Major Depressive Disorder
Conditions
Keywords
Depression, Antidepressant, XEN1101, Azetukalner
Brief summary
X-NOVA3 is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study to evaluate the clinical efficacy, safety, and tolerability of azetukalner as a monotherapy in adult participants diagnosed with Major Depressive Disorder (MDD)
Interventions
DRUGAzetukalner
Azetukalner 20 mg taken orally once a day with food (with the evening meal when possible) for 6 weeks
DRUGPlacebo
Placebo taken orally once a day with food (with the evening meal when possible) for 6 weeks
Sponsors
Xenon Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Adults ≥18 and ≤74 years of age and experienced their first major depressive episode (MDE) prior to 50 years of age * Body Mass Index (BMI) ≤40 kg/m2 * 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) * Participant's current MDE has a duration of ≥6 weeks and ≤24 months. Key
Exclusion criteria
* Participant has a primary diagnosis of a mood disorder other than MDD. * 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. * Participant has a current diagnosis of any of the following: MDD with seasonal pattern; Depression with peripartum or perimenopausal onset; Post traumatic 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. * Participant has a substance (excluding tobacco) or alcohol use disorder within the 12 months prior to screening. * 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. * Participant has a history of non-suicidal self-harm behavior in the 12 months prior to screening. * 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. * 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). * Participants with medical conditions that may interfere with the purpose or conduct of the study * Participant is pregnant, breastfeeding, or planning to become pregnant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in the Hamilton Depression Rating Scale, 17-item (HAMD-17) score at Week 6 | Baseline to Week 6 | The HAMD-17 consists of 17 items that are used to rate the severity of depression symptoms. Each item is scored in a range of 0 to 2 points or 0 to 4 points, with higher scores indicating a greater degree of depression. The score for each item is summed to compute a total score, which ranges from 0 to 52 points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in the Snaith-Hamilton Pleasure Scale (SHAPS) score at Week 6 | Baseline to Week 6 | The SHAPS is a 14-item self-report questionnaire used to assess anhedonia. Each item on the SHAPS is worded so that higher scores indicate greater anhedonia. A total score can be derived by summing the responses to each item. Items answered with "strongly agree" are assigned a score of 1, while "strongly disagree" responses are assigned a score of 4 points. Total scores on the SHAPS can range from 14 to 56 points, with higher scores corresponding to higher levels of anhedonia. |
| Change from baseline in the Hamilton Depression Rating Scale, 17-item (HAMD-17) score at Week 1 | Baseline to Week 1 | The HAMD-17 consists of 17 items that are used to rate the severity of depression symptoms. Each item is scored in a range of 0 to 2 points or 0 to 4 points, with higher scores indicating a greater degree of depression. The score for each item is summed to compute a total score, which ranges from 0 to 52 points. |
| Change from baseline in the Clinical Global Impression of Severity (CGI-S) score at Week 6 | Baseline to Week 6 | The CGI-S is a clinician-rated global measure of participant overall disease severity. Participants are rated on a 7-point severity scale, with higher scores indicating more severe depression. |
| To assess the safety and tolerability of azetukalner (e.g., adverse events) | From screening (approximately 4 weeks prior to baseline) through to 8 weeks post-final dose. | — |
Countries
Finland, Germany, Poland, Romania, Slovakia, Spain, United States
Contacts
CONTACTXenon Medical Affairs
Outcome results
None listed