AzTrials
AzTrials

HIV InfectionsPhase 1NCT04425902

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

A Phase 1 study testing GSK3640254 200 mg, Caffeine 200 mg and Metoprolol 100 mg in people with HIV Infections, run by ViiV Healthcare at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for
HIV Infections
What is being tested?
GSK3640254 200 mg, Caffeine 200 mg and Metoprolol 100 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
16 Dec 2020to 10 Mar 2021
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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:
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  • 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.

Who cannot join

  • 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.
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  • Any pre-existing physical or other psychiatric condition (including alcohol or drug abuse), which, in the opinion of the investigator (with or without psychiatric evaluation), could interfere with the participant's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the participant.
  • Medical history of cardiac arrhythmias, prior myocardial infarction in the past 3 months, or cardiac disease or a family or personal history of long QT syndrome.
  • History of asthma, bronchospasm, or sleep apnea.
  • History of chronic musculoskeletal pain (myalgias).
  • History of rhabdomyolysis.
  • History of a bleeding disorder.
  • History of Raynaud's disease.
  • History indicative of an increased risk of a cardiac arrhythmia or cardiac disease, including the following:
  • History of cardiac arrhythmias or palpitations associated with presyncope or syncope, or history of unexplained syncope.
  • History of clinically relevant cardiac disease including symptomatic or asymptomatic arrhythmias (including but not limited to ventricular fibrillation, ventricular tachycardia, any degree of atrioventricular block, Brugada syndrome, Wolff-Parkinson-White syndrome, and sinus bradycardia, defined as heart rate less than 50 beats per minute (bpm) based on vital signs or ECG), presyncope or syncopal episodes, or additional risk factors for torsades de pointes (e.g., heart failure).
  • History of clinically relevant structural cardiac disease including hypertrophic obstructive cardiomyopathy.
  • History of hypokalemia.
  • History of heart disease (e.g., coronary heart disease).
  • Presence of hepatitis B surface antigen at Screening or within 3 months prior to starting study intervention.
  • Positive hepatitis C antibody test result at Screening or within 3 months prior to starting study intervention and positive on reflex to hepatitis C Ribonucleic Acid (RNA).
  • Positive HIV-1 and 2 antigen/antibody immunoassay at Screening.
  • ALT>=1.5 × upper limit of normal (ULN). A single repeat of ALT is allowed within a single screening period to determine eligibility.
  • Bilirubin >=5 × ULN (isolated bilirubin >=5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). A single repeat of any laboratory abnormality is allowed within a single screening period to determine eligibility.
  • Any acute laboratory abnormality at Screening which, in the opinion of the investigator, should preclude participation in the study of an investigational compound.
  • Any Grade 2 to 4 laboratory abnormality at Screening, with the exception of lipid abnormalities (e.g., total cholesterol, triglycerides), and ALT, will exclude a participant from the study unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the sponsor.
  • A positive test result for drugs of abuse (including marijuana), alcohol, or cotinine (indicating active current smoking) at Screening or before the first dose of study intervention.
  • Unable to refrain from the use of prescription or nonprescription drugs including vitamins, herbal and dietary supplements (including St John's wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study intervention and for the duration of the study.
  • Treatment with any vaccine within 30 days prior to receiving study intervention.
  • Unwillingness to abstain from excessive consumption of any food or drink containing grapefruit and grapefruit juice, Seville oranges, blood oranges, or pomelos or their fruit juices within 7 days prior to the first dose of study intervention(s) until the end of the study.
  • Participation in another concurrent clinical study or prior clinical study (with the exception of imaging trials) prior to the first dosing day in the current study: 30 days, 5 half-lives, or twice the duration of the biological effect of the study intervention (whichever is longer).
  • Prior exposure to GSK3640254 in another clinical study.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56 days.
  • Any positive (abnormal) response confirmed by the investigator on a screening clinician- or qualified designee-administered Columbia-Suicide Severity Rating Scale (C-SSRS).
  • SBP <100 mm Hg. Up to 2 repeats are allowed for confirmation.
  • Any significant arrhythmia or ECG finding (e.g., prior myocardial infarction in the past 3 months, symptomatic bradycardia, non-sustained or sustained atrial arrhythmias, non-sustained or sustained ventricular tachycardia, any degree of atrioventricular block, or conduction abnormality) which will interfere with the safety for the individual participant.
  • Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination): Heart rate- <50 or >100 bpm, PR interval- >200 milliseconds and QTcF- >450 milliseconds.
  • History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >14 units. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of spirits.
  • Unable to refrain from tobacco or nicotine-containing products within 3 months prior to Screening.
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.
  • History of aspirin allergy.
  • A participant with known or suspected active coronavirus disease of 2019 (COVID-19) infection OR contact with an individual with known COVID-19, within 14 days of study enrollment.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • GSK Investigational Site

