Pimavanserin for the Treatment of Irritability Associated With Autism Spectrum Disorder

A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Pimavanserin for the Treatment of Irritability Associated With Autism Spectrum Disorder

6-week, randomized, double-blind, fixed-dose, placebo-controlled, parallel group study in children and adolescents (aged 5 to17 years) with autism spectrum disorder (ASD) with irritability, agitation, or self-injurious behaviors to study the efficacy and safety of pimavanserin

Study Overview

• Status: Completed
• Conditions: Irritability Associated With Autism Spectrum Disorder
• Intervention / Treatment: Drug: Placebo; Drug: Pimavanserin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 237
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • QDL
    • South Brisbane, QDL, Australia, 4101
      • Children's Health Queensland Hospital and Health Service
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health
    • Parkville, Victoria, Australia, 3052
      • Murdoch Children's Research Institute
• France
  • Bordeaux, France, 33076
    • Centre Hospitalier Charles Perrens
  • Bron, France, 69678
    • Centre de Ressources Autisme Rhône-Alpes - Center Hospitalier le Vinatier
  • Nantes, France, 44093
    • CHU de Nantes
  • Paris, France, 75019
    • L'Assistance Publique - Hôpitaux de Paris, labélisé Institut Carnot
• Hungary
  • Budapest, Hungary, H-1021
    • Vadaskert Hospital
  • Budapest, Hungary, H-1146
    • Magyarországi Református Egyház Bethesda Gyermekkórháza
  • Gyula, Hungary, H-5700
    • Békés Megyei Központi Kórház
  • Szeged, Hungary, H-6725
    • Szegedi Tudomanyegyetem
• Italy
  • Bari, Italy, 70124
    • Azienda Ospedaliero Universitaria (AOU) Consorziale Policlinico
  • Bosisio Parini, Italy, 23842
    • La Nostra Famiglia - Scientifica IRCCS Eugenio Medea
  • Cagliari, Italy, 09134
    • The Childhood and Adolescence Neuropsychiatry Clinic - University of Cagliari and Pediatric Hospital "A. Cao" - ASL 8 of Cagliari
  • Foggia, Italy, 71122
    • Policlinico Riuniti - Azienda Ospedaliero Universitaria
  • Genova, Italy, 16147
    • IRCCS Istituto Giannina Gaslini
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Universitaria "Federico II"
  • Pavia, Italy, 27100
    • Fondazione Istituto Neurologico Nazionale Casimiro Mondino - IRCCS
  • Roma, Italy, 00133
    • Fondazione PTV - Policlinico Tor Vergata
  • Rome, Italy, 00165
    • Irccs Ospedale Pediatrico Bambino Gesu
  • Siena, Italy, 53100
    • Azienda Ospedaliera-Universitaria Senese
  • Verona, Italy, 37126
    • Azienda Ospedaliera Universitaria Integrata di Verona (AOUI)
• Poland
  • Gdansk, Poland, 80-546
    • Centrum Badan Klinicznych PI-House sp. z o.o.
  • Gdańsk, Poland, 80-542
    • Gdańskie Centrum Zdrowia Sp. z o.o.
  • Wrocław, Poland, 50-414
    • Ginemedica Sp. Zoo, S.K.
  • Wrocław, Poland, 54-238
    • Centrum Neuropsychiatrii Neuromed SP ZOZ
  • Wrocław, Poland, 54-617
    • MedicMental Indywidualna Specjalistyczna Praktyka Lekarska Monika Szewczuk-Boguslawska
  • Łódź, Poland, 91-129
    • NAVICULA - Centrum Diagnozy i Terapii Autyzmu
• Serbia
  • Belgrade, Serbia, 11000
    • Institute of Mental Health
  • Kragujevac, Serbia, 34000
    • University Clinical Center Kragujevac, Clinic for Psychiatry
  • Nis, Serbia, 18000
    • University Clinical Center Nis, Center for Mental Health
  • Novi Sad, Serbia, 21000
    • Clinical Center of Vojvodina, Clinic for Psychiatry
• Spain
  • Alicante, Spain, 03010
    • Hospital General de Alicante
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08007
    • Institut Global d´Atenció Integral del Neurodesenvolupament (IGAIN)
  • Burgos, Spain, 09006
    • Complejo Asistencial Universitario de Burgos
  • Madrid, Spain, 28031
    • Hospital Universitario Infanta Leonor
  • Zamora, Spain, 49021
    • Complejo Asistencial de Zamora
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Southwest Autism Research & Resource Center
  • California
    • Glendale, California, United States, 91361
      • Cortica Inc. (Glendale)
    • San Rafael, California, United States, 94903
      • Cortica Inc. (San Rafael)
  • Colorado
    • Centennial, Colorado, United States, 80112
      • 1st Allergy and Clinical Research Group, d/b/a IMUNOe Research Centers
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's Research Institute
  • Florida
    • Gainesville, Florida, United States, 32607
      • The EHS Medical Practice, PA, D/B/A Sarkis Clinical Trials
    • Orlando, Florida, United States, 32803
      • Apg Research, Llc
  • Illinois
    • Naperville, Illinois, United States, 60563
