Phase 1
Completed N=20
Evaluation of Pharmacokinetic Interaction Between GSK3640254 and Caffeine, Metoprolol, Montelukast, Flurbiprofen, Omeprazole, Midazolam, Digoxin, and Pravastatin in Healthy Adults
Source: ClinicalTrials.gov NCT04425902 ↗Enrolled (actual)
20
Serious AEs
0.0%
Results posted
May 2022
Primary outcomePrimary: Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Time t (AUC[0-t]) for Caffeine — 37970; 42230 Hour*nanograms per milliliter (h*ng/mL)
Summary
This is an open-label, single sequence study that is being conducted to investigate the potential drug-drug interaction (DDI) when GSK3640254 is co-administered with a cocktail of cytochrome P450 (CYP) enzymes and transporter probe substrates in healthy participants. This study will aid in understanding these interactions and resulting changes in exposure (if any) when drugs that are metabolized via these pathways are given in combination with GSK3640254. The study will consist of a Screening period and 3 sequential treatment regimens. Participants will be administered a single dose of probe substrate drugs (caffeine 200 milligram (mg), metoprolol 100 mg, montelukast 10 mg, flurbiprofen 100 mg, omeprazole 40 mg, midazolam 5 mg, digoxin 0.25 mg and pravastatin 40 mg) on Day 1. Participants will then receive GSK3640254 200 mg once daily on Days 11 to 20 followed by co-administration of probe substrate drugs with GSK3640254 on Day 21.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to Time t (AUC[0-t]) for Caffeine |
37970; 42230 | — |
| PRIMARY AUC From Time Zero Extrapolated to Infinity (AUC[0-infinity]) for Caffeine |
39720; 44440 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) for Caffeine |
4340; 4110 | — |
| PRIMARY Time to Cmax (Tmax) for Caffeine |
2.000; 3.000 | — |
| PRIMARY Apparent Terminal Phase Half-life (t1/2) for Caffeine |
5.380; 6.085 | — |
| PRIMARY AUC(0-t) for Metoprolol |
655.0; 807.3 | — |
| PRIMARY AUC(0-infinity) for Metoprolol |
659.1; 813.1 | — |
| PRIMARY Cmax for Metoprolol |
127.4; 141.1 | — |
| PRIMARY Tmax for Metoprolol |
2.000; 3.000 | — |
| PRIMARY t1/2 for Metoprolol |
4.872; 5.342 | — |
| PRIMARY AUC(0-t) for Montelukast |
2724; 2940 | — |
| PRIMARY AUC(0-infinity) for Montelukast |
2859; 3109 | — |
| PRIMARY Cmax for Montelukast |
379.8; 393.5 | — |
| PRIMARY Tmax for Montelukast |
5.000; 6.000 | — |
| PRIMARY t1/2 for Montelukast |
5.035; 5.135 | — |
| PRIMARY AUC(0-t) for Flurbiprofen |
64930; 66170 | — |
| PRIMARY AUC(0-infinity) for Flurbiprofen |
66700; 68660 | — |
| PRIMARY Cmax for Flurbiprofen |
10220; 10710 | — |
| PRIMARY Tmax for Flurbiprofen |
3.000; 4.000 | — |
| PRIMARY t1/2 for Flurbiprofen |
6.123; 6.088 | — |
| PRIMARY AUC(0-t) for Omeprazole |
728.1; 817.9 | — |
| PRIMARY AUC(0-infinity) for Omeprazole |
1127; 1093 | — |
| PRIMARY Cmax for Omeprazole |
224.4; 256.6 | — |
| PRIMARY Tmax for Omeprazole |
6.000; 6.000 | — |
| PRIMARY t1/2 for Omeprazole |
1.439; 1.219 | — |
| PRIMARY AUC(0-t) for Midazolam |
67.11; 62.95 | — |
| PRIMARY AUC(0-infinity) for Midazolam |
70.08; 65.46 | — |
| PRIMARY Cmax for Midazolam |
15.44; 13.95 | — |
| PRIMARY Tmax for Midazolam |
1.000; 1.000 | — |
| PRIMARY t1/2 for Midazolam |
5.756; 5.222 | — |
| PRIMARY AUC(0-t) for Digoxin |
16690; 17840 | — |
| PRIMARY AUC(0-infinity) for Digoxin |
19180; 20090 | — |
| PRIMARY Cmax for Digoxin |
1026; 1282 | — |
| PRIMARY Tmax for Digoxin |
3.000; 2.000 | — |
| PRIMARY t1/2 for Digoxin |
40.279; 38.784 | — |
| PRIMARY AUC(0-t) for Pravastatin |
69.92; 51.03 | — |
| PRIMARY AUC(0-infinity) for Pravastatin |
72.09; 43.70 | — |
| PRIMARY Cmax for Pravastatin |
19.45; 15.19 | — |
| PRIMARY Tmax for Pravastatin |
1.500; 3.000 | — |
| PRIMARY t1/2 for Pravastatin |
3.189; 3.156 | — |
| SECONDARY Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
1; 5; 5; 0; 0; 0 | — |
| SECONDARY Treatment A: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils |
258.6; 265.9; 5.64; 6.30; 3.1504; 3.7430 | — |
| SECONDARY Treatment B: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils |
265.9; 261.9; 6.30; 5.79; 3.7430; 3.2680 | — |
| SECONDARY Treatment C: Absolute Values of Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils |
262.3; 249.2; 260.7; 5.86; 5.81; 5.98 | — |
| SECONDARY Treatment A: Absolute Values of Hematocrit |
0.4188; 0.4098 | — |
| SECONDARY Treatment B: Absolute Values of Hematocrit |
0.4098; 0.4216 | — |
| SECONDARY Treatment C: Absolute Values of Hematocrit |
0.4239; 0.4022; 0.4168 | — |
| SECONDARY Treatment A: Absolute Values of Hemoglobin |
141.9; 137.7 | — |
| SECONDARY Treatment B: Absolute Values of Hemoglobin |
137.7; 140.0 | — |
| SECONDARY Treatment C: Absolute Values of Hemoglobin |
140.6; 134.7; 138.3 | — |
| SECONDARY Treatment A: Absolute Values of Erythrocytes |
4.836; 4.664 | — |
| SECONDARY Treatment B: Absolute Values of Erythrocytes |
4.664; 4.746 | — |
| SECONDARY Treatment C: Absolute Values of Erythrocytes |
4.769; 4.608; 4.756 | — |
| SECONDARY Treatment A: Absolute Values of Erythrocytes Mean Corpuscular Volume |
86.71; 88.02 | — |
| SECONDARY Treatment B: Absolute Values of Erythrocytes Mean Corpuscular Volume |
88.02; 88.96 | — |
| SECONDARY Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Volume |
89.03; 87.38; 87.74 | — |
| SECONDARY Treatment A: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin |
29.37; 29.57 | — |
| SECONDARY Treatment B: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin |
29.57; 29.52 | — |
| SECONDARY Treatment C: Absolute Values of Erythrocytes Mean Corpuscular Hemoglobin |
29.51; 29.28; 29.12 | — |
| SECONDARY Treatment A: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea |
5.0348; 4.8211; 104.1; 25.4; 4.4570; 3.8118 | — |
| SECONDARY Treatment B: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea |
4.8211; 4.7378; 25.4; 24.9; 3.8118; 3.6915 | — |
| SECONDARY Treatment C: Absolute Values of Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea |
4.7184; 4.8060; 4.8703; 24.9; 25.4; 26.2 | — |
| SECONDARY Treatment A: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin |
347.3632; 365.5046; 84.9524; 86.4110; 9.8325; 8.0028 | — |
| SECONDARY Treatment B: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin |
365.5046; 337.8464; 86.4110; 90.7868; 8.0028; 8.6184 | — |
