DDI (Effect of Metformin and Furosemide on Rosuvastatin PK)

NCT02574845 | Completed Phase 1 Results

• 2 other identifiers: 352.20942015-003052-46
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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)).

Conditions

Healthy

Outcome Measures

Primary Outcomes (2)

• Area Under the Curve of Rosuvastatin From 0 to the Last Quantifiable Data Point (AUC0-tz)

  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).

  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.

• Maximum Concentration of Rosuvastatin (Cmax)

  This outcome measure presents the maximum measured concentration of rosuvastatin in plasma (Cmax).

  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.

Secondary Outcomes (1)

• Area Under the Curve of Rosuvastatin From 0 Extrapolated to Infinity (AUC0-∞)

  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.

Study Arms (6)

R (Reference) Rosuvastatin

EXPERIMENTAL

1film-coated tablet as single dose, fasted

Drug: Rosuvastatin

T1 (Test 1) Rosuvastatin + Metformin HCl

EXPERIMENTAL

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

Drug: Rosuvastatin; Drug: Metformin HCl

T2 (Test 2) Rosuvastatin + Metformin HCl

EXPERIMENTAL

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

Drug: Rosuvastatin; Drug: Metformin HCl

T3 (Test 3) Rosuvastatin + Metformin HCl

EXPERIMENTAL

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

Drug: Rosuvastatin; Drug: Metformin HCl

T4 (Test 4) Rosuvastatin + Furosemide

EXPERIMENTAL

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

Drug: Rosuvastatin; Drug: Furosemide

T5 (Test 5) Rosuvastatin + Furosemide

EXPERIMENTAL

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

Drug: Rosuvastatin; Drug: Furosemide

Interventions

Rosuvastatin DRUG

R (Reference) Rosuvastatin; T1 (Test 1) Rosuvastatin + Metformin HCl; T2 (Test 2) Rosuvastatin + Metformin HCl; T3 (Test 3) Rosuvastatin + Metformin HCl; T4 (Test 4) Rosuvastatin + Furosemide; T5 (Test 5) Rosuvastatin + Furosemide

Metformin HCl DRUG

T1 (Test 1) Rosuvastatin + Metformin HCl; T2 (Test 2) Rosuvastatin + Metformin HCl; T3 (Test 3) Rosuvastatin + Metformin HCl

Furosemide DRUG

T4 (Test 4) Rosuvastatin + Furosemide; T5 (Test 5) Rosuvastatin + Furosemide

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• Age of 18 to 55 years (incl.)
• BMI of 18.5 to 29.9 kg/m2 (incl.)
• Signed and dated written informed consent prior to admission to the study in accordance with GCP and local legislation

You may not qualify if:

• Any finding in the medical examination (including BP, PR or ECG) 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 45 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
• Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics 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
• History of relevant orthostatic hypotension, fainting spells, or blackouts
• Chronic or relevant acute infections
• History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
• 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
• Within 10 days prior to administration of trial medication, use of drugs that might reasonably influence the results of the trial
• Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication
• Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
• Inability to refrain from smoking on specified trial days

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

Humanpharmakologisches Zentrum Biberach

Biberach, 88397, Germany

Location

Related Publications (1)

• Stopfer P, Giessmann T, Hohl K, Sharma A, Ishiguro N, Taub ME, Jungnik A, Gansser D, Ebner T, Muller 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.

  PMID: 28685495 DERIVED

MeSH Terms

Interventions

Rosuvastatin Calcium; Metformin; Furosemide

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Biguanides; Guanidines; Amidines; Sulfanilamides; Aniline Compounds; Amines

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2015
• First Posted: October 14, 2015
• Study Start: October 12, 2015
• Primary Completion: December 9, 2015
• Study Completion: December 14, 2015
• Last Updated: November 7, 2023
• Results First Posted: February 13, 2017

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)