Clinical trial NCT02536911: A Study of the Effects of Hepatic Impairment on the Pharmacokinetics and Tolerability of Eliglustat Tartrate
Official title: An Open-label Pharmacokinetic and Tolerability Study of Eliglustat Tartrate Given as a Single Dose in Subjects With Mild and Moderate Hepatic Impairment, and in Matched Subjects With Normal Hepatic Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gaucher Disease
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2015-09-01
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: The total study duration from screening period is approximately 31 days.

Eligibility criteria: Inclusion criteria :

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).

Exclusion criteria:

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.
* History or presence of drug or alcohol abuse (alcohol consumption more than 40 g per day) within 2 years before inclusion.
* 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.
* For subjects 50 years of age and younger: 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 the 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) given within 4 months before inclusion.
* For subjects older than 50 years of age: any significant change in chronic treatment medication within 14 days before inclusion.
* P-gp inhibitors and/or inducers, CYP2D6 and/or CYP3A inhibitors and/or inducers.
* Positive result on any of the following tests: hepatitis B surface antigen (HBs Ag), anti-hepatitis C virus (anti-HCV) antibodies, anti-HIV1 and anti-HIV2 Ab.
* History or presence of drug or alcohol abuse (alcohol consumption more than 40 g per day) within 2 years before inclusion.
* 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.

Primary outcomes:
measure: Assessment of PK parameter: Maximum plasma concentration observed (Cmax)
timeFrame: 3 days
measure: Assessment of PK parameter: Area under the plasma concentration (AUC)
timeFrame: 3 days
Secondary outcomes:
measure: Assessment of PK parameter: Area under the plasma concentration versus time curve (AUClast)
timeFrame: 3 days
measure: Assessment of PK parameter: Apparent total body clearance (CL/F)
timeFrame: 3 days
measure: Assessment of PK parameter: Apparent volume of distribution during the terminal phase (Vz/F)
timeFrame: 3 days
measure: Assessment of PK parameter: Predicted accumulation ratio (Rac,pred)
timeFrame: 3 days
measure: Assessment of PK parameter: Terminal half-life (t1/2z)
timeFrame: 3 days
measure: Change from baseline in ECG parameter
timeFrame: Baseline, Up to 10 days
measure: Number of adverse events
timeFrame: Up to 10 days
Other outcomes:
Locations:
city: Miami
country: United States
facility: Investigational Site Number 840002
state: Florida
city: Knoxville
country: United States
facility: Investigational Site Number 840001
state: Tennessee
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: