A study assessed the incidence of adverse events (AEs) associated with pimavanserin, a selective serotonin inverse agonist/antagonist, and found that the incidence of treatment-related AEs leading to discontinuation was lower with pimavanserin compared with placebo, according to a study presented at the 13th Clinical Trials on Alzheimer’s Disease Congress 2020. In addition, AEs typically associated with antipsychotics, which impact dopaminergic, muscarinic, cholinergic, and histaminergic receptor activity, were infrequently reported in patients treated with pimavanserin.
Researchers used data from the double-blind, placebo-controlled, randomized, phase III HARMONY study, in which 392 patients received pimavanserin during a 12-week open-label phase. Patients demonstrating sustained response to pimavanserin were then randomized into the double-blind phase for treatment up to 26 weeks. Approximately 62% of eligible patients (n=217/351) achieved stable response of psychosis during the open-label period and were randomized into the double-blind phase.
Researchers particularly assessed the incidence of sedation, falls, cerebrovascular events, thromboembolic events, neuroleptic malignant syndrome (NMS), metabolic disorders (diabetes, dyslipidemia), hyperprolactinemia, seizures, blood dyscrasias, orthostatic hypotension, extrapyramidal symptoms, and cognitive events. The Extrapyramidal Symptom Rating Scale-Abbreviated (ESRS-A) was used to assess motor function, and the Mini-Mental State Examination (MMSE) was used to assess cognition.
The median duration of exposure in the open-label phase was 12 weeks; median exposure duration during the double-blind phase was higher in the pimavanserin group (17.7 weeks; n=105) than the placebo group (10.9 weeks; n=112) due to higher rates of attrition in the placebo group secondary to relapse of psychosis or withdrawals.
No AEs of cerebrovascular events, thromboembolic events, NMS, diabetes, dyslipidemia, hyperprolactinemia, or seizure were reported in the open-label phase. In the open-label phase, the incidence of falls (n=7; 1.8%), somnolence (n=6; 1.5%), confusion state/mental status change (n=9; 2.3%), orthostatic hypotension (n=2; 0.5%), parkinsonism (n=2; 0.5%), akathisia (n=1; 0.3%), tremor (n=1; 0.3%), sleep disorder (n=1; 0.3%), anemia (n=1; 0.3%), and ataxia (n=1; 0.3%) was low.
AEs occurring during the double-blind phase were similar to placebo. The only AEs occurring in ≥3% of patients who remained on pimavanserin and at a higher rate than placebo were headache (9.5% vs. 4.5%) and urinary tract infection (6.7% vs. 3.6%). ESRS-A and MMSE results did not show evidence of worsening from open-label baseline through the double-blind phase.
The study was funded by Acadia Pharmaceuticals Inc.
Presentation: P021:Frequency of Antipsychotic-Associated Adverse Events with Pimavanserin Treatment in Patients with Dementia-related Psychosis. Presented at the 13th Clinical Trials on Alzheimer’s Disease Congress 2020, Nov. 4-7, 2020.