Trial Outcomes & Findings for This Study Tests the Effect of Certain Medicines on the Transport of Other Medicines in the Body of Healthy Men (NCT NCT03307252)
NCT ID: NCT03307252
Last Updated: 2023-11-07
Results Overview
AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. Geometric mean (gMean) presented here is an adjusted gMean and standard error (SE) presented is a geometric SE (gSE).
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
45 participants
Primary outcome timeframe
Samples were taken within 0:20 hour:minutes (hh:mm) prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.
Results posted on
2023-11-07
Participant Flow
The trial consisted of 3 parts investigating different drug transporter inhibitors. All parts of the trial were performed in healthy male participants in a randomised, open-label, three-way (Part 1) or four-way (Part 2 and 3) crossover design.
All participants were screened for eligibility to participate in the trial. Participants were not to be randomised to trial treatment if any of the in- or exclusion criteria were violated at screening.
Participant milestones
| Measure |
Cocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)
In trial part 1 participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 milliliter (mL) of water in period 1. R1 is a drug cocktail that contains a single dose of each, 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by a single dose of 120 mg Verapamil orally with 240 mL of water at 1 hour (h) prior to R1 which is administered with 280 mL of water in period 2. In period 3 participants were administered a single dose of 600 mg Rifampin film-coated tablet with 280 mL of water together with R1. Treatment periods were separated by a wash-out period of 13 days.
|
(Verapamil + R1)/ (Rifampin + R1)/ R1
In trial part 1 participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to R1 which is administered with 280 mL of water in period 1. Followed by a single dose of 600 mg Rifampin film-coated tablet orally with 280 mL of water together with R1 in period 2. In period 3 participants were administered a single dose of R1 with 280 milliliter (mL) of water. R1 is a drug cocktail that contains a single dose of each, 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Treatment periods were separated by a wash-out period of 13 days.
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(Rifampin + R1)/ R1/ (Verapamil + R1)
In trial part 1 participants were administered a single dose of 600 mg Rifampin film-coated tablet orally with 280 mL of water together with R1 in period 1. Followed by a single dose of R1 with 280 mL of water in period 2. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. In period 3 participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 hour (h) prior to the R1 which is administered with 280 mL of water. Treatment periods were separated by a wash-out period of 13 days.
|
R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)
In trial part 2 participants were administered single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains a single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 2. Followed by 400 mg Cimetidine 1 orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 3. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to therapeutic dose of 500mg of Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after metformin (Day 2) in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
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Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)
In trial part 2 participants were administered single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 1. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after metformin (Day 2) in period 2. Followed by a single dose of R1 with 280 mL of water in period 3. R1 is a drug cocktail that contains single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 400 mg Cimetidine 1 orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
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(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin
In trial part 2 participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 1. Followed by single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in period 2. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after Metformin (Day 2) in period 3. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
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(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1
In trial part 2 participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after Metformin (Day 2) in period 1. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 2. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 3. Followed by single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
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R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)
In trial part 3 participants were administered single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 2. Followed by 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 3. Followed by 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
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Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)
In trial part 3 participants were administered single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 1. Followed by 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 2. Followed by single dose of R1 which is administered with 280 milliliter (mL) of water in period 3. R1 is a drug cocktail that contains single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
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(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide
In trial part 3 participants were administered 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 1. Followed by single dose of R1 which is administered with 280 mL of water in period 2. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 3. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
|
(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
In trial part 3 participants were administered 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 1. Followed by 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 2. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 3. Followed by single dose of R1 which is administered with 280 milliliter (mL) of water in period 4. R1 is a drug cocktail that contains a single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
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Part 1, Period 1
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Part 1, Washout Period 1 (13 Days)
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Part 1, Washout Period 2 (13 Days)
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Part 1, Washout Period 2 (13 Days)
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Part 1, Period 3
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Part 1, Period 3
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Part 2, Period 1
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Part 2, Period 4
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Part 3, Period 1
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Part 3, Washout Period 1 (7 Days)
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Part 3, Washout Period 1 (7 Days)
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Part 3, Period 2
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Part 3, Period 2
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Part 3, Period 2
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Part 3, Washout Period 2 (7 Days)
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Part 3, Washout Period 2 (7 Days)
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Part 3, Washout Period 2 (7 Days)
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Part 3, Period 3
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Part 3, Period 3
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Part 3, Period 3
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Part 3, Washout Period 3 (7 Days)
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Part 3, Washout Period 3 (7 Days)
COMPLETED
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Part 3, Washout Period 3 (7 Days)
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Part 3, Period 4
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Part 3, Period 4
COMPLETED
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Part 3, Period 4
NOT COMPLETED
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Reasons for withdrawal
| Measure |
Cocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)
In trial part 1 participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 milliliter (mL) of water in period 1. R1 is a drug cocktail that contains a single dose of each, 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by a single dose of 120 mg Verapamil orally with 240 mL of water at 1 hour (h) prior to R1 which is administered with 280 mL of water in period 2. In period 3 participants were administered a single dose of 600 mg Rifampin film-coated tablet with 280 mL of water together with R1. Treatment periods were separated by a wash-out period of 13 days.
