A Two-part, Randomized, Double-blind, Placebo-controlled, First-In-Human, Phase I Study of the Safety, Tolerability, and Pharmacokinetics of SPR720 Following Administration of Single and Multiple Ascending Oral Doses in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- Treatment emergent adverse events assessments after single and multiple dose administration at baseline and repeatedly until study completion [Safety and Tolerability]
研究概览
简要总结
The purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics (PK) following single and multiple ascending dose administration of SPR720 administered orally in healthy volunteers.
详细描述
This is a single-center, phase I, randomized, double-blind, placebo-controlled, first-in-man study. Up to 120 healthy volunteers may be enrolled in this 2-part, multi-cohort study. In both Part 1 and Part 2, sequential cohorts will be exposed to increasing doses of SPR720. Each cohort will enrol 8 subjects, randomized (3:1) to receive SPR720 (6 subjects) or placebo (2 subjects). Each subject will be assigned to only one cohort.
In Part 1 single ascending dose (SAD):
A single oral dose of SPR720 (n=6) or placebo (n=2) will be administered to 8 subjects at an initial dose level of 100 mg. Additional cohorts of 8 subjects will be enrolled to investigate increasing doses of SPR720 ranging from 250 mg to 3000 mg. All subjects will receive SPR720 (or placebo) by oral administration in the fasted state. One Part 1 cohort (the Food Effect Cohort) will receive an additional single dose of SPR720 (or placebo) in the fed state.
Part 2 multiple ascending dose (MAD):
SPR720 (or placebo) will be administered to approximately 3 planned dose cohorts of 8 subjects each. Subjects will receive SPR720 (or placebo) orally once daily for 7 (or 14) consecutive days starting with a planned initial dose of 500 mg. Additional cohorts of 8 subjects will be enrolled to investigate repeated daily doses of SPR720 ranging from 1000 mg to 1500 mg.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Subjects will be randomized in a 3:1 ratio to receive SPR720 or placebo. The randomization code will produced by Simbec using the PROC PLAN procedure of SAS® version 9.3 or higher. The randomization code will include 2 dose-leaders (1 active:1 placebo) in each cohort who will be randomized prior to the remainder of the cohort. The allocation to SPR720 or placebo will be performed using a block randomization algorithm.
入排标准
- 年龄范围
- 18 Years 至 —（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
- 未提供
研究组 & 干预措施
SPR720 for SAD
6 out of 8 subjects per cohort will be randomized to receive SPR720
干预措施: SPR720 for SAD (Drug)
Placebo for SAD
2 out of 8 subjects per cohort will be randomized to receive placebo
干预措施: Placebo for SAD (Drug)
SPR720 for MAD
6 out of 8 subjects per cohort will be randomized to receive SPR720
干预措施: SPR720 for MAD (Drug)
Placebo for MAD
2 out of 8 subjects per cohort will be randomized to receive placebo
干预措施: Placebo for MAD (Drug)
结局指标
主要结局
Treatment emergent adverse events assessments after single and multiple dose administration at baseline and repeatedly until study completion [Safety and Tolerability]
时间窗: Day 1 through last follow-up visit (5-7 days after last dose)
Incidence and severity of AEs
次要结局
- Assessment of Pharmacokinetic Parameter (plasma): Cmax measurement(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): CmaxSS measurement(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): CminSS(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): Ctrough(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): CavSS(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): Tmax(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): kel(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): t1/2(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): AUC0-24(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): AUC0-tau(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Parameter (plasma): AUC0-t(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): AUC0-inf(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Parameter (plasma): AUC%extrapolated(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): Degree of fluctuation(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (plasma): Swing(From Day 1 pre-dose to 48 hours post last dose)
- Assessment of Pharmacokinetic Parameter (urine): SPR719(From Day 1 pre-dose to 24 hours post last dose)