Trial Outcomes & Findings for Transporter Cocktail Mutual Interaction (NCT NCT02854527)

NCT ID: NCT02854527

Last Updated: 2023-11-07

Results Overview

Area under the concentration-time curve of digoxin in plasma over the time interval from 0 to the last quantifiable data point (AUC 0-tz). Standard error presented is actually geometric standard error. CI - confidence interval, gMean - geometric mean.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 30 participants
• Primary outcome timeframe: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00, 72:00 and 96:00 after drug administration
• Results posted on: 2023-11-07

Participant Flow

This is an open-label, randomised, single-dose, five-way, ten-sequence crossover study. Four drugs (Digoxin (R1), Furosemide, (R2), Metformin hydrochloride (R3), Rosuvastatin (R4)) were given as monotherapy and one as a combination of all four drugs together as test cocktail (T) in pre-defined sequences.

Participant milestones

Measure	ABECD (R1->R2->T->R3->R4) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (reference 1 or R1). Second, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Third, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Fourth, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Fifth, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	AEBDC (R1->T->R2->R4->R3) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (reference 1 or R1). Second, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Third, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Fourth, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Fifth, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	BACED (R2->R1->R3->T->R4) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (reference 2 or R2). Second, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Third, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Fourth, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Fifth, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	BCADE (R2->R3->R1->R4->T) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Second, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Third, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Fourth, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Fifth, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	CBDAE (R3->R2->R4->R1->T) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Second, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Third, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Fourth, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Fifth, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	CDBEA (R3->R4->R2->T->R1) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Second, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Third, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Fourth, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Fifth, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	DCEBA (R4->R3->T->R2->R1) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Second, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Third, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Fourth, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Fifth, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	DECAB (R4->T->R3->R1->R2) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Second, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Third, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Fourth, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Fifth, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	EADBC (T->R1->R4->R2->R3) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Second, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Third, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Fourth, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Fifth, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	EDACB (T->R4->R1->R3->R2) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Second, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Third, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Fourth, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Fifth, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.
Overall Study STARTED	3	3	3	3	3	3	3	3	3	3
Overall Study Received R1	3	3	3	2	2	3	3	3	3	3
Overall Study Received R2	3	3	3	3	3	3	3	3	3	3
Overall Study Received R3	3	3	3	2	3	3	3	3	3	3
Overall Study Received R4	3	3	3	2	3	3	3	3	3	3
Overall Study Received T	3	3	3	2	2	3	3	3	3	3
Overall Study COMPLETED	3	3	3	2	2	3	3	3	3	3
Overall Study NOT COMPLETED	0	0	0	1	1	0	0	0	0	0

Reasons for withdrawal

Measure	ABECD (R1->R2->T->R3->R4) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (reference 1 or R1). Second, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Third, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Fourth, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Fifth, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	AEBDC (R1->T->R2->R4->R3) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (reference 1 or R1). Second, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Third, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Fourth, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Fifth, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	BACED (R2->R1->R3->T->R4) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (reference 2 or R2). Second, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Third, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Fourth, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Fifth, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	BCADE (R2->R3->R1->R4->T) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Second, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Third, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Fourth, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Fifth, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	CBDAE (R3->R2->R4->R1->T) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Second, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Third, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Fourth, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Fifth, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	CDBEA (R3->R4->R2->T->R1) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Second, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Third, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Fourth, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Fifth, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	DCEBA (R4->R3->T->R2->R1) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Second, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Third, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Fourth, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Fifth, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	DECAB (R4->T->R3->R1->R2) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Second, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Third, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Fourth, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Fifth, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	EADBC (T->R1->R4->R2->R3) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Second, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Third, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Fourth, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Fifth, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	EDACB (T->R4->R1->R3->R2) Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Second, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Third, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Fourth, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Fifth, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.
Overall Study Adverse Event	0	0	0	0	1	0	0	0	0	0
Overall Study Lost to Follow-up	0	0	0	1	0	0	0	0	0	0