| SECONDARY Treatment C: Absolute Values of Urate, Creatinine, Bilirubin, Direct Bilirubin |
343.1057; 303.0349; 340.6013; 92.1686; 87.3764; 90.5867 | — |
| SECONDARY Treatment A: Absolute Values of Albumin, Globulin, Protein |
42.9; 42.2; 27.4; 25.9; 70.3; 68.1 | — |
| SECONDARY Treatment B: Absolute Values of Albumin, Globulin, Protein |
42.2; 41.4; 25.9; 26.8; 68.1; 68.2 | — |
| SECONDARY Treatment C: Absolute Values of Albumin, Globulin, Protein |
41.6; 40.5; 42.0; 26.9; 25.1; 26.6 | — |
| SECONDARY Treatment A: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transferase |
103.7; 66.9; 131.3; 114.8; 15.6; 20.1 | — |
| SECONDARY Treatment B: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase |
66.9; 68.9; 114.8; 115.9; 20.1; 20.3 | — |
| SECONDARY Treatment C: Absolute Values of Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase |
71.3; 65.7; 63.8; 116.6; 120.6; 119.3 | — |
| SECONDARY Treatment A: Absolute Values of Amylase, Lipase |
29.4; 31.6; 59.5; 56.9 | — |
| SECONDARY Treatment B: Absolute Values of Amylase, Lipase |
31.6; 32.4; 56.9; 60.1 | — |
| SECONDARY Treatment C: Absolute Values of Amylase, Lipase |
32.9; 33.5; 33.1; 62.2; 64.7; 60.7 | — |
| SECONDARY Treatment A: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils |
7.3; 0.66; 0.5926; 0.0748; -0.0375; 0.0150 | — |
| SECONDARY Treatment B: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils |
-4.1; -0.51; -0.4750; -0.0610; -0.0080; 0.0310 | — |
| SECONDARY Treatment C: Change From Baseline in Platelet Count, Leukocyte Count, Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils |
-13.1; -1.6; -0.05; 0.12; -0.1254; 0.1351 | — |
| SECONDARY Treatment A: Change From Baseline in Hematocrit |
-0.0090 | — |
| SECONDARY Treatment B: Change From Baseline in Hematocrit |
0.0118 | — |
| SECONDARY Treatment C: Change From Baseline in Hematocrit |
-0.0217; -0.0071 | — |
| SECONDARY Treatment A: Change From Baseline in Hemoglobin |
-4.2 | — |
| SECONDARY Treatment B: Change From Baseline in Hemoglobin |
2.3 | — |
| SECONDARY Treatment C: Change From Baseline in Hemoglobin |
-5.8; -2.3 | — |
| SECONDARY Treatment A: Change From Baseline in Erythrocytes |
-0.172 | — |
| SECONDARY Treatment B: Change From Baseline in Erythrocytes |
0.083 | — |
| SECONDARY Treatment C: Change From Baseline in Erythrocytes |
-0.161; -0.013 | — |
| SECONDARY Treatment A: Change From Baseline in Erythrocytes Mean Corpuscular Volume |
1.31 | — |
| SECONDARY Treatment B: Change From Baseline in Erythrocytes Mean Corpuscular Volume |
0.94 | — |
| SECONDARY Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Volume |
-1.64; -1.28 | — |
| SECONDARY Treatment A: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin |
0.20 | — |
| SECONDARY Treatment B: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin |
-0.05 | — |
| SECONDARY Treatment C: Change From Baseline in Erythrocytes Mean Corpuscular Hemoglobin |
-0.23; -0.39 | — |
| SECONDARY Treatment A: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea |
-0.2137; -78.7; -0.6452; -0.0418; 5.9; -0.0624 | — |
| SECONDARY Treatment B: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea |
-0.0833; -0.6; -0.1203; -0.0989; 0.8; 0.0000 | — |
| SECONDARY Treatment C: Change From Baseline in Glucose, Carbon Dioxide, Cholesterol, Triglycerides, Anion Gap, Calcium, Chloride, Phosphate, Potassium, Sodium, Urea |
0.0876; 0.1519; 0.5; 1.2; -0.4355; -0.2926 | — |
| SECONDARY Treatment A: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin |
18.1414; 1.4586; -1.8297; -0.3506 | — |
| SECONDARY Treatment B: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin |
-27.6582; 4.3758; 0.6156; 0.1112 | — |
| SECONDARY Treatment C: Change From Baseline in Urate, Creatinine, Bilirubin, Direct Bilirubin |
-40.0707; -2.5044; -4.7922; -1.5819; 1.1340; 0.2880 | — |
| SECONDARY Treatment A: Change From Baseline in Albumin, Globulin, Protein |
-0.7; -1.5; -2.2 | — |
| SECONDARY Treatment B: Change From Baseline in Albumin, Globulin, Protein |
-0.9; 0.9; 0.1 | — |
| SECONDARY Treatment C: Change From Baseline in Albumin, Globulin, Protein |
-1.1; 0.4; -1.8; -0.3; -2.9; 0.2 | — |
| SECONDARY Treatment A: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase |
-36.9; -16.5; 4.5; -1.9; 1.0; -0.2 | — |
| SECONDARY Treatment B: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase |
2.1; 1.1; 0.3; -2.4; 0.6; -0.6 | — |
| SECONDARY Treatment C: Change From Baseline in Creatine Kinase, Lactate Dehydrogenase, ALT, ALP, AST, Gamma-glutamyl Transferase |
-5.6; -7.5; 4.0; 2.6; -3.1; 0.5 | — |
| SECONDARY Treatment A: Change From Baseline in Amylase, Lipase |
2.2; -2.6 | — |
| SECONDARY Treatment B: Change From Baseline in Amylase, Lipase |
0.9; 3.2 | — |
| SECONDARY Treatment C: Change From Baseline in Amylase, Lipase |
0.6; 0.2; 2.5; -1.5 | — |
| SECONDARY Treatment A: Absolute Values for Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, Corrected QT Interval Using Fridericia's Formula (QTcF) |
154.8; 158.2; 92.5; 95.0; 391.2; 398.3 | — |
| SECONDARY Treatment B: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval |
158.6; 161.8; 94.2; 96.4; 403.1; 408.8 | — |
| SECONDARY Treatment C: Absolute Values for ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF Interval |
160.8; 162.3; 159.6; 95.8; 98.7; 96.8 | — |
| SECONDARY Treatment A: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF |
3.4; 2.5; 7.1; 4.8 | — |
| SECONDARY Treatment B: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF |
3.2; 2.3; 5.7; 5.1 | — |
| SECONDARY Treatment C: Change From Baseline in ECG Parameters: PR Interval, QRS Duration, QT Interval, QTcF |
1.5; -1.2; 2.9; 1.0; 18.0; -3.9 | — |
| SECONDARY Treatment A: Absolute Values of Oral Temperature |
36.38; 36.26 | — |
| SECONDARY Treatment B: Absolute Values of Oral Temperature |
36.31; 36.28 | — |
| SECONDARY Treatment C: Absolute Values of Oral Temperature |
36.31; 36.18; 36.31 | — |
| SECONDARY Treatment A: Absolute Values of Pulse Rate |
64.5; 65.0 | — |
| SECONDARY Treatment B: Absolute Values of Pulse Rate |
61.6; 62.8 | — |
| SECONDARY Treatment C: Absolute Values of Pulse Rate |
63.2; 56.2; 61.7 | — |
| SECONDARY Treatment A: Absolute Values of Respiratory Rate |
16.1; 15.8 | — |
| SECONDARY Treatment B: Absolute Values of Respiratory Rate |
