micromoles per liter	Standard Deviation 1.38266
Treatment A: Probe Substrates	Treatment A: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin	Direct bilirubin	-0.3506 Micromoles per liter	Standard Deviation 0.60895

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.

Time frame: Baseline (Day 11, Pre-Dose) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Baseline (Day 11, Pre-dose): QTcF Interval	403.5 Milliseconds	Standard Deviation 17.63
Treatment A: Probe Substrates	Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Baseline (Day 11, Pre-dose): PR Interval	158.6 Milliseconds	Standard Deviation 19.44
Treatment A: Probe Substrates	Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Day 20: PR Interval	161.8 Milliseconds	Standard Deviation 22.4
Treatment A: Probe Substrates	Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Baseline (Day 11, Pre-dose): QRS Duration	94.2 Milliseconds	Standard Deviation 8.73
Treatment A: Probe Substrates	Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Day 20: QRS Duration	96.4 Milliseconds	Standard Deviation 9.25
Treatment A: Probe Substrates	Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Baseline (Day 11, Pre-dose): QT Interval	403.1 Milliseconds	Standard Deviation 26.27
Treatment A: Probe Substrates	Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Day 20: QT Interval	408.8 Milliseconds	Standard Deviation 25.85
Treatment A: Probe Substrates	Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Day 20: QTcF Interval	408.6 Milliseconds	Standard Deviation 17.26

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.

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Absolute Values of Albumin, Globulin, Protein	Day 20: Protein	68.2 Grams per liter	Standard Deviation 4.93
Treatment A: Probe Substrates	Treatment B: Absolute Values of Albumin, Globulin, Protein	Baseline (Day 10): Albumin	42.2 Grams per liter	Standard Deviation 3.14
Treatment A: Probe Substrates	Treatment B: Absolute Values of Albumin, Globulin, Protein	Day 20: Albumin	41.4 Grams per liter	Standard Deviation 3.31
Treatment A: Probe Substrates	Treatment B: Absolute Values of Albumin, Globulin, Protein	Baseline (Day 10): Globulin	25.9 Grams per liter	Standard Deviation 3.04
Treatment A: Probe Substrates	Treatment B: Absolute Values of Albumin, Globulin, Protein	Day 20: Globulin	26.8 Grams per liter	Standard Deviation 3.58
Treatment A: Probe Substrates	Treatment B: Absolute Values of Albumin, Globulin, Protein	Baseline (Day 10): Protein	68.1 Grams per liter	Standard Deviation 3.77

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.

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Absolute Values of Amylase, Lipase	Baseline (Day 10): Lipase	31.6 Units per liter	Standard Deviation 11.99
Treatment A: Probe Substrates	Treatment B: Absolute Values of Amylase, Lipase	Day 20: Lipase	32.4 Units per liter	Standard Deviation 14.51
Treatment A: Probe Substrates	Treatment B: Absolute Values of Amylase, Lipase	Baseline (Day 10): Amylase	56.9 Units per liter	Standard Deviation 20.93
Treatment A: Probe Substrates	Treatment B: Absolute Values of Amylase, Lipase	Day 20: Amylase	60.1 Units per liter	Standard Deviation 23.22

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.

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Baseline (Day 10): Creatine kinase	66.9 International units per liter	Standard Deviation 34.67
Treatment A: Probe Substrates	Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 20: Creatine kinase	68.9 International units per liter	Standard Deviation 47.98
Treatment A: Probe Substrates	Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Baseline (Day 10): Lactate dehydrogenase	114.8 International units per liter	Standard Deviation 16.87
Treatment A: Probe Substrates	Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 20: Lactate dehydrogenase	115.9 International units per liter	Standard Deviation 17
Treatment A: Probe Substrates	Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Baseline (Day 10): ALT	20.1 International units per liter	Standard Deviation 14.66
Treatment A: Probe Substrates	Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 20: ALT	20.3 International units per liter	Standard Deviation 12.38
Treatment A: Probe Substrates	Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Baseline (Day 10): ALP	60.8 International units per liter	Standard Deviation 18.03
Treatment A: Probe Substrates	Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 20: ALP	58.5 International units per liter	Standard Deviation 15.56
Treatment A: Probe Substrates	Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Baseline (Day 10): AST	15.6 International units per liter	Standard Deviation 5.32
Treatment A: Probe Substrates	Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 20: AST	16.1 International units per liter	Standard Deviation 4.8
Treatment A: Probe Substrates	Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Baseline (Day 10): Gamma-glutamyl transferase	18.9 International units per liter	Standard Deviation 8.1
Treatment A: Probe Substrates	Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 20: Gamma-glutamyl transferase	18.3 International units per liter	Standard Deviation 7.69

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.

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Absolute Values of Erythrocytes	Baseline (Day 10)	4.664 10^12 cells per liter	Standard Deviation 0.4459
Treatment A: Probe Substrates	Treatment B: Absolute Values of Erythrocytes	Day 20	4.746 10^12 cells per liter	Standard Deviation 0.3994

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.

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin	Baseline (Day 10)	29.57 Picograms	Standard Deviation 1.667
Treatment A: Probe Substrates	Treatment B: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin	Day 20	29.52 Picograms	Standard Deviation 1.602

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.

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Absolute Values of Erythrocytes Mean Corpuscular Volume	Baseline (Day 10)	88.02 Femtoliter	Standard Deviation 3.938
Treatment A: Probe Substrates	Treatment B: Absolute Values of Erythrocytes Mean Corpuscular Volume	Day 20	88.96 Femtoliter	Standard Deviation 4.746

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.

