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Pimavanserin for Irritability in Children and Adolescents With Autism Spectrum Disorder: Phase 2 Randomized Trial
Dragana Bugarski-Kirola1, Robert K Hofbauer2, Snjezana Sameljak1
1Acadia Pharmaceuticals GmbH, Basel, Switzerland.
Insights
Pimavanserin showed no significant efficacy in treating irritability in children and adolescents with autism spectrum disorder (ASD). The medication was well-tolerated, with similar side effects to placebo in this short-term study.
Area of Science:
- Pediatric Psychiatry
- Neurodevelopmental Disorders
- Pharmacological Interventions
Background:
- Irritability is a common and challenging symptom in children and adolescents with Autism Spectrum Disorder (ASD).
- Current treatment options for ASD-related irritability are limited, necessitating the exploration of novel therapeutic agents.
- Pimavanserin, a selective serotonin inverse agonist, has shown efficacy in other psychiatric conditions.
Purpose of the Study:
- To evaluate the efficacy and safety of pimavanserin in pediatric and adolescent populations experiencing irritability associated with ASD.
- To compare the effects of two different dosage regimens of pimavanserin against a placebo in a randomized, double-masked, controlled trial.
Main Methods:
- A Phase 2, randomized, double-masked, placebo-controlled study involving 216 children and adolescents with ASD.
- Participants received low-dose pimavanserin, high-dose pimavanserin, or placebo for 6 weeks.
- The primary outcome measure was the change in the Aberrant Behavior Checklist-Irritability (ABC-I) subscale score from baseline to week 6.
Main Results:
- Pimavanserin did not demonstrate statistically significant improvement in the primary endpoint (ABC-I score) compared to placebo.
- No significant differences were observed between pimavanserin groups and placebo for key secondary endpoints.
- Treatment-emergent adverse events were comparable across all groups, with no serious adverse events or deaths reported.
Conclusions:
- Pimavanserin was found to be well-tolerated in children and adolescents with ASD.
- The selected doses of pimavanserin did not prove efficacious for the short-term management of irritability in this population.
- Further research may be needed to explore different dosages or patient subgroups, but current evidence does not support its use for ASD-related irritability.
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.
