Leflunomide 20 mg Tablets Under Fasting Conditions

Study Overview
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Brief Summary
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This study will compare the relative bioavailability (rate and extent of absorption) of 20 mg Leflunomide Tablets by TEVA Pharmaceuticals Industries, Ltd. with that of 20 mg ARAVA™ Tablets by Aventis Pharmaceuticals, Inc. following a single oral dose (1 x 20 mg tablet) in healthy adult 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 20 mg Leflunomide Tablets Under Fasting Conditions

Conditions
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Healthy

Intervention / Treatment
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* Drug: Leflunomide 20 mg Tablets
* Drug: ARAVA™ 20 mg Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Screening Demographics: All subjects selected for this study will be healthy men or women 18 years of age or older at the time of dosing. The weight range will not exceed ± 20% for height and body frame as per Desirable Weights for Adults - 1983 Metropolitan Height and Weight Table. Screening procedures: Each subject will complete the screening process within 28 days prior to dosing. Consent documents for both the screening evaluation and HIV antibody determination will be reviewed, discussed, and signed by each potential participant before full implementation of screening procedures. Screening will include general observations, physical examination, demographics, medical and medication history, an electrocardiogram, sitting blood pressure and heart rate, respiratory rate and temperature. The physical examination will include, but may not be limited to, an evaluation of the cardiovascular, gastrointestinal, respiratory and central nervous systems. The screening clinical laboratory procedures will include: Hematology: hematocrit, hemoglobin, WBC count with differential, RBC count, platelet count; Clinical Chemistry: serum creatinine, BUN, glucose, AST(GOT), ALT(GPT), albumin, total bilirubin, total protein, and alkaline phosphatase; HIV antibody and hepatitis B surface screens; Urinalysis: by dipstick; full microscopic examination if dipstick positive; and Urine Drug Screen: ethyl alcohol, amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine metabolites, opiates and phencyclidine. Serum Pregnancy Screen (female subjects only) Follicle Stimulating Hormone [FSH] (females only to verify postmenopausal status) If male must be vasectomized (at least 3 months) If female and: is postmenopausal for at least 1 year; or is surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy). Exclusion Criteria: Subjects with a recent history of drug or alcohol addiction or abuse. Subjects with the presence of a clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine, or neurologic system(s) or psychiatric disease (as determined by the clinical investigators). Subjects whose clinical laboratory test values are outside the accepted reference range and when confirmed on re-examination are deemed to be clinically significant. Subjects demonstrating a positive hepatitis B surface antigen screen or reactive HIV antibody screen. Subjects demonstrating a positive drug abuse screen when screened for this study. Female subjects who are currently breastfeeding. Female subjects demonstrating a positive pregnancy screen. Subjects with a history of allergic response(s) to leflunomide or related drugs. Subjects with a history of clinically significant allergies including drug allergies. Subjects with a clinically significant illness during the 4 weeks prior to dosing (as determined by the clinical investigators). Subjects who have taken any drug known to induce or inhibit hepatic drug metabolism in the 30 days prior to dosing. Subjects who report donating greater than 150 mL of blood within 30 days prior to dosing. All subjects will be advised not to donate blood for four weeks after completing the study. Subjects who have donated plasma (e.g. plasmapheresis) within 14 days prior to dosing. All subjects will be advised not to donate plasma for four weeks after completing the study. Subjects who report receiving any investigational drug within 30 days prior to dosing. Subjects who report taking any prescription medication in the 14 days prior to dosing, with the exception of postmenopausal women on HRT may continue their HRT and topical products without systemic absorption. Subjects who report an intolerance of direct venipuncture. Subjects who report consuming an abnormal diet during the 28 days prior to dosing. Subjects who report taking any product containing leflunomide within 180 days of dosing. Subjects who report taking any herbal products within 7 days prior to dosing.

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 fasting<br>|
| Active Comparator: Arava™<br>Arava™ 20 mg Tablet | Drug: ARAVA™ 20 mg Tablets<br>* 1 x 20 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 - 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 - 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