    Las Vegas, Nevada, 89113

Other trials in United States

About this study

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

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.

Conditions
HIV Infections
Being tested
GSK3640254 200 mg, Caffeine 200 mg, Metoprolol 100 mg, Montelukast 10 mg, Flurbiprofen 100 mg
Keywords
GSK3640254, Human immunodeficiency virus (HIV) infections, Drug interaction, Pharmacokinetics, Probe substrate
Medical subject headings
HIV Infections, Acquired Immunodeficiency Syndrome, Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK3640254 200 mgDrug

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

  • Caffeine 200 mgDrug

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

  • Metoprolol 100 mgDrug

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

  • Montelukast 10 mgDrug

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

  • Flurbiprofen 100 mgDrug

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

  • Omeprazole 40 mgDrug

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

  • Midazolam 5 mg (2.5 mL)Drug

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

  • Digoxin 0.25 mgDrug

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

  • Pravastatin 40 mgDrug

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

Study groups in NCT04425902
Study groupRoleWhat they receive
Probe Substrates/GSK3640254 200 mg/Probe Substrates+GSK3640254ExperimentalAll participants will receive a single dose of treatment A: Probe substrates (caffeine 200 milligram [mg], metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1; followed by treatment B- GSK3640254 200 mg on Days 11 to 20; further followed by treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
Receives: Drug: GSK3640254 200 mg; Drug: Caffeine 200 mg; Drug: Metoprolol 100 mg; Drug: Montelukast 10 mg; Drug: Flurbiprofen 100 mg; Drug: Omeprazole 40 mg; Drug: Midazolam 5 mg (2.5 mL); Drug: Digoxin 0.25 mg; Drug: Pravastatin 40 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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

  2. 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.

    Measured: 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

  3. Maximum Observed Plasma Concentration (Cmax) for Caffeine

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

    Measured: 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

  4. Time to Cmax (Tmax) for Caffeine

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

    Measured: 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

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

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

    Measured: 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

  6. 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.

    Measured: 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

  7. 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.

    Measured: 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

  8. Cmax for Metoprolol

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

    Measured: 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

  9. Tmax for Metoprolol

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

    Measured: 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

  10. t1/2 for Metoprolol

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

    Measured: 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

  11. 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.

    Measured: 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

  12. 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.

    Measured: 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

  13. Cmax for Montelukast

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

    Measured: 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

  14. Tmax for Montelukast

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

    Measured: 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

  15. t1/2 for Montelukast

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

    Measured: 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

  16. 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.

    Measured: 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

  17. 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.

    Measured: 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

  18. Cmax for Flurbiprofen

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

    Measured: 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

  19. Tmax for Flurbiprofen

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

    Measured: 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

  20. t1/2 for Flurbiprofen

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

    Measured: 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

  21. 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.

    Measured: 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

  22. 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.

    Measured: 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

  23. Cmax for Omeprazole

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

    Measured: 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

  24. Tmax for Omeprazole

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

    Measured: 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

  25. t1/2 for Omeprazole

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

    Measured: 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

  26. 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.

    Measured: 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

  27. 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.

    Measured: 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

  28. Cmax for Midazolam

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

    Measured: 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

  29. Tmax for Midazolam

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

    Measured: 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

  30. t1/2 for Midazolam

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

    Measured: 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

  31. 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.

