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KarXT for manic episodes in Bipolar I disorder

A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-1)

Phase 3 Interventional Bristol-Myers Squibb · NCT06951698

This trial will test whether KarXT can reduce manic symptoms in adults hospitalized for an acute manic episode of Bipolar I disorder during a three-week inpatient treatment period.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment274 (estimated)
Ages18 Years to 65 Years
SexAll
SponsorBristol-Myers Squibb Industry-sponsored
Locations63 sites (Bentonville, Arkansas and 62 other locations)
Trial IDNCT06951698 on ClinicalTrials.gov

What this trial studies

This Phase 3, randomized, double-blind, placebo-controlled, multicenter inpatient trial compares KarXT to placebo in adults with Bipolar I disorder experiencing an acute episode of mania or mania with mixed features. Participants are hospitalized and randomized to receive KarXT or matching placebo for a three-week double-blind treatment period, with screening and a safety follow-up making the total study duration up to seven weeks. Key entry criteria include a YMRS score of ≥20, a CGI-BP score ≥4, requirement for hospitalization, and a brief washout of other psychotropic medications. The primary outcome is change in manic symptoms during the three-week inpatient treatment window.

Who should consider this trial

Good fit: Adults with a confirmed diagnosis of Bipolar I disorder who are currently hospitalized for an acute manic episode or mania with mixed features, meet the YMRS and CGI-BP thresholds, and can undergo the required medication washout are the intended participants.

Not a fit: People with a primary non–Bipolar I psychiatric disorder within the past 12 months, those who do not require hospitalization, or those unable to stop other psychotropic medications for the washout period are unlikely to qualify or benefit from this study.

Why it matters

Potential benefit: If successful, KarXT could provide a new treatment option that reduces manic symptoms during acute hospitalization and speeds clinical improvement.

How similar studies have performed: KarXT and other muscarinic receptor–targeting treatments have shown promising results in schizophrenia and psychosis trials, but applying KarXT specifically to bipolar mania is relatively novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria

* Participants must have a primary diagnosis of Bipolar-I disorder established by a comprehensive psychiatric evaluation.
* Participants must be experiencing an acute episode or relapse of mania or mania with mixed features (≤ 3 weeks).
* Participants must require hospitalization for the acute exacerbation or relapse of mania.
* Participants must have all psychotropic medications washed out in no more than 14 days prior to the first dose of the study drug.
* Participants must have a Young Mania Rating Scale (YMRS) score of ≥ 20 at Screening and at Baseline.
* Participants must have a Clinical Global Impressions-Bipolar (CGI-BP) ≥ 4 at Screening and at Baseline.

Exclusion Criteria:

* Participants must not have any primary Diagnostic and Statistical Manual of Mental Disorders (5th Edition, Text Revision) (DSM-5-TR) disorder, other than BP-I with mania or mania with mixed features within 12 months before screening, including BP-I with depression (for previous 3 months only), BP-II disorder, borderline personality disorder, major depressive disorder, and primary psychotic disorder, with the exception of mild anxiety disorders.
* Participants must not have a primary diagnosis of BP-I with rapid cycling (≥ 4 distinct mood episodes in one year).
* Participants must not have a DSM-5-TR diagnosis of moderate to severe substance use disorder (except tobacco use disorder) within the 12 months before screening, or current use as determined by urine toxicology screen or alcohol test.
* Participants must not be at risk for suicidal behavior at screening or the baseline visit as determined by the Investigator's clinical assessment and the Columbia-Suicide Severity Rating Scale (C-SSRS).
* Participants must not have a history of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months.
* Participants must not have a history or high risk of urinary retention, gastric retention, or untreated narrow-angle glaucoma.
* Other protocol-defined Inclusion/Exclusion criteria apply.

Where this trial is running

Bentonville, Arkansas and 62 other locations

+13 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 Bipolar-I Disorder With Mania or Mania With Mixed FeaturesBipolar-IManiaMixed
Last reviewed 2026-06-15 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.