Safety and Tolerability of KarXT in Adolescents with Schizophrenia and KarXT+KarX-EC in Children/Adolescents with Autism‑Related Irritability

The primary objective is to evaluate the long‑term safety and tolerability of KarXT in adolescents aged 13–17 years with schizophrenia and of the combined regimen KarXT plus KarX‑EC in children and adolescents aged 5–17 years with irritability associated with autism spectrum disorder. This assessment addresses the critical need for safety data in pediatric populations receiving muscarinic‑agonist therapy.

Secondary objectives include:

• Assessment of the impact of KarXT and KarXT+KarX‑EC on procholinergic symptomatology in the respective cohorts.
• Evaluation of changes in the frequency and severity of suicidal ideation and behavior.
• Measurement of extrapyramidal symptoms (EPS) incidence and severity.

In total, 260 participants were enrolled, comprising both male and female patients classified as a vulnerable population. The cohort included adolescents aged 13‑17 years with a confirmed diagnosis of Schizophrenia who had completed the double‑blind treatment phase of a prior study (CN0120020) without any adverse event deemed an unacceptable safety risk, as well as children and adolescents aged 5‑17 years with irritability associated with Autism Spectrum Disorder (ASD) who similarly completed the double‑blind phase of studies CN0120044 or CN0120045 under the same safety criteria. Selection required documented diagnosis of the respective condition, successful completion of the earlier trial’s treatment period, and absence of safety‑related exclusions; general health status was otherwise consistent with the underlying psychiatric condition. No specific dietary or physical activity restrictions were stipulated for enrollment.

The study is a Phase 3, multicenter, open-label evaluation of the long‑term safety and tolerability of KarXT in adolescents (13–17 years) with Schizophrenia and of KarXT combined with KarX‑EC in children and adolescents (5–17 years) with irritability associated with Autism Spectrum Disorder. After an initial screening visit to confirm eligibility, participants enter a baseline visit where the investigational capsules (oral, 9999 mg) are administered. Subsequent scheduled visits occur at regular intervals throughout the treatment period to monitor adverse events, vital signs, and efficacy assessments, culminating in an end‑of‑study visit that includes final safety evaluations and a safety follow‑up. The primary endpoint is the occurrence of treatment‑emergent adverse events, adverse events of special interest, and serious adverse events; secondary endpoints include pro‑cholinergic/anticholinergic symptoms, suicidal ideation via the Columbia Suicide Severity Rating Scale, and changes from baseline on the Simpson‑Angus Scale, Barnes‑Akathisia Rating Scale, and Abnormal Involuntary Movement Scale. The overall trial is scheduled to commence recruitment on 20 May 2026 and conclude on 8 March 2030, with participant involvement extending from the screening visit through the final end‑of‑study assessment.

The investigational regimen for adolescents with schizophrenia comprises KarXT, an oral capsule formulated with the fixed‑dose combination of trospium chloride and xanomeline tartrate. Each dose contains 9999 mg of the active ingredients and is administered by the oral route.

In participants with irritability associated with autism spectrum disorder, the study utilizes a combination of KarX-EC and KarXT. KarX-EC is provided as an oral capsule containing xanomeline tartrate at a dose of 9999 mg and is taken by the oral route.

No additional non‑experimental treatments, such as placebo or standard‑of‑care therapy, are administered within the protocol; participants receive only the investigational products as described.