Evaluation of AV-EC2023 Efficacy and Safety in Insomnia: A Randomized, Placebo-Controlled, Double-Blind, Biphasic Clinical Trial in Adults

The primary objective of this study is to evaluate the **efficacy** and **safety** profile of Escholzia tablets in adults diagnosed with **insomnia** (ICD-10 F51.0). The focus is on assessing the perceived sleep quality and ensuring the safety of this newly developed pharmaceutical product. This is clinically relevant as insomnia is a prevalent condition that significantly impacts quality of life, and effective treatment options are essential for improving patient outcomes.

Secondary objectives include evaluating the impact of Escholzia tablets on various aspects of patient well-being:

• Cognitive function
• Mood, anxiety, and stress
• Quality of life
• Happiness and satisfaction
• Pain
• Physiological sleep quantity

The clinical trial focuses on evaluating the efficacy and safety of Escholzia tablets for the treatment of **insomnia** as per the ICD-10 F51.0 diagnosis. The study population comprises both male and female participants aged between 18 and 65 years. Participants are required to have a diagnosis of insomnia, with an Insomnia Severity Index (ISI) total score greater than 7. The trial does not include a vulnerable population. Participants must have a habitual bedtime between 9 pm and midnight and should have easy access to the internet for maintaining a daily e-diary. Additionally, they need to have freezing capacities available for the storage of saliva samples. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the **efficacy** and safety of Escholzia tablets in adults diagnosed with **insomnia** according to ICD-10 F51.0. This biphasic study consists of a randomized, placebo-controlled, double-blind, 1-month interventional phase (Phase A) followed by a prospective, 1-armed, 2-month interventional phase (Phase B). The trial aims to assess changes in perceived sleep quality using the Insomnia Severity Index (ISI) during Phase A, and evaluate safety and tolerability in Phase B. Secondary endpoints include changes in sleep quantity and quality, daytime sleepiness, anxiety, mood, quality of life, cognitive performance, and various biomarkers.

Participants will be involved in the study for a total duration of three months. The trial will commence with a screening visit to confirm eligibility based on criteria such as age (18-65 years), diagnosis of insomnia, and ISI score greater than 7. Participants must provide informed consent and have access to the internet for daily e-diary entries. The study will include regular follow-up visits to monitor progress and collect data on primary and secondary endpoints. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any remaining queries are addressed.

The trial is expected to start recruitment on January 2, 2024, and conclude by March 31, 2025. Participants may be withdrawn from the study if they experience adverse effects, fail to comply with study procedures, or withdraw consent. The investigational product, AV-EC2023, will be administered orally in tablet form, with a maximum daily dose of 2.01 grams and a total dose not exceeding 85.51 grams over the 12-week period. A matching placebo will be used to maintain blinding. The study is categorized as a therapeutic confirmatory clinical trial phase III, ensuring rigorous evaluation of the investigational product's therapeutic potential.

The clinical trial involves the administration of **AV-EC2023**, an experimental medication formulated as a tablet. The active substance, also named AV-EC2023, is provided by A.VOGEL AG. The pharmaceutical form of the medication is a tablet, intended for **oral** administration. The maximum daily dose is 2.01 grams, with a total maximum dose of 85.51 grams over the course of the treatment. The treatment period is set for a maximum of 12 weeks. The medication is not a pediatric formulation and is not classified as an orphan drug. Participant compliance with the dosing schedule will be monitored throughout the trial.

The study also includes a **placebo** tablet, which is designed to match the experimental medication in sensory properties and posology but does not contain any active pharmaceutical ingredient. The placebo serves as a comparator treatment in the randomized, placebo-controlled, double-blind phase of the trial. The placebo is administered orally, following the same dosing schedule as the experimental medication to ensure blinding and maintain the integrity of the study design.

The efficacy of the clinical trial evaluating Escholzia tablets for the treatment of **insomnia** will be assessed through a series of primary and secondary endpoints. The primary endpoint for Phase A of the trial is the change in perceived sleep quality, which will be measured using the Insomnia Severity Index (ISI). This validated scale will provide a quantitative assessment of the participants' sleep quality improvements over the course of the trial.

Secondary endpoints will include a variety of measures to provide a comprehensive evaluation of the treatment's efficacy. These include changes in perceived sleep quantity and quality as recorded in a daily sleep diary, physiological sleep quantity assessed via actigraphy, and daytime sleepiness measured with the Epworth Sleepiness Scale (ESS). Additionally, changes in state anxiety will be evaluated using the State-Trait Anxiety Inventory (STAI-X1), and mood changes will be assessed with the Depression, Anxiety, Stress Scale (DASS-21). The trial will also measure changes in general quality of life using the WHOQOL-BREF, happiness and satisfaction via the Oxford Happiness Questionnaire (OHQ), and domain-specific cognitive performance through the Computerized Mental Performance Assessment System (COMPASS).

Biomarkers will also be utilized to assess efficacy, including changes in stress levels via salivary evening cortisol, sleep readiness via salivary evening melatonin, and chronic stress through the cortisol awakening response (CAR) determined as area under the curve (AUC) and increase. Additional assessments will include changes in pain intensities and sleep quantity as measured by a polysomnography (PSG) device.