Baseline Characteristics

Transporter Cocktail Mutual Interaction

Baseline characteristics by cohort

Measure	ABECD (R1->R2->T->R3->R4) n=3 Participants Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (reference 1 or R1). Second, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Third, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Fourth, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Fifth, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	AEBDC (R1->T->R2->R4->R3) n=3 Participants Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (reference 1 or R1). Second, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Third, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Fourth, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Fifth, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	BACED (R2->R1->R3->T->R4) n=3 Participants Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (reference 2 or R2). Second, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Third, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Fourth, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Fifth, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	BCADE (R2->R3->R1->R4->T) n=3 Participants Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Second, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Third, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Fourth, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Fifth, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	CBDAE (R3->R2->R4->R1->T) n=3 Participants Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Second, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Third, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Fourth, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Fifth, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	CDBEA (R3->R4->R2->T->R1) n=3 Participants Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Second, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Third, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Fourth, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Fifth, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	DCEBA (R4->R3->T->R2->R1) n=3 Participants Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Second, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Third, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Fourth, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Fifth, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	DECAB (R4->T->R3->R1->R2) n=3 Participants Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Second, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Third, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Fourth, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Fifth, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	EADBC (T->R1->R4->R2->R3) n=3 Participants Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Second, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Third, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Fourth, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). Fifth, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	EDACB (T->R4->R1->R3->R2) n=3 Participants Subjects in this sequence were administered five different treatments in a sequence with a washout period of at least 10 days between each drug administration of adjacent treatment periods. First, they were administered a single dose of test cocktail (T) comprised of 0.25 mg of Digoxin, 0.1 mL (1 mg) of Furosemide, 0.1 mL (10 mg) of Metformin hydrochloride and 10 mg of Rosuvastatin. Second, they were administered a single dose of 10 mg film-coated tablet of Rosuvastatin (R4). Third, they were administered a single dose of 0.25 milligram (mg) tablet of Digoxin (R1). Fourth, they were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride (R3). Fifth, they were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide (R2). All drugs were administered orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Total n=30 Participants Total of all reporting groups
Age, Continuous	26.7 Years STANDARD_DEVIATION 2.5 • n=5 Participants	28.7 Years STANDARD_DEVIATION 8.1 • n=7 Participants	41.3 Years STANDARD_DEVIATION 15.8 • n=5 Participants	42.0 Years STANDARD_DEVIATION 5.3 • n=4 Participants	32.3 Years STANDARD_DEVIATION 9.0 • n=21 Participants	45.7 Years STANDARD_DEVIATION 7.2 • n=10 Participants	30.3 Years STANDARD_DEVIATION 6.4 • n=115 Participants	33.0 Years STANDARD_DEVIATION 9.6 • n=24 Participants	40.3 Years STANDARD_DEVIATION 7.5 • n=42 Participants	34.3 Years STANDARD_DEVIATION 7.2 • n=42 Participants	35.5 Years STANDARD_DEVIATION 9.4 • 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
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	3 Participants n=21 Participants	3 Participants n=10 Participants	3 Participants n=115 Participants	3 Participants n=24 Participants	3 Participants n=42 Participants	3 Participants n=42 Participants	30 Participants n=42 Participants

PRIMARY outcome

Timeframe: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00, 72:00 and 96:00 after drug administration

Population: The Pharmacokinetic (PK) analysis set (PKS) included all randomized subjects who were documented to have taken at least 1 dose of study drug and who have provided at least 1 primary or secondary PK endpoint that was not excluded from analysis due to non-evaluability or protocol violation relevant for the evaluation of the pharmacokinetics.

Area under the concentration-time curve of digoxin in plasma over the time interval from 0 to the last quantifiable data point (AUC 0-tz). Standard error presented is actually geometric standard error. CI - confidence interval, gMean - geometric mean.

