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

NCT01239459 | Completed Phase 1

• 3 other identifiers: POP114322010-022354-16U1111-1117-6723
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Impairment

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetic parameters of Teriflunomide determined from plasma concentration (Maximum plasma concentration (Cmax), Area under the plasma concentration curve (AUClast and AUC))

  56 days

Secondary Outcomes (1)

• Clinical safety evaluation (AE reporting, laboratory tests (hematology, biochemistry and urinalysis), vital signs and ECG parameters)

  Up to 12 weeks (until the end of study visit)

Study Arms (2)

Severe impaired renal function

EXPERIMENTAL

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

Drug: Teriflunomide HMR1726; Drug: Cholestyramine

Normal renal function

EXPERIMENTAL

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

Drug: Teriflunomide HMR1726; Drug: Cholestyramine

Interventions

Teriflunomide HMR1726 DRUG

Pharmaceutical form:film coated tablet Route of administration: oral administration on Day 1 under fasted condition

Normal renal function; Severe impaired renal function

Cholestyramine DRUG

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

Normal renal function; Severe impaired renal function

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (1)

Sanofi-Aventis Administrative Office

Berlin, Germany

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

teriflunomide; Cholestyramine Resin

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Polystyrenes; Plastics; Polymers; Macromolecular Substances; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 9, 2010
• First Posted: November 11, 2010
• Study Start: November 1, 2010
• Primary Completion: February 1, 2011
• Study Completion: March 1, 2011
• Last Updated: March 1, 2012

Record last verified: 2012-02

Locations

DE (1)