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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01068730
First received: February 12, 2010
Last updated: June 4, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: metformin (Diabex)
Drug: metformin (Glucophage™)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: 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

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Metformin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • Metformin PK Parameter Observed Maximum Plasma Concentration (Cmax) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Participants With Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs) [ Time Frame: 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). ] [ Designated as safety issue: Yes ]
    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.

  • Participants With Electrocardiogram Abnormalities Considered Clinically Significant or Reported as an AE [ Time Frame: From study drug administration Day 1/Period 1 till study discharge. Duration of the study was approximately 45 days (including screening). ] [ Designated as safety issue: Yes ]
    Clinically significant was determined by the investigator. ECGs were recorded after participants had been supine for at least 5 minutes.

  • Participants With Abnormal Physical Findings [ Time Frame: From Day 1/Period 1 to study discharge or premature discontinuation. Duration of study was approximately 45 days (including screening). ] [ Designated as safety issue: Yes ]
    Physical findings that were considered abnormal by the investigator.

  • Participants With Abnormal Vital Sign Findings Reported as an AE [ Time Frame: From Day 1/Period 1 to study discharge or premature discontinuation. Duration of study was approximately 45 days (including screening). ] [ Designated as safety issue: Yes ]
    per investigator

  • Participants With Clinical Laboratory Findings Considered Clinically Significant or Reported as an AE: Hematology [ Time Frame: From study drug administration Day 1/Period 1 till study discharge. Duration of the study was approximately 45 days (including screening). ] [ Designated as safety issue: Yes ]
    Clinically significant was determined by the investigator.

  • Participants With Clinical Laboratory Findings Considered Clinically Significant or Reported as an AE: Serum Chemistry [ Time Frame: From study drug administration Day 1/Period 1 till study discharge. Duration of the study was approximately 45 days (including screening). ] [ Designated as safety issue: Yes ]
    Clinically significant was determined by the investigator.

  • Participants With Clinical Laboratory Findings Considered Clinically Significant or Reported as an AE: Urinalysis [ Time Frame: From study drug administration Day 1/Period 1 till study discharge. Duration of the study was approximately 45 days (including screening). ] [ Designated as safety issue: Yes ]
    Clinically significant was determined by the investigator.


Other Outcome Measures:
  • Metformin Pharmacokinetic (PK) Parameter Time to Achieve the Observed Maximum Plasma Concentration (Tmax) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Tmax is the time taken to reach the maximum observed plasma concentration.

  • Metformin Pharmacokinetic (PK) Parameter Terminal Half-life (T 1/2) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. T 1/2 is the time required for the concentration of the drug to reach half of its original value in plasma

  • Metformin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC[0-t] is the area under the plasma concentration-time curve from time zero to time of last measurable concentration.


Enrollment: 28
Study Start Date: February 2010
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Treatment A
500 mg metformin (Diabex): Single oral dose of 500 mg metformin (Diabex) tablet administered in the fed condition
Drug: metformin (Diabex)
Tablets, Oral, 500 mg, Once daily, single dose
Other Name: Diabex
Treatment B
500 mg metformin (Glucophage™): Single oral dose of 500 mg metformin (Glucophage™) tablet administered in the fed condition
Drug: metformin (Glucophage™)
Tablets, Oral, 500 mg, Once Daily, single dose
Other Name: Glucophage™
Treatment C
1000 mg metformin (Diabex): Single oral dose of 1000 mg metformin (Diabex) tablet administered in the fed condition
Drug: metformin (Diabex)
Tablets, Oral, 1000 mg, Once daily, single dose
Other Name: Diabex
Treatment D
1000 mg metformin (Glucophage™): A Single oral dose of 1000 mg metformin (Glucophage™) tablet administered in the fed condition
Drug: metformin (Glucophage™)
Tablets, Oral, 1000 mg, Once daily, single dose
Other Name: Glucophage™

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01068730

Locations
United States, Texas
PPD Development, LP
Austin, Texas, United States, 78744
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01068730     History of Changes
Other Study ID Numbers: CV181-120
Study First Received: February 12, 2010
Results First Received: January 20, 2012
Last Updated: June 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 20, 2014