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

Inclusion Criteria:

• Participants who participated in double-blind placebo-controlled study (CN0120036 orCN0120037): a. Participants must have completed treatment period of parent study.

• De novo participants who did not participate in double-blind placebo-controlledstudies:

1. Participants must have primary diagnosis of Bipolar-I disorder established by acomprehensive psychiatric evaluation based on DSM-5-TR criteria and confirmedby the Mini International Neuropsychiatric Interview (MINI, v7.0.2), withsymptoms of mania or mixed mania.

2. Participants must have Young Mania Rating Scale (YMRS) score of ≥ 14 atScreening 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 orCN0120037): a. Discontinuation from any KarXT parent studies.

• De novo participants who did not participate in double-blind placebo-controlledstudies:

1. All participants with a risk for suicidal behavior at baseline as determined byInvestigator's clinical assessment or history of suicidal behavior as assessedon 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 withmania or mania with mixed features within 12 months before Screening (confirmedusing MINI version 7.0.2 at Screening), including BP-I with depression, (previous 3 months only), Bipolar-II disorder, major depressive disorder, andprimary psychotic disorder, with the exception of mild anxiety disorders.

4. Individual has a DSM-5-TR diagnosis of moderate to severe substance usedisorder (except tobacco use disorder) within the 12 months before Screening (confirmed using MINI version 7.0.2 at Screening), or current use as determinedby urine toxicology screen or alcohol test.

5. Participants must not have history of irritable bowel syndrome (with or withoutconstipation) or serious constipation requiring treatment within the last 6months.

6. Participants must not have history or high risk of urinary retention, gastricretention, or untreated narrow-angle glaucoma.

7. Other protocol-defined Inclusion/Exclusion criteria apply.