DDI (Effect of Metformin and Furosemide on Rosuvastatin PK)

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Furosemide; Drug: Metformin HCl; Drug: Rosuvastatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT02574845

352.2094

2015-003052-46 (EudraCT Number)

Details and patient eligibility

About

The primary objective of this trial is to investigate the relative bioavailability of rosuvastatin when given alone (Reference treatment, R) compared to when given together with one of the three different doses of metformin (10 mg, Test treatment 1 (T1); 50 mg (T2); 500 mg (T3)) or one of the two doses of furosemide (1 mg (T4); 5 mg (T5)).

Enrollment: 18 patients

Sex: Male

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Healthy male subjects according to the investigators assessment, based on a complete medical history including a physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests
2. Age of 18 to 55 years (incl.)
3. BMI 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 GCP and local legislation

Exclusion criteria

1. Any finding in the medical examination (including BP, PR or ECG) 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 45 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. Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics 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

8. History of relevant orthostatic hypotension, fainting spells, or blackouts

9. Chronic or relevant acute infections

10. History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)

11. Intake of drugs with a long half-life (more than 24 h) within 30 days or less than 10 half-lives of the respective drug prior to administration of trial medication

12. Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial

13. Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication

14. Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)

15. Inability to refrain from smoking on specified trial days

16. Alcohol abuse (consumption of more than 30 g per day)

17. Drug abuse or positive drug screening

18. Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial

19. Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial

20. Inability to comply with dietary regimen of trial site

21. Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study

    In addition, the following trial-specific exclusion criteria apply:

22. Myopathy

23. Hereditary galactose or fructose intolerance, lactase deficiency, or glucose-galactose malabsorption

24. Allergy or hypersensitivity against sulfonamides

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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18 participants in 6 patient groups

R (Reference) Rosuvastatin

Experimental group

Description:

1film-coated tablet as single dose, fasted

Treatment:

Drug: Rosuvastatin

T1 (Test 1) Rosuvastatin + Metformin HCl

Experimental group

Description:

Rosuvastatin: 1 film-coated tablet as single dose (10 mg), fasted / Metformin HCl (10 mg) as single dose, fasted

Treatment:

Drug: Metformin HCl

Drug: Rosuvastatin

T2 (Test 2) Rosuvastatin + Metformin HCl

Experimental group

Description:

Rosuvastatin: 1 film-coated tablet as single dose (10 mg), fasted / Metformin HCl (50 mg) as single dose, fasted

Treatment:

Drug: Metformin HCl

Drug: Rosuvastatin

T3 (Test 3) Rosuvastatin + Metformin HCl

Experimental group

Description:

Rosuvastatin: 1 film-coated tablet as single dose (10 mg), fasted / Metformin HCl (500 mg) as single dose, fasted

Treatment:

Drug: Metformin HCl

Drug: Rosuvastatin

T4 (Test 4) Rosuvastatin + Furosemide

Experimental group

Description:

Rosuvastatin: 1 film-coated tablet as single dose (10 mg), fasted / Furosemide: (1 mg) as single dose, fasted

Treatment:

Drug: Furosemide

Drug: Rosuvastatin

T5 (Test 5) Rosuvastatin + Furosemide

Experimental group

Description:

Rosuvastatin: 1 film-coated tablet as single dose (10 mg), fasted / Furosemide: (5 mg) as single dose, fasted

Treatment:

Drug: Furosemide

Drug: Rosuvastatin