A Study to Assess the Long-term Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-3)

• KarXT (Drug), also known as BMS-986510, Xanomeline and trospium chloride: Specified dose on specified days
• Lithium (Drug): Therapeutic dose
• Valproate (Drug): Therapeutic dose
• Lamotrigine (Drug): Therapeutic dose

Primary outcomes

• Number of participants with treatment emergent adverse events (TEAEs) [Up to week 54]

Secondary outcomes

• Number of participants with AEs of special interest (AESIs) [Up to week 54]
• Number of participants with serious AEs (SAEs) [Up to week 54]
• Number of participants with TEAEs leading to treatment discontinuation [Up to week 52]
• Number of participants with change in suicidal ideation as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) [Up to week 54]
• Change from baseline in Barnes Akathisia Rating Scale (BARS) score [Up to week 54]
• Change from baseline in Simpson Angus Scale (SAS) score [Up to week 54]
• Change from baseline in Abnormal Involuntary Movement Scale (AIMS) score [Up to week 54]
• Change from baseline in International Prostate Symptom Score (IPSS) [Up to week 54]: Only for males ≥ 45 years of age

Sex: All, ages: 18 Years to 65 Years

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:

* All participants:

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

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

  1. Participants must not have primary diagnosis of BP-I with rapid cycling (ie, ≥ 4 distinct mood episodes in one year).
  2. 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.
  3. 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.
  4. Participants must not have history of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months.
  5. Participants must not have history or high risk of urinary retention, gastric retention, or untreated narrow-angle glaucoma.
* Other protocol-defined Inclusion/Exclusion criteria apply.

82 more sites not listed.

• Bristol-Myers Squibb, Study director, Bristol-Myers Squibb