A Study to Assess the Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Chinese Adult Subjects With DSM-5 Schizophrenia

Inclusion Criteria:

1. Subject is Chinese national, aged 18 to 65 years, inclusive, at screening.

2. Subject is capable of providing written informed consent.

3. Subject has a primary diagnosis of schizophrenia established by a comprehensivepsychiatric evaluation based on the DSM-5 and MINI.

4. Subject is experiencing an acute exacerbation or relapse of psychotic symptoms, withonset less than 2 months before screening.

5. The subject requires hospitalization for this acute exacerbation or relapse ofpsychotic symptoms at screen.

6. If already an inpatient at screening, hospitalization has to be ≤2 weeks forthe current exacerbation at the time of screening.

7. PANSS total score between 80 and 120,inclusive, with a scores of ≥4 (moderate orgreater) for ≥2 of the following Positive Scale (P) items:

8. Item 1 (P1; delusions)

9. Item 2 (P2; conceptual disorganization)

10. Item 3 (P3; hallucinatory behavior)

11. Item 6 (P6; suspiciousness/persecution)

12. Subjects with no change (improvement) in PANSS total score between screening andbaseline (Day -1) of more than 20%.

13. Subject has a CGI-S score of ≥4 at screening and baseline (Day -1) visits.

14. Subject will have been off lithium therapy for at least 2 weeks before baseline andfree of all oral antipsychotic medications for at least 5 half-lives or 1 week,whichever is longer, before baseline (Day -1).

15. Subjects taking a long-acting injectable antipsychotic could not have received adose of medication for at least 12 weeks (24 weeks for INVEGA TRINZA®) beforebaseline visit (Day -1).

16. Subject is able to be confined to an inpatient setting for the duration of the 5-week double-blind part of the study, follow instructions, and comply with theprotocol requirements.

17. Body mass index of 18 to 40 kg/m2, inclusive.

18. Subject resides in a stable living situation and is anticipated to return to thatsame stable living situation after discharge, in the opinion of the investigator.

19. Subject has an identified reliable informant. An informant is needed at thescreening and baseline visits as well as at the end of the study for relevantassessments (site staff may act as informant while the subject is an inpatient). Aninformant may not be necessary if the subject has been a patient of the investigatorfor ≥1 year.

20. Women of childbearing potential (WOCBP) or men whose sexual partners are WOCBP mustbe willing and able to adhere to the contraception guidelines.

Exclusion Criteria:

1. Any primary DSM-5 disorder other than schizophrenia within 12 months beforescreening (confirmed using MINI version 7.0.2 at screening).

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

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 theinvestigator, would jeopardize the safety of the subject or the validity of thestudy results.

4. Subjects with human immunodeficiency virus (HIV), cirrhosis, biliary ductabnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections basedon either medical history or liver function test results.

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

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

7. Risk for suicidal behavior during the study as determined by the investigator'sclinical assessment and C-SSRS.

8. Clinically significant abnormal findings on the physical examination, medicalhistory, electrocardiogram, or clinical laboratory results at screening that, in theopinion of the investigator, would jeopardize the safety of the subject or thevalidity of the study results.

9. Subjects are receiving or have recently received (within 5 half-lives or 1 week,whichever is longer, before baseline [Day -1]) oral antipsychotic medications;monoamine oxidase inhibitors; anticonvulsants (e.g., lamotrigine, valproate);tricyclic antidepressants (e.g., imipramine, desipramine); selective serotoninreuptake inhibitors; or any other psychoactive medications except for as-neededanxiolytics (e.g., lorazepam, chloral hydrate).

10. Subjects are receiving or have recently received (within 1 week before baseline [Day -1]) metformin.

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

12. In the opinion of the investigator and/or Sponsor, subject is unsuitable forenrollment in the study or subject has any finding that, in the view of theinvestigator and/or Sponsor, may compromise the safety of the subject or affecthis/her ability to adhere to the protocol visit schedule or fulfill visitrequirements.

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

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

15. Subjects with prior exposure to KarXT.

16. Subjects who experienced any significant adverse effects due to trospium chloride.

17. Participation in another clinical study within 3 months before screening in whichthe subject received an experimental or investigational drug agent.

18. Significant risk of violent or destructive behavior.