Long-term evaluation of open-label pimavanserin safety and tolerability in Parkinson's disease psychosis. (August 2020)

• Record Type: Journal Article
• Authors: Ballard, Clive G.; Kreitzman, David L.; Isaacson, Stuart; Liu, I-Yuan; Norton, James C.; Demos, George; Fernandez, Hubert H.; Ilic, Tihomir V.; Azulay, Jean-Philippe; Ferreira, Joaquim J.; Abler, Victor; Stankovic, Srdjan
• Is Part Of: Parkinsonism & related disorders. Volume 77(2020)
• Page Start: 100
• Page End: 106
• Publication Date: 2020-08
• Subjects: Pimavanserin -- Parkinson's disease psychosis -- Tolerability; Parkinson's disease -- Periodicals; Movement disorders -- Periodicals; Movement Disorders -- Periodicals; Nerve Degeneration -- Periodicals; Nervous System Diseases -- Periodicals; Parkinson Disease -- Periodicals; Tremor -- Periodicals; Parkinson, Maladie de -- Périodiques; Parkinson's disease; 616.833
• DOI: 10.1016/j.parkreldis.2020.06.026
• Languages: English
• ISSNs: 1353-8020

Abstract

Abstract: Introduction: Pimavanserin is a selective 5-HT2A inverse agonist/antagonist approved for treating hallucinations and delusions associated with Parkinson's disease psychosis (PDP). Results from short-term, placebo-controlled studies demonstrated a positive benefit/risk profile. This multi-year, open-label study assessed long-term safety and tolerability of pimavanserin. Methods: This was an open-label extension (OLE) study in patients previously completing a double-blind, placebo-controlled study or a previous OLE study. Safety was evaluated from adverse events (AEs), clinical laboratory results, motor symptoms, electrocardiograms (ECG), and mortality. Durability of response was assessed from the Clinical Global Impression-Severity (CGI-S) scale and Caregiver Burden Scale (CBS). Results: Of 459 participants treated in this OLE study (average age 71.2 years), the median duration of treatment was 454 days. Over the entire study period (approximately 11 years), ≥1 AE occurred in 392 (85.4%) patients; the majority were of mild to moderate intensity, with fall (32.0%), urinary tract infection (19.0%), and hallucination (13.7%) most common. Serious AEs occurred in 188 (41.0%) patients, and an AE leading to study termination or dose discontinuation occurred in 133 (29.0%) patients. Sixty-one patients died, 59 (12.9%) during treatment or within 30 days after the last dose of study drug; the observed mortality rate was 6.45 per 100 patient-years of exposure. Mean scores for the CGI-S scale and CBS generally remained stable for up to 192 weeks (>3.5 years). Conclusions: Long-term treatment with pimavanserin 34 mg once daily demonstrated a favorable benefit/risk profile with no unexpected safety concerns. Mortality rates suggested no increased risk following long-term treatment. Highlights: This was an open-label study of long-term safety and tolerability of pimavanserin in PDP patients. 459 patients treated for a median of 454 days had mostly mild or moderate AEs. Pimavanserin 34 mg maintained a positive benefit/risk profile in patients with PDP. Mortality rates suggested no increased risk following long-term treatment.