Pimavanserin for the Treatment of Irritability Associated With Autism Spectrum Disorder

This study will be conducted as a 6-week, randomized, double-blind, fixed-dose, placebo-controlled, parallel group study in children and adolescents (5 through 17 years of age) with ASD with irritability, agitation, or self-injurious behaviors.

Inclusion criteria

• Male or female and 5 through 17 years of age
• Informed consent prior to the conduct of any study procedures
• Patients (to the best of his/her ability), parent/legally accepted representative, and designated caregiver (if applicable) are able to understand the nature of the study, follow protocol requirements, and be willing to comply with study drug administration requirements
• Able to swallow a test placebo capsule without difficulty
• Meets Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for a primary diagnosis of ASD (APA 2013) and diagnosis is confirmed by the Autism Diagnostic Interview-Revised (ADI-R)
• Score ≥18 on the Irritability subscale of the Aberrant Behavior Checklist (ABC)
• Score ≥4 (moderate or greater severity) on the Clinical Global Impression-Severity (CGI-S) of irritability score
• No current comorbid psychiatric disorder other than attention-deficit hyperactivity disorder (ADHD) or anxiety disorder
• Drug-naïve to antipsychotic treatment (or <2 weeks antipsychotic treatment for any reason), or prior lack of tolerability to adequate dose of any duration of antipsychotic confirmed by caregiver and medical records review
• If patient is undergoing concurrent behavioral therapy for autism related symptoms or behaviors, this non-pharmacological treatment regimen has been stable for at least 4 weeks, and will be consistent throughout the study
• For female patients only: unable to become pregnant or agree to use a highly effective non-hormonal method of contraception. Females of childbearing potential must have a negative pregnancy test

Exclusion criteria

• Requires treatment with a medication prohibited by the protocol, including concomitant psychotropic drugs targeting irritability, including those used off-label (clonidine, guanfacine, and propranolol; lithium, valproate), medications that prolong the QT interval, and strong cytochrome P450 (CYP) 3A4 enzyme (CYP3A4) inhibitors and inducers
• Changes in medications or medication doses (for medical and allowed comorbid psychiatric conditions) in the last 4 weeks
• Any known history of angioedema, serotonin or neuroleptic malignant syndromes, dystonic reaction, or tardive dyskinesia, due to an antipsychotic or psychotropic medication
• At a significant risk of suicide, or is a danger to self or others
• At risk of significant violent behavior to the extent that participation would pose an undue risk to other patients, caregivers, or others
• Positive urine drug test
• Met DSM-5 criteria for substance use disorders within the last 6 months
• Confirmed genetic disorder associated with ASD, a cognitive and/ or behavioral disturbance or profound intellectual disability (IQ ≤50)
• History of seizures, unless seizure-free and off epileptic drugs for at least 6 months
• Any condition that, in the opinion of the Investigator, would interfere with the ability to comply with study instructions, or that might confound the interpretation of the study results or put the subject at undue risk
• Current evidence, or history within the last 12 weeks, of a serious and/or unstable psychiatric, neurologic, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical disorder, including cancer or malignancies
• Weight <15 kg
• History or presence on at least one ECG of protocol-defined cardiac conduction abnormalities
• Known family or personal history or symptoms of long QT syndrome or history of cardiac arrhythmias or risk factors for torsade de pointes and/or sudden death, including symptomatic bradycardia, hypokalemia or hypomagnesemia, and presence of congenital prolongation of the QT interval
• Any member of the household has suffered from COVID-19 or had a COVID-19 (PCR or immunoglobulin) positive test in the last 4 weeks
• One or more clinical laboratory test value outside of protocol-defined limits
• Breastfeeding or lactating, or has a positive pregnancy test result (for patients of childbearing potential)
• Sensitivity to pimavanserin or any of the excipients
• Participating in another clinical study of any investigational drug, device, or intervention
• Participated in greater than 2 interventional pharmaceutical clinical research studies in the last 6 months
• Additional inclusion/exclusion criteria apply. Subjects will be evaluated at screening to ensure that all criteria for study participation are met.