Leflunomide 20 mg Tablets, Non-Fasting

Study Overview
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Brief Summary
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The objective of this study is to compare the relative bioavailability of leflunomide 20 mg tablets (manufactured by TEVA Pharmaceutical Industries, Ltd. and distributed by TEVA Pharmaceuticals USA) with that of ARAVA 20 mg tablets (Aventis) in healthy, adult, non-smoking subjects [females (who are unable to become pregnant) and vasectomized males] under non-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, Parallel Study of Leflunomide 20 mg Tablets Under Non-Fasting Conditions

Conditions
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Healthy

Intervention / Treatment
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* Drug: ARAVA® 20 mg tablets
* Drug: Leflunomide 20 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. Females must be physically unable to become pregnant. Males must be vasectomized. Weight of the subjects shall not be more than 20% ± from normal for height and body frame (Metropolitan Life, 1993, Height, Weight, Body Chart). Each subject shall be given a general physical examination within 21 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 21 days before beginning of the first period and at th eend of the trial for clinical laboratory measurements. Clinical laboratory measurements will include the following: Hematology: hematocrit, hemoglobin, red blood cell count, platelets, white 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 check-in before dosing. Subjects will be selected if all above are normal. Exclusion Criteria: Subjects with a history of chronic alcohol consumption (during past 2 years), drug addiction, or recent 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 should be excluded from the study. Subjects who have a history of allergic responses to cholestyramine should be excluded from the study. All subjects will have urine samples assayed for the presence of drugs of abuse as part of the clinical laboratory screening procedures and at check-in before dosing. 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 30 days prior to the first dosing of the study. Subjects who have taken any investigational drug within 30 days prior to the first dosing of the study will not be allowed to participate. Female subjects who are pregnant or who are able (women with child bearing potential) to become pregnant during the study will not be allowed to participate. All female subjects will be screened for pregnancy at check-in. Subjects with positive or inconclusive results will be withdrawn from the study. Male subjects who are physically able to father a child will not be allowed to participate. Male subjects must be vasectomized (at least 3 months) with medical verification. Subjects who smoke or use tobacco in any form will not be eligible to participate in the study. Three months abstinence is required. Subjects who are unable to tolerate multiple venipuncture will be excluded. Subjects who have taken any product containing leflunomide within 180 days of dosing will not be allowed to participate in this study.

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Leflunomide<br>Leflunomide 20 mg Tablet | Drug: Leflunomide 20 mg Tablets<br>* 1 x 20 mg, single-dose non-fasting<br>|
| Active Comparator: Arava®<br>Arava® 20 mg Tablet | Drug: ARAVA® 20 mg tablets<br>* 1 x 20 mg, single-dose non-fasting<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax - Maximum Observed Concentration - Metabolite A77 1726 in Plasma | Bioequivalence based on Cmax | Blood samples collected over 72 hour period | 
| AUC0-72 - Area Under the Concentration-time Curve From Time Zero to 72 Hours Post-dose (Per Participant) - Metabolite A77 1726 | Bioequivalence based on AUC0-72 | Blood samples collected over 72 hour period | 

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