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

Sponsor

Boehringer Ingelheim (Industry)

Overall Status

Completed

CT.gov ID

NCT02231931

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Digoxin Drug: Rosuvastatin Drug: Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin Drug: Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin Drug: Metformin hydrochloride Drug: Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin Drug: Furosemide	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

24 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2014

Actual Primary Completion Date :

Jan 1, 2015

Actual Study Completion Date :

Jan 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion criteria:

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

Exclusion criteria:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	352.2082.1 Boehringer Ingelheim Investigational Site	Biberach		Germany

Sponsors and Collaborators

Boehringer Ingelheim

Investigators

Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Boehringer Ingelheim

ClinicalTrials.gov Identifier:

NCT02231931

Other Study ID Numbers:

352.2082
2014-001940-40

First Posted:

Sep 4, 2014

Last Update Posted:

Jan 26, 2015

Last Verified:

Jan 1, 2015

Additional relevant MeSH terms:

Study Results

No Results Posted as of Jan 26, 2015