Outcome measures

Measure	Test Cocktail (T) n=28 Participants Subjects were administered a single dose of test cocktail (T) comprised of 0.25 mg tablet of Digoxin, 0.1 mL (1 mg) oral solution of Furosemide, 0.1 mL (10 mg) oral solution of Metformin hydrochloride and 10 mg film-coated tablet of Rosuvastatin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Digoxin (R1) n=28 Participants Subjects were administered a single dose of 0.25 milligram (mg) tablet of Digoxin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.
Area Under the Curve of Digoxin From 0 to Last Quantifiable Data Point (AUC 0-tz)	11.549 nanomole hour per liter (nmol·h/L) Standard Error 1.053	11.981 nanomole hour per liter (nmol·h/L) Standard Error 1.053

PRIMARY outcome

Timeframe: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00, 72:00 and 96:00 after drug administration

Population: PKS

This outcome measure presents the maximum measured concentration of digoxin in plasma (Cmax). Standard error presented is actually geometric standard error.

Outcome measures

Measure	Test Cocktail (T) n=28 Participants Subjects were administered a single dose of test cocktail (T) comprised of 0.25 mg tablet of Digoxin, 0.1 mL (1 mg) oral solution of Furosemide, 0.1 mL (10 mg) oral solution of Metformin hydrochloride and 10 mg film-coated tablet of Rosuvastatin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Digoxin (R1) n=28 Participants Subjects were administered a single dose of 0.25 milligram (mg) tablet of Digoxin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.
Maximum Concentration of Digoxin (Cmax)	1.262 nanomole per liter (nmol/L) Standard Error 1.047	1.355 nanomole per liter (nmol/L) Standard Error 1.047

PRIMARY outcome

Timeframe: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00 and 24:00 after drug administration

Population: PKS

Area under the concentration-time curve of furosemide in plasma over the time interval from 0 to the last quantifiable data point (AUC 0-tz). Standard error presented is actually geometric standard error.

Outcome measures

Measure	Test Cocktail (T) n=28 Participants Subjects were administered a single dose of test cocktail (T) comprised of 0.25 mg tablet of Digoxin, 0.1 mL (1 mg) oral solution of Furosemide, 0.1 mL (10 mg) oral solution of Metformin hydrochloride and 10 mg film-coated tablet of Rosuvastatin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Digoxin (R1) n=30 Participants Subjects were administered a single dose of 0.25 milligram (mg) tablet of Digoxin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.
Area Under the Curve of Furosemide From 0 to Last Quantifiable Data Point (AUC 0-tz)	163.614 nmol·h/L Standard Error 1.039	159.434 nmol·h/L Standard Error 1.038

PRIMARY outcome

Timeframe: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00 and 24:00 after drug administration

Population: PKS

This outcome measure presents the maximum measured concentration of furosemide in plasma (Cmax). Standard error presented is actually geometric standard error.

Outcome measures

Measure	Test Cocktail (T) n=28 Participants Subjects were administered a single dose of test cocktail (T) comprised of 0.25 mg tablet of Digoxin, 0.1 mL (1 mg) oral solution of Furosemide, 0.1 mL (10 mg) oral solution of Metformin hydrochloride and 10 mg film-coated tablet of Rosuvastatin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Digoxin (R1) n=30 Participants Subjects were administered a single dose of 0.25 milligram (mg) tablet of Digoxin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.
Maximum Concentration of Furosemide (Cmax)	86.275 nmol/L Standard Error 1.046	82.990 nmol/L Standard Error 1.044

PRIMARY outcome

Timeframe: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00 and 48:00 after drug administration

Population: PKS

Area under the concentration-time curve of metformin in plasma over the time interval from 0 to the last quantifiable data point (AUC 0-tz). Standard error presented is actually geometric standard error.

