Efficacy and Safety of Seltorexant as Adjunctive Therapy in Major Depressive Disorder with Insomnia Symptoms: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the **efficacy** of 20 mg seltorexant as an adjunctive therapy to SSRI/SNRI antidepressants in adult and elderly patients with **Major Depressive Disorder with Insomnia Symptoms** (MDDIS). The study is conducted in two parts: Part 1 aims to assess the improvement in depressive symptoms in participants who have shown an inadequate response to their current SSRI/SNRI therapy. Part 2 focuses on evaluating the efficacy of seltorexant in delaying the relapse of depressive symptoms in participants who have achieved a stable response following open-label seltorexant treatment. This investigation is clinically relevant as it addresses the need for effective adjunctive treatments in patients with MDDIS who do not adequately respond to standard antidepressant therapies, potentially improving patient outcomes and quality of life.

The clinical trial involves a total of **400 participants** diagnosed with **Major Depressive Disorder with Insomnia Symptoms**. The study population includes both male and female subjects, aged between **18 to 74 years**, who are medically stable as determined by physical examination, vital signs, and a 12-lead ECG conducted at screening and baseline. Participants have been selected based on their inadequate response to at least one but no more than two antidepressants, administered at an adequate dose and duration during the current episode of depression. They must be receiving and tolerating a stable dose of an SSRI or SNRI for depressive symptoms for at least six weeks. The trial includes individuals with a **body mass index (BMI)** ranging from 18 to 40 kg/m². The study population is characterized by a major depressive episode of at least moderate severity, as assessed with SIGH-D, without significant improvement during the screening period. The trial also considers vulnerable populations, ensuring comprehensive representation within the study cohort.

The clinical trial is designed to evaluate the **efficacy** and safety of **seltorexant** as an adjunctive therapy to antidepressants in adult and elderly patients with **Major Depressive Disorder with Insomnia Symptoms**. This study is a two-part, multicenter, double-blind, randomized, placebo-controlled trial. The trial aims to assess the efficacy of seltorexant 20 mg compared with placebo in improving depressive symptoms and delaying relapse in participants who have had an inadequate response to current SSRI/SNRI antidepressant therapy. The trial is expected to commence recruitment on March 25, 2025, and conclude by December 30, 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on criteria such as age, medical stability, and a diagnosis of Major Depressive Disorder without psychotic features. The trial will include a double-blind treatment phase, where participants will be randomized to receive either seltorexant or a placebo. The primary endpoint for Part 1 is the change from baseline to Day 43 in the MADRS total score, while Part 2 focuses on the time from randomization to the first relapse during the double-blind maintenance phase.

Follow-up visits will be conducted to monitor the participants' response to the treatment and ensure their safety. The end-of-study visit will mark the conclusion of the participant's involvement in the trial. The expected length of participant involvement is up to 126 days, with conditions for early termination including significant adverse events or withdrawal of consent. Participants must consistently tolerate the study drug to continue in the trial. The study will adhere to rigorous scientific standards to ensure the reliability and validity of the results.

The clinical trial involves the administration of **seltorexant**, an investigational medication, as an adjunctive therapy to standard antidepressants in patients with Major Depressive Disorder with Insomnia Symptoms (MDDIS). The experimental medication, identified by the sponsor product code JNJ-42847922, is formulated as a **film-coated tablet**. Each tablet contains the active substance **seltorexant**, a chemical compound classified as an orexin-2 receptor antagonist. The dosage of seltorexant is 20 mg, administered orally once daily. The maximum treatment period for this study is 126 days. The trial aims to evaluate the efficacy of seltorexant in improving depressive symptoms and delaying relapse in participants who have shown an inadequate response to their current SSRI/SNRI antidepressant therapy.

In addition to the experimental treatment, a **placebo** film-coated tablet is used as a comparator in this double-blind, randomized, placebo-controlled study. The placebo is designed to match the appearance of the seltorexant tablet but contains no active pharmaceutical ingredients. The placebo is administered orally with the same frequency and duration as the seltorexant tablets to maintain the study's blinding and ensure the integrity of the trial results.

Participants in the study will continue their existing SSRI/SNRI antidepressant therapy throughout the trial. Compliance with the dosing schedule will be monitored to ensure adherence to the treatment regimen. The study's design includes measures to assess participant compliance, such as pill counts and participant diaries, to accurately evaluate the efficacy and safety of the investigational medication.

The efficacy of **seltorexant** as an adjunctive therapy to antidepressants in adult and elderly patients with Major Depressive Disorder with Insomnia Symptoms (MDDIS) will be assessed in a two-part, multicenter, double-blind, randomized, placebo-controlled study. The primary efficacy endpoint for Part 1 is the change from baseline to Day 43 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. This scale is a validated tool used to measure the severity of depressive episodes. For Part 2, the primary endpoint is the time from randomization to the first relapse during the double-blind Maintenance Phase in participants who achieve a stable response at the end of open-label seltorexant treatment.