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)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Number of subjects with adverse events to assess safety and tolerability
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- •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
研究组 & 干预措施
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
干预措施: AT1001 150 mg (Drug)
结局指标
主要结局
Number of subjects with adverse events to assess safety and tolerability
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- 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)