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.
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).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
32
AT1001 150mg is available as a capsule
GSK Investigational Site
Costa Mesa, California, United States
GSK Investigational Site
Miami, Florida, United States
GSK Investigational Site
Miami, Florida, United States
GSK Investigational Site
Orlando, Florida, United States
Number of subjects with adverse events to assess safety and tolerability
Adverse events will be evaluated from Day 1 to the end of study (Day 10 +1).
Time frame: Day 1 to Day 10 (+1)
Clinical laboratory test values to assess safety and tolerability
Clinical laboratory evaluations (hematology, clinical chemistry, urinalysis, Hepatitis A and HIV screen) will be evaluated from screening to the end of the study.
Time frame: Day -28 to Day 10 (+1)
Vital signs to assess safety and tolerability
Vital signs (oral temperature, respiratory rate, and seated blood pressure) will be performed from screening to the end of the study.
Time frame: Day -28 to Day 10 (+1)
Physician examination to assess safety and tolerability
Physical examination (general appearance, skin, thorax/lungs, cardiovascular and abdomen) will be performed from screening to the end of the study.
Time frame: Day -28 to Day 10 (+1)
Measure of ECG to assess safety and tolerability
Electrocardiogram (ECG) measures the electrical activity of the heart and the hearts' rhythm. All subjects will undergo ECG testing.
Time frame: Day -28 to Day 10 (+1)
Maximum observed concentration (Cmax) of AT1001
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 frame: Day 1 to Day 6
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Time to achieve maximum concentration (Tmax) of AT1001
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.
Time frame: Day 1 to Day 6
Apparent terminal elimination half life (t1/2 ) of AT1001
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.
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
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
Time frame: Day 1 to Day 6
Area under the concentration-time curve extrapolated to infinity (AUC 0-inf) of AT1001
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
Time frame: Day 1 to Day 6
Apparent terminal elimination rate constant for AT1001
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
Time frame: Day 1 to Day 6
Oral clearance of AT1001
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
Time frame: Day 1 to Day 6
Oral volume of distribution of AT1001
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
Time frame: Day 1 to Day 6