Actively Recruiting

Phase 3
Age: 18Years - 74Years
All Genders
ID07076407

A Phase 3, Randomized, Double-blind, Placebo-Controlled Study to Evaluate Azetukalner in Moderate-to-Severe Major Depressive Disorder

Led by Xenon Pharmaceuticals Inc. · Updated on 2026-06-02

450

Participants Needed

44

Research Sites

8 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

Researchers are evaluating azetukalner as a treatment for adults diagnosed with Moderate-to-Severe Major Depressive Disorder (MDD). This Phase 3, randomized, double-blind, placebo-controlled study aims to assess the clinical effectiveness, safety, and tolerability of azetukalner when used alone in adults aged 18 to 74 years who are currently experiencing a major depressive episode. The study is sponsored by Xenon Pharmaceuticals Inc. and focuses on improving depressive symptoms over a six-week period. Participants will be randomly assigned to receive either azetukalner 20 mg or a placebo once daily, taken orally with food, preferably with the evening meal. Treatment lasts for six weeks, during which the effects of the medication will be closely monitored. The study uses a quadruple-blind design, meaning that participants, care providers, investigators, and outcome assessors will not know which treatment is given to ensure unbiased results. During the study, participants will undergo regular assessments including the Hamilton Depression Rating Scale (HAMD-17) to measure changes in depression severity from baseline to Week 6, along with other scales like the Snaith-Hamilton Pleasure Scale (SHAPS) and Clinical Global Impression of Severity (CGI-S). Safety and tolerability will be monitored from about four weeks before treatment through eight weeks after the final dose. The total participation duration covers treatment and follow-up to evaluate both short-term effects and safety outcomes.

CONDITIONS

Brief Title

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

Who Can Participate

Age: 18Years - 74Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Adults aged 18 to 74 years
  • Experienced first major depressive episode before age 50
  • Body Mass Index (BMI) 40 kg/m2 or less
  • Meets DSM-5-TR criteria for current major depressive disorder confirmed by MINI
  • Current major depressive episode lasting between 6 weeks and 24 months
Not Eligible

You will not qualify if you...

  • Primary diagnosis of mood disorder other than Major Depressive Disorder
  • History of psychotic or catatonic features, mixed features, Bipolar I or II, OCD, schizophrenia, or other psychotic disorders
  • Current diagnosis of seasonal pattern MDD, peripartum or perimenopausal depression, PTSD, antisocial or borderline personality disorder, panic disorder or agoraphobia, unstable ADHD
  • Substance or alcohol use disorder within 12 months prior to screening (excluding tobacco)
  • Active suicidal plan or intent within 6 months prior to screening, suicidal behavior within 2 years, or more than one suicide attempt after age 24
  • History of non-suicidal self-harm within 12 months prior to screening
  • Use of antidepressants or prohibited medications within 2 weeks (4 weeks for fluoxetine) or less than 5 times drug half-life before randomization
  • History of non-response to two or more antidepressants in current episode
  • Medical conditions interfering with study conduct or purpose
  • Pregnant, breastfeeding, or planning pregnancy

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Treatment

Duration - 6 weeks

Participants take Azetukalner 20 mg or placebo orally once a day with food for 6 weeks.

Weekly visits for up to 6 weeks

Follow-up

Duration - 8 weeks post-final dose

Participants are monitored for safety and tolerability of the study medication after treatment ends.

