Glyburide/Metformin 5 mg/500 mg Film-Coated Tablets, Fasting

Official Title: “Randomized, 2-Way Crossover, Bioequivalence Study of Glyburide/Metformin 5 mg/500 mg Film-Coated Tablets and Glucovance® 5 mg/500 mg Film-Coated Tablets in Healthy Subjects Under Fasting Conditions”

The objective of this study is to compare the rate and extent of absorption of Glyburide/Metformin 5 mg/500 mg film-coated tablets (test) versus Glucovance® (reference) administered as 1 x 5 mg/500 mg film-coated tablet under fasting conditions.

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Intervention(s) in this Clinical Trial

• Drug: Glyburide/Metformin 5 mg/500 mg Tablets
  • 1 x 5 mg/500 mg, single-dose fasting
• Drug: Glucovance® 5 mg/500 mg Tablets
  • 1 x 5 mg/500 mg, single-dose fasting

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Glyburide Metformin
  • Glyburide Metformin 5/500 mg Film-Coated Tablet (test) dosed in first period followed by Glucovance® 5/500 mg Tablet (reference) dosed in second period
• Active Comparator: Glucovance®
  • Glucovance® 5/500 mg Tablet (reference) dosed in first period followed by Glyburide Metformin 5/500 mg Film-Coated Tablet (test) dosed in second period

Primary Measures

• Cmax (Maximum Observed Concentration) - Glyburide
  • Time Frame: Blood samples collected over 36 hour period
    Safety Issue?: No
• AUC0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)] - Glyburide
  • Time Frame: Blood samples collected over 36 hour period
    Safety Issue?: No
• AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant)] - Glyburide
  • Time Frame: Blood samples collected over 36 hour period
    Safety Issue?: No
• Cmax (Maximum Observed Concentration) - Metformin
  • Time Frame: Blood samples collected over 36 hour period
    Safety Issue?: No
• AUC0-inf [Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated)] - Metformin
  • Time Frame: Blood samples collected over 36 hour period
    Safety Issue?: No
• AUC0-t [Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration (Per Participant) - Metformin
  • Time Frame: Blood samples collected over 36 hour period
    Safety Issue?: No

Inclusion Criteria:

• Subjects will be females and/or males, non-smokers, 18 years of age and older.

Exclusion Criteria:

• Clinically significant illnesses within 4 weeks of the administration of study medication.
• Clinically significant surgery within 4 weeks prior to the administration of the study medication.
• Any clinically significant abnormality found during medical screening.
• Any reason which, in the opinion of the medical sub-investigator, would prevent the subject from participating in the study.
• Abnormal laboratory tests judged clinically significant.
• Positive urine drug screen at screening.
• Positive testing for hepatitis B, hepatitis C or HIV at screening.
• Subjects with BMI less than or equal to 30.0.
• History of significant alcohol abuse within six months of the screening visit or any indication of the regular use of more than fourteen units of alcohol per week (1 Unit
• = 150 mL of wine or 360 mL of beer or 45 mL of alcohol 40%).
• History of drug abuse or use of illegal drugs: use of soft drugs (such as marijuana) within 3 months of the screening visit or hard drugs (such as cocaine, phencyclidine (PCP) and crack) within 1 year of the screening visit.
• History of allergic reactions to glyburide or to metformin or other related drugs (e.g. chlorpropamide, gliclazide, tolbutamide, furosemide, sulfamethoxazole, sulfadiazine and sulfisoxazole).
• Use of any drugs known to induce or inhibit hepatic drug metabolism (examples of inducers: barbiturates, carbamazepine, phenytoin, glucocorticoids, rifampin/rifabutin; examples of inhibitors: antidepressants, cimetidine, diltiazem, erythromycin, ketoconazole, MAO inhibitors, neuroleptics, verapamil, quinidine) within 30 days prior to administration of the study medication.
• Use of an investigational drug or participation in an investigational study within 30 days prior to administration of the study medication.
• History or presence of any clinically significant gastrointestinal pathology (e.g.
• chronic diarrhea, inflammatory bowel diseases), unresolved gastrointestinal symptoms (e.g. diarrhea, vomiting), liver or kidney disease or other conditions known to interfere with the absorption, distribution, metabolism or excretion of the drug.
• Any history or presence of clinically significant neurological, endocrinal, cardiovascular, pulmonary, hematologic, immunologic, psychiatric or metabolic disease.
• Use of prescription medication within 14 days prior to administration of study medication or over-the-counter products (including natural food supplements, vitamins, garlic as supplement) within 7 days prior to administration of study medication except for topical products without systemic absorption.
• Positive alcohol breath test at screening.
• subjects who have used tobacco in any form within the 90 days preceding study drug administration.
• Intolerance to venipuncture.
• Any food allergy, intolerance, restriction, or special diet that, in the opinion of the medical sub-investigator, contraindicates the subject's participation in this study.
• Subjects who have had a depot injection or an implant of any drug 3 months prior to administration of study medication.
• Donation of plasma (500 mL) within 7 days. Donation or loss of whole blood prior to administration of the study medication as follows: less than 300 mL of whole blood within 30 days or; 300 mL to 500 mL of whole blood within 45 days or; more than 500 mL of whole blood within 56 days.
• Subjects with a clinically significant history of tuberculosis, epilepsy, asthma, diabetes, psychosis or glaucoma will not be eligible for this study.
• History of metabolic acidosis, congestive heart failure and myocardial infarction.
• Breast-feeding subjects.
• Positive urine pregnancy test at screening (performed on all females).
• Female subjects of childbearing potential who have had unprotected sexual intercourse with any non-steril male partner (i.e. male who has not been sterilized by vasectomy for at least 6 months) within 14 days prior to study drug administration. The acceptable methods of contraception are:
• 1. Condom + spermicide
• 2. Diaphragm + spermicide
• 3. Intrauterine contraceptive device (placed at least 4 weeks prior to study drug administration)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: Teva Pharmaceuticals USA Industry

Overall Clinical Trial Officials and Contacts

Richard Larouche, M.D. Principal Investigator Anapharm  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00836472

Study ID Number: 02349

ClinicalTrials.gov Identifier: NCT00836472

Health Authority: Canada: Ethics Review Committee