Transporter Cocktail Mutual Interaction

NCT02854527 | Completed Phase 1 Results

• 2 other identifiers: 352.20962016-001893-14
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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

Conditions

Healthy

Outcome Measures

Primary Outcomes (8)

• Area Under the Curve of Digoxin From 0 to Last Quantifiable Data Point (AUC 0-tz)

  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.

  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

• Maximum Concentration of Digoxin (Cmax)

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

  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 Curve of Furosemide From 0 to Last Quantifiable Data Point (AUC 0-tz)

  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.

  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

• Maximum Concentration of Furosemide (Cmax)

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

  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 Curve of Metformin From 0 to Last Quantifiable Data Point (AUC 0-tz)

  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.

  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

• Maximum Concentration of Metformin (Cmax)

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

  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 Curve of Rosuvastatin From 0 to Last Quantifiable Data Point (AUC 0-tz)

  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.

  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

• Maximum Concentration of Rosuvastatin (Cmax)

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

  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

Secondary Outcomes (4)

• 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 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 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 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

Study Arms (5)

R1 (Reference 1) Digoxin

EXPERIMENTAL

1 tablet (0.25 mg) digoxin as single dose

Drug: Digoxin

R2 Furosemide

EXPERIMENTAL

0.1 mL (1 mg) furosemide oral solution as single dose

Drug: Furosemide

R3 Metformin hydrochloride

EXPERIMENTAL

0.1 mL (10 mg) metformin oral solution as single dose

Drug: Metformin

R4 Rosuvastatin

EXPERIMENTAL

1 tablet (10 mg) rosuvastatin as single dose

Drug: Rosuvastatin

T (Test)

EXPERIMENTAL

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')

Drug: Digoxin; Drug: Furosemide; Drug: Metformin hydrochloride; Drug: Rosuvastatin

Interventions

Digoxin DRUG

single dose

R1 (Reference 1) Digoxin

Furosemide DRUG

single dose

R2 Furosemide

Metformin DRUG

single dose

R3 Metformin hydrochloride

Rosuvastatin DRUG

single dose

R4 Rosuvastatin

Metformin hydrochloride DRUG

10 mg metformin hydrochloride as single dose (all 4 drugs given together as a cocktail at the same time point)

T (Test)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male subjects according to the investigator's assessment, based on a complete medical history including a physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests
• Age of 18 to 55 years (incl.)
• Body Mass Index (BMI) of 18.5 to 29.9 kg/m2 (incl.)
• Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and local legislation

You may not qualify if:

• Any finding in the medical examination (including BP, PR or ECG) is deviating from normal and judged as clinically relevant by the investigator
• Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 bpm
• Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
• Any evidence of a concomitant disease judged as clinically relevant by the investigator
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and simple hernia repair)
• Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
• History of relevant orthostatic hypotension, fainting spells, or blackouts
• Chronic or relevant acute infections
• History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients, sulphonamides, or cardiac glycosides)
• Use of drugs within 30 days prior to administration of trial medication that might reasonably influence the results of the trial (incl. QT/QTc interval prolongation (corrected Q-T interval)
• Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug
• Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
• Inability to refrain from smoking on specified trial days
• Alcohol abuse (consumption of more than 30 g per day)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

Humanpharmakologisches Zentrum Biberach

Biberach, 88397, Germany

Location

MeSH Terms

Interventions

Digoxin; Furosemide; Metformin; Rosuvastatin Calcium

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds; Biguanides; Guanidines; Amidines; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2016
• First Posted: August 3, 2016
• Study Start: August 22, 2016
• Primary Completion: November 11, 2016
• Study Completion: November 19, 2016
• Last Updated: November 7, 2023
• Results First Posted: August 6, 2018

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)