Abstract Details

Title Impact of Baseline Sleep Disturbances on Pimavanserin Response in Parkinson’s Disease Psychosis: A Post Hoc Analysis

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P11 - Poster Session 11 (11:45 AM-12:45 PM)

Poster/Presentation
Number 13-007

Objective To evaluate the impact of baseline sleep disturbances on antipsychotic response to pimavanserin vs placebo in patients with Parkinson’s disease psychosis (PDP).

Background Sleep-related disturbances are commonly associated with PDP. Pimavanserin is approved in the US for hallucinations and delusions associated with PDP, but the impact of sleep disturbances on pimavanserin response is unclear.

Design/Methods To identify patients with sleep-related disturbances, data from the pivotal phase 3 trial (NCT01174004) were stratified by baseline Scales for Outcomes in Parkinson’s Disease-nighttime sleep (SCOPA-NS) scores (≥7 or <7) and SCOPA-daytime sleepiness (SCOPA-DS) scores (≥5 or <5). The impact of baseline sleep disturbances was assessed using a mixed model for repeated measures including treatment, visit, SCOPA subgroup, and their interactions. The primary endpoint was the least squares mean (LSM) change from baseline in Scale for the Assessment of Positive Symptoms-Parkinson's Disease (SAPS-PD) score at week 6. Treatment differences (LSMD) vs placebo were estimated within each SCOPA subgroup, and an interaction test was conducted (not powered to detect differences; all nominal P values).

Results Overall, pimavanserin improved psychosis symptoms vs placebo at week 6: SAPS-PD LSMD (95% CI), −3.02 (−4.89, −1.14); P=0.0018. For baseline SCOPA-DS<5, SAPS-PD LSMD (95% CI) was −5.27 (−8.41, −2.12); P=0.0015; for SCOPA-DS≥5, −1.97 (−4.24, 0.29); P=0.0872 (interaction test P=0.1429). For baseline SCOPA-NS<7, SAPS-PD LSMD (95% CI) was −3.35 (−5.79, −0.92); P=0.0074; for baseline SCOPA-NS≥7, −2.56 (−5.53, 0.40); P=0.0893 (interaction test P=0.6716). Notably, patients with nighttime sleep disturbances (baseline SCOPA-NS≥7) experienced sleep improvement with pimavanserin vs placebo: SCOPA-NS LSMD (95% CI), −2.54 (−4.14, −0.93); P=0.0025.

Conclusions Pimavanserin demonstrated consistent antipsychotic efficacy vs placebo in patients with PDP regardless of baseline sleep-disturbance status. Additionally, patients with baseline impairment in nighttime sleep experienced improved nighttime sleep with pimavanserin. These findings support the consistent efficacy of pimavanserin in the presence or absence of daytime or nighttime sleep disturbance.

Authors/Disclosures
Lambros Chrones, MD PRESENTER	Dr. Chrones has received personal compensation for serving as an employee of Acadia Pharmaceuticals.
Karla E. Naujoks, PhD	Dr. Becerril has received personal compensation for serving as an employee of Acadia Pharmaceuticals. Dr. Becerril has stock in Acadia Pharmaceuticals.
Peter Zhang, PhD	Dr. Zhang has nothing to disclose.
Xiaoshu Feng, PhD	Dr. Feng has nothing to disclose.
Greg Brunson, PharmD	Dr. Brunson has received personal compensation for serving as an employee of Acadia Pharmaceuticals. Dr. Brunson has or had stock in Acadia Pharmceuticals.
Andrew Krystal	Andrew Krystal has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Axsome Therapeutics, Abbvie, Big Health, Eisai, Evecxia, Harmony Biosciences, Idorsia, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Neurocrine Biosciences, Neumora, Neurawell, Otsuka Pharmaceuticals, Sage, Takeda. Andrew Krystal has stock in Neurawell, Big Health. The institution of Andrew Krystal has received research support from Alkermes; Janssen Pharmaceuticals, Axsome Pharmaceutics, Attune, Eisai, Harmony, Neumora; Neurocrine Biosciences, Reveal Biosensors, The Ray and Dagmar Dolby Family Fund, Weill Institute for Neurosciences, and the National Institutes of Health.

��ɫ��

��ɫ��