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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01068730
• Other study ID #: CV181-120
• Status: Completed
• Phase: Phase 1
• First received: February 12, 2010
• Last updated: April 21, 2015
• Start date: February 2010
• Est. completion date: April 2010

Study information

• Verified date: March 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: April 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• metformin (Diabex)
Tablets, Oral, 500 mg, Once daily, single dose
• metformin (Glucophage™)
Tablets, Oral, 500 mg, Once Daily, single dose
• metformin (Glucophage™)
Tablets, Oral, 1000 mg, Once daily, single dose
• metformin (Diabex)
Tablets, Oral, 1000 mg, Once daily, single dose

Locations

Country	Name	City	State
United States	PPD Development, LP	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Metformin Pharmacokinetic (PK) Parameter Time to Achieve the Observed Maximum Plasma Concentration (Tmax)	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.	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	No
Other	Metformin Pharmacokinetic (PK) Parameter Terminal Half-life (T 1/2)	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	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	No
Other	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])	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.	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	No
Primary	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	No
Primary	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	No
Secondary	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).	Yes
Secondary	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).	Yes
Secondary	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).	Yes
Secondary	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).	Yes
Secondary	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).	Yes
Secondary	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).	Yes
Secondary	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).	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form