|
(Verapamil + R1)/ (Rifampin + R1)/ R1
In trial part 1 participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to R1 which is administered with 280 mL of water in period 1. Followed by a single dose of 600 mg Rifampin film-coated tablet orally with 280 mL of water together with R1 in period 2. In period 3 participants were administered a single dose of R1 with 280 milliliter (mL) of water. R1 is a drug cocktail that contains a single dose of each, 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Treatment periods were separated by a wash-out period of 13 days.
|
(Rifampin + R1)/ R1/ (Verapamil + R1)
In trial part 1 participants were administered a single dose of 600 mg Rifampin film-coated tablet orally with 280 mL of water together with R1 in period 1. Followed by a single dose of R1 with 280 mL of water in period 2. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. In period 3 participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 hour (h) prior to the R1 which is administered with 280 mL of water. Treatment periods were separated by a wash-out period of 13 days.
|
R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)
In trial part 2 participants were administered single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains a single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 2. Followed by 400 mg Cimetidine 1 orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 3. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to therapeutic dose of 500mg of Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after metformin (Day 2) in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
|
Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)
In trial part 2 participants were administered single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 1. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after metformin (Day 2) in period 2. Followed by a single dose of R1 with 280 mL of water in period 3. R1 is a drug cocktail that contains single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 400 mg Cimetidine 1 orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
|
(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin
In trial part 2 participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 1. Followed by single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in period 2. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after Metformin (Day 2) in period 3. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
|
(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1
In trial part 2 participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after Metformin (Day 2) in period 1. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 2. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 3. Followed by single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
|
R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)
In trial part 3 participants were administered single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 2. Followed by 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 3. Followed by 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
|
Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)
In trial part 3 participants were administered single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 1. Followed by 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 2. Followed by single dose of R1 which is administered with 280 milliliter (mL) of water in period 3. R1 is a drug cocktail that contains single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
|
(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide
In trial part 3 participants were administered 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 1. Followed by single dose of R1 which is administered with 280 mL of water in period 2. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 3. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
|
(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
In trial part 3 participants were administered 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 1. Followed by 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 2. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 3. Followed by single dose of R1 which is administered with 280 milliliter (mL) of water in period 4. R1 is a drug cocktail that contains a single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
|
|---|---|---|---|---|---|---|---|---|---|---|---|
|
Part 2, Period 1
Treatment not received
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Part 2, Period 3
Other than listed
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part 2, Period 4
Other than listed
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Part 3, Washout Period 3 (7 Days)
Treatment not received due to AE
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
Baseline Characteristics
This Study Tests the Effect of Certain Medicines on the Transport of Other Medicines in the Body of Healthy Men
Baseline characteristics by cohort
| Measure |
Cocktail (R1)/ (Verapamil + R1)/ (Rifampin + R1)
n=4 Participants
In trial part 1 participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 milliliter (mL) of water in period 1. R1 is a drug cocktail that contains a single dose of each, 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by a single dose of 120 mg Verapamil orally with 240 mL of water at 1 hour (h) prior to R1 which is administered with 280 mL of water in period 2. In period 3 participants were administered a single dose of 600 mg Rifampin film-coated tablet with 280 mL of water together with R1. Treatment periods were separated by a wash-out period of 13 days.
|
(Verapamil + R1)/ (Rifampin + R1)/ R1
n=4 Participants
In trial part 1 participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to R1 which is administered with 280 mL of water in period 1. Followed by a single dose of 600 mg Rifampin film-coated tablet orally with 280 mL of water together with R1 in period 2. In period 3 participants were administered a single dose of R1 with 280 milliliter (mL) of water. R1 is a drug cocktail that contains a single dose of each, 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Treatment periods were separated by a wash-out period of 13 days.
