Trial Outcomes & Findings for Evaluation of Pharmacokinetic Interaction Between GSK3640254 and Caffeine, Metoprolol, Montelukast, Flurbiprofen, Omeprazole, Midazolam, Digoxin, and Pravastatin in Healthy Adults (NCT NCT04425902)
NCT ID: NCT04425902
Last Updated: 2024-01-05
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
20 participants
Primary outcome timeframe
Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3
Results posted on
2024-01-05
Participant Flow
This study was conducted in the United States.
A total of 20 participants were enrolled and received study treatment.
Participant milestones
| Measure |
All Treated Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 milligram \[mg\], metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1; followed by treatment B- GSK3640254 200 mg once daily from Days 11 to 20; further followed by treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
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|---|---|
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Treatment Period 1 (Days 1 to 10)
STARTED
|
20
|
|
Treatment Period 1 (Days 1 to 10)
COMPLETED
|
20
|
|
Treatment Period 1 (Days 1 to 10)
NOT COMPLETED
|
0
|
|
Treatment Period 2 (Days 11 to 20)
STARTED
|
20
|
|
Treatment Period 2 (Days 11 to 20)
COMPLETED
|
19
|
|
Treatment Period 2 (Days 11 to 20)
NOT COMPLETED
|
1
|
|
Treatment Period 3 (Days 21 to 26)
STARTED
|
19
|
|
Treatment Period 3 (Days 21 to 26)
COMPLETED
|
19
|
|
Treatment Period 3 (Days 21 to 26)
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
All Treated Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 milligram \[mg\], metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1; followed by treatment B- GSK3640254 200 mg once daily from Days 11 to 20; further followed by treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
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|---|---|
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Treatment Period 2 (Days 11 to 20)
Adverse Event
|
1
|
Baseline Characteristics
Evaluation of Pharmacokinetic Interaction Between GSK3640254 and Caffeine, Metoprolol, Montelukast, Flurbiprofen, Omeprazole, Midazolam, Digoxin, and Pravastatin in Healthy Adults
Baseline characteristics by cohort
| Measure |
All Treated Participants
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1; followed by treatment B- GSK3640254 200 mg once daily from Days 11 to 20; further followed by treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
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|---|---|
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Age, Continuous
|
36.4 Years
STANDARD_DEVIATION 9.65 • n=99 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
9 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
White - Arabic/North African Heritage
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2 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
White - White/Caucasian/European Heritage
|
9 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: The Pharmacokinetic (PK) Parameter Population included all participants who underwent plasma PK sampling and had evaluable PK parameters estimated. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
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|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Time t (AUC[0-t]) for Caffeine
|
37970 Hour*nanograms per milliliter (h*ng/mL)
Geometric Coefficient of Variation 31.1
|
42230 Hour*nanograms per milliliter (h*ng/mL)
Geometric Coefficient of Variation 32.4
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
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|---|---|---|---|
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AUC From Time Zero Extrapolated to Infinity (AUC[0-infinity]) for Caffeine
|
39720 h*ng/mL
Geometric Coefficient of Variation 30.6
|
44440 h*ng/mL
Geometric Coefficient of Variation 30.6
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
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|---|---|---|---|
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Maximum Observed Plasma Concentration (Cmax) for Caffeine
|
4340 Nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 22.1
|
4110 Nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 25.9
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
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|---|---|---|---|
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Time to Cmax (Tmax) for Caffeine
|
2.000 Hours
Interval 1.0 to 6.0
|
3.000 Hours
Interval 0.5 to 6.0
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of caffeine.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
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|---|---|---|---|
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Apparent Terminal Phase Half-life (t1/2) for Caffeine
|
5.380 Hours
Geometric Coefficient of Variation 21.2
|
6.085 Hours
Geometric Coefficient of Variation 17.4
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
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|---|---|---|---|
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AUC(0-t) for Metoprolol
|
655.0 h*ng/mL
Geometric Coefficient of Variation 135.2
|
807.3 h*ng/mL
Geometric Coefficient of Variation 136.4
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
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|---|---|---|---|
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AUC(0-infinity) for Metoprolol
|
659.1 h*ng/mL
Geometric Coefficient of Variation 134.4
|
813.1 h*ng/mL
Geometric Coefficient of Variation 135.3
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
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Cmax for Metoprolol
|
127.4 ng/mL
Geometric Coefficient of Variation 90.0
|
141.1 ng/mL
Geometric Coefficient of Variation 94.4
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Tmax for Metoprolol
|
2.000 Hours
Interval 1.0 to 6.0
|
3.000 Hours
Interval 1.0 to 4.0
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of metoprolol.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
t1/2 for Metoprolol
|
4.872 Hours
Geometric Coefficient of Variation 65.6
|
5.342 Hours
Geometric Coefficient of Variation 59.6
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
AUC(0-t) for Montelukast
|
2724 h*ng/mL
Geometric Coefficient of Variation 19.9
|
2940 h*ng/mL
Geometric Coefficient of Variation 18.4
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
AUC(0-infinity) for Montelukast
|
2859 h*ng/mL
Geometric Coefficient of Variation 20.6
|
3109 h*ng/mL
Geometric Coefficient of Variation 18.6
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Cmax for Montelukast
|
379.8 Nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 25.2
|
393.5 Nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 19.5
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Tmax for Montelukast
|
5.000 Hours
Interval 2.0 to 8.03
|
6.000 Hours
Interval 3.0 to 8.07
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of montelukast.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
t1/2 for Montelukast
|
5.035 Hours
Geometric Coefficient of Variation 10.2
|
5.135 Hours
Geometric Coefficient of Variation 7.4
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
AUC(0-t) for Flurbiprofen
|
64930 h*ng/mL
Geometric Coefficient of Variation 28.9
|
66170 h*ng/mL
Geometric Coefficient of Variation 27.6
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
AUC(0-infinity) for Flurbiprofen
|
66700 h*ng/mL
Geometric Coefficient of Variation 28.1
|
68660 h*ng/mL
Geometric Coefficient of Variation 26.7
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Cmax for Flurbiprofen
|
10220 ng/mL
Geometric Coefficient of Variation 24.7
|
10710 ng/mL
Geometric Coefficient of Variation 19.8
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Tmax for Flurbiprofen
|
3.000 Hours
Interval 1.0 to 8.03
|
4.000 Hours
Interval 1.0 to 6.07
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of flurbiprofen.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
t1/2 for Flurbiprofen
|
6.123 Hours
Geometric Coefficient of Variation 31.0
|
6.088 Hours
Geometric Coefficient of Variation 30.4
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
AUC(0-t) for Omeprazole
|
728.1 h*ng/mL
Geometric Coefficient of Variation 114.7
|
817.9 h*ng/mL
Geometric Coefficient of Variation 82.1
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=9 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=11 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
AUC(0-infinity) for Omeprazole
|
1127 h*ng/mL
Geometric Coefficient of Variation 98.6
|
1093 h*ng/mL
Geometric Coefficient of Variation 75.5
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Cmax for Omeprazole
|
224.4 ng/mL
Geometric Coefficient of Variation 121.6
|
256.6 ng/mL
Geometric Coefficient of Variation 72.0
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Tmax for Omeprazole
|
6.000 Hours
Interval 1.5 to 12.07
|
6.000 Hours
Interval 1.5 to 12.0
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of omeprazole.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=9 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=11 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
t1/2 for Omeprazole
|
1.439 Hours
Geometric Coefficient of Variation 32.0
|
1.219 Hours
Geometric Coefficient of Variation 28.1
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
AUC(0-t) for Midazolam
|
67.11 h*ng/mL
Geometric Coefficient of Variation 31.3
|
62.95 h*ng/mL
Geometric Coefficient of Variation 31.0
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
AUC(0-infinity) for Midazolam
|
70.08 h*ng/mL
Geometric Coefficient of Variation 31.4
|
65.46 h*ng/mL
Geometric Coefficient of Variation 31.2
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Cmax for Midazolam
|
15.44 ng/mL
Geometric Coefficient of Variation 39.5
|
13.95 ng/mL
Geometric Coefficient of Variation 42.3
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Tmax for Midazolam
|
1.000 Hours
Interval 0.25 to 2.0
|
1.000 Hours
Interval 0.25 to 4.0
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of midazolam.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
t1/2 for Midazolam
|
5.756 Hours
Geometric Coefficient of Variation 13.2
|
5.222 Hours
Geometric Coefficient of Variation 20.6
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
AUC(0-t) for Digoxin
|
16690 Hours*picogram per milliliter (h*pg/mL)
Geometric Coefficient of Variation 21.7
|
17840 Hours*picogram per milliliter (h*pg/mL)
Geometric Coefficient of Variation 26.9
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
AUC(0-infinity) for Digoxin
|
19180 h*pg/mL
Geometric Coefficient of Variation 21.5
|
20090 h*pg/mL
Geometric Coefficient of Variation 27.1
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Cmax for Digoxin
|
1026 Picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 48.3
|
1282 Picogram per milliliter (pg/mL)
Geometric Coefficient of Variation 56.5
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Tmax for Digoxin
|
3.000 Hours
Interval 1.5 to 6.0
|
2.000 Hours
Interval 1.0 to 4.0
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of digoxin.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
t1/2 for Digoxin
|
40.279 Hours
Geometric Coefficient of Variation 14.3
|
38.784 Hours
Geometric Coefficient of Variation 12.0
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
AUC(0-t) for Pravastatin
|
69.92 h*ng/mL
Geometric Coefficient of Variation 63.9
|
51.03 h*ng/mL
Geometric Coefficient of Variation 75.5
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=16 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
AUC(0-infinity) for Pravastatin
|
72.09 h*ng/mL
Geometric Coefficient of Variation 62.9
|
43.70 h*ng/mL
Geometric Coefficient of Variation 47.5
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Cmax for Pravastatin
|
19.45 ng/mL
Geometric Coefficient of Variation 79.8
|
15.19 ng/mL
Geometric Coefficient of Variation 76.9
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Tmax for Pravastatin
|
1.500 Hours
Interval 0.5 to 6.0
|
3.000 Hours
Interval 1.0 to 4.0
|
—
|
PRIMARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of pravastatin.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=16 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
t1/2 for Pravastatin
|
3.189 Hours
Geometric Coefficient of Variation 43.4
|
3.156 Hours
Geometric Coefficient of Variation 47.2
|
—
|
SECONDARY outcome
Timeframe: Up to Day 26Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=20 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
SAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AEs
|
1 Participants
|
5 Participants
|
5 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 10: Leukocyte count
|
6.30 10^9 cells per liter
Standard Deviation 1.343
|
—
|
—
|
|
Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day -1): Neutrophils
|
3.1504 10^9 cells per liter
Standard Deviation 1.25074
|
—
|
—
|
|
Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day -1): Platelet count
|
258.6 10^9 cells per liter
Standard Deviation 59.14
|
—
|
—
|
|
Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 10: Platelet count
|
265.9 10^9 cells per liter
Standard Deviation 60.21
|
—
|
—
|
|
Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day -1): Leukocyte count
|
5.64 10^9 cells per liter
Standard Deviation 1.338
|
—
|
—
|
|
Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 10: Neutrophils
|
3.7430 10^9 cells per liter
Standard Deviation 1.27763
|
—
|
—
|
|
Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day -1): Lymphocytes
|
1.8217 10^9 cells per liter
Standard Deviation 0.39628
|
—
|
—
|
|
Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 10: Lymphocytes
|
1.8965 10^9 cells per liter
Standard Deviation 0.33426
|
—
|
—
|
|
Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day -1): Monocytes
|
0.4890 10^9 cells per liter
Standard Deviation 0.15889
|
—
|
—
|
|
Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 10: Monocytes
|
0.4515 10^9 cells per liter
Standard Deviation 0.12708
|
—
|
—
|
|
Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day -1): Eosinophils
|
0.1461 10^9 cells per liter
Standard Deviation 0.15067
|
—
|
—
|
|
Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 10: Eosinophils
|
0.1610 10^9 cells per liter
Standard Deviation 0.15071
|
—
|
—
|
|
Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day -1): Basophils
|
0.0331 10^9 cells per liter
Standard Deviation 0.01657
|
—
|
—
|
|
Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 10: Basophils
|
0.0440 10^9 cells per liter
Standard Deviation 0.01569
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day 10): Platelet count
|
265.9 10^9 cells per liter
Standard Deviation 60.21
|
—
|
—
|
|
Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 20: Platelet count
|
261.9 10^9 cells per liter
Standard Deviation 58.51
|
—
|
—
|
|
Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day 10): Leukocyte count
|
6.30 10^9 cells per liter
Standard Deviation 1.343
|
—
|
—
|
|
Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 20: Leukocyte count
|
5.79 10^9 cells per liter
Standard Deviation 1.192
|
—
|
—
|
|
Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day 10): Neutrophils
|
3.7430 10^9 cells per liter
Standard Deviation 1.27763
|
—
|
—
|
|
Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 20: Neutrophils
|
3.2680 10^9 cells per liter
Standard Deviation 1.17833
|
—
|
—
|
|
Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day 10): Lymphocytes
|
1.8965 10^9 cells per liter
Standard Deviation 0.33426
|
—
|
—
|
|
Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 20: Lymphocytes
|
1.8355 10^9 cells per liter
Standard Deviation 0.52512
|
—
|
—
|
|
Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day 10): Monocytes
|
0.4515 10^9 cells per liter
Standard Deviation 0.12708
|
—
|
—
|
|
Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 20: Monocytes
|
0.4435 10^9 cells per liter
Standard Deviation 0.16662
|
—
|
—
|
|
Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day 10): Eosinophils
|
0.1610 10^9 cells per liter
Standard Deviation 0.15071
|
—
|
—
|
|
Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 20: Eosinophils
|
0.1920 10^9 cells per liter
Standard Deviation 0.18981
|
—
|
—
|
|
Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day 10): Basophils
|
0.0440 10^9 cells per liter
Standard Deviation 0.01569
|
—
|
—
|
|
Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 20: Basophils
|
0.0460 10^9 cells per liter
Standard Deviation 0.02981
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 22: Neutrophils
|
3.1925 10^9 cells per liter
Standard Deviation 1.29353
|
—
|
—
|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day 20): Basophils
|
0.0474 10^9 cells per liter
Standard Deviation 0.02997
|
—
|
—
|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day 20): Platelet count
|
262.3 10^9 cells per liter
Standard Deviation 60.09
|
—
|
—
|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 22: Platelet count
|
249.2 10^9 cells per liter
Standard Deviation 51.84
|
—
|
—
|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 25: Platelet count
|
260.7 10^9 cells per liter
Standard Deviation 54.96
|
—
|
—
|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day 20): Leukocyte count
|
5.86 10^9 cells per liter
Standard Deviation 1.184
|
—
|
—
|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 22: Leukocyte count
|
5.81 10^9 cells per liter
Standard Deviation 1.400
|
—
|
—
|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 25: Leukocyte count
|
5.98 10^9 cells per liter
Standard Deviation 1.255
|
—
|
—
|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day 20): Neutrophils
|
3.3179 10^9 cells per liter
Standard Deviation 1.18871
|
—
|
—
|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 25: Neutrophils
|
3.4529 10^9 cells per liter
Standard Deviation 1.16823
|
—
|
—
|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day 20): Lymphocytes
|
1.8437 10^9 cells per liter
Standard Deviation 0.53820
|
—
|
—
|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 22: Lymphocytes
|
1.8787 10^9 cells per liter
Standard Deviation 0.57389
|
—
|
—
|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 25: Lymphocytes
|
1.9280 10^9 cells per liter
Standard Deviation 0.63546
|
—
|
—
|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day 20): Monocytes
|
0.4505 10^9 cells per liter
Standard Deviation 0.16811
|
—
|
—
|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 22: Monocytes
|
0.4689 10^9 cells per liter
Standard Deviation 0.14658
|
—
|
—
|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 25: Monocytes
|
0.3576 10^9 cells per liter
Standard Deviation 0.12355
|
—
|
—
|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Baseline (Day 20): Eosinophils
|
0.1953 10^9 cells per liter
Standard Deviation 0.19443
|
—
|
—
|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 22: Eosinophils
|
0.2282 10^9 cells per liter
Standard Deviation 0.23748
|
—
|
—
|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 25: Eosinophils
|
0.1837 10^9 cells per liter
Standard Deviation 0.20635
|
—
|
—
|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 22: Basophils
|
0.0380 10^9 cells per liter
Standard Deviation 0.02395
|
—
|
—
|
|
Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 25: Basophils
|
0.0408 10^9 cells per liter
Standard Deviation 0.02134
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Absolute Values of Hematocrit
Day 10
|
0.4098 Proportion of red blood cells in blood
Standard Deviation 0.03577
|
—
|
—
|
|
Treatment A: Absolute Values of Hematocrit
Baseline (Day -1)
|
0.4188 Proportion of red blood cells in blood
Standard Deviation 0.03442
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Absolute Values of Hematocrit
Baseline (Day 10)
|
0.4098 Proportion of red blood cells in blood
Standard Deviation 0.03577
|
—
|
—
|
|
Treatment B: Absolute Values of Hematocrit
Day 20
|
0.4216 Proportion of red blood cells in blood
Standard Deviation 0.03420
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Absolute Values of Hematocrit
Baseline (Day 20)
|
0.4239 Proportion of red blood cells in blood
Standard Deviation 0.03352
|
—
|
—
|
|
Treatment C: Absolute Values of Hematocrit
Day 22
|
0.4022 Proportion of red blood cells in blood
Standard Deviation 0.04433
|
—
|
—
|
|
Treatment C: Absolute Values of Hematocrit
Day 25
|
0.4168 Proportion of red blood cells in blood
Standard Deviation 0.04079
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Absolute Values of Hemoglobin
Baseline (Day -1)
|
141.9 Grams per liter
Standard Deviation 13.27
|
—
|
—
|
|
Treatment A: Absolute Values of Hemoglobin
Day 10
|
137.7 Grams per liter
Standard Deviation 13.07
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Absolute Values of Hemoglobin
Baseline (Day 10)
|
137.7 Grams per liter
Standard Deviation 13.07
|
—
|
—
|
|
Treatment B: Absolute Values of Hemoglobin
Day 20
|
140.0 Grams per liter
Standard Deviation 12.22
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Absolute Values of Hemoglobin
Baseline (Day 20)
|
140.6 Grams per liter
Standard Deviation 12.21
|
—
|
—
|
|
Treatment C: Absolute Values of Hemoglobin
Day 22
|
134.7 Grams per liter
Standard Deviation 15.54
|
—
|
—
|
|
Treatment C: Absolute Values of Hemoglobin
Day 25
|
138.3 Grams per liter
Standard Deviation 13.83
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Absolute Values of Erythrocytes
Day 10
|
4.664 10^12 cells per liter
Standard Deviation 0.4459
|
—
|
—
|
|
Treatment A: Absolute Values of Erythrocytes
Baseline (Day -1)
|
4.836 10^12 cells per liter
Standard Deviation 0.4125
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Absolute Values of Erythrocytes
Baseline (Day 10)
|
4.664 10^12 cells per liter
Standard Deviation 0.4459
|
—
|
—
|
|
Treatment B: Absolute Values of Erythrocytes
Day 20
|
4.746 10^12 cells per liter
Standard Deviation 0.3994
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Absolute Values of Erythrocytes
Baseline (Day 20)
|
4.769 10^12 cells per liter
Standard Deviation 0.3966
|
—
|
—
|
|
Treatment C: Absolute Values of Erythrocytes
Day 22
|
4.608 10^12 cells per liter
Standard Deviation 0.5308
|
—
|
—
|
|
Treatment C: Absolute Values of Erythrocytes
Day 25
|
4.756 10^12 cells per liter
Standard Deviation 0.4718
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Absolute Values of Erythrocytes Mean Corpuscular Volume
Baseline (Day -1)
|
86.71 Femtoliter
Standard Deviation 3.748
|
—
|
—
|
|
Treatment A: Absolute Values of Erythrocytes Mean Corpuscular Volume
Day 10
|
88.02 Femtoliter
Standard Deviation 3.938
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Absolute Values of Erythrocytes Mean Corpuscular Volume
Baseline (Day 10)
|
88.02 Femtoliter
Standard Deviation 3.938
|
—
|
—
|
|
Treatment B: Absolute Values of Erythrocytes Mean Corpuscular Volume
Day 20
|
88.96 Femtoliter
Standard Deviation 4.746
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Volume
Baseline (Day 20)
|
89.03 Femtoliter
Standard Deviation 4.865
|
—
|
—
|
|
Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Volume
Day 22
|
87.38 Femtoliter
Standard Deviation 4.217
|
—
|
—
|
|
Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Volume
Day 25
|
87.74 Femtoliter
Standard Deviation 4.045
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin
Baseline (Day -1)
|
29.37 Picograms
Standard Deviation 1.546
|
—
|
—
|
|
Treatment A: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin
Day 10
|
29.57 Picograms
Standard Deviation 1.667
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin
Baseline (Day 10)
|
29.57 Picograms
Standard Deviation 1.667
|
—
|
—
|
|
Treatment B: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin
Day 20
|
29.52 Picograms
Standard Deviation 1.602
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin
Baseline (Day 20)
|
29.51 Picograms
Standard Deviation 1.645
|
—
|
—
|
|
Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin
Day 22
|
29.28 Picograms
Standard Deviation 1.670
|
—
|
—
|
|
Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin
Day 25
|
29.12 Picograms
Standard Deviation 1.626
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 10: Glucose
|
4.8211 Millimoles per liter
Standard Deviation 0.44125
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day -1): Anion Gap