      • AMR Baber Research Incorporated
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Clinical Research of Southern Nevada, LLC
  • New York
    • Staten Island, New York, United States, 10314
      • ERG Clinical Research - New York, PLLC DBA Richmond Behavioral Associates
  • Ohio
    • Avon Lake, Ohio, United States, 44012
      • Quest Therapeutics of Avon Lake dba Haidar Almhana Nieding LLC
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19146
      • The Children's Hospital of Philadelphia
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75243
      • Relaro Medical Trials, LLC
    • Houston, Texas, United States, 77090
      • Red Oak Psychiatry Associates, PA
    • Plano, Texas, United States, 75093
      • AIM Trials, LLC
  • Washington
    • Everett, Washington, United States, 98201
      • Eastside Therapeutic Resource, Inc. dba Core Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo given once daily, as one capsule matching in size and color the respective pimavanserin treatment	Drug: Placebo; Pimavanserin matching placebo
Experimental: Pimavanserin low dose; Patients aged 5 to 12 years: 10 mg/day pimavanserin Patients aged 13 to 17 years: 20 mg/day pimavanserin Pimavanserin given once daily, as capsule of 10 or 20 mg dose strength, respectively, according to the patient's age	Drug: Pimavanserin; Pimavanserin; Other Names: Nuplazid
Experimental: Pimavanserin high dose; Patients aged 5 to 12 years: 20 mg/day pimavanserin Patients aged 13 to 17 years: 34 mg/day pimavanserin Pimavanserin given once daily, as capsule of 20 or 34 mg dose strength, respectively, according to the patient's age	Drug: Pimavanserin; Pimavanserin; Other Names: Nuplazid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline at Week 6 in Caregiver-rated Aberrant Behavior Checklist Irritability (ABC-I) Subscale Score	The Aberrant Behavior Checklist (ABC) is a caregiver-rated scale comprised of 5 empirically-derived subscales encompassing 58 items that describe various behavior problems. It measures domains of irritability, lethargy/social withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech. ABC-I is one of the subscales and comprises of 15 items. Minimum score is 0, maximum is 45. A score for each item ranges from 0 indicating "not at all a problem" to 3 indicating "the problem is severe in degree". Subscale scores are calculated by summing the items within that subscale. Higher scores indicate greater impairment.	6 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from Baseline at Week 6 in caregiver-rated ABC subscale scores: Stereotypic Behavior; Lethargy; Hyperactivity; Inappropriate speech	6 weeks
Change from Baseline at Week 6 in Clinical Global Impression-Severity (CGI-S) of Irritability score	6 weeks
Clinical Global Impression-Improvement (CGI-I) of irritability score at Week 6	6 weeks
Change from Baseline at Week 6 in Repetitive Behavior Scale-Revised (RBS-R) scores	6 weeks
Change from Baseline at Week 6 in Vineland Adaptive Behavior Scales (VABS)-Socialization subscale score	6 weeks
Change from Baseline at Week 6 in Caregiver Strain Questionnaire (CGSQ) scores	6 weeks
Proportion of patients with at least 25% reduction from Baseline in ABC-Irritability subscale score at Week 6	6 weeks
Proportion of patients with CGI-I of irritability score of 1 (very much improved) or 2 (much improved) at Week 6	6 weeks
Proportion of patients with at least 25% reduction from Baseline in ABC-Irritability subscale score and CGI-I of irritability score of 1 or 2 at Week 6	6 weeks

Collaborators and Investigators

• Sponsor: ACADIA Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2022
• Primary Completion (Actual): September 27, 2024
• Study Completion (Actual): September 27, 2024

Study Registration Dates

• First Submitted: August 29, 2022
• First Submitted That Met QC Criteria: August 29, 2022
• First Posted (Actual): August 31, 2022

Study Record Updates

• Last Update Posted (Actual): August 24, 2025
• Last Update Submitted That Met QC Criteria: August 7, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Placebo-controlled; Randomized
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Autism Spectrum Disorder; Autistic Disorder; Child Development Disorders, Pervasive; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Neurotransmitter Agents; Tranquilizing Agents; Psychotropic Drugs; Antiparkinson Agents; Anti-Dyskinesia Agents; Serotonin Antagonists; Serotonin Agents; Antipsychotic Agents; Serotonin 5-HT2 Receptor Antagonists; Pimavanserin
• Other Study ID Numbers: ACP-103-069

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No