Pharmacokinetic and Tolerability Study of 14 mg Single Dose of Teriflunomide in Subjects With Severe Renal Impairment

NCT ID: NCT01239459

Last Updated: 2012-03-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2011-03-31

Brief Summary

Primary Objective:

• To determine the effect of severe renal impairment on the pharmacokinetic profile of teriflunomide administered as a single 14 mg dose as compared to healthy subjects

Secondary Objective:

• To assess the tolerability of teriflunomide administered as a single 14 mg dose in subjects with severe renal impairment compared to subjects with normal renal function.

Detailed Description

The total study duration per subject is 11-15 weeks broken down as follows:

• Screening: up to 3 weeks
• Hospitalization: 3 days (admission 1 day prior to study drug intake)
• Follow-up: 10 -12 weeks

Conditions

Renal Impairment

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Severe impaired renal function

Subjects with severe renal impairment as defined by Cockroft-Gault formula

Group Type: EXPERIMENTAL

Teriflunomide HMR1726

Intervention Type: DRUG

Pharmaceutical form:film coated tablet

Route of administration: oral administration on Day 1 under fasted condition

Cholestyramine

Intervention Type: DRUG

Pharmaceutical form:powder

Route of administration: oral administration 3 times per day on Day 54 and 55

Normal renal function

Subjects with normal renal function as defined by Cockroft-Gault formula

Group Type: EXPERIMENTAL

Teriflunomide HMR1726

Intervention Type: DRUG

Pharmaceutical form:film coated tablet

Route of administration: oral administration on Day 1 under fasted condition

Cholestyramine

Intervention Type: DRUG

Pharmaceutical form:powder

Route of administration: oral administration 3 times per day on Day 54 and 55

Interventions

Teriflunomide HMR1726

Pharmaceutical form:film coated tablet

Route of administration: oral administration on Day 1 under fasted condition

Intervention Type: DRUG

Cholestyramine

Pharmaceutical form:powder

Route of administration: oral administration 3 times per day on Day 54 and 55

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Subjects with renal impairment:

• Male subject between 18 and 75 years of age inclusive and postmenopausal female between 45 and 75 years of age inclusive.
• Chronic severe renal impairment as defined by Cockroft-Gault formula (creatinine clearance (CLcr) < 30mL/min, but not requiring hemodialysis).
• Laboratory parameters within the acceptable range for subjects with renal impairment; in particular, hepatic enzymes (ALT, AST) and bilirubin should be < 2 x upper limit of normal range and neutrophils should be within normal ranges.

Matched healthy subjects:

• Male subject between 18 and 75 years of age inclusive and postmenopausal female between 45 and 75 years of age inclusive, matched by age.
• Body weight within 15% of the body weight of the subjects with renal impairment to be matched and Body Mass Index between 18.0 and 30.0 mg/kg2 inclusive.
• Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination).
• Normal renal function as defined by Cockroft-Gault formula (creatinine clearance (CLcr) > 80mL/min)
• Laboratory parameters within the normal range, unless the Investigator considers an abnormality to be clinically irrelevant for healthy subjects; however serum creatinine, alkaline phosphatase, hepatic enzymes (AST, ALT), bilirubin (unless the subject has documented Gilbert syndrome) should not exceed the upper limit of normal range.

Exclusion Criteria

Subjects with renal impairment:

• Uncontrolled clinically relevant cardiovascular, pulmonary, gastro-intestinal, metabolic, hematological, neurological, psychiatric, systemic, ocular, gynecologic (if female) or infectious disease, or signs of acute illness.
• Active hepatitis, hepatic insufficiency.
• Acute renal failure (de novo or superimposed to pre-existing chronic renal impairment), nephrotic syndrome.
• Subject requiring dialysis during the study.
• Any significant change in chronic treatment medication within 14-days before inclusion.
• Any drug, which could impact by any mechanism of action, the pharmacokinetic of the investigational product.
• Positive reaction to Human Immunodeficiency Virus (HIV) tests: anti-HIV1 antibodies, anti-HIV2 antibodies
• Positive results on urine drug screen (amphetamines / methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates) unless this result is secondary to a documented medical prescription.
• Positive alcohol test.
• Man who disagrees to use a double barrier method of contraception with their partner during the study.

Matched healthy subjects:

• Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, psychiatric, systemic, ocular, gynecologic (if female), or infectious disease, or signs of acute illness.
• For subjects 50 years old and below:

• any medication (including St John's Wort) within 14 days before inclusion, or within 5 times the elimination half-life or pharmacodynamic halflife of that drug, whichever the longest, with the exception of menopausal hormone replacement therapy.
• any significant change in chronic treatment medication within 14-days before inclusion.
• Any drug, which could impact by any mechanism of action, the pharmacokinetic of the investigational product.
• Positive reaction to any of the following tests: hepatitis B surface (HBs) antigen, antihepatitis C virus (anti-HCV) antibodies, HIV1 antibodies, anti-HIV2 antibodies.
• Positive results on urine drug screen (amphetamines / methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates).
• Positive alcohol test.
• Man who disagrees to use a double barrier method of contraception with their partner during the study

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Sanofi-Aventis Administrative Office

Berlin, , Germany

Countries

Germany

Other Identifiers

2010-022354-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1117-6723

Identifier Type: OTHER

Identifier Source: secondary_id

POP11432

Identifier Type: -

Identifier Source: org_study_id