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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Biological: Genz-682452; Biological: Placebo

• Registration Number: NCT01710826
• Lead Sponsor: Genzyme, a Sanofi Company

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2012-10
• Study First Submitted: 2012-10-17
• Study First Submitted QC: 2012-10-17
• Study First Posted: 2012-10-19
• Primary Completion: 2013-02
• Study Completion: 2013-02
• Status Verified: 2014-03
• Last Update Submitted: 2014-03-17
• Last Update Posted: 2014-03-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Genz-682452	Genz-682452	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.
Placebo	Placebo	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.

Primary Outcome Measures

Name	Time	Method
Participants with Treatment-Emergent Adverse Events (TEAEs)	Day 1 through Day 14

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics as measure by plasma parameters	Day 1 through Day 14	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)
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