Changes on the CGI subscores were also significantly different. Patients in the placebo group experienced a mean decrease of less than half a point on the improvement subscale, compared with a decrease of about 1 point in the pimavanserin group. On the severity subscale, the placebo group stayed close to baseline, while the pimavanserin group decreased by about 1 point. About 27% of those taking placebo and 49% of those taking pimavanserin were considered responders.
Caregiver burden also significantly improved with the study drug.
In an exploratory analysis examining pimavanserin’s effect on sleep, the drug was associated with improvements in both nighttime sleep and daytime wakefulness on the Scale for Outcomes in Parkinson’s Disease sleep measure, Dr. Ballard said.
There were three deaths during the study – one in the placebo group (sudden cardiac death) and two in the active group (sepsis and septic shock). There were also four urinary tract infections – one in the placebo group and three in the active group. Other adverse events reported during the trial included peripheral edema (7% active vs. 3% placebo), falls (11% vs. 6%), confusion (6% vs. 3%), headache (1% vs. 5%), and hallucination (7% vs. 4%).
Based on the favorable results, Acadia announced that it had discontinued its work on a planned confirmatory phase III study. A New Drug Application for pimavanserin is in preparation, Dr. Ballard said.*
Acadia is also planning to study the drug’s effect in Alzheimer’s-associated psychosis in a phase II feasibility trial later this year, according to the company’s website.
"Similar to Parkinson’s disease psychosis, there is no therapy approved to treat Alzheimer’s psychosis in the U.S.," the company said in a written statement. "As symptoms progress and become more severe, physicians often resort to off-label use of antipsychotic medications in these patients. ... Antipsychotic drugs may exacerbate the cognitive disturbances associated with Alzheimer’s disease and also have a black box warning for use in elderly patients with dementia-related psychosis due to increased risks of mortality and morbidity."
The trial was funded by Acadia. Dr. Ballard disclosed that he has received honoraria and consulting fees from the company.
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* Correction 7/30/13: An earlier version of this article misstated pimavanserin's mechanism of action and the status of its New Drug Application.