Extension Study of Pimavanserin in Irritability Associated With Autism Spectrum Disorder

A 52-Week Open-Label Extension Study of Pimavanserin in Children and Adolescents With Irritability Associated With Autism Spectrum Disorder (ASD)

52-week, open-label extension study of double-blind study ACP-103-069 to determine the long-term safety and tolerability of pimavanserin for the treatment of irritability associated with ASD in children and adolescents (aged 5 to 17 years).

ACP-103-069 is a 6-week, randomized, double-blind, fixed-dose, placebo controlled, parallel group study of pimavanserin in children and adolescents with irritability associated with autism spectrum disorder (ASD).

Study Overview

• Status: Terminated
• Conditions: Irritability Associated With Autism Spectrum Disorder
• Intervention / Treatment: Drug: Pimavanserin

Detailed Description

This study will be conducted as a 52-week, open-label extension study of the antecedent double-blind study to determine the long-term safety and tolerability of pimavanserin for the treatment of irritability associated with ASD in children and adolescents (5 through 17 years old at the time of enrolling into the antecedent double-blind study).

• Study Type: Interventional
• Enrollment (Actual): 209
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • South Brisbane, Queensland, 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-1146
    • Magyarországi Református Egyház Bethesda Gyermekkórháza
  • Gyula, Hungary, H-5700
    • Békés Megyei Központi Kórház
  • Szeged, Hungary, H-6725
    • Szegedi Tudomanyegyetem
• Italy
  • Foggia, Italy, 71122
    • Policlinico Riuniti - Azienda Ospedaliero Universitaria
  • Napoli, Italy, 80131
    • Azienda Ospedaliera Universitaria "Federico II"
  • Pavia, Italy, 27100
    • Fondazione Istituto Neurologico Nazionale Casimiro Mondino - IRCCS
  • Rome, Italy, 00133
    • Fondazione PTV - Policlinico Tor Vergata
  • Verona, Italy, 37126
    • Azienda Ospedaliera Universitaria Integrata di Verona (AOUI)
  • LC
    • Bosisio Parini, LC, Italy, 23842
      • La Nostra Famiglia - Scientifica IRCCS Eugenio Medea
• Poland
  • Gdansk, Poland, 80-546
    • Centrum Badan Klinicznych Pi-House Sp. Z O.O.
  • Gdansk, Poland, 80-542
    • Gdańskie Centrum Zdrowia Sp. z o.o.
  • Lodz, Poland, 91-129
    • NAVICULA - Centrum Diagnozy i Terapii Autyzmu
  • Wroclaw, Poland, 50-414
    • Ginemedica Sp. Zoo, S. K.
  • Wroclaw, Poland, 54-238
    • Centrum Neuropsychiatrii Neuromed SP ZOZ
  • Wroclaw, Poland, 54-617
    • MedicMental Indywidualna Specjalistyczna Praktyka Lekarska Monika Szewczuk-Boguslawska
• Serbia
  • Belgrade, Serbia, 11000
    • Institute of Mental Health
  • Kragujevac, Serbia, 34000
    • University Clinical Center Kragujevac, Clinic for Psychiatry
  • Niš, 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)
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Southwest Autism Research and Resource Center
  • California
    • Glendale, California, United States, 91361
      • Cortica Inc. (Glendale)
    • San Rafael, California, United States, 94903
      • Cortica Inc.
  • Colorado
    • Centennial, Colorado, United States, 80112
      • 1st Allergy and Clinical Research Group, d/b/a IMUNOe Research Centers
  • District of Columbia
    • Washington D.C., 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, 32803-3809
      • 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 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA:

• Has completed the treatment period of study ACP-103-069
• Informed consent prior to the conduct of any study procedures
• Continues to be both clinically stable and not at imminent risk of suicide or injury to self, others, or property
• Continues to be medically stable at enrollment
• 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:

• Patient or parent/legally accepted representative is judged by the Investigator to be inappropriate for the study
• 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
• 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
• Serious and/or unstable psychiatric, neurologic, cardiovascular, respiratory, gastrointestinal, renal, hepatic, hematologic, or other medical disorder, including cancer or malignancies
• Any change in medical or treatment status that may increase the risk associated with taking pimavanserin, would interfere with safety assessments, or would confound the interpretation of study results
• Clinically significant abnormal ECG of protocol-defined cardiac conduction abnormalities
• Weight <15 kg
• 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pimavanserin; Pimavanserin once daily. All patients will receive the pimavanserin low dose (patients aged 5 to 12 years: 10 mg/day pimavanserin; patients aged 13 to 17 years: 20 mg/day) the first 2 weeks of the study. Thereafter, the dose may be increased to the high dose (5 to 12 years: 20 mg/day; 13 to 17 years: 34 mg/day) based on the Investigator's assessment of clinical response. After Week 2 and up to Week 20, dose adjustments are allowed at any clinic visit based on the Investigator's assessment of clinical response and tolerability. No further dose adjustments are allowed after Week 20.

Drug: Pimavanserin; Pimavanserin given once daily, as capsule of 10, 20, or 34 mg dose strength, respectively, according to the patient's age; Other Names: Nuplazid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-emergent Adverse Events	Number (%) of patients with treatment emergent adverse events	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aberrant Behavior Checklist-Irritability (ABC-I) and Clinical Global Impression-Improvement (CGI-I) Response Rate	The response rate was defined as the proportion of patients with at least 25% reduction from baseline to Week 52 in ABC-I and a CGI-I of irritability score of 1 (very much improved) or 2 (much improved) at Week 52, compared to baseline. Baseline was the baseline of the antecedent double-blind study APC-103-069. The ABC is a parent/caregiver-rated scale comprised of 5 subscales encompassing 58 items. Subscales are irritability, lethargy, stereotypic behavior, hyperactivity, and inappropriate speech. Items are rated on a 4-point Likert scale ranging from 0 (not at all a problem) to 3 (the problem is severe), with higher scores indicating more severe problems. Subscale scores are calculated by summing the items within that subscale. The CGI-I is a clinician-rated, 7-point scale to assess how much the patient's illness (here: the patient's irritability) has changed relative to baseline. Scores range from 1 (very much improved) to 7 (very much worse).	52 weeks

Collaborators and Investigators

• Sponsor: ACADIA Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2022
• Primary Completion (Actual): February 14, 2025
• Study Completion (Actual): February 14, 2025

Study Registration Dates

• First Submitted: August 30, 2022
• First Submitted That Met QC Criteria: September 23, 2022
• First Posted (Actual): September 27, 2022

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• 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-103-070

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