|
(Rifampin + R1)/ R1/ (Verapamil + R1)
n=4 Participants
In trial part 1 participants were administered a single dose of 600 mg Rifampin film-coated tablet orally with 280 mL of water together with R1 in period 1. Followed by a single dose of R1 with 280 mL of water in period 2. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. In period 3 participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 hour (h) prior to the R1 which is administered with 280 mL of water. Treatment periods were separated by a wash-out period of 13 days.
|
R1/ Metformin/ (Cimetidine+R1)/ (Cimetidine+Metformin)
n=4 Participants
In trial part 2 participants were administered single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains a single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 2. Followed by 400 mg Cimetidine 1 orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 3. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to therapeutic dose of 500mg of Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after metformin (Day 2) in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
|
Metformin/ (Cimetidine+Metformin)/ R1/ (Cimetidine+R1)
n=4 Participants
In trial part 2 participants were administered single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 1. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after metformin (Day 2) in period 2. Followed by a single dose of R1 with 280 mL of water in period 3. R1 is a drug cocktail that contains single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 400 mg Cimetidine 1 orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
|
(Cimetidine+R1)/ R1/ (Cimetidine+Metformin)/ Metformin
n=4 Participants
In trial part 2 participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 1. Followed by single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in period 2. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after Metformin (Day 2) in period 3. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
|
(Cimetidine+Metformin)/ (Cimetidine+R1)/ Metformin/ R1
n=5 Participants
In trial part 2 participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after Metformin (Day 2) in period 1. Followed by 400 mg Cimetidine 1 tablet orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2) in period 2. Followed by single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in period 3. Followed by single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in period 4. All doses of Cimetidine administered with 240 mL water and R1 and dose of Metformin with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
|
R1/ Furosemide/ (Probenecid + R1)/ (Probenecid + Furosemide)
n=4 Participants
In trial part 3 participants were administered single dose of R1 which is administered with 280 mL of water in period 1. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 2. Followed by 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 3. Followed by 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
|
Furosemide/ (Probenecid + Furosemide)/ R1/ (Probenecid + R1)
n=4 Participants
In trial part 3 participants were administered single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 1. Followed by 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 2. Followed by single dose of R1 which is administered with 280 milliliter (mL) of water in period 3. R1 is a drug cocktail that contains single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
|
(Probenecid + R1)/ R1/ (Probenecid + Furosemide)/ Furosemide
n=4 Participants
In trial part 3 participants were administered 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 1. Followed by single dose of R1 which is administered with 280 mL of water in period 2. R1 is a drug cocktail that contains single dose of each 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. Followed by 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 3. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 4. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
|
(Probenecid + Furosemide)/ (Probenecid + R1)/ Furosemide/ R1
n=4 Participants
In trial part 3 participants were administered 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in period 1. Followed by 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 h prior and again 1 h prior to the administration of R1 on day 1 in period 2. Followed by single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in period 3. Followed by single dose of R1 which is administered with 280 milliliter (mL) of water in period 4. R1 is a drug cocktail that contains a single dose of each 0.25 milligram (mg) Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet. All doses of Cimetidine administered with 240 mL water and dose of Furosemide and R1 with 280 mL of water. Treatment periods were separated by a wash-out period of at least 7 days.
