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Oral icalcaprant for adults with bipolar I or II: safety and symptom change

A Phase 2, Multicenter, 6-Week, Double Blind, Placebo- Controlled Study to Evaluate the Efficacy and Safety of Icalcaprant in Subjects With Bipolar Depression

PHASE2 · AbbVie · NCT06696755

This trial will test whether taking oral icalcaprant once daily for six weeks is safe and helps reduce depressive symptoms in adults with bipolar I or II disorder.

Quick facts

PhasePHASE2
Study typeInterventional
Enrollment195 (estimated)
Ages18 Years to 65 Years
SexAll
SponsorAbbVie (industry)
Locations31 sites (Huntsville, Alabama and 30 other locations)
Trial IDNCT06696755 on ClinicalTrials.gov

What this trial studies

This Phase 2, randomized interventional trial enrolls about 195 adults with bipolar I or II disorder experiencing a major depressive episode and randomizes them into three treatment arms, with roughly one-third receiving placebo. Participants take oral icalcaprant or matching placebo once daily for six weeks and are followed for safety for an additional four weeks. Key entry criteria include absence of psychotic features, a YMRS score ≤ 12, CGI-S-BP ≥ 4 for depression, BMI between 18 and 35, and stable use of a single mood stabilizer when applicable. The study will monitor adverse events and changes in disease activity measures to determine safety and preliminary signal of benefit.

Who should consider this trial

Good fit: Adults with bipolar I or II currently in a major depressive episode (without psychotic features), with BMI 18–35, YMRS ≤ 12, CGI-S-BP ≥ 4, and who meet stability requirements (for example, on a single mood stabilizer at a stable dose) are the ideal candidates.

Not a fit: People currently experiencing manic or mixed episodes, those with psychotic features, unstable medical conditions, those on multiple concurrent mood stabilizers, children, or those unable to attend in-person visits are unlikely to benefit from participating.

Why it matters

Potential benefit: If successful, icalcaprant could provide a new oral option to reduce depressive symptoms in adults with bipolar I or II disorder while demonstrating an acceptable safety profile.

How similar studies have performed: Icalcaprant is investigational for bipolar depression and there is limited published clinical evidence for this specific agent, so the approach is relatively novel with only preliminary data available.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Participants with a diagnosis of bipolar I or II according to the (Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) DSM-5-TR) without psychotic features, confirmed by the Mini International Neuropsychiatric Interview (MINI) 7.0.2, and currently experiencing an (major depressive episode) MDE beginning at least 4 weeks prior to consent and not exceeding 6 months prior to screening.
* Body Mass Index (BMI) is ≥ 18.0 to ≤ 35.0 kg/m\^2.
* A condition of general good health, based upon the results of a medical history, physical examination, vital signs, laboratory profile and a 12-lead ECG.
* CGI-S-BP score of ≥ 4 for depression and overall bipolar illness at screening (Visit 1) and baseline (Visit 2).
* YMRS total score ≤ 12 at screening (Visit 1) and baseline (Visit 2).
* Participants on treatment with a single mood stabilizer (lithium, valproate, or lamotrigine), maintained at a stable dose for ≥ 28 days prior to screening. Current mood stabilizer dose must remain unchanged for the duration of the study.

  * If taking lithium or valproate, participant must have a therapeutic blood level at screening of lithium (0.8 - 1.2 mg/dL) or valproate (50 - 125 mg/dL).
  * If taking lamotrigine, participant must be taking a locally approved maintenance dose.

Exclusion Criteria:

* History of an allergic reaction or significant sensitivity to constituents of the study drug (and its excipients) and/or other products in the same class.
* History of or active medical conditions(s) that might interfere with the conduct of the study, confound the interpretation of the study results, or endanger the subject's well-being. This includes any unstable condition, history or evidence of malignancy (other than treated basal or squamous cell carcinoma), or any significant hematologic, endocrine, cardiovascular, respiratory, renal, hepatic, gastrointestinal, or neurological disorder (if there is a history of such disease but the condition has been stable for more than 1 year, does not require treatment with prohibited medications, and is judged by the investigator not to interfere with the participant's participation in the study, the participant may be included in the study).

Where this trial is running

Huntsville, Alabama and 30 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Bipolar I Disorder, Bipolar II Disorder, Bipolar Disorder, lcalcaprant, ABBV-1354, CVL-354

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.