A Long-term, Open-Label Study to Evaluate the Safety, Tolerability, and Efficacy of Azetukalner in Patients with Bipolar I or II Depression

The primary objective is to evaluate the safety and tolerability of long-term administration of 20 mg azetukalner once daily in individuals diagnosed with bipolar depression. The secondary objectives involve the assessment of efficacy through several parameters:

• Clinician-perceived and participant-perceived efficacy of long-term treatment.
• The impact of long-term treatment on anhedonia.

This study involves 320 participants diagnosed with bipolar depression. The study population includes both male and female individuals belonging to the age groups designated by codes 3 and 4. The subjects are patients who have successfully completed a prior Phase 3 antecedent study evaluating the study medication. Key requirements for participation include the ability to provide informed consent and a willingness to adhere to established contraception protocols.

This multicenter, long-term, open-label study is designed to evaluate the safety, tolerability, and efficacy of azetukalner in individuals diagnosed with bipolar depression. Participants will receive an oral dose of 20 mg of azetukalner once daily in a capsule form. The primary objectives involve assessing the severity and frequency of treatment-emergent adverse events, serious adverse events, adverse events of special interest, and exposure to concomitant medications. Secondary endpoints include monitoring changes from baseline in the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impressions-Severity scale, and the Snaith-Hamilton Pleasure Scale. The study involves participants who have successfully completed a prior Phase 3 antecedent study. The estimated period for study activities spans from June 2026 to July 2029.

The experimental medication, azetukalner (XPF-010), is administered in a capsule pharmaceutical form. The prescribed dosage is 20 mg, which is provided via the oral route of administration. This medication is intended for once daily frequency to manage bipolar depression.

The efficacy of azetukalner in the treatment of bipolar depression is evaluated through several secondary endpoints. The assessment includes the measurement of the change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score over time. Additionally, changes in the Clinical Global Impressions-Severity (CGI-S) score are monitored throughout the study period. The Snaith-Hamilton Pleasure Scale (SHAPS) total score is also utilized to track changes from baseline over time.