Clinical trial NCT06143904: A Study to Evaluate Absolute Bioavailability, Absorption, Metabolism, and Excretion of Genz-112638 in Healthy Male Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gaucher's Disease Type I
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2023-11-22
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Assessment of pharmacokinetic (PK) parameter: Cmax
timeFrame: Multiple timepoints up to Day 26
measure: Assessment of pharmacokinetic (PK) parameter: Tmax
timeFrame: Multiple timepoints up to Day 26
measure: Assessment of pharmacokinetic (PK) parameter: AUC0-∞
timeFrame: Multiple timepoints up to Day 26
measure: Assessment of pharmacokinetic (PK) parameter: AUC0 -τ
timeFrame: Multiple timepoints up to Day 26
measure: Assessment of pharmacokinetic (PK) parameter: AUC0-∞/D
timeFrame: Multiple timepoints up to Day 26
measure: Assessment of pharmacokinetic (PK) parameter: AUC0-τ/D
timeFrame: Multiple timepoints up to Day 26
measure: Assessment of pharmacokinetic (PK) parameter: F
timeFrame: Multiple timepoints up to Day 26
measure: Assessment of pharmacokinetic (PK) parameter: CL/F
timeFrame: Multiple timepoints up to Day 26
measure: Assessment of pharmacokinetic (PK) parameter: t½
timeFrame: Multiple timepoints up to Day 26
measure: Pharmacokinetic (PK) parameter: Absolute bioavailability (F) of single-dose oral versus single-dose IV administration
timeFrame: Multiple timepoints up to Day 26
measure: Assessment of pharmacokinetic (PK) parameter: Total radioactivity excreted in urine and feces
timeFrame: Multiple timepoints up to Day 26
measure: Assessment of pharmacokinetic (PK) parameter: Total radioactivity in whole blood and plasma
timeFrame: Multiple timepoints up to Day 26
measure: Assessment of pharmacokinetic (PK) parameter: % relative abundance of each component in samples of plasma or excreta
timeFrame: Multiple timepoints up to Day 26
measure: Assessment of pharmacokinetic (PK) parameter: The percentage of the administered dose attributed to each component in samples of urine or feces
timeFrame: Multiple timepoints up to Day 26
measure: Assessment of pharmacokinetic (PK) parameter: The radioactivity of [14C]-Genz-99067 and each major metabolite in plasma, as identified by radio-profiling
timeFrame: Multiple timepoints up to Day 26
measure: Noncompartmental PK parameters: AUC0-t
timeFrame: Multiple timepoints up to Day 26
measure: Noncompartmental PK parameters: AUC0-∞
timeFrame: Multiple timepoints up to Day 26
measure: Noncompartmental PK parameters: Cmax
timeFrame: Multiple timepoints up to Day 26
measure: Noncompartmental PK parameters: Tmax
timeFrame: Multiple timepoints up to Day 26
measure: Noncompartmental PK parameters: t½
timeFrame: Multiple timepoints up to Day 26
measure: Noncompartmental PK parameters: Vz/F
timeFrame: Multiple timepoints up to Day 26
measure: Noncompartmental PK parameters: CL/F
timeFrame: Multiple timepoints up to Day 26
measure: Noncompartmental PK parameters for urine and feces: Cum Ae
timeFrame: Multiple timepoints up to Day 26
measure: Noncompartmental PK parameters for urine and feces: % dose
timeFrame: Multiple timepoints up to Day 26
measure: Renal clearance (CLR) for total plasma radioactivity and Genz-99067
timeFrame: Multiple timepoints up to Day 26
measure: PK parameters [AUC0-τ, AUC0-∞, Cmax, Tmax, t½] and metabolite ratio for metabolite(s) of Genz-99067
timeFrame: Multiple timepoints up to Day 26
Secondary outcomes:
measure: Number of participants with treatment-emergent adverse events (TEAEs), serious adverse event (SAEs), and adverse event of special interest (AESI)
timeFrame: Up to Day 33
Other outcomes:
Locations:
Study officials:
References: