Pimavanserin for the Treatment of Irritability Associated With Autism Spectrum Disorder

NCT ID: NCT05523895

Last Updated: 2025-08-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 237 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-09
• Study Completion Date: 2024-09-27

Brief Summary

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

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.

Conditions

Irritability Associated With Autism Spectrum Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Placebo given once daily, as one capsule matching in size and color the respective pimavanserin treatment

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Pimavanserin matching placebo

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

Group Type: EXPERIMENTAL

Pimavanserin

Intervention Type: DRUG

Pimavanserin

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

Group Type: EXPERIMENTAL

Pimavanserin

Intervention Type: DRUG

Pimavanserin

Interventions

Pimavanserin

Pimavanserin

Intervention Type: DRUG

Placebo

Pimavanserin matching placebo

Intervention Type: DRUG

Other Intervention Names

Nuplazid

Eligibility Criteria

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

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ACADIA Pharmaceuticals Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Southwest Autism Research & Resource Center

Phoenix, Arizona, United States

Cortica Inc. (Glendale)

Glendale, California, United States

Cortica Inc. (San Rafael)

San Rafael, California, United States

1st Allergy and Clinical Research Group, d/b/a IMUNOe Research Centers

Centennial, Colorado, United States

Children's Research Institute

Washington D.C., District of Columbia, United States

The EHS Medical Practice, PA, D/B/A Sarkis Clinical Trials

Gainesville, Florida, United States

APG Research, LLC

Orlando, Florida, United States

AMR Baber Research Incorporated

Naperville, Illinois, United States

Clinical Research of Southern Nevada, LLC

Las Vegas, Nevada, United States

ERG Clinical Research - New York, PLLC DBA Richmond Behavioral Associates

Staten Island, New York, United States

Quest Therapeutics of Avon Lake dba Haidar Almhana Nieding LLC

Avon Lake, Ohio, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Relaro Medical Trials, LLC

Dallas, Texas, United States

Red Oak Psychiatry Associates, PA

Houston, Texas, United States

AIM Trials, LLC

Plano, Texas, United States

Eastside Therapeutic Resource, Inc. dba Core Clinical Research

Everett, Washington, United States

Children's Health Queensland Hospital and Health Service

South Brisbane, QDL, Australia

Monash Health

Clayton, Victoria, Australia

Murdoch Children's Research Institute

Parkville, Victoria, Australia

Centre Hospitalier Charles Perrens

Bordeaux, , France

Centre de Ressources Autisme Rhône-Alpes - Center Hospitalier le Vinatier

Bron, , France

CHU de Nantes

Nantes, , France

L'Assistance Publique - Hôpitaux de Paris, labélisé Institut Carnot

Paris, , France

Vadaskert Hospital

Budapest, , Hungary

Magyarországi Református Egyház Bethesda Gyermekkórháza

Budapest, , Hungary

Békés Megyei Központi Kórház

Gyula, , Hungary

Szegedi Tudományegyetem

Szeged, , Hungary

Azienda Ospedaliero Universitaria (AOU) Consorziale Policlinico

Bari, , Italy

La Nostra Famiglia - Scientifica IRCCS Eugenio Medea

Bosisio Parini, , Italy

The Childhood and Adolescence Neuropsychiatry Clinic - University of Cagliari and Pediatric Hospital "A. Cao" - ASL 8 of Cagliari

Cagliari, , Italy

Policlinico Riuniti - Azienda Ospedaliero Universitaria

Foggia, , Italy

IRCCS Istituto Giannina Gaslini

Genova, , Italy

Azienda Ospedaliera Universitaria "Federico II"

Napoli, , Italy

Fondazione Istituto Neurologico Nazionale Casimiro Mondino - IRCCS

Pavia, , Italy

Fondazione PTV - Policlinico Tor Vergata

Roma, , Italy

IRCCS Ospedale Pediatrico Bambino Gesù

Rome, , Italy

Azienda Ospedaliera-Universitaria Senese

Siena, , Italy

Azienda Ospedaliera Universitaria Integrata di Verona (AOUI)

Verona, , Italy

Gdańskie Centrum Zdrowia Sp. z o.o.

Gdansk, , Poland

Centrum Badań Klinicznych PI-House Sp. z o.o.

Gdansk, , Poland

NAVICULA - Centrum Diagnozy i Terapii Autyzmu

Lodz, , Poland

Ginemedica Sp. Zoo, S.K.

Wroclaw, , Poland

Centrum Neuropsychiatrii NEUROMED SP ZOZ

Wroclaw, , Poland

MedicMental Indywidualna Specjalistyczna Praktyka Lekarska Monika Szewczuk-Boguslawska

Wroclaw, , Poland

Institute of Mental Health

Belgrade, , Serbia

University Clinical Center Kragujevac, Clinic for Psychiatry

Kragujevac, , Serbia

University Clinical Center Nis, Center for Mental Health

Niš, , Serbia

Clinical Center of Vojvodina, Clinic for Psychiatry

Novi Sad, , Serbia

Hospital General de Alicante

Alicante, , Spain

Institut Global d´Atenció Integral del Neurodesenvolupament (IGAIN)

Barcelona, , Spain

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Hospital Clínic de Barcelona

Barcelona, , Spain

Complejo Asistencial Universitario de Burgos

Burgos, , Spain

Hospital Universitario Infanta Leonor

Madrid, , Spain

Complejo Asistencial de Zamora

Zamora, , Spain

Countries

United States; Australia; France; Hungary; Italy; Poland; Serbia; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

ACP-103-069

Identifier Type: -

Identifier Source: org_study_id