A Study to Assess Adverse Events and Change in Disease Activity of Oral Icalcaprant in Adult Participants With Bipolar I or II Disorder

Phase 2

Not yet recruiting

• Conditions: Bipolar I Disorder; Bipolar II Disorder
• Interventions: Drug: Icalcaprant; Drug: Placebo for Icalcaprant

• Registration Number: NCT06696755
• Lead Sponsor: AbbVie

Brief Summary

Bipolar disorder is a severe chronic mood disorder that affects up to 4% of the adult population and 1.8% of the pediatric population in the United States. This study will assess how safe and effective Icalcaprant is in treating adult participants with bipolar I or II disorder.

Icalcaprant is an investigational drug being developed for the treatment of depressive episodes in adult participants with bipolar I or II disorder. Participants are placed in 1 of 3 groups, called treatment arms. There is a 1 in 3 chance that a participant will be assigned to a placebo. Around 195 adult participants with bipolar I or II disorder will be enrolled in approximately 35 sites across the United States of America.

Participants will receive oral capsules of Icalcaprant or matching placebo once daily for 6 weeks, with a 4-week safety follow-up period.

There may be a higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-11-18
• Study First Submitted QC: 2024-11-18
• Study First Posted: 2024-11-20
• Status Verified: 2025-10
• Last Update Submitted: 2025-10-17
• Last Update Posted: 2025-10-20
• Study Start: 2026-02-05
• Primary Completion: 2027-11
• Study Completion: 2027-11-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 195

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1: Icalcaprant Dose A	Icalcaprant	Participants will receive oral Icalcaprant dose A once daily for 6 weeks and followed for 4 weeks.
Group 2: Icalcaprant Dose B	Icalcaprant	Participants will receive oral Icalcaprant dose B once daily for 6 weeks and followed for 4 weeks.
Group 3: Placebo for Icalcaprant	Placebo for Icalcaprant	Participants will receive oral placebo for Icalcaprant daily for 6 weeks and followed for 4 weeks.

Primary Outcome Measures

Name	Time	Method
Change from Baseline to Week 6 in the MADRS (Montgomery-Åsberg Depression Rating Scale) total score	Up to approximately Week 6	MADRS is a depression rating scale consisting of 10 items representing the core symptoms of depressive illness, each rated 0 (no symptom) to 6 (severe symptom). Total score ranges from 0 (no depression) to 60 (severely depressed).
Number of Participants with Adverse Events (AEs)	Up to approximately 10 weeks	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study

Secondary Outcome Measures

Name	Time	Method
Change from Baseline to Week 6 in Clinician Global Impression of Severity - Bipolar Disorder (CGI-S-BP) score	Up to approximately Week 6	Clinician Global Impression of Severity - Bipolar Disorder (CGI-S-BP) is a clinician-reported measure of severity of mania, depression, and overall bipolar disorder. Clinicians are asked to consider their total clinical experience with bipolar subjects and assess how severely ill has the participant been during the past 7 days. Response options range from 'Normal, not ill' to 'Very severely ill'.