A Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics Study of Genz-682452 in Healthy Volunteers

Study Overview
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Brief Summary
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To assess in healthy adult subjects: The tolerability and safety of ascending repeated oral doses of Genz-682452. The pharmacokinetic parameters of Genz-682452 after ascending repeated oral doses. The pharmacodynamics of Genz-682452 after ascending repeated oral doses.

Official Title
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A Single-center, Double-blind, Randomized, Placebo-controlled Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Ascending 14-day Repeated Oral Doses of Genz-682452 in Healthy Male and Female Subjects

Conditions
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Healthy

Intervention / Treatment
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* Biological: Genz-682452
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body weight between 50.0 and 95.0 kg, inclusive, if male and between 40.0 and 85.0 kg inclusive, if female, body mass index between 18.0 and 30.0 kg/m^2, inclusive. Certified as healthy by a comprehensive clinical assessment. Exclusion Criteria: Any history or presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, hepatic, renal, metabolic, hematological, neurological, osteomuscular, articular, psychiatric, systemic, ocular, gynecologic (if female), or infectious disease, or signs of acute illness. Frequent headaches and/or migraine, recurrent nausea and/or vomiting. Blood donation, any volume, within 2 months before inclusion. Symptomatic postural hypotension. History or presence of drug or alcohol abuse. Positive result on any of the following tests: hepatitis B surface (HBs Ag) antigen, antihepatitis 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Genz-682452<br>This study will include three cohorts for doses of Genz-682452: Dose 1, Dose 2, Dose 3. Each cohort will include 12 participants, 9 of whom will be administered Genz-682452 and 3 will be administered placebo. | Biological: Genz-682452<br>* Capsules for oral administration.<br>|
| Placebo Comparator: Placebo<br>Placebo comparator taken by participants randomized to the placebo arm in each of the three cohorts. Each cohort will include 12 participants, 9 of whom will be administered Genz-682452 and 3 will be administered placebo. | Biological: Placebo<br>* Placebo capsules matching the Genz-682452 capsules.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants with Treatment-Emergent Adverse Events (TEAEs) |  | Day 1 through Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics as measure by plasma parameters | Maximum plasma concentration (Cmax), Plasma Concentration Observed Just Before Treatment Administration During Repeated Dosing (Ctrough), First time to reach Cmax (Tmax), Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval 0-23 hours (AUC0-24), Terminal Half-Life (t1/2z), Apparent Total Body Clearance of Genz-682452 at steady state (CLss/F), plasma 4 beta-hydroxycholesterol (4β-HC) | Day 1 through Day 14 | 
| Pharmacodynamics as measure by Plasma concentrations of Glucosylceramide (GL-1), Globotriaosylceramide (GL-3) and GM3 ganglioside (GM3) |  | Day 1, through Day 14 | 
| Pharmacokinetics Urine parameter as measure by assessment of Genz-682452 in Urine, Ae0-t, fe0-t (Exploratory) |  | Day 1 through Day 14 |