Clinical trial • Phase III • Psychiatry

AZETUKALNER for Bipolar depression

Phase III trial of AZETUKALNER for Bipolar depression.

Overview

Trial Therapeutic Area
Psychiatry
Trial Disease
Bipolar depression
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
06-11-2025
First CTIS Authorization Date
10-03-2026

Trial design

Randomised, placebo, administered qd (matching placebo) versus 20 mg azetukalner qd for 6 weeks.-controlled Phase III trial across 22 sites in Bulgaria, Germany, Spain and others.

Randomised
Yes
Comparator
Placebo, administered QD (matching placebo) versus 20 mg azetukalner QD for 6 weeks.
Target Sample Size
256
Trial Duration For Participant
42

Stratification factors

  • Bipolar disorder type (I vs II)

Eligibility

Recruits 256 No vulnerable population selected. Study enrols adults (≥18 years). Informed consent will be obtained using Subject Information Sheet (SIS) and Informed Consent Form (ICF) documents (multiple language versions provided); no assent procedures or other vulnerable-population consent processes are described..

Pregnancy Exclusion
27. Participant is pregnant, breastfeeding, or planning to become pregnant.
Vulnerable Population
No vulnerable population selected. Study enrols adults (≥18 years). Informed consent will be obtained using Subject Information Sheet (SIS) and Informed Consent Form (ICF) documents (multiple language versions provided); no assent procedures or other vulnerable-population consent processes are described.

Inclusion criteria

  • {"criterion_text":"- 3. Adults ≥18 and ≤74 years of age who experienced their first major depressive episode (MDE) prior to 50 years of age."}
  • {"criterion_text":"- 4. Body Mass Index (BMI) ≥18 kg/m2 and ≤40 kg/m2."}
  • {"criterion_text":"- 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)."}
  • {"criterion_text":"- 6. Current MDE must has a duration of ≥4 weeks and ≤12 months."}

Exclusion criteria

  • {"criterion_text":"- 1. Participant has any type of MDD, including MDD with psychotic features, MDD with catatonia, MDD with seasonal pattern, or postpartum depression."}
  • {"criterion_text":"- 27. Participant is pregnant, breastfeeding, or planning to become pregnant."}
  • {"criterion_text":"- 2. Participant has any nonbipolar psychiatric diagnosis."}
  • {"criterion_text":"- 3. Participant has a substance use disorder (excluding tobacco) within the 6 months prior to screening visit."}
  • {"criterion_text":"- 5. Participant has a YMRS score >12 points at screening visit or randomization."}
  • {"criterion_text":"- 6. Participant has been hospitalized for mania within the 30 days prior to screening visit."}
  • {"criterion_text":"- 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)."}
  • {"criterion_text":"- 9. Participant has had an active suicidal plan/intent prior to screening, presence of suicidal behavior."}
  • {"criterion_text":"- 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."}
  • {"criterion_text":"- Participants with medical conditions that may interfere with the purpose or conduct of the study."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Change from baseline in the MADRS total score at Week 6.","definition_or_measurement_approach":"Change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score measured at Week 6."}

Secondary endpoints

  • {"endpoint_text":"- Change from baseline in the CGI-S score at Week 6.","definition_or_measurement_approach":"Change from baseline in the Clinical Global Impression - Severity (CGI-S) score measured at Week 6."}
  • {"endpoint_text":"- Change from baseline in the MADRS total score at Week 1.","definition_or_measurement_approach":"Change from baseline in the MADRS total score measured at Week 1."}
  • {"endpoint_text":"- Change from baseline in the SHAPS total score at Week 6.","definition_or_measurement_approach":"Change from baseline in the Snaith-Hamilton Pleasure Scale (SHAPS) total score measured at Week 6."}

Recruitment

Planned Sample Size
256
Recruitment Window Months
25
Consent Approach
Informed consent obtained from adult participants using Subject Information Sheet (SIS) and Informed Consent Form (ICF). ICF/SIS documents are available in multiple languages (English, German, Spanish, Bulgarian, Polish, French). A specific ICF is provided for pregnant partners where applicable. No assent process is described.

