Bioequivalence Study of 500 mg and 1000 mg Glucophage (Metformin) Tablets in Healthy Subjects

Study Overview
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Brief Summary
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To demonstrate the bioequivalence of 500 mg and 1000 mg Glucophage tablets manufactured by BMS relative to the respective strengths of 500 mg and 1000 mg Diabex tablets marketed in Australia by Alphapharm in the fed state

Official Title
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Bioequivalence Study of 500 mg and 1000 mg Glucophage (Metformin) Tablets Manufactured by Bristol-Myers Squibb Relative to 500 mg and 1000 mg Diabex (Metformin) Tablets Marketed in Australia by Alphapharm Administered to Healthy Subjects in the Fed State

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: metformin (Diabex)
* Drug: metformin (Glucophage™)
* Drug: metformin (Glucophage™)
* Drug: metformin (Diabex)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women ages 18 to 55 inclusive Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examination, electrocardiograms (ECGs), and clinical laboratory determinations Body Mass Index (BMI) of 18 to 32 kg/m², inclusive. BMI = weight (kg)/ [height (m)]² Exclusion Criteria: Any significant acute or chronic medical illness Current or recent (within 3 months) gastrointestinal disease Any major surgery within 4 weeks of study drug administration History of allergy or intolerance to metformin or other similar acting agents Prior exposure to metformin within 3 months of study drug administration Estimated creatinine clearance (Clcr) of < 80ml/min using the Cockcroft Gault formula

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment A<br>500 mg metformin (Diabex): Single oral dose of 500 mg metformin (Diabex) tablet administered in the fed condition | Drug: metformin (Diabex)<br>* Tablets, Oral, 500 mg, Once daily, single dose<br>* Other names: Diabex;|
| Other: Treatment B<br>500 mg metformin (Glucophage™): Single oral dose of 500 mg metformin (Glucophage™) tablet administered in the fed condition | Drug: metformin (Glucophage™)<br>* Tablets, Oral, 500 mg, Once Daily, single dose<br>* Other names: Glucophage™;|
| Other: Treatment C<br>1000 mg metformin (Diabex): Single oral dose of 1000 mg metformin (Diabex) tablet administered in the fed condition | Drug: metformin (Diabex)<br>* Tablets, Oral, 1000 mg, Once daily, single dose<br>* Other names: Diabex;|
| Other: Treatment D<br>1000 mg metformin (Glucophage™): A Single oral dose of 1000 mg metformin (Glucophage™) tablet administered in the fed condition | Drug: metformin (Glucophage™)<br>* Tablets, Oral, 1000 mg, Once daily, single dose<br>* Other names: Glucophage™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metformin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time. | Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing | 
| Metformin PK Parameter Observed Maximum Plasma Concentration (Cmax) | PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma. | Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants With Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs) | AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event. | AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening). | 
| Participants With Electrocardiogram Abnormalities Considered Clinically Significant or Reported as an AE | Clinically significant was determined by the investigator. ECGs were recorded after participants had been supine for at least 5 minutes. | From study drug administration Day 1/Period 1 till study discharge. Duration of the study was approximately 45 days (including screening). | 
| Participants With Abnormal Physical Findings | Physical findings that were considered abnormal by the investigator. | From Day 1/Period 1 to study discharge or premature discontinuation. Duration of study was approximately 45 days (including screening). | 
| Participants With Abnormal Vital Sign Findings Reported as an AE | per investigator | From Day 1/Period 1 to study discharge or premature discontinuation. Duration of study was approximately 45 days (including screening). | 
| Participants With Clinical Laboratory Findings Considered Clinically Significant or Reported as an AE: Hematology | Clinically significant was determined by the investigator. | From study drug administration Day 1/Period 1 till study discharge. Duration of the study was approximately 45 days (including screening). | 
| Participants With Clinical Laboratory Findings Considered Clinically Significant or Reported as an AE: Serum Chemistry | Clinically significant was determined by the investigator. | From study drug administration Day 1/Period 1 till study discharge. Duration of the study was approximately 45 days (including screening). | 
| Participants With Clinical Laboratory Findings Considered Clinically Significant or Reported as an AE: Urinalysis | Clinically significant was determined by the investigator. | From study drug administration Day 1/Period 1 till study discharge. Duration of the study was approximately 45 days (including screening). |