A Study to Assess Efficacy and Safety of KarXT in Acutely Psychotic Hospitalized Adult Patients With Schizophrenia (EMERGENT-2)

Inclusion Criteria

• Subject is aged 18 to 65 years, inclusive, at screening.
• Subject is capable of providing informed consent.
• A signed informed consent form must be provided before any study assessments are performed.
• Subject must be fluent (oral and written) in English to consent
• Subject has a primary diagnosis of schizophrenia established by a comprehensive psychiatric evaluation based on the DSM-5 criteria and confirmed by Mini International Neuropsychiatric Interview for Schizophrenia and Psychotic Disorder Studies (MINI) version 7.0.2.
• Subject is experiencing an acute exacerbation or relapse of psychotic symptoms, with onset less than 2 months before screening.
• The subject requires hospitalization for this acute exacerbation or relapse of psychotic symptoms.
• If already an inpatient at screening, has been hospitalized for less than 2 weeks for the current exacerbation at the time of screening.
• Positive and Negative Syndrome Scale total score between 80 and 120, inclusive. Score of ≥4 (moderate or greater) for ≥2 of the following Positive Scale (P) items:
• Item 1 (P1; delusions)
• Item 2 (P2; conceptual disorganization)
• Item 3 (P3; hallucinatory behavior)
• Item 6 (P6; suspiciousness/persecution)
• Subjects with no change (improvement) in PANSS total score between screening and baseline (Day -1) of more than 20%.
• Subject has a CGI-S score of ≥4 at screening and baseline (Day -1) visits.
• Subject will have been off lithium therapy for at least 2 weeks before baseline and free of all oral antipsychotic medications for at least 5 half-lives or 1 week, whichever is longer, before baseline (Day -1).
• Subjects taking a long-acting injectable antipsychotic could not have received a dose of medication for at least 12 weeks (24 weeks for INVEGA TRINZA) before baseline visit (Day -1).
• Subject is willing and able to be confined to an inpatient setting for the study duration, follow instructions, and comply with the protocol requirements.
• BMI must be ≥18 and ≤40 kg/m2.
• Subject resides in a stable living situation and is anticipated to return to that same stable living situation after discharge, in the opinion of the investigator.
• Subject has an identified reliable informant.
• Women of childbearing potential, or men with sexual partners of childbearing potential, must be able and willing to use at least 1 highly effective method of contraception during the study and for 30 days after the last dose of study drug. Sperm donation is not allowed for 30 days after the final dose of study drug.

Exclusion Criteria

• Any primary DSM-5 disorder other than schizophrenia within 12 months before screening (confirmed using MINI version 7.0.2 at screening). Symptoms of mild mood dysphoria or anxiety are allowed as long as these symptoms are not the primary focus of treatment. A screening subject with mild substance abuse disorder within the 12 months before screening must be discussed and agreed upon with the medical monitor before they can be allowed into the study.
• Subjects who are newly diagnosed or are experiencing their first treated episode of schizophrenia.
• History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or oncologic disease or any other condition that, in the opinion of the investigator, would jeopardize the safety of the subject or the validity of the study results.
• Subjects with HIV, cirrhosis, biliary duct abnormalities, hepatobiliary carcinoma, and/or active hepatic viral infections based on either medical history or liver function test results.
• History or high risk of urinary retention, gastric retention, or narrow-angle glaucoma.
• History of irritable bowel syndrome (with or without constipation) or serious constipation requiring treatment within the last 6 months.
• Risk for suicidal behavior during the study as determined by the in