Geography

Total Number Of Sites
22
Total Number Of Participants
123

Bulgaria

Earliest CTIS Part Ii Submission Date
19-02-2026
Latest Decision Or Authorization Date
13-03-2026
Processing Time Days
22
Number Of Sites
9
Number Of Participants
46

Sites

Site Name
Medical Center Hera EOOD
Department Name
Psychiatry
Principal Investigator Name
Spiridon Aleksiev Spiridonov
Principal Investigator Email
spiridon.aleksiev@gmail.com
Contact Person Name
Spiridon Aleksiev Spiridonov
Contact Person Email
spiridon.aleksiev@gmail.com
Site Name
Diagnostics-Consultancy Center Mladost M Varna OOD
Department Name
Psychiatry
Principal Investigator Name
Petar Petrov
Principal Investigator Email
pmdown@abv.bg
Contact Person Name
Petar Petrov
Contact Person Email
pmdown@abv.bg
Site Name
University Multiprofile Hospital For Active Treatment Dr. Georgi Stranski EAD
Department Name
Psychiatry
Principal Investigator Name
Maya Yordanova Stoimenova-Popova
Principal Investigator Email
dr.maya.stoimenova@gmail.com
Contact Person Name
Maya Yordanova Stoimenova-Popova
Contact Person Email
dr.maya.stoimenova@gmail.com
Site Name
Medical Center Saint Naum EOOD
Department Name
Psychiatry
Principal Investigator Name
Assen Jivkov Karadaliev
Principal Investigator Email
karadaliev@hotmail.com
Contact Person Name
Assen Jivkov Karadaliev
Contact Person Email
karadaliev@hotmail.com
Site Name
State Psychiatric Hospital Lovech
Department Name
Psychiatry
Principal Investigator Name
Lyudmil Zdravkov Tumbev
Principal Investigator Email
tumbev.dpb.lovech@abv.bg
Contact Person Name
Lyudmil Zdravkov Tumbev
Contact Person Email
tumbev.dpb.lovech@abv.bg
Site Name
Multiprofile Hospital For Active Treatment Dr. Hristo Stambolski EOOD
Department Name
Psychiatry
Principal Investigator Name
Ivan Todorov Dimitrov
Principal Investigator Email
itdim@abv.bg
Contact Person Name
Ivan Todorov Dimitrov
Contact Person Email
itdim@abv.bg
Site Name
Center For Mental Health Vratsa EOOD
Department Name
Psychiatry
Principal Investigator Name
Nadya Emilova Ivanova
Principal Investigator Email
nadia_odpzs@abv.bg
Contact Person Name
Nadya Emilova Ivanova
Contact Person Email
nadia_odpzs@abv.bg
Site Name
Diagnostics-Consultancy Center Mladost M Varna OOD
Department Name
Psychiatry
Principal Investigator Name
Hristo Vasilev Kozhuharov
Principal Investigator Email
christokojuharov@abv.bg
Contact Person Name
Hristo Vasilev Kozhuharov
Contact Person Email
christokojuharov@abv.bg
Site Name
Instituto De Investigaciones Neuropsiquiatricas Doctor Lopez Ibor S.A. (Bulgaria listing site)
Department Name
Psychiatry

Germany

Earliest CTIS Part Ii Submission Date
11-02-2026
Latest Decision Or Authorization Date
10-03-2026
Processing Time Days
27
Number Of Sites
3
Number Of Participants
21

Sites

Site Name
Goethe University Frankfurt
Department Name
Psychiatry
Principal Investigator Name
Andreas Reif
Principal Investigator Email
andreas.reif@med.uni-frankfurt.de
Contact Person Name
Andreas Reif
Site Name
Technische Universitaet Dresden
Department Name
Psychiatry
Principal Investigator Name
Philipp Ritter
Principal Investigator Email
philipp.ritter@uniklinikum-dresden.de
Contact Person Name
Philipp Ritter
Site Name
Universitaetsklinikum Muenster AöR
Department Name
Psychiatry
Principal Investigator Name
Bernhard Theodor Baune
Principal Investigator Email
bernhard.baune@ukmuenter.de
Contact Person Name
Bernhard Theodor Baune
Contact Person Email
bernhard.baune@ukmuenter.de

Spain

Earliest CTIS Part Ii Submission Date
09-01-2026
Latest Decision Or Authorization Date
13-03-2026
Processing Time Days
63
Number Of Sites
7
Number Of Participants
30

