Efficacy results of pimavanserin from a multi-center, open-label extension study in Parkinson's disease psychosis patients

• Published in: Parkinsonism & related disorders Vol. 87; pp. 25 - 31
• Main Authors: Isaacson, Stuart H., Ballard, Clive G., Kreitzman, David L., Coate, Bruce, Norton, James C., Fernandez, Hubert H., Ilic, Tihomir V., Azulay, Jean-Philippe, Ferreira, Joaquim J., Abler, Victor, Stankovic, Srdjan
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-06-2021; Elsevier
• Subjects: Aged; Aged, 80 and over; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - adverse effects; Antipsychotic Agents - pharmacology; Double-Blind Method; Female; Humans; Male; Middle Aged; Outcome Assessment, Health Care; Parkinson Disease - complications; Parkinson Disease - drug therapy; Piperidines - administration & dosage; Piperidines - adverse effects; Piperidines - pharmacology; Psychotic Disorders - drug therapy; Psychotic Disorders - etiology; Urea - administration & dosage; Urea - adverse effects; Urea - analogs & derivatives; Urea - pharmacology
• ISSN: 1353-8020; 1873-5126
• DOI: 10.1016/j.parkreldis.2021.04.012

Pimavanserin, a selective 5-HT2A inverse agonist/antagonist, was approved for hallucinations and delusions associated with Parkinson's disease psychosis (PDP). We present durability of response with pimavanserin in patients with PDP for an additional 4 weeks of treatment.
This was an open-label extension (OLE) study in patients previously completing one of three double-blind, placebo-controlled (Core) studies. All patients received pimavanserin 34 mg once daily. Efficacy assessments included the Scale for the Assessment of Positive Symptoms (SAPS) PD and H + D scales, Clinical Global Impression (CGI) Improvement and Severity scales and Caregiver Burden Scale (CBS), through 4 weeks in the OLE. Safety assessments were conducted at each visit.
Of 459 patients, 424 (92.4%) had a Week 4 efficacy assessment. At Week 4 (10 weeks total treatment), SAPS-PD mean (standard deviation) change from OLE baseline was −1.8 (5.5) and for SAPS-H + D was −2.1 (6.2) with pimavanserin 34 mg. Patients receiving placebo during the Core studies had greater improvements (SAPS-PD -2.9 [5.6]; SAPS-H + D −3.5 [6.3]) during the OLE. For participants treated with pimavanserin 8.5 or 17 mg during the Core studies, further improvement was observed during the OLE with pimavanserin 34 mg. The mean change from Core Study baseline for SAPS-PD score was similar among prior pimavanserin 34 mg and prior placebo-treated participants (−7.1 vs. −7.0). The CGI-I response rate (score of 1 or 2) at Week 4 was 51.4%. Adverse events were reported by 215 (46.8%) patients during the first 4 weeks of OLE. The most common AEs were fall (5.9%), hallucination (3.7%), urinary tract infection (2.8%), insomnia (2.4%), and peripheral edema (2.2%)
Patients previously on pimavanserin 34 mg during three blinded core studies had durability of efficacy during the subsequent 4 week OLE SAPS-PD assessment. Patients previously on blinded placebo improved after 4 weeks of OL pimavanserin treatment. These results in over 400 patients from 14 countries support the efficacy of pimavanserin for treating PDP.
•In this open label study, 424 patients had a 4 week efficacy extension assessment with pimavanserin 34 mg.•Mean scores for SAPS-PD and for SAPS-H + D continued to improve during open-label therapy after double-blind treatment.•Those receiving double-blind placebo demonstrated the greatest improvements.•CGI-I response rates were 42.5% and 51.4% at Weeks 2 and 4, respectively.•Pimavanserin is effective for the treatment of PDP.