An 8-week Open-label Study of an Accelerated and Slower Switching to Xanomeline/Trospium Following Atypical Antipsychotic Treatment in Participants With Schizophrenia

Exclusion Criteria

• •1. Any primary DSM-5 disorder other than schizophrenia within 6 months before Screening (confirmed using MINI version 7.0.2 at Screening). Exclusionary disorders include, but are not limited to, major depressive disorder, bipolar I or II disorder, schizoaffective disorder, obsessive compulsive disorder, and posttraumatic stress disorder. Symptoms of mild mood dysphoria or anxiety are allowed as long as these symptoms are not the primary focus of treatment.
• •2. Participant has a history of moderate to severe alcohol use disorder or a substance (other than nicotine or caffeine) use disorder within the past 6 months or a positive urine drug screen (UDS) for a substance other than cannabis at Screening or Baseline.
• •1. Participants with mild substance use disorder within the 6 months before Screening must be discussed and agreed upon with the Principal Investigator (PI) before they can be allowed into the study.
• •2. Participants with positive UDS for cannabis are permitted to enroll in the study provided that the participants' pattern of use is not indicative of a substance use disorder.
• •3. Urine toxicology screen positive for phencyclidine, amphetamines, opiates, cocaine, or alcohol (clinically significant alcohol use in the opinion of the Investigator).
• •3. History or presence of clinically significant cardiovascular (e.g., untreated or unstable hypertension, clinically significant tachycardia), pulmonary, renal, hematologic, gastrointestinal (GI, e.g., obstructive disorders \[including conditions that may decrease GI motility, such as ulcerative colitis, intestinal atony, and myasthenia gravis\], endocrine, immunologic, dermatologic, neurologic, or oncologic 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.
• •4. Participant with cirrhosis, biliary duct abnormalities, and/or hepatobiliary carcinoma based on either medical history or liver function test results.
• •5. All grades of hepatic impairment (mild \[Child-Pugh Class A\], moderate \[Child-Pugh Class B\], and severe \[Child-Pugh Class C\]).
• •6. History or high risk of urinary retention or gastric retention.
• •7. History of narrow-angle glaucoma.
• •8. History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months.
• •9. Risk for suicidal behavior during the study as determined by the Investigator's clinical assessment. Non-suicidal self-injurious behavior is not exclusionary.
• •10. Clinically significant abnormal finding on the physical examination, medical history, or clinical laboratory results at Screening.
• •11. An eGFR of \< 60 mL/min
• •12. Elevations in hepatic transaminases at screening ≥3× ULN for ALT and AST and/or bilirubin \> 2× ULN, unless in the context of Gilbert's syndrome
• •13. History of unstable hypertension or tachycardia as evidenced by:
• •1. Blood pressure of ≥160/100 mmHg (single seated measure) at screening
• •2. Heart rate of ≥110 bpm (single seated measure) at Screening
• •14. Participant is receiving other psychotropic medications for psychiatric and neurological conditions with Anticholinergic Risk Scale (ARS) scores \>1 (tricyclic antidepressants, paroxetine, antispasmodics, antihistamines with anticholinergic properties).
• •15. History of treatment resistance to schizophrenia medications defined as:
• •1. Failure to respond to 2 adequate courses of pharmacotherapy (a minimum of 4 weeks at an adequate dose per the label) within the past 12 months OR
• •2. Has a history of having received clozapine
• •16. Participant is receiving a long-acting injectable AP.
• •17. Developmental disorder, intellectual disability, or autism spectrum disorder (by history), with the exception of participants diagnosed with autism at age \<18 due to historic diagnostic criteria precluding schizophrenia diagnoses of minors (at discretion of Investigator).
• •18. Lifetime history of clinically significant head trauma.
• •19. Pregnant, breastfeeding, or less than 3 months postpartum.
• •20. Active biliary disease (e.g., symptomatic gallstones). Participants with other biliary histories are eligible and should be discussed with the Medical Monitor.
• •21. Participants with any of the following:
• •1. History of bladder stones
• •2. History of recurrent urinary tract infections
• •3. For male participants, serum prostate-specific antigen \>10 ng/mL at Screening
• •4. For male participants ≥45 years of age, International Prostate Symptom Score (IPSS) of 5 (i.e., "almost always") on items 1, 3, 5, or 6
• •5. For male participants ≥45 years of age, an IPSS ≥9 for the sum of items 1, 3, 5, and 6
• •22. In the opinion of the Investigator (and/or Sponsor), participant is unsuitable for enrollment in the study, or participant has any finding that, in the opinion of the Investigator (and/or Sponsor), may compromise the safety of the participant or affect their ability to adhere to the protocol visit schedule or fulfill visit requirements.
• •23. Participant has had psychiatric hospitalization(s) for more than 30 days (cumulative) within the 12 months before Screening.
• •24. Participant with prior exposure to X/T or who has a history of prior X/T intolerability (allergy/hypersensitivity).
• •25. Risk of violent or destructive behavior in the opinion of the Investigator.
• •26. Current involuntary hospitalization or incarceration.
• •27. Participation in another clinical study in which the participant received an experimental or investigational drug agent within 3 months prior to Screening.