Healthy
Conditions
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)
Interventions
DRUGMerck Glucophage® high dose
Part I: Treatment A
DRUGBMS Glucophage® high dose
Part I: Treatment B
DRUGMerck Glucophage® low dose
Part II: Treatment C
DRUGBMS Glucophage® low dose
Part II: Treatment D
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| tmax (time from dosing to the maximum concentration of metformin in plasma) | up to 48 h after drug administration |
| λz (terminal rate constant in plasma) | up to 48 h after drug administration |
| t1/2 (terminal half-life of metformin in plasma) | 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 |
| CL/F (apparent clearance of metformin in the plasma after extravascular administration) | 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 |
| 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 |
| 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 12-lead ECG (electrocardiogram) | 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 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 |
| Number of patients with clinically relevant differences in physical examination | Baseline, day 1 prior, within 2-10 days following the last study 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 |
Outcome results
None listed