A Phase 3 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Azetukalner in Patients with Bipolar Depression

The primary objective is to evaluate the efficacy and safety of 20 mg azetukalner once daily compared to placebo in the treatment of bipolar depression. Secondary objectives include:

• Assessment of clinician-perceived efficacy.
• Evaluation of the rapidity of onset of action.
• Assessment of efficacy in treating anhedonia.

The study includes a total of 256 patients experiencing bipolar depression. The population consists of both male and female adults aged 18 to 74 years. Participants must have experienced their first major depressive episode before the age of 50. Selection is based on a diagnosis of bipolar I disorder or bipolar II disorder according to the DSM-5-TR criteria, as confirmed by the Mini International Neuropsychiatric Interview. Eligible individuals must present with a current depressive episode lasting between 4 weeks and 12 months. Additionally, a body mass index between 18 kg/m2 and 40 kg/m2 is required.

This Phase 3, randomized, double-blind, placebo-controlled, multicenter study is designed to evaluate the efficacy and safety of azetukalner compared to a placebo in patients experiencing bipolar depression. Participants are assigned to receive either a 20 mg oral capsule of azetukalner once daily or a placebo. The primary objective is to assess the change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6. Secondary endpoints include changes in the Clinical Global Impression-Severity (CGI-S) score, the SHAPS total score, and the MADRS total score at Week 1. The study methodology involves an initial screening period to confirm diagnosis via the Mini International Neuropsychiatric Interview (MINI) and adherence to DSM-5-TR criteria. The clinical trial is estimated to conclude by June 2028.

The experimental medication azetukalner is administered as a 20 mg capsule. This substance is provided via the oral route once daily for the treatment of bipolar depression.

The comparator is a placebo administered in a double-blind manner to evaluate efficacy and safety during depressive episodes associated with bipolar I or II disorder.

The efficacy of azetukalner in the treatment of bipolar depression is evaluated using specific clinical endpoints. The primary endpoint is the change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 6.

Secondary efficacy assessments include the following:

• Change from baseline in the Clinical Global Impressions-Severity (CGI-S) score at Week 6.
• Change from baseline in the MADRS total score at Week 1.
• Change from baseline in the Snaith-Hamilton Pleasure Scale (SHAPS) total score at Week 6.