    Measured: 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

  32. 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.

    Measured: 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

  33. Cmax for Digoxin

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

    Measured: 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

  34. Tmax for Digoxin

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

    Measured: 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

  35. t1/2 for Digoxin

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

    Measured: 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

  36. 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.

    Measured: 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

  37. 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.

    Measured: 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

  38. Cmax for Pravastatin

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

    Measured: 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

  39. Tmax for Pravastatin

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

    Measured: 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

  40. t1/2 for Pravastatin

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

    Measured: 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

Secondary outcomes (131)

  1. 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.

    Measured: Up to Day 26

  2. 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.

    Measured: Baseline (Day -1) and Day 10

  3. 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.

    Measured: Baseline (Day 10) and Day 20

  4. 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.

    Measured: Baseline (Day 20), Days 22 and 25

  5. 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.

    Measured: Baseline (Day -1) and Day 10

  6. 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.

    Measured: Baseline (Day 10) and Day 20

  7. 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.

    Measured: Baseline (Day 20), Days 22 and 25

  8. 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.

    Measured: Baseline (Day -1) and Day 10

  9. 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.

    Measured: Baseline (Day 10) and Day 20

  10. 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.

    Measured: Baseline (Day 20), Days 22 and 25

  11. 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.

    Measured: Baseline (Day -1) and Day 10

  12. 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.

    Measured: Baseline (Day 10) and Day 20

  13. 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.

    Measured: Baseline (Day 20), Days 22 and 25

  14. 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.

    Measured: Baseline (Day -1) and Day 10

  15. 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.

    Measured: Baseline (Day 10) and Day 20

  16. 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.

    Measured: Baseline (Day 20), Days 22 and 25

  17. 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.

    Measured: Baseline (Day -1) and Day 10

  18. 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.

    Measured: Baseline (Day 10) and Day 20

  19. 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.

    Measured: Baseline (Day 20), Days 22 and 25

  20. 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.

    Measured: Baseline (Day -1) and Day 10

  21. 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.

    Measured: Baseline (Day 10) and Day 20

  22. 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.

    Measured: Baseline (Day 20), Days 22 and 25

  23. 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.

    Measured: Baseline (Day -1) and Day 10

  24. 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.

    Measured: Baseline (Day 10) and Day 20

  25. 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.

    Measured: Baseline (Day 20), Days 22 and 25

  26. 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.

    Measured: Baseline (Day -1) and Day 10

  27. 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.

    Measured: Baseline (Day 10) and Day 20

  28. 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.

    Measured: Baseline (Day 20), Days 22 and 25

  29. 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.

    Measured: Baseline (Day -1) and Day 10

  30. 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.

    Measured: Baseline (Day 10) and Day 20

  31. 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.

    Measured: Baseline (Day 20), Days 22 and 25

  32. 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.

    Measured: Baseline (Day -1) and Day 10

  33. 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.

    Measured: Baseline (Day 10) and Day 20

  34. 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.

    Measured: Baseline (Day 20), Days 22 and 25

  35. Treatment A: 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 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.

    Measured: Baseline (Day -1) and Day 10

  36. 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.

    Measured: Baseline (Day 10) and Day 20

  37. 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.

    Measured: Baseline (Day 20), Days 22 and 25

  38. Treatment A: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day -1) and Day 10

  39. Treatment B: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day 10) and Day 20

  40. Treatment C: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day 20), Days 22 and 25

  41. Treatment A: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day -1) and Day 10

  42. Treatment B: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day 10) and Day 20

  43. Treatment C: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day 20), Days 22 and 25

  44. Treatment A: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day -1) and Day 10

  45. Treatment B: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day 10) and Day 20

  46. Treatment C: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day 20), Days 22 and 25

  47. Treatment A: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day -1) and Day 10

  48. Treatment B: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day 10) and Day 20

  49. Treatment C: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day 20), Days 22 and 25

  50. Treatment A: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day -1) and Day 10

  51. Treatment B: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day 10) and Day 20

  52. Treatment C: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day 20), Days 22 and 25

  53. 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.

