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

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.

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

What this study is about

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

What this study is about