A phase 1 study to investigate the absorption, metabolism and excretion of [14C] AT1001 (migalastat hydrochloride) following a single oral administration in healthy volunteers.

In a previous study in more than 100 healthy volunteers, with doses up to 2000
mg in single doses and up to 300 mg daily in multiple doses (150 mg twice
daily) AT1001 was well tolerated. In studies with patients that were given
doses of up to 500 mg daily, the following adverse effects were reported:
headache, arthralgia, diarrhea, and nausea. In all studies with AT1001, one
serious adverse event has been reported (short heartblock) that is considered
unlikely related to the study medication.
With the dose(s) used in this study no serious adverse effects are expected.
However, the possibility that any of the above-mentioned or other adverse
effects could occur cannot be entirely excluded.

Primary :
to assess the mass balance profile (i.e., excretion in urine and feces) of a
single dose of AT1001 using 14C-labeled AT1001
to characterize the absorption and elimination profiles of a single dose of
AT1001 using 14C-labeled AT1001
to generate samples that will be used to characterize the metabolic profile, if
feasible, of AT1001 in plasma, urine and/or feces, following administration of
a single oral dose of AT1001 using 14C-labeled AT1001

Secondary :
to evaluate the safety and tolerability of a single oral dose of 150 mg
AT1001/1 *Ci 14C AT1001 to healthy subjects

Design: an open-label, tracer label study in six healthy male subject receiving
a single oral dose of [14C]-AT1001, containing approximately 37 kBq radiocarbon

Screening and follow-up: clinical laboratory (including coagulation), vital
signs, physical examination, 12-lead ECG; at eligibility screening: medical
history, height, weight, drug screen, HBsAg, anti HCV, anti-HIV 1/2; alcohol
and drug screen, vital signs, physical examination, clinical laboratory
(including coagulation) and 12-lead ECG to be repeated upon admission

Observation period: one period in clinic from -17 h up to 240 h after drug
administration (=Day 11); follow-up on Day 29

Blood sampling : for pharmacokinetics of AT1001 and total radioactivity in
plasma: pre-dose and 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96,
120, 144, 168, 192, 216 and 240 h post-dose
for metabolite elucidation and identification (20 mL samples): 1, 4, 6 and 24 h
post-dose

Urine sampling: for pharmacokinetics of AT1001, total radioactivity and
metabolite elucidation and identification: pre-dose (-12-0 hours) and intervals
0-12 and 12-24 post-dose, and thereafter at 24-hour intervals on Days 2-10; the
last sample will be collected before release from the clinical unit on Day 11
Faeces sampling: for pharmacokinetics of AT1001, total radioactivity and
metabolite elucidation and identification: pre-dose (-24 to 0 hours); all bowel
movements post-dose are to be collected on Days 2-10; the last sample will be
collected before release from the clinical unit on
Day 11

Enterotest (bile sampling): once on Days -1 and 1

Safety assessments: adverse events: throughout the study; vital signs: once
daily on Days 1-11; physical examination, clinical laboratory (including
coagulation) and 12-lead ECG: once on Day 11

Bioanalysis : analysis of plasma, urine and faeces AT1001 samples using
validated methods by Sponsor
analysis of total radioactivity in plasma, urine and faeces using validated
methods by Sponsor
metabolite elucidation and identification by Sponsor

Study Medication
Active substance: AT1001 and [14C]-AT1001
Activity : pharmacological chaperone for *-Gal A
Indication : Fabry disease
Dosage form: oral solution

Treatment
A single oral dose of 150 mg [14C]-AT1001, containing approximately 37 kBq
radiocarbon, on Day 1 in the fasted state

Not applicable.