|
Total
n=45 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
Part 1
|
30.0 Years
STANDARD_DEVIATION 6.8 • n=5 Participants
|
51.5 Years
STANDARD_DEVIATION 1.3 • n=7 Participants
|
36.3 Years
STANDARD_DEVIATION 10.6 • n=5 Participants
|
32.8 Years
STANDARD_DEVIATION 10.2 • n=4 Participants
|
38.3 Years
STANDARD_DEVIATION 13.1 • n=21 Participants
|
35.3 Years
STANDARD_DEVIATION 11.1 • n=10 Participants
|
41.6 Years
STANDARD_DEVIATION 10.5 • n=115 Participants
|
29.3 Years
STANDARD_DEVIATION 7.9 • n=24 Participants
|
30.0 Years
STANDARD_DEVIATION 8.8 • n=42 Participants
|
33.0 Years
STANDARD_DEVIATION 13.2 • n=42 Participants
|
43.5 Years
STANDARD_DEVIATION 8.1 • n=42 Participants
|
36.6 Years
STANDARD_DEVIATION 10.8 • n=42 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
4 Participants
n=10 Participants
|
5 Participants
n=115 Participants
|
4 Participants
n=24 Participants
|
4 Participants
n=42 Participants
|
4 Participants
n=42 Participants
|
4 Participants
n=42 Participants
|
45 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
4 Participants
n=10 Participants
|
5 Participants
n=115 Participants
|
4 Participants
n=24 Participants
|
4 Participants
n=42 Participants
|
4 Participants
n=42 Participants
|
4 Participants
n=42 Participants
|
45 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
1 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
1 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
3 Participants
n=10 Participants
|
5 Participants
n=115 Participants
|
4 Participants
n=24 Participants
|
4 Participants
n=42 Participants
|
4 Participants
n=42 Participants
|
4 Participants
n=42 Participants
|
44 Participants
n=42 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
0 Participants
n=42 Participants
|
PRIMARY outcome
Timeframe: Samples were taken within 0:20 hour:minutes (hh:mm) prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.Population: Pharmacokinetic (PK) parameter analysis set (PKS): All subjects in the TS providing at least 1 primary or secondary PK parameter that was not excluded due to a protocol violation relevant to the evaluation of PK or due to PK non-evaluability.
AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. Geometric mean (gMean) presented here is an adjusted gMean and standard error (SE) presented is a geometric SE (gSE).
Outcome measures
| Measure |
Verapamil + R1 (T1)
n=12 Participants
Participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to the R1 which is administered with 280 mL of water in trial part 1.
|
Cocktail (R1)
n=12 Participants
Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.
|
|---|---|---|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Verapamil + R1 (T1) vs. R1)
Digoxin
|
13.71 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.10
|
13.61 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.10
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Verapamil + R1 (T1) vs. R1)
Furosemide
|
165.80 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.06
|
176.85 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.06
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Verapamil + R1 (T1) vs. R1)
Metformin
|
1126.22 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.05
|
1357.34 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.05
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Verapamil + R1 (T1) vs. R1)
Rosuvastatin
|
98.98 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.11
|
87.29 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.11
|
PRIMARY outcome
Timeframe: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.Population: PKS
AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.
Outcome measures
| Measure |
Verapamil + R1 (T1)
n=12 Participants
Participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to the R1 which is administered with 280 mL of water in trial part 1.
|
Cocktail (R1)
n=12 Participants
Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.
|
|---|---|---|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Rifampin + R1 (T2) vs. R1)
Digoxin
|
17.89 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.10
|
13.61 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.10
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Rifampin + R1 (T2) vs. R1)
Furosemide
|
211.82 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.06
|
176.85 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.06
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Rifampin + R1 (T2) vs. R1)
Metformin
|
1473.38 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.05
|
1357.34 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.05
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Rifampin + R1 (T2) vs. R1)
Rosuvastatin
|
303.81 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.11
|
87.29 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.11
|
PRIMARY outcome
Timeframe: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.Population: PKS
AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.
Outcome measures
| Measure |
Verapamil + R1 (T1)
n=15 Participants
Participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to the R1 which is administered with 280 mL of water in trial part 1.
|
Cocktail (R1)
n=13 Participants
Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.
|
|---|---|---|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Cimetidine + R1 (T3) vs. R1)
Digoxin
|
19.03 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.07
|
15.15 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.07
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Cimetidine + R1 (T3) vs. R1)
Furosemide
|
196.39 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.05
|
194.05 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.05
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Cimetidine + R1 (T3) vs. R1)
Metformin
|
2006.60 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.06
|
1532.41 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.07
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Cimetidine + R1 (T3) vs. R1)
Rosuvastatin
|
139.54 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.13
|
129.90 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.13
|
PRIMARY outcome
Timeframe: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.Population: PKS
AUC0-tz, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 to the last quantifiable data point is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.
Outcome measures
| Measure |
Verapamil + R1 (T1)
n=15 Participants
Participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to the R1 which is administered with 280 mL of water in trial part 1.
|
Cocktail (R1)
n=16 Participants
Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.
|
|---|---|---|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Probenecid + R1 (T4) vs. R1)
Digoxin
|
14.44 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.08
|
13.52 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.08
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Probenecid + R1 (T4) vs. R1)
Furosemide
|
483.38 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.08
|
177.96 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.07
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Probenecid + R1 (T4) vs. R1)
Metformin
|
1331.83 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.08
|
1321.20 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.08
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) (Probenecid + R1 (T4) vs. R1)
Rosuvastatin
|
238.16 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.10
|
106.69 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.10
|
PRIMARY outcome
Timeframe: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.Population: PKS
Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.
