A Double-Blind, Placebo-Controlled, Phase 2, Efficacy and Safety Study of ACP-204 in Adults with Lewy Body Dementia Psychosis (LBDP)

The primary objective of this study is to evaluate the efficacy and dose response of ACP-204 30 mg and ACP-204 60 mg compared with placebo in subjects with Lewy body dementia psychosis (LBDP), encompassing both Parkinson's disease dementia psychosis (PDDP) and dementia with Lewy bodies psychosis (DLBP). The primary endpoint is measured by the Scale for the Assessment of Positive Symptoms–Lewy Body Dementia Psychosis (SAPS-LBDP), a modified 9-item scale comprising SAPS Hallucinations and Delusions subscales items. This assessment is clinically relevant as hallucinations and delusions represent core psychotic features in LBDP that significantly impact patient quality of life and caregiver burden.

The secondary objectives include:

• To evaluate efficacy and dose response of ACP-204 30 mg and ACP-204 60 mg compared with placebo in subjects with LBDP as measured by Clinical Global Impression–Severity in the LBDP context (CGI-S-LBDP)

• To evaluate efficacy and dose response of ACP-204 30 mg and ACP-204 60 mg compared to placebo in subjects with LBDP in the following domains: symptoms of hallucinations and delusions, and sleep disturbance

• To evaluate the safety and tolerability of ACP-204 30 mg and ACP-204 60 mg compared to placebo in subjects with LBDP

The clinical trial enrolled a total of **103 participants** diagnosed with **Lewy Body Dementia Psychosis (LBDP)**, encompassing both Parkinson's disease dementia psychosis and dementia with Lewy bodies psychosis. The study population consisted of both **male and female subjects** aged **55 years to less than 85 years** at the time of screening. Participants were required to meet either the clinical criteria for **Parkinson's disease with dementia** as defined by the Movement Disorder Society's Task Force or the revised clinical criteria for probable **dementia with Lewy bodies** according to the Fourth consensus report of the DLB Consortium. Additionally, subjects met the revised criteria for **psychosis** in major or mild **neurocognitive disorder** as established by the International Psychogeriatrics Association. Participants were living in the community or, where permitted by local regulations, in an institutionalized setting. The trial included a **vulnerable population**, and informed consent procedures were adapted accordingly, with provisions for legally authorized representatives or study partners to provide consent when subjects were deemed not competent to do so independently.

This is a double-blind, placebo-controlled, Phase 2 clinical trial evaluating the efficacy and safety of ACP-204 in adults with Lewy body dementia psychosis. The study employs a randomized design to assess two dose levels of ACP-204 (30 mg and 60 mg) compared with placebo. The investigational medicinal product ACP-204 tartrate is administered as capsules via oral use. The primary objective is to evaluate the efficacy and dose response of ACP-204 30 mg and ACP-204 60 mg compared with placebo in subjects with Lewy body dementia psychosis, including both Parkinson's disease dementia psychosis and dementia with Lewy bodies psychosis, as measured by the Scale for the Assessment of Positive Symptoms–Lewy Body Dementia Psychosis (SAPS-LBDP), a modified 9-item scale comprising SAPS Hallucinations and Delusions subscales items. The primary endpoint is the change from baseline in SAPS-LBDP total score at Week 6.

The maximum treatment period is 6 weeks. The maximum daily dose is 60 mg for the higher dose group and 30 mg for the lower dose group. The maximum total dose amount is 2520 mg for the 60 mg daily dose group and 1260 mg for the 30 mg daily dose group over the treatment period. The estimated recruitment start date is November 2025, with an estimated study completion date of June 2027.

Eligible participants include male or female individuals aged 55 years to less than 85 years at the screening visit who are living in the community or, if permitted by local regulations, in an institutionalized setting. Participants must be able to provide written informed consent, or if deemed not competent, their legally authorized representative must provide written informed consent and the subject must provide written informed assent per local regulations. Participants must meet either the clinical criteria for Parkinson's disease with dementia as defined by the Movement Disorder Society's Task Force or the revised clinical criteria for probable dementia with Lewy bodies by consensus criteria (Fourth consensus report of the DLB Consortium). Additionally, participants must meet the revised criteria for psychosis in major or mild neurocognitive disorder established by the International Psychogeriatrics Association.

The study involves a screening visit to assess eligibility and establish baseline measurements, followed by treatment visits during the 6-week treatment period, and an end-of-study visit. The expected length of participant involvement encompasses the screening period, the 6-week treatment phase, and any required follow-up assessments. Conditions that may lead to early termination from the study include withdrawal of consent, adverse events, protocol violations, or investigator decision based on safety or efficacy considerations.

The experimental medication **ACP-204** is administered as **capsules** containing **ACP-204 tartrate** as the active substance. The investigational product is supplied by ACADIA PHARMACEUTICALS and is administered via the **oral route**. Two dose levels are evaluated in this clinical trial: **30 mg** and **60 mg** daily. The maximum daily dose amount is 60 mg for the higher dose cohort and 30 mg for the lower dose cohort. The maximum total dose amount administered during the treatment period is 2520 mg for the 60 mg daily dose group and 1260 mg for the 30 mg daily dose group. The maximum treatment period for both dose levels is **6 weeks**. The active substance is of chemical origin.

**Placebo** for ACP-204 capsules is used as the comparator treatment in this double-blind, placebo-controlled study. The placebo is formulated to match the appearance of the active ACP-204 capsules to maintain blinding throughout the trial. The placebo does not contain any active pharmaceutical ingredient and serves as the control arm against which the efficacy and safety of the two doses of ACP-204 are evaluated. The route of administration, dosing frequency, and treatment duration for the placebo arm correspond to those of the active treatment arms to ensure consistency in trial conduct and participant compliance monitoring.

Efficacy will be assessed using the Scale for the Assessment of Positive Symptoms–Lewy Body Dementia Psychosis (SAPS-LBDP), a modified 9-item scale comprising SAPS Hallucinations and Delusions subscales items. The primary endpoint is the change from baseline in SAPS-LBDP total score at Week 6. This evaluation will compare the efficacy and dose response of ACP-204 30 mg and ACP-204 60 mg against placebo in subjects with Lewy body dementia psychosis, including both Parkinson's disease dementia psychosis and dementia with Lewy bodies psychosis.