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 10): Urea	5.9458 Millimoles per liter	Standard Deviation 1.43309
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 20: Urea	5.6335 Millimoles per liter	Standard Deviation 1.72537
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 10): Glucose	4.8211 Millimoles per liter	Standard Deviation 0.44125
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 20: Glucose	4.7378 Millimoles per liter	Standard Deviation 0.45996
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 10): Carbon Dioxide	25.4 Millimoles per liter	Standard Deviation 2.11
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 20: Carbon Dioxide	24.9 Millimoles per liter	Standard Deviation 2.11
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 10): Cholesterol	3.8118 Millimoles per liter	Standard Deviation 0.85065
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 20: Cholesterol	3.6915 Millimoles per liter	Standard Deviation 0.94881
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 10): Triglycerides	1.1814 Millimoles per liter	Standard Deviation 0.82178
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 20: Triglycerides	1.0825 Millimoles per liter	Standard Deviation 0.84563
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 10): Anion Gap	13.8 Millimoles per liter	Standard Deviation 1.71
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 20: Anion Gap	14.5 Millimoles per liter	Standard Deviation 2.12
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 10): Calcium	2.3141 Millimoles per liter	Standard Deviation 0.10267
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 20: Calcium	2.3141 Millimoles per liter	Standard Deviation 0.08825
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 10): Chloride	103.7 Millimoles per liter	Standard Deviation 1.81
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 20: Chloride	103.6 Millimoles per liter	Standard Deviation 2.3
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 10): Phosphate	1.1754 Millimoles per liter	Standard Deviation 0.16141
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 20: Phosphate	1.2593 Millimoles per liter	Standard Deviation 0.13294
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 10): Potassium	4.43 Millimoles per liter	Standard Deviation 0.256
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 20: Potassium	4.39 Millimoles per liter	Standard Deviation 0.383
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 10): Sodium	138.4 Millimoles per liter	Standard Deviation 1.93
Treatment A: Probe Substrates	Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 20: Sodium	138.6 Millimoles per liter	Standard Deviation 1.64

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.

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Absolute Values of Hematocrit	Baseline (Day 10)	0.4098 Proportion of red blood cells in blood	Standard Deviation 0.03577
Treatment A: Probe Substrates	Treatment B: Absolute Values of Hematocrit	Day 20	0.4216 Proportion of red blood cells in blood	Standard Deviation 0.0342

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.

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Absolute Values of Hemoglobin	Baseline (Day 10)	137.7 Grams per liter	Standard Deviation 13.07
Treatment A: Probe Substrates	Treatment B: Absolute Values of Hemoglobin	Day 20	140.0 Grams per liter	Standard Deviation 12.22

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.

Time frame: Baseline (Day 11, Pre-Dose) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Absolute Values of Oral Temperature	Baseline (Day 11, Pre-dose)	36.31 Degrees Celsius	Standard Deviation 0.32
Treatment A: Probe Substrates	Treatment B: Absolute Values of Oral Temperature	Day 20	36.28 Degrees Celsius	Standard Deviation 0.246

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.

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day 10): Platelet count	265.9 10^9 cells per liter	Standard Deviation 60.21
Treatment A: Probe Substrates	Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 20: Platelet count	261.9 10^9 cells per liter	Standard Deviation 58.51
Treatment A: Probe Substrates	Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day 10): Leukocyte count	6.30 10^9 cells per liter	Standard Deviation 1.343
Treatment A: Probe Substrates	Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 20: Leukocyte count	5.79 10^9 cells per liter	Standard Deviation 1.192
Treatment A: Probe Substrates	Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day 10): Neutrophils	3.7430 10^9 cells per liter	Standard Deviation 1.27763
Treatment A: Probe Substrates	Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 20: Neutrophils	3.2680 10^9 cells per liter	Standard Deviation 1.17833
Treatment A: Probe Substrates	Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day 10): Lymphocytes	1.8965 10^9 cells per liter	Standard Deviation 0.33426
Treatment A: Probe Substrates	Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 20: Lymphocytes	1.8355 10^9 cells per liter	Standard Deviation 0.52512
Treatment A: Probe Substrates	Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day 10): Monocytes	0.4515 10^9 cells per liter	Standard Deviation 0.12708
Treatment A: Probe Substrates	Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 20: Monocytes	0.4435 10^9 cells per liter	Standard Deviation 0.16662
Treatment A: Probe Substrates	Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day 10): Eosinophils	0.1610 10^9 cells per liter	Standard Deviation 0.15071
Treatment A: Probe Substrates	Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 20: Eosinophils	0.1920 10^9 cells per liter	Standard Deviation 0.18981
Treatment A: Probe Substrates	Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day 10): Basophils	0.0440 10^9 cells per liter	Standard Deviation 0.01569
Treatment A: Probe Substrates	Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 20: Basophils	0.0460 10^9 cells per liter	Standard Deviation 0.02981

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.

Time frame: Baseline (Day 11, Pre-Dose) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Absolute Values of Pulse Rate	Baseline (Day 11, Pre-dose)	61.6 Beats per minute	Standard Deviation 9.95
Treatment A: Probe Substrates	Treatment B: Absolute Values of Pulse Rate	Day 20	62.8 Beats per minute	Standard Deviation 10.22

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.

Time frame: Baseline (Day 11, Pre-Dose) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Absolute Values of Respiratory Rate	Baseline (Day 11, Pre-dose)	15.0 Breaths per minute	Standard Deviation 2.29
Treatment A: Probe Substrates	Treatment B: Absolute Values of Respiratory Rate	Day 20	14.7 Breaths per minute	Standard Deviation 2.27

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.

Time frame: Baseline (Day 11, Pre-Dose) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Absolute Values of SBP and DBP	Baseline (Day 11, Pre-dose): SBP	107.7 Millimeters of mercury	Standard Deviation 8.46
Treatment A: Probe Substrates	Treatment B: Absolute Values of SBP and DBP	Day 20: SBP	107.2 Millimeters of mercury	Standard Deviation 9.52
Treatment A: Probe Substrates	Treatment B: Absolute Values of SBP and DBP	Baseline (Day 11, Pre-dose): DBP	61.6 Millimeters of mercury	Standard Deviation 6.56
Treatment A: Probe Substrates	Treatment B: Absolute Values of SBP and DBP	Day 20: DBP	59.6 Millimeters of mercury	Standard Deviation 5.55

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.

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Baseline (Day 10): Urate	365.5046 Micromoles per liter	Standard Deviation 75.74195
Treatment A: Probe Substrates	Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 20: Urate	337.8464 Micromoles per liter	Standard Deviation 76.6006
Treatment A: Probe Substrates	Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Baseline (Day 10): Creatinine	86.4110 Micromoles per liter	Standard Deviation 21.46247
Treatment A: Probe Substrates	Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 20: Creatinine	90.7868 Micromoles per liter	Standard Deviation 22.81174
Treatment A: Probe Substrates	Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Baseline (Day 10): Bilirubin	8.0028 Micromoles per liter	Standard Deviation 3.01005
Treatment A: Probe Substrates	Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 20: Bilirubin	8.6184 Micromoles per liter	Standard Deviation 3.04856
Treatment A: Probe Substrates	Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Baseline (Day 10): Direct bilirubin	1.7015 Micromoles per liter	Standard Deviation 0.63856
Treatment A: Probe Substrates	Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 20: Direct bilirubin	1.8126 Micromoles per liter	Standard Deviation 0.64557

Secondary

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

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Albumin, Globulin, Protein	Albumin	-0.9 Grams per liter	Standard Deviation 2.43
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Albumin, Globulin, Protein	Globulin	0.9 Grams per liter	Standard Deviation 2.07
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Albumin, Globulin, Protein	Protein	0.1 Grams per liter	Standard Deviation 3.71

Secondary

Treatment B: Change From Baseline in Amylase, Lipase

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Amylase, Lipase	Lipase	0.9 Units per liter	Standard Deviation 6.07
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Amylase, Lipase	Amylase	3.2 Units per liter	Standard Deviation 6.31

Secondary

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

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Creatine kinase	2.1 International units per liter	Standard Deviation 24.48
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Lactate dehydrogenase	1.1 International units per liter	Standard Deviation 13.15
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	ALT	0.3 International units per liter	Standard Deviation 6.78
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	ALP	-2.4 International units per liter	Standard Deviation 6.21
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	AST	0.6 International units per liter	Standard Deviation 3.03
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Gamma-glutamyl transferase	-0.6 International units per liter	Standard Deviation 2.74

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.

Time frame: Baseline (Day 11, Pre-Dose) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF	PR Interval	3.2 Milliseconds	Standard Deviation 8.79
Treatment A: Probe Substrates	Treatment B: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF	QRS Duration	2.3 Milliseconds	Standard Deviation 2.77
Treatment A: Probe Substrates	Treatment B: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF	QT Interval	5.7 Milliseconds	Standard Deviation 13.3
Treatment A: Probe Substrates	Treatment B: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF	QTcF Interval	5.1 Milliseconds	Standard Deviation 10.69

Secondary

Treatment B: Change From Baseline in Erythrocytes

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Erythrocytes	0.083 10^12 cells per liter	Standard Deviation 0.1768

Secondary

Treatment B: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin	-0.05 Picograms	Standard Deviation 0.298

Secondary

Treatment B: Change From Baseline in Erythrocytes Mean Corpuscular Volume

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Erythrocytes Mean Corpuscular Volume	0.94 Femtoliter	Standard Deviation 2.519

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.

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Glucose	-0.0833 Millimoles per liter	Standard Deviation 0.29345
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Carbon Dioxide	-0.6 Millimoles per liter	Standard Deviation 1.79
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Cholesterol	-0.1203 Millimoles per liter	Standard Deviation 0.30774
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Triglycerides	-0.0989 Millimoles per liter	Standard Deviation 0.30531
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Anion Gap	0.8 Millimoles per liter	Standard Deviation 1.94
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Calcium	0.0000 Millimoles per liter	Standard Deviation 0.06575
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Chloride	-0.1 Millimoles per liter	Standard Deviation 1.52
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Phosphate	0.0840 Millimoles per liter	Standard Deviation 0.08601
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Potassium	-0.05 Millimoles per liter	Standard Deviation 0.378
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Sodium	0.3 Millimoles per liter	Standard Deviation 1.41
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Urea	-0.3124 Millimoles per liter	Standard Deviation 0.72202

Secondary

Treatment B: Change From Baseline in Hematocrit

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Hematocrit	0.0118 Proportion of red blood cells in blood	Standard Deviation 0.01667

Secondary

Treatment B: Change From Baseline in Hemoglobin

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Hemoglobin	2.3 Grams per liter	Standard Deviation 4.91

Secondary

Treatment B: Change From Baseline in Oral Temperature

Time frame: Baseline (Day 11, Pre-Dose) and Day 20

Population: Safety Population.

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Oral Temperature	-0.03 Degrees Celsius	Standard Deviation 0.249

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.

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Platelet count	-4.1 10^9 cells per liter	Standard Deviation 17.31
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Leukocyte count	-0.51 10^9 cells per liter	Standard Deviation 0.947
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Neutrophils	-0.4750 10^9 cells per liter	Standard Deviation 0.63752
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Lymphocytes	-0.0610 10^9 cells per liter	Standard Deviation 0.39045
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Monocytes	-0.0080 10^9 cells per liter	Standard Deviation 0.11134
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Eosinophils	0.0310 10^9 cells per liter	Standard Deviation 0.10686
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Basophils	0.0020 10^9 cells per liter	Standard Deviation 0.02526

Secondary

Treatment B: Change From Baseline in Pulse Rate

Time frame: Baseline (Day 11, Pre-Dose) and Day 20

Population: Safety Population.

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Pulse Rate	1.3 Beats per minute	Standard Deviation 7.44

Secondary

Treatment B: Change From Baseline in Respiratory Rate

Time frame: Baseline (Day 11, Pre-Dose) and Day 20

Population: Safety Population.

Arm	Measure	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Respiratory Rate	-0.3 Breaths per minute	Standard Deviation 2.36

Secondary

Treatment B: Change From Baseline in SBP and DBP

Time frame: Baseline (Day 11, Pre-Dose) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Change From Baseline in SBP and DBP	SBP	-0.5 Millimeters of mercury	Standard Deviation 8.56
Treatment A: Probe Substrates	Treatment B: Change From Baseline in SBP and DBP	DBP	-2.0 Millimeters of mercury	Standard Deviation 5.75

Secondary

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

Time frame: Baseline (Day 10) and Day 20

Population: Safety Population.

