A Phase 1 Study To Evaluate the Safety of Migalastat Hydrochloride Given Intravenously to Healthy Volunteers

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Dose Escalation Trial to Evaluate the Safety, Tolerability and Pharmacokinetics of Migalastat Hydrochloride Given Intravenously to Healthy Volunteers With an Open-Label, Randomized, Two-Way Crossover Arm

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of IV migalastat HCl alone and to determine absolute bioavailability for oral migalastat HCl as compared to IV administered migalastat HCl in healthy volunteers. The data from this study will help us understand how migalastat works in the body and will help us determine what would be an effective dose in future studies with migalastat hydrochloride.

Study Overview

• Status: Completed
• Conditions: Fabry Disease
• Intervention / Treatment: Drug: IV migalastat HCl; Drug: IV placebo; Drug: oral migalastat HCl

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • PRA International

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females between 18 and 45 years of age.
• Body weight range ≥ 50 kg ≤ 100 kg and BMI within the range 18.5 - 29.9 kg/m2.
• Healthy as determined by a responsible and experienced physician, based on a medial evaluation.
• Male and female subjects of childbearing potential agree to adhere to the contraception requirements.
• Capable of giving written informed consent.

Exclusion Criteria:

• History of sensitivity to migalastat HCl or related iminosugars (eg, miglitol, miglustat), or other significant drug allergy.
• Past medical history, or physical examination findings, of clinically significant abnormalities that may put the subject at risk or interfere with outcome variables.
• Positive pre-study drug/alcohol screen.
• Pregnant or lactating females.
• The subject has participated in a clinical trial and has received an investigational product within 60 days prior to the first dosing day in the current study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.3 mg/kg; IV infusion of migalastat HCl or placebo	Drug: IV migalastat HCl; Other Names: AT1001; Drug: IV placebo; Other Names: Sodium Chloride 0.9%
Experimental: 1 mg/kg; IV infusion of migalastat HCl or placebo	Drug: IV migalastat HCl; Other Names: AT1001; Drug: IV placebo; Other Names: Sodium Chloride 0.9%
Experimental: 10 mg/kg; IV infusion of migalastat HCl or placebo	Drug: IV migalastat HCl; Other Names: AT1001; Drug: IV placebo; Other Names: Sodium Chloride 0.9%
Experimental: 150 mg IV; 150 mg single IV infusion	Drug: IV migalastat HCl; Other Names: AT1001; Drug: oral migalastat HCl; Other Names: AT1001
Experimental: 150 mg oral; 150 mg single oral dose	Drug: IV migalastat HCl; Other Names: AT1001; Drug: oral migalastat HCl; Other Names: AT1001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma pharmacokinetics of migalastat	To investigate the effect on the body of migalastat following a single 2 hour IV infusion in healthy subjects.	Pre-dose, 0.25, 0.5, 1, 1.5, 2.0, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48
Safety and tolerability of migalastat	Adverse events, clinical laboratory test values, vital signs, ECG, physical examinations	48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma pharmacokinetics of migalastat	To assess the dose proportionality of migalastat following a single 2 hour IV infusion	Pre-dose, 0.25, 0.5, 1, 1.5, 2.0, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48
Urinary pharmacokinetics	To estimate the urinary excretion of unchanged migalastat following a single 2 hour IV infusion in healthy subjects	Pre dose, between 0-6, 6-12 and 12-24 hours after start of infusion

Collaborators and Investigators

• Sponsor: Amicus Therapeutics

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: March 6, 2014
• First Submitted That Met QC Criteria: March 6, 2014
• First Posted (Estimate): March 10, 2014

Study Record Updates

• Last Update Posted (Estimate): June 18, 2014
• Last Update Submitted That Met QC Criteria: June 17, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Fabry; AT1001; Fabry Disease; LSD; Lysosomal storage disorders; Amicus; migalastat HCl; migalastat
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Cerebral Small Vessel Diseases; Lipidoses; Lipid Metabolism, Inborn Errors; Fabry Disease; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; 1-Deoxynojirimycin
• Other Study ID Numbers: AT1001-018; 2013-005553-75 (EudraCT Number)