PANSS Total Score is a clinical tool used to measure the severity of symptoms in individuals with schizophrenia. It includes 30 items divided into three subscales: Positive Symptoms (e.g., hallucinations, delusions) Negative Symptoms (e.g., social withdrawal, lack of motivation) General Psychopathology (e.g., anxiety, depression) Each item is rated from 1 (absent) to 7 (extreme), resulting in a total score range from 30 to 210. Higher PANSS Total Scores indicate more severe symptoms and worse clinical outcomes. Baseline is defined as last non-missing assessment prior to the first dose of study drug.

PANSS Total Score is a clinician administered measure of schizophrenia symptom severity used widely in antipsychotic research. It includes 30 items across 3 subscales: * Positive Symptoms (7 items) assessing excesses or distortions such as hallucinations, delusions, or grandiosity * Negative Symptoms (7 items) assessing diminished function such as social withdrawal or reduced motivation and * General Psychopathology (16 items) capturing broader symptoms like anxiety, depression, guilt, or cognitive impairment Each item is scored from 1 (absent) to 7 (extreme), producing a PANSS Total Score ranging from 30 to 210, with higher scores indicating more severe symptoms. Baseline is defined as the last non missing PANSS Total Score before first dose. This endpoint evaluates change from Baseline to Week 6, with negative values indicating improvement.

TEAEs are defined as events with an onset date on or after the first dose of KarXT. An Adverse Event is any symptom, physical sign, syndrome, or disease that either emerges during the study or, if present at baseline, worsens during the study, regardless of the suspected cause of the event using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.

The Positive and Negative Syndrome Scale (PANSS) is a medical scale used for measuring symptom severity of participants with schizophrenia and is widely used in the study of antipsychotic therapy. The PANSS rating form contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. Participants are rated from 1 to 7 on each symptom scale. The positive symptoms in schizophrenia are the excess or distortion of normal function such as hallucinations, delusions, grandiosity, and hostility, and the negative symptoms in schizophrenia are the diminution or loss of normal functions. PANSS total score is the sum of all 30 items with a minimum score of 30 and a maximum score of 210. Higher scores indicate more severe symptoms. The PANSS Total Score is then the sum of the positive, negative, and general psychopathology symptom scores. Baseline is defined as the PANSS score at screening.

TEAEs are defined as events with an onset date on or after the first dose of KarXT. An Adverse Event is any symptom, physical sign, syndrome, or disease that either emerges during the study or, if present at baseline, worsens during the study, regardless of the suspected cause of the event using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0.