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin	Direct bilirubin	0.1112 Micromoles per liter	Standard Deviation 0.46509
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin	Urate	-27.6582 Micromoles per liter	Standard Deviation 25.47573
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin	Creatinine	4.3758 Micromoles per liter	Standard Deviation 4.38239
Treatment A: Probe Substrates	Treatment B: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin	Bilirubin	0.6156 Micromoles per liter	Standard Deviation 1.92059

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.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Day 25: PR Interval	159.6 Milliseconds	Standard Deviation 23.55
Treatment A: Probe Substrates	Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Baseline (Day 21, Pre-dose): PR Interval	160.8 Milliseconds	Standard Deviation 20.26
Treatment A: Probe Substrates	Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Day 22: PR Interval	162.3 Milliseconds	Standard Deviation 22.07
Treatment A: Probe Substrates	Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Baseline (Day 21, Pre-dose): QRS Duration	95.8 Milliseconds	Standard Deviation 9.49
Treatment A: Probe Substrates	Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Day 22: QRS Duration	98.7 Milliseconds	Standard Deviation 10.3
Treatment A: Probe Substrates	Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Day 25: QRS Duration	96.8 Milliseconds	Standard Deviation 8.42
Treatment A: Probe Substrates	Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Baseline (Day 21, Pre-dose): QT Interval	402.6 Milliseconds	Standard Deviation 21.06
Treatment A: Probe Substrates	Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Day 22: QT Interval	420.6 Milliseconds	Standard Deviation 21.16
Treatment A: Probe Substrates	Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Day 25: QT Interval	398.7 Milliseconds	Standard Deviation 22.25
Treatment A: Probe Substrates	Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Baseline (Day 21, Pre-dose): QTcF Interval	408.7 Milliseconds	Standard Deviation 16.31
Treatment A: Probe Substrates	Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Day 22: QTcF Interval	407.3 Milliseconds	Standard Deviation 13.75
Treatment A: Probe Substrates	Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval	Day 25: QTcF Interval	402.5 Milliseconds	Standard Deviation 17.03

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.

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Absolute Values of Albumin, Globulin, Protein	Baseline (Day 20): Albumin	41.6 Grams per liter	Standard Deviation 3.24
Treatment A: Probe Substrates	Treatment C: Absolute Values of Albumin, Globulin, Protein	Day 22: Albumin	40.5 Grams per liter	Standard Deviation 3.82
Treatment A: Probe Substrates	Treatment C: Absolute Values of Albumin, Globulin, Protein	Day 25: Albumin	42.0 Grams per liter	Standard Deviation 3.04
Treatment A: Probe Substrates	Treatment C: Absolute Values of Albumin, Globulin, Protein	Baseline (Day 20): Globulin	26.9 Grams per liter	Standard Deviation 3.65
Treatment A: Probe Substrates	Treatment C: Absolute Values of Albumin, Globulin, Protein	Day 22: Globulin	25.1 Grams per liter	Standard Deviation 3.69
Treatment A: Probe Substrates	Treatment C: Absolute Values of Albumin, Globulin, Protein	Day 25: Globulin	26.6 Grams per liter	Standard Deviation 3.67
Treatment A: Probe Substrates	Treatment C: Absolute Values of Albumin, Globulin, Protein	Baseline (Day 20): Protein	68.5 Grams per liter	Standard Deviation 4.85
Treatment A: Probe Substrates	Treatment C: Absolute Values of Albumin, Globulin, Protein	Day 22: Protein	65.6 Grams per liter	Standard Deviation 5.74
Treatment A: Probe Substrates	Treatment C: Absolute Values of Albumin, Globulin, Protein	Day 25: Protein	68.6 Grams per liter	Standard Deviation 4.34

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.

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Absolute Values of Amylase, Lipase	Baseline (Day 20): Lipase	32.9 Units per liter	Standard Deviation 14.74
Treatment A: Probe Substrates	Treatment C: Absolute Values of Amylase, Lipase	Day 22: Lipase	33.5 Units per liter	Standard Deviation 15.19
Treatment A: Probe Substrates	Treatment C: Absolute Values of Amylase, Lipase	Day 25: Lipase	33.1 Units per liter	Standard Deviation 14.58
Treatment A: Probe Substrates	Treatment C: Absolute Values of Amylase, Lipase	Baseline (Day 20): Amylase	62.2 Units per liter	Standard Deviation 21.79
Treatment A: Probe Substrates	Treatment C: Absolute Values of Amylase, Lipase	Day 22: Amylase	64.7 Units per liter	Standard Deviation 25.32
Treatment A: Probe Substrates	Treatment C: Absolute Values of Amylase, Lipase	Day 25: Amylase	60.7 Units per liter	Standard Deviation 21.08

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.

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Baseline (Day 20): Creatine kinase	71.3 International units per liter	Standard Deviation 48.03
Treatment A: Probe Substrates	Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 22: Creatine kinase	65.7 International units per liter	Standard Deviation 34.56
Treatment A: Probe Substrates	Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 25: Creatine kinase	63.8 International units per liter	Standard Deviation 30.9
Treatment A: Probe Substrates	Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Baseline (Day 20): Lactate dehydrogenase	116.6 International units per liter	Standard Deviation 17.13
Treatment A: Probe Substrates	Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 22: Lactate dehydrogenase	120.6 International units per liter	Standard Deviation 23.62
Treatment A: Probe Substrates	Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 25: Lactate dehydrogenase	119.3 International units per liter	Standard Deviation 19.18
Treatment A: Probe Substrates	Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Baseline (Day 20): ALT	20.4 International units per liter	Standard Deviation 12.7
Treatment A: Probe Substrates	Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 22: ALT	17.3 International units per liter	Standard Deviation 9.36
Treatment A: Probe Substrates	Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 25: ALT	20.9 International units per liter	Standard Deviation 11.92
Treatment A: Probe Substrates	Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Baseline (Day 20): ALP	58.5 International units per liter	Standard Deviation 15.98
Treatment A: Probe Substrates	Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 22: ALP	57.6 International units per liter	Standard Deviation 16.26
Treatment A: Probe Substrates	Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 25:ALP	58.6 International units per liter	Standard Deviation 16.4
Treatment A: Probe Substrates	Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Baseline (Day 20): AST	16.2 International units per liter	Standard Deviation 4.91
Treatment A: Probe Substrates	Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 22: AST	14.7 International units per liter	Standard Deviation 3.78
Treatment A: Probe Substrates	Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 25: AST	16.4 International units per liter	Standard Deviation 4.56
Treatment A: Probe Substrates	Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Baseline (Day 20): Gamma-glutamyl transferase	18.5 International units per liter	Standard Deviation 7.83
Treatment A: Probe Substrates	Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 22: Gamma-glutamyl transferase	17.1 International units per liter	Standard Deviation 6.77
Treatment A: Probe Substrates	Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 25: Gamma-glutamyl transferase	18.7 International units per liter	Standard Deviation 8.23

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.

