Recruiting
Phase 3

Azetukalner

Sponsor:

Xenon Pharmaceuticals Inc.

Code:

NCT07076407

Conditions

Major Depressive Disorder

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Azetukalner

Placebo

Study Details

Brief summary:

X-NOVA3 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety, and tolerability of azetukalner as a monotherapy in adult participants diagnosed with Major Depressive Disorder (MDD)

Conditions

Major Depressive Disorder

Study ID

NCT07076407

Start date

Jul 8, 2025

Status verified date

Jul, 2025

Completion date

Jul, 2027

Anticipated

Primary completion date

May, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

450 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Azetukalner

Azetukalner 20 mg

placebo comparator: Placebo

Placebo

Interventions

Azetukalner

Azetukalner 20 mg taken orally once a day with food (with the evening meal when possible) for 6 weeks

Placebo

Placebo taken orally once a day with food (with the evening meal when possible) for 6 weeks

Primary outcome measure

  • Change from baseline in the Hamilton Depression Rating Scale, 17-item (HAMD-17) score at Week 6 [ Time Frame: Baseline to Week 6 ]

Central Contacts and Locations

Central contacts

Xenon Medical Affairs

1-604-484-3300XenonCares@xenon-pharma.com

Locations

University of Alabama at Birmingham, Huntsville Regional Medical Campus

Recruiting

Huntsville, Alabama, United States, 35801

Pillar Clinical Research

Recruiting

Bentonville, Arkansas, United States, 72712

SanRo Clinical Research Group

Recruiting

Bryant, Arkansas, United States, 72022

Clinical Innovations Inc

Recruiting

Bellflower, California, United States, 90706

Center for Neurohealth

Recruiting

La Jolla, California, United States, 93037

Artemis Institute for Clinical Research

Recruiting

San Diego, California, United States, 92103

California Neuroscience Research

Recruiting

Sherman Oaks, California, United States, 91403

Institute of Living

Recruiting

Hartford, Connecticut, United States, 06106

Gulfcoast Clinical Research Center

Recruiting

Fort Myers, Florida, United States, 33912

Sarkis Clinical Trials

Recruiting

Gainesville, Florida, United States, 32607

Equipath Health and Research Tampa Bay, Llc

Recruiting

Riverview, Florida, United States, 33578

Delricht Research

Recruiting

Atlanta, Georgia, United States, 30329

Emory University Brain Health Center

Recruiting

Atlanta, Georgia, United States, 30329

Advanced Quality Medical Research

Recruiting

Orland Park, Illinois, United States, 60462

Smart Trials, LLC

Recruiting

Jefferson, Louisiana, United States, 70121

Pharmasite Research Inc.

Recruiting

Baltimore, Maryland, United States, 21208-6605

Adams Clinical Boston

Recruiting

Boston, Massachusetts, United States, 02116

Activmed Practices & Research, Llc - Methuen

Recruiting

Methuen, Massachusetts, United States, 01844

Adams Clinical Watertown

Recruiting

Watertown, Massachusetts, United States, 02472

Vitalix Clinical, Inc

Recruiting

Worcester, Massachusetts, United States, 01608

Psychiatric Care and Research Center

Recruiting

O'Fallon, Missouri, United States, 63368

St. Charles Psychiatric Associates - Midwest Research Group

Recruiting

Saint Charles, Missouri, United States, 63304

Lumina Clinical Research Center

Recruiting

Cherry Hill, New Jersey, United States, 08002

Princeton Medical Institute

Recruiting

Princeton, New Jersey, United States, 08540

Bio Behavioral Health

Recruiting

Toms River, New Jersey, United States, 08755

Bioscience Research, LLC

Recruiting

Mount Kisco, New York, United States, 10549

Fieve Clinical Research, Inc.

Recruiting

New York, New York, United States, 10017

IMA Clinical Research

Recruiting

New York, New York, United States, 10128

Magnolia Clinical Research, Llc

Recruiting

Cary, North Carolina, United States, 27511

Insight Clinical Trials

Recruiting

Independence, Ohio, United States, 44195

Sooner Clinical Research

Recruiting

Oklahoma City, Oklahoma, United States, 73116

Austin Clinical Trial Partners

Recruiting

Austin, Texas, United States, 78737

Boeson Research

Recruiting

Provo, Utah, United States, 84604

More Information

Sponsor

Xenon Pharmaceuticals Inc.

Last update posted

Aug 3, 2026

Last verified

Jul, 2025

Keywords

  • Depression
  • Antidepressant
  • XEN1101
  • Azetukalner

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Xenon Pharmaceuticals Inc. on 2026-08-03.