Recruiting
Phase 3

Azetukalner

Sponsor:

Xenon Pharmaceuticals Inc.

Code:

NCT06775379

Conditions

Major Depressive Disorder

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Azetukalner

Placebo

Study Details

Brief summary:

X-NOVA2 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

NCT06775379

Start date

Dec 20, 2024

Status verified date

Mar, 2026

Completion date

Oct, 2026

Anticipated

Primary completion date

Aug, 2026

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

IMA Clinical Research Phoenix

Recruiting

Phoenix, Arizona, United States, 85012

Woodland International Research Group

Recruiting

Little Rock, Arkansas, United States, 72211

Woodland Research Northwest

Recruiting

Rogers, Arkansas, United States, 72758

Behavioral Research Specialists, Llc

Recruiting

Glendale, California, United States, 91206

Irvine Clinical Research

Recruiting

Irvine, California, United States, 92614

CalNeuro Research Group, Inc.

Recruiting

Los Angeles, California, United States, 90025

Excell Research Inc.

Recruiting

Oceanside, California, United States, 92056

Atp Clinical Research

Recruiting

Orange, California, United States, 92866

Nrc Research Institute

Recruiting

Orange, California, United States, 92868

CenExel CNS-TO (Collaborative Neuroscience Research)

Recruiting

Torrance, California, United States, 90504

Sunwise Clinical Research

Recruiting

Walnut Creek, California, United States, 94596

Kinetic Clinical Research, LLC

Recruiting

West Covina, California, United States, 91790

Mountain View Clinical Research

Recruiting

Denver, Colorado, United States, 80209

Ct Clinical Research Associates

Recruiting

Cromwell, Connecticut, United States, 06416

CNS Clinical Research Group

Recruiting

Coral Springs, Florida, United States, 33067

Clinical Neuroscience Solutions, Inc.

Recruiting

Jacksonville, Florida, United States, 32256

Accel Research Sites Lakeland

Recruiting

Lakeland, Florida, United States, 33803

Accel Research Sites - St. Petersburg-Largo

Recruiting

Largo, Florida, United States, 33777

PharmaSouth Research

Recruiting

Miami, Florida, United States, 33165

Clinical Neuroscience Solutions, Inc.

Recruiting

Orlando, Florida, United States, 32801

Panhandle Research and Medical Clinic

Recruiting

Pensacola, Florida, United States, 32503

Advanced Discovery Research

Recruiting

Atlanta, Georgia, United States, 30318

Synexus - Atlanta

Recruiting

Atlanta, Georgia, United States, 30328

Psych Atlanta, Pc

Recruiting

Marietta, Georgia, United States, 30060

Cenexel Iresearch - Savannah

Recruiting

Savannah, Georgia, United States, 31405

Northwest Clinical Trials Inc

Recruiting

Boise, Idaho, United States, 83704

Boston Clinical Trials Llc

Recruiting

Boston, Massachusetts, United States, 02131

ELIXIA

Recruiting

Springfield, Massachusetts, United States, 01103

Tekton Research

Recruiting

St Louis, Missouri, United States, 63128

IMA Clinical Research Las Vegas

Recruiting

Las Vegas, Nevada, United States, 89102

IMA Clinical Research

Recruiting

Albuquerque, New Mexico, United States, 87109

Integrative Clinical Trials

Recruiting

Brooklyn, New York, United States, 11229

Richmond Behavioral Associates

Recruiting

Staten Island, New York, United States, 10314

New Hope Clinical Research

Recruiting

Charlotte, North Carolina, United States, 28211

Neuro-Behavioral Clinical Research

Recruiting

North Canton, Ohio, United States, 44720

Pahl Pharmaceutical Professionals Llc

Recruiting

Oklahoma City, Oklahoma, United States, 73112

Lehigh Center For Clinical Research

Recruiting

Allentown, Pennsylvania, United States, 18103

Adams Clinical - Philadelphia

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Clinical Neuroscience Solutions, Inc.

Recruiting

Memphis, Tennessee, United States, 38119

Delricht Research - Plano

Recruiting

Plano, Texas, United States, 75024

Aim Trials, Llc

Recruiting

Plano, Texas, United States, 75093

Grayline Research Center

Recruiting

Wichita Falls, Texas, United States, 76309

Core Clinical Research

Recruiting

Everett, Washington, United States, 98201

More Information

Sponsor

Xenon Pharmaceuticals Inc.

Last update posted

Aug 3, 2026

Last verified

Mar, 2026

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.