A Phase 1 Study of TAK-925 to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Single Dose of TAK-925 in Healthy Adult and Elderly 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
- 58
- 试验地点
- 3
- 主要终点
- Part 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2
研究概览
简要总结
The purpose of this study is to investigate safety, tolerability, and pharmacokinetics of TAK-925 when a single dose of TAK-925 is administered to healthy adult participants, healthy elderly participants and patients with type 1 narcolepsy.
详细描述
Orexins are neuropeptides that play a role in the regulation of sleep and wakefulness. In type 1 narcolepsy, there is a loss of orexin producing neurons in the brain. The investigational drug, TAK-925, is an orexin 2 receptor agonist that is being tested in healthy adult participants, healthy elderly participants and patients with narcolepsy in order to evaluate the safety, tolerability, and pharmacokinetics (PK) of a single intravenous administration.
The study will enroll approximately 20 healthy participants and 16 healthy elderly participants in Part 1 of the study and approximately 20 patients with narcolepsy in Part 2.
In Part 1, the study consists of 4 cohorts of 8 or 4 participants each. Participants will be randomly assigned (by chance, like flipping a coin) to one of the following treatment groups to receive TAK-925 or placebo:
- Part 1, Cohort 1; TAK-925 (Dose Level 1, 3, 5), Cohort 2; TAK-925 (Dose Level 2, 4, 6), Cohort 3 and 4; TAK-925 (Dose Level 5)
For Cohort 1-4, healthy adult and elderly participants will be administered TAK-925 or placebo once in each cohort or dose level. The dose at the start (Cohort 1 dose level 1) is 7 mg of TAK-925 and following doses in Cohorts 1-4 will be determined based on available data from previous Cohorts/dose levels.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 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 kilogram (kg) (Healthy adults participants) / 40 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 patients:
- •Patient weighs at least 40 kg inclusive at Screening.
- •A diagnosis of narcolepsy Type 1, as defined by the International Classification of Sleep Disorders, Third Edition (ICSD-3).
- •HLA narcolepsy test positivity.
- •At Day -1, Epworth sleepiness scale (ESS) score greater than or equal to (>=) 10
- •Blood pressure less than (<) 140 systolic and < 90 diastolic. The patient may have a history of hypertension and be on antihypertensive medication treatment as long as the BP meets these criteria.
排除标准
- •All Participants:
- •Participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 2 years prior to the Screening visit.
- •Past or current epilepsy, convulsion, tremor or the disorders of related symptoms.
- •Has a lifetime history of major psychiatric disorder, such as major depressive disorder, bipolar disorder, or schizophrenia.
- •HV (only Cohort 4):
- •Participant has had CSF collection performed within 14 days prior to check-in (Day -1).
- •Narcolepsy patients
- •Medical disorder associated with excessive sleepiness other than narcolepsy (including sleep apnea syndrome).
- •Excessive caffeine (greater than [>] 400 milligram per day [mg/day]) use one week prior to study.
研究组 & 干预措施
Part 1: Placebo (Cohort 3)
TAK-925 Placebo, Intravenous single administration. Healthy elderly participants will be enrolled in double blind manner.
干预措施: Placebo (Drug)
Part 1: TAK-925 (Cohort 1; Dose Level 1)
TAK-925, Intravenous single administration. Healthy adults will be enrolled in double blind manner.
干预措施: TAK-925 (Drug)
Part 1: TAK-925 (Cohort 2; Dose Level 2)
TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 2). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner.
干预措施: TAK-925 (Drug)
Part 1: TAK-925 (Cohort 1; Dose Level 3)
TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 3). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner.
干预措施: TAK-925 (Drug)
Part 1: TAK-925 (Cohort 2; Dose Level 4)
TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 4). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner.
干预措施: TAK-925 (Drug)
Part 1: TAK-925 (Cohort 1; Dose Level 5)
TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 5). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner.
干预措施: TAK-925 (Drug)
Part 1: TAK-925 (Cohort 2; Dose Level 6)
TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 6). Dose selected based on safety, tolerability and PK data from previous Cohorts. Healthy adults will be enrolled in double blind manner.
干预措施: TAK-925 (Drug)
Part 1: Placebo (Cohort 1-2)
TAK-925 Placebo, Intravenous single administration. Healthy adults will be enrolled in double blind manner.
干预措施: Placebo (Drug)
Part 1: TAK-925 (Cohort 3; Dose Level 5)
TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 5). Healthy elderly participants will be enrolled in double blind manner.
干预措施: TAK-925 (Drug)
Part 1: TAK-925 (Cohort 4; Dose Level 5)
TAK-925, Intravenous single administration. Dose level will be determined by targeted plasma level of TAK-925 (Dose level 5). Healthy adults will be enrolled in non-blinded manner.
