A Phase 3 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy of Azetukalner in Patients with Moderate-to-Severe Major Depressive Disorder

The primary objective of this study is to evaluate the efficacy of 20 mg azetukalner administered once daily for the treatment of major depressive disorder. The secondary objectives include the assessment of:

• Efficacy in the treatment of anhedonia;
• Rapidity of onset of therapeutic effect;
• Clinician-perceived efficacy.

This clinical trial involves a total of 310 patients. The study population includes both male and female adults ranging from 18 to 74 years of age. Participants must have experienced their first major depressive disorder episode prior to the age of 50. Eligible individuals are required to meet the DSM-5-TR criteria for a current major depressive episode, which must be confirmed via the Mini International Neuropsychiatric Interview. The current episode must have a duration of at least 6 weeks and no more than 24 months. Additionally, a Body Mass Index of 40 kg/m² or less is required for inclusion.

This Phase 3, randomized, double-blind, placebo-controlled, multicenter study is designed to evaluate the efficacy of azetukalner in patients diagnosed with major depressive disorder. Participants are assigned to receive either a 20 mg oral capsule of azetukalner once daily or a matching placebo. The research methodology includes a screening period to confirm eligibility based on DSM-5-TR criteria, a body mass index of ≤40 kg/m2, and a major depressive episode duration of ≥6 weeks to ≤24 months. The primary endpoint is the change from baseline in the HAMD-17 score at Week 6. Secondary endpoints include assessments of the SHAPS score, CGI-S score, and HAMD-17 score at Week 1. The study involves scheduled clinical visits to monitor efficacy and safety throughout the treatment period.

The investigational medicinal product is azetukalner, administered as a 20 mg capsule. This substance is intended for oral use and is to be taken once daily to treat major depressive disorder.

The control group receives a placebo designed to match the appearance of XPF-010.

The efficacy of 20 mg azetukalner in the treatment of major depressive disorder will be evaluated through several predefined endpoints. The primary endpoint is the change from baseline in the Hamilton Depression Rating Scale-17 (HAMD-17) score at Week 6.

Secondary efficacy assessments include the following:

• Change from baseline in the SHAPS score at Week 6.
• Change from baseline in the HAMD-17 score at Week 1.
• Change from baseline in the Clinical Global Impression-Severity (CGI-S) score at Week 6.