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

This will be an open-label, non-randomized, multiple-center, sequential group, safety, tolerability, and PK study of a single dose of AT1001 (migalastat HCl, GR181413A) administered orally as a 150 mg dose in fasted healthy control male and female subjects with normal renal function compared to mild, moderate, and severe renally-impaired subjects (classified by level of creatinine clearance [CLcr] as determined by the Cockcroft-Gault formula).

Screening will occur from Day -28 to Day -2. Subjects will check-in to the clinic on Day -1 and receive a single oral dose of 150 mg AT1001 on Day 1. Subjects will be discharged from the clinic on Day 2 (if stable as determined by the Investigator) and return for daily visits on Day 3 through Day 6 for a safety assessment and PK sampling. Subjects will undergo a follow-up visit on Day 7 (+1) and an end of study visit on Day 10 (+1).

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