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: Recruiting
• 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 (Estimated): 228
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Sharon Ortiz; Phone Number: 646-397-7336; Email: Sharon.Ortiz@acadia-pharm.com
• Study Contact Backup: Name: Robert Hofbauer; Phone Number: 609-250-6221; Email: rhofbauer@acadia-pharm.com

Study Locations

• Australia
  • QDL
    • South Brisbane, QDL, Australia, 4101
      • Recruiting
      • Children's Health Queensland Hospital and Health Service
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Health
    • Parkville, Victoria, Australia, 3052
      • Recruiting
      • Murdoch Children's Research Institute
• France
  • Bordeaux, France, 33076
    • Recruiting
    • Centre Hospitalier Charles Perrens
  • Bron, France, 69678
    • Recruiting
    • Centre de Ressources Autisme Rhône-Alpes - Center Hospitalier le Vinatier
  • Nantes, France, 44093
    • Recruiting
    • CHU de Nantes
  • Paris, France, 75019
    • Recruiting
    • L'Assistance Publique - Hôpitaux de Paris, labélisé Institut Carnot
  • Rouen, France, 76301
    • Withdrawn
    • Centre Hospitalier Universitaire (C.H.U) de Rouen
• Hungary
  • Budapest, Hungary, H-1146
    • Recruiting
    • Magyarországi Református Egyház Bethesda Gyermekkórháza
  • Budapest, Hungary, H-1021
    • Active, not recruiting
    • Vadaskert Hospital
  • Gyula, Hungary, H-5700
    • Active, not recruiting
    • Békés Megyei Központi Kórház
  • Szeged, Hungary, H-6725
    • Recruiting
    • Szegedi Tudomanyegyetem
• Italy
  • Bari, Italy, 70124
    • Recruiting
    • Azienda Ospedaliero Universitaria (AOU) Consorziale Policlinico
  • Bosisio Parini, Italy, 23842
    • Recruiting
    • La Nostra Famiglia - Scientifica IRCCS Eugenio Medea
  • Cagliari, Italy, 09134
    • Recruiting
    • The Childhood and Adolescence Neuropsychiatry Clinic - University of Cagliari and Pediatric Hospital "A. Cao" - ASL 8 of Cagliari
  • Foggia, Italy, 71122
    • Recruiting
    • Policlinico Riuniti - Azienda Ospedaliero Universitaria
  • Genova, Italy, 16147
    • Recruiting
    • IRCCS Istituto Giannina Gaslini
  • Napoli, Italy, 80131
    • Recruiting
    • Azienda Ospedaliera Universitaria "Federico II"
  • Pavia, Italy, 27100
    • Recruiting
    • Fondazione Istituto Neurologico Nazionale Casimiro Mondino - IRCCS
  • Roma, Italy, 00133
    • Recruiting
    • Fondazione PTV - Policlinico Tor Vergata
  • Rome, Italy, 00165
    • Recruiting
    • IRCCS Ospedale Pediatrico Bambino Gesù
  • Siena, Italy, 53100
    • Recruiting
    • Azienda Ospedaliera-Universitaria Senese
  • Verona, Italy, 37126
    • Recruiting
    • Azienda Ospedaliera Universitaria Integrata di Verona (AOUI)
• Poland
  • Gdansk, Poland, 80-546
    • Recruiting
    • Centrum Badań Klinicznych PI-House sp. z o.o.
  • Gdańsk, Poland, 80-542
    • Recruiting
    • Gdańskie Centrum Zdrowia Sp. z o.o.
  • Wrocław, Poland, 50-414
    • Recruiting
    • Ginemedica Sp. Zoo, S.K.
  • Wrocław, Poland, 54-617
    • Recruiting
    • MedicMental Indywidualna Specjalistyczna Praktyka Lekarska Monika Szewczuk-Boguslawska
  • Wrocław, Poland, 54-238
    • Recruiting
    • Centrum Neuropsychiatrii NEUROMED SP ZOZ
  • Łódź, Poland, 91-129
    • Recruiting
    • NAVICULA - Centrum Diagnozy i Terapii Autyzmu
• Serbia
  • Belgrade, Serbia, 11000
    • Recruiting
    • Institute of Mental Health
  • Kragujevac, Serbia, 34000
    • Recruiting
    • University Clinical Center Kragujevac, Clinic for Psychiatry
  • Nis, Serbia, 18000
    • Recruiting
    • University Clinical Center Nis, Center for Mental Health
  • Novi Sad, Serbia, 21000
    • Recruiting
    • Clinical Center of Vojvodina, Clinic for Psychiatry
• Spain
  • Alicante, Spain, 03010
    • Recruiting
    • Hospital General de Alicante
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08007
