Long-Term Safety and Tolerability Assessment of Trospium Chloride and Xanomeline Tartrate in Psychosis Associated with Alzheimer's Disease

The primary objective of this open-label extension study is to assess the long-term **safety** and **tolerability** of KarXT in subjects with **psychosis associated with Alzheimer's disease**. This evaluation is clinically relevant as it aims to determine the sustained safety profile of KarXT, which is crucial for its potential use in managing psychosis in this patient population. The study will provide insights into the long-term effects of the active substances, **trospium chloride** and **xanomeline tartrate**, administered in capsule form. The secondary objectives are not specified in the provided data.

The clinical trial involves a total of **56 participants** diagnosed with **psychosis associated with Alzheimer's Disease**. The study population includes both male and female subjects, aged between **55 to 90 years**. Participants were selected based on their completion of previous studies, specifically KAR-031, KAR-032, or CN0120056. The trial population is characterized by individuals who are capable of self-locomotion, either independently or with the aid of an assistive device, and have a caregiver available to assist with study requirements. Participants are required to understand the study's nature and provide informed consent, with provisions for legally acceptable representatives if necessary. Female participants must not be pregnant or breastfeeding, and all participants must adhere to effective contraception methods if applicable. The study includes a vulnerable population, reflecting the specific health challenges associated with Alzheimer's Disease. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the long-term safety and tolerability of **KarXT** in subjects with **psychosis associated with Alzheimer's disease**. This study is an open-label extension, following a randomized, double-blind, controlled trial. Participants who have completed previous studies (KAR-031, KAR-032, CN0120056) are eligible for inclusion. The trial is expected to commence on March 1, 2024, and conclude by June 30, 2026, with a maximum treatment period of 52 weeks. The study involves oral administration of KarXT capsules, containing the active substances **trospium chloride** and **xanomeline tartrate**.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as age (55-90 years), ability to provide informed consent, and capability of self-locomotion. The screening visit will also ensure that participants have a caregiver willing to assist with study requirements. Follow-up visits will be scheduled at regular intervals to monitor the incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs, which are primary and secondary endpoints, respectively. The end-of-study visit will assess the overall safety and tolerability of the treatment.

Participant involvement is expected to last up to 52 weeks, with conditions for early termination including the occurrence of serious TEAEs or TEAEs leading to discontinuation of the investigational medicinal product (IMP). Participants may also be withdrawn if they relocate to a nursing home facility without prior approval from the Sponsor/Medical Monitor. The study aims to provide comprehensive data on the long-term effects of KarXT in managing psychosis symptoms in the specified patient population.

The clinical trial involves the administration of the experimental medication **KarXT**, which is formulated as a **capsule**. The active substances in KarXT are **trospium chloride** and **xanomeline tartrate**, both of which are of chemical origin. The medication is produced by Karuna Therapeutics Inc. and is administered orally. The maximum daily dose of KarXT is 200,999.20 mg, with a total maximum dose of 728,009,997,280 mg over the course of the study. The treatment period extends up to 52 weeks. The trial aims to assess the long-term safety and tolerability of KarXT in subjects with psychosis associated with Alzheimer's disease.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on the administration of KarXT. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen. The study does not involve any pediatric formulations or orphan drug designations. The pharmaceutical form remains consistent as a capsule throughout the trial, and all substances involved are confirmed to be chemical in nature.

The efficacy of the investigational product, KarXT, in the clinical trial will be assessed through the evaluation of primary and secondary endpoints. The primary endpoint focuses on the incidence of **Treatment-Emergent Adverse Events (TEAEs)**. Secondary endpoints include the incidence of serious TEAEs and the incidence of TEAEs leading to the discontinuation of the investigational medicinal product (IMP). These endpoints are critical in determining the safety and tolerability of KarXT in subjects with psychosis associated with Alzheimer's Disease.