Evaluation of Long-Term Safety and Tolerability of NBI-1065845 as Adjunctive Therapy in Adults with Major Depressive Disorder

The primary objective of this study is to evaluate the long-term **safety** and **tolerability** of NBI-1065845 as an adjunctive treatment in subjects with **Major Depressive Disorder** (MDD). This is clinically relevant as it aims to ensure that the medication can be safely used over an extended period, which is crucial for chronic conditions like MDD where long-term treatment is often necessary.

Secondary objectives include evaluating the effects of NBI-1065845 on symptoms of depression, as reported by the subjects, and their ability to complete daily activities. These objectives are important for understanding the broader impact of the treatment on patients' quality of life and functional outcomes, beyond just the primary safety and tolerability measures.

The clinical trial involves a total of **286 participants** diagnosed with **Major Depressive Disorder** (MDD). The study population includes both male and female subjects, with an age range spanning from 18 to 65 years. Participants were selected based on their primary diagnosis of recurrent MDD, either moderate or severe, or persistent depressive disorder. All subjects have experienced an inadequate response to oral antidepressant treatments during their current depressive episode and have been on such treatments for at least 8 weeks. They are required to continue their current antidepressant regimen throughout the study. The trial includes individuals who are willing and able to comply with all study procedures and restrictions. The population is not limited by gender, and it includes vulnerable groups. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. Key inclusion criteria include a total **Montgomery-Åsberg Depression Rating Scale (MADRS)** score of 18 or higher at screening. The trial aims to evaluate the long-term safety and tolerability of NBI-1065845 as an adjunctive treatment in subjects with MDD.

The clinical trial is designed to evaluate the long-term safety and tolerability of **NBI-1065845** as an adjunctive treatment in subjects with **Major Depressive Disorder** (MDD). This is a Phase 3, open-label study, which means that both the researchers and participants know which treatment is being administered. The trial is expected to last until May 31, 2030, with recruitment starting on July 31, 2025. Participants will be involved in the study for a maximum treatment period of 156 weeks. The study will include several key visits: an initial screening visit, regular follow-up visits, and an end-of-study visit. The screening visit will determine eligibility based on criteria such as a primary diagnosis of recurrent MDD or persistent depressive disorder, inadequate response to oral antidepressants, and a total **Montgomery-Åsberg Depression Rating Scale** (MADRS) score of 18 or higher. Follow-up visits will monitor the occurrence of adverse events, which is the primary endpoint of the study, up to Week 52. The end-of-study visit will conclude the participant's involvement in the trial. Participants are expected to continue their current oral antidepressant regimen throughout the study. Conditions that may lead to early termination from the study include non-compliance with study procedures or the occurrence of significant adverse events. The investigational product, NBI-1065845, is administered orally in tablet form. The study is not classified as low intervention, and the investigational product is not currently authorized for the population involved in this trial. The trial is conducted under the sponsorship of Neurocrine Biosciences Inc. and does not involve any pediatric formulations or orphan drug designations.

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 trial is designed to assess the long-term safety and tolerability of NBI-1065845 as an adjunctive treatment in subjects with Major Depressive Disorder (MDD). The maximum treatment period for participants is 156 weeks. The dosage and frequency of administration are determined by the study protocol, with compliance monitored throughout the trial.

In addition to the experimental treatment, participants may receive standard-of-care therapy for Major Depressive Disorder as part of their treatment regimen. The study does not utilize a placebo or comparator treatment. The trial is open-label, meaning that both the participants and the investigators are aware of the treatment being administered. Participant compliance with the dosing schedule is monitored to ensure adherence to the study protocol.

The efficacy of the investigational product, NBI-1065845, in the clinical trial will be assessed primarily through the occurrence of adverse events (AEs) up to Week 52. This endpoint is designed to evaluate the long-term safety and tolerability of NBI-1065845 as an adjunctive treatment in subjects with **Major Depressive Disorder (MDD)**. The trial will involve subjects who have a primary diagnosis of recurrent MDD, either moderate or severe, or persistent depressive disorder, and who have had an inadequate response to oral antidepressant treatments in their current episode of depression. Participants must have been taking oral antidepressants for at least 8 weeks and are required to continue the same oral antidepressants at the same dose and frequency throughout the study.