Major Depressive DisorderPhase 2X-NOVANCT05376150
A Study to Evaluate the Safety, Tolerability and Efficacy of XEN1101 in Major Depressive Disorder
A Phase 2 study testing XEN1101 10 mg and XEN1101 20 mg in people with Major Depressive Disorder, run by Xenon Pharmaceuticals Inc. at 20 sites in United States.
Trial summary
This is a multicenter, Phase 2, double-blind, randomized, parallel-arm, placebo-controlled clinical trial to evaluate the efficacy, safety, and tolerability of XEN1101 in subjects with Major Depressive Disorder. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- XEN1101 10 mg and XEN1101 20 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 168 participants
- Where
- 20 sitesUnited States
- Study dates
- 19 May 2022to 16 Oct 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be properly informed of the nature and risks of the study and given written informed consent.
- Male or female, aged 18 through 65 years (inclusive) with a body mass index (BMI) ≤35 kg/m².
- Subject must meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for current MDD and currently in a moderate to severe major depressive episode (MDE), confirmed using the Mini International Neuropsychiatric Interview (MINI).
- Current MDE duration ≥2 months and <24 months at the time of screening.
- Current illness severity that is at least moderate, defined as a score of ≥20 on the HAM-D17 at screening and on Day 1.
- Score ≥20 on the SHAPS at screening and on Day1.
- Must be willing to comply with the study protocol for the full term of the study.
Who cannot join
- A primary psychiatric diagnosis other than MDD as defined by DSM-5 (comorbid anxiety disorders [including agoraphobia, generalized anxiety disorder, social anxiety disorder, post-traumatic stress disorder (PTSD), and panic disorder] are allowed).
- Concomitant use of antidepressants and/or other disallowed pharmacotherapy (including benzodiazepines).
- History of schizophrenia or other psychotic disorder, MDD with psychotic features, bipolar I or II disorder, or MDD with mixed features.
- History of non-response to >1 antidepressant drug due to lack of efficacy in the current MDE.
- Failing >3 antidepressant drug trials, for any reason, in the current MDE.
- History of non-response to electroconvulsive therapy (ECT) in the past 10 years.
Show all 10Show fewer
- Active suicidal plan/intent in the past 6 months, or more than 1 lifetime suicide attempt.
- Females who are pregnant, breastfeeding, or planning to become pregnant during the first administration of study drug until 3 months after the last dose of study drug.
- Meets criteria for a substance use disorder within the past 12 months, with the exception of tobacco use, and/or has a positive urine toxicology screen for drugs of abuse.
- Any medical condition or personal circumstance that, in the opinion of the investigator, exposes the subject to unacceptable risk by participating in the study or prevents adherence to the protocol.
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
United States20 sites
Advanced Research Center
Anaheim, California, 92805
Neurobehavioral Research, Inc. (NBR)
Cedarhurst, New York, 11516
FutureSearch Trials of Dallas, LP
Dallas, Texas, 75231
i-Research, Atlanta
Decatur, Georgia, 30030
Revive Research Institute, Inc.
Elgin, Illinois, 60123
Sunwise Clinical Research, LLC
Lafayette, California, 94549
Altea Research
Las Vegas, Nevada, 89102
Psych Atlanta, PC
Marietta, Georgia, 30060
Hassman Research Institute
Marlton, New Jersey, 08009
Meridian International Research
Miami, Florida, 33014
Global Medical Institutes (GMI)
Miami, Florida, 33125
CCM Clinical Reseach Group, LLC
Miami, Florida, 33133
Manhattan Behavioral Medicine, PLLC
New York, New York, 10036
California Neuropsychopharmacology Clinical Research Institute
Pico Rivera, California, 90660
AIM Trials
Plano, Texas, 75093
Richard M Weisler and Association
Raleigh, North Carolina, 27609
Artemis Institute for Clinical Research
Riverside, California, 92503
Artemis Institute for Clinical Research
San Diego, California, 92103
iResearch
Savannah, Georgia, 31405
Bio Behavioral Health
Toms River, New Jersey, 08755
About this study
Official title: A Proof-of-Concept, Randomized, Double-blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety, Tolerability, and Efficacy of XEN1101 in Major Depressive Disorder
This is a multicenter, Phase 2, double-blind, randomized, parallel-arm, placebo-controlled clinical trial to evaluate the efficacy, safety, and tolerability of XEN1101 in subjects with Major Depressive Disorder.
