Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05523895




Registration number
NCT05523895
Ethics application status
Date submitted
29/08/2022
Date registered
31/08/2022
Date last updated
12/11/2024

Titles & IDs
Public title
Pimavanserin for the Treatment of Irritability Associated with Autism Spectrum Disorder
Scientific title
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
Secondary ID [1] 0 0
ACP-103-069
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Irritability Associated with Autism Spectrum Disorder 0 0
Condition category
Condition code
Mental Health 0 0 0 0
Autistic spectrum disorders
Mental Health 0 0 0 0
Other mental health disorders
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pimavanserin
Treatment: Drugs - Placebo

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

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

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


Treatment: Drugs: Pimavanserin
Pimavanserin

Treatment: Drugs: Placebo
Pimavanserin matching placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change from Baseline at Week 6 in caregiver-rated Aberrant Behavior Checklist (ABC) Irritability subscale score
Timepoint [1] 0 0
6 weeks
Secondary outcome [1] 0 0
Change from Baseline at Week 6 in caregiver-rated ABC subscale scores: Stereotypic Behavior; Lethargy; Hyperactivity; Inappropriate speech
Timepoint [1] 0 0
6 weeks
Secondary outcome [2] 0 0
Change from Baseline at Week 6 in Clinical Global Impression-Severity (CGI-S) of Irritability score
Timepoint [2] 0 0
6 weeks
Secondary outcome [3] 0 0
Clinical Global Impression-Improvement (CGI-I) of irritability score at Week 6
Timepoint [3] 0 0
6 weeks
Secondary outcome [4] 0 0
Change from Baseline at Week 6 in Repetitive Behavior Scale-Revised (RBS-R) scores
Timepoint [4] 0 0
6 weeks
Secondary outcome [5] 0 0
Change from Baseline at Week 6 in Vineland Adaptive Behavior Scales (VABS)-Socialization subscale score
Timepoint [5] 0 0
6 weeks
Secondary outcome [6] 0 0
Change from Baseline at Week 6 in Caregiver Strain Questionnaire (CGSQ) scores
Timepoint [6] 0 0
6 weeks
Secondary outcome [7] 0 0
Proportion of patients with at least 25% reduction from Baseline in ABC-Irritability subscale score at Week 6
Timepoint [7] 0 0
6 weeks
Secondary outcome [8] 0 0
Proportion of patients with CGI-I of irritability score of 1 (very much improved) or 2 (much improved) at Week 6
Timepoint [8] 0 0
6 weeks
Secondary outcome [9] 0 0
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
Timepoint [9] 0 0
6 weeks

Eligibility
Key inclusion 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
* Additional inclusion/exclusion criteria apply. Subjects will be evaluated at screening to ensure that all criteria for study participation are met.
Minimum age
5 Years
Maximum age
17 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/08/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/09/2024
Sample size
Target
Accrual to date
Final
237
Recruitment in Australia
Recruitment state(s)
QDLVIC
Recruitment hospital [1] 0 0
Children's Health Queensland Hospital and Health Service - South Brisbane
Recruitment hospital [2] 0 0
Monash Health - Clayton
Recruitment hospital [3] 0 0
Murdoch Children's Research Institute - Parkville
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment postcode(s) [2] 0 0
3168 - Clayton
Recruitment postcode(s) [3] 0 0
3052 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Nevada
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
South Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
France
State/province [14] 0 0
Bordeaux
Country [15] 0 0
France
State/province [15] 0 0
Bron
Country [16] 0 0
France
State/province [16] 0 0
Nantes
Country [17] 0 0
France
State/province [17] 0 0
Paris
Country [18] 0 0
Hungary
State/province [18] 0 0
Budapest
Country [19] 0 0
Hungary
State/province [19] 0 0
Gyula
Country [20] 0 0
Hungary
State/province [20] 0 0
Szeged
Country [21] 0 0
Italy
State/province [21] 0 0
Bari
Country [22] 0 0
Italy
State/province [22] 0 0
Bosisio Parini
Country [23] 0 0
Italy
State/province [23] 0 0
Cagliari
Country [24] 0 0
Italy
State/province [24] 0 0
Foggia
Country [25] 0 0
Italy
State/province [25] 0 0
Genova
Country [26] 0 0
Italy
State/province [26] 0 0
Napoli
Country [27] 0 0
Italy
State/province [27] 0 0
Pavia
Country [28] 0 0
Italy
State/province [28] 0 0
Roma
Country [29] 0 0
Italy
State/province [29] 0 0
Rome
Country [30] 0 0
Italy
State/province [30] 0 0
Siena
Country [31] 0 0
Italy
State/province [31] 0 0
Verona
Country [32] 0 0
Poland
State/province [32] 0 0
Gdansk
Country [33] 0 0
Poland
State/province [33] 0 0
Wroclaw
Country [34] 0 0
Poland
State/province [34] 0 0
Lódz
Country [35] 0 0
Serbia
State/province [35] 0 0
Belgrade
Country [36] 0 0
Serbia
State/province [36] 0 0
Kragujevac
Country [37] 0 0
Serbia
State/province [37] 0 0
Nis
Country [38] 0 0
Serbia
State/province [38] 0 0
Novi Sad
Country [39] 0 0
Spain
State/province [39] 0 0
Alicante
Country [40] 0 0
Spain
State/province [40] 0 0
Barcelona
Country [41] 0 0
Spain
State/province [41] 0 0
Burgos
Country [42] 0 0
Spain
State/province [42] 0 0
Madrid
Country [43] 0 0
Spain
State/province [43] 0 0
Zamora

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
ACADIA Pharmaceuticals Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/study/NCT05523895
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Sharon Ortiz
Address 0 0
Country 0 0
Phone 0 0
646-397-7336
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05523895