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

NCT06143904 | Completed Phase 1 FDA Drug

• 2 other identifiers: GZGD02107U1111-1294-7994
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Gaucher's Disease Type I

Outcome Measures

Primary Outcomes (26)

• 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 Outcomes (1)

• Number of participants with treatment-emergent adverse events (TEAEs), serious adverse event (SAEs), and adverse event of special interest (AESI)

  Up to Day 33

Study Arms (2)

Treatment Period 1 -2

EXPERIMENTAL

Single-dose Intravenous (IV) Genz-112638 Day 1 followed by single dose GenZ-112638 oral capsules Day 8

Drug: Genz-112638

Treatment Period 1-4

EXPERIMENTAL

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; Drug: [14C]-Genz-112638

Interventions

Genz-112638 DRUG

Pharmaceutical form:Solution-Route of administration:IV

Also known as: GZ385660/ eliglustat, Cerdelga

Treatment Period 1 -2; Treatment Period 1-4

[14C]-Genz-112638 DRUG

Pharmaceutical form:Solution-Route of administration:Oral

Also known as: GZ385660/ eliglustat

Treatment Period 1-4

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

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 Design

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

Study Record Dates

• First Submitted: November 16, 2023
• First Posted: November 22, 2023
• Study Start: June 3, 2009
• Primary Completion: July 5, 2009
• Study Completion: July 5, 2009
• Last Updated: November 22, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will share