Home › Trials › NCT07140913

KarXT added to lithium, valproate, or lamotrigine for treating mania in Bipolar I

A Phase 3, Randomized, Double-blind, Placebo-controlled, Study to Evaluate the Efficacy and Safety of Adjunctive KarXT for the Treatment of Mania, With or Without Mixed Features, in Individuals With Bipolar-I Disorder Taking Lithium, Valproate, or Lamotrigine

Phase 3 Interventional Bristol-Myers Squibb · NCT07140913

This will test whether adding KarXT to a stable mood stabilizer (lithium, valproate, or lamotrigine) helps adults hospitalized for an acute manic episode of bipolar I disorder reduce their manic symptoms.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment424 (estimated)
Ages18 Years to 65 Years
SexAll
SponsorBristol-Myers Squibb Industry-sponsored
Locations103 sites (Bentonville, Arkansas and 102 other locations)
Trial IDNCT07140913 on ClinicalTrials.gov

What this trial studies

This Phase 3, randomized, placebo-controlled interventional trial enrolls adults hospitalized for an acute manic episode of bipolar I disorder who are already taking a stable therapeutic dose of lithium, valproate, or lamotrigine. Participants are randomized to receive adjunctive KarXT (xanomeline/trospium chloride) or placebo in addition to their mood stabilizer while inpatient. Key entry requirements include a confirmed DSM-5-TR diagnosis, recent onset or relapse of mania (≤3 weeks), a YMRS score ≥18, and stable mood-stabilizer dosing prior to screening. The study will monitor safety and changes in manic symptoms over the treatment period using standardized rating scales.

Who should consider this trial

Good fit: Adults with bipolar I disorder experiencing an acute manic episode (with or without mixed features) who require hospitalization and are on a stable, therapeutic dose of lithium, valproate, or lamotrigine with BMI 18–40 and YMRS ≥18 are the intended participants.

Not a fit: Patients who are not hospitalized, not taking lithium/valproate/lamotrigine, have bipolar II or other primary psychiatric diagnoses, or have significant medical contraindications may not be eligible or likely to benefit from this specific adjunctive approach.

Why it matters

Potential benefit: If successful, adjunctive KarXT could provide a faster or more effective option to reduce manic symptoms and potentially shorten hospital stays for patients with acute bipolar I mania.

How similar studies have performed: Related xanomeline–trospium programs have shown efficacy for psychotic symptoms in schizophrenia and Alzheimer's disease psychosis, but using KarXT specifically as adjunctive therapy for bipolar mania is a more novel application being tested in late-phase trials.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.
* 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.

Exclusion Criteria:

* Any primary DSM-5-TR disorder other than BP-I within 12 months before screening (confirmed using MINI version 7.0.2 at screening) including BP-I depression (for previous 3 months only), BP-I with rapid cycling, first manic episode, BP-II, primary psychotic disorder, borderline personality disorder, and major depressive disorder, with the exception of mild anxiety disorders.
* 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 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 "Yes" to any of the 5 items (C-SSRS behavior) with an event occurring within the 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 or 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.

Where this trial is running

Bentonville, Arkansas and 102 other locations

+53 more sites — see ClinicalTrials.gov for the full list.

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 → Find more trials like this →
Conditions ManiaBipolar DisorderBipolar-I DisorderKarXTadjunctive treatmentmood stabilizer
Last reviewed 2026-06-13 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.