Glimepiride 4 mg Tablets Under Fasting Conditions

Study Overview
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Brief Summary
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The objective of this study is to compare the relative bioavailability of glimepiride 4 mg tablets (manufactured by TEVA Pharmaceutical Industries, Ltd. and distributed by TEVA Pharmaceuticals USA) with that of AMARYL® tablets (Aventis) in healthy, adult, non-smoking subjects under fasting conditions.

Detailed Description
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Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA bioequivalence statistical methods

Official Title
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A Relative Bioavailability Study of Glimepiride 4 mg Tablets Under Fasting Conditions

Conditions
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Healthy

Intervention / Treatment
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* Drug: Glimepiride 4 mg Tablets
* Drug: AMARYL® 4 mg Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects selected for this study will be non-smokers at least 18 years of age. Subjects will have a BMI (body mass index) of 30 or less. Each subject shall be given a general physical examination within 28 days of initiation of the study. Such examination includes, but is not limited to, blood pressure, general observations, and history. Each female subject will be given a serum pregnancy test as part of the pre-study screening process. Adequate blood and urine samples should be obtained within 28 days before beginning of the first period and at the end of the trial for clinical laboratory measurements. Clinical laboratory measurements will include the following: Hematology: hemoglobin, hematocrit, red blood cell count, platelets, whit blood cell count (with differential). Clinical Chemistry: creatinine, BUN, glucose, SGOT/AST, SGPT/ALT, bilirubin, and alkaline phosphatase. Urine Analysis: pH, specific gravity, protein, glucose, ketones, bilirubin, occult blood, and cells. HIV Screen: pre-study only. Hepatitis-B, C Screen: pre-study only. Drugs of Abuse Screen: pre-study and at each check-in. Subjects will be selected if all above are normal. Exclusion Criteria: Subjects with a significant recent history of chronic alcohol consumption, drug addiction, or serious gastrointestinal, renal, hepatic or cardiovascular disease, tuberculosis, epilepsy, asthma, diabetes, psychosis or glaucoma will not be eligible for this study. Subjects whose clinical laboratory test values are greater than 20% outside the normal range may be retested. If the clinical values are outside the range on retesting, the subject will not be eligible to participate in the study unless the clinical investigator deems the result to not be significant. Subjects who have a history of allergic responses to the class of drug being tested will be excluded from the study. Subjects who use tobacco in any form will not be eligible to participate in the study. Three months abstinence is required. All subjects will have urine samples assayed for the presence of drugs of abuse as part of the clinical laboratory screening procedures and at each dosing period check-in. Subjects found to have urine concentrations of any of the tested drugs will not be allowed to participate. Subjects should not have donated blood and/or plasma for at least thirty (30) days prior to the first dosing of the study. Subjects who have taken any investigational drug within thirty (30) days prior to the first dosing of the study will not be allowed to participate. Female subjects who are pregnant, breast-feeding, or who are likely to become pregnant during the study will not be allowed to participate. Female subjects of childbearing potential must either abstain from sexual intercourse or use a reliable barrier method (e.g. condom, IUD) of contraception during the course of the study (first dosing until last blood collection) or they will not be allowed to participate. Female subjects who have used hormonal oral contraceptives within 14 days of dosing or implanted or injected hormonal contraceptives within 180 days of dosing will not be allowed to participate. All female subjects will be screened for pregnancy at check-in each study period. Subjects with positive or inconclusive results will be withdrawn from the study. Subjects who do not tolerate venipuncture will not be allowed to participate.

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Experimental: Glimepiride<br>Glimepiride 4 mg Tablet (test) dosed in first period followed by Amaryl® 4 mg Tablet (reference) dosed in second period | Drug: Glimepiride 4 mg Tablets<br>* 1 x 4 mg, single-dose fasting<br>|
| Active Comparator: Amaryl®<br>Amaryl® 4 mg Tablet (reference) dosed in first period followed by Glimepiride 4 mg Tablet (test) dosed in second period | Drug: AMARYL® 4 mg Tablets<br>* 1 x 4 mg, single-dose fasting<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax - Maximum Observed Concentration | Bioequivalence based on Cmax | Blood samples collected over 24 hour period | 
| AUCinf - Area Under the Concentration-time Curve From Time Zero to Infinity (Extrapolated) | Bioequivalence based on AUCinf | Blood samples collected over 24 hour period | 
| AUC0-t - Area Under the Concentration-time Curve From Time Zero to Time of Last Non-zero Concentration | Bioequivalence based on AUC0-t | Blood samples collected over 24 hour period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bioequivalence, Healthy Subjects