Gaucher's Disease Type I
Conditions
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.
Interventions
DRUGGenz-112638
Pharmaceutical form:Solution-Route of administration:IV
DRUG[14C]-Genz-112638
Pharmaceutical form:Solution-Route of administration:Oral
Sponsors
Sanofi
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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: 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 | — |
Secondary
| Measure | 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 |
Outcome results
None listed