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
  Purpose

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.


Condition Intervention Phase
Renal Impairment
Drug: Teriflunomide HMR1726
Drug: Cholestyramine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 16
Study Start Date: November 2010
Study Completion Date: March 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Severe impaired renal function
Subjects with severe renal impairment as defined by Cockroft-Gault formula
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: Normal renal function
Subjects with normal renal function as defined by Cockroft-Gault formula
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


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

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01239459

Locations
Germany
Sanofi-Aventis Administrative Office
Berlin, Germany
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01239459     History of Changes
Other Study ID Numbers: POP11432, 2010-022354-16, U1111-1117-6723
Study First Received: November 9, 2010
Last Updated: February 28, 2012
Health Authority: Germany: Ethics Commission

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on September 30, 2014