Azetukalner for Bipolar Depression

(X-CEED Trial)

Recruiting at 4 trial locations

Overseen By Xenon Medical Affairs

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Xenon Pharmaceuticals Inc.

Must not be taking: Antidepressants, Mood stabilizers

Disqualifiers: Major depressive disorder, Substance use, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

1 Power Preferred Clinic 1 of this trial's clinic is considered top 20 on Power

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests azetukalner, a new treatment for individuals with bipolar depression. The goal is to determine if azetukalner is safe and more effective at reducing symptoms than a placebo (a pill with no active medicine). Participants must have bipolar I or II disorder and currently experience a depressive episode lasting between 4 weeks and 12 months. Those with other types of depression, substance use issues, or recent hospitalizations for mania are not eligible. As a Phase 3 trial, this treatment represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in bipolar depression treatment.

Do I need to stop my current medications for the trial?

Yes, you will need to stop taking antidepressants, mood stabilizers, anticonvulsants, antipsychotics, or other prohibited medications at least one week before joining the trial, or longer if the medication stays in your body for a while.

Is there any evidence suggesting that azetukalner is likely to be safe for humans?

Research has shown that azetukalner is generally safe. Studies have found that people with major depressive disorder (MDD) usually tolerate it well. Common side effects include mild headaches and dizziness. In studies on bipolar depression, the safety results were similar. The treatment is also being tested for epilepsy, and the data supports its safety in that context as well. Overall, this suggests that azetukalner is generally safe for use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bipolar depression?

Unlike the standard treatments for bipolar depression, which often include mood stabilizers and antipsychotics, Azetukalner is unique because it targets the condition with a new active ingredient. Researchers are particularly excited about Azetukalner because it may offer a different mechanism of action, potentially working more effectively or having fewer side effects than current options. This new approach could provide a significant advancement in how we manage bipolar depression, offering hope for patients who have not found relief with existing treatments.

What evidence suggests that azetukalner might be an effective treatment for bipolar depression?

Research has shown that azetukalner, which participants in this trial may receive, may help with symptoms of bipolar depression. In studies, patients taking 20 mg of azetukalner experienced a noticeable improvement in their ability to feel pleasure compared to those taking a placebo. This improvement was measured at week 6 using the SHAPS tool, which assesses enjoyment. Additionally, azetukalner reduced depression symptoms based on the MADRS score, a common method for rating depression. These findings suggest that azetukalner could be effective for people experiencing depressive episodes related to bipolar I or II disorder. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

Adults aged 18-74 with bipolar I or II disorder currently experiencing a depressive episode lasting 4 weeks to 12 months, BMI between 18 and 40. Must have had their first major depressive episode before age 50. Excludes those with recent self-harm, nonbipolar psychiatric diagnoses, substance abuse within the last six months, high mania scores, certain medical conditions, pregnancy/breastfeeding intentions, other types of depression including treatment-resistant cases or recent hospitalization for mania.

Inclusion Criteria

Were you first depressed before the age of 50?

Are you currently experiencing depression?

Exclusion Criteria

Have you been diagnosed with Major Depressive Disorder?

Have you been hospitalized for mania in the past month?

Have you used illicit substances in the past 6 months?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either azetukalner 20 mg or placebo during the double-blind phase

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Azetukalner

Trial Overview The X-CEED study is testing Azetukalner against a placebo in adults with bipolar depression. It's a Phase 3 trial where participants are randomly assigned to either receive the experimental drug or an inactive substance (placebo), without knowing which one they're getting (double-blind).

How Is the Trial Designed?

Group I: Azetukalner Experimental Treatment 1 Intervention

Azetukalner 20 mg

Group II: Placebo Placebo Group 1 Intervention

Placebo

Who Is Running the Clinical Trial?

Xenon Pharmaceuticals Inc.

Lead Sponsor

Trials

19

Recruited

3,400+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07172516

NCT07172516 | A Randomized Study of Azetukalner ... A Randomized Study of Azetukalner Versus Placebo in Depressive Episodes Associated With Bipolar I or II Disorder (Bipolar Depression) (X-CEED).

2. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2834419

Azetukalner, a Novel KV7 Potassium Channel Opener, in ... These results suggest that azetukalner has the potential to improve symptoms of depression in patients with MDD, with a safety profile ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12117446/

Azetukalner, a Novel KV7 Potassium Channel Opener, in ... In this study, 20 mg of azetukalner demonstrated a significant reduction in anhedonia at week 6 compared with placebo as measured by SHAPS, ...

4. xenon-pharma.com xenon-pharma.com/product-pipeline/azetukalner-bpd/

Azetukalner (BPD) The primary efficacy endpoint is the change from baseline in the MADRS score at week 6 in patients who received azetukalner compared to placebo. Upon completion ...

5. medpagetoday.com medpagetoday.com/psychiatry/depression/115761

Novel Agent for Major Depression Moves to Phase III, Even ... For patients with major depression, there was a clinically meaningful but not statistically significant improvement in the primary endpoint with ...

6. psychiatryonline.org psychiatryonline.org/doi/10.1176/appi.pn.2025.07.7.12

Med Check: FDA Clears At-Home Calming Device for ... Azetukalner is also being developed for the treatment of epilepsy and bipolar depression. ... data demonstrating that the compound's safety ...