|
7.9 Millimoles per liter
Standard Deviation 1.80
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 10: Phosphate
|
1.1754 Millimoles per liter
Standard Deviation 0.16141
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day -1): Potassium
|
4.48 Millimoles per liter
Standard Deviation 0.339
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 10: Sodium
|
138.4 Millimoles per liter
Standard Deviation 1.93
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day -1): Glucose
|
5.0348 Millimoles per liter
Standard Deviation 0.37437
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day -1): Carbon Dioxide
|
104.1 Millimoles per liter
Standard Deviation 2.04
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 10: Carbon Dioxide
|
25.4 Millimoles per liter
Standard Deviation 2.11
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day -1): Cholesterol
|
4.4570 Millimoles per liter
Standard Deviation 1.00121
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 10: Cholesterol
|
3.8118 Millimoles per liter
Standard Deviation 0.85065
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day -1): Triglycerides
|
1.2232 Millimoles per liter
Standard Deviation 0.51018
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 10: Triglycerides
|
1.1814 Millimoles per liter
Standard Deviation 0.82178
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 10: Anion Gap
|
13.8 Millimoles per liter
Standard Deviation 1.71
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day -1): Calcium
|
2.3765 Millimoles per liter
Standard Deviation 0.09976
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 10: Calcium
|
2.3141 Millimoles per liter
Standard Deviation 0.10267
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day -1): Chloride
|
25.8 Millimoles per liter
Standard Deviation 2.10
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 10: Chloride
|
103.7 Millimoles per liter
Standard Deviation 1.81
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day -1): Phosphate
|
1.1075 Millimoles per liter
Standard Deviation 0.16734
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 10: Potassium
|
4.43 Millimoles per liter
Standard Deviation 0.256
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day -1): Sodium
|
137.7 Millimoles per liter
Standard Deviation 2.00
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day -1): Urea
|
4.8195 Millimoles per liter
Standard Deviation 0.78983
|
—
|
—
|
|
Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 10: Urea
|
5.9458 Millimoles per liter
Standard Deviation 1.43309
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 20: Glucose
|
4.7378 Millimoles per liter
Standard Deviation 0.45996
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 10): Carbon Dioxide
|
25.4 Millimoles per liter
Standard Deviation 2.11
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 20: Carbon Dioxide
|
24.9 Millimoles per liter
Standard Deviation 2.11
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 10): Anion Gap
|
13.8 Millimoles per liter
Standard Deviation 1.71
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 20: Calcium
|
2.3141 Millimoles per liter
Standard Deviation 0.08825
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 10): Chloride
|
103.7 Millimoles per liter
Standard Deviation 1.81
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 20: Chloride
|
103.6 Millimoles per liter
Standard Deviation 2.30
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 10): Phosphate
|
1.1754 Millimoles per liter
Standard Deviation 0.16141
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 20: Phosphate
|
1.2593 Millimoles per liter
Standard Deviation 0.13294
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 10): Potassium
|
4.43 Millimoles per liter
Standard Deviation 0.256
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 20: Sodium
|
138.6 Millimoles per liter
Standard Deviation 1.64
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 10): Urea
|
5.9458 Millimoles per liter
Standard Deviation 1.43309
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 10): Cholesterol
|
3.8118 Millimoles per liter
Standard Deviation 0.85065
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 20: Cholesterol
|
3.6915 Millimoles per liter
Standard Deviation 0.94881
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 10): Triglycerides
|
1.1814 Millimoles per liter
Standard Deviation 0.82178
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 20: Triglycerides
|
1.0825 Millimoles per liter
Standard Deviation 0.84563
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 20: Anion Gap
|
14.5 Millimoles per liter
Standard Deviation 2.12
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 10): Calcium
|
2.3141 Millimoles per liter
Standard Deviation 0.10267
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 20: Potassium
|
4.39 Millimoles per liter
Standard Deviation 0.383
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 10): Sodium
|
138.4 Millimoles per liter
Standard Deviation 1.93
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 20: Urea
|
5.6335 Millimoles per liter
Standard Deviation 1.72537
|
—
|
—
|
|
Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 10): Glucose
|
4.8211 Millimoles per liter
Standard Deviation 0.44125
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Carbon Dioxide
|
26.2 Millimoles per liter
Standard Deviation 1.80
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 20): Triglycerides
|
1.0783 Millimoles per liter
Standard Deviation 0.86858
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Triglycerides
|
1.0836 Millimoles per liter
Standard Deviation 0.78925
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Triglycerides
|
1.1074 Millimoles per liter
Standard Deviation 0.81372
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 20): Anion Gap
|
14.6 Millimoles per liter
Standard Deviation 2.14
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Calcium
|
2.2810 Millimoles per liter
Standard Deviation 0.10822
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Chloride
|
104.8 Millimoles per liter
Standard Deviation 2.02
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Chloride
|
102.6 Millimoles per liter
Standard Deviation 1.86
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 20): Phosphate
|
1.2661 Millimoles per liter
Standard Deviation 0.13297
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Sodium
|
139.8 Millimoles per liter
Standard Deviation 1.34
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 20): Glucose
|
4.7184 Millimoles per liter
Standard Deviation 0.46406
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Glucose
|
4.8060 Millimoles per liter
Standard Deviation 0.37890
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Glucose
|
4.8703 Millimoles per liter
Standard Deviation 0.40699
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 20): Carbon Dioxide
|
24.9 Millimoles per liter
Standard Deviation 2.12
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Carbon Dioxide
|
25.4 Millimoles per liter
Standard Deviation 1.74
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 20): Cholesterol
|
3.6898 Millimoles per liter
Standard Deviation 0.97478
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Cholesterol
|
3.2543 Millimoles per liter
Standard Deviation 0.88216
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Cholesterol
|
3.3972 Millimoles per liter
Standard Deviation 0.89603
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Anion Gap
|
13.9 Millimoles per liter
Standard Deviation 1.27
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Anion Gap
|
14.5 Millimoles per liter
Standard Deviation 1.95
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 20): Calcium
|
2.3217 Millimoles per liter
Standard Deviation 0.08377
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Calcium
|
2.3519 Millimoles per liter
Standard Deviation 0.09440
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 20): Chloride
|
103.4 Millimoles per liter
Standard Deviation 2.22
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Phosphate
|
1.1981 Millimoles per liter
Standard Deviation 0.14871
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Phosphate
|
1.3477 Millimoles per liter
Standard Deviation 0.18638
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 20): Potassium
|
4.38 Millimoles per liter
Standard Deviation 0.392
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Potassium
|
4.34 Millimoles per liter
Standard Deviation 0.347
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Potassium
|
4.35 Millimoles per liter
Standard Deviation 0.355
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 20): Sodium
|
138.6 Millimoles per liter
Standard Deviation 1.67
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Sodium
|
139.0 Millimoles per liter
Standard Deviation 1.67
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Baseline (Day 20): Urea
|
5.7364 Millimoles per liter
Standard Deviation 1.70835
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Urea
|
4.9078 Millimoles per liter
Standard Deviation 1.44100
|
—
|
—
|
|
Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Urea
|
5.3099 Millimoles per liter
Standard Deviation 1.18355
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Baseline (Day -1): Urate
|
347.3632 Micromoles per liter
Standard Deviation 69.50981
|
—
|
—
|
|
Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 10: Urate
|
365.5046 Micromoles per liter
Standard Deviation 75.74195
|
—
|
—
|
|
Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Baseline (Day -1): Creatinine
|
84.9524 Micromoles per liter
Standard Deviation 19.89935
|
—
|
—
|
|
Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 10: Creatinine
|
86.4110 Micromoles per liter
Standard Deviation 21.46247
|
—
|
—
|
|
Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Baseline (Day -1): Bilirubin
|
9.8325 Micromoles per liter
Standard Deviation 3.13227
|
—
|
—
|
|
Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 10: Bilirubin
|
8.0028 Micromoles per liter
Standard Deviation 3.01005
|
—
|
—
|
|
Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Baseline (Day -1): Direct bilirubin
|
2.0520 Micromoles per liter
Standard Deviation 0.70177
|
—
|
—
|
|
Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 10: Direct bilirubin
|
1.7015 Micromoles per liter
Standard Deviation 0.63856
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Baseline (Day 10): Urate
|
365.5046 Micromoles per liter
Standard Deviation 75.74195
|
—
|
—
|
|
Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 20: Urate
|
337.8464 Micromoles per liter
Standard Deviation 76.60060
|
—
|
—
|
|
Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Baseline (Day 10): Creatinine
|
86.4110 Micromoles per liter
Standard Deviation 21.46247
|
—
|
—
|
|
Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 20: Creatinine
|
90.7868 Micromoles per liter
Standard Deviation 22.81174
|
—
|
—
|
|
Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Baseline (Day 10): Bilirubin
|
8.0028 Micromoles per liter
Standard Deviation 3.01005
|
—
|
—
|
|
Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 20: Bilirubin
|
8.6184 Micromoles per liter
Standard Deviation 3.04856
|
—
|
—
|
|
Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Baseline (Day 10): Direct bilirubin
|
1.7015 Micromoles per liter
Standard Deviation 0.63856
|
—
|
—
|
|
Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 20: Direct bilirubin
|
1.8126 Micromoles per liter
Standard Deviation 0.64557
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 22: Urate
|
303.0349 Micromoles per liter
Standard Deviation 71.88291
|
—
|
—
|
|
Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 25: Creatinine
|
90.5867 Micromoles per liter
Standard Deviation 21.29029
|
—
|
—
|
|
Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Baseline (Day 20): Urate
|
343.1057 Micromoles per liter
Standard Deviation 74.89791
|
—
|
—
|
|
Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 25: Urate
|
340.6013 Micromoles per liter
Standard Deviation 67.89995
|
—
|
—
|
|
Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Baseline (Day 20): Creatinine
