Efficacy and Safety of NBI-1065845 as Adjunctive Therapy in Adults with Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the **efficacy** of NBI-1065845 compared with placebo as an adjunctive treatment in subjects with **Major Depressive Disorder** (MDD) on improving symptoms of depression, as measured by the Montgomery-Asberg Depression Rating Scale (MADRS). This is clinically relevant as it aims to determine the potential of NBI-1065845 to enhance treatment outcomes in MDD, a condition characterized by persistent and severe depressive symptoms that significantly impact daily functioning.

Secondary objectives include:

• Evaluating the efficacy of NBI-1065845 compared with placebo in improving overall functioning, as measured by the Sheehan Disability Scale (SDS), and in improving the overall severity of depression, as measured by the Clinical Global Impression-Severity Scale (CGI-S).
• Assessing the safety and tolerability of NBI-1065845 as an adjunctive treatment in subjects with MDD.

The clinical trial involves a total of **145 participants** diagnosed with **Major Depressive Disorder** (MDD). The study population includes both male and female subjects, aged 18 years and older, who have a primary diagnosis of recurrent MDD, either moderate or severe, or persistent depressive disorder. Participants are required to have an inadequate response to oral antidepressant treatments, as assessed by the Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire (MGH-ATRQ). The trial population was selected based on their ability to comply with study procedures and restrictions, as well as their current treatment regimen. The study does not specify any particular lifestyle considerations such as diet or physical activity. Participants are required to have a Total Hamilton Depression Rating Scale-17 Item (HAM-D17) score of 22 or higher at screening and baseline. The trial includes a vulnerable population, ensuring a comprehensive evaluation of the efficacy of NBI-1065845 as an adjunctive treatment for improving symptoms of depression, measured by the Montgomery-Asberg Depression Rating Scale (MADRS).

The clinical trial is designed to evaluate the efficacy and safety of **NBI-1065845** as an adjunctive treatment in adults with **Major Depressive Disorder** (MDD). This study is a randomized, double-blind, placebo-controlled trial, which aims to assess the improvement in depressive symptoms using the Montgomery-Asberg Depression Rating Scale (MADRS). The trial will span a total duration of 56 days, with participants receiving either the active drug or a placebo in tablet form, administered orally.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of MDD, and inadequate response to current antidepressant treatments. The diagnosis will be confirmed using the Mini-International Neuropsychiatric Interview (MINI). Baseline assessments will be conducted on Day 1, including the Hamilton Depression Rating Scale-17 Item (HAM-D17) to ensure a score of 22 or higher. Follow-up visits will occur at regular intervals to monitor safety, adherence, and efficacy, with the primary endpoint being the change in MADRS score from baseline to Day 56. Secondary endpoints include changes in the Sheehan Disability Scale (SDS) and Clinical Global Impressions-Severity (CGI-S) scores.

The expected length of participant involvement is approximately 8 weeks, with conditions for early termination including non-compliance with study procedures, adverse events, or withdrawal of consent. The trial is not categorized as low intervention and is classified as a Phase 3 study, indicating it involves a drug not currently authorized for the population in question. The study aims to provide valuable data on the potential benefits of NBI-1065845 as an adjunctive therapy for individuals with MDD who have not adequately responded to existing treatments.

The clinical trial involves the administration of the experimental medication **NBI-1065845**, which is formulated as a **tablet**. The active substance in this medication is **9-(4-cyclohexyloxyphenyl)-7-methyl-3,4-dihydropyrazino[2,1-c][1,2,4]thiadiazine 2,2-dioxide**, a chemical compound developed by Neurocrine Biosciences Inc. The medication is administered orally. The dosing schedule and specific dosage amounts are not explicitly detailed in the provided data, but the maximum treatment period is specified as 56 days. The medication is not a pediatric formulation and is not classified as an orphan drug.

The study also includes a **placebo** group, where participants receive tablets identical in appearance to the NBI-1065845 tablets but without the active drug. The placebo serves as a comparator treatment to evaluate the efficacy of the experimental medication. The placebo tablets are administered in the same manner as the active drug, ensuring the study remains double-blind. The placebo is used to assess the adjunctive treatment effects of NBI-1065845 in subjects with Major Depressive Disorder (MDD), with efficacy measured by the Montgomery-Asberg Depression Rating Scale (MADRS).

The efficacy of NBI-1065845 as an adjunctive treatment in subjects with **Major Depressive Disorder (MDD)** will be assessed through a randomized, double-blind, placebo-controlled study. The primary objective is to evaluate the improvement in symptoms of depression, as measured by the Montgomery-Asberg Depression Rating Scale (MADRS). The primary endpoint is defined as the change from baseline in the total MADRS score at Day 56. Secondary endpoints include the change from baseline in the Sheehan Disability Scale (SDS) total score and the Clinical Global Impressions-Severity (CGI-S) score, both assessed at Day 56.

Participants will be required to have a primary diagnosis of recurrent MDD or persistent depressive disorder, confirmed using the Mini-International Neuropsychiatric Interview (MINI). They must also demonstrate an inadequate response to oral antidepressant treatments, as assessed by the Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire (MGH-ATRQ). The study will involve the administration of NBI-1065845 in tablet form, with a maximum treatment period of 56 days. Efficacy assessments will be conducted at specified timepoints, with data collected and analyzed to determine the treatment's impact on depressive symptoms and overall functioning.