Outcome measures

Measure	Test Cocktail (T) n=28 Participants Subjects were administered a single dose of test cocktail (T) comprised of 0.25 mg tablet of Digoxin, 0.1 mL (1 mg) oral solution of Furosemide, 0.1 mL (10 mg) oral solution of Metformin hydrochloride and 10 mg film-coated tablet of Rosuvastatin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Digoxin (R1) n=29 Participants Subjects were administered a single dose of 0.25 milligram (mg) tablet of Digoxin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.
Area Under the Curve of Metformin From 0 to Last Quantifiable Data Point (AUC 0-tz)	1283.797 nmol·h/L Standard Error 1.034	1316.790 nmol·h/L Standard Error 1.033

PRIMARY outcome

Timeframe: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00 and 48:00 after drug administration

Population: PKS

This outcome measure presents the maximum measured concentration of metformin in plasma (Cmax). Standard error presented is actually geometric standard error.

Outcome measures

Measure	Test Cocktail (T) n=28 Participants Subjects were administered a single dose of test cocktail (T) comprised of 0.25 mg tablet of Digoxin, 0.1 mL (1 mg) oral solution of Furosemide, 0.1 mL (10 mg) oral solution of Metformin hydrochloride and 10 mg film-coated tablet of Rosuvastatin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Digoxin (R1) n=29 Participants Subjects were administered a single dose of 0.25 milligram (mg) tablet of Digoxin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.
Maximum Concentration of Metformin (Cmax)	225.156 nmol/L Standard Error 1.045	229.171 nmol/L Standard Error 1.044

PRIMARY outcome

Timeframe: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00, 72:00 and 96:00 after drug administration

Population: PKS

Area under the concentration-time curve of rosuvastatin in plasma over the time interval from 0 to the last quantifiable data point (AUC 0-tz). Standard error presented is actually geometric standard error.

Outcome measures

Measure	Test Cocktail (T) n=28 Participants Subjects were administered a single dose of test cocktail (T) comprised of 0.25 mg tablet of Digoxin, 0.1 mL (1 mg) oral solution of Furosemide, 0.1 mL (10 mg) oral solution of Metformin hydrochloride and 10 mg film-coated tablet of Rosuvastatin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Digoxin (R1) n=29 Participants Subjects were administered a single dose of 0.25 milligram (mg) tablet of Digoxin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.
Area Under the Curve of Rosuvastatin From 0 to Last Quantifiable Data Point (AUC 0-tz)	81.925 nmol·h/L Standard Error 1.070	78.016 nmol·h/L Standard Error 1.069

PRIMARY outcome

Timeframe: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00, 72:00 and 96:00 after drug administration

Population: PKS

This outcome measure presents the maximum measured concentration of rosuvastatin in plasma (Cmax). Standard error presented is actually geometric standard error.

Outcome measures

Measure	Test Cocktail (T) n=28 Participants Subjects were administered a single dose of test cocktail (T) comprised of 0.25 mg tablet of Digoxin, 0.1 mL (1 mg) oral solution of Furosemide, 0.1 mL (10 mg) oral solution of Metformin hydrochloride and 10 mg film-coated tablet of Rosuvastatin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Digoxin (R1) n=29 Participants Subjects were administered a single dose of 0.25 milligram (mg) tablet of Digoxin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.
Maximum Concentration of Rosuvastatin (Cmax)	8.135 nmol/L Standard Error 1.074	7.801 nmol/L Standard Error 1.073

SECONDARY outcome

Timeframe: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00, 72:00 and 96:00 after drug administration

Population: PKS

Area under the concentration-time curve of digoxin in plasma over the time interval from 0 extrapolated to infinity (AUC 0-∞). Standard error presented is actually geometric standard error.

Outcome measures

Measure	Test Cocktail (T) n=27 Participants Subjects were administered a single dose of test cocktail (T) comprised of 0.25 mg tablet of Digoxin, 0.1 mL (1 mg) oral solution of Furosemide, 0.1 mL (10 mg) oral solution of Metformin hydrochloride and 10 mg film-coated tablet of Rosuvastatin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Digoxin (R1) n=28 Participants Subjects were administered a single dose of 0.25 milligram (mg) tablet of Digoxin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.
Area Under the Curve of Digoxin From 0 Extrapolated to Infinity (AUC 0-∞)	17.668 nmol·h/L Standard Error 1.039	18.303 nmol·h/L Standard Error 1.039

SECONDARY outcome

Timeframe: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00 and 24:00 after drug administration

Population: PKS

Area under the concentration-time curve of furosemide in plasma over the time interval from 0 extrapolated to infinity (AUC 0-∞). Standard error presented is actually geometric standard error.

Outcome measures

Measure	Test Cocktail (T) n=20 Participants Subjects were administered a single dose of test cocktail (T) comprised of 0.25 mg tablet of Digoxin, 0.1 mL (1 mg) oral solution of Furosemide, 0.1 mL (10 mg) oral solution of Metformin hydrochloride and 10 mg film-coated tablet of Rosuvastatin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Digoxin (R1) n=20 Participants Subjects were administered a single dose of 0.25 milligram (mg) tablet of Digoxin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.
Area Under the Curve of Furosemide From 0 Extrapolated to Infinity (AUC 0-∞)	156.382 nmol·h/L Standard Error 1.049	160.551 nmol·h/L Standard Error 1.052

SECONDARY outcome

Timeframe: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00 and 48:00 after drug administration

Population: PKS

Area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity (AUC 0-∞). Standard error presented is actually geometric standard error.

Outcome measures

Measure	Test Cocktail (T) n=28 Participants Subjects were administered a single dose of test cocktail (T) comprised of 0.25 mg tablet of Digoxin, 0.1 mL (1 mg) oral solution of Furosemide, 0.1 mL (10 mg) oral solution of Metformin hydrochloride and 10 mg film-coated tablet of Rosuvastatin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Digoxin (R1) n=29 Participants Subjects were administered a single dose of 0.25 milligram (mg) tablet of Digoxin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.
Area Under the Curve of Metformin From 0 Extrapolated to Infinity (AUC 0-∞)	1290.928 nmol·h/L Standard Error 1.033	1324.078 nmol·h/L Standard Error 1.033

SECONDARY outcome

Timeframe: Blood sampling at 2:00 (hour: minute) before drug administration, 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 10:00, 12:00, 24:00, 36:00, 48:00, 72:00 and 96:00 after drug administration

Population: PKS

Area under the concentration-time curve of rosuvastatin in plasma over the time interval from 0 extrapolated to infinity (AUC 0-∞). Standard error presented is actually geometric standard error.

Outcome measures

Measure	Test Cocktail (T) n=22 Participants Subjects were administered a single dose of test cocktail (T) comprised of 0.25 mg tablet of Digoxin, 0.1 mL (1 mg) oral solution of Furosemide, 0.1 mL (10 mg) oral solution of Metformin hydrochloride and 10 mg film-coated tablet of Rosuvastatin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Digoxin (R1) n=25 Participants Subjects were administered a single dose of 0.25 milligram (mg) tablet of Digoxin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.
Area Under the Curve of Rosuvastatin From 0 Extrapolated to Infinity (AUC 0-∞)	97.385 nmol·h/L Standard Error 1.072	90.479 nmol·h/L Standard Error 1.069

Adverse Events

Digoxin (R1)