    • Recruiting
    • Institut Global d´Atenció Integral del Neurodesenvolupament (IGAIN)
  • Burgos, Spain, 09006
    • Recruiting
    • Complejo Asistencial Universitario de Burgos
  • Madrid, Spain, 28031
    • Active, not recruiting
    • Hospital Universitario Infanta Leonor
  • Madrid, Spain, 28009
    • Active, not recruiting
    • Hospital Infantil Universitario Nino Jesus
  • Zamora, Spain, 49021
    • Active, not recruiting
    • Complejo Asistencial de Zamora
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Recruiting
      • Southwest Autism Research & Resource Center
  • California
    • Glendale, California, United States, 91361
      • Recruiting
      • Cortica Inc. (Glendale)
    • San Rafael, California, United States, 94903
      • Recruiting
      • Cortica Inc. (San Rafael)
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Recruiting
      • 1st Allergy and Clinical Research Group, d/b/a IMUNOe Research Centers
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Recruiting
      • Children's Research Institute
  • Florida
    • Gainesville, Florida, United States, 32607
      • Recruiting
      • The EHS Medical Practice, PA, D/B/A Sarkis Clinical Trials
    • Loxahatchee Groves, Florida, United States, 33470
      • Withdrawn
      • Axcess Medical Research
    • Orlando, Florida, United States, 32803
      • Recruiting
      • APG Research, LLC
  • Illinois
    • Naperville, Illinois, United States, 60563
      • Recruiting
      • AMR Baber Research Incorporated
  • Michigan
    • Bloomfield Hills, Michigan, United States, 48302
      • Withdrawn
      • Neurobehavorial Medical Group
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Recruiting
      • Clinical Research of Southern Nevada, LLC
  • New Jersey
    • Neptune, New Jersey, United States, 07753
      • Withdrawn
      • Jersey Shore University Medical Center, a division of HMH Hospitals Corporation
  • New York
    • Staten Island, New York, United States, 10314
      • Active, not recruiting
      • ERG Clinical Research - New York, PLLC DBA Richmond Behavioral Associates
    • White Plains, New York, United States, 10605
      • Recruiting
      • Research Foundation for Mental Hygiene, Inc.
  • Ohio
    • Avon Lake, Ohio, United States, 44012
      • Active, not recruiting
      • Quest Therapeutics of Avon Lake dba Haidar Almhana Nieding LLC
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19146
      • Recruiting
      • The Children's Hospital of Philadelphia
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75243
      • Recruiting
      • Relaro Medical Trials, LLC
    • Houston, Texas, United States, 77090
      • Active, not recruiting
      • Red Oak Psychiatry Associates, PA
    • Plano, Texas, United States, 75093
      • Recruiting
      • AIM Trials, LLC
  • Utah
    • Draper, Utah, United States, 84020
      • Withdrawn
      • Cedar Clinical Research
  • Washington
    • Everett, Washington, United States, 98201
      • Recruiting
      • Eastside Therapeutic Resource, Inc. dba Core Clinical Research
    • Tacoma, Washington, United States, 98405
      • Withdrawn
      • MultiCare Health System

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 (ABC) Irritability subscale score	The Aberrant Behavior Checklist (ABC) is a caregiver-rated scale comprised of five 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-Irritability is one of the subscales and comprises of 15 items. Minimum score is 0, maximum is 45. The ABC will be administered at Screening and Baseline, and at all post-Baseline visits from Week 1 through Week 6. 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 (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 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): May 9, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

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