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

Inclusion Criteria

• Subject is aged ≥18 to 3 psychiatric hospitalizations over the last 12 months or 2 over the last 6 months
• Current APD is other than aripiprazole, risperidone, paliperidone, or their LAI versions, ziprasidone, lurasidone, or cariprazine
• Subjects who are diagnosed with schizophreniform disorder or are experiencing their first treated episode of schizophrenia
• 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 the Investigator, could jeopardize the safety of the subject or the validity of the study results
• eGFR 1.5 x upper limit of normal (ULN)
• Total bilirubin > 1.5 x ULN (Subjects with Gilbert's syndrome can be included as long as direct bilirubin is ≤ 1.5 x ULN)
• Subjects with human immunodeficiency virus (HIV), cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections as indicated by medical history, serologies or LFT results
• History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma as evaluated by the Investigator
• History of irritable bowel syndrome (with or without constipation) or any serious constipation requiring treatment within the last 6 months
• Risk for suicidal behavior during the study as determined by the Investigator's clinical assessment and/or C-SSRS as confirmed by the following:
• Answers "Yes" on items 4 or 5 (C-SSRS - ideation) with the most recent episode occurring within the 2 months before Screening or,
• Answers "Yes" to any of the 5 items (C-SSRS behavior) with an episode occurring within the 12 months before Screening
• Clinically significant abnormal finding on the physical examination, medical history, ECG, or clinical laboratory results at Screening
• Urine toxicology screen is positive for phencyclidine, amphetamines, opiates, cocaine, or alcohol (clinically significant alcohol use in the opinion of the Investigator)
• Subject is currently taking, or plans to take while in the study, any prohibited concomitant medication.
• Pregnant, lactating, or less than 3 months postpartum
• If, in the opinion of the Investigator and/or Sponsor/Medical Monitor subject is unsuitable for enrollment in the study or subject has any finding that, in the view of the Investigator and/or Sponsor/Medical Monitor, may compromise the safety of the subject or affect his/her ability to adhere to the protocol visit schedule or fulfill visit requirements
• Positive test for coronavirus (COVID-19) within 2 weeks or at Screening
• Subjects with extreme concerns relating to global pandemics, such as COVID-19, that would obscure ratings or be expected to disrupt adherence to trial procedures
• Unable to taper and discontinue a concomitant medication that would preclude participation in the double-blind adjunctive treatment (e.g., cannot stop anticholinergic)
• Subjects with prior exposure to KarXT
• Subjects who experienced any adverse effects due to xanomeline or trospium
• Subjects who received investigational product as part of a clinical trial within 3 months of Screening
• Risk of violent or destructive behavior as per Investigator's judgment that would interfere with subject's participation
• Current involuntary hospitalization or incarcerationor on parole/probation
• For all male subjects only, any one of the following:
• History of bladder stones
• History of recurrent urinary tract infections
• Serum prostate specific antigen (PSA) >10 ng/mL
• An International Prostate Symptom Score (IPSS) of 5 (almost always) on either item 1, 3, 5, or 6
• A sum of scores on IPSS items 1, 3, 5, and 6 of ≥9 Note: IPSS will be required only for male subjects ≥ 45 years of age. Subjects already enrolled in the study will have these assessments at their next clinic visit planned after re-conse