A Phase 1, Double Blind, Placebo-Controlled, Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of LYT-300 in Healthy Volunteers, and a Phase 1b/2a Study Part to Assess Effects of a Single Dose of LYT-300 vs. Placebo on the Response to a Standardized Behavioural Challenge in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- PureTech
- 入组人数
- 186
- 试验地点
- 1
- 主要终点
- Effect of food in healthy volunteers
研究概览
简要总结
Part 1 is a single ascending dose (SAD) trial in healthy volunteers (HV) to assess the safety, tolerability, and pharmacokinetic (PK) profile of orally administered LYT-300.
Part 2 is a crossover assessment in HV of the effects of food on the safety, tolerability, and PK profile of orally administered LYT-300.
Part 3 is a multiple ascending dose (MAD) trial in HV to assess the safety, tolerability, and PK profile of multiple doses (up to 7 days) of orally administered LYT-300.
Part 4 is an assessment of the effects of LYT-300 vs. placebo on pharmacodynamic and patient reported outcome response to a validated clinical model of anxiety.
详细描述
Part 1: This is a randomized, double-blind, placebo-controlled, SAD design to assess the safety, tolerability, and PK profile of orally administered LYT-300 in HV, in a 3-period, 3-sequence, crossover, dose escalation design.
Part 2: This is a randomized, open label, 3-period, 3-sequence, crossover assessment of the effects of food on the PK, safety, and tolerability of orally administered LYT-300 in HV. A single dose of LYT-300 will be administered on 3 occasions, separated by a minimum 7-day washout period. Part 2 is planned as a single dosing cohort.
Part 3: This is a randomized, double-blind, placebo-controlled, sequential, MAD trial in HV to assess the safety, tolerability, and PK profile of multiple doses (up to 7 days) of orally administered LYT-300. This part will include ascending doses given either once daily in the morning (QAM), once daily in the evening (QHS), or twice daily (BID).
Part 4: This is a double-blind, randomized assessment of the effects in HV of a single dose of LYT-300 vs. placebo on pharmacodynamic and patient reported outcome response to a validated clinical model of anxiety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Parts 1, 2 and 3 are double blind during the data collection. Determination for dose escalation may be made under unblinded conditions by assessors.
Part 4 consists of 2 groups. Group 1 (the validation group) will be single-arm placebo. Group 2 (the test group) will be double blind during data collection.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Parts 1, 2, 3 and 4: Healthy Volunteers
- •Male or female between 18 and 55 years old (inclusive) at the time of screening.
- •In good general health at screening, free from clinically significant unstable medical, surgical or psychiatric illness, at the discretion of the Investigator.
排除标准
- •Parts 1, 2, 3 and 4: Healthy Volunteers
- •Evidence or history of any condition or situation that adversely impacts a normal sleep-wake cycle.
- •Confirmed COVID-19 infection within 2 months of screening, known exposure to another person with COVID-19 within 14 days of screening
- •History of illness with fever within 28 days prior to the first dose.
- •A history of, or current evidence for, serious mental illness
研究组 & 干预措施
LYT-300 in healthy volunteers LYT-300, Doses TBD
Subjects will crossover across 3 dosing periods in which they will receive placebo and two experimental dose levels
干预措施: Placebo (Other)
LYT-300
干预措施: LYT-300 (Drug)
LYT-300 in healthy volunteers LYT-300, Doses TBD
Subjects will crossover across 3 dosing periods in which they will receive placebo and two experimental dose levels
干预措施: LYT-300 (Drug)
LYT-300 in healthy volunteers LYT-300
LYT-300, Dose TBD with and without food, separated by 7-day washout
干预措施: LYT-300 (Drug)
LYT-300, Dose TBD QAM every 24 h for 7 days
干预措施: LYT-300 (Drug)
Placebo QAM every 24 h for 7 days
干预措施: Placebo (Other)
Placebo QHS every 24 h for 7 days
干预措施: LYT-300 (Drug)
Placebo QHS every 24 h for 7 days
干预措施: Placebo (Other)
LYT-300 in healthy volunteers LYT-300, Dose TBD QHS every 24 h for 7 days
干预措施: LYT-300 (Drug)
LYT-300 in healthy volunteers LYT-300, Dose TBD QHS every 24 h for 7 days
干预措施: Placebo (Other)
Placebo
干预措施: Placebo (Other)
结局指标
主要结局
Effect of food in healthy volunteers
时间窗: 2 days (main time frame)
Measure concentration of allopregnanolone in blood plasma in fed or fasted subjects administered a single dose of LYT-300
Safety and tolerability: treatment-emergent adverse events [TEAEs]
时间窗: 7 days (main time frame)
Evaluate the safety and tolerability in healthy volunteers following single or multiple oral doses of LYT-300 as measured by TEAEs.
Salivary cortisol
时间窗: 60 minutes
Change in salivary cortisol
次要结局
- Use pharmacokinetics to characterize the blood plasma concentration of allopregnanolone after administration of LYT-300(7 days (main time frame))