Azetukalner versus placebo for major depressive disorder (X‑NOVA3)

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

X‑NOVA3 is a Phase 3, multicenter, randomized, double‑blind, placebo‑controlled trial testing azetukalner as a monotherapy in adults with current major depressive disorder. Eligible participants are aged 18–74, had their first depressive episode before age 50, and have a current episode lasting 6 weeks to 24 months, with diagnosis confirmed by the MINI per DSM‑5‑TR criteria. Participants will be randomized to receive azetukalner or matched placebo and will be monitored for changes in depressive symptoms, safety, and tolerability using standardized outcome measures and adverse event reporting. The study is conducted at several U.S. clinical centers including University of Alabama at Birmingham and regional research clinics in Alabama and Arkansas.

Why it matters

Who can join: the full rules

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 or perimenopausal onset; Post traumatic 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 \>1 suicide attempt \> 24 years of age.
* 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.

Where it's running

• Harmonex Neuroscience Research
  Dothan, Alabama, United States Recruiting
• University of Alabama at Birmingham, Huntsville Regional Medical Campus
  Huntsville, Alabama, United States Recruiting
• Pillar Clinical Research
  Bentonville, Arkansas, United States Recruiting
• SanRo Clinical Research Group
  Bryant, Arkansas, United States Recruiting
• Clinical Innovations Inc
  Bellflower, California, United States Recruiting
• Center for Neurohealth
  La Jolla, California, United States Recruiting

Study contacts

• Study coordinator: Xenon Medical Affairs
• Email: XenonCares@xenon-pharma.com
• Phone: 1-604-484-3300

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.