Long-term Safety and Tolerability Evaluation of Trospium Chloride and Xanomeline Tartrate in Agitation Associated with Alzheimer's Disease

The primary objective is to assess the long‑term safety and tolerability of the oral combination of KarXT and KarX‑EC in participants with agitation associated with Alzheimer’s disease, providing essential data on the sustained risk‑benefit profile of this therapeutic regimen in a vulnerable population.

A total of 409 participants were enrolled, comprising both male and female individuals classified as vulnerable patients with agitation associated with Alzheimer’s disease. Enrollment required completion of prior studies CN0120023 or CN0120024, signing of a new informed consent form, and the continuous involvement of a caregiver capable of attending all study visits, overseeing medication administration, and participating in behavioral interviews and questionnaires (approximately ten hours per week). Participants were selected on the basis of these criteria, with no additional lifestyle restrictions reported; general health status was limited to the presence of the target condition without further specification of comorbidities or physical activity levels.

The study is an open‑label, single‑arm Phase III extension trial designed to evaluate the long‑term safety and tolerability of the oral combination of KarXT and KarX‑EC in participants with agitation associated with Alzheimer’s disease. The trial enrolment period is projected from November 2025 to July 2029, with each enrolled participant remaining in the study for up to three years of continuous treatment. After obtaining a new informed consent, participants who have completed the preceding CN0120023 or CN0120024 studies undergo a screening visit to confirm eligibility, followed by a baseline visit that initiates the extension phase. Subsequent scheduled visits occur at regular intervals (e.g., monthly or quarterly) to collect safety data, record treatment‑emergent adverse events, monitor vital signs, body weight, laboratory parameters, urinary retention, involuntary movements, cognition, and suicidal ideation, and to document any adverse events of special interest. The final end‑of‑study visit concludes the trial and includes a comprehensive safety assessment. Primary efficacy assessment focuses on the incidence of treatment‑emergent adverse events, while secondary assessments capture serious adverse events, events leading to withdrawal, deaths, and the additional safety parameters listed. Early termination may occur if a participant experiences a serious adverse event, develops a condition contraindicating continued study drug exposure, demonstrates poor adherence, or is lost to follow‑up.

The investigational regimen comprises two oral capsule products. KarXT is a fixed‑dose combination capsule containing trospium chloride and xanomeline tartrate. Each capsule delivers a total of 9999 mg of the combined active substances and is administered by the oral route.

The second investigational product, KarX‑EC, is an oral capsule containing xanomeline tartrate alone, with a strength of 9999 mg per capsule. It is also administered orally.

No concomitant non‑experimental therapies, placebo, or standard‑of‑care treatments are specified for this open‑label extension study; participants receive only the aforementioned investigational capsules according to the study protocol.