Read the detailed description
The study is divided into 3 stages: Screening - up to 4 weeks duration; Treatment - 6 weeks duration; Follow-up - 4 weeks duration. The total study duration per subject is estimated to be approximately 14 weeks.
- Conditions
- Major Depressive Disorder
- Being tested
- XEN1101 10 mg, XEN1101 20 mg, Placebo
- Keywords
- Major Depressive Disorder, Potassium channel, Depression
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XEN1101 10 mgDrug
XEN1101 oral capsule
XEN1101 20 mgDrug
XEN1101 oral capsule
PlaceboDrug
Placebo capsule
| Study group | Role | What they receive |
|---|---|---|
| XEN1101 10 mg | Experimental | During the double blind treatment period (42 days), subjects will take 1 capsule of XEN1101 10 mg, orally with food, per day Receives: Drug: XEN1101 10 mg |
| XEN1101 20 mg | Experimental | During the double blind treatment period (42 days), subjects will take 1 capsule of XEN1101 20 mg, orally with food, per day Receives: Drug: XEN1101 20 mg |
| placebo | Placebo comparator | During the double blind treatment period (42 days), subjects will take 1 capsule of placebo, orally with food, per day Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Score.
Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-rated, 10-item scale used to assess the severity of depressive symptoms. Each item is scored from 0 (normal/absent) to 6 (severe), yielding a total score ranging from 0 to 60, with higher scores indicating greater depression severity.
MADRS total score change from baseline at week 6.
Measured: From baseline to end of treatment (Week 6).
Secondary outcomes (2)
Change in Snaith-Hamilton Pleasure Scale (SHAPS) Score.
Snaith-Hamilton Pleasure Scale (SHAPS) is a validated 14-item self-report questionnaire commonly used to assess anhedonia (reduced ability to experience pleasure). Each of the 14 items is rated from 1 (strongly agree) to 4 (strongly disagree). Total scores range from 14 to 56, with higher scores indicating greater levels of anhedonia.
SHAPS total score change from baseline at week 6
Measured: From baseline to end of treatment (Week 6).
Change in Beck Anxiety Inventory (BAI) Score.
Beck Anxiety Inventory (BAI) is a 21-item self-report questionnaire used to assess the severity of anxiety symptoms. Each item is scored on a scale from 0 (not at all) to 3 (severely), yielding a total score ranging from 0 to 63, with higher scores indicating greater anxiety severity.
BAI total score change from baseline at week 6
Measured: From baseline to end of treatment (Week 6).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2022
- Study start19 May 2022
- Primary completion18 Sep 2023
- Study completion16 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 168 participants (actual)
Sponsor and investigators
- Lead sponsor
- Xenon Pharmaceuticals Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Xenon Pharmaceuticals Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05376150
- Sponsor's protocol ID
- XPF-008-204
- Acronym
- X-NOVA
- Status last verified
- Aug 2026
- First submitted
- 11 May 2022
- Last updated
- 21 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Butterfield NN, Luzon Rosenblut C, Fava M, Correll CU, Rothschild AJ, Murrough JW, Mathew SJ, Beatch GN, Grayson C, Harden C, Qian J, McIntosh J, Namdari R, Kenney C. Azetukalner, a Novel KV7 Potassium Channel Opener, in Adults With Major Depressive Disorder: A Randomized Clinical Trial. JAMA Netw Open. 2025 May 1;8(5):e2514278. doi: 10.1001/jamanetworkopen.2025.14278.
PubMed 40423966
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Proof-of-Concept, Randomized, Double-blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety, Tolerability, and Efficacy of XEN1101 in Major Depressive Disorder
- ClinicalTrials.gov ID
- NCT05376150
- Acronym / sponsor ID
- X-NOVA / XPF-008-204
- Conditions
- Major Depressive Disorder
- Keywords
- Major Depressive Disorder, Potassium channel, Depression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 168 participants (actual)
- Lead sponsor
- Xenon Pharmaceuticals Inc.Industry (pharma, biotech, devices)
- Study start
- 19 May 2022 (actual)
- Primary completion
- 18 Sep 2023 (actual)
- Study completion
- 16 Oct 2023 (actual)
- First posted
- 17 May 2022 (actual)
- Results
- Posted 21 Sep 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, Phase 2, double-blind, randomized, parallel-arm, placebo-controlled clinical trial to evaluate the efficacy, safety, and tolerability of XEN1101 in subjects with Major Depressive Disorder.
