Safety, Tolerability and Pharmacokinetics of Genz-682452 in Healthy Men

A Randomized, Double-blind, Placebo-controlled Study of the Safety, Tolerability and Pharmacokinetics of Ascending Single Oral Doses of Genz-682452 With a Pilot Investigation of Food Effect in Healthy Adult Male Subjects.

The objectives of this study are to assess the tolerability, safety and pharmacokinetic parameters of Genz-682452 in healthy adult males, in two parts.

Part 1 (GZFD00111TDU12766): double-blind, randomized, placebo-controlled, sequential ascending single dose study;

Part 2 (GZFD00211FED12767): open-label, randomized, 2-sequence, 2-period, 2-treatment crossover study with a minimum wash-out period; to obtain preliminary information on the pharmacokinetics, tolerability and safety of Genz-682452 after single oral doses in fed and fasted conditions.

Subjects are not allowed to participate in more than 1 part of the study.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: Genz-682452; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Body weight between 50.0 and 100.0 kg, inclusive, body mass index between 18.0 and 32.0 kg/m^2, inclusive.
• Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination).

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.
• Blood donation, greater than 100 mL, within 2 months before inclusion.
• Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician.
• History or presence of drug or alcohol abuse.
• Unable to stop smoking cigarettes during the study.
• Excessive consumption of beverages containing xanthine bases.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 (GZFD00111/TDU12766): Genz-682452; Participants will receive a single oral dose of Genz-682452. Six ascending single doses and an optional seventh dose under fasted conditions will be used.	Drug: Genz-682452; Capsules for oral administration.
Placebo Comparator: Part 1 (GZFD00111/TDU12766): Placebo; Participants will receive a single oral dose of placebo.	Drug: Placebo; Placebo to Genz-682452
Experimental: Part 2 (GZFD00211/FED12767): Genz-682452; Participants will receive two single doses of Genz-682452 separated by a 7-day wash-out period, one dose given under fed (standardized high-fat breakfast) and one under fasted conditions. The dose will be based on the blind review of the safety/tolerability/pharmacokinetic data of single dose level cohorts in Part 1.	Drug: Genz-682452; Capsules for oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with adverse events in Part 1	Up to 4 weeks
Number of participants with adverse events in Part 2	Up to 5 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics Plasma Parameters for Part 1 as measured by Cmax, tmax, AUC last, AUC, t1/2z, Vss/F, CL/F	Day 1 through Day 5
Pharmacokinetics Urine Parameters for Part 1 as measured by assessment of Genz-682452 urinary excretion, Ae0-t, fe0-t	Day 1 through Day 5
Pharmacokinetics Plasma Parameters for Part 2 as measured by Cmax, tmax, tlag, AUC last, AUC, t1/2z	Day 1 to Day 3

Collaborators and Investigators

• Sponsor: Genzyme, a Sanofi Company

Publications and helpful links

General Publications

• Peterschmitt MJ, Crawford NPS, Gaemers SJM, Ji AJ, Sharma J, Pham TT. Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Oral Venglustat in Healthy Volunteers. Clin Pharmacol Drug Dev. 2021 Jan;10(1):86-98. doi: 10.1002/cpdd.865. Epub 2020 Aug 26.

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: August 24, 2012
• First Submitted That Met QC Criteria: August 24, 2012
• First Posted (Estimate): August 28, 2012

Study Record Updates

• Last Update Posted (Estimate): March 19, 2014
• Last Update Submitted That Met QC Criteria: March 17, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Other Study ID Numbers: GZFD00111/GZFD00211; TDU12766/FED12767 (Other Identifier: Sanofi Study Number)