A Study to Evaluate Pharmacokinetic Parameters of Eliglustat in Healthy Volunteers Who Are CYP2D6 Extensive or Poor Metabolizers

A Randomized, Three-Period Crossover Study of Single and Repeated Doses for Three Different Strengths of Eliglustat in Healthy Adult, CYP2D6 Extensive and Poor Metabolizers

The primary objective of the study is to evaluate dose proportionality and pharmacokinetics for three different dose levels of eliglustat after single and repeated administration.

Study Overview

• Status: Completed
• Conditions: Gaucher's Disease
• Intervention / Treatment: Drug: Eliglustat

Detailed Description

Duration of the study for each subject will be between 42 to 79 days, including a screening period up to 28 days, 3 treatment periods of 7 days each period, a washup period of 7-10 days, and an end-of-study visit 8+/-2 days after the last administration.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • M.D.Covance Clinical Research Unit 1341 W

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Body weight between 50.0 and 100.0 kg, inclusive, if male, and between 40.0 and 90.0 kg, inclusive, if female, body mass index between 18.0 and 30.0 kg/m2, inclusive.
• Certified as healthy by a comprehensive clinical assessment (detailed medical history, complete physical examination, laboratory parameters, electrocardiograms (ECG)).
• Having given written informed consent prior to undertaking any study-related procedure
• Having given written informed consent prior to undertaking any study-related procedure

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

• 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.

The following classes of drugs administered within 14 days before inclusion or within 5 times the elimination half-life or pharmacodynamic half-life of the medication, with the exception of hormonal contraception or menopausal hormone replacement therapy:

• Drugs that are strong inducers of CYP3A (eg, rifampin, carbamazepine, phenobarbital,phenytoin, St. John's Wort).
• Drugs that inhibit CYP2D6 or CYP3A (eg, paroxetine, ketoconazole, fluconazole,ranitidine).
• Drugs that are substrates for P-gp (phenytoin, colchicine and dabigatran etexilate) or CYP2D6 (metoprolol, tricyclic antidepressants such as nortriptyline, amitriptyline, or imipramine, and phenothiazines such as perphenazine and chloropromazine).

The above information is not intended to contain all considerations relevant to the potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; CYP2D6 Extensive metabolizers - dose 1, 2 and 3 of eliglustat	Drug: Eliglustat; Pharmaceutical form:Capsule-Route of administration:Oral; Other Names: Cerdelga; GZ385660
Experimental: Group 2; CYP2D6 Poor metabolizers - dose 1, 2 and 3 of eliglustat	Drug: Eliglustat; Pharmaceutical form:Capsule-Route of administration:Oral; Other Names: Cerdelga; GZ385660

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) parameter: Cmax	Eliglustat after single and repeated doses: Maximum plasma concentration observed (Cmax)	Multiple timepoints up to Day 35
Pharmacokinetic (PK) parameter: tmax	Eliglustat after single and repeated doses: Time to reach Cmax	Multiple timepoints up to Day 35
Pharmacokinetic (PK) parameter: AUC0-T	Eliglustat after single and repeated doses: Area under the plasma concentration versus time curve calculated using the trapezoidal method (AUC0-T)	Multiple timepoints up to Day 35
Pharmacokinetic (PK) parameter: AUC	Eliglustat after single and repeated doses: Area under the plasma concentration versus time curve (AUC)	Multiple timepoints up to Day 35

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) parameter: AUClast	Eliglustat after single and repeated doses: Area under the plasma concentration versus time curve calculated using the trapezoidal method from time zero to the real time tlast	Multiple timepoints up to Day 35
Pharmacokinetic (PK) parameter: tlast	Eliglustat after single and repeated doses: Time corresponding to the last concentration above the limit of quantification, Clast	Multiple timepoints up to Day 35
Pharmacokinetic (PK) parameter: CL/F	Eliglustat after single and repeated doses: Eliglustat after repeated dose: CL/F	Multiple timepoints up to Day 35
Pharmacokinetic (PK) parameter: t1/2z	Eliglustat after single and repeated doses: Terminal half-life associated with the terminal slope (λz)	Multiple timepoints up to Day 35
Pharmacokinetic (PK) parameter: Ctrough	Eliglustat after single and repeated doses: Plasma concentration observed just before treatment administration during repeated dosing	Multiple timepoints up to Day 35
Number of participants with treatment emergent adverse events, serious adverse events, and adverse event of special interest	Safety was assessed using clinical laboratory evaluations, ECG parameters, and adverse events spontaneously reported by the subject or observed by the Investigator	Up to Day 42

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): March 26, 2018
• Study Completion (Actual): March 26, 2018

Study Registration Dates

• First Submitted: December 18, 2023
• First Submitted That Met QC Criteria: December 18, 2023
• First Posted (Actual): January 3, 2024

Study Record Updates

• Last Update Posted (Actual): January 10, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: December 1, 2023

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: PKM14281; U1111-1294-8432 (Registry Identifier: ICTRP)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No