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

Gaucher Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02536937
• Other study ID #: POP13778
• Secondary ID: U1111-1170-3686
• Status: Completed
• Phase: Phase 1
• First received: August 28, 2015
• Last updated: March 7, 2017
• Start date: September 2015
• Est. completion date: January 2017

Study information

• Verified date: March 2017
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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 [ß-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 ß-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.

Related Conditions & MeSH terms

• Gaucher Disease
• Renal Insufficiency

Intervention

Drug:
• eliglustat
Pharmaceutical form: capsule Route of administration: oral

Locations

Country	Name	City	State
United States	Investigational Site Number 840001	Knoxville	Tennessee
United States	Investigational Site Number 840004	Miami	Florida
United States	Investigational Site Number 840002	St. Paul	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Country where clinical trial is conducted

United States, 

Outcome

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