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)
Overview
- Phase
- Phase 1
- Intervention
- AT1001 150 mg
- Conditions
- Fabry Disease
- Sponsor
- Amicus Therapeutics
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Number of subjects with adverse events to assess safety and tolerability
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This study will assess the safety, tolerability, and pharmacokinetics (PK) study of a single dose of 150 mg AT1001 (migalastat HCl, GR181413A) administered orally to healthy subjects with normal renal function and to subjects with mild, moderate, and severe renal impairment.
Detailed Description
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
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
Arms & Interventions
AT1001 150 mg
Each subject will receive a single oral dose of AT1001 150 mg administered orally with 240 mL room temperature water after at least a 4-hour fast
Intervention: AT1001 150 mg
Outcomes
Primary Outcomes
Number of subjects with adverse events to assess safety and tolerability
Time Frame: Day 1 to Day 10 (+1)
Adverse events will be evaluated from Day 1 to the end of study (Day 10 +1).
Physician examination to assess safety and tolerability
Time Frame: Day -28 to Day 10 (+1)
Physical examination (general appearance, skin, thorax/lungs, cardiovascular and abdomen) will be performed from screening to the end of the study.
Measure of ECG to assess safety and tolerability
Time Frame: Day -28 to Day 10 (+1)
Electrocardiogram (ECG) measures the electrical activity of the heart and the hearts' rhythm. All subjects will undergo ECG testing.
Clinical laboratory test values to assess safety and tolerability
Time Frame: Day -28 to Day 10 (+1)
Clinical laboratory evaluations (hematology, clinical chemistry, urinalysis, Hepatitis A and HIV screen) will be evaluated from screening to the end of the study.
Vital signs to assess safety and tolerability
Time Frame: Day -28 to Day 10 (+1)
Vital signs (oral temperature, respiratory rate, and seated blood pressure) will be performed from screening to the end of the study.
Secondary Outcomes
- Area under the concentration-time curve from time zero to the last measurable concentration (AUC 0-t ) of AT1001(Day 1 to Day 6)
- Apparent terminal elimination rate constant for AT1001(Day 1 to Day 6)
- Oral clearance of AT1001(Day 1 to Day 6)
- Maximum observed concentration (Cmax) of AT1001(Day 1 to Day 6)
- Time to achieve maximum concentration (Tmax) of AT1001(Day 1 to Day 6)
- Oral volume of distribution of AT1001(Day 1 to Day 6)
- Apparent terminal elimination half life (t1/2 ) of AT1001(Day 1 to Day 6)
- Area under the concentration-time curve extrapolated to infinity (AUC 0-inf) of AT1001(Day 1 to Day 6)