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Absolute Values of Erythrocytes	Baseline (Day 20)	4.769 10^12 cells per liter	Standard Deviation 0.3966
Treatment A: Probe Substrates	Treatment C: Absolute Values of Erythrocytes	Day 22	4.608 10^12 cells per liter	Standard Deviation 0.5308
Treatment A: Probe Substrates	Treatment C: Absolute Values of Erythrocytes	Day 25	4.756 10^12 cells per liter	Standard Deviation 0.4718

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.

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin	Baseline (Day 20)	29.51 Picograms	Standard Deviation 1.645
Treatment A: Probe Substrates	Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin	Day 22	29.28 Picograms	Standard Deviation 1.67
Treatment A: Probe Substrates	Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin	Day 25	29.12 Picograms	Standard Deviation 1.626

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.

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Volume	Baseline (Day 20)	89.03 Femtoliter	Standard Deviation 4.865
Treatment A: Probe Substrates	Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Volume	Day 22	87.38 Femtoliter	Standard Deviation 4.217
Treatment A: Probe Substrates	Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Volume	Day 25	87.74 Femtoliter	Standard Deviation 4.045

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.

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 20): Glucose	4.7184 Millimoles per liter	Standard Deviation 0.46406
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Glucose	4.8060 Millimoles per liter	Standard Deviation 0.3789
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Glucose	4.8703 Millimoles per liter	Standard Deviation 0.40699
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 20): Carbon Dioxide	24.9 Millimoles per liter	Standard Deviation 2.12
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Carbon Dioxide	25.4 Millimoles per liter	Standard Deviation 1.74
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Carbon Dioxide	26.2 Millimoles per liter	Standard Deviation 1.8
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 20): Cholesterol	3.6898 Millimoles per liter	Standard Deviation 0.97478
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Cholesterol	3.2543 Millimoles per liter	Standard Deviation 0.88216
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Cholesterol	3.3972 Millimoles per liter	Standard Deviation 0.89603
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 20): Triglycerides	1.0783 Millimoles per liter	Standard Deviation 0.86858
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Triglycerides	1.0836 Millimoles per liter	Standard Deviation 0.78925
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Triglycerides	1.1074 Millimoles per liter	Standard Deviation 0.81372
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 20): Anion Gap	14.6 Millimoles per liter	Standard Deviation 2.14
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Anion Gap	13.9 Millimoles per liter	Standard Deviation 1.27
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Anion Gap	14.5 Millimoles per liter	Standard Deviation 1.95
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 20): Calcium	2.3217 Millimoles per liter	Standard Deviation 0.08377
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Calcium	2.2810 Millimoles per liter	Standard Deviation 0.10822
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Calcium	2.3519 Millimoles per liter	Standard Deviation 0.0944
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 20): Chloride	103.4 Millimoles per liter	Standard Deviation 2.22
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Chloride	104.8 Millimoles per liter	Standard Deviation 2.02
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Chloride	102.6 Millimoles per liter	Standard Deviation 1.86
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 20): Phosphate	1.2661 Millimoles per liter	Standard Deviation 0.13297
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Phosphate	1.1981 Millimoles per liter	Standard Deviation 0.14871
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Phosphate	1.3477 Millimoles per liter	Standard Deviation 0.18638
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 20): Potassium	4.38 Millimoles per liter	Standard Deviation 0.392
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Potassium	4.34 Millimoles per liter	Standard Deviation 0.347
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Potassium	4.35 Millimoles per liter	Standard Deviation 0.355
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 20): Sodium	138.6 Millimoles per liter	Standard Deviation 1.67
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Sodium	139.8 Millimoles per liter	Standard Deviation 1.34
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Sodium	139.0 Millimoles per liter	Standard Deviation 1.67
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Baseline (Day 20): Urea	5.7364 Millimoles per liter	Standard Deviation 1.70835
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Urea	4.9078 Millimoles per liter	Standard Deviation 1.441
Treatment A: Probe Substrates	Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Urea	5.3099 Millimoles per liter	Standard Deviation 1.18355

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.

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Absolute Values of Hematocrit	Baseline (Day 20)	0.4239 Proportion of red blood cells in blood	Standard Deviation 0.03352
Treatment A: Probe Substrates	Treatment C: Absolute Values of Hematocrit	Day 22	0.4022 Proportion of red blood cells in blood	Standard Deviation 0.04433
Treatment A: Probe Substrates	Treatment C: Absolute Values of Hematocrit	Day 25	0.4168 Proportion of red blood cells in blood	Standard Deviation 0.04079

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.

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Absolute Values of Hemoglobin	Baseline (Day 20)	140.6 Grams per liter	Standard Deviation 12.21
Treatment A: Probe Substrates	Treatment C: Absolute Values of Hemoglobin	Day 22	134.7 Grams per liter	Standard Deviation 15.54
Treatment A: Probe Substrates	Treatment C: Absolute Values of Hemoglobin	Day 25	138.3 Grams per liter	Standard Deviation 13.83

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.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Absolute Values of Oral Temperature	Baseline (Day 21, Pre-dose)	36.31 Degrees Celsius	Standard Deviation 0.284
Treatment A: Probe Substrates	Treatment C: Absolute Values of Oral Temperature	Day 22	36.18 Degrees Celsius	Standard Deviation 0.21
Treatment A: Probe Substrates	Treatment C: Absolute Values of Oral Temperature	Day 25	36.31 Degrees Celsius	Standard Deviation 0.3

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.

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day 20): Leukocyte count	5.86 10^9 cells per liter	Standard Deviation 1.184
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 22: Leukocyte count	5.81 10^9 cells per liter	Standard Deviation 1.4
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 25: Leukocyte count	5.98 10^9 cells per liter	Standard Deviation 1.255
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 22: Neutrophils	3.1925 10^9 cells per liter	Standard Deviation 1.29353
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 25: Neutrophils	3.4529 10^9 cells per liter	Standard Deviation 1.16823
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day 20): Lymphocytes	1.8437 10^9 cells per liter	Standard Deviation 0.5382
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day 20): Platelet count	262.3 10^9 cells per liter	Standard Deviation 60.09
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 22: Platelet count	249.2 10^9 cells per liter	Standard Deviation 51.84
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 25: Platelet count	260.7 10^9 cells per liter	Standard Deviation 54.96
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day 20): Neutrophils	3.3179 10^9 cells per liter	Standard Deviation 1.18871
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 22: Lymphocytes	1.8787 10^9 cells per liter	Standard Deviation 0.57389
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 25: Lymphocytes	1.9280 10^9 cells per liter	Standard Deviation 0.63546
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day 20): Monocytes	0.4505 10^9 cells per liter	Standard Deviation 0.16811
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 22: Monocytes	0.4689 10^9 cells per liter	Standard Deviation 0.14658
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 25: Monocytes	0.3576 10^9 cells per liter	Standard Deviation 0.12355
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day 20): Eosinophils	0.1953 10^9 cells per liter	Standard Deviation 0.19443
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 22: Eosinophils	0.2282 10^9 cells per liter	Standard Deviation 0.23748
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 25: Eosinophils	0.1837 10^9 cells per liter	Standard Deviation 0.20635
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Baseline (Day 20): Basophils	0.0474 10^9 cells per liter	Standard Deviation 0.02997
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 22: Basophils	0.0380 10^9 cells per liter	Standard Deviation 0.02395
Treatment A: Probe Substrates	Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 25: Basophils	0.0408 10^9 cells per liter	Standard Deviation 0.02134

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.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Absolute Values of Pulse Rate	Baseline (Day 21, Pre-dose)	63.2 Beats per minute	Standard Deviation 7.04
Treatment A: Probe Substrates	Treatment C: Absolute Values of Pulse Rate	Day 22	56.2 Beats per minute	Standard Deviation 6.83
Treatment A: Probe Substrates	Treatment C: Absolute Values of Pulse Rate	Day 25	61.7 Beats per minute	Standard Deviation 7.27

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.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Absolute Values of Respiratory Rate	Baseline (Day 21, Pre-dose)	15.7 Breaths per minute	Standard Deviation 1.56
Treatment A: Probe Substrates	Treatment C: Absolute Values of Respiratory Rate	Day 22	15.7 Breaths per minute	Standard Deviation 1.38
Treatment A: Probe Substrates	Treatment C: Absolute Values of Respiratory Rate	Day 25	16.5 Breaths per minute	Standard Deviation 2.2

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.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Absolute Values of SBP and DBP	Baseline (Day 21, Pre-dose): DBP	62.7 Millimeters of mercury	Standard Deviation 5.31
Treatment A: Probe Substrates	Treatment C: Absolute Values of SBP and DBP	Baseline (Day 21, Pre-dose): SBP	107.5 Millimeters of mercury	Standard Deviation 8.49
Treatment A: Probe Substrates	Treatment C: Absolute Values of SBP and DBP	Day 22: SBP	105.6 Millimeters of mercury	Standard Deviation 11.93
Treatment A: Probe Substrates	Treatment C: Absolute Values of SBP and DBP	Day 25: SBP	109.7 Millimeters of mercury	Standard Deviation 7.96
Treatment A: Probe Substrates	Treatment C: Absolute Values of SBP and DBP	Day 22: DBP	58.4 Millimeters of mercury	Standard Deviation 5.87
Treatment A: Probe Substrates	Treatment C: Absolute Values of SBP and DBP	Day 25: DBP	62.2 Millimeters of mercury	Standard Deviation 5.06

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.

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Baseline (Day 20): Urate	343.1057 Micromoles per liter	Standard Deviation 74.89791
Treatment A: Probe Substrates	Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 22: Urate	303.0349 Micromoles per liter	Standard Deviation 71.88291
Treatment A: Probe Substrates	Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 25: Urate	340.6013 Micromoles per liter	Standard Deviation 67.89995
Treatment A: Probe Substrates	Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Baseline (Day 20): Creatinine	92.1686 Micromoles per liter	Standard Deviation 22.56047
Treatment A: Probe Substrates	Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 22: Creatinine	87.3764 Micromoles per liter	Standard Deviation 22.63812
Treatment A: Probe Substrates	Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 25: Creatinine	90.5867 Micromoles per liter	Standard Deviation 21.29029
Treatment A: Probe Substrates	Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Baseline (Day 20): Bilirubin	8.7480 Micromoles per liter	Standard Deviation 3.07497
Treatment A: Probe Substrates	Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 22: Bilirubin	9.8820 Micromoles per liter	Standard Deviation 3.24579
Treatment A: Probe Substrates	Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 25: Bilirubin	9.0360 Micromoles per liter	Standard Deviation 3.89534
Treatment A: Probe Substrates	Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Baseline (Day 20): Direct bilirubin	1.8450 Micromoles per liter	Standard Deviation 0.64634
Treatment A: Probe Substrates	Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 22: Direct bilirubin	2.0790 Micromoles per liter	Standard Deviation 0.6093
Treatment A: Probe Substrates	Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 25: Direct bilirubin	1.9980 Micromoles per liter	Standard Deviation 0.70286

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: AUC(0-t) for GSK3640254	51840 h*ng/mL	Geometric Coefficient of Variation 48.8

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: AUC From Time Zero to the End of the Dosing Interval at Steady State (AUC[0-tau]) for GSK3640254	22920 h*ng/mL	Geometric Coefficient of Variation 37.3

Secondary

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

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Albumin, Globulin, Protein	Day 25: Globulin	-0.3 Grams per liter	Standard Deviation 1.76
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Albumin, Globulin, Protein	Day 22: Albumin	-1.1 Grams per liter	Standard Deviation 2.44
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Albumin, Globulin, Protein	Day 25: Albumin	0.4 Grams per liter	Standard Deviation 1.71
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Albumin, Globulin, Protein	Day 22: Globulin	-1.8 Grams per liter	Standard Deviation 1.98
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Albumin, Globulin, Protein	Day 22: Protein	-2.9 Grams per liter	Standard Deviation 4.15
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Albumin, Globulin, Protein	Day 25: Protein	0.2 Grams per liter	Standard Deviation 2.81

