A Randomized Study of Azetukalner Versus Placebo in Depressive Episodes Associated With Bipolar I or II Disorder (Bipolar Depression) - X-CEED

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]

Decision date (initial)

2026-03-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Xenon Pharmaceuticals Inc.

External identifiers

EU CT number

2025-522775-29-00

ClinicalTrials.gov

NCT07172516

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To assess the efficacy and safety of 20 mg azetukalner QD versus placebo for the treatment of bipolar depression.

Secondary objectives 1

1. To assess clinician-perceived efficacy of 20 mg azetukalner once daily VS placebo for the treatment of bipolar depression; To assess the rapidity of efficacy onset of 20 mg azetukalner once daily VS placebo for the treatment of bipolar depression; and To assess the efficacy of 20 mg azetukalner once daily VS placebo for the treatment of anhedonia.

Conditions and MedDRA coding

Depressive episodes associated with Bipolar disorder I or II (Bipolar Depression)

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 3. Adults ≥18 and ≤74 years of age who experienced their first major depressive episode (MDE) prior to 50 years of age.
2. 4. Body Mass Index (BMI) ≥18 kg/m2 and ≤40 kg/m2.
3. 5. Meets the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) criteria for bipolar I or II disorder and is currently in a MDE, confirmed using the Mini International Neuropsychiatric Interview (MINI).
4. 6. Current MDE must has a duration of ≥4 weeks and ≤12 months.

Exclusion criteria 10

1. 1. Participant has any type of MDD, including MDD with psychotic features, MDD with catatonia, MDD with seasonal pattern, or postpartum depression.
2. 2. Participant has any nonbipolar psychiatric diagnosis.
3. 3. Participant has a substance use disorder (excluding tobacco) within the 6 months prior to screening visit.
4. 5. Participant has a YMRS score >12 points at screening visit or randomization.
5. 6. Participant has been hospitalized for mania within the 30 days prior to screening visit.
6. 7. Participant is considered treatment-resistant in the current bipolar depressive episode, defined as having treatment resistance (no remission) to ≥2 different medications approved by the regional regulatory authority at an adequate dose (per regulatory-approved label) and for an adequate duration (at least 6 weeks).
7. 9. Participant has had an active suicidal plan/intent prior to screening, presence of suicidal behavior.
8. 11. Participant has used antidepressants, mood stabilizers, anticonvulsants, antipsychotics, or other prohibited medications within the 1 week prior to randomization or within a period less than 5-times the drug's half-life prior to randomization, whichever is longer.
9. Participants with medical conditions that may interfere with the purpose or conduct of the study.
10. 27. 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 MADRS total score at Week 6.

Secondary endpoints 3

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

Clinical Trial responsible person: Vice President Psychiatry Clinical Development

Public contact point

Organisation

Xenon Pharmaceuticals Inc.

Contact name

Clinical Trial responsible person: Senior Director, Trial Operations

Third parties 17

Locations

4 EU/EEA countries · 20 investigational sites

By country

Investigational sites

Results and documents

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

Documents 99 files

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

Application history

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