An Open-Label Study to Evaluate the Efficacy and Tolerability of Xanomeline/Trospium In First Episode/Early Phase Schizophrenia Patients

Inclusion Criteria:

1. Participant is aged 18-40 years, inclusive, at time of signing the ICF

2. Participant has a primary diagnosis of schizophrenia established by a comprehensivepsychiatric evaluation based on the DSM-5 (American Psychiatric Association 2013)criteria and confirmed by Mini International Neuropsychiatric Interview forSchizophrenia and Psychotic Disorder Studies (MINI) version 7.0.2.

3. Participant Scores MSQ ≤3 for the Medication Satisfaction Questionnaire (MSQ)

4. Within 5 years of first antipsychotic treatment for psychosis at time of signing ICF

5. Clinical reason to seek a change in antipsychotic treatment due to psychosis symptomseverity, it is clinically appropriate for the participant to seek a change inantipsychotic treatment due to psychosis symptom severity, adverse effects, both, oroverall patient judgement/choice.

6. Symptom Severity Criteria:

7. Clinical reasons include Positive and Negative Syndrome Scale (PANSS) totalscore of ≤ 120 at screening if participant is experiencing inefficacy fromcurrent antipsychotic treatment and

8. A score of ≥ 4 (moderate or greater) for ≥ 1 of the following PANSS PositiveSubscale (P) items: i. Item 1 (P1; delusions), ii. Item 2 (P2; conceptualdisorganization), iii. Item 3 (P3; hallucinatory behavior), iv. Item 6 (P6;suspiciousness/persecution) and

9. A Clinical Global Impressions-Severity scale (CGI-S) score of ≥ 4 at screeningand baseline visits. OR

10. Adverse Event or Overall Patient Choice Criteria:

11. A score of <4 for all the following PANSS Positive Subscale (P) items: i. Item 1 (P1; delusions), ii. Item 2 (P2; conceptual disorganization), iii. Item 3 (P3; hallucinatory behavior), iv. Item 6 (P6; suspiciousness/persecution)

12. Participant Scores MSQ ≤3 for the Medication Satisfaction Questionnaire (MSQ)Clinical reason to seek a change in antipsychotic treatment due to adverseeffects or overall patient judgement/choice.

13. Upon screening, the treatment plan is for outpatient level of care. Transition toinpatient level of care after enrollment does not exclude the patient fromparticipating in the study

14. Participant is taking an antipsychotic (AP) and the AP regimen has been stable forat least 8 weeks with at least the last 4 weeks on the same dose (i.e., untreatedpatients or patients receiving antipsychotic polypharmacy are excluded) prior toScreening. Participants are permitted to remain on non-prohibited (see, ExclusionCriterion, and Section 9) psychotropic medications (that are not secondary APtreatments) other than the primary pre-switch AP that have been part of theirongoing treatment regimen. a. Anticholinergic drugs (e.g., benztropine) are allowed at baseline but need to bewashed out during cross titration within 1 week after initiatingxanomeline/trospium.

15. Subject can provide informed consent. A signed informed consent form must beprovided before any study assessments are performed. Subject must be fluent (oraland written) in English to consent. Female participants must be willing and capableto use birth control throughout the time of the trial as defined in Section 3.1.3

Exclusion Criteria:

1. Any DSM-5 disorder other than schizophrenia within 6 months before screening (confirmed using MINI version 7.0.2 at screening) requiring clinical attention.

2. Active substance or alcohol abuse or dependence in the past 6 months (cannabis useis allowed if not fulfilling abuse criteria)

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

4. Developmental disorder or intellectual disability

5. History of serious suicide attempt within the past 6 months

6. Risk of suicidal behavior as determined by the Investigator's clinical assessment.Lifetime history of clinically significant head trauma, or current history of otheracute or serious medical condition or

7. History or presence of clinically significant cardiovascular (eg, untreated orunstable hypertension, clinically significant tachycardia), pulmonary, renal,hematologic, gastrointestinal ([GI] e.g., obstructive disorders [includingconditions that may decrease GI motility, such as ulcerative colitis, intestinalatony, and myasthenia gravis], endocrine, immunologic, dermatologic, neurologic, oroncologic disease or any other condition that, in the opinion of the investigator,would jeopardize the safety of the participant or the validity of the study results.

8. Active biliary disease (eg, symptomatic gallstones). Participants with other biliaryhistories are eligible and should be discussed with the medical monitor

9. History or high risk of urinary retention, gastric retention,

10. Untreated narrow-angle glaucoma

11. An estimated glomerular filtration rate (eGFR) of < 60 mL/min at the screeningvisit.

12. Elevations in hepatic transaminases at screening ≥ 3× ULN for ALT and AST and/or ≥ 2× ULN for total bilirubin

13. History of hypersensitivity or prior exposure to xanomeline/trospium or trospiumchloride

14. History of any significant drug allergy (such as anaphylaxis or hepatotoxicity).

15. Intellectual disability or autism spectrum disorder (by history)

16. Active substance dependence within the past 3 months (except for tobacco andcannabis)

17. Participant has a history of treatment resistance to schizophrenia medicationsdefined as failure to respond to 2 adequate courses of pharmacotherapy (a minimum of 6 weeks at an adequate dose per the label), based on TRIPP guidelines (Howes, et al 2017).

18. Participant is on or has history of clozapine treatment

19. Participant is on≥ 2 antipsychotics at baseline

20. Participant has received a long-acting injectable antipsychotic within one injectioncycle for that formulation at the time of baseline (i.e., cycles are defined by theinterval in which the LAI is administered. If it is a monthly administration, thenthe exclusion is for one month since the last LAI administration).

21. Participant is receiving other psychotropic medications other than the antipsychoticto be switched, for psychiatric and neurological drugs with Anticholinergic RiskScale (ARS) scores >1 (tricyclic antidepressants, paroxetine, antispasmodics,antihistamines with anticholinergic properties).

22. Active biliary disease (eg, symptomatic gallstones). Participants with other biliaryhistories are eligible and should be discussed with the medical monitor

23. Pregnancy, breastfeeding or less than 3 months postpartum or intent to get pregnantwithin the next 6 months

24. Participants with any of the following:

25. history of bladder stones

26. history of recurrent urinary tract infections

27. History of unstable hypertension or tachycardia as evidenced by:

28. Blood pressure of ≥ 160/100 mmHg (seated measures) at screening

29. Heart rate of ≥ 110 bpm (seated measures) at screening

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

31. Current participation in another clinical trial, or participation in anotherclinical study in which the participant received an experimental or investigationaldrug agent within 3 months prior to screening