Clinical trial NCT05238714: Excretion Balance, Pharmacokinetics, and Metabolism Following of [14C]-Venglustat Administration in Healthy Male Subjects
Official title: An Open-label Study of Excretion Balance and Pharmacokinetics Following a Single Oral Dose of [14C]-Venglustat (2.67 MBq) in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Disorders of Sphingolipid Metabolism
Healthy Volunteers
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2022-02-14
Enrollment: 6
Sex: MALE
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

Brief summary: Primary Objectives:

* To determine the excretion balance and systemic exposure of radioactivity after oral administration of \[14C\]-venglustat.
* To determine the pharmacokinetics (PK) of venglustat and its contribution to the overall exposure of radioactivity.
* To determine the metabolic pathways, metabolite profile, chemical structures and main excretion route of the main venglustat metabolites and the metabolite contribution to the overall exposure of radioactivity.

Secondary Objective:

To assess the clinical and biological tolerability of oral solution of venglustat

Detailed description: 43 days

Eligibility criteria: Inclusion Criteria:

* Body weight between 50.0 and 100.0 kg, inclusive, body Mass Index 18 to 32 kg/m2, inclusive
* Certified as healthy by a comprehensive clinical assessment
* Normal vital signs after 10 minutes resting in supine position
* Standard 12-lead electrocardiogram (ECG) parameters after 10 minutes resting in supine position in the following ranges; 120 ms≤PR≤230 msec, QRS≤120 msec, QTc≤450 msec and normal ECG tracing unless the Investigator considers an ECG tracing abnormality to be not clinically relevant
* Laboratory parameters within the normal range
* Having given written informed consent prior to undertaking any study-related procedure
* Covered by a health insurance system where applicable, and/or in compliance with the recommendations of the national laws in force relating to biomedical research
* Not under any administrative or legal supervision
* Normal renal function as expressed by a creatinine clearance \>80 mL/min as calculated by the Cockroft and Gault formula
* Male subjects who agree to use condoms, whose female partner(s) are of childbearing potential (including lactating women), must accept to use, during sexual intercourse, a double contraception method (unless they underwent surgical sterilization) until 90 days after the end of study

Exclusion Criteria:

* Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, or infectious disease, or signs of acute illness
* Frequent headaches and/or migraine, recurrent nausea and/or vomiting (for vomiting only: more than twice a month).
* Blood donation, any volume, within 3 months before inclusion.
* Symptomatic postural hypotension, irrespective of the decrease in blood pressure.
* Presence or history of clinically significant drug hypersensitivity, or allergic disease diagnosed and treated by a physician that in the opinion of the Investigator would compromise subject safety.
* History or presence of drug or alcohol abuse (alcohol consumption more than 14 units per week on a regular basis) in the 5 years prior to screening.
* Smoking or using nicotine replacement products or e-cigarettes regularly more than 5 cigarettes or equivalent per week, unable to stop smoking during the study (occasional smoker can be enrolled).
* Excessive consumption of beverages containing xanthine bases (more than 4 cups or glasses per day)
* Any medication (including St John's Wort) within 14 days before inclusion or within 5 times the elimination half-life or pharmacodynamic half-life of the medication; any vaccination or any medications known to be CYP3A4 inducers within the last 28 days and any biologics (antibody or its derivatives) given within 4 months before inclusion
* Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the Investigator at screening.
* Any subject who, in the judgment of the Investigator, is likely to be noncompliant during the study, or unable to cooperate because of a language problem or poor mental development.
* Any subject enrolled in or having participated, in \[this or\] any other clinical study involving an investigational medicinal product (IMP) according to applicable regulations/guidelines in the 3 months prior to dosing of this study.
* Any subject who cannot be contacted in case of emergency.
* Any subject who is the Investigator or any sub investigator, research assistant, pharmacist, study coordinator, or other staff thereof, directly involved in conducting the study
* Positive result on any of the following tests: hepatitis B surface (HBs Ag) antigen, anti-hepatitis C virus (anti-HCV) antibodies, anti-human immunodeficiency virus 1 and 2 antibodies (anti-HIV1 and anti HIV2 Ab).
* Confirmed positive result on urine drug screen (amphetamines/methamphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, tricyclic antidepressants, opiates including methadone).
* Positive alcohol breath test
* Any subject with specific dietary habits, such as vegan.
* Any subject with irregular bowel habits (more than 3 bowel movements/day or less than 1 every 2 days).
* Any subject undergoing dental care or presenting with dental caries.
* Any subject who is occupationally exposed to radiation as defined in the Ionizing Radiations Regulations 2017
* Participation in a trial with 14C-radiolabelled medication in the 12 months preceding the study.
* Radiation exposure, including that from the present study and radiopharmaceuticals or radionuclides in therapeutic or diagnostic procedures, but excluding background radiation, exceeding 5 millisievert (mSv) in the last 12 months or 10 mSv in the last 5 years.
* Any consumption of citrus (grapefruit, orange, etc) or their juices within 5 days before inclusion

The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial.

Primary outcomes:
measure: Percentage of radioactive dose excreted in urine and faeces
timeFrame: Day -1 up to max Day 43
measure: Cmax of plasma and blood radioactivity
timeFrame: Day 1 up to max Day 43
measure: AUC Last of plasma and blood radioactivity
timeFrame: Day 1 up to max Day 43
measure: AUC Last of plasma venglustat
timeFrame: Day 1 up to max Day 43
measure: tmax of plasma and blood radioactivity
timeFrame: Day 1 up to max Day 43
measure: tmax of plasma venglustat
timeFrame: Day 1 up to max Day 43
Secondary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Day 1 up to max Day 43
measure: Percentage of venglustat metabolites in plasma
timeFrame: Day 1 up to max Day 43
measure: Percentage of venglustat metabolites in urine
timeFrame: Day 1 up to max Day 43
measure: Percentage of venglustat metabolites in faeces
timeFrame: Day 1 up to max Day 43
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Investigational Site Number :8260001
state: Nottinghamshire
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: