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

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT02231931

352.2082

2014-001940-40 (EudraCT Number)

Details and patient eligibility

About

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

Enrollment: 24 patients

Sex: Male

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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24 participants in 7 patient groups

A (Reference 1) Digoxin

Experimental group

Description:

1 tablet as single dose, fasted

Treatment:

Drug: Digoxin

B (Reference 2) Furosemide

Experimental group

Description:

oral solution, as single dose, fasted

Treatment:

Drug: Furosemide

C (Reference 3) Metformin hydrochloride

Experimental group

Description:

1 film-coated tablet as single dose, fasted

Treatment:

Drug: Metformin hydrochloride

D (Reference 4) Rosuvastatin

Experimental group

Description:

1 film-coated tablet as single dose, fasted

Treatment:

Drug: Rosuvastatin

E (Test) 1

Experimental group

Description:

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

Treatment:

Drug: Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin

Drug: Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin

Drug: Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin

F (Test 2)

Experimental group

Description:

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

Treatment:

Drug: Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin

Drug: Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin

Drug: Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin

G (Test 3)

Experimental group

Description:

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

Treatment:

Drug: Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin

Drug: Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin

Drug: Digoxin, Furosemide, Metformin hydrochloride, Rosuvastatin