A Study to Evaluate Absolute Bioavailability, Absorption, Metabolism, and Excretion of Genz-112638 in Healthy Male Participants
- Conditions
- Gaucher's Disease Type I
- Interventions
- Drug: [14C]-Genz-112638
- Registration Number
- NCT06143904
- Lead Sponsor
- Sanofi
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 10
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.
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Treatment Period 1 -2 Genz-112638 Single-dose Intravenous (IV) Genz-112638 Day 1 followed by single dose GenZ-112638 oral capsules Day 8 Treatment Period 1-4 Genz-112638 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 Treatment Period 1-4 [14C]-Genz-112638 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
- Primary Outcome Measures
Name Time Method Assessment of pharmacokinetic (PK) parameter: AUC0-∞ Multiple timepoints up to Day 26 Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints
Assessment of pharmacokinetic (PK) parameter: t½ Multiple timepoints up to Day 26 Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints
Assessment of pharmacokinetic (PK) parameter: AUC0-∞/D Multiple timepoints up to Day 26 Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints
Assessment of pharmacokinetic (PK) parameter: AUC0-τ/D Multiple timepoints up to Day 26 Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints
Assessment of pharmacokinetic (PK) parameter: % relative abundance of each component in samples of plasma or excreta Multiple timepoints up to Day 26 It will be estimated as \[(radioactivity for the HPLC peak)/(total radioactivity injected per HPLC run) x 100\].
Noncompartmental PK parameters: AUC0-t Multiple timepoints up to Day 26 Noncompartmental PK parameters: CL/F Multiple timepoints up to Day 26 Assessment of pharmacokinetic (PK) parameter: F Multiple timepoints up to Day 26 Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints
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 Assessment of pharmacokinetic (PK) parameter: Cmax Multiple timepoints up to Day 26 Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints
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 in whole blood and plasma Multiple timepoints up to Day 26 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.
Assessment of pharmacokinetic (PK) parameter: The percentage of the administered dose attributed to each component in samples of urine or feces Multiple timepoints up to Day 26 It will be estimated as \[(% relative abundance)/100 x (percentage of radioactive dose in the sample)\].
Assessment of pharmacokinetic (PK) parameter: The radioactivity of [14C]-Genz-99067 and each major metabolite in plasma, as identified by radio-profiling Multiple timepoints up to Day 26 It will be converted to equivalent concentrations as \[(% relative abundance)/100 x (equivalent concentration of total radioactivity in the sample)\].
Noncompartmental PK parameters: Cmax Multiple timepoints up to Day 26 Noncompartmental PK parameters: t½ Multiple timepoints up to Day 26 Noncompartmental PK parameters for urine and feces: Cum Ae Multiple timepoints up to Day 26 Assessment of pharmacokinetic (PK) parameter: Tmax Multiple timepoints up to Day 26 Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints
Assessment of pharmacokinetic (PK) parameter: AUC0 -τ Multiple timepoints up to Day 26 Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints
Assessment of pharmacokinetic (PK) parameter: CL/F Multiple timepoints up to Day 26 Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints
Noncompartmental PK parameters: Vz/F 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 Assessment of pharmacokinetic (PK) parameter: Total radioactivity excreted in urine and feces Multiple timepoints up to Day 26 Total radioactivity excreted in urine and feces will be converted to percentage of radioactive dose.
Noncompartmental PK parameters: AUC0-∞ Multiple timepoints up to Day 26 Noncompartmental PK parameters: Tmax Multiple timepoints up to Day 26
- Secondary Outcome Measures
Name Time Method Number of participants with treatment-emergent adverse events (TEAEs), serious adverse event (SAEs), and adverse event of special interest (AESI) Up to Day 33