Drug-drug Interaction Between Digoxin, Furosemide, Metformin, and Rosuvastatin

NCT02231931 | Completed Phase 1

• 2 other identifiers: 352.20822014-001940-40
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate the mutual interaction potential of digoxin, furosemide, metformin, and rosuvastatin when given alone or together as a cocktail, and to investigate the effect of high doses of metformin or furosemide on pharmacokinetics of the other cocktail compounds

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• Digoxin, Metformin, Rosuvastatin: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)

  up to 96 hours

• Furosemide: AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point)

  up to 36 hours

• Furosemide: Cmax (maximum measured concentration of the analyte in plasma)

  up to 36 hours

• Digoxin, Metformin, Rosuvastatin: Cmax (maximum measured concentration of the analyte in plasma)

  up to 96 hours

Secondary Outcomes (2)

• Furosemide: AUC0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)

  up to 36 hours

• Digoxin, Metformin, Rosuvastatin: AUC0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)

  up to 96 hours

Study Arms (7)

A (Reference 1) Digoxin

EXPERIMENTAL

1 tablet as single dose, fasted

Drug: Digoxin

B (Reference 2) Furosemide

EXPERIMENTAL

oral solution, as single dose, fasted

Drug: Furosemide

C (Reference 3) Metformin hydrochloride

EXPERIMENTAL

1 film-coated tablet as single dose, fasted

Drug: Metformin hydrochloride

D (Reference 4) Rosuvastatin

EXPERIMENTAL

1 film-coated tablet as single dose, fasted

Drug: Rosuvastatin

E (Test) 1

EXPERIMENTAL

Digoxin (1 tablet), Furosemide (0.5 mL oral solution), Metformin hydrochloride (1 film-coated tablet), Rosuvastatin (1 film-coated tablet), fasted

Drug: Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin

F (Test 2)

EXPERIMENTAL

Digoxin (1 tablet), Furosemide (0.5 mL oral solution), Metformin hydrochloride (2 film-coated tablets), Rosuvastatin (1 film-coated tablet), fasted

Drug: Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin

G (Test 3)

EXPERIMENTAL

Digoxin (1 tablet), Furosemide (2.0 mL oral solution), Metformin hydrochloride (1 film-coated tablet), Rosuvastatin (1 film-coated tablet), fasted

Drug: Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin

Interventions

Digoxin DRUG

single dose, fasted

A (Reference 1) Digoxin

Rosuvastatin DRUG

single dose, fasted

D (Reference 4) Rosuvastatin

Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin DRUG

fasted

E (Test) 1

Metformin hydrochloride DRUG

single dose, fasted

C (Reference 3) Metformin hydrochloride

Furosemide DRUG

single dose, fasted

B (Reference 2) Furosemide

Eligibility Criteria

• Age: 18 Years - 50 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, Pulse Rate), 12-lead Electrocardiogram, and clinical laboratory tests
• Age of 18 to 50 years (incl.)
• Body Mass Index 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 (GCP) and local legislation

You may not qualify if:

• Any finding in the medical examination (including Blood Pressure, Pulse Rate, or Electrocardiogram) 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
• Surgery of the gastrointestinal tract that could interfere with kinetics 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

352.2082.1 Boehringer Ingelheim Investigational Site

Biberach, Germany

Location

MeSH Terms

Interventions

Digoxin; Rosuvastatin Calcium; Furosemide; Metformin

Intervention Hierarchy (Ancestors)

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

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

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: September 3, 2014
• First Posted: September 4, 2014
• Study Start: September 1, 2014
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: October 24, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)