A Study to Evaluate Absolute Bioavailability, Absorption, Metabolism, and Excretion of Genz-112638 in Healthy Male Participants
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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 Design
Arms and Interventions
| 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:
Drug: Genz-112638
Pharmaceutical form:Capsule-Route of administration:Oral
Other Names:
|
| 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:
Drug: Genz-112638
Pharmaceutical form:Capsule-Route of administration:Oral
Other Names:
Drug: [14C]-Genz-112638
Pharmaceutical form:Solution-Route of administration:Oral
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Assessment of pharmacokinetic (PK) parameter: Cmax [Multiple timepoints up to Day 26]
Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints
- 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-∞ [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: 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: F [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
- Assessment of pharmacokinetic (PK) parameter: t½ [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 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.
- 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: % 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].
- 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: 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
- Number of participants with treatment-emergent adverse events (TEAEs), serious adverse event (SAEs), and adverse event of special interest (AESI) [Up to Day 33]
Eligibility Criteria
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.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Sanofi
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GZGD02107
- U1111-1294-7994