    Measured: Baseline (Day -1) and Day 10

  54. 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.

    Measured: Baseline (Day 10) and Day 20

  55. 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.

    Measured: Baseline (Day 20), Days 22 and 25

  56. Treatment A: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day -1) and Day 10

  57. Treatment B: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day 10) and Day 20

  58. Treatment C: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day 20), Days 22 and 25

  59. Treatment A: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day -1) and Day 10

  60. Treatment B: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day 10) and Day 20

  61. Treatment C: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day 20), Days 22 and 25

  62. Treatment A: Change From Baseline in 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 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.

    Measured: Baseline (Day -1) and Day 10

  63. Treatment B: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day 10) and Day 20

  64. Treatment C: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day 20), Days 22 and 25

  65. Treatment A: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day -1) and Day 10

  66. Treatment B: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day 10) and Day 20

  67. Treatment C: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

    Measured: Baseline (Day 20), Days 22 and 25

  68. 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.

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

  69. 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.

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

  70. 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.

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

  71. Treatment A: 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 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.

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

  72. 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.

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

  73. 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.

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

  74. 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.

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

  75. 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.

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

  76. 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.

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

  77. 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.

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

  78. 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.

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

  79. 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.

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

  80. 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.

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

  81. 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.

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

  82. 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.

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

  83. 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.

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

  84. 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.

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

  85. 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.

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

  86. Treatment A: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

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

  87. Treatment B: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

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

  88. Treatment C: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

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

  89. Treatment A: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

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

  90. Treatment B: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

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

  91. Treatment C: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

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

  92. Treatment A: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

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

  93. Treatment B: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

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

  94. Treatment C: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

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

  95. Treatment A: Change From Baseline in 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 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.

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

  96. Treatment B: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

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

  97. Treatment C: Change From Baseline in 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. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.

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

  98. 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.

    Measured: 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

  99. 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.

    Measured: 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

  100. Treatment C: Cmax for GSK3640254

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

    Measured: 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

  101. 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.

    Measured: 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

  102. Treatment C: Tmax for GSK3640254

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

    Measured: 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

  103. Treatment C: t1/2 for GSK3640254

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

    Measured: 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

  104. 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.

    Measured: 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

  105. 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.

    Measured: 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

  106. 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.

    Measured: 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

  107. 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.

    Measured: 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

  108. 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.

    Measured: 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

  109. 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.

    Measured: 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

  110. 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.

    Measured: 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

  111. 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.

    Measured: 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

  112. 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.

    Measured: 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

  113. 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.

    Measured: 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

  114. 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.

    Measured: 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

  115. 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.

    Measured: 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

  116. 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.

    Measured: 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

  117. 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.

    Measured: 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

  118. 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.

    Measured: 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

  119. 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.

    Measured: 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

  120. 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.

    Measured: 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

  121. 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.

    Measured: 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

  122. 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.

    Measured: 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

  123. 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.

    Measured: 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

  124. 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.

    Measured: 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

  125. 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.

    Measured: 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

  126. 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.

    Measured: 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

  127. 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.

    Measured: 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

  128. 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.

    Measured: 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

  129. 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.

    Measured: 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

  130. 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.

    Measured: 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

  131. 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.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Jun 2020
  2. Study start16 Dec 2020
  3. Primary completion10 Mar 2021
  4. Study completion10 Mar 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This is a single-sequence, one-way drug interaction study.
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04425902
Sponsor's protocol ID
213052
Status last verified
Dec 2023
First submitted
5 Jun 2020
Last updated
5 Jan 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on ViiV's data sharing criteria can be found at: https://viivhealthcare.com/about-viiv/corporate-ethics-compliance/commitment-to-data-transparency/

Publications

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

    PubMed 36822839

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK3640254 200 mg, Caffeine 200 mg and Metoprolol 100 mg in people with HIV Infections, run by ViiV Healthcare at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Time t (AUC[0-t]) for 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). The study lists 40 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04425902, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jan 2024.

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