Evaluating the Efficacy and Safety of Daridorexant Transition From BZRAs in Insomnia Patients（EASY-TIP）
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 156
- 试验地点
- 1
- 主要终点
- Proportion of Participants Successfully Transitioning from BZRAs to Daridorexant at Week 5
研究概览
简要总结
Brief Summary:
This study is a prospective, multicenter, open-label cohort study designed to evaluate the efficacy and safety of transitioning adult patients with insomnia from benzodiazepine receptor agonists (BZRAs) to daridorexant.
A total of 156 participants will be enrolled. The study consists of a 1-week baseline phase and a 9-week daridorexant treatment phase. During the treatment phase, daridorexant 50 mg is initiated once daily while BZRAs are gradually tapered and discontinued based on individual patient response.
The primary outcome is the proportion of patients who successfully transition from BZRAs to daridorexant at Week 5, defined as a ≥50% reduction or complete discontinuation of the original BZRA dose, with continued willingness to take daridorexant and no withdrawal due to worsening insomnia or adverse events. Secondary outcomes include changes in Insomnia Severity Index (ISI) scores and patient-reported sleep outcomes.
This study aims to provide real-world evidence for the safe and effective transition from BZRAs to daridorexant in clinical practice.
详细描述
Detailed Description:
Background: Insomnia is a prevalent disorder that significantly impacts quality of life and daytime functioning. Benzodiazepine receptor agonists (BZRAs), including benzodiazepines and non-benzodiazepines, are commonly used but are associated with tolerance, dependence, withdrawal symptoms, and disruption of sleep architecture. Daridorexant, a dual orexin receptor antagonist (DORA), offers a novel mechanism by reducing hyperarousal and promoting physiological sleep, with a favorable safety profile and no withdrawal effects upon discontinuation. However, real-world evidence on transitioning patients from BZRAs to daridorexant remains limited.
Study Objective: To evaluate the efficacy and safety of transitioning adult insomnia patients from BZRAs to daridorexant in a clinical practice setting.
Study Design: This is a prospective, multicenter, open-label, cohort study. Patients will be enrolled across multiple sites in China. The study consists of two phases: a 1-week baseline phase (during which patients continue their usual BZRA therapy) and a 9-week daridorexant treatment phase. During the treatment phase, daridorexant 50 mg is initiated once daily, 30 minutes before bedtime, while the original BZRA is tapered and discontinued according to individual patient response, following a cross-tapering approach.
Population: A total of 156 adult patients (aged 18-70 years) with insomnia disorder according to DSM-5 criteria, who have been on stable BZRA monotherapy for at least 3 nights per week for the past month, and who are dissatisfied with or intolerant to their current therapy, will be enrolled. Key exclusion criteria include chronic insomnia >5 years, severe psychiatric disorders, significant comorbidities, and prior use of DORA agents without response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged ≥18 and ≤70 years.
- •Meet DSM-5 diagnostic criteria for insomnia disorder: dissatisfaction with nighttime sleep despite adequate sleep opportunity, manifested as difficulty initiating sleep, difficulty maintaining sleep (frequent awakenings or difficulty returning to sleep after awakening), or early-morning awakening with inability to resume sleep, accompanied by subjective experience of daytime dysfunction. Symptoms occur ≥3 times per week and persist for ≥3 months.
- •Received stable BZRA monotherapy for at least 3 nights per week during the 1 month prior to enrollment.
- •Bedtime duration of no less than 7 hours per night.
- •Unsatisfactory response or intolerance to current therapy, with clinical need to adjust insomnia medication regimen.
- •Hamilton Anxiety Rating Scale (HAMA-14) score <
- •Hamilton Depression Rating Scale (HAMD-17) score <
- •Willing and able to comply with the study protocol and provide written informed consent.
排除标准
- •History of chronic insomnia >5 years.
- •Other sleep disorders such as narcolepsy-related symptoms, restless legs syndrome, circadian rhythm sleep disorder, REM sleep behavior disorder, etc.
- •Daytime napping ≥1 hour/day and ≥3 days/week.
- •Daily BZRA dose exceeding the maximum recommended dose for insomnia treatment per package insert.
- •BZRA use >5 nights per week.
- •History of BZRA treatment ≥3 years.
- •Concurrent use of two or more BZRAs within the past 3 months.
- •Use of central nervous system depressants within the past 3 months.
- •Use of long-acting sedative-hypnotics (e.g., clonazepam) within the past 3 months.
- •Use of anxiolytics or antidepressants for off-label insomnia treatment within the past 3 months.
- •Initiation of cognitive behavioral therapy for insomnia (CBT-I) within 1 month prior to Visit
- •Prior non-response to orexin receptor antagonists (daridorexant, lemborexant, suvorexant, etc.).
- •Clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal) that may affect participant safety or interfere with study assessments, as judged by the investigator. Participants for whom sedative medications are contraindicated due to occupational or safety reasons are also excluded.
- •Severe psychiatric disorder within the past 6 months, or severe alcohol/substance abuse/dependence within the past 2 years.
- •Active suicidal ideation or behavior within the past 6 months.
- •Pregnancy, lactation, or planned pregnancy within 90 days.
- •Unable to avoid excessive alcohol consumption during the study.
- •History of hypersensitivity to any component of daridorexant tablets.
- •Severe hepatic impairment (Child-Pugh score ≥10).
- •Unable to discontinue strong CYP3A4 inhibitors and strong or moderate CYP3A4 inducers during the study.
研究组 & 干预措施
Daridorexant Transition Group
Participants receive daridorexant 50 mg orally once nightly for 9 weeks, with gradual tapering and discontinuation of their prior benzodiazepine receptor agonist (BZRA) therapy based on individual clinical response. Dose reduction of daridorexant to 25 mg is permitted if clinically indicated. The study includes 6 visits over 10 weeks, with the primary endpoint assessed at Week 5.
干预措施: Daridorexant (Drug)
结局指标
主要结局
Proportion of Participants Successfully Transitioning from BZRAs to Daridorexant at Week 5
时间窗: At Week 5 (Visit 5, Day 42 ± 3 days)
Defined as a ≥50% reduction or complete discontinuation of the original BZRA dose, with continued willingness to take daridorexant, and no withdrawal due to worsening insomnia or adverse events at Week 5 (Visit 5, Day 42 ± 3 days).
次要结局
未报告次要终点