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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Fabry Disease

Intervention / Treatment
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* Drug: IV migalastat HCl
* Drug: IV placebo
* Drug: oral migalastat HCl


Participation Criteria
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Eligibility Criteria
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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.

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LSD, Fabry Disease, Fabry, Lysosomal storage disorders, Amicus, migalastat HCl, migalastat, AT1001