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

Migalastat hydrochloride is a new investigational compound that may eventually
be used for the treatment of Fabry disease. Fabry disease is a rare disorder
caused by a mutation, which leads to reduced activity of a certain enzyme.
Migalastat hydrochloride binds to this enzyme and as a result the enzyme
activity will be increased. Migalastat hydrochloride is not approved as a drug
in any country but has been given to humans before in other drug studies as an
oral capsule formulation.

Primary Objectives:
* To investigate the pharmacokinetics of migalastat following a single 2hr IV
infusion in healthy subjects.
* To investigate the safety and tolerability of a single migalastat HCl 2hr IV
infusion in healthy subjects.

Secondary Objectives:
* To assess dose proportionality of migalastat following a single 2hr IV
infusion in healthy subjects (planned doses 0.3, 1.0, and 10.0 mg/kg), as data
permit.
* To estimate the urinary excretion of unchanged migalastat following a single
2hr IV infusion in healthy subjects.
* To evaluate the absolute bioavailability of plasma migalastat.

This is a first in human study with a randomized, double blind, placebo
controlled, single ascending dose escalation
design. Cohort 4 is an open-label, randomized, two-way crossover arm.

The study will consist of 1 period during which you will receive migalastat
hydrochloride once or placebo once. Migalastat hydrochloride and placebo will
be given as a 2 hour intravenous infusion.

Please refer to the table below to see the planned dose levels for the groups.
The dose for the next group will only be increased if the lower dose of the
previous group was found to be well tolerated and after approval by the local
Medical Ethics Review Committee. Should, in the opinion of the investigators,
unacceptable adverse effects appear, the study may be discontinued.

The planning of the study is as follows:

Group Day Treatment How often
1 1 migalastat hydrochloride 0.3 mg/kg Once
2 1 migalastat hydrochloride 1.0 mg/kg* Once
3 1 migalastat hydrochloride 10 mg/kg* Once
*This indicated dose can be adapted dose is an indication, the final dose will
be determined based on the results of previous groups


Cohort 4 will contain 2 sequential dosing periods with a 7 day washout between
each administration. Five subjects will receive an oral dose of 150 mg
migalastat HCl during Period 1 then will return to the clinic for a 150 mg dose
IV infusion of migalastat HCl during Period 2. Simultaneously, an additional
five subjects will be receiving a 150 mg IV infusion of migalastat HCl during
Period 1 then will return for a 150 mg oral dose of migalastat HCl. Thus, all
Cohort 4 subjects will receive oral migalastat HCl and IV migalastat HCl to be
considered as having completed the study.

- possible side-effect as described under E9
- blood draws via punction of the vena
- blood draws via indwelling cannula
- intraveneous administration
- screening and follow-up visit
- admission to the clinic
- study activities: physical examinations, vital signs, ECG and injection site
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