A Study to Evaluate the Efficacy and Safety of Adjunctive KarXT for the Treatment of Mania, With or Without Mixed Features, in Participants With Bipolar-I Disorder Taking Lithium, Valproate, or Lamotrigine

Inclusion Criteria:

• Individuals have a primary diagnosis of Bipolar-I disorder established by acomprehensive psychiatric evaluation based on the DSM-5-TR criteria and confirmed bythe Mini International Neuropsychiatric Interview (MINI) version 7.0.2.

• Individual is experiencing an acute exacerbation or relapse of manic episode, withor without mixed features (≤ 3 weeks).

• The individual requires hospitalization for the acute exacerbation or relapse ofmania.

• Body mass index ≥ 18 and ≤ 40 kg/m2.

• Currently experiencing an acute episode of mania or mania with mixed features with atherapeutic dose of lithium, valproate, or lamotrigine. The dose of the moodstabilizer must have remained stable for at least two weeks prior to screening.Additionally, participants on valproate must have been receiving treatment withvalproate for a minimum of seven months.

• YMRS Total Score of ≥ 18 at Screening and at Baseline, and < 20% reduction in YMRSfrom 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 (forprevious 3 months only), BP-I with rapid cycling, first manic episode, BP-II,primary psychotic disorder, borderline personality disorder, and major depressivedisorder, 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 usingMINI version 7.0.2 at screening), or current use as determined by urine toxicologyscreen or alcohol test.

• Risk for suicidal behavior at screening as determined by the investigator's clinicalassessment and the C-SSRS with an answer "Yes" to item 4 or 5 within 6 months beforescreening or between screening and baseline, or "Yes" to any of the 5 items (C-SSRSbehavior) with an event occurring within the 12 months before screening, or betweenscreening and baseline.

• History of irritable bowel syndrome (with or without constipation) or any seriousconstipation requiring treatment within the last 6 months.

• History or high risk of urinary retention, gastric retention, or narrow-angleglaucoma.

• Participants with HIV, cirrhosis, biliary duct abnormalities, hepatobiliarycarcinoma, and/or active hepatic viral infections based on either medical history orthe LFT results.

• Elevations in hepatic transaminases at screening ≥ 2 × ULN for ALT or AST and/orbilirubin > 1.5× ULN, unless in the context of Gilbert's syndrome.

• All grades of hepatic impairment (mild [Child-Pugh Class A], moderate [Child-PughClass B], and severe [Child-Pugh Class C]).

• Other protocol-defined Inclusion/Exclusion criteria apply.