15.0; 14.7 | — |
| SECONDARY Treatment C: Absolute Values of Respiratory Rate |
15.7; 15.7; 16.5 | — |
| SECONDARY Treatment A: Absolute Values of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
111.0; 107.7; 65.1; 59.7 | — |
| SECONDARY Treatment B: Absolute Values of SBP and DBP |
107.7; 107.2; 61.6; 59.6 | — |
| SECONDARY Treatment C: Absolute Values of SBP and DBP |
107.5; 105.6; 109.7; 62.7; 58.4; 62.2 | — |
| SECONDARY Treatment A: Change From Baseline in Oral Temperature |
-0.12 | — |
| SECONDARY Treatment B: Change From Baseline in Oral Temperature |
-0.03 | — |
| SECONDARY Treatment C: Change From Baseline in Oral Temperature |
-0.13; 0.01 | — |
| SECONDARY Treatment A: Change From Baseline in Pulse Rate |
0.5 | — |
| SECONDARY Treatment B: Change From Baseline in Pulse Rate |
1.3 | — |
| SECONDARY Treatment C: Change From Baseline in Pulse Rate |
-7.1; -1.5 | — |
| SECONDARY Treatment A: Change From Baseline in Respiratory Rate |
-0.3 | — |
| SECONDARY Treatment B: Change From Baseline in Respiratory Rate |
-0.3 | — |
| SECONDARY Treatment C: Change From Baseline in Respiratory Rate |
-0.1; 0.8 | — |
| SECONDARY Treatment A: Change From Baseline in SBP and DBP |
-3.3; -5.4 | — |
| SECONDARY Treatment B: Change From Baseline in SBP and DBP |
-0.5; -2.0 | — |
| SECONDARY Treatment C: Change From Baseline in SBP and DBP |
-1.9; 2.2; -4.3; -0.5 | — |
| SECONDARY Treatment C: AUC(0-t) for GSK3640254 |
51840 | — |
| SECONDARY Treatment C: AUC From Time Zero to the End of the Dosing Interval at Steady State (AUC[0-tau]) for GSK3640254 |
22920 | — |
| SECONDARY Treatment C: Cmax for GSK3640254 |
1450 | — |
| SECONDARY Treatment C: Plasma Concentration at the End of the Dosing Interval (Ctau) for GSK3640254 |
729.5 | — |
| SECONDARY Treatment C: Tmax for GSK3640254 |
4.500 | — |
| SECONDARY Treatment C: t1/2 for GSK3640254 |
29.556 | — |
| SECONDARY AUC(0-t) for Alpha-hydroxymetoprolol |
531.3; 487.9 | — |
| SECONDARY AUC(0-infinity) for Alpha-hydroxymetoprolol |
682.8; 632.8 | — |
| SECONDARY Cmax for Alpha-hydroxymetoprolol |
45.70; 39.21 | — |
| SECONDARY Tmax for Alpha-hydroxymetoprolol |
3.033; 4.000 | — |
| SECONDARY t1/2 for Alpha-hydroxymetoprolol |
8.040; 8.339 | — |
| SECONDARY AUC(0-t) for 36-hydroxymontelukast |
234.2; 230.9 | — |
| SECONDARY AUC(0-infinity) for 36-hydroxymontelukast |
252.5; 249.3 | — |
| SECONDARY Cmax for 36-hydroxymontelukast |
24.62; 23.22 | — |
| SECONDARY Tmax for 36-hydroxymontelukast |
6.000; 6.000 | — |
| SECONDARY t1/2 for 36-hydroxymontelukast |
5.310; 5.644 | — |
| SECONDARY AUC(0-t) for 5-hydroxyomeprazole |
713.5; 785.1 | — |
| SECONDARY AUC(0-infinity) for 5-hydroxyomeprazole |
767.4; 762.0 | — |
| SECONDARY Cmax for 5-hydroxyomeprazole |
181.1; 203.3 | — |
| SECONDARY Tmax for 5-hydroxyomeprazole |
6.000; 6.000 | — |
| SECONDARY t1/2 for 5-hydroxyomeprazole |
1.580; 1.569 | — |
| SECONDARY AUC(0-t) for 1-hydroxymidazolam |
31.07; 28.07 | — |
| SECONDARY AUC(0-infinity) for 1-hydroxymidazolam |
31.86; 28.99 | — |
| SECONDARY Cmax for 1-hydroxymidazolam |
7.933; 6.722 | — |
| SECONDARY Tmax for 1-hydroxymidazolam |
