Clinical trial NCT01239459: Pharmacokinetic and Tolerability Study of 14 mg Single Dose of Teriflunomide in Subjects With Severe Renal Impairment
Official title: An Open-label Pharmacokinetic and Tolerability Study of Teriflunomide Given as a Single 14 mg Dose in Subjects With Severe Renal Impairment, and in Matched Subjects With Normal Renal Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2010-11-11
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

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.

Primary outcomes:
measure: Pharmacokinetic parameters of Teriflunomide determined from plasma concentration (Maximum plasma concentration (Cmax), Area under the plasma concentration curve (AUClast and AUC))
timeFrame: 56 days
Secondary outcomes:
measure: Clinical safety evaluation (AE reporting, laboratory tests (hematology, biochemistry and urinalysis), vital signs and ECG parameters)
timeFrame: Up to 12 weeks (until the end of study visit)
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: