A Study to Assess Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Adult Patients With Schizophrenia (EMERGENT-3)

1. Any primary DSM-5 disorder other than schizophrenia within 12 months before screening (confirmed using MINI version 7.0.2 at screening). Symptoms of mild mood dysphoria or anxiety are allowed as long as these symptoms are not the primary focus of treatment. A screening subject with mild substance abuse disorder within the 12 months before screening must be discussed and agreed upon with the medical monitor before they can be allowed into the study.

2. Subjects who are newly diagnosed or are experiencing their first treated episode of schizophrenia.

3. History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the investigator, would jeopardize the safety of the subject or the validity of the study results.

4. Subjects with HIV, cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections based on either medical history or liver function test results.

5. History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma.

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

7. Risk for suicidal behavior during the study as determined by the investigator's clinical assessment and Columbia-Suicide Severity Rating Scale (C-SSRS).

8. Clinically significant abnormal finding on the physical examination, medical history, ECG, or clinical laboratory results at screening.

9. Subjects cannot currently (within 5 half-lives or 1 week, whichever is longer, before baseline \[Day -1\]) be receiving oral antipsychotic medications; monoamine oxidase inhibitors; anticonvulsants (eg, lamotrigine, Depakote); tricyclic antidepressants (eg, imipramine, desipramine); selective serotonin reuptake inhibitors; or any other psychoactive medications except for as needed anxiolytics (eg, lorazepam, chloral hydrate).

10. Pregnant, lactating, or less than 3 months postpartum.

11. If, in the opinion of the investigator (and/or Sponsor), subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the investigator (and/or Sponsor), may compromise the safety of the subject or affect his/her ability to adhere to the protocol visit schedule or fulfill visit requirements.

12. Positive test for coronavirus (COVID-19) within 2 weeks before screening and at screening.

13. Subjects with extreme concerns relating to global pandemics, such as COVID-19, that preclude study participation.

14. Subject has had psychiatric hospitalization(s) for more than 30 days (cumulative) during the 90 days before screening.

15. Subject has a history of treatment resistance to schizophrenia medications defined as failure to respond to 2 adequate courses of pharmacotherapy (a minimum of 4 weeks at an adequate dose per the label) or required clozapine within the last 12 months.

16. Subjects with prior exposure to KarXT.

17. Subjects who experienced any adverse effects due to xanomeline or trospium.

18. Participation in another clinical study in which the subject received an experimental or investigational drug agent within 3 months before screening.

19. Risk of violent or destructive behavior.

20. Current involuntary hospitalization or incarceration.

What this study is about