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

Relative Bioavailability of a Single Oral Dose of Digoxin, Furosemide, Metformin, and Rosuvastatin Given Alone and All Together as a Cocktail, and Investigation of the Effect of Increased Doses of Metformin or Furosemide on Relative Bioavailability of the Other Cocktail Compounds in Healthy Male Subjects

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Digoxin; Drug: Furosemide; Drug: Metformin hydrochloride; Drug: Rosuvastatin; Drug: Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Biberach, Germany
    • 352.2082.1 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria:

1. 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
2. Age of 18 to 50 years (incl.)
3. Body Mass Index of 18.5 to 29.9 kg/m2 (incl.)
4. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation

Exclusion criteria:

1. 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
2. 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
3. Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
4. Any evidence of a concomitant disease judged as clinically relevant by the investigator
5. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, or hormonal disorders
6. Surgery of the gastrointestinal tract that could interfere with kinetics of the trial medication (except appendectomy and simple hernia repair)
7. Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A (Reference 1) Digoxin; 1 tablet as single dose, fasted	Drug: Digoxin; single dose, fasted
Experimental: B (Reference 2) Furosemide; oral solution, as single dose, fasted	Drug: Furosemide; single dose, fasted
Experimental: C (Reference 3) Metformin hydrochloride; 1 film-coated tablet as single dose, fasted	Drug: Metformin hydrochloride; single dose, fasted
Experimental: D (Reference 4) Rosuvastatin; 1 film-coated tablet as single dose, fasted	Drug: Rosuvastatin; single dose, fasted
Experimental: E (Test) 1; 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; fasted
Experimental: F (Test 2); 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; fasted
Experimental: G (Test 3); 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; fasted

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Investigators: Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2014
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: September 3, 2014
• First Submitted That Met QC Criteria: September 3, 2014
• First Posted (Estimated): September 4, 2014

Study Record Updates

• Last Update Posted (Actual): October 24, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Enzyme Inhibitors; Antimetabolites; Protective Agents; Natriuretic Agents; Cardiotonic Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Digoxin; Rosuvastatin Calcium; Metformin; Furosemide
• Other Study ID Numbers: 352.2082; 2014-001940-40 (EudraCT Number: EudraCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization).

For more details refer to: https://www.mystudywindow.com/msw/datatransparency