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Furosemide (R2)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Metformin Hydrochloride (R3)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Rosuvastatin (R4)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Test Cocktail (T)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Measure	Digoxin (R1) n=28 participants at risk Subjects were administered a single dose of 0.25 milligram (mg) tablet of Digoxin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Furosemide (R2) n=30 participants at risk Subjects were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Metformin Hydrochloride (R3) n=29 participants at risk Subjects were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Rosuvastatin (R4) n=29 participants at risk Subjects were administered a single dose of 10 mg film-coated tablet of Rosuvastatin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Test Cocktail (T) n=28 participants at risk Subjects were administered a single dose of test cocktail (T) comprised of 0.25 mg tablet of Digoxin, 0.1 mL (1 mg) oral solution of Furosemide, 0.1 mL (10 mg) oral solution of Metformin hydrochloride and 10 mg film-coated tablet of Rosuvastatin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.
Injury, poisoning and procedural complications Exposure to toxic agent	3.6% 1/28 • Adverse events (AEs) occurring up to 192 hours after intake of trial drug administration in each treatment period were assigned to treatment. The treated set (TS) included all randomized subjects who were documented to have taken at least 1 dose of study drug.	0.00% 0/30 • Adverse events (AEs) occurring up to 192 hours after intake of trial drug administration in each treatment period were assigned to treatment. The treated set (TS) included all randomized subjects who were documented to have taken at least 1 dose of study drug.	0.00% 0/29 • Adverse events (AEs) occurring up to 192 hours after intake of trial drug administration in each treatment period were assigned to treatment. The treated set (TS) included all randomized subjects who were documented to have taken at least 1 dose of study drug.	0.00% 0/29 • Adverse events (AEs) occurring up to 192 hours after intake of trial drug administration in each treatment period were assigned to treatment. The treated set (TS) included all randomized subjects who were documented to have taken at least 1 dose of study drug.	0.00% 0/28 • Adverse events (AEs) occurring up to 192 hours after intake of trial drug administration in each treatment period were assigned to treatment. The treated set (TS) included all randomized subjects who were documented to have taken at least 1 dose of study drug.

Other adverse events

Measure	Digoxin (R1) n=28 participants at risk Subjects were administered a single dose of 0.25 milligram (mg) tablet of Digoxin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Furosemide (R2) n=30 participants at risk Subjects were administered a single dose of 0.1 milliliter (mL) or 1 mg oral solution of Furosemide orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Metformin Hydrochloride (R3) n=29 participants at risk Subjects were administered a single dose of 0.1 mL (10 mg) oral solution of Metformin hydrochloride orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Rosuvastatin (R4) n=29 participants at risk Subjects were administered a single dose of 10 mg film-coated tablet of Rosuvastatin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.	Test Cocktail (T) n=28 participants at risk Subjects were administered a single dose of test cocktail (T) comprised of 0.25 mg tablet of Digoxin, 0.1 mL (1 mg) oral solution of Furosemide, 0.1 mL (10 mg) oral solution of Metformin hydrochloride and 10 mg film-coated tablet of Rosuvastatin orally with 320 mL of non-sparkling drinking water after overnight fasting of 10 hours.
Nervous system disorders Headache	0.00% 0/28 • Adverse events (AEs) occurring up to 192 hours after intake of trial drug administration in each treatment period were assigned to treatment. The treated set (TS) included all randomized subjects who were documented to have taken at least 1 dose of study drug.	0.00% 0/30 • Adverse events (AEs) occurring up to 192 hours after intake of trial drug administration in each treatment period were assigned to treatment. The treated set (TS) included all randomized subjects who were documented to have taken at least 1 dose of study drug.	3.4% 1/29 • Adverse events (AEs) occurring up to 192 hours after intake of trial drug administration in each treatment period were assigned to treatment. The treated set (TS) included all randomized subjects who were documented to have taken at least 1 dose of study drug.	3.4% 1/29 • Adverse events (AEs) occurring up to 192 hours after intake of trial drug administration in each treatment period were assigned to treatment. The treated set (TS) included all randomized subjects who were documented to have taken at least 1 dose of study drug.	10.7% 3/28 • Adverse events (AEs) occurring up to 192 hours after intake of trial drug administration in each treatment period were assigned to treatment. The treated set (TS) included all randomized subjects who were documented to have taken at least 1 dose of study drug.

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place