Clinical trial NCT01730482: A Study to Assess the Absorption, Metabolism and Excretion of Migalastat Hydrochloride (AT1001-014)
Official title: A Phase 1 Study to Investigate the Absorption, Metabolism and Excretion of [14C] AT1001 (Migalastat Hydrochloride) Following a Single Oral Administration in Healthy Volunteers (AT1001-014)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Fabry Disease
Keywords: excretion
healthy volunteer
migalastat hydrochloride
AT1001
pharmacokinetics
Fabry disease
Lead sponsor: Amicus Therapeutics
Sponsor class: INDUSTRY
First posted: 2012-11-21
Enrollment: 6
Sex: MALE
Minimum age (years): 30
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is designed to describe the metabolism of AT1001 (migalastat HCl) and the contribution of metabolism and urinary excretion to its overall elimination as part of the continuing assessment of the safety and effectiveness of the drug.

This is a Phase 1, single-site, open-label, single dose study of the absorption, metabolism and excretion of radiolabeled AT1001 in healthy male subjects between 30 and 55 years of age, inclusive. Six subjects will be dosed, with the goal of having at least 4 subjects complete the study through follow-up. All subjects will be screened within 28 days before admission to the Clinical Unit. Subjects will be confined to the clinical unit for 10 days after dosing and will return to the clinic for a follow-up visit 28 days after dosing.

Each subject will receive a single oral dose of AT1001 as an aqueous solution containing 150 mg \[14C\] AT1001 (1 μCi). Blood, duodenal bile, expired air, urine, and feces samples will be collected at specified time points after dosing throughout the period of confinement at the study site. Safety will be assessed throughout the study by monitoring clinical laboratory tests, ECGs, physical examinations, vital signs, and adverse events. The total duration of the study for each subject is approximately 8 weeks.


Eligibility criteria: Inclusion Criteria:

* Healthy male subjects between the ages of 30 and 55 years, inclusive
* Body mass index (BMI) of \>=18.0 to \<=30.0 and weighing at least 60 kg
* Anticipated, regular, average bowel movements of 1-2 per day
* No clinically significant abnormal findings on the physical exam, vital signs, serum chemistry, hematology, and urinalysis values, as deemed by the principal investigator
* Willing to avoid taking of all over-the-counter medications 7 days and all prescription drugs 14 days prior to Day -1
* Willing to abstain from sexual intercourse or employ a barrier method of contraception during the inpatient clinic confinement and until the follow-up visit
* Willing to avoid ingestion of broccoli, brussels sprouts, grapefruit, grapefruit juice, or charbroiled meat during the period of confinement in the clinical unit
* Willingness to consume a fiber-rich diet during the period of confinement in the clinic
* Willingness to avoid vigorous physical activity during inpatient clinic confinement and through the follow-up visit
* Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, other study procedures, and study restrictions
* Provide written informed consent to participate in the study

Exclusion Criteria:

* Any previous or ongoing clinically significant illness, medical condition, medical history, physical findings, ECG finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the subject, or alter the absorption, distribution, metabolism, or excretion of the study drug, or could impair the assessment of study results
* History or presence of significant ophthalmic, cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic or psychiatric disease
* History of a major surgical procedure within 30 days before screening
* History of blood or plasma donation or blood loss (\>400 mL) within 60 days before screening
* History of drug or alcohol abuse or addiction within 2 years before screening
* Intake of more than 2 alcoholic drinks per day within the past 7 days or use of alcohol-, grapefruit-, or caffeine-containing foods or beverages within 72 hours prior to Day -1
* Self-reported smoker (occasional or frequent) or positive urine cotinine test (measured at screening and baseline) exceeding the local laboratory's lower limit of detection.
* Presence or history of severe adverse reaction to any drug; history of hypersensitivity or allergic reaction to AT1001 or related iminosugars
* Receipt of any investigational agent or participation in any other interventional clinical trial within the past 30 days
* Participation in any clinical study involving administration of \[14C\] labeled compound(s) within the last 12 months. A subject's previous effective dose will be reviewed by the medical investigator to ensure there is no risk of contamination/carryover into the current study
* At Day -1, a drug toxicology screen positive for any illicit substances, or alcohol
* Anticipated need for alcohol, tobacco, or any drug during the period of confinement in the clinical unit

Primary outcomes:
measure: Recovery of total radioactivity in urine
timeFrame: Days 1 to 11
measure: Recovery of total radioactivity in feces
timeFrame: Days 1 to 11
measure: Presence of radioactivity in expired air
timeFrame: Day 1
measure: Plasma AT1001 pharmacokinetic parameters
timeFrame: Days 1 to 10
measure: Plasma total radioactivity pharmacokinetic parameters
timeFrame: Days 1 to 10
Secondary outcomes:
measure: Number of subjects with adverse events as a measure of safety and tolerability
timeFrame: Day 1 to Day 29
measure: Measure of clinical laboratory test values to access safety and tolerability
timeFrame: Upto 8 weeks
measure: Physical examination to access safety and tolerability
timeFrame: Upto 8 weeks
measure: Measure of vital signs to access safety and tolerability
timeFrame: Upto 8 weeks
measure: Measure of ECG to access safety and tolerability
timeFrame: Upto 8 weeks
measure: The blood to plasma ratio of total radioactivity
timeFrame: Day 1
measure: Characterization of metabolites in plasma, urine, duodenal bile and fecal homogenates
timeFrame: Day -1 to Day 11
Other outcomes:
Locations:
Study officials:
affiliation: Amicus Therapeutics
name: Medical Monitor, Clinical Research
role: STUDY_DIRECTOR
References: