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

NCT ID: NCT02536937

Last Updated: 2017-03-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2017-01-31

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.

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.

Conditions

Gaucher Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GZ385660 (healthy subjects)

Single dose of eliglustat tartrate will be given under fed conditions

Group Type: EXPERIMENTAL

eliglustat

Intervention Type: DRUG

Pharmaceutical form: capsule

Route of administration: oral

GZ385660 (subjects with mild renal impairment)

Single dose of eliglustat tartrate will be given under fed conditions

Group Type: EXPERIMENTAL

eliglustat

Intervention Type: DRUG

Pharmaceutical form: capsule

Route of administration: oral

GZ385660 (subjects with moderate renal impairment)

Single dose of eliglustat tartrate will be given under fed conditions

Group Type: EXPERIMENTAL

eliglustat

Intervention Type: DRUG

Pharmaceutical form: capsule

Route of administration: oral

GZ385660 (subjects with severe renal impairment)

Single dose of eliglustat tartrate will be given under fed conditions

Group Type: EXPERIMENTAL

eliglustat

Intervention Type: DRUG

Pharmaceutical form: capsule

Route of administration: oral

Interventions

eliglustat

Pharmaceutical form: capsule

Route of administration: oral

Intervention Type: DRUG

Other Intervention Names

GZ385660

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 840004

Miami, Florida, United States

Investigational Site Number 840002

Saint Paul, Minnesota, United States

Investigational Site Number 840001

Knoxville, Tennessee, United States

Countries

United States

Other Identifiers

U1111-1170-3686

Identifier Type: OTHER

Identifier Source: secondary_id

POP13778

Identifier Type: -

Identifier Source: org_study_id