Secondary

Treatment C: Change From Baseline in Amylase, Lipase

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Amylase, Lipase	Day 22: Lipase	0.6 Units per liter	Standard Deviation 10.08
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Amylase, Lipase	Day 25: Lipase	0.2 Units per liter	Standard Deviation 4.88
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Amylase, Lipase	Day 22: Amylase	2.5 Units per liter	Standard Deviation 7.1
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Amylase, Lipase	Day 25: Amylase	-1.5 Units per liter	Standard Deviation 4.98

Secondary

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

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 25: Gamma-glutamyl transferase	0.2 International units per liter	Standard Deviation 1.26
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 22: Creatine kinase	-5.6 International units per liter	Standard Deviation 21.78
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 25: Creatine kinase	-7.5 International units per liter	Standard Deviation 26.1
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 22: Lactate dehydrogenase	4.0 International units per liter	Standard Deviation 18.94
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 25: Lactate dehydrogenase	2.6 International units per liter	Standard Deviation 16.3
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 22: ALT	-3.1 International units per liter	Standard Deviation 4.12
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 25: ALT	0.5 International units per liter	Standard Deviation 2.61
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 22: ALP	-0.9 International units per liter	Standard Deviation 5.83
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 25:ALP	0.1 International units per liter	Standard Deviation 3.91
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 22: AST	-1.5 International units per liter	Standard Deviation 2.78
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 25: AST	0.2 International units per liter	Standard Deviation 1.89
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase	Day 22: Gamma-glutamyl transferase	-1.5 International units per liter	Standard Deviation 1.61

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.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF	Day 22: QTcF Interval	-1.4 Milliseconds	Standard Deviation 9.44
Treatment A: Probe Substrates	Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF	Day 25: QTcF Interval	-6.3 Milliseconds	Standard Deviation 8.41
Treatment A: Probe Substrates	Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF	Day 22: PR Interval	1.5 Milliseconds	Standard Deviation 9.99
Treatment A: Probe Substrates	Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF	Day 25: PR Interval	-1.2 Milliseconds	Standard Deviation 10.07
Treatment A: Probe Substrates	Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF	Day 22: QRS Duration	2.9 Milliseconds	Standard Deviation 4.24
Treatment A: Probe Substrates	Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF	Day 25: QRS Duration	1.0 Milliseconds	Standard Deviation 3.43
Treatment A: Probe Substrates	Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF	Day 22: QT Interval	18.0 Milliseconds	Standard Deviation 20.32
Treatment A: Probe Substrates	Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF	Day 25: QT Interval	-3.9 Milliseconds	Standard Deviation 16.18

Secondary

Treatment C: Change From Baseline in Erythrocytes

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Erythrocytes	Day 22	-0.161 10^12 cells per liter	Standard Deviation 0.219
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Erythrocytes	Day 25	-0.013 10^12 cells per liter	Standard Deviation 0.2027

Secondary

Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin	Day 22	-0.23 Picograms	Standard Deviation 0.407
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin	Day 25	-0.39 Picograms	Standard Deviation 0.519

Secondary

Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Volume

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Volume	Day 22	-1.64 Femtoliter	Standard Deviation 1.849
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Volume	Day 25	-1.28 Femtoliter	Standard Deviation 2.234

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.

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Glucose	0.0876 Millimoles per liter	Standard Deviation 0.29392
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Glucose	0.1519 Millimoles per liter	Standard Deviation 0.3257
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Carbon Dioxide	0.5 Millimoles per liter	Standard Deviation 2.12
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Carbon Dioxide	1.2 Millimoles per liter	Standard Deviation 1.81
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Cholesterol	-0.4355 Millimoles per liter	Standard Deviation 0.31287
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Cholesterol	-0.2926 Millimoles per liter	Standard Deviation 0.25147
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Triglycerides	0.0054 Millimoles per liter	Standard Deviation 0.14595
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Triglycerides	0.0291 Millimoles per liter	Standard Deviation 0.1828
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Anion Gap	-0.6 Millimoles per liter	Standard Deviation 1.8
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Anion Gap	-0.1 Millimoles per liter	Standard Deviation 0.97
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Calcium	-0.0407 Millimoles per liter	Standard Deviation 0.07165
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Calcium	0.0302 Millimoles per liter	Standard Deviation 0.05553
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Chloride	1.4 Millimoles per liter	Standard Deviation 1.64
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Chloride	-0.8 Millimoles per liter	Standard Deviation 1.78
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Phosphate	-0.0680 Millimoles per liter	Standard Deviation 0.0986
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Phosphate	0.0816 Millimoles per liter	Standard Deviation 0.09527
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Potassium	-0.04 Millimoles per liter	Standard Deviation 0.373
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Potassium	-0.03 Millimoles per liter	Standard Deviation 0.441
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Sodium	1.2 Millimoles per liter	Standard Deviation 1.51
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Sodium	0.4 Millimoles per liter	Standard Deviation 2.41
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 22: Urea	-0.8286 Millimoles per liter	Standard Deviation 0.88169
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea	Day 25: Urea	-0.4265 Millimoles per liter	Standard Deviation 0.85981

Secondary

Treatment C: Change From Baseline in Hematocrit

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Hematocrit	Day 22	-0.0217 Proportion of red blood cells in blood	Standard Deviation 0.0209
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Hematocrit	Day 25	-0.0071 Proportion of red blood cells in blood	Standard Deviation 0.02129

Secondary

Treatment C: Change From Baseline in Hemoglobin

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Hemoglobin	Day 22	-5.8 Grams per liter	Standard Deviation 6.52
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Hemoglobin	Day 25	-2.3 Grams per liter	Standard Deviation 5.82

Secondary

Treatment C: Change From Baseline in Oral Temperature

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Oral Temperature	Day 25	0.01 Degrees Celsius	Standard Deviation 0.286
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Oral Temperature	Day 22	-0.13 Degrees Celsius	Standard Deviation 0.242

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.

