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KarXT for treating manic episodes in bipolar I disorder (BALSAM-2)

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-2)

Phase 3 Interventional Bristol-Myers Squibb · NCT06951711

This trial tests whether KarXT helps adults hospitalized for an acute manic episode of bipolar I disorder (including mixed features) compared with placebo during a 3-week inpatient treatment.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment274 (estimated)
Ages18 Years to 65 Years
SexAll
SponsorBristol-Myers Squibb Industry-sponsored
Locations74 sites (Little Rock, Arkansas and 73 other locations)
Trial IDNCT06951711 on ClinicalTrials.gov

What this trial studies

BALSAM-2 is a Phase 3, randomized, double-blind, placebo-controlled, multicenter inpatient trial comparing KarXT to placebo in adults hospitalized for acute mania or mania with mixed features. Participants must have a primary diagnosis of bipolar I disorder, a YMRS score ≥20 and CGI-BP ≥4, require hospitalization, and undergo washout of other psychotropic medications before dosing. The core double-blind inpatient treatment period lasts up to three weeks, and total participation including screening and safety follow-up is no more than seven weeks. Standard mania rating scales and safety monitoring are used to measure symptom change and tolerability.

Who should consider this trial

Good fit: Adults with a primary diagnosis of bipolar I disorder who are currently hospitalized for an acute manic episode or mania with mixed features, have YMRS ≥20 and CGI-BP ≥4, and can complete medication washout are the intended participants.

Not a fit: Patients with a different primary DSM-5-TR psychiatric disorder within the past year, those not requiring hospitalization, or those with prolonged (>3 weeks) mania or significant medical contraindications are unlikely to benefit from joining this trial.

Why it matters

Potential benefit: If successful, KarXT could offer a new oral option that reduces mania symptoms and may shorten hospital stays compared with current treatments.

How similar studies have performed: KarXT has shown promising results in earlier trials for psychotic symptoms in schizophrenia and related conditions, but its use specifically for acute bipolar mania is novel and not yet established.

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 cirrhosis, liver cancer, clinically significant liver disease based on the liver function test results.
* Other protocol-defined Inclusion/Exclusion criteria apply.

Where this trial is running

Little Rock, Arkansas and 73 other locations

+24 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 Disorder Type I With Mania or Mania With Mixed FeaturesBipolar-I disorderManiaBipolar-I disorder with Mania
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.