|
92.1686 Micromoles per liter
Standard Deviation 22.56047
|
—
|
—
|
|
Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 22: Creatinine
|
87.3764 Micromoles per liter
Standard Deviation 22.63812
|
—
|
—
|
|
Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Baseline (Day 20): Bilirubin
|
8.7480 Micromoles per liter
Standard Deviation 3.07497
|
—
|
—
|
|
Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 22: Bilirubin
|
9.8820 Micromoles per liter
Standard Deviation 3.24579
|
—
|
—
|
|
Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 25: Bilirubin
|
9.0360 Micromoles per liter
Standard Deviation 3.89534
|
—
|
—
|
|
Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Baseline (Day 20): Direct bilirubin
|
1.8450 Micromoles per liter
Standard Deviation 0.64634
|
—
|
—
|
|
Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 22: Direct bilirubin
|
2.0790 Micromoles per liter
Standard Deviation 0.60930
|
—
|
—
|
|
Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 25: Direct bilirubin
|
1.9980 Micromoles per liter
Standard Deviation 0.70286
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Absolute Values of Albumin, Globulin, Protein
Baseline (Day -1): Albumin
|
42.9 Grams per liter
Standard Deviation 2.95
|
—
|
—
|
|
Treatment A: Absolute Values of Albumin, Globulin, Protein
Day 10: Albumin
|
42.2 Grams per liter
Standard Deviation 3.14
|
—
|
—
|
|
Treatment A: Absolute Values of Albumin, Globulin, Protein
Baseline (Day -1): Globulin
|
27.4 Grams per liter
Standard Deviation 3.14
|
—
|
—
|
|
Treatment A: Absolute Values of Albumin, Globulin, Protein
Day 10: Globulin
|
25.9 Grams per liter
Standard Deviation 3.04
|
—
|
—
|
|
Treatment A: Absolute Values of Albumin, Globulin, Protein
Baseline (Day -1): Protein
|
70.3 Grams per liter
Standard Deviation 4.52
|
—
|
—
|
|
Treatment A: Absolute Values of Albumin, Globulin, Protein
Day 10: Protein
|
68.1 Grams per liter
Standard Deviation 3.77
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Absolute Values of Albumin, Globulin, Protein
Baseline (Day 10): Albumin
|
42.2 Grams per liter
Standard Deviation 3.14
|
—
|
—
|
|
Treatment B: Absolute Values of Albumin, Globulin, Protein
Day 20: Albumin
|
41.4 Grams per liter
Standard Deviation 3.31
|
—
|
—
|
|
Treatment B: Absolute Values of Albumin, Globulin, Protein
Baseline (Day 10): Globulin
|
25.9 Grams per liter
Standard Deviation 3.04
|
—
|
—
|
|
Treatment B: Absolute Values of Albumin, Globulin, Protein
Day 20: Globulin
|
26.8 Grams per liter
Standard Deviation 3.58
|
—
|
—
|
|
Treatment B: Absolute Values of Albumin, Globulin, Protein
Baseline (Day 10): Protein
|
68.1 Grams per liter
Standard Deviation 3.77
|
—
|
—
|
|
Treatment B: Absolute Values of Albumin, Globulin, Protein
Day 20: Protein
|
68.2 Grams per liter
Standard Deviation 4.93
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Absolute Values of Albumin, Globulin, Protein
Baseline (Day 20): Albumin
|
41.6 Grams per liter
Standard Deviation 3.24
|
—
|
—
|
|
Treatment C: Absolute Values of Albumin, Globulin, Protein
Day 22: Albumin
|
40.5 Grams per liter
Standard Deviation 3.82
|
—
|
—
|
|
Treatment C: Absolute Values of Albumin, Globulin, Protein
Day 25: Albumin
|
42.0 Grams per liter
Standard Deviation 3.04
|
—
|
—
|
|
Treatment C: Absolute Values of Albumin, Globulin, Protein
Baseline (Day 20): Globulin
|
26.9 Grams per liter
Standard Deviation 3.65
|
—
|
—
|
|
Treatment C: Absolute Values of Albumin, Globulin, Protein
Day 22: Globulin
|
25.1 Grams per liter
Standard Deviation 3.69
|
—
|
—
|
|
Treatment C: Absolute Values of Albumin, Globulin, Protein
Day 25: Globulin
|
26.6 Grams per liter
Standard Deviation 3.67
|
—
|
—
|
|
Treatment C: Absolute Values of Albumin, Globulin, Protein
Baseline (Day 20): Protein
|
68.5 Grams per liter
Standard Deviation 4.85
|
—
|
—
|
|
Treatment C: Absolute Values of Albumin, Globulin, Protein
Day 22: Protein
|
65.6 Grams per liter
Standard Deviation 5.74
|
—
|
—
|
|
Treatment C: Absolute Values of Albumin, Globulin, Protein
Day 25: Protein
|
68.6 Grams per liter
Standard Deviation 4.34
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase
Day 10: ALT
|
20.1 International units per liter
Standard Deviation 14.66
|
—
|
—
|
|
Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase
Baseline (Day -1): ALP
|
62.7 International units per liter
Standard Deviation 18.46
|
—
|
—
|
|
Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase
Day 10: ALP
|
60.8 International units per liter
Standard Deviation 18.03
|
—
|
—
|
|
Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase
Baseline (Day -1): Gamma-glutamyl transferase
|
19.1 International units per liter
Standard Deviation 7.16
|
—
|
—
|
|
Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase
Baseline (Day -1): Creatine kinase
|
103.7 International units per liter
Standard Deviation 79.68
|
—
|
—
|
|
Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase
Day 10: Creatine kinase
|
66.9 International units per liter
Standard Deviation 34.67
|
—
|
—
|
|
Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase
Baseline (Day -1): Lactate dehydrogenase
|
131.3 International units per liter
Standard Deviation 19.59
|
—
|
—
|
|
Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase
Day 10: Lactate dehydrogenase
|
114.8 International units per liter
Standard Deviation 16.87
|
—
|
—
|
|
Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase
Baseline (Day -1): ALT
|
15.6 International units per liter
Standard Deviation 7.66
|
—
|
—
|
|
Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase
Baseline (Day -1): AST
|
14.6 International units per liter
Standard Deviation 3.89
|
—
|
—
|
|
Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase
Day 10: AST
|
15.6 International units per liter
Standard Deviation 5.32
|
—
|
—
|
|
Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase
Day 10: Gamma-glutamyl transferase
|
18.9 International units per liter
Standard Deviation 8.10
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Baseline (Day 10): Creatine kinase
|
66.9 International units per liter
Standard Deviation 34.67
|
—
|
—
|
|
Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 20: Creatine kinase
|
68.9 International units per liter
Standard Deviation 47.98
|
—
|
—
|
|
Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Baseline (Day 10): Lactate dehydrogenase
|
114.8 International units per liter
Standard Deviation 16.87
|
—
|
—
|
|
Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 20: Lactate dehydrogenase
|
115.9 International units per liter
Standard Deviation 17.00
|
—
|
—
|
|
Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Baseline (Day 10): ALT
|
20.1 International units per liter
Standard Deviation 14.66
|
—
|
—
|
|
Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 20: ALT
|
20.3 International units per liter
Standard Deviation 12.38
|
—
|
—
|
|
Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Baseline (Day 10): ALP
|
60.8 International units per liter
Standard Deviation 18.03
|
—
|
—
|
|
Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 20: ALP
|
58.5 International units per liter
Standard Deviation 15.56
|
—
|
—
|
|
Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Baseline (Day 10): AST
|
15.6 International units per liter
Standard Deviation 5.32
|
—
|
—
|
|
Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 20: AST
|
16.1 International units per liter
Standard Deviation 4.80
|
—
|
—
|
|
Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Baseline (Day 10): Gamma-glutamyl transferase
|
18.9 International units per liter
Standard Deviation 8.10
|
—
|
—
|
|
Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 20: Gamma-glutamyl transferase
|
18.3 International units per liter
Standard Deviation 7.69
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Baseline (Day 20): Creatine kinase
|
71.3 International units per liter
Standard Deviation 48.03
|
—
|
—
|
|
Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 22: Creatine kinase
|
65.7 International units per liter
Standard Deviation 34.56
|
—
|
—
|
|
Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 25: Creatine kinase
|
63.8 International units per liter
Standard Deviation 30.90
|
—
|
—
|
|
Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Baseline (Day 20): Lactate dehydrogenase
|
116.6 International units per liter
Standard Deviation 17.13
|
—
|
—
|
|
Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 22: Lactate dehydrogenase
|
120.6 International units per liter
Standard Deviation 23.62
|
—
|
—
|
|
Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 25: Lactate dehydrogenase
|
119.3 International units per liter
Standard Deviation 19.18
|
—
|
—
|
|
Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Baseline (Day 20): ALT
|
20.4 International units per liter
Standard Deviation 12.70
|
—
|
—
|
|
Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 22: ALT
|
17.3 International units per liter
Standard Deviation 9.36
|
—
|
—
|
|
Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 25: ALT
|
20.9 International units per liter
Standard Deviation 11.92
|
—
|
—
|
|
Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Baseline (Day 20): ALP
|
58.5 International units per liter
Standard Deviation 15.98
|
—
|
—
|
|
Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 22: ALP
|
57.6 International units per liter
Standard Deviation 16.26
|
—
|
—
|
|
Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 25:ALP
|
58.6 International units per liter
Standard Deviation 16.40
|
—
|
—
|
|
Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Baseline (Day 20): AST
|
16.2 International units per liter
Standard Deviation 4.91
|
—
|
—
|
|
Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 22: AST
|
14.7 International units per liter
Standard Deviation 3.78
|
—
|
—
|
|
Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 25: AST
|
16.4 International units per liter
Standard Deviation 4.56
|
—
|
—
|
|
Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Baseline (Day 20): Gamma-glutamyl transferase
|
18.5 International units per liter
Standard Deviation 7.83
|
—
|
—
|
|
Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 22: Gamma-glutamyl transferase
|
17.1 International units per liter
Standard Deviation 6.77
|
—
|
—
|
|
Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 25: Gamma-glutamyl transferase
|
18.7 International units per liter
Standard Deviation 8.23
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Absolute Values of Amylase, Lipase
Baseline (Day -1): Lipase
|
29.4 Units per liter
Standard Deviation 14.73
|
—
|
—
|
|
Treatment A: Absolute Values of Amylase, Lipase
Day 10: Lipase
|
31.6 Units per liter
Standard Deviation 11.99
|
—
|
—
|
|
Treatment A: Absolute Values of Amylase, Lipase
Baseline (Day -1): Amylase
|
59.5 Units per liter
Standard Deviation 22.37
|
—
|
—
|
|
Treatment A: Absolute Values of Amylase, Lipase
Day 10: Amylase
|
56.9 Units per liter
Standard Deviation 20.93
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Absolute Values of Amylase, Lipase
Baseline (Day 10): Amylase
|
56.9 Units per liter
Standard Deviation 20.93
|
—
|
—
|
|
Treatment B: Absolute Values of Amylase, Lipase
Baseline (Day 10): Lipase
|
31.6 Units per liter
Standard Deviation 11.99
|
—
|
—
|
|
Treatment B: Absolute Values of Amylase, Lipase
Day 20: Lipase
|
32.4 Units per liter
Standard Deviation 14.51
|
—
|
—
|
|
Treatment B: Absolute Values of Amylase, Lipase
Day 20: Amylase
|
60.1 Units per liter
Standard Deviation 23.22
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Absolute Values of Amylase, Lipase
Baseline (Day 20): Lipase
|
32.9 Units per liter
Standard Deviation 14.74
|
—
|
—
|
|
Treatment C: Absolute Values of Amylase, Lipase
Day 22: Lipase
|
33.5 Units per liter
Standard Deviation 15.19
|
—
|
—
|
|
Treatment C: Absolute Values of Amylase, Lipase
Day 25: Lipase
|
33.1 Units per liter
Standard Deviation 14.58
|
—
|
—
|
|
Treatment C: Absolute Values of Amylase, Lipase
Baseline (Day 20): Amylase
|
62.2 Units per liter
Standard Deviation 21.79
|
—
|
—
|
|
Treatment C: Absolute Values of Amylase, Lipase
Day 22: Amylase
|
64.7 Units per liter
Standard Deviation 25.32
|
—
|
—
|
|
Treatment C: Absolute Values of Amylase, Lipase
