DDI (Effect of Metformin and Furosemide on Rosuvastatin PK)

• ClinicalTrials.gov Identifier: NCT02574845
• Recruitment Status: Completed
• First Posted: October 14, 2015
• Results First Posted: February 13, 2017
• Last Update Posted: February 13, 2017
• Sponsor: Boehringer Ingelheim
• Information provided by (Responsible Party): Boehringer Ingelheim

Study Description

Brief Summary:

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)).

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Rosuvastatin; Drug: Metformin HCl; Drug: Furosemide	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Effect of Different Doses of Metformin or Furosemide on Rosuvastatin Pharmacokinetics Following Oral Administration in Healthy Male Subjects (an Open-label, Randomised, Single-dose, Six-way Crossover Study)
• Study Start Date: October 2015
• Actual Primary Completion Date: December 2015
• Actual Study Completion Date: December 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: R (Reference) Rosuvastatin; 1film-coated tablet as single dose, fasted	Drug: Rosuvastatin
Experimental: T1 (Test 1) Rosuvastatin + Metformin HCl; Rosuvastatin: 1 film-coated tablet as single dose (10 mg), fasted / Metformin HCl (10 mg) as single dose, fasted	Drug: Rosuvastatin; Drug: Metformin HCl
Experimental: T2 (Test 2) Rosuvastatin + Metformin HCl; Rosuvastatin: 1 film-coated tablet as single dose (10 mg), fasted / Metformin HCl (50 mg) as single dose, fasted	Drug: Rosuvastatin; Drug: Metformin HCl
Experimental: T3 (Test 3) Rosuvastatin + Metformin HCl; Rosuvastatin: 1 film-coated tablet as single dose (10 mg), fasted / Metformin HCl (500 mg) as single dose, fasted	Drug: Rosuvastatin; Drug: Metformin HCl
Experimental: T4 (Test 4) Rosuvastatin + Furosemide; Rosuvastatin: 1 film-coated tablet as single dose (10 mg), fasted / Furosemide: (1 mg) as single dose, fasted	Drug: Rosuvastatin; Drug: Furosemide
Experimental: T5 (Test 5) Rosuvastatin + Furosemide; Rosuvastatin: 1 film-coated tablet as single dose (10 mg), fasted / Furosemide: (5 mg) as single dose, fasted	Drug: Rosuvastatin; Drug: Furosemide

Outcome Measures

Primary Outcome Measures :

1. Area Under the Curve of Rosuvastatin From 0 to the Last Quantifiable Data Point (AUC0-tz) [ Time Frame: Blood sampling within 3 hours (h) prior to the study drug administration, at the time of administration (0:00) and 30 minutes, 1h, 1:30h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11h, 12h, 24h, 34h, and 48h thereafter. ]
   This outcome measure presents the area under the concentration-time curve of rosuvastatin in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz).
2. Maximum Concentration of Rosuvastatin (Cmax) [ Time Frame: Blood sampling within 3 hours (h) prior to the study drug administration, at the time of administration (0:00) and 30 minutes, 1h, 1:30h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11h, 12h, 24h, 34h, and 48h thereafter. ]
   This outcome measure presents the maximum measured concentration of rosuvastatin in plasma (Cmax).

Secondary Outcome Measures :

1. Area Under the Curve of Rosuvastatin From 0 Extrapolated to Infinity (AUC0-∞) [ Time Frame: Blood sampling within 3 hours (h) prior to the study drug administration, at the time of administration (0:00) and 30 minutes, 1h, 1:30h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 11h, 12h, 24h, 34h, and 48h thereafter. ]
   This outcome measure presents area under the concentration-time curve of rosuvastatin in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

Germany

Boehringer Ingelheim Investigational Site

Biberach, Germany

Sponsors and Collaborators

Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim; Boehringer Ingelheim

More Information

Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Stopfer P, Giessmann T, Hohl K, Sharma A, Ishiguro N, Taub ME, Jungnik A, Gansser D, Ebner T, Müller F. Effects of Metformin and Furosemide on Rosuvastatin Pharmacokinetics in Healthy Volunteers: Implications for Their Use as Probe Drugs in a Transporter Cocktail. Eur J Drug Metab Pharmacokinet. 2018 Feb;43(1):69-80. doi: 10.1007/s13318-017-0427-9.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT02574845
• Other Study ID Numbers: 352.2094; 2015-003052-46 ( EudraCT Number: EudraCT )
• First Posted: October 14, 2015
• Results First Posted: February 13, 2017
• Last Update Posted: February 13, 2017
• Last Verified: December 2016

Additional relevant MeSH terms:

Metformin; Furosemide; Rosuvastatin Calcium; Hypoglycemic Agents; Physiological Effects of Drugs; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors; Diuretics; Natriuretic Agents; Sodium Potassium Chloride Symporter Inhibitors; Membrane Transport Modulators