Safety and Pharmacokinetics of AT1001 (Migalastat HCl) in Healthy Subjects and Subjects With Impaired Renal Function

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01730469
• Date of registration: 08/11/2012
• Prospective Registration: No
• Primary sponsor: Amicus Therapeutics
• Public title: Safety and Pharmacokinetics of AT1001 (Migalastat HCl) in Healthy Subjects and Subjects With Impaired Renal Function
• Scientific title: An Open-Label Study to Determine the Safety and Pharmacokinetics of AT1001 in Subjects With Impaired Renal Function and Healthy Subjects With Normal Renal Function (AT1001-015)
• Date of first enrolment: August 2011
• Target sample size: 32
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01730469
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Medical Monitor, Clinical Research
• Affiliation: Amicus Therapeutics

Key inclusion & exclusion criteria

Inclusion Criteria All subjects

- males or females aged 18 to 70 years inclusive (subjects with normal renal function,
mild or moderate renal impairment), and 18 to 75 years inclusive (subjects with severe
renal impairment)

- body mass index 18.0 to 40.0 kilogram (kg)/square meter (m^2) inclusive

- females who are non-pregnant, non-lactating, or postmenopausal for >=1 year,
surgically sterile for >= 90 days, or agree to use approved methods of contraception

- males will be sterile or use approved methods of contraception

- understands and signs informed consent form Healthy subjects with normal renal
function

- negative test for selected drugs of abuse (excludes alcohol) at Screening and Check-in

- good health with no clinically significant medical history, physical examination,
vital signs, or 12-lead ECG

- clinical laboratory tests within the reference range or not clinically significant

- normal renal function (estimated CLcr >90 mL/min) at Screening Subjects with mild,
moderate or severe renal impairment

- negative test for selected drugs of abuse (excludes alcohol) at Screening and Check-in
or verification of a prescription for a positive test

- renal impairment (estimated CLcr <90 mL/min)

- evidence of stable renal impairment defined as two separate estimated CLcr values
within 25%

- clinical laboratory results consistent with their renal condition or of no clinical
significance for the study

- abnormal laboratory values must not be clinically significant. Anemia secondary to
renal disease is acceptable if hemoglobin is =9 g/dL and no clinically significant
symptoms. Liver enzymes and bilirubin must be below twice the upper normal level

- subjects with renal impairment must have stable underlying medical conditions < 90
days before study start

- stable medication regimen(s) (no new drug(s) or changed dosage(s) <30 days before
study drug)

- in good general health, allowing for concurrent illnesses associated with chronic
kidney disease

Exclusion Criteria:

All subjects:

- history of hypersensitivity or allergies to any drug, unless approved by the
Investigator and reviewed by Sponsor/Medical Monitor

- participation in a study with receipt of an investigational drug < 5 half-lives or 30
days (whichever is longer) before Check-in

- use of alcohol, grapefruit, or caffeine-containing foods or beverages < 72 hours
before Check-in, unless approved by the Investigator and reviewed by the
Sponsor/Medical Monitor

- poor peripheral venous access

- whole blood donation < 56 days before dosing or plasma donation < 14 days before
dosing

- receipt of blood products < 2 months before Check-in

- history or presence of any clinically significant abnormal ECG

- history of alcoholism or drug addiction < 1 year before Check-in

- positive test for HIV antibody, HBsAg or anti-HCV

- pregnant or breastfeeding

Healthy subjects with normal renal function:

- use of any tobacco- or nicotine-containing products < 6 months before Check-in

- clinically significant (history of or active) cardiac, hepatic, pulmonary, endocrine,
neurological, infectious, gastrointestinal, hematologic, oncologic, or psychiatric
disease putting the subject at increased risk or could interfere with study objectives

- screening laboratory values outside normal range and deemed clinically significant by
the Investigator

- use of a prescription drug < 14 days of dosing or a non-prescription drug < 7 days
before dosing or need of concomitant medication during the study

Subjects with mild, moderate, or severe renal impairment:

- unstable disease (concurrent medical conditions that have changed significantly < 90
days)

- changes in concomitant prescription medications < 30 days before dosing or expected
changes during study

- use of new non-prescription medication < 30 days before dosing

- renal transplant

- acute or chronic non-renal condition limiting the subject's ability to complete and/or
participate in the study



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Fabry Disease

Intervention(s)

Drug: AT1001 150 mg

Primary Outcome(s)

Number of subjects with adverse events to assess safety and tolerability [Time Frame: Day 1 to Day 10 (+1)]

Vital signs to assess safety and tolerability [Time Frame: Day -28 to Day 10 (+1)]

Measure of ECG to assess safety and tolerability [Time Frame: Day -28 to Day 10 (+1)]

Clinical laboratory test values to assess safety and tolerability [Time Frame: Day -28 to Day 10 (+1)]

Physician examination to assess safety and tolerability [Time Frame: Day -28 to Day 10 (+1)]

Secondary Outcome(s)

Apparent terminal elimination half life (t1/2 ) of AT1001 [Time Frame: Day 1 to Day 6]

Area under the concentration-time curve extrapolated to infinity (AUC 0-inf) of AT1001 [Time Frame: Day 1 to Day 6]

Time to achieve maximum concentration (Tmax) of AT1001 [Time Frame: Day 1 to Day 6]

Area under the concentration-time curve from time zero to the last measurable concentration (AUC 0-t ) of AT1001 [Time Frame: Day 1 to Day 6]

Oral clearance of AT1001 [Time Frame: Day 1 to Day 6]

Oral volume of distribution of AT1001 [Time Frame: Day 1 to Day 6]

Maximum observed concentration (Cmax) of AT1001 [Time Frame: Day 1 to Day 6]

Apparent terminal elimination rate constant for AT1001 [Time Frame: Day 1 to Day 6]

Secondary ID(s)

116431

Source(s) of Monetary Support

Please refer to primary and secondary sponsors