A Phase I, Single Centre, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability and Pharmacokinetics in Plasma and Urine of Multiple Ascending Doses of ALZ-801 in Healthy Elderly Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Alzheon Inc.
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Number of participants with adverse events as a measure of safety and tolerability
研究概览
简要总结
Phase I, single-center, double-blind, randomized, placebo-controlled, parallel-group study of the safety, tolerability, and pharmacokinetics (PK) in plasma and urine, of multiple ascending doses of ALZ-801 (capsule, Part 1; prototype tablet Part 2) and the primary metabolite in healthy male or female subjects.
详细描述
The study was conducted in two parts:
Part 1 Primary objective: To evaluate the safety, tolerability, and pharmacokinetics, of multiple doses of ALZ-801 capsule formulation in healthy elderly subjects.
Methodology: Phase I, single center, in-patient and out-patient, double-blind, randomized, placebo-controlled, parallel-group study of the safety, tolerability and pharmacokinetics (PK) in plasma and urine of multiple ascending doses of ALZ-801 in healthy male or female subjects aged 50 to 75 years, inclusive. A total of 36 subjects were enrolled into 3 successive cohorts (A, B, C with 12 subjects per cohort) and randomized in a 3:1 ratio to receive treatment with ALZ-801 capsules (9 subjects) or placebo capsules (3 subjects) for 2 weeks. Progression to the next cohort was permitted after review of safety and available PK data suggested that it was safe to do so. Subjects were confined to the clinical unit for the first day of dosing (Day 1 and for Days 7 through 14). Subjects took investigational drug at home for Days 2 through 6).
Cohorts A was dosed in the fasted state and evaluated 171 mg ALZ-801 or placebo QD for 1 day, followed by 171 mg ALZ-801 or placebo BID for 6 days and 256.5 mg or placebo QD for 7 days.
Cohort B was dosed in the fasted state and evaluated 256.5 mg ALZ-801 or placebo QD for 1 day, followed by 256.5 mg ALZ-801 or placebo BID for 6 days and 340 mg or placebo QD for 7 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
double blind, placebo controlled, matching placebo
入排标准
- 年龄范围
- 50 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy males, and females
- •Age: 50-75 years, Part 1; 60-75 years Part 2
- •Females must be of non-childbearing potential
- •Body Mass Index 18-35 kg/m squared;
- •Vital signs normal for age: BP 90-160/40-90 mmHg; HR 50 to 90 bpm)
- •No clinically significant electrocardiogram readings
排除标准
- •Body weight < 50 kg
- •History of any drug or alcohol abuse in the past 2 years
- •Subjects known to have a creatinine clearance of <60 mL/min
- •Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
- •History of clinically significant cardiovascular, pulmonary, chronic respiratory, renal, hepatic, GI, immunologic, endocrine, neurologic, psychiatric or thromboembolic disease
- •History of metabolic disturbances;
研究组 & 干预措施
Cohort D Tablet - Fed
ALZ-801 265 mg or matching placebo once daily Day 1, ALZ-801 265 mg or matching placebo twice daily Days 2-6, ALZ-801 265 mg or matching placebo once daily Day 7
干预措施: ALZ-801 or matching placebo (Drug)
Cohort C Capsule - Fed
ALZ-801 256.5 mg or matching placebo once daily Day 1, ALZ-801 256.5 mg or matching placebo twice daily Days 2-7, ALZ-801 340 mg or matching placebo twice daily Days 8-13, ALZ-801 340 mg or matching placebo once daily Day 14
干预措施: ALZ-801 or matching placebo (Drug)
Cohort A Capsule - Fasted
ALZ-801 171 mg or matching placebo once daily Day 1, ALZ-801 171 mg or matching placebo twice daily Days 2-7, ALZ-801 256.5 mg or matching placebo once daily Days 8-14
干预措施: ALZ-801 or matching placebo (Drug)
Cohort B Capsule - Fasted
ALZ-801 256.5 mg or matching placebo once daily Day 1, ALZ-801 256.5 or matching placebo mg twice daily Days 2-7, ALZ-801 340 mg or matching placebo once daily Days 8-14
干预措施: ALZ-801 or matching placebo (Drug)
结局指标
主要结局
Number of participants with adverse events as a measure of safety and tolerability
时间窗: Duration of dosing: 14 days for Part 1; 7 days for Part 2
Incidence and nature of adverse events (AEs) and serious adverse events (SAEs). Assessments reported as AEs or SAEs include physical examination, clinical laboratory tests, and 12-lead electrocardiogram (ECG) findings
Cmax for ALZ-801 and tramiprosate
时间窗: Days 1, 7 and 14
Maximum concentration after dosing \[Cmax\] measured as ng/ml
AUC for ALZ-801 and tramiprosate
时间窗: Days 1, 7 and 14
AUC from time zero to time t (AUCt)
Tmax for ALZ-801 and tramiprosate
时间窗: Days 1, 7 and 14
Time to reach Cmax \[Tmax\] measured in hours (h) after dosing
Renal clearance of ALZ-801 and tramiprosate
时间窗: Days 1, 7 and 14
Clearance (CLr) measured in mL/min
t1/2 for ALZ-801 and tramiprosate
时间窗: Days 1, 7, 14
Elimination half-life (t1/2) measured in hours after dosing
次要结局
未报告次要终点