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

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ClinicalTrials.gov Identifier: NCT01239459
Recruitment Status : Completed
First Posted : November 11, 2010
Last Update Posted : March 1, 2012
Sponsor:
Information provided by (Responsible Party):
Sanofi

Tracking Information
First Submitted Date  ICMJE November 9, 2010
First Posted Date  ICMJE November 11, 2010
Last Update Posted Date March 1, 2012
Study Start Date  ICMJE November 2010
Actual Primary Completion Date February 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 10, 2010)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01239459 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 10, 2010)
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) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetic and Tolerability Study of 14 mg Single Dose of Teriflunomide in Subjects With Severe Renal Impairment
Official Title  ICMJE 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
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Renal Impairment
Intervention  ICMJE
  • 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

Study Arms  ICMJE
  • 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
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 10, 2010)
16
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2011
Actual Primary Completion Date February 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01239459
Other Study ID Numbers  ICMJE POP11432
2010-022354-16 ( EudraCT Number )
U1111-1117-6723 ( Other Identifier: UTN )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Sciences & Operations Sanofi
PRS Account Sanofi
Verification Date February 2012

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