Extension Study of Pimavanserin in Irritability Associated With Autism Spectrum Disorder

Study Overview
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Brief Summary
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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).

Detailed Description
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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).

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

Conditions
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Irritability Associated With Autism Spectrum Disorder

Intervention / Treatment
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* Drug: Pimavanserin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pimavanserin<br>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<br>* Pimavanserin given once daily, as capsule of 10, 20, or 34 mg dose strength, respectively, according to the patient's age<br>* Other names: Nuplazid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-emergent adverse events | Number of Subjects With Adverse Events (AEs), Discontinuations Due to AEs and Serious AEs (SAEs) over 52 weeks of treatment. The Safety population consists of all subjects who received at least one dose of study drug in this study. | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the continued response to long-term pimavanserin treatment in children and adolescents with irritability associated with ASD, defined by a composite endpoint of ABC-I and CGI-I response. | Evaluate the continued response to long-term pimavanserin treatment in children and adolescents with irritability associated with ASD as assessed by a composite of a reduction in the Aberrant Behavior Checklist-Irritability (ABC-I) subscale score from baseline combined with a reduction in Clinical Global Impression-Improvement (CGI-I) of irritability score from baseline. | 52 weeks |