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

NCT02536911 | Completed Phase 1

• 2 other identifiers: POP13777U1111-1170-3678
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

Primary Objective: To study the effect of mild and moderate hepatic 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 and moderate hepatic impairment in comparison with matched subjects with normal hepatic function.

Conditions

Gaucher Disease

Outcome Measures

Primary Outcomes (2)

• Assessment of PK parameter: Maximum plasma concentration observed (Cmax)

  3 days

• Assessment of PK parameter: Area under the plasma concentration (AUC)

  3 days

Secondary Outcomes (7)

• 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

Study Arms (3)

GZ385660 (healthy subjects)

EXPERIMENTAL

Single dose of eliglustat tartrate will be given under fed conditions

Drug: eliglustat

GZ385660 (subjects with mild hepatic impairment)

EXPERIMENTAL

Single dose of eliglustat tartrate will be given under fed conditions

Drug: eliglustat

GZ385660 (subjects with moderate hepatic impairment)

EXPERIMENTAL

Single dose of eliglustat tartrate will be given under fed conditions

Drug: eliglustat

Interventions

eliglustat DRUG

Pharmaceutical form: capsule Route of administration: oral

Also known as: GZ385660

GZ385660 (healthy subjects); GZ385660 (subjects with mild hepatic impairment); GZ385660 (subjects with moderate hepatic impairment)

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For subjects with hepatic impairment:
• Male or female subjects, between 18 and 79 years of age, inclusive.
• Body weight between 50.0 and 125.0 kg, inclusive if male, and between 40.0 and 110.0 kg, inclusive if female, body mass index (BMI) between 18.0 and 37 kg/m\^2, inclusive.
• Stable chronic liver disease assessed by medical history, physical examination, laboratory values.
• For moderate hepatic impairment cohort: Child-Pugh total score ranging from 7 to 9, inclusive.
• For mild hepatic impairment cohort: Child-Pugh total score ranging from 5 to 6, inclusive.
• For matched subjects:
• Male or female subjects, between 18 and 79 years of age, inclusive.
• Body weight within 15% of the body weight of the subjects with hepatic impairment and BMI between 18.0 and 37 kg/m\^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).

You may not qualify if:

• For subjects with hepatic impairment:
• Uncontrolled clinically relevant cardiovascular, pulmonary, gastrointestinal, metabolic, hematological, neurological, psychiatric, systemic, ocular, gynecologic (if female), or infectious disease, or signs of acute illness.
• Hepatocarcinoma.
• Acute hepatitis.
• Hepatic encephalopathy grade 2, 3, and 4.
• Presence or history of drug hypersensitivity, or allergic disease, including active seasonal rhinitis, diagnosed and treated by a physician.
• If female, pregnancy (defined as positive beta-human chorionic gonadotropin \[β -HCG\] blood test), breastfeeding.
• P-gp inhibitors and/or inducers, CYP2D6 and/or CYP3A inhibitors and/or inducers.
• 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 subjects:
• 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), breastfeeding.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (2)

Investigational Site Number 840002

Miami, Florida, 33014, United States

Location

Investigational Site Number 840001

Knoxville, Tennessee, 37920, United States

Location

MeSH Terms

Conditions

Gaucher Disease

Interventions

eliglustat

Condition Hierarchy (Ancestors)

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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2015
• First Posted: September 1, 2015
• Study Start: September 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: February 10, 2017

Record last verified: 2017-02

Locations

US (2)