Clive G Ballard1, David L Kreitzman2, Stuart Isaacson3, I-Yuan Liu4, James C Norton4, George Demos4, Hubert H Fernandez5, Tihomir V Ilic6, Jean-Philippe Azulay7, Joaquim J Ferreira8, Victor Abler4, Srdjan Stankovic4. 1. University of Exeter Medical School, Exeter, UK. Electronic address: c.ballard@exeter.ac.uk. 2. Parkinson's Disease and Movement Disorders Center of Long Island, Commack, NY, USA. 3. Parkinson's Disease and Movement Disorders Center of Boca Raton, Boca Raton, FL, USA. 4. ACADIA Pharmaceuticals Inc., San Diego, CA, USA. 5. Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH, USA. 6. Medical Faculty of Military Medical Academy, Belgrade, Serbia. 7. Timone Hospital, Marseille, France. 8. Faculty of Medicine, University of Lisbon, Lisbon, Portugal.
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.
RCT Entities:
INTRODUCTION:Pimavanserin is a selective 5-HT2A inverse agonist/antagonist approved for treating hallucinations and delusions associated with Parkinson's diseasepsychosis (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 patientsdied, 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.
Authors: Zahinoor Ismail; Byron Creese; Dag Aarsland; Helen C Kales; Constantine G Lyketsos; Robert A Sweet; Clive Ballard Journal: Nat Rev Neurol Date: 2022-01-04 Impact factor: 44.711