Pimavanserin for Irritability in Children and Adolescents With Autism Spectrum Disorder: Phase 2 Randomized Trial

OBJECTIVE: This study evaluated the efficacy and safety of pimavanserin in children and adolescents with irritability associated with autism spectrum disorder (ASD). METHOD: In this phase 2, randomized, double-masked, placebo-controlled study (NCT05523895), patients were randomized 1:1:1 to low-dose pimavanserin (5-12 years, 10 mg/d; 13-17 years, 20 mg/d), high-dose pimavanserin (5-12 years, 20 mg/d; 13-17 years, 34 mg/d), or placebo for 6 weeks, followed by a 30-day follow-up period. The primary endpoint was the change from baseline at week 6 in the caregiver-rated Aberrant Behavior Checklist-Irritability (ABC-I) subscale score. Key secondary endpoints included week 6 change from baseline in Clinical Global Impression (CGI)-Severity irritability score, CGI-Improvement irritability score, Repetitive Behavior Scale-Revised, Vineland Adaptive Behavior Scales-socialization subscale score, and the Caregiver Strain Questionnaire. Treatment-emergent adverse events were assessed. RESULTS: A total of 216 (93.1%) randomized patients completed double-masked treatment (low-dose pimavanserin, n = 76; high-dose pimavanserin, n = 78; placebo, n = 78). The least squares mean (LSM [95% CI]) improvement in the ABC-I subscale score was not significantly different from placebo for either pimavanserin group (placebo, -9.6 [-11.7, -7.5]; low-dose pimavanserin, -11.2 [-13.3, -9.0]; high-dose pimavanserin, -11.2 [-13.3, -9.1]). No statistically significant differences occurred between the placebo and pimavanserin groups for any secondary endpoint. Treatment-emergent adverse events (TEAEs) were similar across groups (placebo, n = 39 [50.0%]; low-dose pimavanserin, n = 36 [46.8%]; high-dose pimavanserin, n = 43 [53.1%]). No serious TEAEs or deaths occurred. CONCLUSION: Pimavanserin was well tolerated, but selected doses were not demonstrated to be efficacious compared with placebo for the short-term treatment of irritability in children or adolescents with ASD. CLINICAL TRIAL REGISTRATION INFORMATION: A study to evaluate the efficacy and safety of Pimavanserin for the treatment of irritability associated with Autism Spectrum Disorder; https://clinicaltrials.gov/study/NCT05523895 DIVERSITY & INCLUSION STATEMENT: We worked to ensure that the study questionnaires were prepared in an inclusive way.