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

Launched by XENON PHARMACEUTICALS INC. · Jul 14, 2025

Keywords

ClinConnect Summary

This clinical trial is testing a new medicine called azetukalner to see if it helps adults with Major Depressive Disorder (MDD), a condition that causes ongoing feelings of sadness and loss of interest. The study is a Phase 3 trial, which means it is one of the final steps before the medicine might become widely available. Participants will be randomly assigned to receive either azetukalner or a placebo (a pill with no active medicine) without knowing which one they get, allowing researchers to fairly compare the effects. The study will look at how well the medicine works, how safe it is, and how well participants tolerate it.

To join the study, adults between 18 and 74 years old who have been diagnosed with MDD and are currently experiencing a depressive episode lasting between 6 weeks and 24 months may be eligible. Participants must have had their first major depressive episode before age 50 and meet specific health criteria, such as having a body weight within a certain range. People with other mental health disorders, recent substance use problems, recent suicidal behavior, or who are pregnant or breastfeeding are not eligible. If you take part, you can expect regular visits to the study center where your health and mood will be carefully monitored. This trial aims to find out if azetukalner could be a new treatment option for people struggling with depression.

Gender

ALL

Eligibility criteria

• 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 Text Revised (DSM-5-TR) criteria for current major depressive disorder and is currently in 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 catatonic features; MDD with mixed features; Bipolar I or II disorder; Obsessive-compulsive disorder; Schizophrenia, primary thought disorder, or other psychotic disorder.
• • Participant has a current diagnosis of any of the following: MDD with seasonal pattern; Depression with peripartum onset; Posttraumatic stress disorder; Antisocial or borderline personality disorder (or presence of clinically significant borderline personality traits); Panic disorder and/or agoraphobia; ADHD treated with a psychostimulant, diagnosed during the current MDE, or with unstable symptoms, 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 to screening, presence of suicidal behavior in the last 2 years, or ≥2 lifetime suicide attempts.
• • Participant has a history of non-suicidal self-harm behavior in the 12 months prior to screening.
• • Participant has used antidepressants or other prohibited medications (including benzodiazepines), within the 2 weeks (4 weeks for fluoxetine) or within a period less 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 adequate dose and duration in the current MDE as determined by the Antidepressant Treatment Response Questionnaire (ATRQ).
• • Participants with medical conditions that may interfere with the purpose or conduct of the study
• • Participant is pregnant, breastfeeding, or planning to become pregnant.