Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

DDI (Effect of Metformin and Furosemide on Rosuvastatin PK)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
Information provided by (Responsible Party):
Boehringer Ingelheim

Tracking Information
First Submitted Date  ICMJE October 12, 2015
First Posted Date  ICMJE October 14, 2015
Results First Submitted Date  ICMJE December 8, 2016
Results First Posted Date  ICMJE February 13, 2017
Last Update Posted Date February 13, 2017
Study Start Date  ICMJE October 2015
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 20, 2016)
  • 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).
  • 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).
Original Primary Outcome Measures  ICMJE
 (submitted: October 12, 2015)
  • Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point [ Time Frame: up to 48 hours ]
  • Maximum measured concentration of the analyte in plasma [ Time Frame: up to 48 hours ]
Change History Complete list of historical versions of study NCT02574845 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2016)
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-∞).
Original Secondary Outcome Measures  ICMJE
 (submitted: October 12, 2015)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity [ Time Frame: up to 48 hours ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE DDI (Effect of Metformin and Furosemide on Rosuvastatin PK)
Official Title  ICMJE 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)
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)).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Healthy
Intervention  ICMJE
  • Drug: Rosuvastatin
  • Drug: Metformin HCl
  • Drug: Furosemide
Study Arms  ICMJE
  • Experimental: R (Reference) Rosuvastatin
    1film-coated tablet as single dose, fasted
    Intervention: 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
    Interventions:
    • 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
    Interventions:
    • 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
    Interventions:
    • 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
    Interventions:
    • 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
    Interventions:
    • Drug: Rosuvastatin
    • Drug: Furosemide
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 12, 2015)
18
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 2015
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02574845
Other Study ID Numbers  ICMJE 352.2094
2015-003052-46 ( EudraCT Number: EudraCT )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Boehringer Ingelheim
Study Sponsor  ICMJE Boehringer Ingelheim
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
PRS Account Boehringer Ingelheim
Verification Date December 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP