A 3-Part, Randomized, Double-Blind, Placebo-Controlled, Multiple Rising Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TAK-925 in Healthy Volunteers and Patients With Narcolepsy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 57
- 试验地点
- 3
- 主要终点
- Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
The purpose of this study is to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-925 when administered to healthy participants and narcolepsy participants.
详细描述
The drug being tested in this study is called TAK-925. TAK-925 is being tested in healthy participants and participants with narcolepsy. This study will look at the safety, tolerability, pharmacokinetics, and efficacy of TAK-925.
This study will consist of three parts. Part A will be a randomized, double-blind, placebo-controlled, multiple rising dose (MRD) study in healthy participants. Part B is a randomized, double-blind, placebo-controlled MRD study in participants with narcolepsy. Part C is a randomized, double-blind, placebo-controlled, parallel group, multiple repeat dose study in participants with narcolepsy. Part A' is a single dose study in healthy participants.
The study will enroll approximately 96 participants planned as total. All participants except Part A' will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the participants and study doctor during the study (unless there is an urgent medical need):
Part A:
- TAK-925 (Dose Levels A1-A6)
- Placebo
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adult participants and Healthy elderly participants:
- •Participant weighs at least 50 kg (Healthy adults participants) / 40 kilogram (kg) (Healthy elderly participants) and has a body mass index (BMI) from 18.5 to 30 kilogram per square meter (kg/m^2), inclusive at Screening.
- •Narcolepsy participants:
- •Participants weighs at least 40 kg inclusive at Screening (>=50 kg is required for Cohort B4).
- •A diagnosis of narcolepsy, as defined by the International Classification of Sleep Disorders, Third Edition (ICSD-3).
- •At Day -1, Epworth sleepiness scale (ESS) score >=10
排除标准
- •All Participants:
- •Participants consume excessive amounts, defined as greater than 6 servings (1 serving is approximately equivalent to 120 mg of caffeine) of coffee, tea, cola, energy drinks, or other caffeinated beverages per day.
- •Participants have a moderate to severe substance use disorder.
- •Participants have a risk of suicide according to endorsement of item 4 or 5 with Screening/Baseline visit C-SSRS (Columbia Suicide Severity Rating Scale) or has made a suicide attempt in the previous 6 months.
- •Participants have a lifetime history of major psychiatric disorder, such as bipolar disorder or schizophrenia.
- •Participants experienced sleep wake cycle disturbance with external factors such as irregular work hours.
研究组 & 干预措施
Cohort A1; TAK-925 (Dose Level A1)
TAK-925, Dose Level A, once daily for up to 7 days in healthy participants.
干预措施: TAK-925 (Drug)
Cohort A2; TAK-925 (Dose Level A2)
TAK-925, Dose Level A2, once daily for up to 7 days in healthy participants. Dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.
干预措施: TAK-925 (Drug)
Cohort A3; TAK-925 (Dose Level A3)
TAK-925, Dose Level A3, once daily for up to 7 days in healthy participants. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.
干预措施: TAK-925 (Drug)
Cohort A4; TAK-925 (Dose Level A4)
TAK-925, Dose Level A4, once daily for up to 7 days in healthy participants. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.
干预措施: TAK-925 (Drug)
Cohort A5; TAK-925 (Dose Level A5)
TAK-925, Dose Level A5, once daily for up to 7 days in healthy participants. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.
干预措施: TAK-925 (Drug)
Cohort A6; TAK-925 (Dose Level A6)
TAK-925, Dose Level A6, once daily for up to 7 days in healthy elderly participants. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.
干预措施: TAK-925 (Drug)
Part A (Cohorts A1-A6); TAK-925 Placebo
TAK-925 Placebo, once daily for up to 7 days in healthy participants.
干预措施: Placebo (Drug)
Cohort B1; TAK-925 (Dose Level B1)
TAK-925, Dose Level B1, once daily for up to 7 days in participants with narcolepsy.
干预措施: TAK-925 (Drug)
Cohort B2; TAK-925 (Dose Level B2)
TAK-925, Dose Level B2, once daily for up to 7 days in participants with narcolepsy. Dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.
干预措施: TAK-925 (Drug)
Cohort B3; TAK-925 (Dose Level B3)
TAK-925, Dose Level B3, once daily for up to 7 days in participants with narcolepsy. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.
干预措施: TAK-925 (Drug)
Cohort B4; TAK-925 (Dose Level B4)
TAK-925, Dose Level B4, once daily for up to 7 days in participants with narcolepsy. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.
干预措施: TAK-925 (Drug)
Part B (Cohorts B1-B4); TAK-925 Placebo
TAK-925 Placebo, once daily for up to 7 days in participants with narcolepsy.
干预措施: Placebo (Drug)
Cohort C1; TAK-925 (Dose Level C1)
TAK-925, Dose Level C1, once daily for up to 7 days in participants with narcolepsy. Dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.
干预措施: TAK-925 (Drug)
Cohort C2; TAK-925 (Dose Level C2)
TAK-925, Dose Level C2, once daily for up to 7 days in participants with narcolepsy. This group is an additional optional cohort and dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.
干预措施: TAK-925 (Drug)
Part C (Cohorts C1-C2); TAK-925 Placebo
TAK-925 Placebo, once daily for up to 7 days in participants with narcolepsy.
干预措施: Placebo (Drug)
Cohort A'1; TAK-925 (Dose Level A'1)
TAK-925, Dose Level A'1, single dose in healthy participants.
干预措施: TAK-925 (Drug)
Cohort A'2; TAK-925 (Dose Level A'2)
TAK-925, Dose Level A'2, single dose in healthy participants. Dose level will be determined based on the data of safety, tolerability and PK data from previous cohorts.
干预措施: TAK-925 (Drug)
结局指标
主要结局
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
时间窗: From the first dose of study drug up to 7 days after the last dose of study drug (up to Day 15)
An Adverse Event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE was defined as an AE with an onset that occurs after receiving study drug.
次要结局
- Parts A, B and C; Ceoi: Observed Plasma Concentration at the End of Infusion for TAK-925(Part A,Days 1,7:pre-infusion(inf),0.5,1, 1.5, 2, 4, 6, 8, 9 hours(h)post start of inf;0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 6, 10, 15 h post end of inf;Part B,C:Days 1,7:Pre-inf, 1, 2, 4, 6, 9 h post start of inf; 0.17, 0.5, 2, 6, 10, 15 h post end of inf)
- Parts A, B and C; AUCtau: Area Under the Plasma Concentration-Time Curve During a Dosing Interval for TAK-925(Part A,Days 1,7:pre-infusion(inf),0.5,1, 1.5, 2, 4, 6, 8, 9 hours(h)post start of inf;0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 6, 10, 15 h post end of inf;Part B,C:Days 1,7:Pre-inf, 1, 2, 4, 6, 9 h post start of inf; 0.17, 0.5, 2, 6, 10, 15 h post end of inf)
- Parts A, B and C; Rac (AUC): Accumulation Ratio Based on AUCtau for TAK-925(Part A,Days 1,7:pre-infusion(inf),0.5,1, 1.5, 2, 4, 6, 8, 9 hours(h)post start of inf;0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 6, 10, 15 h post end of inf;Part B,C:Days 1,7:Pre-inf, 1, 2, 4, 6, 9 h post start of inf; 0.17, 0.5, 2, 6, 10, 15 h post end of inf)
- Parts B and C: Change From Baseline in Sleep Latency in the Maintenance of Wakefulness Test (MWT) at Days 1 and 7(Baseline, Day 1 and Day 7)