A Study of the Safety, Tolerability, and Pharmacokinetics of Orally Administered Venglustat and Itraconazole in Healthy Adult Male Participants

A Phase I, Single-Center, Open-Label, Two-Period, Single Sequence, Two Treatment Drug-Drug Interaction Study of GZ/SAR402671 (Venglustat) and Itraconazole in Healthy Male Subjects

The purpose of this study is to assess in healthy adult male participants the effects of itraconazole on the pharmacokinetics of venglustat and to assess the safety and tolerability of venglustat with and without coadministration of itraconazole. The maximum duration for participants from screening is between 32 to 62 days.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Venglustat; Drug: Itraconazole

Detailed Description

Total study duration for participants is up to 62 days including screening up to 28 days, 1 day of treatment in period 1, washout of 7 days, 13 days of treatment in period 2, and follow up period 10-14 days after last dose.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78744
      • PPD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria: -Male participants, between 18 and 55 years of age, inclusive.

• Body weight between 50.0 and 100.0 kg, inclusive, body mass index between 18.0 and 30.0 kg/m2, inclusive.
• Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination).
• Normal vital signs, electrocardiogram, and laboratory parameters.
• Having given written informed consent prior to undertaking any study-related procedure.
• Not under any administrative or legal supervision.
• Male participant, whose partners are of childbearing potential (including lactating women), must accept to use, during sexual intercourse, a double contraception method according to the following algorithm: (condom) plus (spermicide or intra-uterine device or hormonal contraceptive) from the inclusion up to 4 months after the last dosing.
• Male participant, whose partners are pregnant, must use, during sexual intercourse, a condom from the inclusion up to 4 months after the last dosing.
• Male participant has agreed not to donate sperm from the inclusion up to 4 months after the last dosing. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply:
• 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 2 months before inclusion.
• Symptomatic postural hypotension excluding vasovagal episode associated with a blood draw.
• Presence or history of clinically significant drug hypersensitivity, or allergic disease diagnosed and treated by a physician.
• History or presence of drug or alcohol abuse (alcohol consumption more than 40 g per day on a regular basis).
• Smoking 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, with the exception of hormonal contraception or menopausal hormone replacement therapy; any vaccination within the last 28 days and any biologics (antibody or its derivatives) given within 4 months before inclusion.
• 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).
• Positive result on urine drug screen or urine alcohol test.
• Any contraindications to itraconazole, according to the applicable labeling.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Venglustat and Itraconazole; The first period will include a single dose administration of venglustat followed by a second period including a multiple dose administration of itraconazole for 12 days and a second single dose administration of venglustat on the 6th day of itraconazole administration	Drug: Venglustat; Pharmaceutical form:Capsule-Route of administration:Oral; Other Names: GZ/SAR402671; Drug: Itraconazole; Pharmaceutical form:Capsule-Route of administration:Oral; Other Names: Sporanox; ITZ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the plasma concentration versus time curve (AUC) of venglustat	Multiple time points up to 21 days
Area under the plasma concentration versus time curve calculated from time zero to the real time (tlast) (AUClast) of venglustat	Multiple time points up to 21 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum plasma concentration observed (Cmax) of venglustat	Multiple time points up to 21 days
Plasma concentration observed just before treatment administration during repeated dosing (Ctrough) of venglustat	Multiple time points up to 21 days
Time to reach Cmax (tmax) of venglustat	Multiple time points up to 21 days
Terminal half-life (t1/2) of venglustat	Multiple time points up to 21 days
Maximum plasma concentration observed (Cmax) of itraconazole	Multiple time points up to 21 days
Plasma concentration observed just before treatment administration during repeated dosing (Ctrough) of itraconazole	Multiple time points up to 21 days
Time to reach Cmax (tmax) of itraconazole	Multiple time points up to 21 days
Area under the plasma concentration versus time curve calculated over the dosing interval (12 h) (AUC0-12) of itraconazole	Multiple time points up to 21 days
Maximum plasma concentration observed (Cmax) of hydroxyitraconazole	Multiple time points up to 21 days
Plasma concentration observed just before treatment administration during repeated dosing (Ctrough) of hydroxyitraconazole	Multiple time points up to 21 days
Time to reach Cmax (tmax) of hydroxyitraconazole	Multiple time points up to 21 days
Area under the plasma concentration versus time curve over the dosing interval (12 h) (AUC0-12) of hydroxyitraconazole	Multiple time points up to 21 days

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2018
• Primary Completion (Actual): October 14, 2018
• Study Completion (Actual): October 14, 2018

Study Registration Dates

• First Submitted: May 13, 2024
• First Submitted That Met QC Criteria: May 17, 2024
• First Posted (Actual): May 20, 2024

Study Record Updates

• Last Update Posted (Actual): May 20, 2024
• Last Update Submitted That Met QC Criteria: May 17, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole; Venglustat
• Other Study ID Numbers: INT14339; 2014-002550-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No