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Long-term KarXT safety for manic episodes in bipolar I (BALSAM-3)

A Phase 3, Open-label Extension Study to Assess the Long-term Safety of KarXT for the Treatment of Mania or Mania With Mixed Features in Bipolar-I Disorder (BALSAM-3)

Phase 3 Interventional Bristol-Myers Squibb · NCT06929273

This open-label phase 3 study will test whether long-term KarXT is safe and tolerable for adults with bipolar I disorder experiencing mania or mixed mania.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment450 (estimated)
Ages18 Years to 65 Years
SexAll
SponsorBristol-Myers Squibb Industry-sponsored
Locations172 sites (Glendale, Arizona and 171 other locations)
Trial IDNCT06929273 on ClinicalTrials.gov

What this trial studies

BALSAM-3 is an open-label, phase 3 extension that enrolls participants who completed prior double-blind KarXT parent studies as well as new participants meeting DSM-5-TR criteria for bipolar I with mania or mixed features. Participants receive KarXT, with concomitant mood stabilizers such as lithium, valproate, or lamotrigine allowed per protocol, and are followed long-term for safety and tolerability outcomes. De novo enrollees must have a confirmed diagnosis via the MINI and meet symptom thresholds (YMRS ≥14 and CGI-BP ≥3) while not requiring hospitalization for acute mania. Safety monitoring includes regular clinical assessments and adverse event reporting across U.S. sites in Arizona and Arkansas.

Who should consider this trial

Good fit: Ideal candidates are adults with bipolar I disorder experiencing mania or mixed mania who either completed a parent KarXT study or meet screening thresholds (YMRS ≥14 and CGI-BP ≥3) and do not require hospitalization.

Not a fit: Patients who previously discontinued KarXT in a parent study, who require hospitalization for acute mania, or who meet other protocol exclusion criteria are unlikely to benefit from enrolling.

Why it matters

Potential benefit: If long-term safety is demonstrated, KarXT could provide an additional treatment option that helps manage manic episodes with an acceptable tolerability profile.

How similar studies have performed: Earlier double-blind, placebo-controlled parent studies of KarXT have been conducted, and this open-label extension builds on those results to examine long-term safety.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Participants who participated in double-blind placebo-controlled study (CN0120036, CN0120037, or CN0120046):

  a. Participants must have completed treatment period of parent study.
* De novo participants who did not participate in double-blind placebo-controlled studies:

  1. Participants must have primary diagnosis of Bipolar-I disorder established by a comprehensive psychiatric evaluation based on DSM-5-TR criteria and confirmed by the Mini International Neuropsychiatric Interview (MINI, v7.0.2), with symptoms of mania or mixed mania.
  2. Participants must have Young Mania Rating Scale (YMRS) score of ≥ 14 at Screening and at baseline.
  3. Participants must have CGI-BP score of ≥ 3 at Screening and at baseline.
  4. Participants does not require hospitalization for acute mania.

Exclusion Criteria:

* Participants who participated in double-blind placebo-controlled study (CN0120036, CN0120037, or CN0120046):

  a. Discontinuation from any KarXT parent studies.
* De novo participants who did not participate in double-blind placebo-controlled studies:

  1. All participants with a risk for suicidal behavior at baseline as determined by Investigator's clinical assessment or history of suicidal behavior as assessed on C-SSRS.
  2. Participants must not have primary diagnosis of BP-I with rapid cycling (ie, ≥ 4 distinct mood episodes in one year).
  3. Participants must not have any primary DSM-5-TR disorder other than BP-I with mania or mania with mixed features within 12 months before Screening (confirmed using MINI version 7.0.2 at Screening), including BP-I with depression, (previous 3 months only), Bipolar-II disorder, major depressive disorder, borderline personality disorder, and primary psychotic disorder, with the exception of mild anxiety disorders.
  4. 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.
  5. Participants must not have history of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months.
  6. Participants must not have history or high risk of urinary retention, gastric retention, or untreated narrow-angle glaucoma.
  7. Other protocol-defined Inclusion/Exclusion criteria apply.

Where this trial is running

Glendale, Arizona and 171 other locations

+122 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 ManiaBipolar-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.