Bioavailability Study of Leflunomide Tablets Under Fed Conditions

To Compare the Relative Bioavailability of Leflunomide 20mg Tablets (Kali) With That of ARAVA 20mg Tablets(Aventis) Under Fed Conditions

To compare the single-dose Bioavailability of Kali and Aventis

Study Overview

• Status: Completed
• Conditions: To Determine Bioequivalence Under Fed Conditions
• Intervention / Treatment: Drug: Leflunomide; Drug: ARAVA

Detailed Description

To compare the relative Bioavailability of leflunomide 20mg tablets with that of ARAVA 20mg tablets in healthy female subjects under fed conditions

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Subjects will meet all of the following criteria within 30 days prior to first drug administration(except inclusion #8)
• Healthy, surgically sterile (hysterectomy, bilateral oophorectomy) or postmenopausal (for al least 1 year)female subjects, 18 to 65 years of age(inclusive)
• Indicate non-child bearing status by one of the following criteria:

Indication of successful hysterectomy. No spontaneous menses for al least 1 year, must have luteinizing hormone (LH) and follicle stimulating hormone(FSH) levels within postmenopausal range.

Indication of successful bilateral oophorectomy.

• Body weight within 20% of the appropriate weight for the subject's height and frame (as published in the 1983 Metropolitan Life Insurance Company Scale, Statistical Bureau)
• Negative for:

HIV Hepatitis B surface antigen and Hepatitis C antibody Urine tests for drugs of abuse (marijuana, amphetamines, barbiturates, cocaine, opiates, benzodiazepines and methadone).

Serum HCG consistent with pregnancy.

• No significant disease or clinically significant findings in a physical examination.
• No clinically significant findings in vital signs measurements and a 12-lead electrocardiogram(ECG)
• Subjects who have received leflunomide within 4 months must have an A77-1726(Metabolite) level below 0.01ug/ml and no subsequent administration of leflunomide since that test. Note: The 30 day screening limit does not apply to this inclusion criterion.
• Be informed of the nature of the study and given written consent prior to receiving any study procedures.

Exclusion Criteria:

• Subject fulfilling any of the following criteria will be excluded from the study.
• Known history or presence of any clinically significant medical condition.
• Known or suspected carcinoma.
• Known history or presence of:
• Hypersensitivity or idiosyncratic reaction to leflunomide and/or any other drug substances with similar activity.
• Alcoholism within the last 12 months.
• Drug dependence and/ or substance abuse.
• On a special diet within 4 weeks prior to drug administration(e.g. liquid, protein, raw food diet).
• Participated in another clinical trail or received an investigational product 30 days prior to drug administration.
• Donated up to 250 ml of blood in the past 45 days OR donated from 250 ml to 500 ml in the past 45 days OR donated 501 ml or more of blood in the past 56 days (based on the Canadian Blood Services guideline for blood donation).
• Requirement of any medication (prescription and/ or over-the-counter) on a routine basis, with the exception of hormonal replacement therapy, nutritional supplements and/or occasional use of common analgesics.
• Difficulty fasting or consuming the standard meals.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Subjects received Kali formulated product under fed conditions	Drug: Leflunomide; tablets, 20mg, single-dose; Other Names: ARAVA
Active Comparator: B; Subjects received Aventis formulated products under fed conditions	Drug: ARAVA; Tablets, 20mg, single-dose; Other Names: Leflunomide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate and Extend of Absorption	24 Hours

Collaborators and Investigators

• Sponsor: Par Pharmaceutical, Inc.
• Collaborators: Novum Pharmaceutical Research Services
• Investigators: Principal Investigator: Xueyu Chen, Pharma Medica Research, Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2003
• Primary Completion (Actual): January 1, 2004
• Study Completion (Actual): January 1, 2004

Study Registration Dates

• First Submitted: April 1, 2008
• First Submitted That Met QC Criteria: April 3, 2008
• First Posted (Estimate): April 4, 2008

Study Record Updates

• Last Update Posted (Actual): September 26, 2017
• Last Update Submitted That Met QC Criteria: September 22, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Bioequivalence, Leflunomide, fed
• Additional Relevant MeSH Terms: Pathologic Processes; Nutrition Disorders; Disease; Malnutrition; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Leflunomide
• Other Study ID Numbers: 2004-704