A POST HOC ANALYSIS OF STUDY ACP-103-019 EVALUATING THE IMPACT OF A REDUCTION IN PSYCHOSIS ON THE SEVERITY OF AGITATION AND AGGRESSION IN PATIENTS WITH ALZHEIMER'S DISEASE

Abstract

Introduction The objective of this post hoc analysis was to evaluate whether Alzheimer's disease (AD) patients with psychosis who experience an improvement in their hallucinations and delusions with pimavanserin treatment also experience an improvement in agitation and aggression. Methods ACP-103-019 was a 12 week, randomized, double-blind, placebo-controlled study that evaluated the efficacy of pimavanserin (PIM) 34mg once-daily in reducing the frequency and/or severity of hallucinations and delusions in patients with AD psychosis. The primary endpoint was change from baseline in the Neuropsychiatric Inventory Nursing Home Version Psychosis Score (NPI-NH PS) [domain A (delusions) + domain B (hallucinations)] at Week 6. A post hoc analysis was conducted to determine if there was a greater reduction in agitation and aggression, as measured by NPI-NH Domain C (agitation/aggression) and Cohen-Mansfield Agitation Inventory-Short Form (CMAI-SF), in patients who experienced a reduction in the frequency and/or severity of their hallucinations and delusions when compared with those who did not experience a reduction in hallucinations and delusions. Results Overall in ACP-103-019, there were only minor differences between the placebo (n=91) and PIM (n=87) treatment arms when evaluating changes from baseline to Week 6 in Agitation/Aggression based on CMAI SF total score or NPI-NH Domain C score (0.30 [p=0.8031] and -0.66 [p=0.254], respectively). However, when subjects treated with PIM who responded to the treatment (n=48), defined as a 30% reduction in NPI-NH PS at Week 6, were compared with those who did not respond to PIM treatment (n=28), there was a greater reduction in both CMAI-SF and NPI-NH Domain C scores: -3.74 (p=0.0550) and -2.75 (p=0.0021), respectively. When response was defined as a 50% reduction in NPI-NH PS at Week 6, the greater improvement of agitation/aggression in responders (n=44) vs non-responders (n=32) was also observed for both CMAI-SF and NPI-NH Domain C: -3.714 (p=0.0483) and -3.64 (p Conclusions In this post-hoc analysis, some AD patients whose hallucinations and delusions responded to pimavanserin also experienced improvement in their symptoms of agitation and aggression. These results suggest a correlation between a reduction in hallucinations and delusions and a reduction in agitation/aggression in AD patients with psychosis. This research was funded by Sponsored by ACADIA Pharmaceuticals Inc. (San Diego, CA, USA).