Pimavanserin and concomitant anti‐dementia medication use in patients with neurodegenerative and/or neurovascular disorders: Safety outcomes from pooled clinical data and the HARMONY study

Abstract

AbstractBackgroundPimavanserin, a selective serotonin receptor modulating agent, is approved to treat hallucinations and delusions associated with Parkinson’s disease psychosis and is being investigated for the treatment of hallucinations and delusions associated with dementia‐related psychosis (DRP). Many DRP patients also receive concomitant antidementia medication (cADM), such as acetylcholinesterase inhibitors or memantine. We evaluated the tolerability of cADM use in pimavanserin‐treated patients with neurologic disease.MethodsTreatment‐emergent adverse events (TEAEs) were examined using pooled data from 8 double‐blind, placebo‐controlled, parallel‐group studies of patients with neurodegenerative and/or neurovascular disease (collectively, NDD) who received pimavanserin 34 mg (N=580) or placebo (N=649) once daily and data from HARMONY, the phase 3 randomized discontinuation study of pimavanserin for DRP. HARMONY included a 12‐week open‐label (OL) period (N=392) followed by a 26‐week double‐blind (DB) period where subjects were randomized to continue pimavanserin treatment (N=105) or switch to placebo (N=112).ResultsIn the pooled NDD population, 291 (50.2%) pimavanserin‐treated and 305 (47.0%) placebo‐treated patients had cADM use. Those with cADM use had lower rates of TEAEs (pimavanserin: 51.2%, placebo: 52.1%) vs those without (pimavanserin: 56.7%, placebo: 59.6%). Rates of serious TEAEs were also similar in patients treated with cADM (pimavanserin: 6.9%, placebo: 4.6%) vs those without cADM (pimavanserin: 7.3%, placebo: 4.1%). In the OL period of HARMONY, 273 (69.6%) patients had cADM use; their rates of TEAEs (with cADM: 32.2%, without cADM: 45.4%) and serious TEAEs (with cADM: 3.3%; without cADM: 9.2%) were similar to patients without. In the DB period, 81 (77.1%) pimavanserin‐treated and 72 (64.3%) placebo‐treated patients used cADM. DB patients with cADM use exhibited rates of TEAEs (pimavanserin: 37.0%, placebo: 31.9%) and serious TEAEs (pimavanserin: 3.7%, placebo: 4.2%) similar to patients without (TEAEs, pimavanserin: 54.2%, placebo: 45.0%; serious TEAEs, pimavanserin: 8.3%, placebo: 2.5%).ConclusionsPatients with NDD receiving pimavanserin in clinical trials commonly took cADMs. There was no evidence that concomitant pimavanserin use resulted in a differential TEAE or serious TEAE profile in patients taking antidementia medications.