A multi-center, double-blind, randomized, placebo-controlled, 2-way cross-over post approval study to investigate the efficacy of daridorexant in subjects with insomnia and comorbid nocturia

The primary objective of this study is to assess whether **daridorexant** improves insomnia in subjects with insomnia and comorbid nocturia. Insomnia Disorder is a prevalent condition characterized by difficulty in initiating or maintaining sleep, which can significantly impact quality of life and daily functioning. The presence of comorbid **nocturia**, a condition involving frequent urination during the night, can exacerbate sleep disturbances, making effective management crucial for patient well-being.

Secondary objectives include evaluating the efficacy of daridorexant on nocturia. Addressing nocturia is clinically relevant as it may contribute to the overall improvement of sleep quality and reduce the burden of insomnia symptoms in affected individuals.

The clinical trial involves a total of **15 participants** who are being studied to assess the efficacy of daridorexant in improving **insomnia** in individuals with comorbid **nocturia**. The study population includes both male and female subjects aged **55 years and older**. Participants were selected based on specific criteria, including having insomnia complaints for at least three months and a nocturia severity of at least three nocturnal voids per night for a minimum of one month prior to the initial visit. The trial does not include a vulnerable population. Participants are required to have the ability to communicate effectively with the investigator and demonstrate an understanding of the study requirements. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The sponsor has not provided additional information regarding the general health status of the participants.

The clinical trial is a **randomized**, **double-blind**, **placebo-controlled** study designed to evaluate the efficacy of **daridorexant** in subjects with **insomnia** and comorbid **nocturia**. This phase 4, post-marketing study involves a 2-way cross-over design, ensuring that each participant receives both the active treatment and the placebo at different times during the trial. The trial is expected to run from March 6, 2023, to April 30, 2024, with the primary objective being to assess changes in subjective total sleep time from baseline to Week 4.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥ 55 years), insomnia complaints for at least three months, and nocturia severity. Following successful screening, participants will be randomized to receive either **QUVIVIQ 50 mg film-coated tablets** or a matching placebo. The study includes multiple follow-up visits to monitor safety and efficacy, with the end-of-study visit marking the completion of the trial. The expected length of participant involvement is approximately 29 days, corresponding to the maximum treatment period.

Conditions that may lead to early termination from the study include non-compliance with study procedures, adverse events, or withdrawal of consent. The trial's design ensures that all participants are blinded to the treatment allocation, maintaining the integrity of the study results. The study's endpoints focus on improvements in sleep parameters, with the primary endpoint being the change in subjective total sleep time. This trial aims to provide valuable insights into the therapeutic potential of **daridorexant** for individuals suffering from insomnia and nocturia.

The clinical trial involves the administration of **QUVIVIQ** 50 mg film-coated tablets, which contain the active substance **daridorexant**. These tablets are manufactured by Idorsia Pharmaceuticals Deutschland GmbH and are intended for **oral use**. The pharmaceutical form is a film-coated tablet, and the maximum daily dose is 50 mg, with a total maximum dose of 1450 mg over the treatment period. The treatment duration is set for a maximum of 29 days. The tablets have undergone modifications in primary and secondary packaging, and they do not present any debossing. The administration schedule requires participants to take the medication as prescribed, with compliance monitored throughout the study.

In addition to the experimental treatment, the study employs a placebo control, using daridorexant placebo matching film-coated tablets. These placebo tablets are designed to match the appearance of the QUVIVIQ tablets to maintain the double-blind nature of the trial. The placebo is also administered orally, following the same dosing schedule as the active treatment. The use of a placebo allows for the assessment of the efficacy of daridorexant in improving insomnia symptoms in subjects with insomnia and comorbid nocturia, by providing a comparator to evaluate the treatment effect.

The efficacy of **daridorexant** in the clinical trial will be assessed through a primary endpoint focused on the change from baseline to Week 4 in subjective total sleep time (sTST). This endpoint is designed to evaluate the improvement in sleep duration among subjects with insomnia and comorbid nocturia. The trial is structured as a multi-center, double-blind, randomized, placebo-controlled, 2-way cross-over study, ensuring rigorous assessment of the treatment's efficacy.

Participants will be evaluated using the Insomnia Severity Index (ISI©) score, with a requirement of a score of 13 or higher at Visit 1, indicating significant insomnia symptoms. The study will involve male and female subjects aged 55 years or older, who have experienced insomnia complaints for at least three months and report an average of three or more nocturnal voids per night for at least one month prior to the initial visit. The trial will utilize daridorexant 50 mg film-coated tablets, with a maximum treatment period of 29 days, to determine its impact on sleep parameters.