Long‑Term Open‑Label Safety, Tolerability, and Efficacy of Azetukalner (XPF‑010) in Adults with Major Depressive Disorder

The primary objective is to evaluate the safety and tolerability of long‑term oral administration of azetukalner (20 mg capsule) in adults diagnosed with Major Depressive Disorder, thereby defining the risk‑benefit profile for chronic therapy.

Secondary objectives include:

• assessment of the efficacy of long‑term azetukalner treatment for Major Depressive Disorder;
• evaluation of efficacy for the symptom of anhedonia;
• determination of clinician‑perceived efficacy of the regimen;
• measurement of the impact on patients' quality of life.

The trial enrolled 320 individuals diagnosed with Major Depressive Disorder, comprising both male and female patients. Participants were adults falling within the age categories identified by codes 3 and 4, representing a broad adult age spectrum. All subjects had successfully completed the treatment phase of a preceding Phase 3 study of azetukalner for this condition, thereby forming the selected population. Key inclusion elements required written informed consent, the ability to understand study procedures, adherence to study requirements, and compliance with contraception mandates; male participants agreed not to donate sperm and female participants not to donate ova for three months after the final dose. No additional lifestyle restrictions were specified beyond the contraception criteria.

The study is an open-label, multicenter, long‑term safety, tolerability, and efficacy investigation of azetukalner in adults with Major Depressive Disorder. Participants who have completed a preceding Phase 3 trial undergo a screening visit to confirm eligibility, obtain written informed consent, and record baseline assessments. Eligible subjects begin daily oral dosing of XPF‑010 (20 mg) and attend follow‑up visits at weeks 4, 12, 24, and thereafter every 12 weeks for clinical evaluation, adverse‑event monitoring, and efficacy measurements (HAMD‑17, SHAPS, CGI‑S, Q‑LES‑Q‑SF, SDS). Treatment continues for up to 12 months, after which an end‑of‑study visit captures final outcomes; total participant involvement is approximately 13 months including screening. Early termination may occur for serious adverse events, predefined safety concerns, or non‑adherence to study procedures or contraception requirements. Primary endpoints assess the incidence and severity of treatment‑emergent adverse events, while secondary endpoints evaluate changes from baseline in depressive symptom scales and quality‑of‑life measures.

The investigational product, identified as XPF-010, consists of the active substance azetukalner formulated as a 20 mg oral capsule. The medication is administered by oral ingestion, typically once daily, throughout the long‑term treatment period.

Adherence to the dosing regimen is evaluated by pill count at each scheduled visit and by review of a patient‑maintained dosing diary. Study personnel verify compliance during regular clinic assessments and reinforce proper administration procedures.

Efficacy will be evaluated using several secondary endpoints, including change from baseline in the HAMD-17 total score, change from baseline in the SHAPS total score, change in the CGI‑S score, and change from baseline in the Q‑LES‑Q‑SF total score, its medication and life satisfaction and contentment item scores, as well as the SDS total score and subscale scores over time.

These parameters will be measured with validated clinical rating scales (HAMD‑17, SHAPS, CGI‑S, Q‑LES‑Q‑SF, SDS) at baseline and at subsequent study visits throughout the trial. Collected data will be analyzed to determine the magnitude of change from baseline for each endpoint, allowing assessment of treatment effect over the study period.