Visits as needed during 8 weeks post-treatment

Trial Site Locations

Total: 44 locations

1

Harmonex Neuroscience Research

Dothan, Alabama, United States, 36303

Terminated

2

University of Alabama at Birmingham, Huntsville Regional Medical Campus

Huntsville, Alabama, United States, 35801

Actively Recruiting

3

Pillar Clinical Research

Bentonville, Arkansas, United States, 72712

Actively Recruiting

4

SanRo Clinical Research Group

Bryant, Arkansas, United States, 72022

Actively Recruiting

5

Clinical Innovations Inc

Bellflower, California, United States, 90706

Actively Recruiting

6

Center for Neurohealth

La Jolla, California, United States, 93037

Actively Recruiting

7

Artemis Institute for Clinical Research

San Diego, California, United States, 92103

Actively Recruiting

8

California Neuroscience Research

Sherman Oaks, California, United States, 91403

Actively Recruiting

9

Pacific Clinical Research Management Group

Upland, California, United States, 91786

Terminated

10

Institute of Living

Hartford, Connecticut, United States, 06106

Actively Recruiting

11

Gulfcoast Clinical Research Center

Fort Myers, Florida, United States, 33912

Actively Recruiting

12

Sarkis Clinical Trials

Gainesville, Florida, United States, 32607

Actively Recruiting

13

Equipath Health and Research Tampa Bay, Llc

Riverview, Florida, United States, 33578

Actively Recruiting

14

Delricht Research

Atlanta, Georgia, United States, 30329

Actively Recruiting

15

Emory University Brain Health Center

Atlanta, Georgia, United States, 30329

Actively Recruiting

16

Advanced Quality Medical Research

Orland Park, Illinois, United States, 60462

Actively Recruiting

17

Smart Trials, LLC

Jefferson, Louisiana, United States, 70121

Actively Recruiting

18

Pharmasite Research Inc.

Baltimore, Maryland, United States, 21208-6605

Actively Recruiting

19

Adams Clinical Boston

Boston, Massachusetts, United States, 02116

Actively Recruiting

20

Activmed Practices & Research, Llc - Methuen

Methuen, Massachusetts, United States, 01844

Actively Recruiting

21

Adams Clinical Watertown

Watertown, Massachusetts, United States, 02472

Actively Recruiting

22

Vitalix Clinical, Inc

Worcester, Massachusetts, United States, 01608

Actively Recruiting

23

Psychiatric Care and Research Center

O'Fallon, Missouri, United States, 63368

Actively Recruiting

24

St. Charles Psychiatric Associates - Midwest Research Group

Saint Charles, Missouri, United States, 63304

Actively Recruiting

25

Lumina Clinical Research Center

Cherry Hill, New Jersey, United States, 08002

Actively Recruiting

26

Princeton Medical Institute

Princeton, New Jersey, United States, 08540

Actively Recruiting

27

Bio Behavioral Health

Toms River, New Jersey, United States, 08755

Actively Recruiting

28

Bioscience Research, LLC

Mount Kisco, New York, United States, 10549

Actively Recruiting

29

Fieve Clinical Research, Inc.

New York, New York, United States, 10017

Actively Recruiting

30

IMA Clinical Research

New York, New York, United States, 10128

Actively Recruiting

31

Magnolia Clinical Research, Llc

Cary, North Carolina, United States, 27511

Actively Recruiting

32

Insight Clinical Trials

Independence, Ohio, United States, 44195

Actively Recruiting

33

Sooner Clinical Research

Oklahoma City, Oklahoma, United States, 73116

Actively Recruiting

34

Austin Clinical Trial Partners

Austin, Texas, United States, 78737

Actively Recruiting

35

Boeson Research

Provo, Utah, United States, 84604

Actively Recruiting

36

Suomen Terveystalo Oy

Helsinki, Finland, 00180

Actively Recruiting

37

Oulu Mentalcare Oy

Oulu, Finland, 90100

Actively Recruiting

38

In Vivo Sp. z.o.o.

Bydgoszcz, Poland, 85-048

Actively Recruiting

39

Clinical Medical Research Sp. z o.o.

Katowice, Poland, 40156

Actively Recruiting

40

Praktyka Lekarska Malgorzata Wojtanowska-Bogacka

Poznan, Poland, 60192

Actively Recruiting

41

Specjalistyczna Praktyka Lekarska, Filip Rybakowski

Poznan, Poland, 60744

Actively Recruiting

42

Clinica Nutrimed Cercetare Sr

Bucharest, Romania, 020744

Actively Recruiting

43

Liptovska Nemocnica S Poliklinikou Mudr. Ivana Stodolu Liptovsky Mikulas

Liptovský Mikuláš, Slovakia, 03123

Actively Recruiting

44

Hospital Universitari Vall D'Hebron

Barcelona, Spain, 8035

Actively Recruiting

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Research Team

X

Xenon Medical Affairs

How is the study designed?

Study Type

INTERVENTIONAL

Masking

QUADRUPLE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

2

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