A Study to Evaluate the Efficacy and Safety of Adjunctive KarXT for the Treatment of Mania, With or Without Mixed Features, in Participants With Bipolar-I Disorder Taking Lithium, Valproate, or Lamotrigine

Bristol-Myers Squibb (BMS)

Status and phase: Enrolling; Phase 3

Conditions: Bipolar Disorder; Mania

Treatments: Drug: Valproate; Drug: Lamotrigine; Drug: Placebo; Drug: Lithium; Drug: Xanomeline/Trospium Chloride

Study type: Interventional

Funder types: Industry

Identifiers

NCT07140913

CN012-0046

U1111-1321-1513 (Other Identifier)

2025-521845-26 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy and safety of adjunctive KarXT for the treatment of mania in participants with Bipolar-I Disorder.

Enrollment: 424 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Individuals have a primary diagnosis of Bipolar-I disorder established by a comprehensive psychiatric evaluation based on the DSM-5-TR criteria and confirmed by the Mini International Neuropsychiatric Interview (MINI) version 7.0.2 Standard.
• Individual is experiencing an acute exacerbation or relapse of manic episode, with or without mixed features (≤ 3 weeks).
• The individual requires hospitalization for the acute exacerbation or relapse of mania.
• Body mass index ≥ 18 and ≤ 40 kg/m2
• Currently experiencing an acute episode of mania or mania with mixed features with a therapeutic dose of lithium, valproate, or lamotrigine. The dose of the mood stabilizer must have remained stable for at least two weeks prior to screening. Additionally, participants on valproate must have been receiving treatment with valproate for a minimum of seven months.
• YMRS Total Score of ≥ 18 at Screening and at Baseline, and < 20% reduction in YMRS from screening to baseline.
• Clinical Global Impression Severity scale (CGI-BP) ≥ 4

Exclusion criteria

• Any primary DSM-5-TR disorder other than BP-I within 12 months before screening (confirmed using MINI version 7.0.2 Standard) including BP-I depression, BP-I with rapid cycling, first manic episode, BP-II, and major depressive disorder.
• Individual has a DSM-5-TR diagnosis of moderate to severe substance use disorder (except tobacco use disorder) within the 12 months before screening (confirmed using MINI version 7.0.2 Standard at screening), or current use as determined by urine toxicology screen or alcohol test.
• Risk for suicidal behavior at screening as determined by the investigator's clinical assessment and the C-SSRS with an answer "Yes" to item 4 or 5 within 6 months before screening or between screening and baseline, or suicide attempt within 12 months before screening, or between screening and baseline
• History of irritable bowel syndrome (with or without constipation) or any serious constipation requiring treatment within the last 6 months.
• History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma.
• Participants with HIV, cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections based on either medical history or the LFT results.
• Elevations in hepatic transaminases at screening ≥ 2 × ULN for ALT and AST and/or bilirubin > 1.5× ULN, unless in the context of Gilbert's syndrome.
• All grades of hepatic impairment (mild [Child-Pugh Class A], moderate [Child-Pugh Class B], and severe [Child-Pugh Class C]).
• Other protocol-defined Inclusion/Exclusion criteria apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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424 participants in 2 patient groups, including a placebo group

KarXT + Lithium, Valproate, or Lamotrigine

Experimental group

Treatment:

Drug: Xanomeline/Trospium Chloride

Drug: Lithium

Drug: Lamotrigine

Drug: Valproate

Placebo + Lithium, Valproate, or Lamotrigine

Placebo Comparator group

Treatment:

Drug: Lithium

Drug: Placebo

Drug: Lamotrigine

Drug: Valproate