Detailed description
The study is divided into 3 stages: Screening - up to 4 weeks duration; Treatment - 6 weeks duration; Follow-up - 4 weeks duration. The total study duration per subject is estimated to be approximately 14 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| XEN1101 10 mg | Experimental | Drug: XEN1101 10 mgDuring the double blind treatment period (42 days), subjects will take 1 capsule of XEN1101 10 mg, orally with food, per day |
| XEN1101 20 mg | Experimental | Drug: XEN1101 20 mgDuring the double blind treatment period (42 days), subjects will take 1 capsule of XEN1101 20 mg, orally with food, per day |
| placebo | Placebo comparator | Drug: PlaceboDuring the double blind treatment period (42 days), subjects will take 1 capsule of placebo, orally with food, per day |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Be properly informed of the nature and risks of the study and given written informed consent.
- Male or female, aged 18 through 65 years (inclusive) with a body mass index (BMI) ≤35 kg/m².
- Subject must meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for current MDD and currently in a moderate to severe major depressive episode (MDE), confirmed using the Mini International Neuropsychiatric Interview (MINI).
- Current MDE duration ≥2 months and <24 months at the time of screening.
- Current illness severity that is at least moderate, defined as a score of ≥20 on the HAM-D17 at screening and on Day 1.
Key exclusion criteria (10 listed)
- A primary psychiatric diagnosis other than MDD as defined by DSM-5 (comorbid anxiety disorders [including agoraphobia, generalized anxiety disorder, social anxiety disorder, post-traumatic stress disorder (PTSD), and panic disorder] are allowed).
- Concomitant use of antidepressants and/or other disallowed pharmacotherapy (including benzodiazepines).
- History of schizophrenia or other psychotic disorder, MDD with psychotic features, bipolar I or II disorder, or MDD with mixed features.
- History of non-response to >1 antidepressant drug due to lack of efficacy in the current MDE.
- Failing >3 antidepressant drug trials, for any reason, in the current MDE.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| XEN1101 10 mgXEN1101 oral capsule | Drug | XEN1101 10 mg |
| XEN1101 20 mgXEN1101 oral capsule | Drug | XEN1101 20 mg |
| PlaceboPlacebo capsule | Drug | placebo |
Primary outcome
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Score.
Time frame: From baseline to end of treatment (Week 6).
Montgomery-Åsberg Depression Rating Scale (MADRS) is a clinician-rated, 10-item scale used to assess the severity of depressive symptoms. Each item is scored from 0 (normal/absent) to 6 (severe), yielding a total score ranging from 0 to 60, with higher scores indicating greater depression severity. MADRS total score change from baseline at week 6.
2 secondary outcomes
Change in Snaith-Hamilton Pleasure Scale (SHAPS) Score.
Time frame: From baseline to end of treatment (Week 6).
Change in Beck Anxiety Inventory (BAI) Score.
Time frame: From baseline to end of treatment (Week 6).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 40423966Butterfield NN, Luzon Rosenblut C, Fava M, Correll CU, Rothschild AJ, Murrough JW, Mathew SJ, Beatch GN, Grayson C, Harden C, Qian J, McIntosh J, Namdari R, Kenney C. Azetukalner, a Novel KV7 Potassium Channel Opener, in Adults With Major Depressive Disorder: A Randomized Clinical Trial. JAMA Netw Open. 2025 May 1;8(5):e2514278. doi: 10.1001/jamanetworkopen.2025.14278.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Xenon Pharmaceuticals Inc.
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing XEN1101 10 mg and XEN1101 20 mg in people with Major Depressive Disorder, run by Xenon Pharmaceuticals Inc. at 20 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Score. (time frame: From baseline to end of treatment (Week 6).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05376150, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.