A Randomized Study of Azetukalner Versus Placebo in Major Depressive Disorder

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Xenon Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

26 Feb 2026 → ongoing

Decision date (initial)

2026-02-02

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Xenon Pharmaceuticals Inc.

External identifiers

EU CT number

2025-523202-32-00

ClinicalTrials.gov

NCT07076407

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Others, Therapy, Efficacy

To assess the efficacy of 20 mg azetukalner once daily for the treatment of Major Depressive Disorder.

Secondary objectives 3

1. To assess the efficacy of 20 mg azetukalner QD for the treatment of anhedonia.
2. To assess rapidity of efficacy onset of 20 mg azetukalner QD for the treatment of MDD.
3. To assess clinician-perceived efficacy of 20 mg azetukalner QD for the treatment of MDD.

Conditions and MedDRA coding

Major Depressive Disorder

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Adults ≥18 and ≤74 years of age and experienced their first major depressive episode (MDE) prior to 50 years of age
2. Body Mass Index (BMI) ≤40 kg/m2
3. 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)
4. Participant's current MDE has a duration of ≥6 weeks and ≤24 months.

Exclusion criteria 10

1. Participant has a primary diagnosis of a mood disorder other than MDD.
2. 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.
3. Participant has a current diagnosis of any of the following: MDD with seasonal pattern; Depression with peripartum onset; Posttraumatic 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.
4. Participant has a substance (excluding tobacco) or alcohol use disorder within the 12 months prior to screening.
5. 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.
6. Participant has a history of non-suicidal self-harm behavior in the 12 months prior to screening.
7. 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.
8. 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).
9. Participants with medical conditions that may interfere with the purpose or conduct of the study.
10. Participant is pregnant, breastfeeding, or planning to become pregnant

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in the HAMD-17 score at Week 6.

Secondary endpoints 3

1. Change from baseline in the SHAPS score at Week 6
2. Change from baseline in the HAMD-17 score at Week 1
3. Change from baseline in the CGI-S score at Week 6

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Xenon Pharmaceuticals Inc.

Sponsor organisation

Xenon Pharmaceuticals Inc.

Address

3650 Gilmore Way

City

Burnaby

Postcode

V5G 4W8

Country

Canada

Scientific contact point

Organisation

Xenon Pharmaceuticals Inc.

Contact name

Medical Affairs

Public contact point

Organisation

Xenon Pharmaceuticals Inc.

Contact name

Medical Affairs

Third parties 17

Locations

7 EU/EEA countries · 21 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 95 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications