A Randomized Study of Azetukalner Versus Placebo in Major Depressive Disorder (X-NOVA3)

Key Inclusion Criteria:

• Adults ≥18 and ≤74 years of age and experienced their first major depressive episode (MDE) prior to 50 years of age

• Body Mass Index (BMI) ≤40 kg/m2

• Meets the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition TextRevised (DSM-5-TR) criteria for current major depressive disorder and is currentlyin an MDE, confirmed using the Mini International Neuropsychiatric Interview (MINI)

• Participant's current MDE has a duration of ≥6 weeks and ≤24 months.

Key Exclusion Criteria:

• Participant has a primary diagnosis of a mood disorder other than MDD.

• Participant has a history of any of the following: MDD with psychotic or catatonicfeatures; MDD with mixed features; Bipolar I or II disorder; Obsessive-compulsivedisorder; Schizophrenia, primary thought disorder, or other psychotic disorder.

• Participant has a current diagnosis of any of the following: MDD with seasonalpattern; Depression with peripartum or perimenopausal onset; Post traumatic stressdisorder; Antisocial or borderline personality disorder (or presence of clinicallysignificant borderline personality traits); Panic disorder and/or agoraphobia; ADHDtreated with a psychostimulant, diagnosed during the current MDE, or with unstablesymptoms, as judged by the investigator.

• Participant has a substance (excluding tobacco) or alcohol use disorder within the 12 months prior to screening.

• Participant has had an active suicidal plan/intent within the 6 months prior toscreening, presence of suicidal behavior in the last 2 years, or >1 suicide attempt > 24 years of age.

• Participant has a history of non-suicidal self-harm behavior in the 12 months priorto screening.

• Participant has used antidepressants or other prohibited medications (includingbenzodiazepines), within the 2 weeks (4 weeks for fluoxetine) or within a periodless than 5 times the drug's half-life, whichever is longer, prior to randomization.

• Participant has a history of non-response to ≥2 antidepressant drugs of adequatedose and duration in the current MDE as determined by the Antidepressant TreatmentResponse Questionnaire (ATRQ).

• Participants with medical conditions that may interfere with the purpose or conductof the study

• Participant is pregnant, breastfeeding, or planning to become pregnant.