Pimavanserin for the Treatment of Irritability Associated with Autism Spectrum Disorder

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 thestudy, follow protocol requirements, and be willing to comply with study drugadministration 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 theAutism 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 hyperactivitydisorder (ADHD) or anxiety disorder

• Drug-naïve to antipsychotic treatment (or <2 weeks antipsychotic treatment for anyreason), or prior lack of tolerability to adequate dose of any duration ofantipsychotic confirmed by caregiver and medical records review

• If patient is undergoing concurrent behavioral therapy for autism related symptomsor behaviors, this non-pharmacological treatment regimen has been stable for atleast 4 weeks, and will be consistent throughout the study

• For female patients only: unable to become pregnant or agree to use a highlyeffective non-hormonal method of contraception. Females of childbearing potentialmust have a negative pregnancy test

EXCLUSION CRITERIA:

• Requires treatment with a medication prohibited by the protocol, includingconcomitant psychotropic drugs targeting irritability, including those usedoff-label (clonidine, guanfacine, and propranolol; lithium, valproate), medicationsthat 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 comorbidpsychiatric 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 psychotropicmedication

• 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 posean 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 behavioraldisturbance or profound intellectual disability (IQ ≤50)

• History of seizures, unless seizure-free and off epileptic drugs for at least 6months

• Any condition that, in the opinion of the Investigator, would interfere with theability to comply with study instructions, or that might confound the interpretationof the study results or put the subject at undue risk

• Current evidence, or history within the last 12 weeks, of a serious and/or unstablepsychiatric, 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 conductionabnormalities

• Known family or personal history or symptoms of long QT syndrome or history ofcardiac arrhythmias or risk factors for torsade de pointes and/or sudden death,including symptomatic bradycardia, hypokalemia or hypomagnesemia, and presence ofcongenital prolongation of the QT interval

• Any member of the household has suffered from COVID-19 or had a COVID-19 (PCR orimmunoglobulin) 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 ofchildbearing potential)

• Sensitivity to pimavanserin or any of the excipients

• Participating in another clinical study of any investigational drug, device, orintervention

• Participated in greater than 2 interventional pharmaceutical clinical researchstudies in the last 6 months

• Additional inclusion/exclusion criteria apply. Subjects will be evaluated atscreening to ensure that all criteria for study participation are met.