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

Study Overview
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Brief Summary
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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.

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

Official Title
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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

Conditions
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Gaucher's Disease Type I

Intervention / Treatment
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* Drug: Genz-112638
* Drug: Genz-112638
* Drug: [14C]-Genz-112638


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Period 1 -2<br>Single-dose Intravenous (IV) Genz-112638 Day 1 followed by single dose GenZ-112638 oral capsules Day 8 | Drug: Genz-112638<br>* Pharmaceutical form:Solution-Route of administration:IV<br>* Other names: Cerdelga;Drug: Genz-112638<br>* Pharmaceutical form:Capsule-Route of administration:Oral<br>* Other names: GZ385660/ eliglustat;|
| Experimental: Treatment Period 1-4<br>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<br>* Pharmaceutical form:Solution-Route of administration:IV<br>* Other names: Cerdelga;Drug: Genz-112638<br>* Pharmaceutical form:Capsule-Route of administration:Oral<br>* Other names: GZ385660/ eliglustat;Drug: [14C]-Genz-112638<br>* Pharmaceutical form:Solution-Route of administration:Oral<br>* Other names: GZ385660/ eliglustat;|

What is the study measuring?
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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 | Measure Description | 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 |