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 25: Leukocyte count	0.12 10^9 cells per liter	Standard Deviation 0.82
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 22: Platelet count	-13.1 10^9 cells per liter	Standard Deviation 19.31
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 25: Platelet count	-1.6 10^9 cells per liter	Standard Deviation 24.62
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 22: Leukocyte count	-0.05 10^9 cells per liter	Standard Deviation 0.906
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 22: Neutrophils	-0.1254 10^9 cells per liter	Standard Deviation 0.74916
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 25: Neutrophils	0.1351 10^9 cells per liter	Standard Deviation 0.72701
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 22: Lymphocytes	0.0351 10^9 cells per liter	Standard Deviation 0.42962
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 25: Lymphocytes	0.0843 10^9 cells per liter	Standard Deviation 0.41536
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 22: Monocytes	0.0184 10^9 cells per liter	Standard Deviation 0.08808
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 25: Monocytes	-0.0929 10^9 cells per liter	Standard Deviation 0.17694
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 22: Eosinophils	0.0329 10^9 cells per liter	Standard Deviation 0.12007
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 25: Eosinophils	-0.0115 10^9 cells per liter	Standard Deviation 0.06076
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 22: Basophils	-0.0094 10^9 cells per liter	Standard Deviation 0.03787
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils	Day 25: Basophils	-0.0066 10^9 cells per liter	Standard Deviation 0.03173

Secondary

Treatment C: Change From Baseline in Pulse Rate

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Pulse Rate	Day 22	-7.1 Beats per minute	Standard Deviation 7.48
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Pulse Rate	Day 25	-1.5 Beats per minute	Standard Deviation 6.17

Secondary

Treatment C: Change From Baseline in Respiratory Rate

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Respiratory Rate	Day 22	-0.1 Breaths per minute	Standard Deviation 1.9
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Respiratory Rate	Day 25	0.8 Breaths per minute	Standard Deviation 2.37

Secondary

Treatment C: Change From Baseline in SBP and DBP

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Change From Baseline in SBP and DBP	Day 22: SBP	-1.9 Millimeters of mercury	Standard Deviation 10.84
Treatment A: Probe Substrates	Treatment C: Change From Baseline in SBP and DBP	Day 25: SBP	2.2 Millimeters of mercury	Standard Deviation 8.67
Treatment A: Probe Substrates	Treatment C: Change From Baseline in SBP and DBP	Day 22: DBP	-4.3 Millimeters of mercury	Standard Deviation 4.75
Treatment A: Probe Substrates	Treatment C: Change From Baseline in SBP and DBP	Day 25: DBP	-0.5 Millimeters of mercury	Standard Deviation 4.78

Secondary

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

Time frame: Baseline (Day 20), Days 22 and 25

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 22: Urate	-40.0707 Micromoles per liter	Standard Deviation 26.51457
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 25: Urate	-2.5044 Micromoles per liter	Standard Deviation 26.62359
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 22: Creatinine	-4.7922 Micromoles per liter	Standard Deviation 5.82901
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 25: Creatinine	-1.5819 Micromoles per liter	Standard Deviation 4.6083
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 22: Bilirubin	1.1340 Micromoles per liter	Standard Deviation 1.91202
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 25: Bilirubin	0.2880 Micromoles per liter	Standard Deviation 2.14494
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 22: Direct bilirubin	0.2340 Micromoles per liter	Standard Deviation 0.38326
Treatment A: Probe Substrates	Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin	Day 25: Direct bilirubin	0.1530 Micromoles per liter	Standard Deviation 0.39447

Secondary

Treatment C: Cmax for GSK3640254

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

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Cmax for GSK3640254	1450 ng/mL	Geometric Coefficient of Variation 41.7

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.

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: Plasma Concentration at the End of the Dosing Interval (Ctau) for GSK3640254	729.5 ng/mL	Geometric Coefficient of Variation 35.5

Secondary

Treatment C: t1/2 for GSK3640254

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

Time frame: 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

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Treatment A: Probe Substrates	Treatment C: t1/2 for GSK3640254	29.556 Hours	Geometric Coefficient of Variation 16.9

Secondary

Treatment C: Tmax for GSK3640254

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

Time frame: 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

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

Arm	Measure	Value (MEDIAN)
Treatment A: Probe Substrates	Treatment C: Tmax for GSK3640254	4.500 Hours

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

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

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Masking description

Intervention model description

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

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

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

AUC(0-infinity) for Digoxin

AUC(0-infinity) for Flurbiprofen

AUC(0-infinity) for Metoprolol

AUC(0-infinity) for Midazolam

AUC(0-infinity) for Montelukast

AUC(0-infinity) for Omeprazole

AUC(0-infinity) for Pravastatin

AUC(0-t) for Digoxin

AUC(0-t) for Flurbiprofen

AUC(0-t) for Metoprolol

AUC(0-t) for Midazolam

AUC(0-t) for Montelukast

AUC(0-t) for Omeprazole

AUC(0-t) for Pravastatin

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

Cmax for Digoxin

Cmax for Flurbiprofen

Cmax for Metoprolol

Cmax for Midazolam

Cmax for Montelukast

Cmax for Omeprazole

Cmax for Pravastatin

Maximum Observed Plasma Concentration (Cmax) for Caffeine

t1/2 for Digoxin

t1/2 for Flurbiprofen

t1/2 for Metoprolol

t1/2 for Midazolam

t1/2 for Montelukast

t1/2 for Omeprazole

t1/2 for Pravastatin

Time to Cmax (Tmax) for Caffeine

Tmax for Digoxin

Tmax for Flurbiprofen

Tmax for Metoprolol

Tmax for Midazolam

Tmax for Montelukast

Tmax for Omeprazole

Tmax for Pravastatin

AUC(0-infinity) for 1-hydroxymidazolam

AUC(0-infinity) for 36-hydroxymontelukast

AUC(0-infinity) for 5-hydroxyomeprazole

AUC(0-infinity) for Alpha-hydroxymetoprolol

AUC(0-t) for 1-hydroxymidazolam

AUC(0-t) for 36-hydroxymontelukast

AUC(0-t) for 5-hydroxyomeprazole

AUC(0-t) for Alpha-hydroxymetoprolol

Cmax for 1-hydroxymidazolam

Cmax for 36-hydroxymontelukast

Cmax for 5-hydroxyomeprazole

Cmax for Alpha-hydroxymetoprolol

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

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

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