1.000; 1.000 | — |
| SECONDARY t1/2 for 1-hydroxymidazolam |
3.632; 3.717 | — |
| SECONDARY Ratio of Cmax of Alpha-hydroxymetoprolol to Metoprolol |
0.7869; 0.7066 | — |
| SECONDARY Ratio of AUC(0-infinity) of Alpha-hydroxymetoprolol to Metoprolol |
1.733; 1.449 | — |
| SECONDARY Ratio of Cmax of 36-hydroxymontelukast to Montelukast |
0.06766; 0.06308 | — |
| SECONDARY Ratio of AUC(0-infinity) of 36-hydroxymontelukast to Montelukast |
0.09182; 0.08562 | — |
| SECONDARY Ratio of Cmax of 5-hydroxyomeprazole to Omeprazole |
0.9461; 0.8810 | — |
| SECONDARY Ratio of AUC(0-infinity) of 5-hydroxyomeprazole to Omeprazole |
1.151; 1.077 | — |
| SECONDARY Ratio of Cmax of 1-hydroxymidazolam to Midazolam |
0.5286; 0.4955 | — |
| SECONDARY Ratio of AUC(0-infinity) of 1-hydroxymidazolam to Midazolam |
0.4677; 0.4618 | — |
Eligibility Criteria
Inclusion Criteria
- Participant must be 18 to 50 years of age inclusive, at the time of signing the informed consent.
- Participants who are overtly healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination (including cardiopulmonary examination), laboratory tests, and cardiac monitoring (history and ECG).
- Body weight more than or equal to (>=) 50.0 kilograms (kg) (110 pounds [lbs]) for men and >=45.0 kg (99 lbs) for women and body mass index within the range 18.5 to 31.0 kilogram per square meter (kg/m^2) (inclusive).
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- Male participants should not engage in intercourse while confined in the clinic. There is no need for an extended period of double barrier use or prolonged abstinence after study discharge.
- A female participant is eligible to participate if she is not pregnant or breastfeeding and at least one of the following conditions applies:
- Is not a woman of childbearing potential (WOCBP) or
- Is a WOCBP and using a non-hormonal contraceptive method that is highly effective, with a failure rate of less than ( 6 months) outpatient treatment.
Participants with other conditions such as adjustment disorder or dysthymia that have required shorter term medical therapy ( =1.5 × upper limit of normal (ULN). A single repeat of ALT is allowed within a single screening period to determine eligibility.
- Bilirubin >=5 × ULN (isolated bilirubin >=5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin 100 bpm, PR interval- >200 milliseconds and QTcF- >450 milliseconds.
- History of regular alcohol consumption within 6 months of the study defined as an average weekly intake of >14 units. One unit is equivalent to 8 grams (g) of alcohol: a half-pint (approximately 240 mL) of beer, 1 glass (125 mL) of wine, or 1 (25 mL) measure of spirits.
- Unable to refrain from tobacco or nicotine-containing products within 3 months prior to Screening.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.
- History of aspirin allergy.
- A participant with known or suspected active coronavirus disease of 2019 (COVID-19) infection OR contact with an individual with known COVID-19, within 14 days of study enrollment.
Data sourced from ClinicalTrials.gov (NCT04425902). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.