Leflunomide 20 mg Tablets, Non-Fasting

A Relative Bioavailability, Parallel Study of Leflunomide 20 mg Tablets Under Non-Fasting Conditions

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Leflunomide 20 mg Tablets; Drug: ARAVA® 20 mg tablets

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St. Charles, Missouri, United States, 63301
      • Gateway Medical Research, Inc.
  • Texas
    • Houston, Texas, United States, 77099
      • Bioassay Laboratory, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Teva Pharmaceuticals USA
• Investigators: Principal Investigator: David B. Erasmus, M.D., Cetero Research, San Antonio

Study record dates

Study Major Dates

• Study Start: April 1, 2002
• Primary Completion (Actual): May 1, 2002
• Study Completion (Actual): May 1, 2002

Study Registration Dates

• First Submitted: January 30, 2009
• First Submitted That Met QC Criteria: January 30, 2009
• First Posted (Estimate): February 3, 2009

Study Record Updates

• Last Update Posted (Estimate): September 15, 2009
• Last Update Submitted That Met QC Criteria: September 9, 2009
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: Bioequivalence; Healthy Subjects
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Leflunomide
• Other Study ID Numbers: B026504