干预措施: TAK-925 (Drug)
Part 2: TAK-925 TBD (Cohort 5)
TAK-925, Intravenous single administration. Dose in Cohort 5 will be based on safety and tolerability in the Part 1. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open).
干预措施: TAK-925 (Drug)
Part 2: TAK-925 TBD (Cohort 6)
TAK-925, Intravenous single administration. Dose in Cohort 6 TBD based on safety, tolerability, PK data, and results of the Maintenance Wakefulness Test (MWT) from previous Cohorts. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open).
干预措施: TAK-925 (Drug)
Part 2: TAK-925 TBD (Cohort 7)
TAK-925, Intravenous single administration. Dose in Cohort 7 TBD based on safety, tolerability, PK data, and results of the Maintenance of Wakefulness Test (MWT) from previous Cohorts. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open).
干预措施: TAK-925 (Drug)
Part 2: Placebo (Cohort 5-7)
TAK-925 Placebo, Intravenous single administration. Patients with Narcolepsy will be enrolled in double blind manner (sponsor open).
干预措施: Placebo (Drug)
结局指标
主要结局
Part 2, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2
时间窗: Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion
Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2
时间窗: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion
Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2
时间窗: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion
Number of Participants Who Experience at Least One TEAE Related to Body Weight
时间窗: Baseline up to Day 7
Number of Participants Who Experience at Least One TEAE Related to 12-lead Electrocardiogram (ECG)
时间窗: Baseline up to Day 7
Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-925 and Its Metabolites M1 and M2
时间窗: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion
Part 1, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2
时间窗: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion
Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2
时间窗: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
时间窗: Baseline up to Day 7
Number of Participants Who Experience at Least One TEAE Related to Vital Signs
时间窗: Baseline up to Day 7
Number of Participants Who Experience at Least One TEAE Related to Clinical Laboratory Tests
时间窗: Baseline up to Day 7
Part 2, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-925 and Its Metabolites M1 and M2
时间窗: Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion
Part 2, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-925 and Its Metabolites M1 and M2
时间窗: Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion
Part 1, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2
时间窗: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion
Part 2, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925
时间窗: Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion
Part 2, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925
时间窗: Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion
Part 1, CL: Total Clearance After Intravenous Administration for TAK-925
时间窗: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion
Part 1, Fe(0-24): Fraction of Administered Dose of Drug Excreted in Urine From Time 0 to Time 24 for TAK-925 and Its Metabolites M1 and M2
时间窗: Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6, 6-15 and 15-24 hours post-infusion
Urine assessments were done only in Part 1, as planned.
Part 1, CLR: Renal Clearance of TAK-925 and Its Metabolites M1 and M2
时间窗: Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6 and 6-15 hours post-infusion
Urine assessments were done only in Part 1, as planned.
Part 1, Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-925
时间窗: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion
Part 1, Ae(0-24): Amount of TAK-925 and Its Metabolites M1 and M2 Excreted in Urine From Time 0 to Time 24
时间窗: Day 1 pre-infusion and 0-9 hours after the start of infusion and at 0-3, 3-6, 6-15 and 15-24 hours post-infusion
Urine assessments were done only in Part 1, as planned.
Part 2, Cmax: Maximum Observed Plasma Concentration for TAK-925 and Its Metabolites M1 and M2
时间窗: Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion
Part 2, t1/2z: Terminal Disposition Phase Half-life of TAK-925 and Its Metabolites M1 and M2
时间窗: Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion
Part 2, Ceoi: Concentration at the End of Infusion for TAK-925 and Its Metabolites M1 and M2
时间窗: Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion
Part 1, Vz: Volume of Distribution During the Terminal Phase After Intravenous Administration for TAK-925
时间窗: Day 1 pre-infusion and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 9 hours after the start of infusion and at 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 10 and 15 hours post-infusion
Part 2, CL: Total Clearance After Intravenous Administration for TAK-925
时间窗: Days 1-4 pre-infusion and at 1, 2, 4, 6 and 9 hours after the start of infusion and at 0.17, 0.5, 1, 2 and 15 hours post-infusion
Part 1, R(CSF/Plasma,ss): Cerebrospinal Fluid/Plasma Drug Concentration at Steady State for TAK-925 and Its Metabolites M1 and M2 in Cohort 4
时间窗: Day 1 at 6 hours after start of infusion
次要结局
- Part 2: Average Sleep Latency in Maintenance of Wakefulness Test (MWT)(Days 1 and 3 up to 8 hours following the start of infusion)