Efficacy and Safety Evaluation of ACP-204 Tartrate in Adults with Alzheimer's Disease Psychosis: A Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the **efficacy** and dose response of ACP-204 at doses of 30 mg and 60 mg compared to placebo in adults with **Alzheimer's Disease Psychosis**. This is clinically relevant as it aims to determine the therapeutic potential and optimal dosing of ACP-204, which could provide a new treatment option for managing psychosis in Alzheimer's disease, a condition with limited effective therapies.

The clinical trial involves a total of **792 participants** diagnosed with **Alzheimer Disease psychosis**. The study population includes both male and female subjects aged between 55 and 85 years, residing either in the community or in an institutionalized setting. Participants were selected based on their ability to complete all study visits with a designated study partner or caregiver. They must be on a stable dose of a cholinesterase inhibitor or memantine, if applicable, and meet the clinical criteria for possible or probable Alzheimer's Disease as per the 2011 National Institute on Aging-Alzheimer Association criteria. Additionally, participants must have psychotic symptoms for at least two months and live in a stable place of residence with no plans to change living arrangements. The trial population includes individuals with either blood-based biomarkers or documented evidence indicating amyloid plaque deposition and neuropathologic changes consistent with Alzheimer's Disease. A prior magnetic resonance imaging or computed tomography scan of the brain consistent with the diagnosis of Alzheimer's Disease is also required. The study includes a vulnerable population, and participants must have a Mini-Mental State Examination (MMSE) score between 6 and 24.

The clinical trial is designed to evaluate the **efficacy** and dose response of ACP-204 in adults with **Alzheimer's Disease Psychosis**. This study is structured as a randomized, double-blind, placebo-controlled trial, ensuring that neither the participants nor the researchers know who is receiving the active treatment or the placebo, thus minimizing bias. The trial is divided into three independent sub-studies, with the first sub-study being a Phase 2 trial focusing on the efficacy of 30 mg and 60 mg doses of ACP-204 compared to a placebo. The trial is expected to commence recruitment on June 30, 2024, and conclude by August 30, 2028, with a maximum treatment period of 6 weeks for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, such as age, living conditions, and medical history. Following successful screening, participants will be randomized to receive either ACP-204 or a placebo. The primary endpoint is the change in the Scale for the Assessment of Positive Symptoms-Hallucinations and Delusions subscales (SAPS-H+D) total score from baseline to Week 6. Secondary endpoints include the Clinical Global Impression-Improvement scale for Alzheimer's Disease Psychosis (CGI-I-ADP).

Throughout the trial, participants will attend regular follow-up visits to monitor their response to the treatment and any adverse effects. These visits are crucial for collecting data on the safety and efficacy of the treatment. The end-of-study visit will occur at the conclusion of the 6-week treatment period, where final assessments will be conducted. Participants are expected to be involved in the study for the duration of the treatment period, with conditions for early termination including significant adverse events or withdrawal of consent. The trial aims to provide valuable insights into the potential therapeutic benefits of ACP-204 for individuals with Alzheimer's Disease Psychosis.

The clinical trial involves the administration of **ACP-204 TARTRATE**, an investigational medication developed by ACADIA PHARMACEUTICALS. This compound is provided in a **capsule** form and is intended for **oral use**. The trial evaluates two dosage levels: 30 mg and 60 mg. The maximum daily dose is set at 60 mg, with a cumulative maximum dose of 2520 mg over a treatment period of up to 6 weeks. The active substance, ACP-204 TARTRATE, is of chemical origin, and the trial does not involve a pediatric formulation. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

In addition to the experimental medication, a **placebo** is utilized as a comparator treatment. The placebo is designed to match the ACP-204 capsules in appearance but contains no active pharmaceutical ingredient. The use of a placebo allows for a double-blind study design, ensuring that neither the participants nor the investigators are aware of the treatment assignments, thereby reducing bias and enhancing the reliability of the efficacy and safety assessments.

Efficacy in the clinical trial will be assessed through a series of predefined endpoints. The primary endpoint is the change in the total score of the Scale for the Assessment of Positive Symptoms-Hallucinations and Delusions subscales (SAPS-H+D) from baseline to Week 6. This scale is a validated tool used to measure the severity of psychotic symptoms, specifically hallucinations and delusions, in patients with Alzheimer's Disease Psychosis. The secondary endpoint includes the Clinical Global Impression-Improvement scale for Alzheimer's Disease Psychosis (CGI-I-ADP), which provides a clinician's assessment of the patient's improvement over time.

Data collection will occur at specified timepoints, with the primary endpoint being evaluated at Week 6. The trial will employ a double-blind, placebo-controlled design to ensure the reliability and validity of the results. The efficacy of the investigational product, ACP-204, will be compared against a placebo to determine its effectiveness in treating psychotic symptoms associated with Alzheimer's Disease. The trial will include adults aged 55 to 85 who meet specific inclusion criteria, such as having a stable dose of cholinesterase inhibitors or memantine and evidence of amyloid plaque deposition consistent with Alzheimer's Disease.