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A Study of the Effects of Renal Impairment on the Pharmacokinetics and Tolerability of Eliglustat Tartrate

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02536937
Recruitment Status : Completed
First Posted : September 1, 2015
Last Update Posted : March 8, 2017
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

Primary Objective:

To study the effect of mild, moderate, and severe renal impairment on the pharmacokinetics (PK) of eliglustat.

Secondary Objective:

To assess the tolerability of eliglustat tartrate given as a single dose in subjects with mild, moderate, and severe renal impairment in comparison with matched subjects with normal renal function.


Condition or disease Intervention/treatment Phase
Gaucher Disease Drug: eliglustat Phase 1

Detailed Description:
The total study duration from screening period is approximately 31 days. In stage 1, only subjects with severe renal impairment and normal renal function will be enrolled. Subjects with mild and moderate renal impairment may be enrolled in stage 2 if the results in subjects with severe renal impairment show a substantial effect of reduced renal function on pharmacokinetics.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label Two-stage Pharmacokinetic and Tolerability Study of Eliglustat Tartrate Given as a Single Dose in Subjects With Mild, Moderate and Severe Renal Impairment, and in Matched Subjects With Normal Renal Function
Study Start Date : September 2015
Actual Primary Completion Date : January 2017
Actual Study Completion Date : January 2017


Arm Intervention/treatment
Experimental: GZ385660 (healthy subjects)
Single dose of eliglustat tartrate will be given under fed conditions
Drug: eliglustat

Pharmaceutical form: capsule

Route of administration: oral

Other Name: GZ385660

Experimental: GZ385660 (subjects with mild renal impairment)
Single dose of eliglustat tartrate will be given under fed conditions
Drug: eliglustat

Pharmaceutical form: capsule

Route of administration: oral

Other Name: GZ385660

Experimental: GZ385660 (subjects with moderate renal impairment)
Single dose of eliglustat tartrate will be given under fed conditions
Drug: eliglustat

Pharmaceutical form: capsule

Route of administration: oral

Other Name: GZ385660

Experimental: GZ385660 (subjects with severe renal impairment)
Single dose of eliglustat tartrate will be given under fed conditions
Drug: eliglustat

Pharmaceutical form: capsule

Route of administration: oral

Other Name: GZ385660




Primary Outcome Measures :
  1. - Assessment of PK parameter: Maximum plasma concentration observed (Cmax) [ Time Frame: 3 days ]
  2. - Assessment of PK parameter: Area under the plasma concentration (AUC) [ Time Frame: 3 days ]

Secondary Outcome Measures :
  1. Assessment of PK parameter: Area under the plasma concentration versus time curve (AUClast) [ Time Frame: 3 days ]
  2. Assessment of PK parameter: Apparent total body clearance (CL/F) [ Time Frame: 3 days ]
  3. Assessment of PK parameter: Apparent volume of distribution during the terminal phase (Vz/F) [ Time Frame: 3 days ]
  4. Assessment of PK parameter: Predicted accumulation ratio (Rac,pred) [ Time Frame: 3 days ]
  5. Assessment of PK parameter: Terminal half-life (t1/2z) [ Time Frame: 3 days ]
  6. Number of adverse events [ Time Frame: Up to 10 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria :

For renal impaired:

  • Male or female subjects, between 18 and 79 years of age, inclusive.
  • Body weight between 50.0 kg and 125.0 kg inclusive if male, between 40.0 kg and 110.0 kg inclusive if female, body mass index (BMI) between 18.0 and 37.0 kg/m^2, inclusive.
  • Stable chronic renal impairment, as defined by Cockroft-Gault formula.
  • For severe renal impairment: CrCl <30 mL/min.
  • For moderate renal impairment: 30 mL/min ≤CrCl <50 mL/min.
  • For mild renal impairment: 50 mL/min ≤CrCl ≤80 mL/min.

For matched subjects:

  • Male or female subject, between 18 and 79 years inclusive, matched by age.
  • Body weight within 15% of the body weight of the subjects with renal impairment to be matched and BMI between 18.0 and 37.0 mg/kg^2 inclusive.
  • Matched by cytochrome P450 (CYP) 2D6 predicted phenotype based on genotype.
  • Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination).
  • For healthy subjects: CrCl >80 mL/min.

Exclusion criteria:

For renal impairment patients:

  • Uncontrolled clinically relevant cardiovascular, pulmonary, gastrointestinal, 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.
  • History of or current hematuria of urologic origin that limits the subject's participation in the study.
  • Subjects requiring dialysis during the study.
  • Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician.
  • If female, pregnancy (defined as positive beta-human chorionic gonadotropin [β-hCG] blood test), breastfeeding.
  • Any significant change in chronic treatment medication within 14 days before inclusion.
  • P-gp inhibitors and/or inducers, CYP2D6 and/or CYP3A inducers, and strong and/or moderate CYP2D6 and/or CYP3A inhibitors. Up to one weak CYP2D6 inhibitor and/or one weak CYP3A inhibitor are allowed (as defined in The Metabolism and Transport Drug Interaction Database™ (DIDB).
  • Positive result on any of the following tests: anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti-HIV2 Ab).
  • Pre-existing cardiac disease (current congestive heart failure, recent acute myocardial infarction, bradycardia, heart block, ventricular arrhythmia), long QT syndrome, or use of Class IA (eg, quinidine, procainamide) and Class III (eg, amiodarone, sotalol) anti-arrhythmic medications.
  • Any subject with CYP2D6 indeterminate or ultra-rapid metabolizer (URM) phenotype.

For matched volunteers:

  • Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynecologic (if female), or infectious disease, or signs of acute illness.
  • Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician.
  • If female, pregnancy (defined as positive β-hCG blood test), breast feeding.
  • 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 half-life of that medication, whichever is longest, with the exception of hormonal contraception or menopausal hormone replacement therapy; any vaccination within the last 28 days, and any biologics (antibody or its derivatives) within 4 months before inclusion.
  • For subjects above 50 years old: any significant change in chronic treatment medication within 14 days before inclusion.
  • P-gp inhibitors and/or inducers, CYP2D6 and/or CYP3A inducers, and strong and/or moderate CYP2D6 and/or CYP3A inhibitors. Up to one weak CYP2D6 inhibitor and/or one weak CYP3A inhibitor are allowed (as defined in The Metabolism and Transport Drug Interaction Database™ (DIDB).
  • Positive result on any of the following tests: hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (anti-HCV) Ab, anti-HIV1 and anti-HIV2 Ab.
  • Pre-existing cardiac disease (current congestive heart failure, recent acute myocardial infarction, bradycardia, heart block, ventricular arrhythmia), long QT syndrome, or use of Class IA (eg, quinidine, procainamide) and Class III (eg, amiodarone, sotalol) anti-arrhythmic medications.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02536937


Locations
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United States, Florida
Investigational Site Number 840004
Miami, Florida, United States, 33014
United States, Minnesota
Investigational Site Number 840002
St. Paul, Minnesota, United States, 55144
United States, Tennessee
Investigational Site Number 840001
Knoxville, Tennessee, United States, 37920
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT02536937    
Other Study ID Numbers: POP13778
U1111-1170-3686 ( Other Identifier: UTN )
First Posted: September 1, 2015    Key Record Dates
Last Update Posted: March 8, 2017
Last Verified: March 2017
Additional relevant MeSH terms:
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Gaucher Disease
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Eliglustat
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action