Clinical trial NCT02183571: Bioequivalence Study of Two Strengths of Two Different Metformin Tablets Administered to Healthy Male and Female Subjects
Official title: Bioequivalence of Two Strengths (1000 mg and 500 mg) of Two Different Metformin Tablets Administered to Healthy Male and Female Subjects in an Open, Randomised, Single-dose, Two-period Crossover, Phase I Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-07-08
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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)


Eligibility criteria: 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

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