Outcome measures
| Measure |
Verapamil + R1 (T1)
n=12 Participants
Participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to the R1 which is administered with 280 mL of water in trial part 1.
|
Cocktail (R1)
n=12 Participants
Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.
|
|---|---|---|
|
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T1 vs. R1)
Digoxin
|
1.42 Nanomole/ litre (nmol/ L)
Standard Error 1.09
|
1.17 Nanomole/ litre (nmol/ L)
Standard Error 1.09
|
|
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T1 vs. R1)
Furosemide
|
84.32 Nanomole/ litre (nmol/ L)
Standard Error 1.06
|
88.59 Nanomole/ litre (nmol/ L)
Standard Error 1.06
|
|
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T1 vs. R1)
Metformin
|
179.45 Nanomole/ litre (nmol/ L)
Standard Error 1.04
|
223.78 Nanomole/ litre (nmol/ L)
Standard Error 1.04
|
|
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T1 vs. R1)
Rosuvastatin
|
7.90 Nanomole/ litre (nmol/ L)
Standard Error 1.14
|
6.84 Nanomole/ litre (nmol/ L)
Standard Error 1.14
|
PRIMARY outcome
Timeframe: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.Population: PKS
Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.
Outcome measures
| Measure |
Verapamil + R1 (T1)
n=12 Participants
Participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to the R1 which is administered with 280 mL of water in trial part 1.
|
Cocktail (R1)
n=12 Participants
Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.
|
|---|---|---|
|
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T2 vs. R1)
Digoxin
|
2.55 Nanomole/ litre (nmol/ L)
Standard Error 1.09
|
1.17 Nanomole/ litre (nmol/ L)
Standard Error 1.09
|
|
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T2 vs. R1)
Furosemide
|
119.66 Nanomole/ litre (nmol/ L)
Standard Error 1.06
|
88.59 Nanomole/ litre (nmol/ L)
Standard Error 1.06
|
|
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T2 vs. R1)
Metformin
|
251.32 Nanomole/ litre (nmol/ L)
Standard Error 1.04
|
223.78 Nanomole/ litre (nmol/ L)
Standard Error 1.04
|
|
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T2 vs. R1)
Rosuvastatin
|
77.00 Nanomole/ litre (nmol/ L)
Standard Error 1.14
|
6.84 Nanomole/ litre (nmol/ L)
Standard Error 1.14
|
PRIMARY outcome
Timeframe: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.Population: PKS
Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.
Outcome measures
| Measure |
Verapamil + R1 (T1)
n=15 Participants
Participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to the R1 which is administered with 280 mL of water in trial part 1.
|
Cocktail (R1)
n=13 Participants
Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.
|
|---|---|---|
|
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T3 vs. R1)
Digoxin
|
1.65 Nanomole/ litre (nmol/ L)
Standard Error 1.07
|
1.35 Nanomole/ litre (nmol/ L)
Standard Error 1.08
|
|
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T3 vs. R1)
Furosemide
|
97.69 Nanomole/ litre (nmol/ L)
Standard Error 1.08
|
93.23 Nanomole/ litre (nmol/ L)
Standard Error 1.08
|
|
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T3 vs. R1)
Metformin
|
316.83 Nanomole/ litre (nmol/ L)
Standard Error 1.07
|
258.33 Nanomole/ litre (nmol/ L)
Standard Error 1.08
|
|
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T3 vs. R1)
Rosuvastatin
|
13.21 Nanomole/ litre (nmol/ L)
Standard Error 1.15
|
11.30 Nanomole/ litre (nmol/ L)
Standard Error 1.15
|
PRIMARY outcome
Timeframe: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.Population: PKS
Cmax, maximum measured concentration of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) is presented. gMean presented here is an adjusted gMean and SE presented is a gSE.
