Evaluation of the Efficacy and Safety of Xanomeline Tartrate and Trospium Chloride in Cognitive Impairment Associated with Mild to Moderate Alzheimer's Disease

The primary objective of this study is to evaluate the efficacy of KarXT + KarX-EC in improving cognitive impairment and global functioning in patients with Alzheimer’s disease. The secondary objectives include:

• Assessment of improvement in functional impairment regarding the ability to perform daily tasks.
• Evaluation of changes in behavioral symptoms, specifically mood or behavior disturbances.
• Evaluation of the safety and tolerability of the intervention.

This clinical trial involves 294 participants diagnosed with mild to moderate Alzheimer’s disease. The study population consists of males and females between the ages of 60 and 85 years. Inclusion requires a Mini-Mental State Examination score between 12 and 22 inclusive. Eligible subjects must have a designated caregiver who provides at least 10 hours of contact per week and assists with medication administration and study compliance. Participants currently utilizing acetylcholinesterase inhibitors or memantine must have maintained a stable dosage for a minimum of 12 weeks prior to screening and must continue this dosage throughout the study period.

This Phase 3, randomized, double-blind, placebo-controlled, parallel-group study evaluates the efficacy and safety of KarXT and KarX-EC in treating cognitive impairment associated with Alzheimer’s disease. The research methodology involves assigning participants to receive either the test products or a matching placebo. The trial includes a screening visit to assess eligibility, such as age requirements, MMSE scores, and the presence of a designated caregiver. Following screening, participants undergo a period of intervention and follow-up visits to monitor primary endpoints, including changes in ADAS-Cog11 and CIBIC+ at Week 24. Secondary endpoints include assessments of ADCS-ADL, NPI total score, and various safety parameters such as adverse events and changes in vital signs. The study duration for participant involvement is focused on the 24-week treatment period, and the trial may be subject to early termination based on safety or efficacy data.

The experimental treatment includes KarXT, which consists of trospium chloride and xanomeline tartrate. This medication is administered as an oral capsule at a dosage of 9999 mg.

The experimental treatment also includes KarX-EC, containing xanomeline tartrate. This substance is administered via the oral route in capsule form at a dosage of 9999 mg.

Non-experimental treatments consist of KarXT matching placebo and KarX-EC matching placebo to serve as a control in the study for Alzheimer’s disease.

The assessment of efficacy in this study focuses on evaluating changes in cognitive and functional capabilities in patients with Alzheimer's disease. The primary endpoints include the change from baseline in the ADAS-Cog11 and the CIBIC+ score at Week 24.

Secondary efficacy parameters measured at Week 24 consist of the following:

• Change from baseline in the ADCS-ADL.
• Change from baseline in the NPI total score.