Bioequivalence Study of Two Strengths of Two Different Metformin Tablets Administered to Healthy Male and Female Subjects

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Merck Glucophage® high dose; Drug: Merck Glucophage® low dose; Drug: BMS Glucophage® high dose; Drug: BMS Glucophage® low dose

• Registration Number: NCT02183571
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

Investigation of bioequivalence of BMS Glucophage® tablets and Merck Glucophage® tablets in the strengths of 1000 mg (part I) and 500 mg (part II)

Detailed Description

Not available

Study Timeline

• Study Start: 2009-02
• Primary Completion: 2009-04
• Status Verified: 2014-07
• Study First Submitted: 2014-07-07
• Study First Submitted QC: 2014-07-07
• Last Update Submitted: 2014-07-07
• Study First Posted: 2014-07-08
• Last Update Posted: 2014-07-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 56

Inclusion Criteria

• Healthy males and females according to the following criteria: a complete medical history, including the physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead electrocardiogram (ECG) and clinical laboratory tests
• Age ≥ 18 and Age ≤ 55 years
• BMI ≥ 18.5 and ≤ 29.9 kg/m2 (Body Mass Index)
• Signed and dated written informed consent prior to admission to the study in accordance with Good clinical practice (GCP) and the local legislation

Exclusion Criteria

• Any finding of the medical examination deviating from normal and of clinical relevance. Repeated measurement of a systolic blood pressure greater than 140 mm Hg or diastolic blood pressure greater than 90 mm Hg
• Any evidence of a clinically relevant concomitant disease
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Surgery of the gastrointestinal tract (except appendectomy)
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• History of relevant orthostatic hypotension, fainting spells or blackouts
• Chronic or relevant acute infections
• History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
• Intake of drugs within one month or less than 10 half-lives of the respective drug prior to first study drug administration except if a relevant interaction can be ruled out
• Participation in another trial with an investigational drug within two months prior to first study drug administration
• Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day)
• Inability to refrain from smoking on trial days
• Alcohol abuse (average consumption of more than 20 g/day in females and 30 g/day in males)
• Drug abuse
• Blood donation (more than 100 mL within four weeks prior to the start of study)
• Any laboratory value outside the reference range that is of clinical relevance
• Inability to comply with dietary regimen of trial site
• A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 ms)
• A history of additional risk factors for Torsade de pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)

For female subjects:

• Positive pregnancy test, pregnancy or planning to become pregnant during the study or within 1 month after study completion
• No adequate contraception during the study and until 1 month after study completion, i.e. not any of the following: implants, injectables, combined oral contraceptives, IUD (intrauterine device), sexual abstinence for at least 1 month prior to enrolment, vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or surgical sterilisation (including hysterectomy). Females, who do not have a vasectomised partner, are not sexually abstinent or surgically sterile will be asked to use an additional barrier method (e.g. condom, diaphragm with spermicide)
• Lactation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Glucophage® high dose	Merck Glucophage® high dose	Part I: Treatment A + B
Glucophage® high dose	BMS Glucophage® high dose	Part I: Treatment A + B
Glucophage® low dose	Merck Glucophage® low dose	Part II: Treatment C+ D
Glucophage® low dose	BMS Glucophage® low dose	Part II: Treatment C+ D

Primary Outcome Measures

Name	Time	Method
AUC0-infinity (area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity)	up to 48 h after drug administration
Cmax (maximum measured concentration of metformin in plasma)	up to 48 hours after drug administration

Secondary Outcome Measures

Name	Time	Method
AUC0-tz (area under the concentration-time curve of metformin in plasma over the time interval from 0 to the time of the last quantifiable data point)	up to 48 h after drug administration
CL/F (apparent clearance of metformin in the plasma after extravascular administration)	up to 48 h after drug administration
t1/2 (terminal half-life of metformin in plasma)	up to 48 h after drug administration
Number of patients with clinically relevant differences in physical examination	Baseline, day 1 prior, within 2-10 days following the last study drug administration
λz (terminal rate constant in plasma)	up to 48 h after drug administration
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)	up to 48 h after drug administration
Number of patients with clinically relevant differences in vital signs (BP (Blood pressure), PR (Pulse rate))	Baseline, day 1 prior, within 2-10 days following the last study drug administration
Number of patients with clinically relevant differences in clinical laboratory tests	Baseline, day 1 prior, within 2-10 days following the last study drug administration
Number of patients with clinically relevant differences in 12-lead ECG (electrocardiogram)	Baseline, day 1 prior, within 2-10 days following the last study drug administration
tmax (time from dosing to the maximum concentration of metformin in plasma)	up to 48 h after drug administration
AUCt1-t2 (Area under the concentration time curve of metformin in plasma over the time interval t1 to t2)	up to 48 h after drug administration
MRTpo (mean residence time of metformin in the body after po administration)	up to 48 h after drug administration
Number of patients with adverse events	within 2- 10 after last study drug administration
Assessment of tolerability by investigator on a 4 point scale	within 2- 10 after last study drug administration