Outcome measures
| Measure |
Verapamil + R1 (T1)
n=15 Participants
Participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to the R1 which is administered with 280 mL of water in trial part 1.
|
Cocktail (R1)
n=16 Participants
Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.
|
|---|---|---|
|
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T4 vs. R1)
Digoxin
|
1.13 Nanomole/ litre (nmol/ L)
Standard Error 1.07
|
1.30 Nanomole/ litre (nmol/ L)
Standard Error 1.07
|
|
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T4 vs. R1)
Furosemide
|
110.64 Nanomole/ litre (nmol/ L)
Standard Error 1.07
|
90.00 Nanomole/ litre (nmol/ L)
Standard Error 1.07
|
|
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T4 vs. R1)
Metformin
|
246.78 Nanomole/ litre (nmol/ L)
Standard Error 1.12
|
243.49 Nanomole/ litre (nmol/ L)
Standard Error 1.12
|
|
Maximum Measured Concentration of the Analytes: Digoxin, Furosemide, Metformin, and Rosuvastatin (Cmax) (T4 vs. R1)
Rosuvastatin
|
43.29 Nanomole/ litre (nmol/ L)
Standard Error 1.11
|
10.11 Nanomole/ litre (nmol/ L)
Standard Error 1.10
|
SECONDARY outcome
Timeframe: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.Population: PKS
AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.
Outcome measures
| Measure |
Verapamil + R1 (T1)
n=12 Participants
Participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to the R1 which is administered with 280 mL of water in trial part 1.
|
Cocktail (R1)
n=12 Participants
Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.
|
|---|---|---|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T1 vs. R1)
Furosemide
|
176.44 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.06
|
191.29 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.06
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T1 vs. R1)
Metformin
|
1147.23 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.05
|
1365.85 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.05
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T1 vs. R1)
Rosuvastatin
|
116.80 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.10
|
94.14 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.10
|
SECONDARY outcome
Timeframe: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.Population: PKS
AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.
Outcome measures
| Measure |
Verapamil + R1 (T1)
n=12 Participants
Participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to the R1 which is administered with 280 mL of water in trial part 1.
|
Cocktail (R1)
n=12 Participants
Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.
|
|---|---|---|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T2 vs. R1)
Furosemide
|
215.63 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.06
|
191.29 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.06
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T2 vs. R1)
Metformin
|
1482.76 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.05
|
1365.85 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.05
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T2 vs. R1)
Rosuvastatin
|
320.72 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.10
|
94.14 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.10
|
SECONDARY outcome
Timeframe: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.Population: PKS
AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.
Outcome measures
| Measure |
Verapamil + R1 (T1)
n=15 Participants
Participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to the R1 which is administered with 280 mL of water in trial part 1.
|
Cocktail (R1)
n=13 Participants
Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.
|
|---|---|---|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T3 vs. R1)
Furosemide
|
202.17 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.04
|
200.61 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.05
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T3 vs. R1)
Metformin
|
2023.33 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.06
|
1540.21 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.07
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T3 vs. R1)
Rosuvastatin
|
148.32 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.13
|
139.21 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.13
|
SECONDARY outcome
Timeframe: Samples were taken within 0:20 hh:mm prior to first study drug administration and at 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 11:00, 12:00, 24:00, 36:00, 47:00, 71:00 and 95:00 after drug administration.Population: PKS
AUC0-∞, area under the concentration-time curve of the analytes: digoxin, furosemide, metformin, and rosuvastatin (at cocktail doses) in plasma over the time interval from 0 extrapolated to infinity is presented. AUC0-∞ not displayed for Digoxin analyte as precision was considered non-sufficient. gMean presented here is an adjusted gMean and SE presented is a gSE.
Outcome measures
| Measure |
Verapamil + R1 (T1)
n=15 Participants
Participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to the R1 which is administered with 280 mL of water in trial part 1.
|
Cocktail (R1)
n=16 Participants
Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.
|
|---|---|---|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T4 vs. R1)
Furosemide
|
489.28 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.07
|
188.11 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.07
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T4 vs. R1)
Metformin
|
1346.62 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.08
|
1330.47 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.07
|
|
Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) (T4 vs. R1)
Rosuvastatin
|
244.94 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.10
|
113.78 Nanomole*hour/litre (nmol*h/L)
Standard Error 1.10
|
Adverse Events
Cocktail (R1)
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Verapamil + R1 (T1)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Rifampin + R1 (T2)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Metformin (R2)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Cimetidine + R1 (T3)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Cimetidine + R2 (T5)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Furosemide (R3)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Probenecid + R1 (T4)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Probenecid + R3 (T6)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cocktail (R1)
n=42 participants at risk
Participants were administered a single dose of Cocktail (reference treatment 1, R1) with 280 mL of water. R1 is a drug cocktail that contains a single dose of each, 0.25 mg Digoxin tablet, 1 mg Furosemide oral solution, 10 mg Metformin oral solution and 10 mg Rosuvastatin film-coated tablet in trial part 1, 2 and 3.
