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

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

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.

Study Overview

• Status: Completed
• Conditions: Gaucher Disease
• Intervention / Treatment: Drug: eliglustat

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33014
      • Investigational Site Number 840004
  • Minnesota
    • St. Paul, Minnesota, United States, 55144
      • Investigational Site Number 840002
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Investigational Site Number 840001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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 Names: 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 Names: GZ385660

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
- Assessment of PK parameter: Maximum plasma concentration observed (Cmax)	3 days
- Assessment of PK parameter: Area under the plasma concentration (AUC)	3 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: August 28, 2015
• First Submitted That Met QC Criteria: August 28, 2015
• First Posted (Estimate): September 1, 2015

Study Record Updates

• Last Update Posted (Actual): March 8, 2017
• Last Update Submitted That Met QC Criteria: March 7, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Gaucher Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Eliglustat
• Other Study ID Numbers: POP13778; U1111-1170-3686 (Other Identifier: UTN)