Day 25: Amylase
|
60.7 Units per liter
Standard Deviation 21.08
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Eosinophils
|
0.0150 10^9 cells per liter
Standard Deviation 0.07023
|
—
|
—
|
|
Treatment A: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Basophils
|
0.0110 10^9 cells per liter
Standard Deviation 0.02138
|
—
|
—
|
|
Treatment A: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Platelet count
|
7.3 10^9 cells per liter
Standard Deviation 20.01
|
—
|
—
|
|
Treatment A: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Leukocyte count
|
0.66 10^9 cells per liter
Standard Deviation 0.844
|
—
|
—
|
|
Treatment A: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Neutrophils
|
0.5926 10^9 cells per liter
Standard Deviation 0.68577
|
—
|
—
|
|
Treatment A: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Lymphocytes
|
0.0748 10^9 cells per liter
Standard Deviation 0.25872
|
—
|
—
|
|
Treatment A: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Monocytes
|
-0.0375 10^9 cells per liter
Standard Deviation 0.09379
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Platelet count
|
-4.1 10^9 cells per liter
Standard Deviation 17.31
|
—
|
—
|
|
Treatment B: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Leukocyte count
|
-0.51 10^9 cells per liter
Standard Deviation 0.947
|
—
|
—
|
|
Treatment B: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Neutrophils
|
-0.4750 10^9 cells per liter
Standard Deviation 0.63752
|
—
|
—
|
|
Treatment B: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Lymphocytes
|
-0.0610 10^9 cells per liter
Standard Deviation 0.39045
|
—
|
—
|
|
Treatment B: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Monocytes
|
-0.0080 10^9 cells per liter
Standard Deviation 0.11134
|
—
|
—
|
|
Treatment B: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Eosinophils
|
0.0310 10^9 cells per liter
Standard Deviation 0.10686
|
—
|
—
|
|
Treatment B: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Basophils
|
0.0020 10^9 cells per liter
Standard Deviation 0.02526
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 22: Platelet count
|
-13.1 10^9 cells per liter
Standard Deviation 19.31
|
—
|
—
|
|
Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 25: Platelet count
|
-1.6 10^9 cells per liter
Standard Deviation 24.62
|
—
|
—
|
|
Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 22: Leukocyte count
|
-0.05 10^9 cells per liter
Standard Deviation 0.906
|
—
|
—
|
|
Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 25: Leukocyte count
|
0.12 10^9 cells per liter
Standard Deviation 0.820
|
—
|
—
|
|
Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 22: Neutrophils
|
-0.1254 10^9 cells per liter
Standard Deviation 0.74916
|
—
|
—
|
|
Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 25: Neutrophils
|
0.1351 10^9 cells per liter
Standard Deviation 0.72701
|
—
|
—
|
|
Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 22: Lymphocytes
|
0.0351 10^9 cells per liter
Standard Deviation 0.42962
|
—
|
—
|
|
Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 25: Lymphocytes
|
0.0843 10^9 cells per liter
Standard Deviation 0.41536
|
—
|
—
|
|
Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 22: Monocytes
|
0.0184 10^9 cells per liter
Standard Deviation 0.08808
|
—
|
—
|
|
Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 25: Monocytes
|
-0.0929 10^9 cells per liter
Standard Deviation 0.17694
|
—
|
—
|
|
Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 22: Eosinophils
|
0.0329 10^9 cells per liter
Standard Deviation 0.12007
|
—
|
—
|
|
Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 25: Eosinophils
|
-0.0115 10^9 cells per liter
Standard Deviation 0.06076
|
—
|
—
|
|
Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 22: Basophils
|
-0.0094 10^9 cells per liter
Standard Deviation 0.03787
|
—
|
—
|
|
Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils
Day 25: Basophils
|
-0.0066 10^9 cells per liter
Standard Deviation 0.03173
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Change From Baseline in Hematocrit
|
-0.0090 Proportion of red blood cells in blood
Standard Deviation 0.02082
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Change From Baseline in Hematocrit
|
0.0118 Proportion of red blood cells in blood
Standard Deviation 0.01667
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Change From Baseline in Hematocrit
Day 22
|
-0.0217 Proportion of red blood cells in blood
Standard Deviation 0.02090
|
—
|
—
|
|
Treatment C: Change From Baseline in Hematocrit
Day 25
|
-0.0071 Proportion of red blood cells in blood
Standard Deviation 0.02129
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Change From Baseline in Hemoglobin
|
-4.2 Grams per liter
Standard Deviation 6.34
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Change From Baseline in Hemoglobin
|
2.3 Grams per liter
Standard Deviation 4.91
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Change From Baseline in Hemoglobin
Day 22
|
-5.8 Grams per liter
Standard Deviation 6.52
|
—
|
—
|
|
Treatment C: Change From Baseline in Hemoglobin
Day 25
|
-2.3 Grams per liter
Standard Deviation 5.82
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Change From Baseline in Erythrocytes
|
-0.172 10^12 cells per liter
Standard Deviation 0.2219
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Change From Baseline in Erythrocytes
|
0.083 10^12 cells per liter
Standard Deviation 0.1768
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Change From Baseline in Erythrocytes
Day 22
|
-0.161 10^12 cells per liter
Standard Deviation 0.2190
|
—
|
—
|
|
Treatment C: Change From Baseline in Erythrocytes
Day 25
|
-0.013 10^12 cells per liter
Standard Deviation 0.2027
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Change From Baseline in Erythrocytes Mean Corpuscular Volume
|
1.31 Femtoliter
Standard Deviation 1.539
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Change From Baseline in Erythrocytes Mean Corpuscular Volume
|
0.94 Femtoliter
Standard Deviation 2.519
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Volume
Day 22
|
-1.64 Femtoliter
Standard Deviation 1.849
|
—
|
—
|
|
Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Volume
Day 25
|
-1.28 Femtoliter
Standard Deviation 2.234
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin
|
0.20 Picograms
Standard Deviation 0.352
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin
|
-0.05 Picograms
Standard Deviation 0.298
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin
Day 22
|
-0.23 Picograms
Standard Deviation 0.407
|
—
|
—
|
|
Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin
Day 25
|
-0.39 Picograms
Standard Deviation 0.519
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Glucose
|
-0.2137 Millimoles per liter
Standard Deviation 0.29663
|
—
|
—
|
|
Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Carbon Dioxide
|
-78.7 Millimoles per liter
Standard Deviation 3.12
|
—
|
—
|
|
Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Cholesterol
|
-0.6452 Millimoles per liter
Standard Deviation 0.47501
|
—
|
—
|
|
Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Triglycerides
|
-0.0418 Millimoles per liter
Standard Deviation 0.59458
|
—
|
—
|
|
Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Anion Gap
|
5.9 Millimoles per liter
Standard Deviation 2.21
|
—
|
—
|
|
Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Calcium
|
-0.0624 Millimoles per liter
Standard Deviation 0.04889
|
—
|
—
|
|
Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Chloride
|
78.0 Millimoles per liter
Standard Deviation 2.98
|
—
|
—
|
|
Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Phosphate
|
0.0678 Millimoles per liter
Standard Deviation 0.10522
|
—
|
—
|
|
Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Potassium
|
-0.05 Millimoles per liter
Standard Deviation 0.402
|
—
|
—
|
|
Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Sodium
|
0.7 Millimoles per liter
Standard Deviation 2.16
|
—
|
—
|
|
Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Urea
|
1.1263 Millimoles per liter
Standard Deviation 0.97483
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Glucose
|
-0.0833 Millimoles per liter
Standard Deviation 0.29345
|
—
|
—
|
|
Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Carbon Dioxide
|
-0.6 Millimoles per liter
Standard Deviation 1.79
|
—
|
—
|
|
Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Cholesterol
|
-0.1203 Millimoles per liter
Standard Deviation 0.30774
|
—
|
—
|
|
Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Triglycerides
|
-0.0989 Millimoles per liter
Standard Deviation 0.30531
|
—
|
—
|
|
Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Anion Gap
|
0.8 Millimoles per liter
Standard Deviation 1.94
|
—
|
—
|
|
Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Calcium
|
0.0000 Millimoles per liter
Standard Deviation 0.06575
|
—
|
—
|
|
Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Chloride
|
-0.1 Millimoles per liter
Standard Deviation 1.52
|
—
|
—
|
|
Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Phosphate
|
0.0840 Millimoles per liter
Standard Deviation 0.08601
|
—
|
—
|
|
Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Potassium
|
-0.05 Millimoles per liter
Standard Deviation 0.378
|
—
|
—
|
|
Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Sodium
|
0.3 Millimoles per liter
Standard Deviation 1.41
|
—
|
—
|
|
Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Urea
|
-0.3124 Millimoles per liter
Standard Deviation 0.72202
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Glucose
|
0.0876 Millimoles per liter
Standard Deviation 0.29392
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Glucose
|
0.1519 Millimoles per liter
Standard Deviation 0.32570
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Carbon Dioxide
|
0.5 Millimoles per liter
Standard Deviation 2.12
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Carbon Dioxide
|
1.2 Millimoles per liter
Standard Deviation 1.81
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Cholesterol
|
-0.4355 Millimoles per liter
Standard Deviation 0.31287
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Cholesterol
|
-0.2926 Millimoles per liter
Standard Deviation 0.25147
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Triglycerides
|
0.0054 Millimoles per liter
Standard Deviation 0.14595
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Triglycerides
|
0.0291 Millimoles per liter
Standard Deviation 0.18280
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Anion Gap
|
-0.6 Millimoles per liter
Standard Deviation 1.80
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Anion Gap
|
-0.1 Millimoles per liter
Standard Deviation 0.97
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Calcium
|
-0.0407 Millimoles per liter
Standard Deviation 0.07165
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Calcium
|
0.0302 Millimoles per liter
Standard Deviation 0.05553
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Chloride
|
1.4 Millimoles per liter
Standard Deviation 1.64
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Chloride
|
-0.8 Millimoles per liter
Standard Deviation 1.78
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Phosphate
|
-0.0680 Millimoles per liter
Standard Deviation 0.09860
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Phosphate
|
0.0816 Millimoles per liter
Standard Deviation 0.09527
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Potassium
|
-0.04 Millimoles per liter
Standard Deviation 0.373
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Potassium
|
-0.03 Millimoles per liter
Standard Deviation 0.441
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Sodium
|
1.2 Millimoles per liter
Standard Deviation 1.51
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Sodium
|
0.4 Millimoles per liter
Standard Deviation 2.41
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 22: Urea
|
-0.8286 Millimoles per liter
Standard Deviation 0.88169
|
—
|
—
|
|
Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea
Day 25: Urea
|
-0.4265 Millimoles per liter
Standard Deviation 0.85981
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
Urate
|
18.1414 Micromoles per liter
Standard Deviation 39.28786
|
—
|
—
|
|
Treatment A: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
Creatinine
|
1.4586 Micromoles per liter
Standard Deviation 5.65145
|
—
|
—
|
|
Treatment A: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
Bilirubin
|
-1.8297 Micromoles per liter
Standard Deviation 1.38266
|
—
|
—
|
|
Treatment A: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
Direct bilirubin
|
-0.3506 Micromoles per liter
Standard Deviation 0.60895
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
Urate
|
-27.6582 Micromoles per liter
Standard Deviation 25.47573
|
—
|
—
|
|
Treatment B: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
Creatinine
|
4.3758 Micromoles per liter
Standard Deviation 4.38239
|
—
|
—
|
|
Treatment B: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
Bilirubin
|
0.6156 Micromoles per liter
Standard Deviation 1.92059
|
—
|
—
|
|
Treatment B: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
Direct bilirubin
|
0.1112 Micromoles per liter
Standard Deviation 0.46509
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 22: Creatinine
|
-4.7922 Micromoles per liter
Standard Deviation 5.82901
|
—
|
—
|
|
Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 22: Urate
|
-40.0707 Micromoles per liter
Standard Deviation 26.51457
|
—
|
—
|
|
Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 25: Urate
|
-2.5044 Micromoles per liter
Standard Deviation 26.62359
|
—
|
—
|
|
Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 25: Creatinine
|
-1.5819 Micromoles per liter
Standard Deviation 4.60830
|
—
|
—
|
|
Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 22: Bilirubin
|
1.1340 Micromoles per liter
Standard Deviation 1.91202
|
—
|
—
|
|
Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 25: Bilirubin
|
0.2880 Micromoles per liter
Standard Deviation 2.14494
|
—
|
—
|
|
Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 22: Direct bilirubin
|
0.2340 Micromoles per liter
Standard Deviation 0.38326
|
—
|
—
|
|
Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin
Day 25: Direct bilirubin
|
0.1530 Micromoles per liter
Standard Deviation 0.39447
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Change From Baseline in Albumin, Globulin, Protein
Albumin
|
-0.7 Grams per liter
Standard Deviation 1.75
|
—
|
—
|
|
Treatment A: Change From Baseline in Albumin, Globulin, Protein
Globulin
|
-1.5 Grams per liter
Standard Deviation 1.61
|
—
|
—
|
|
Treatment A: Change From Baseline in Albumin, Globulin, Protein
Protein
|
-2.2 Grams per liter
Standard Deviation 2.57
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Change From Baseline in Albumin, Globulin, Protein
Albumin
|
-0.9 Grams per liter
Standard Deviation 2.43
|
—
|
—
|
|
Treatment B: Change From Baseline in Albumin, Globulin, Protein
Globulin
|
0.9 Grams per liter
Standard Deviation 2.07
|
—
|
—
|
|
Treatment B: Change From Baseline in Albumin, Globulin, Protein
Protein
|
0.1 Grams per liter
Standard Deviation 3.71
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Change From Baseline in Albumin, Globulin, Protein
Day 22: Albumin
|
-1.1 Grams per liter
Standard Deviation 2.44
|
—
|
—
|
|
Treatment C: Change From Baseline in Albumin, Globulin, Protein
Day 25: Albumin
|
0.4 Grams per liter
Standard Deviation 1.71
|
—
|
—
|
|
Treatment C: Change From Baseline in Albumin, Globulin, Protein
Day 22: Globulin
|
-1.8 Grams per liter
Standard Deviation 1.98
|
—
|
—
|
|
Treatment C: Change From Baseline in Albumin, Globulin, Protein
Day 25: Globulin
|
-0.3 Grams per liter
Standard Deviation 1.76
|
—
|
—
|
|
Treatment C: Change From Baseline in Albumin, Globulin, Protein
Day 22: Protein
|
-2.9 Grams per liter
Standard Deviation 4.15
|
—
|
—
|
|
Treatment C: Change From Baseline in Albumin, Globulin, Protein
Day 25: Protein
|
0.2 Grams per liter
Standard Deviation 2.81
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Creatine kinase
|
-36.9 International units per liter
Standard Deviation 59.38
|
—
|
—
|
|
Treatment A: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Lactate dehydrogenase
|
-16.5 International units per liter
Standard Deviation 15.50
|
—
|
—
|
|
Treatment A: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
ALT
|
4.5 International units per liter
Standard Deviation 11.51
|
—
|
—
|
|
Treatment A: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
ALP
|
-1.9 International units per liter
Standard Deviation 6.39
|
—
|
—
|
|
Treatment A: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
AST
|
1.0 International units per liter
Standard Deviation 4.52
|
—
|
—
|
|
Treatment A: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Gamma-glutamyl transferase
|
-0.2 International units per liter
Standard Deviation 3.86
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Creatine kinase
|
2.1 International units per liter
Standard Deviation 24.48
|
—
|
—
|
|
Treatment B: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Lactate dehydrogenase
|
1.1 International units per liter
Standard Deviation 13.15
|
—
|
—
|
|
Treatment B: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
ALT
|
0.3 International units per liter
Standard Deviation 6.78
|
—
|
—
|
|
Treatment B: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
ALP
|
-2.4 International units per liter
Standard Deviation 6.21
|
—
|
—
|
|
Treatment B: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
AST
|
0.6 International units per liter
Standard Deviation 3.03
|
—
|
—
|
|
Treatment B: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Gamma-glutamyl transferase
|
-0.6 International units per liter
Standard Deviation 2.74
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 22: Creatine kinase
|
-5.6 International units per liter
Standard Deviation 21.78
|
—
|
—
|
|
Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 25: Creatine kinase
|
-7.5 International units per liter
Standard Deviation 26.10
|
—
|
—
|
|
Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 22: Lactate dehydrogenase
|
4.0 International units per liter
Standard Deviation 18.94
|
—
|
—
|
|
Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 25: Lactate dehydrogenase
|
2.6 International units per liter
Standard Deviation 16.30
|
—
|
—
|
|
Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 22: ALT
|
-3.1 International units per liter
Standard Deviation 4.12
|
—
|
—
|
|
Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 25: ALT
|
0.5 International units per liter
Standard Deviation 2.61
|
—
|
—
|
|
Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 22: ALP
|
-0.9 International units per liter
Standard Deviation 5.83
|
—
|
—
|
|
Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 25:ALP
|
0.1 International units per liter
Standard Deviation 3.91
|
—
|
—
|
|
Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 22: AST
|
-1.5 International units per liter
Standard Deviation 2.78
|
—
|
—
|
|
Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 25: AST
|
0.2 International units per liter
Standard Deviation 1.89
|
—
|
—
|
|
Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 22: Gamma-glutamyl transferase
|
-1.5 International units per liter
Standard Deviation 1.61
|
—
|
—
|
|
Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase
Day 25: Gamma-glutamyl transferase
|
0.2 International units per liter
Standard Deviation 1.26
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day -1) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Change From Baseline in Amylase, Lipase
Lipase
|
2.2 Units per liter
Standard Deviation 6.81
|
—
|
—
|
|
Treatment A: Change From Baseline in Amylase, Lipase
Amylase
|
-2.6 Units per liter
Standard Deviation 7.86
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 10) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Change From Baseline in Amylase, Lipase
Lipase
|
0.9 Units per liter
Standard Deviation 6.07
|
—
|
—
|
|
Treatment B: Change From Baseline in Amylase, Lipase
Amylase
|
3.2 Units per liter
Standard Deviation 6.31
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 20), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Change From Baseline in Amylase, Lipase
Day 22: Lipase
|
0.6 Units per liter
Standard Deviation 10.08
|
—
|
—
|
|
Treatment C: Change From Baseline in Amylase, Lipase
Day 25: Lipase
|
0.2 Units per liter
Standard Deviation 4.88
|
—
|
—
|
|
Treatment C: Change From Baseline in Amylase, Lipase
Day 22: Amylase
|
2.5 Units per liter
Standard Deviation 7.10
|
—
|
—
|
|
Treatment C: Change From Baseline in Amylase, Lipase
Day 25: Amylase
|
-1.5 Units per liter
Standard Deviation 4.98
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1, Pre-Dose) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)
Baseline (Day 1, Pre-dose): PR Interval
|
154.8 Milliseconds
Standard Deviation 20.92
|
—
|
—
|
|
Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)
Day 10: PR Interval
|
158.2 Milliseconds
Standard Deviation 22.67
|
—
|
—
|
|
Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)
Baseline (Day 1, Pre-dose): QRS Duration
|
92.5 Milliseconds
Standard Deviation 8.34
|
—
|
—
|
|
Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)
Day 10: QRS Duration
|
95.0 Milliseconds
Standard Deviation 10.11
|
—
|
—
|
|
Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)
Baseline (Day 1, Pre-dose): QT Interval
|
391.2 Milliseconds
Standard Deviation 22.41
|
—
|
—
|
|
Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)
Day 10: QT Interval
|
398.3 Milliseconds
Standard Deviation 22.19
|
—
|
—
|
|
Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)
Baseline (Day 1, Pre-dose): QTcF Interval
|
401.0 Milliseconds
Standard Deviation 16.48
|
—
|
—
|
|
Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF)
Day 10: QTcF Interval
|
405.8 Milliseconds
Standard Deviation 16.25
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 11, Pre-Dose) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
Baseline (Day 11, Pre-dose): PR Interval
|
158.6 Milliseconds
Standard Deviation 19.44
|
—
|
—
|
|
Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
Day 20: PR Interval
|
161.8 Milliseconds
Standard Deviation 22.40
|
—
|
—
|
|
Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
Baseline (Day 11, Pre-dose): QRS Duration
|
94.2 Milliseconds
Standard Deviation 8.73
|
—
|
—
|
|
Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
Day 20: QRS Duration
|
96.4 Milliseconds
Standard Deviation 9.25
|
—
|
—
|
|
Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
Baseline (Day 11, Pre-dose): QT Interval
|
403.1 Milliseconds
Standard Deviation 26.27
|
—
|
—
|
|
Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
Day 20: QT Interval
|
408.8 Milliseconds
Standard Deviation 25.85
|
—
|
—
|
|
Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
Baseline (Day 11, Pre-dose): QTcF Interval
|
403.5 Milliseconds
Standard Deviation 17.63
|
—
|
—
|
|
Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
Day 20: QTcF Interval
|
408.6 Milliseconds
Standard Deviation 17.26
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 21, Pre-Dose), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
Baseline (Day 21, Pre-dose): QT Interval
|
402.6 Milliseconds
Standard Deviation 21.06
|
—
|
—
|
|
Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
Day 25: PR Interval
|
159.6 Milliseconds
Standard Deviation 23.55
|
—
|
—
|
|
Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
Baseline (Day 21, Pre-dose): QRS Duration
|
95.8 Milliseconds
Standard Deviation 9.49
|
—
|
—
|
|
Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
Day 22: QRS Duration
|
98.7 Milliseconds
Standard Deviation 10.30
|
—
|
—
|
|
Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
Day 25: QRS Duration
|
96.8 Milliseconds
Standard Deviation 8.42
|
—
|
—
|
|
Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
Day 22: QT Interval
|
420.6 Milliseconds
Standard Deviation 21.16
|
—
|
—
|
|
Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
Day 25: QT Interval
|
398.7 Milliseconds
Standard Deviation 22.25
|
—
|
—
|
|
Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
Baseline (Day 21, Pre-dose): QTcF Interval
|
408.7 Milliseconds
Standard Deviation 16.31
|
—
|
—
|
|
Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
Day 22: QTcF Interval
|
407.3 Milliseconds
Standard Deviation 13.75
|
—
|
—
|
|
Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
Day 25: QTcF Interval
|
402.5 Milliseconds
Standard Deviation 17.03
|
—
|
—
|
|
Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
Baseline (Day 21, Pre-dose): PR Interval
|
160.8 Milliseconds
Standard Deviation 20.26
|
—
|
—
|
|
Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval
Day 22: PR Interval
|
162.3 Milliseconds
Standard Deviation 22.07
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1, Pre-dose) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
PR Interval
|
3.4 Milliseconds
Standard Deviation 9.28
|
—
|
—
|
|
Treatment A: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
QRS Duration
|
2.5 Milliseconds
Standard Deviation 4.37
|
—
|
—
|
|
Treatment A: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
QT Interval
|
7.1 Milliseconds
Standard Deviation 12.81
|
—
|
—
|
|
Treatment A: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
QTcF Interval
|
4.8 Milliseconds
Standard Deviation 9.27
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 11, Pre-Dose) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
PR Interval
|
3.2 Milliseconds
Standard Deviation 8.79
|
—
|
—
|
|
Treatment B: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
QRS Duration
|
2.3 Milliseconds
Standard Deviation 2.77
|
—
|
—
|
|
Treatment B: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
QT Interval
|
5.7 Milliseconds
Standard Deviation 13.30
|
—
|
—
|
|
Treatment B: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
QTcF Interval
|
5.1 Milliseconds
Standard Deviation 10.69
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 21, Pre-Dose), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
Day 25: QRS Duration
|
1.0 Milliseconds
Standard Deviation 3.43
|
—
|
—
|
|
Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
Day 22: PR Interval
|
1.5 Milliseconds
Standard Deviation 9.99
|
—
|
—
|
|
Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
Day 25: PR Interval
|
-1.2 Milliseconds
Standard Deviation 10.07
|
—
|
—
|
|
Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
Day 22: QRS Duration
|
2.9 Milliseconds
Standard Deviation 4.24
|
—
|
—
|
|
Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
Day 22: QT Interval
|
18.0 Milliseconds
Standard Deviation 20.32
|
—
|
—
|
|
Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
Day 25: QT Interval
|
-3.9 Milliseconds
Standard Deviation 16.18
|
—
|
—
|
|
Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
Day 22: QTcF Interval
|
-1.4 Milliseconds
Standard Deviation 9.44
|
—
|
—
|
|
Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF
Day 25: QTcF Interval
|
-6.3 Milliseconds
Standard Deviation 8.41
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1, Pre-dose) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Absolute Values of Oral Temperature
Baseline (Day 1, Pre-dose)
|
36.38 Degrees Celsius
Standard Deviation 0.293
|
—
|
—
|
|
Treatment A: Absolute Values of Oral Temperature
Day 10
|
36.26 Degrees Celsius
Standard Deviation 0.252
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 11, Pre-Dose) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Absolute Values of Oral Temperature
Baseline (Day 11, Pre-dose)
|
36.31 Degrees Celsius
Standard Deviation 0.320
|
—
|
—
|
|
Treatment B: Absolute Values of Oral Temperature
Day 20
|
36.28 Degrees Celsius
Standard Deviation 0.246
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 21, Pre-Dose), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Absolute Values of Oral Temperature
Baseline (Day 21, Pre-dose)
|
36.31 Degrees Celsius
Standard Deviation 0.284
|
—
|
—
|
|
Treatment C: Absolute Values of Oral Temperature
Day 22
|
36.18 Degrees Celsius
Standard Deviation 0.210
|
—
|
—
|
|
Treatment C: Absolute Values of Oral Temperature
Day 25
|
36.31 Degrees Celsius
Standard Deviation 0.300
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1, Pre-dose) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Absolute Values of Pulse Rate
Baseline (Day 1, Pre-dose)
|
64.5 Beats per minute
Standard Deviation 8.97
|
—
|
—
|
|
Treatment A: Absolute Values of Pulse Rate
Day 10
|
65.0 Beats per minute
Standard Deviation 8.19
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 11, Pre-Dose) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Absolute Values of Pulse Rate
Baseline (Day 11, Pre-dose)
|
61.6 Beats per minute
Standard Deviation 9.95
|
—
|
—
|
|
Treatment B: Absolute Values of Pulse Rate
Day 20
|
62.8 Beats per minute
Standard Deviation 10.22
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 21, Pre-Dose), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Absolute Values of Pulse Rate
Baseline (Day 21, Pre-dose)
|
63.2 Beats per minute
Standard Deviation 7.04
|
—
|
—
|
|
Treatment C: Absolute Values of Pulse Rate
Day 22
|
56.2 Beats per minute
Standard Deviation 6.83
|
—
|
—
|
|
Treatment C: Absolute Values of Pulse Rate
Day 25
|
61.7 Beats per minute
Standard Deviation 7.27
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1, Pre-dose) and Day 2Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Absolute Values of Respiratory Rate
Baseline (Day 1, Pre-dose)
|
16.1 Breaths per minute
Standard Deviation 1.37
|
—
|
—
|
|
Treatment A: Absolute Values of Respiratory Rate
Day 2
|
15.8 Breaths per minute
Standard Deviation 2.33
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 11, Pre-Dose) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Absolute Values of Respiratory Rate
Baseline (Day 11, Pre-dose)
|
15.0 Breaths per minute
Standard Deviation 2.29
|
—
|
—
|
|
Treatment B: Absolute Values of Respiratory Rate
Day 20
|
14.7 Breaths per minute
Standard Deviation 2.27
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 21, Pre-Dose), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Absolute Values of Respiratory Rate
Baseline (Day 21, Pre-dose)
|
15.7 Breaths per minute
Standard Deviation 1.56
|
—
|
—
|
|
Treatment C: Absolute Values of Respiratory Rate
Day 22
|
15.7 Breaths per minute
Standard Deviation 1.38
|
—
|
—
|
|
Treatment C: Absolute Values of Respiratory Rate
Day 25
|
16.5 Breaths per minute
Standard Deviation 2.20
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1, Pre-dose) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Absolute Values of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Baseline (Day 1, Pre-dose): SBP
|
111.0 Millimeters of mercury
Standard Deviation 9.03
|
—
|
—
|
|
Treatment A: Absolute Values of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Day 10: SBP
|
107.7 Millimeters of mercury
Standard Deviation 9.32
|
—
|
—
|
|
Treatment A: Absolute Values of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Baseline (Day 1, Pre-dose): DBP
|
65.1 Millimeters of mercury
Standard Deviation 6.73
|
—
|
—
|
|
Treatment A: Absolute Values of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Day 10: DBP
|
59.7 Millimeters of mercury
Standard Deviation 6.24
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 11, Pre-Dose) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Absolute Values of SBP and DBP
Baseline (Day 11, Pre-dose): DBP
|
61.6 Millimeters of mercury
Standard Deviation 6.56
|
—
|
—
|
|
Treatment B: Absolute Values of SBP and DBP
Baseline (Day 11, Pre-dose): SBP
|
107.7 Millimeters of mercury
Standard Deviation 8.46
|
—
|
—
|
|
Treatment B: Absolute Values of SBP and DBP
Day 20: SBP
|
107.2 Millimeters of mercury
Standard Deviation 9.52
|
—
|
—
|
|
Treatment B: Absolute Values of SBP and DBP
Day 20: DBP
|
59.6 Millimeters of mercury
Standard Deviation 5.55
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 21, Pre-Dose), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Absolute Values of SBP and DBP
Baseline (Day 21, Pre-dose): SBP
|
107.5 Millimeters of mercury
Standard Deviation 8.49
|
—
|
—
|
|
Treatment C: Absolute Values of SBP and DBP
Day 22: SBP
|
105.6 Millimeters of mercury
Standard Deviation 11.93
|
—
|
—
|
|
Treatment C: Absolute Values of SBP and DBP
Day 25: SBP
|
109.7 Millimeters of mercury
Standard Deviation 7.96
|
—
|
—
|
|
Treatment C: Absolute Values of SBP and DBP
Baseline (Day 21, Pre-dose): DBP
|
62.7 Millimeters of mercury
Standard Deviation 5.31
|
—
|
—
|
|
Treatment C: Absolute Values of SBP and DBP
Day 22: DBP
|
58.4 Millimeters of mercury
Standard Deviation 5.87
|
—
|
—
|
|
Treatment C: Absolute Values of SBP and DBP
Day 25: DBP
|
62.2 Millimeters of mercury
Standard Deviation 5.06
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1, Pre-dose) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Change From Baseline in Oral Temperature
|
-0.12 Degrees Celsius
Standard Deviation 0.314
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 11, Pre-Dose) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Change From Baseline in Oral Temperature
|
-0.03 Degrees Celsius
Standard Deviation 0.249
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 21, Pre-Dose), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Change From Baseline in Oral Temperature
Day 22
|
-0.13 Degrees Celsius
Standard Deviation 0.242
|
—
|
—
|
|
Treatment C: Change From Baseline in Oral Temperature
Day 25
|
0.01 Degrees Celsius
Standard Deviation 0.286
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1, Pre-dose) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Change From Baseline in Pulse Rate
|
0.5 Beats per minute
Standard Deviation 6.27
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 11, Pre-Dose) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Change From Baseline in Pulse Rate
|
1.3 Beats per minute
Standard Deviation 7.44
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 21, Pre-Dose), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Change From Baseline in Pulse Rate
Day 22
|
-7.1 Beats per minute
Standard Deviation 7.48
|
—
|
—
|
|
Treatment C: Change From Baseline in Pulse Rate
Day 25
|
-1.5 Beats per minute
Standard Deviation 6.17
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1, Pre-dose) and Day 2Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Change From Baseline in Respiratory Rate
|
-0.3 Breaths per minute
Standard Deviation 2.62
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 11, Pre-Dose) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Change From Baseline in Respiratory Rate
|
-0.3 Breaths per minute
Standard Deviation 2.36
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 21, Pre-Dose), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Change From Baseline in Respiratory Rate
Day 22
|
-0.1 Breaths per minute
Standard Deviation 1.90
|
—
|
—
|
|
Treatment C: Change From Baseline in Respiratory Rate
Day 25
|
0.8 Breaths per minute
Standard Deviation 2.37
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 1, Pre-dose) and Day 10Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment A: Change From Baseline in SBP and DBP
SBP
|
-3.3 Millimeters of mercury
Standard Deviation 9.67
|
—
|
—
|
|
Treatment A: Change From Baseline in SBP and DBP
DBP
|
-5.4 Millimeters of mercury
Standard Deviation 5.96
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 11, Pre-Dose) and Day 20Population: Safety Population.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment B: Change From Baseline in SBP and DBP
SBP
|
-0.5 Millimeters of mercury
Standard Deviation 8.56
|
—
|
—
|
|
Treatment B: Change From Baseline in SBP and DBP
DBP
|
-2.0 Millimeters of mercury
Standard Deviation 5.75
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 21, Pre-Dose), Days 22 and 25Population: Safety Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Change From Baseline in SBP and DBP
Day 22: SBP
|
-1.9 Millimeters of mercury
Standard Deviation 10.84
|
—
|
—
|
|
Treatment C: Change From Baseline in SBP and DBP
Day 25: SBP
|
2.2 Millimeters of mercury
Standard Deviation 8.67
|
—
|
—
|
|
Treatment C: Change From Baseline in SBP and DBP
Day 22: DBP
|
-4.3 Millimeters of mercury
Standard Deviation 4.75
|
—
|
—
|
|
Treatment C: Change From Baseline in SBP and DBP
Day 25: DBP
|
-0.5 Millimeters of mercury
Standard Deviation 4.78
|
—
|
—
|
SECONDARY outcome