|
Verapamil + R1 (T1)
n=12 participants at risk
Participants were administered a single dose of 120 mg Verapamil orally with 240 mL of water at 1 h prior to the R1 which is administered with 280 mL of water in trial part 1.
|
Rifampin + R1 (T2)
n=12 participants at risk
Participants were administered a single dose of 600 mg Rifampin film-coated tablet orally with 280 mL of water together with R1 in trial part 1.
|
Metformin (R2)
n=16 participants at risk
Participants were administered a single therapeutic dose of 500 mg Metformin oral solution with 280 mL of water in trial part 2.
|
Cimetidine + R1 (T3)
n=17 participants at risk
Participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to R1 and at 4 h, 8 h, 12 h, 24 h (Day 2) and 36 h after R1 (Day 2). All doses of Cimetidine administered with 240 mL water and dose of R1 which is administered with 280 mL of water in trial part 2.
|
Cimetidine + R2 (T5)
n=17 participants at risk
Participants were administered 400 mg Cimetidine 1 tablet orally at 1 h prior to Metformin and at 4 h, 8 h, 12, 24 h (Day 2) and 36 h after therapeutic dose of 500 mg Metformin (Day 2) in trial part 2.
|
Furosemide (R3)
n=16 participants at risk
Participants were administered orally a single therapeutic dose of 40 mg Furosemide oral solution with 280 mL of water in trial part 3.
|
Probenecid + R1 (T4)
n=16 participants at risk
Participants were administered 2 tablets of 500 mg Probenecid (2\*500 mg) orally 13 h prior and again 1 h prior to the administration of R1 on day 1. All doses of Cimetidine administered with 240 mL water and dose of R1 which is administered with 280 mL of water in trial part 3.
|
Probenecid + R3 (T6)
n=15 participants at risk
Participants were administered 2 tablets of 500 mg Probenecid (2\*500 mg) administered orally 13 hours prior and again 1 h prior to the administration of Furosemide on Day 1 in trial part 3.
|
|---|---|---|---|---|---|---|---|---|---|
|
Cardiac disorders
Palpitations
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
5.9%
1/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
5.9%
1/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
5.9%
1/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
6.7%
1/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Eye disorders
Dry eye
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
6.2%
1/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
5.9%
1/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
5.9%
1/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
5.9%
1/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Gastrointestinal disorders
Diarrhoea
|
2.4%
1/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
6.2%
1/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
5.9%
1/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
5.9%
1/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
5.9%
1/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
5.9%
1/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Gastrointestinal disorders
Flatulence
|
2.4%
1/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
5.9%
1/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
6.2%
1/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
5.9%
1/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
11.8%
2/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
6.2%
1/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
6.7%
1/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Gastrointestinal disorders
Vomiting
|
2.4%
1/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
8.3%
1/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
5.9%
1/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
6.2%
1/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
General disorders
Chest pain
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
5.9%
1/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
General disorders
Influenza like illness
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
6.2%
1/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
General disorders
Malaise
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
6.7%
1/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
6.2%
1/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Infections and infestations
Nasopharyngitis
|
2.4%
1/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
8.3%
1/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
8.3%
1/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
6.2%
1/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
5.9%
1/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
6.2%
1/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
6.2%
1/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
6.2%
1/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
6.2%
1/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
6.2%
1/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Nervous system disorders
Headache
|
4.8%
2/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
8.3%
1/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
25.0%
4/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
17.6%
3/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
11.8%
2/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
12.5%
2/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
6.7%
1/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Nervous system disorders
Orthostatic intolerance
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
8.3%
1/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Psychiatric disorders
Conversion disorder
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
5.9%
1/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Psychiatric disorders
Restlessness
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
5.9%
1/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
5.9%
1/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
6.2%
1/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
5.9%
1/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/42 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/12 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/17 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
6.2%
1/16 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
0.00%
0/15 • From first drug administration until 7 days thereafter in each treatment period, up to 22 days for part 1 and 27 days for part 2 and 3.
Treatment emergent adverse events (AE's) are presented are on-treatment and treated set (TS) was used for AE reporting.
|
Additional Information
Boehringer Ingelheim, Call Centre
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER