A Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, and Tolerability of TAK-861 for the Treatment of Narcolepsy With Cataplexy (Narcolepsy Type 1)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 112
- 试验地点
- 57
- 主要终点
- Change From Baseline in the Average Sleep Latency as Determined From the MWT at Week 8
研究概览
简要总结
The main aim of this study is to see how TAK-861 works on symptoms of narcolepsy, including excessive daytime sleepiness and cataplexy. Approximately 100 participants will take part in the study across North America, Europe and Asia Pacific.
The treatment (TAK-861 or placebo) will be administered for 8 or 12 weeks. After this treatment period the participant will have the option to participate in a separate, long- term extension study during which all participants will be treated with TAK-861.
详细描述
The drug being tested in this study is called TAK-861. This study will look at the effect of TAK-861 on improvement in narcolepsy symptoms, including excessive daytime sleepiness (EDS) and number of cataplexy episodes.
The study will enroll approximately 100 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the five treatment groups which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):
- TAK-861 Dose 1
- TAK-861 Dose 2
- TAK-861 Dose 3
- TAK-861 Dose 4
- Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient
This multi-center trial will be conducted worldwide. The overall time to participate in this study is up to 23 weeks. Participants will make multiple visits to the clinic during the treatment period and then will either enroll in a long-term extension study in which all participants will receive TAK-861 or have 2 final visits 7 and 28 days after last dose of study drug for follow-up assessments.
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, Care Provider)
入排标准
- 年龄范围
- 16 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The participant is aged 18 to 70 years, inclusive, at the time of signing the informed consent form (ICF).
- •Note: In Japan, participants aged 16 to 70 years, inclusive, may be included.
- •The participant has body mass index (BMI) within the range 18 to 40 kilogram per square meter [kg/m^2] (inclusive).
- •The participant has an International Classification of Sleep Disorders, 3rd Edition (ICSD-3) diagnosis of narcolepsy type 1 (NT1) by polysomnography (PSG)/Multiple Sleep Latency Test (MSLT), performed within the past 10 years.
- •The participant is positive for the human leukocyte antigen (HLA) genotype HLA-DQB1*06:02 or results from cerebrospinal fluid (CSF) testing indicate the participant's CSF orexin (OX)/hypocretin-1 concentration is <110 picograms per milliliter ([pg/mL] (or less than one-third of the mean values obtained in normal participants within the same standardized assay).
排除标准
- •The participant has a current medical disorder, other than narcolepsy with cataplexy, associated with EDS.
- •The participant has medically significant hepatic or thyroid disease.
- •The participant has a history of cancer in the past 5 years (does not apply to participants with carcinoma in situ that has been resolved without further treatment or basal cell cancer).
- •The participant has clinically significant coronary artery disease, a history of myocardial infarction, clinically significant angina, clinically significant cardiac rhythm abnormality, or heart failure.
- •The participant has a clinically significant history of head injury or head trauma.
- •The participant has history of epilepsy, seizure, or convulsion, or has a family history of inherited disorders associated with seizure (except for a single febrile seizure in childhood).
- •The participant has one or more of the following psychiatric disorders:
- •Any current unstable psychiatric disorder.
- •Current or history of manic or hypomanic episode, schizophrenia or any other psychotic disorder, including schizoaffective disorder, major depression with psychotic features, bipolar depression with psychotic features, obsessive compulsive disorder, intellectual disability, organic mental disorders, or mental disorders due to a general medical condition as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5).
- •Current diagnosis or history of substance use disorder as defined in the DSM-
- •Current active major depressive episode (MDE) or who have had an active MDE in the past 6 months.
- •The participant has a history of cerebral ischemia, transient ischemic attack (<5 years ago), intracranial aneurysm, or arteriovenous malformation.
- •The participant has a positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or human immunodeficiency virus (HIV) antibody/antigen.
- •The participant's renal creatinine clearance (Cockcroft-Gault Equation) is ≤50 mL/minute.
- •The participant has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values >1.5 times the upper limit of normal (ULN).
- •The participant is considered by the investigator to be at imminent risk of suicide or injury to self, others, or property, or the participant has attempted suicide within the past year.
研究组 & 干预措施
TAK-861 2 mg and 5 mg
Participants received TAK-861 2 mg followed by 5 mg dose, orally, BID, from Days 1 to 56.
干预措施: TAK-861 (Drug)
Placebo
Participants received placebo tablets matching TAK-861, orally, twice daily (BID), from Days 1 to 56.
干预措施: Placebo (Drug)
TAK-861 0.5 mg BID
Participants received TAK-861 0.5 milligrams (mg), orally, BID, from Days 1 to 56.
干预措施: TAK-861 (Drug)
TAK-861 2 mg BID
Participants received TAK-861 2 mg, orally, BID, from Days 1 to 56.
干预措施: TAK-861 (Drug)
TAK-861 7 mg QD
Participants received TAK-861 7 mg, orally, once daily (QD), from Day 1 to 56. Placebo was given as the second dose.
干预措施: TAK-861 (Drug)
TAK-861 7 mg QD
Participants received TAK-861 7 mg, orally, once daily (QD), from Day 1 to 56. Placebo was given as the second dose.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in the Average Sleep Latency as Determined From the MWT at Week 8
时间窗: Baseline, Week 8
The MWT is a validated, objective measure that evaluates a participant's ability to remain awake under soporific conditions for a defined period. During each MWT session (1 session = 40 minutes), participants were instructed to sit quietly and remain awake for as long as possible. Sleep latency in each session was recorded on EEG. If no sleep was observed according to these rules, then the latency was defined as 40 minutes. The linear mixed effects model for repeated measures (MMRM) was used for analysis.
次要结局
- Change From Baseline in Epworth Sleepiness Scale (ESS) Total Score at Week 8(Baseline, Week 8)
- Weekly Cataplexy Rate (WCR) at Week 8(Week 8)
- Number of Participants With at Least One Treatment-emergent Adverse Event (TEAE)(From first dose of the study drug up to end of the study (up to 3 months))