Timeframe: 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 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: AUC(0-t) for GSK3640254
|
51840 h*ng/mL
Geometric Coefficient of Variation 48.8
|
—
|
—
|
SECONDARY outcome
Timeframe: 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 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: AUC From Time Zero to the End of the Dosing Interval at Steady State (AUC[0-tau]) for GSK3640254
|
22920 h*ng/mL
Geometric Coefficient of Variation 37.3
|
—
|
—
|
SECONDARY outcome
Timeframe: 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 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Cmax for GSK3640254
|
1450 ng/mL
Geometric Coefficient of Variation 41.7
|
—
|
—
|
SECONDARY outcome
Timeframe: 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 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Plasma Concentration at the End of the Dosing Interval (Ctau) for GSK3640254
|
729.5 ng/mL
Geometric Coefficient of Variation 35.5
|
—
|
—
|
SECONDARY outcome
Timeframe: 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 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: Tmax for GSK3640254
|
4.500 Hours
Interval 2.0 to 8.03
|
—
|
—
|
SECONDARY outcome
Timeframe: 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 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for steady-state pharmacokinetic analysis of GSK3640254.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=18 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Treatment C: t1/2 for GSK3640254
|
29.556 Hours
Geometric Coefficient of Variation 16.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
AUC(0-t) for Alpha-hydroxymetoprolol
|
531.3 h*ng/mL
Geometric Coefficient of Variation 159.4
|
487.9 h*ng/mL
Geometric Coefficient of Variation 174.4
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=18 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
AUC(0-infinity) for Alpha-hydroxymetoprolol
|
682.8 h*ng/mL
Geometric Coefficient of Variation 34.1
|
632.8 h*ng/mL
Geometric Coefficient of Variation 50.7
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol. Alpha-hydroxymetoprolol is a metabolite of metoprolol.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Cmax for Alpha-hydroxymetoprolol
|
45.70 ng/mL
Geometric Coefficient of Variation 199.8
|
39.21 ng/mL
Geometric Coefficient of Variation 212.6
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol. Alpha-hydroxymetoprolol is a metabolite of metoprolol.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Tmax for Alpha-hydroxymetoprolol
|
3.033 Hours
Interval 1.0 to 6.0
|
4.000 Hours
Interval 1.0 to 8.0
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of alpha-hydroxymetoprolol. Alpha-hydroxymetoprolol is a metabolite of metoprolol.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=19 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=18 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
t1/2 for Alpha-hydroxymetoprolol
|
8.040 Hours
Geometric Coefficient of Variation 31.4
|
8.339 Hours
Geometric Coefficient of Variation 23.0
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
AUC(0-t) for 36-hydroxymontelukast
|
234.2 h*ng/mL
Geometric Coefficient of Variation 47.2
|
230.9 h*ng/mL
Geometric Coefficient of Variation 59.1
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
AUC(0-infinity) for 36-hydroxymontelukast
|
252.5 h*ng/mL
Geometric Coefficient of Variation 48.2
|
249.3 h*ng/mL
Geometric Coefficient of Variation 58.7
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukast. 36-hydroxymontelukast is a metabolite of montelukast.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Cmax for 36-hydroxymontelukast
|
24.62 ng/mL
Geometric Coefficient of Variation 45.7
|
23.22 ng/mL
Geometric Coefficient of Variation 55.0
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukast. 36-hydroxymontelukast is a metabolite of montelukast.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Tmax for 36-hydroxymontelukast
|
6.000 Hours
Interval 3.0 to 8.03
|
6.000 Hours
Interval 4.0 to 8.13
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of 36-hydroxymontelukast. 36-hydroxymontelukast is a metabolite of montelukast.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
t1/2 for 36-hydroxymontelukast
|
5.310 Hours
Geometric Coefficient of Variation 14.3
|
5.644 Hours
Geometric Coefficient of Variation 15.1
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
AUC(0-t) for 5-hydroxyomeprazole
|
713.5 h*ng/mL
Geometric Coefficient of Variation 38.0
|
785.1 h*ng/mL
Geometric Coefficient of Variation 24.7
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=14 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=14 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
AUC(0-infinity) for 5-hydroxyomeprazole
|
767.4 h*ng/mL
Geometric Coefficient of Variation 30.9
|
762.0 h*ng/mL
Geometric Coefficient of Variation 25.6
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole. 5-hydroxyomeprazole is a metabolite of omeprazole.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Cmax for 5-hydroxyomeprazole
|
181.1 ng/mL
Geometric Coefficient of Variation 63.1
|
203.3 ng/mL
Geometric Coefficient of Variation 28.6
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole. 5-hydroxyomeprazole is a metabolite of omeprazole.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Tmax for 5-hydroxyomeprazole
|
6.000 Hours
Interval 2.05 to 12.07
|
6.000 Hours
Interval 1.5 to 12.0
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of 5-hydroxyomeprazole. 5-hydroxyomeprazole is a metabolite of omeprazole.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=14 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=14 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
t1/2 for 5-hydroxyomeprazole
|
1.580 Hours
Geometric Coefficient of Variation 15.4
|
1.569 Hours
Geometric Coefficient of Variation 13.5
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
AUC(0-t) for 1-hydroxymidazolam
|
31.07 h*ng/mL
Geometric Coefficient of Variation 33.0
|
28.07 h*ng/mL
Geometric Coefficient of Variation 37.0
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
AUC(0-infinity) for 1-hydroxymidazolam
|
31.86 h*ng/mL
Geometric Coefficient of Variation 32.5
|
28.99 h*ng/mL
Geometric Coefficient of Variation 36.6
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of 1-hydroxymidazolam. 1-hydroxymidazolam is a metabolite of midazolam.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Cmax for 1-hydroxymidazolam
|
7.933 ng/mL
Geometric Coefficient of Variation 53.8
|
6.722 ng/mL
Geometric Coefficient of Variation 48.1
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of 1-hydroxymidazolam. 1-hydroxymidazolam is a metabolite of midazolam.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Tmax for 1-hydroxymidazolam
|
1.000 Hours
Interval 0.25 to 3.0
|
1.000 Hours
Interval 0.25 to 4.0
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
Blood samples were collected at the indicated time points for pharmacokinetic analysis of 1-hydroxymidazolam. 1-hydroxymidazolam is a metabolite of midazolam.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
t1/2 for 1-hydroxymidazolam
|
3.632 Hours
Geometric Coefficient of Variation 15.6
|
3.717 Hours
Geometric Coefficient of Variation 21.0
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Ratio of Cmax of Alpha-hydroxymetoprolol to Metoprolol
|
0.7869 Ratio
Standard Deviation 0.76896
|
0.7066 Ratio
Standard Deviation 0.93732
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Ratio of AUC(0-infinity) of Alpha-hydroxymetoprolol to Metoprolol
|
1.733 Ratio
Standard Deviation 1.6208
|
1.449 Ratio
Standard Deviation 1.6511
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Ratio of Cmax of 36-hydroxymontelukast to Montelukast
|
0.06766 Ratio
Standard Deviation 0.025068
|
0.06308 Ratio
Standard Deviation 0.025951
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Ratio of AUC(0-infinity) of 36-hydroxymontelukast to Montelukast
|
0.09182 Ratio
Standard Deviation 0.033472
|
0.08562 Ratio
Standard Deviation 0.036555
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Ratio of Cmax of 5-hydroxyomeprazole to Omeprazole
|
0.9461 Ratio
Standard Deviation 0.56833
|
0.8810 Ratio
Standard Deviation 0.49954
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Ratio of AUC(0-infinity) of 5-hydroxyomeprazole to Omeprazole
|
1.151 Ratio
Standard Deviation 0.66463
|
1.077 Ratio
Standard Deviation 0.59178
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Ratio of Cmax of 1-hydroxymidazolam to Midazolam
|
0.5286 Ratio
Standard Deviation 0.23819
|
0.4955 Ratio
Standard Deviation 0.20616
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 48, 72, 96, and 120 hours post-dose in treatment period 1 and 3Population: PK Parameter Population. Only those participants with data available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Treatment A: Probe Substrates
n=20 Participants
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 Participants
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Ratio of AUC(0-infinity) of 1-hydroxymidazolam to Midazolam
|
0.4677 Ratio
Standard Deviation 0.19853
|
0.4618 Ratio
Standard Deviation 0.20637
|
—
|
Adverse Events
Treatment A: Probe Substrates
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Treatment B: GSK3640254 200 mg
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Treatment C: Probe Substrates + GSK3640254 200 mg
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A: Probe Substrates
n=20 participants at risk
All treated participants received a single dose of treatment A: Probe substrates (caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) on Day 1.
|
Treatment B: GSK3640254 200 mg
n=20 participants at risk
All treated participants received a single dose of treatment treatment B- GSK3640254 200 mg once daily from Days 11 to 20.
|
Treatment C: Probe Substrates + GSK3640254 200 mg
n=19 participants at risk
All treated participants received a single dose of treatment C: Probe substrates (Caffeine 200 mg, metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg, and pravastatin 40 mg) co-administered with GSK3640254 200 mg on Day 21.
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Dry throat
|
0.00%
0/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
5.0%
1/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
0.00%
0/19 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
5.0%
1/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
0.00%
0/19 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
15.0%
3/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
0.00%
0/19 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
|
Nervous system disorders
Headache
|
5.0%
1/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
5.0%
1/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
5.3%
1/19 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
|
Nervous system disorders
Taste disorder
|
0.00%
0/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
0.00%
0/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
5.3%
1/19 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
5.0%
1/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
5.3%
1/19 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
0.00%
0/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
5.3%
1/19 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
5.0%
1/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
0.00%
0/19 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
0.00%
0/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
5.3%
1/19 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
5.0%
1/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
0.00%
0/19 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
5.0%
1/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
0.00%
0/19 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
0.00%
0/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
5.0%
1/20 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
0.00%
0/19 • All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to Day 26
Safety Population consisted of all participants who received at least 1 dose of study medication.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER