A Study to Assess Efficacy and Safety of Adjunctive KarXT in Subjects With Inadequately Controlled Symptoms of Schizophrenia

Inclusion Criteria:

1. Subject is aged ≥18 to <65 years at the time of randomization

2. Subject is capable of providing signed Informed Consent Form before any studyassessments will be performed

3. Subject has a primary diagnosis of schizophrenia established by a comprehensivepsychiatric evaluation based on the DSM-5 criteria and confirmed by MiniInternational Neuropsychiatric Interview for Schizophrenia and Psychotic DisorderStudies (MINI) version 7.0.2

4. Subject is currently being treated with stable dosing of monotherapy risperidone,paliperidone, aripiprazole, or their LAIs ziprasidone, lurasidone, or cariprazineand has been taking this treatment with the same dosing regimen for at least 8 weeksat the time of Day 1 (Visit 3)

5. The subject has had at least 1 previous inadequate response to above antipsychoticsthat was dosed appropriately (within the label) for at least 6 weeks

6. The subject has not required psychiatric hospitalization, incarceration in prison,acute crisis intervention, or other increase in the level of care due to symptomexacerbation within 8 weeks of Screening and is psychiatrically stable in theopinion of the Investigator

7. To be eligible for randomization, subjects need to have detectable levels ofbackground antipsychotic medication (measured at Visit 1)

8. Positive and Negative Syndrome Scale (PANSS) total score ≥ 70 at Screening andrandomization

9. Clinical Global Impression-Severity (CGI-S) scale with a score ≥ 4 (moderate) atScreening and randomization

10. PANSS Marder Positive symptom factor ≥ 4 on 2 (or more) items (PANSS items,delusions, hallucinations, grandiosity, suspiciousness and persecution, stereotypedthinking, somatic concern, unusual thought content or lack of judgment and insight),at Screening and randomization

11. Subjects with ≤ 20-point decrease in PANSS Total score between Visit 1 and Visit 3

12. Subject is willing and able to visit the clinic in an outpatient setting for thestudy duration, follow instructions, and comply with the protocol requirements

13. Body Mass Index (BMI) must be within 18 to 40 kg/m2 (inclusive of both values)

14. Subject resides in a stable living situation in the opinion of the Investigator

15. Subject has identified a reliable informant/ caregiver willing and able to assistwith study activities as needed throughout the subject's participation in the study.The informant needs to be physically present at the Baseline visit, but can completethe remaining study visits assessments via phone (as needed and as per localregulations). In Bulgaria, the informant needs to physically present at the Baselinevisit and should be physically present at all study visits where the Investigatordetermines that his/her input would be beneficial.

16. Women of childbearing potential (WOCP), or men whose sexual partners are WOCP, mustbe able and willing to use at least 1 highly effective method of contraceptionduring the study and for at least 1 menstrual cycle (e.g., 30 days) after the lastdose of study drug. Sperm donation is not allowed for 30 days after the final doseof the study drug. A female subject is considered to be a WOCP after menarche anduntil she is in a postmenopausal state for 12 months or otherwise permanentlysterile (for which acceptable methods include hysterectomy, bilateral salpingectomy,or bilateral oophorectomy)

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. The subject has a history of moderate to severe substance use disorder (other thannicotine) within the past 12 months

3. A Screening subject with mild substance use disorder within the 12 monthsbefore Screening must be discussed with the Medical Monitor before beingallowed into the study

4. Subjects who test positive for cannabis at Screening may be permitted to enrollin consultation with the Medical Monitor if the subject's pattern of use is notindicative of a moderate to severe substance use disorder

5. Subject has a history of treatment-resistant schizophrenia defined as: a. Failure to minimally respond to 2 adequate courses of antipsychotic drug (APD)pharmacotherapy Note: Failure to minimally respond is defined as persistencesymptoms of moderate severity in 2 or more psychotic symptom domains or persistenceof severe symptoms in 1 or more psychotic symptom domains despite adequate dose andduration (6 weeks or longer) of APD treatment.

6. History of symptom instability a. > 3 psychiatric hospitalizations over the last 12 months or 2 over the last 6months

7. Current APD is other than aripiprazole, risperidone, paliperidone, or their LAIversions, ziprasidone, lurasidone, or cariprazine

8. Subjects who are diagnosed with schizophreniform disorder or are experiencing theirfirst treated episode of schizophrenia

9. Significant or severe medical conditions including pulmonary, cardiovascular,hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic,neurologic, or oncologic disease or any other condition that, in the opinion of theInvestigator, could jeopardize the safety of the subject or the validity of thestudy results

10. eGFR < 60 mL/min

11. Alanine transaminase or aspartate transaminase (AST) > 1.5 x upper limit ofnormal (ULN)

12. Total bilirubin > 1.5 x ULN (Subjects with Gilbert's syndrome can be includedas long as direct bilirubin is ≤ 1.5 x ULN)

13. Subjects with human immunodeficiency virus (HIV), cirrhosis, biliary ductabnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections asindicated by medical history, serologies or LFT results

14. History or high risk of urinary retention, gastric retention, or narrow-angleglaucoma as evaluated by the Investigator

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

16. Risk for suicidal behavior during the study as determined by the Investigator'sclinical assessment and/or C-SSRS as confirmed by the following:

17. Answers "Yes" on items 4 or 5 (C-SSRS - ideation) with the most recent episodeoccurring within the 2 months before Screening or,

18. Answers "Yes" to any of the 5 items (C-SSRS behavior) with an episode occurringwithin the 12 months before Screening

19. Clinically significant abnormal finding on the physical examination, medicalhistory, ECG, or clinical laboratory results at Screening

20. Urine toxicology screen is positive for phencyclidine, amphetamines, opiates,cocaine, or alcohol (clinically significant alcohol use in the opinion of theInvestigator)

21. Subject is currently taking, or plans to take while in the study, any prohibitedconcomitant medication.

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

23. If, in the opinion of the Investigator and/or Sponsor/Medical Monitor subject isunsuitable for enrollment in the study or subject has any finding that, in the viewof the Investigator and/or Sponsor/Medical Monitor, may compromise the safety of thesubject or affect his/her ability to adhere to the protocol visit schedule orfulfill visit requirements

24. Positive test for coronavirus (COVID-19) within 2 weeks or at Screening

25. Subjects with extreme concerns relating to global pandemics, such as COVID-19, thatwould obscure ratings or be expected to disrupt adherence to trial procedures

26. Unable to taper and discontinue a concomitant medication that would precludeparticipation in the double-blind adjunctive treatment (e.g., cannot stopanticholinergic)

27. Subjects with prior exposure to KarXT

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

29. Subjects who received investigational product as part of a clinical trial within 3months of Screening

30. Risk of violent or destructive behavior as per Investigator's judgment that wouldinterfere with subject's participation

31. Current involuntary hospitalization or incarcerationor on parole/probation

32. For all male subjects only, any one of the following:

33. History of bladder stones

34. History of recurrent urinary tract infections

35. Serum prostate specific antigen (PSA) >10 ng/mL

36. An International Prostate Symptom Score (IPSS) of 5 (almost always) on eitheritem 1, 3, 5, or 6

37. A sum of scores on IPSS items 1, 3, 5, and 6 of ≥9 Note: IPSS will be requiredonly for male subjects ≥ 45 years of age. Subjects already enrolled in thestudy will have these assessments at their next clinic visit planned afterre-consenting to determine current eligibility.