Safety and Pharmacokinetics of AT1001 (Migalastat HCl) in Healthy Subjects and Subjects With Impaired Renal Function
- Conditions
- Fabry Disease
- Interventions
- Drug: AT1001 150 mg
- Registration Number
- NCT01730469
- Lead Sponsor
- Amicus Therapeutics
- 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).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
Not provided
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description AT1001 150 mg 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
- Primary Outcome Measures
Name Time Method Number of subjects with adverse events to assess safety and tolerability 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 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 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 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 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 Outcome Measures
Name Time Method Area under the concentration-time curve from time zero to the last measurable concentration (AUC 0-t ) of AT1001 Day 1 to Day 6 Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and AUC 0-t will be measured in subjects with impaired renal function and normal renal function
Apparent terminal elimination rate constant for AT1001 Day 1 to Day 6 Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the apparent terminal elimination rate constant will be measured in subjects with impaired renal function and normal renal function
Oral clearance of AT1001 Day 1 to Day 6 Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the oral clearance will be measured in subjects with impaired renal function and normal renal function
Maximum observed concentration (Cmax) of AT1001 Day 1 to Day 6 Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the resultant maximum plasma concentration (Cmax) will be measured in subjects with impaired renal function and normal renal function.
Time to achieve maximum concentration (Tmax) of AT1001 Day 1 to Day 6 Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and time to maximum concentration (tmax) will be measured in subjects with impaired renal function and normal renal function.
Oral volume of distribution of AT1001 Day 1 to Day 6 Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the oral volume of distribution will be measured in subjects with impaired renal function and normal renal function
Apparent terminal elimination half life (t1/2 ) of AT1001 Day 1 to Day 6 Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and and apparent terminal elimination half-life (t1/2) will be measured in subjects with impaired renal function and normal renal function.
Area under the concentration-time curve extrapolated to infinity (AUC 0-inf) of AT1001 Day 1 to Day 6 Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and AUC 0-inf will be measured in subjects with impaired renal function and normal renal function
Trial Locations
- Locations (1)
GSK Investigational Site
🇺🇸Orlando, Florida, United States