Transporter Cocktail Mutual Interaction

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Furosemide; Drug: Metformin; Drug: Digoxin; Drug: Metformin hydrochloride; Drug: Rosuvastatin

• Registration Number: NCT02854527
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

Main objective is to investigate mutual pharmacokinetic drug-drug interactions of digoxin, furosemide, metformin, and rosuvastatin when given all together as a cocktail

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-08-01
• Study First Submitted QC: 2016-08-01
• Study First Posted: 2016-08-03
• Study Start: 2016-08-22
• Primary Completion: 2016-11-11
• Study Completion: 2016-11-19
• Results First Submitted: 2017-10-26
• Results First Submitted QC: 2017-10-26
• Results First Posted: 2018-08-06
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-23
• Last Update Posted: 2023-11-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
R2 Furosemide	Furosemide	0.1 mL (1 mg) furosemide oral solution as single dose
R3 Metformin hydrochloride	Metformin	0.1 mL (10 mg) metformin oral solution as single dose
T (Test)	Metformin hydrochloride	1 tablet (0.25 mg) digoxin, 0.1 mL (1 mg) furosemide oral solution, 0.1 mL (10 mg) metformin oral solution, and 1 tablet (10 mg) rosuvastatin, all together as a single dose ('cocktail')
T (Test)	Rosuvastatin	1 tablet (0.25 mg) digoxin, 0.1 mL (1 mg) furosemide oral solution, 0.1 mL (10 mg) metformin oral solution, and 1 tablet (10 mg) rosuvastatin, all together as a single dose ('cocktail')
R1 (Reference 1) Digoxin	Digoxin	1 tablet (0.25 mg) digoxin as single dose
R4 Rosuvastatin	Rosuvastatin	1 tablet (10 mg) rosuvastatin as single dose
T (Test)	Digoxin	1 tablet (0.25 mg) digoxin, 0.1 mL (1 mg) furosemide oral solution, 0.1 mL (10 mg) metformin oral solution, and 1 tablet (10 mg) rosuvastatin, all together as a single dose ('cocktail')
T (Test)	Furosemide	1 tablet (0.25 mg) digoxin, 0.1 mL (1 mg) furosemide oral solution, 0.1 mL (10 mg) metformin oral solution, and 1 tablet (10 mg) rosuvastatin, all together as a single dose ('cocktail')

Primary Outcome Measures

Name	Time	Method
Area Under the Curve of Rosuvastatin From 0 to Last Quantifiable Data Point (AUC 0-tz)	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	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.
Maximum Concentration of Rosuvastatin (Cmax)	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	This outcome measure presents the maximum measured concentration of rosuvastatin in plasma (Cmax). Standard error presented is actually geometric standard error.
Area Under the Curve of Digoxin From 0 to Last Quantifiable Data Point (AUC 0-tz)	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	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.
Area Under the Curve of Furosemide From 0 to Last Quantifiable Data Point (AUC 0-tz)	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	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.
Maximum Concentration of Digoxin (Cmax)	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	This outcome measure presents the maximum measured concentration of digoxin in plasma (Cmax). Standard error presented is actually geometric standard error.
Maximum Concentration of Furosemide (Cmax)	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	This outcome measure presents the maximum measured concentration of furosemide in plasma (Cmax). Standard error presented is actually geometric standard error.
Area Under the Curve of Metformin From 0 to Last Quantifiable Data Point (AUC 0-tz)	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	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.
Maximum Concentration of Metformin (Cmax)	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	This outcome measure presents the maximum measured concentration of metformin in plasma (Cmax). Standard error presented is actually geometric standard error.

Secondary Outcome Measures

Name	Time	Method
Area Under the Curve of Rosuvastatin From 0 Extrapolated to Infinity (AUC 0-∞)	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	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.
Area Under the Curve of Furosemide From 0 Extrapolated to Infinity (AUC 0-∞)	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	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.
Area Under the Curve of Digoxin From 0 Extrapolated to Infinity (AUC 0-∞)	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	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.
Area Under the Curve of Metformin From 0 Extrapolated to Infinity (AUC 0-∞)	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	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.

Trial Locations

Locations (1)

Humanpharmakologisches Zentrum Biberach; 🇩🇪 Biberach, Germany