Leflunomide 20 mg Tablets, Non-Fasting
Condition: Healthy
Intervention: ARAVA® 20 mg tablets; Leflunomide 20 mg Tablets
Intervention description: 1 x 20 mg, single-dose non-fasting; 1 x 20 mg, single-dose non-fasting
Intervention MeSH terms: Leflunomide
Phase: Phase 1
Study type: Interventional
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 37.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Bioequivalence; Healthy Subjects

Summary:

      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.
    

Eligibility criteria:

        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:

               1. Hematology: hematocrit, hemoglobin, red blood cell count, platelets, white blood
                  cell count (with differential).

               2. Clinical chemistry: creatinine, BUN, glucose, SGOT/AST, SGPT/ALT, bilirubin, and
                  alkaline phosphatase.

               3. Urine Analysis: pH, specific gravity, protein, glucose, ketones, bilirubin,
                  occult blood, and cells.

               4. HIV Screen: pre-study only.

               5. Hepatitis-B, C Screen: pre-study only.

               6. 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.