pharmacokinetic and tolerability study of 14 mg single dose of teriflunomide in subjects with severe renal impairment

Conditions: Renal Impairment

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.

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

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.