Evaluating the Efficacy and Safety of Daridorexant Transition From BZRAs in Insomnia Patients（EASY-TIP）

Insomnia Disorders

Insomnia Disorder, Daridorexant, BZRAs, Drug Transition

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.

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. Intervention: Daridorexant tablets (50 mg) taken orally once nightly. Dose adjustment to 25 mg is permitted based on tolerability, but the maximum dose is 50 mg daily. Outcomes: Primary Outcome: 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: Changes from baseline in Insomnia Severity Index (ISI) scores; patient-reported sleep outcomes (subjective total sleep time, sleep quality) assessed by electronic sleep diary; and patterns of daridorexant and BZRA dosing adjustments. Safety Outcomes: Incidence and severity of treatment-emergent adverse events (TEAEs); assessment of benzodiazepine withdrawal symptoms using the Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ). Visit Schedule: Patients will undergo 6 visits: at Day 0 (V1, screening), Day 7 (V2, baseline, daridorexant initiation), Day 14 (V3), Day 21 (V4), Day 42 (V5, primary endpoint), and Day 70 (V6, end of treatment). Assessments include ISI, electronic sleep diary, BWSQ, and safety monitoring at each visit. Sample Size: Based on an expected transition success rate of 80% at Week 5, with a 95% confidence interval and 10% margin of error, and accounting for a 10% dropout rate, a total of 156 patients will be enrolled (78 per BZRA subgroup). Statistical Analysis: The primary analysis will be performed on the full analysis set (FAS). Descriptive statistics will be used for baseline characteristics. The primary endpoint will be presented with a 95% confidence interval. Secondary endpoints will be analyzed using appropriate parametric or non-parametric methods. Safety data will be summarized descriptively. Ethical Considerations: The study will be conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. The protocol has been approved by the Ethics Committee of Xuanwu Hospital, Capital Medical University. Written informed consent will be obtained from all participants. Expected Impact: This study aims to provide real-world evidence on the safe and effective transition from BZRAs to daridorexant, informing clinical decision-making and potentially improving long-term insomnia management in Chinese patients.

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