A Study to Evaluate Absolute Bioavailability, Absorption, Metabolism, and Excretion of Genz-112638 in Healthy Male Participants

An Open-Label Study to Evaluate the Absolute Bioavailability of Genz-112638 and the Absorption, Metabolism, and Excretion of [14C]-Genz-112638 in Male Subjects

Objectives:

To determine pharmacokinetic (PK) variables, including absolute bioavailability (F), of Genz-99067, the free base of the L-tartaric acid salt of Genz-112638 as it exists in plasma, after a single intravenous (IV) dose and after a single oral dose of Genz-112638 (unlabeled).

To determine the PK, total recovery, routes and rates of excretion, and the metabolic profile of Genz-99067 after 5 days of BID oral dosing with unlabeled Genz-112638 followed by a single dose of [14C]-Genz-112638.

Study Overview

• Status: Completed
• Conditions: Gaucher's Disease Type I
• Intervention / Treatment: Drug: Genz-112638; Drug: Genz-112638; Drug: [14C]-Genz-112638

Detailed Description

The maximum study duration for an individual subject was approximately 65 days from the beginning of Screening through the Safety Follow-up visit.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria: Having given written informed consent prior to undertaking any study-related procedure The subject has a body weight of 50 to 100 kg [110 to 220 pounds (lb)] with a body mass index (BMI) less than 30 kilograms per square meter (kg/m2) at Screening.

The subject's physical examination results, vital signs, laboratory assessments, and cardiac assessments are within normal limits or, if abnormal, are not clinically significant at Screening and Day -1. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply:

Prolonged QTc interval (eg, repeated demonstration of a QTc interval ≥450 msec), family history of long QT or Brugada Syndrome, and/or history of sudden death in a first-degree relative.

The subject receives an immunization within 30 days of providing informed consent.

The subject has a history of drug allergies (eg, significant rash, hives, etc in response to antibiotics).

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: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Period 1 -2; Single-dose Intravenous (IV) Genz-112638 Day 1 followed by single dose GenZ-112638 oral capsules Day 8	Drug: Genz-112638; Pharmaceutical form:Solution-Route of administration:IV; Other Names: Cerdelga; GZ385660/ eliglustat; Drug: Genz-112638; Pharmaceutical form:Capsule-Route of administration:Oral; Other Names: GZ385660/ eliglustat
Experimental: Treatment Period 1-4; Single-dose Intravenous (IV) Genz-112638 Day 1; single dose GenZ-112638 oral capsules Day 8; oral capsule Genz-112638 Days 9-14; single dose [14C]-Genz-112638 oral solution Day 15	Drug: Genz-112638; Pharmaceutical form:Solution-Route of administration:IV; Other Names: Cerdelga; GZ385660/ eliglustat; Drug: Genz-112638; Pharmaceutical form:Capsule-Route of administration:Oral; Other Names: GZ385660/ eliglustat; Drug: [14C]-Genz-112638; Pharmaceutical form:Solution-Route of administration:Oral; Other Names: GZ385660/ eliglustat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of pharmacokinetic (PK) parameter: Cmax	Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints	Multiple timepoints up to Day 26
Assessment of pharmacokinetic (PK) parameter: Tmax	Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints	Multiple timepoints up to Day 26
Assessment of pharmacokinetic (PK) parameter: AUC0-∞	Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints	Multiple timepoints up to Day 26
Assessment of pharmacokinetic (PK) parameter: AUC0 -τ	Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints	Multiple timepoints up to Day 26
Assessment of pharmacokinetic (PK) parameter: AUC0-∞/D	Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints	Multiple timepoints up to Day 26
Assessment of pharmacokinetic (PK) parameter: AUC0-τ/D	Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints	Multiple timepoints up to Day 26
Assessment of pharmacokinetic (PK) parameter: F	Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints	Multiple timepoints up to Day 26
Assessment of pharmacokinetic (PK) parameter: CL/F	Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints	Multiple timepoints up to Day 26
Assessment of pharmacokinetic (PK) parameter: t½	Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints	Multiple timepoints up to Day 26
Pharmacokinetic (PK) parameter: Absolute bioavailability (F) of single-dose oral versus single-dose IV administration		Multiple timepoints up to Day 26
Assessment of pharmacokinetic (PK) parameter: Total radioactivity excreted in urine and feces	Total radioactivity excreted in urine and feces will be converted to percentage of radioactive dose.	Multiple timepoints up to Day 26
Assessment of pharmacokinetic (PK) parameter: Total radioactivity in whole blood and plasma	Total radioactivity in whole blood and plasma will be converted to ngEq/g Genz-99067 concentration for whole blood and ngEq/mL for plasma, based on the dose specific activity.	Multiple timepoints up to Day 26
Assessment of pharmacokinetic (PK) parameter: % relative abundance of each component in samples of plasma or excreta	It will be estimated as [(radioactivity for the HPLC peak)/(total radioactivity injected per HPLC run) x 100].	Multiple timepoints up to Day 26
Assessment of pharmacokinetic (PK) parameter: The percentage of the administered dose attributed to each component in samples of urine or feces	It will be estimated as [(% relative abundance)/100 x (percentage of radioactive dose in the sample)].	Multiple timepoints up to Day 26
Assessment of pharmacokinetic (PK) parameter: The radioactivity of [14C]-Genz-99067 and each major metabolite in plasma, as identified by radio-profiling	It will be converted to equivalent concentrations as [(% relative abundance)/100 x (equivalent concentration of total radioactivity in the sample)].	Multiple timepoints up to Day 26
Noncompartmental PK parameters: AUC0-t		Multiple timepoints up to Day 26
Noncompartmental PK parameters: AUC0-∞		Multiple timepoints up to Day 26
Noncompartmental PK parameters: Cmax		Multiple timepoints up to Day 26
Noncompartmental PK parameters: Tmax		Multiple timepoints up to Day 26
Noncompartmental PK parameters: t½		Multiple timepoints up to Day 26
Noncompartmental PK parameters: Vz/F		Multiple timepoints up to Day 26
Noncompartmental PK parameters: CL/F		Multiple timepoints up to Day 26
Noncompartmental PK parameters for urine and feces: Cum Ae		Multiple timepoints up to Day 26
Noncompartmental PK parameters for urine and feces: % dose		Multiple timepoints up to Day 26
Renal clearance (CLR) for total plasma radioactivity and Genz-99067		Multiple timepoints up to Day 26
PK parameters [AUC0-τ, AUC0-∞, Cmax, Tmax, t½] and metabolite ratio for metabolite(s) of Genz-99067		Multiple timepoints up to Day 26

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with treatment-emergent adverse events (TEAEs), serious adverse event (SAEs), and adverse event of special interest (AESI)	Up to Day 33

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2009
• Primary Completion (Actual): July 5, 2009
• Study Completion (Actual): July 5, 2009

Study Registration Dates

• First Submitted: November 16, 2023
• First Submitted That Met QC Criteria: November 16, 2023
• First Posted (Estimated): November 22, 2023

Study Record Updates

• Last Update Posted (Estimated): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 16, 2023
• Last Verified: November 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: GZGD02107; U1111-1294-7994 (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