Leflunomide 20 mg Tablets, Non-Fasting

• Sponsor: Teva Pharmaceuticals USA (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00834405
• Collaborator: (none)
• Enrollment: 37
• Locations: 2
• Arms: 2
• Duration (Days): 30
• Patients Per Site: 18.5
• Patients Per Site Per Month: 18.8

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: ARAVA® 20 mg tablets; Drug: Leflunomide 20 mg Tablets	Phase 1

Detailed Description

Criteria for Evaluation: FDA Bioequivalence Criteria

Statistical Methods: FDA bioequivalence statistical methods

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Official Title: A Relative Bioavailability, Parallel Study of Leflunomide 20 mg Tablets Under Non-Fasting Conditions
• Study Start Date: Apr 1, 2002
• Actual Primary Completion Date: May 1, 2002
• Actual Study Completion Date: May 1, 2002

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Cmax - Maximum Observed Concentration - Metabolite A77 1726 in Plasma [Blood samples collected over 72 hour period]

   Bioequivalence based on Cmax

2. AUC0-72 - Area Under the Concentration-time Curve From Time Zero to 72 Hours Post-dose (Per Participant) - Metabolite A77 1726 [Blood samples collected over 72 hour period]

   Bioequivalence based on AUC0-72

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gateway Medical Research, Inc.	St. Charles	Missouri	United States	63301
2	Bioassay Laboratory, Inc.	Houston	Texas	United States	77099

Sponsors and Collaborators

• Teva Pharmaceuticals USA

Investigators

• Principal Investigator: David B. Erasmus, M.D., Cetero Research, San Antonio

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00834405
• Other Study ID Numbers: B026504
• First Posted: Feb 3, 2009
• Last Update Posted: Sep 15, 2009
• Last Verified: Sep 1, 2009

• Keywords provided by , ,: Bioequivalence; Healthy Subjects
• Additional relevant MeSH terms: Leflunomide

Study Results

Participant Flow

Arm/Group Title	Leflunomide	Arava®
Arm/Group Description	Leflunomide 20 mg Tablet	Arava® 20 mg Tablet
Period Title: Overall Study
STARTED	20	17
COMPLETED	20	17
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Leflunomide	Arava®	Total
Arm/Group Description	Leflunomide 20 mg Tablet	Arava® 20 mg Tablet	Total of all reporting groups
Overall Participants	20	17	37
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	19 95%	16 94.1%	35 94.6%
>=65 years	1 5%	1 5.9%	2 5.4%
Sex: Female, Male (Count of Participants)
Female	13 65%	10 58.8%	23 62.2%
Male	7 35%	7 41.2%	14 37.8%
Race/Ethnicity, Customized (Number) [Number]
Caucasian	19 95%	17 100%	36 97.3%
Black	1 5%	0 0%	1 2.7%
Region of Enrollment (participants) [Number]
United States	20 100%	17 100%	37 100%

Outcome Measures

1. Primary Outcome

Title	Cmax - Maximum Observed Concentration - Metabolite A77 1726 in Plasma
Description	Bioequivalence based on Cmax
Time Frame	Blood samples collected over 72 hour period

Outcome Measure Data

Analysis Population Description

Data from all subjects who completed the study were included in the statistical analysis.

Arm/Group Title	Leflunomide	Arava®
Arm/Group Description	Leflunomide 20 mg Tablet	Arava® 20 mg Tablet
Measure Participants	20	17
Mean (Standard Deviation) [ng/mL]	2488.000 (385.181)	2345.294 (266.156)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Leflunomide, Arava®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-72 and Cmax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Test/Ref Ratio x 100
	Estimated Value	106
	Confidence Interval	() 90%; 98.0 to 114
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established when 90% Confidence Interval falls within 80-125.

2. Primary Outcome

Title	AUC0-72 - Area Under the Concentration-time Curve From Time Zero to 72 Hours Post-dose (Per Participant) - Metabolite A77 1726
Description	Bioequivalence based on AUC0-72
Time Frame	Blood samples collected over 72 hour period

Outcome Measure Data

Analysis Population Description

Data from all subjects who completed the study were included in the statistical analysis.

Arm/Group Title	Leflunomide	Arava®
Arm/Group Description	Leflunomide 20 mg Tablet	Arava® 20 mg Tablet
Measure Participants	20	17
Mean (Standard Deviation) [ng*h/mL]	132584.730 (18639.707)	123335.784 (13732.783)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Leflunomide, Arava®
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Analysis of variance (ANOVA) was performed on pharmacokinetic parameters of AUC0-72 and Cmax.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Test/Ref Ratio x 100
	Estimated Value	107
	Confidence Interval	() 90%; 100 to 115
	Parameter Dispersion	Type: Value:
	Estimation Comments	Bioequivalence is established when 90% Confidence Interval falls within 80-125.

Adverse Events

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Principal Investigator is not permitted to discuss or publish trial results.