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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01239459
First received: November 9, 2010
Last updated: February 28, 2012
Last verified: February 2012

November 9, 2010
February 28, 2012
November 2010
February 2011   (final data collection date for primary outcome measure)
Pharmacokinetic parameters of Teriflunomide determined from plasma concentration (Maximum plasma concentration (Cmax), Area under the plasma concentration curve (AUClast and AUC)) [ Time Frame: 56 days ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01239459 on ClinicalTrials.gov Archive Site
Clinical safety evaluation (AE reporting, laboratory tests (hematology, biochemistry and urinalysis), vital signs and ECG parameters) [ Time Frame: Up to 12 weeks (until the end of study visit) ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Pharmacokinetic and Tolerability Study of 14 mg Single Dose of Teriflunomide in Subjects With Severe Renal Impairment
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

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
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Renal Impairment
  • Drug: Teriflunomide HMR1726

    Pharmaceutical form:film coated tablet

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

  • Drug: Cholestyramine

    Pharmaceutical form:powder

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

  • Experimental: Severe impaired renal function
    Subjects with severe renal impairment as defined by Cockroft-Gault formula
    Interventions:
    • Drug: Teriflunomide HMR1726
    • Drug: Cholestyramine
  • Experimental: Normal renal function
    Subjects with normal renal function as defined by Cockroft-Gault formula
    Interventions:
    • Drug: Teriflunomide HMR1726
    • Drug: Cholestyramine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
16
March 2011
February 2011   (final data collection date for primary outcome measure)

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.

Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT01239459
POP11432, 2010-022354-16, U1111-1117-6723
No
Sanofi
Sanofi
Not Provided
Study Director: Clinical Sciences & Operations Sanofi
Sanofi
February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP