An Open-Label Study of Azetukalner in Major Depressive Disorder (X-NOVA-OLE)

A Multicenter, Open-label, Long-term, Safety, Tolerability, and Efficacy Study of Azetukalner in Major Depressive Disorder

X-NOVA-OLE is a multicenter, open-label study to evaluate the long-term safety, tolerability, and efficacy of azetukalner as a monotherapy in adult participants who successfully completed an antecedent Phase 3 study of azetukalner in Major Depressive Disorder (MDD).

Study Overview

• Status: Enrolling by invitation
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Azetukalner

• Study Type: Interventional
• Enrollment (Estimated): 460
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Ima Clinical Research - Phoenix
  • Arkansas
    • Bryant, Arkansas, United States, 72022
      • Sanro Clinical Research Group, Llc
    • Little Rock, Arkansas, United States, 72211
      • Woodland International Research Group
    • Rogers, Arkansas, United States, 72758
      • Woodland Research Northwest
  • California
    • Bellflower, California, United States, 90706
      • Cenexel Cit - Bellflower
    • Los Angeles, California, United States, 90025
      • Calneuro Research Group, Inc.
    • Oceanside, California, United States, 92056
      • Excell Research Inc.
    • Orange, California, United States, 92868
      • Nrc Research Institute
    • Orange, California, United States, 92866
      • ATP Clinical Research
    • San Diego, California, United States, 92123
      • Artemis Institute For Clinical Research - San Diego
    • Sherman Oaks, California, United States, 91403-2131
      • Cenexel Cnr - Sherman Oaks
    • Torrance, California, United States, 90501
      • Cenexel Cns - Torrance
    • Upland, California, United States, 91786
      • Pacific Clinical Research Management
    • Walnut Creek, California, United States, 94596
      • Sunwise Clinical Research
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Institute of Living - Clinical Trials Unit
  • Florida
    • Coral Gables, Florida, United States, 33146
      • Pharmasouth Research
    • Coral Springs, Florida, United States, 33067
      • Cns Clinical Research - Coral Springs
    • Fort Myers, Florida, United States, 33912
      • Gulfcoast Clinical Research Center
    • Gainesville, Florida, United States, 32607
      • Sarkis Clinical Trials
    • Hialeah, Florida, United States, 33016
      • Neoclinical Research
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions Inc. - Jacksonville
    • Lakeland, Florida, United States, 33803
      • Accel Research Sites - Lakeland
    • Largo, Florida, United States, 33777
      • Accel Research Sites - St. Petersburg-Largo
    • North Miami Beach, Florida, United States, 33162
      • Harmony Clinical Research Inc
    • Orlando, Florida, United States, 32807
      • Combined Research Orlando Phase I-Iv
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions Inc. - Orlando
    • Pensacola, Florida, United States, 32502
      • Panhandle Research and Medical Clinic
    • Riverview, Florida, United States, 33578
      • Equipath Health and Research Tampa Bay, Llc
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Advanced Discovery Research, Llc
    • Atlanta, Georgia, United States, 30329
      • DelRicht Research
    • Atlanta, Georgia, United States, 30328
      • Synexus - Atlanta
    • Decatur, Georgia, United States, 30030
      • Cenexel Iresearch - Atlanta
    • Marietta, Georgia, United States, 30060
      • Psych Atlanta, Pc
    • Savannah, Georgia, United States, 31405
      • Cenexel Iresearch - Savannah
  • Illinois
    • Chicago, Illinois, United States, 60634
      • IMA Clinical Research
    • Orland Park, Illinois, United States, 60462
      • Advanced Quality Medical Research, LLC
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials Llc
    • Boston, Massachusetts, United States, 02116
      • Adams Clinical - Boston
    • Springfield, Massachusetts, United States, 01103
      • Elixia MA, LLC
    • Watertown, Massachusetts, United States, 02472
      • Adams Clinical - Watertown
    • Worcester, Massachusetts, United States, 01608
      • Vitalix Clinical - Worcester
  • Missouri
    • O'Fallon, Missouri, United States, 63368
      • Psychiatric Care and Research Center
    • Saint Charles, Missouri, United States, 63304
      • St. Charles Psychiatric Associates - Midwest Research Group
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Redbird Research
    • Las Vegas, Nevada, United States, 89102
      • Ima Clinical Research - Las Vegas
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08002
      • Center For Emotional Fitness
    • Toms River, New Jersey, United States, 08755
      • Bio Behavioral Health
  • New York
    • Brooklyn, New York, United States, 11229
      • Integrative Clinical Trials, Llc
    • Mount Kisco, New York, United States, 10549
      • Bioscience Research Llc.
    • New York, New York, United States, 10128
      • Ima Clinical Research - Nyc Uptown
    • New York, New York, United States, 10017-1921
      • Fieve Clinical Research (Fcr), Inc.
    • Staten Island, New York, United States, 10314
      • Richmond Behavioral Associates
  • North Carolina
    • Charlotte, North Carolina, United States, 28211
      • New Hope Clinical Research
  • Ohio
    • Independence, Ohio, United States, 44131
      • Insight Clinical Trials Llc
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Pahl Pharmaceutical Professionals Llc
    • Oklahoma City, Oklahoma, United States, 73116
      • Sooner Clinical Research
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Center For Clinical Research
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions, Inc.
  • Texas
    • Austin, Texas, United States, 78737
      • Austin Clinical Trial Partners
    • Plano, Texas, United States, 75024
      • Delricht Research - Plano
    • Wichita Falls, Texas, United States, 76309
      • Grayline Research Center
  • Utah
    • Provo, Utah, United States, 84604
      • Boeson Research Pvu
  • Washington
    • Everett, Washington, United States, 98201
      • Core Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant successfully completed the treatment period of an antecedent azetukalner Phase 3 study in MDD.
• Participant provides written informed consent to participate in the study, is able to understand the procedures and study requirements, and agrees to abide by them.
• Participant is willing to comply with the contraception requirements.
• Male participants must agree not to donate sperm until 3 months after the last dose of study drug. Female participants must agree not to donate ova until 3 months after the last dose of study drug.

Exclusion Criteria:

• Participant met any of the withdrawal criteria, or discontinued study drug early, or was terminated early from an antecedent study.
• Participant had any protocol deviations in an antecedent azetukalner study that, in the opinion of the investigator, would preclude participation in this study.
• Participant is unable to comply with study procedures or is inappropriate for the study, as judged by the investigator.
• Participant has any medical condition, personal circumstance, or ongoing AE (from an antecedent study) that, in the opinion of the investigator, exposes the participant to unacceptable risk by participating in the study or prevents adherence to the protocol.
• Female participant who is pregnant, breastfeeding, or planning to become pregnant within 3 months after the last dose of study drug.
• Participant is planning to enter a clinical study with a different investigational drug or planning to use any experimental device for treatment of any medical condition during the study or within 28 days after completion of this study.
• Participant is judged to have a significant risk for self-harm or suicidal behavior or is considered to be an imminent danger to themself or others, as determined by the C-SSRS or in the opinion of the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Azetukalner 20 mg	Drug: Azetukalner; Azetukalner 20 mg taken orally once a day with food (with the evening meal when possible) for 52 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Severity and frequency of treatment-emergent adverse events, serious adverse events, adverse events of special interest, and events of clinical interest	From the start of treatment in the open-label extension study through 8 weeks after the last dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in the Hamilton Depression Rating Scale, 17-Item (HAMD-17) total score over time	From baseline through the active extension treatment (Week 52)
Change from baseline in the Snaith-Hamilton Pleasure Scale (SHAPS) total score over time	From baseline through the active extension treatment (Week 52)
Change in the Clinical Global Impression of Severity (CGI-S) score over time	From baseline through the active extension treatment (Week 52)
Change from baseline in Quality of Life Enjoyment and Satisfaction Questionnaire - Short Form (Q-LES-Q-SF) total score, Q-LES-Q-SF medication and life satisfaction and contentment in item scores over time	From baseline through the active extension treatment (Week 52)
Change from baseline in Sheehan Disability Scale (SDS) total score and subscale scores over time	From baseline through the active extension treatment (Week 52)

Collaborators and Investigators

• Sponsor: Xenon Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: March 20, 2025
• First Submitted That Met QC Criteria: April 8, 2025
• First Posted (Actual): April 10, 2025

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Depression; Antidepressant; XEN1101; Azetukalner
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Mood Disorders; Depressive Disorder; Behavior; Depression; Depressive Disorder, Major
• Other Study ID Numbers: XPF-010-D303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No