Sites

Site Name
Instituto De Investigaciones Neuropsiquiatricas Doctor Lopez Ibor S.A.
Department Name
Psychiatry
Principal Investigator Name
Ignacio Basurte Villamor
Principal Investigator Email
i.basurte@lopezibor.com
Contact Person Name
Ignacio Basurte Villamor
Contact Person Email
i.basurte@lopezibor.com
Site Name
Hospital Universitario De Salamanca
Department Name
Psychiatry
Principal Investigator Name
Ángel Luis Montejo González
Principal Investigator Email
amontejo@usal.es
Contact Person Name
Ángel Luis Montejo González
Contact Person Email
amontejo@usal.es
Site Name
Hospital Universitario Infanta Elena
Department Name
Psychiatry
Principal Investigator Name
Enrique Baca García
Principal Investigator Email
ebaca@fjd.es
Contact Person Name
Enrique Baca García
Contact Person Email
ebaca@fjd.es
Site Name
Hospital Alvaro Cunqueiro
Department Name
Psychiatry
Principal Investigator Name
José Antonio Campos Pérez
Principal Investigator Email
Jose.antonio.campos.perez@sergas.es
Contact Person Name
José Antonio Campos Pérez
Site Name
University Hospital Son Espases
Department Name
Psychiatry
Principal Investigator Name
Joan Salva Coll
Principal Investigator Email
joan.salva@ssib.es
Contact Person Name
Joan Salva Coll
Contact Person Email
joan.salva@ssib.es
Site Name
Hospital General Universitario Gregorio Maranon
Department Name
Psychiatry
Principal Investigator Name
Eva María Sánchez Morla
Principal Investigator Email
emsmorla@gmail.com
Contact Person Name
Eva María Sánchez Morla
Contact Person Email
emsmorla@gmail.com
Site Name
Hospital Universitario Infanta Elena (additional listing)
Department Name
Psychiatry

Poland

Earliest CTIS Part Ii Submission Date
26-02-2026
Latest Decision Or Authorization Date
16-03-2026
Processing Time Days
18
Number Of Sites
3
Number Of Participants
26

Sites

Site Name
Centrum Badan Klinicznych Pi-House Sp. z o.o.
Department Name
Psychiatry
Principal Investigator Name
Hanna Badzio-Jagiełło
Principal Investigator Email
hanna@pihouse.pl
Contact Person Name
Hanna Badzio-Jagiełło
Contact Person Email
hanna@pihouse.pl
Site Name
Clinic BBP Bożena Pawełczyk
Department Name
Psychiatry
Principal Investigator Name
Bożena B Pawełczyk
Principal Investigator Email
bozena.pawelczyk@clinicbbp.com
Contact Person Name
Bożena B Pawełczyk
Contact Person Email
bozena.pawelczyk@clinicbbp.com
Site Name
Instytut Psychiatrii I Neurologii
Department Name
Psychiatry
Principal Investigator Name
Adam Wichniak
Principal Investigator Email
wichniak@ipin.edu.pl
Contact Person Name
Adam Wichniak
Contact Person Email
wichniak@ipin.edu.pl

Sponsor

Primary sponsor

Full Name
Xenon Pharmaceuticals Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
Canada

Contract research organisations

Name
Lotus Clinical Research LLC
Responsibilities
codes: 13,5,6
Name
Merit CRO Inc.
Responsibilities
Ophthalmologic assessment (code: 15)
Name
Pivotal S.L.
Responsibilities
codes: 1,12,13,2,5
Name
IQVIA Limited
Responsibilities
codes: 8

Third parties

  • {"country":"United States","full_name":"Lotus Clinical Research LLC","duties_or_roles":"codes: 13,5,6","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"codes: 3","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Verified Clinical Trials LLC","duties_or_roles":"Enrolment verification for duplicate subjects (code: 15)","organisation_type":"Pharmaceutical company"}
  • {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"codes: 4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"codes: 7","organisation_type":"Pharmaceutical company"}
  • {"country":"Spain","full_name":"Pivotal S.L.","duties_or_roles":"codes: 1,12,13,2,5","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Labcorp","duties_or_roles":"codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Aicure LLC","duties_or_roles":"codes: 14,15 (Medicinal Product Compliance)","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Canada","full_name":"Altasciences Compagnie Inc.","duties_or_roles":"codes: 4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Ctsdatabase LLC","duties_or_roles":"Enrollment Verification for duplicate subjects (code: 15)","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Patients’ reimbursement (code: 15)","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"Spain","full_name":"Taxi Travel Ticket S.L.","duties_or_roles":"Patients’ reimbursement (code: 15)","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Merit CRO Inc.","duties_or_roles":"Ophthalmologic assessment (code: 15)","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"codes: 8","organisation_type":"Pharmaceutical company"}
  • {"country":"Germany","full_name":"PCI Pharma Services Germany GmbH","duties_or_roles":"codes: 14","organisation_type":"Pharmaceutical company"}
  • {"country":"Spain","full_name":"Ipsory S.L.","duties_or_roles":"Patients’ reimbursement (code: 15)","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc. (additional listing)","duties_or_roles":"ECG (code: 15)","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
XPF-010
Active Substance
AZETUKALNER
Modality
Small molecule
Routes Of Administration
ORAL
Route
Oral
Starting Dose
20 mg
Dose Levels
20 mg
Frequency
QD
Maximum Dose
20 mg
Investigational Product Name
Placebo
Modality
Other
Frequency
QD

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