Efficacy, Safety, and Tolerability of Brexanolone Caprilcerbate in Adults with Major Depressive Disorder with or without Anxious Distress: A Randomized, Double-Blind Study

The primary objective of this study is to **characterize** the effects of SPT-300 as a monotherapy on depressive symptoms in participants with **Major Depressive Disorder (MDD)**, with or without anxious distress. This is clinically relevant as it aims to evaluate the potential of SPT-300 to alleviate depressive symptoms, which could offer a new therapeutic option for individuals suffering from MDD, a condition that significantly impacts quality of life and daily functioning.

Secondary objectives include:

• To characterize the effects of SPT-300 on overall illness severity in participants with MDD, with or without anxious distress.

The clinical trial involves a total of **94 participants** diagnosed with **Major Depressive Disorder (MDD)**, with or without anxious distress. The study population comprises both male and female subjects, aged between 18 and 65 years. Participants were selected based on their ability and willingness to provide written informed consent, and they must have a primary diagnosis of MDD. Individuals with comorbid conditions such as generalized anxiety disorder, social anxiety disorder, or panic disorder may be included, provided these conditions have not been the focus of treatment in the six months prior to screening, and MDD is considered the primary diagnosis. Eligible participants must be experiencing a current depressive episode lasting between 4 weeks and 18 months prior to screening. The trial includes a vulnerable population, indicating careful consideration of ethical standards in participant selection. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as a **randomized**, parallel-group, **double-blind**, placebo-controlled study to evaluate the efficacy, safety, and tolerability of SPT-300 in adults diagnosed with **Major Depressive Disorder (MDD)**, with or without anxious distress. The trial will involve the administration of SPT-300 in capsule form, with a maximum daily dose of 375 mg, over a treatment period of up to six weeks. The study will include a placebo group for comparison, ensuring the reliability of the results through the use of a control group.

Participants will be involved in the study for a total duration of approximately six weeks, with the trial expected to conclude by December 2026. The sequence of study visits will begin with an inclusion (screening) visit, where eligibility criteria will be assessed. Participants must be between 18 and 65 years of age, have a primary diagnosis of MDD, and have experienced a current depressive episode lasting between four weeks and 18 months prior to screening. The primary endpoint of the study is the change in the Hamilton Depression Rating Scale-17 (HAM-D-17) total score from baseline to Visit 6, which occurs on Study Day 42. Secondary endpoints include changes in the Clinician Global Impression-Severity (CGI-S) score over the same period.

Following the screening visit, participants will attend regular follow-up visits to monitor their response to the treatment and any potential side effects. The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments will be conducted. Conditions that may lead to early termination from the study include the development of significant adverse effects, withdrawal of consent, or any other medical reasons deemed necessary by the investigator. The trial is categorized as a Phase 4 study, focusing on the characterization of SPT-300's effects as a monotherapy on depressive symptoms in the specified patient population.

The clinical trial involves the administration of **SPT-300**, an investigational medication, to evaluate its efficacy, safety, and tolerability in adults diagnosed with Major Depressive Disorder (MDD), with or without anxious distress. **SPT-300** is formulated as a **capsule** and contains the active substance **brexanolone caprilcerbate**. The medication is administered **orally** with a maximum daily dose of **375 mg**. The treatment period extends up to **6 weeks**. The pharmaceutical form of the capsule is designed for adult use, and the active substance is of chemical origin. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

The study also includes a **placebo** group to serve as a comparator for the experimental treatment. The placebo is designed to match the **SPT-300** capsule in appearance but does not contain the active substance. The placebo is administered **orally** with the same frequency and duration as the experimental medication, ensuring blinding of the study participants and investigators. The use of a placebo control allows for the assessment of the true therapeutic effects of **SPT-300** by comparing outcomes between the treatment and placebo groups.

The efficacy of SPT-300 in the treatment of adults with Major Depressive Disorder (MDD), with or without anxious distress, will be assessed through a randomized, parallel-group, double-blind, placebo-controlled monotherapy study. The primary endpoint for evaluating efficacy is the change from baseline to Visit 6 (Study Day 42) in the Hamilton Depression Rating Scale-17 (HAM-D-17) total score. This scale is a widely used and validated tool for measuring the severity of depressive symptoms.

Secondary efficacy will be assessed by the change from baseline to Visit 6 (Study Day 42) in the Clinician Global Impression-Severity (CGI-S) score. The CGI-S is a standardized assessment tool used to evaluate the severity of a patient's mental illness. These assessments will be conducted at specified timepoints to ensure consistent and reliable data collection. The trial is designed to provide a comprehensive evaluation of the effects of SPT-300 on depressive symptoms in the target population.