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

Gaucher's Disease Type I Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06143904
• Other study ID #: GZGD02107
• Secondary ID: U1111-1294-7994
• Status: Completed
• Phase: Phase 1
• Start date: June 3, 2009
• Est. completion date: July 5, 2009

Study information

• Verified date: November 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: July 5, 2009
• Est. primary completion date: July 5, 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Gaucher Disease
• Gaucher's Disease Type I

Intervention

Drug:
• Genz-112638
Pharmaceutical form:Solution-Route of administration:IV
• Genz-112638
Pharmaceutical form:Capsule-Route of administration:Oral
• [14C]-Genz-112638
Pharmaceutical form:Solution-Route of administration:Oral

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of pharmacokinetic (PK) parameter: Cmax	Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints	Multiple timepoints up to Day 26
Primary	Assessment of pharmacokinetic (PK) parameter: Tmax	Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints	Multiple timepoints up to Day 26
Primary	Assessment of pharmacokinetic (PK) parameter: AUC0-8	Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints	Multiple timepoints up to Day 26
Primary	Assessment of pharmacokinetic (PK) parameter: AUC0 -t	Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints	Multiple timepoints up to Day 26
Primary	Assessment of pharmacokinetic (PK) parameter: AUC0-8/D	Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints	Multiple timepoints up to Day 26
Primary	Assessment of pharmacokinetic (PK) parameter: AUC0-t/D	Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints	Multiple timepoints up to Day 26
Primary	Assessment of pharmacokinetic (PK) parameter: F	Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints	Multiple timepoints up to Day 26
Primary	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
Primary	Assessment of pharmacokinetic (PK) parameter: t½	Plasma concentrations of Genz-99067 will be collected at pre-specified timepoints	Multiple timepoints up to Day 26
Primary	Pharmacokinetic (PK) parameter: Absolute bioavailability (F) of single-dose oral versus single-dose IV administration		Multiple timepoints up to Day 26
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Noncompartmental PK parameters: AUC0-t		Multiple timepoints up to Day 26
Primary	Noncompartmental PK parameters: AUC0-8		Multiple timepoints up to Day 26
Primary	Noncompartmental PK parameters: Cmax		Multiple timepoints up to Day 26
Primary	Noncompartmental PK parameters: Tmax		Multiple timepoints up to Day 26
Primary	Noncompartmental PK parameters: t½		Multiple timepoints up to Day 26
Primary	Noncompartmental PK parameters: Vz/F		Multiple timepoints up to Day 26
Primary	Noncompartmental PK parameters: CL/F		Multiple timepoints up to Day 26
Primary	Noncompartmental PK parameters for urine and feces: Cum Ae		Multiple timepoints up to Day 26
Primary	Noncompartmental PK parameters for urine and feces: % dose		Multiple timepoints up to Day 26
Primary	Renal clearance (CLR) for total plasma radioactivity and Genz-99067		Multiple timepoints up to Day 26
Primary	PK parameters [AUC0-t, AUC0-8, Cmax, Tmax, t½] and metabolite ratio for metabolite(s) of Genz-99067		Multiple timepoints up to Day 26
Secondary	Number of participants with treatment-emergent adverse events (TEAEs), serious adverse event (SAEs), and adverse event of special interest (AESI)		Up to Day 33