Pimavanserin for Autism Spectrum Disorder

No longer recruiting at 59 trial locations

Overseen By Sharon Ortiz

Age: < 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: ACADIA Pharmaceuticals Inc.

Must not be taking: Psychotropic drugs, QT prolongers

Disqualifiers: Suicide risk, Violent behavior, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the long-term safety and tolerability of pimavanserin, a treatment for irritability in children and teens with autism spectrum disorder (ASD). By continuing from a previous 6-week study, participants will help researchers assess whether pimavanserin remains a safe option over a longer period. The study specifically targets those who have completed the initial study and are clinically stable with ongoing irritability linked to ASD. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

You may need to stop taking certain medications, especially those that target irritability or affect heart rhythm, as well as some other specific drugs. It's best to discuss your current medications with the study team to see if any changes are needed.

Do I need to stop my current medications to join the trial?

Yes, you may need to stop certain medications. The trial prohibits medications that target irritability, prolong the QT interval, or are strong CYP3A4 inhibitors and inducers.

Is there any evidence suggesting that pimavanserin is likely to be safe for humans?

Research has shown that pimavanserin is being studied for safety and tolerance in children and teens with autism. Earlier studies tested pimavanserin for its effects on irritability in individuals with autism spectrum disorder (ASD). These studies assessed treatment management and monitored side effects.

The FDA has already approved pimavanserin for other uses, indicating general safety. However, side effects can vary; some individuals have reported dizziness or headaches.

Overall, various studies have tested the treatment, and it is generally well-tolerated. However, like any medication, it can have side effects. Consulting a doctor and considering all information is important before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for autism?

Most treatments for Autism Spectrum Disorder focus on behavioral therapies or medications that address specific symptoms, like irritability, through altering neurotransmitter activity such as dopamine or serotonin. However, Pimavanserin is unique because it primarily targets the serotonin 5-HT2A receptor, which differentiates it from standard treatments. Researchers are excited about Pimavanserin because it offers a new mechanism of action, potentially providing benefits for managing symptoms without some of the side effects associated with typical antipsychotics. This approach could mean more effective management of symptoms with potentially fewer drawbacks, offering a new avenue of hope for individuals with autism and their families.

What evidence suggests that pimavanserin might be an effective treatment for irritability associated with autism spectrum disorder?

Research shows that pimavanserin might help reduce irritability in children and teens with autism spectrum disorder (ASD). An earlier study found pimavanserin to be safe and well-tolerated by young people with ASD, showing early signs of reducing irritability. In this trial, participants will take pimavanserin once daily, with doses adjusted based on clinical response and tolerability. Previous studies suggested that pimavanserin could alleviate irritability symptoms without causing serious side effects. These findings offer hope for those seeking new ways to manage irritability linked to ASD. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for children and adolescents aged 5 to 17 with Autism Spectrum Disorder who completed the ACP-103-069 study. Participants must be clinically stable, not at immediate risk of harm to self or others, medically stable, and females able to bear children must use effective contraception.

Inclusion Criteria

Has completed the treatment period of study ACP-103-069

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

Exclusion Criteria

I weigh less than 15 kg.

Patient or parent/legally accepted representative is judged by the Investigator to be inappropriate for the study

Clinically significant abnormal ECG of protocol-defined cardiac conduction abnormalities

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pimavanserin for 52 weeks to assess long-term safety and tolerability

52 weeks

Regular clinic visits for dose adjustments and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pimavanserin

Trial Overview The trial tests the long-term safety and effectiveness of Pimavanserin in treating irritability associated with ASD over a period of 52 weeks. It's an extension of a previous study where Pimavanserin was compared to a placebo.

How Is the Trial Designed?

Group I: Pimavanserin Experimental Treatment 1 Intervention

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.

Pimavanserin is already approved in United States for the following indications:

Approved in United States as Nuplazid for:

• Hallucinations and delusions associated with Parkinson's disease psychosis

Who Is Running the Clinical Trial?

ACADIA Pharmaceuticals Inc.

Lead Sponsor

Trials

49

Recruited

11,700+

Founded

1993

Headquarters

San Diego, USA

Known For

Neurological Disorders

Top Products

Nuplazid (pimavanserin), Daybue (trofinetide)

Published Research Related to This Trial

In a clinical trial involving 59 children and adolescents with autism spectrum disorders, both aripiprazole and risperidone were effective in reducing irritability, as measured by the Aberrant Behavior Checklist (ABC) scores over 2 months.

The study found that the rates of adverse effects were similar for both medications, indicating that aripiprazole (mean dose 5.5 mg/day) and risperidone (mean dose 1.12 mg/day) have comparable safety profiles, allowing treatment choice to be based on patient preference and clinical considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A head-to-head comparison of aripiprazole and risperidone for safety and treating autistic disorders, a randomized double blind clinical trial. Ghanizadeh, A., Sahraeizadeh, A., Berk, M.[2022]

Aripiprazole has been shown to effectively reduce irritability, hyperactivity, and stereotypical behaviors in children and adolescents with autism spectrum disorders (ASD), based on two randomized controlled trials involving 316 participants over eight weeks.

While aripiprazole is effective, it is associated with notable side effects such as weight gain, sedation, and tremors, which need to be carefully considered when evaluating its use for treating ASD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole for autism spectrum disorders (ASD). Hirsch, LE., Pringsheim, T.[2023]

Pimavanserin is a selective serotonin 2A receptor inverse agonist that has been approved in the US specifically for treating hallucinations and delusions in patients with Parkinson's disease psychosis, a condition affecting up to 60% of Parkinson's patients.

The approval of pimavanserin is significant as it provides a treatment option for a condition that has limited therapeutic alternatives and is associated with increased morbidity and mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pimavanserin: First Global Approval. Markham, A.[2022]

Pimavanserin is the first FDA-approved treatment for Parkinson's disease psychosis (PDP) and has been shown to be well-tolerated with minimal adverse effects and no worsening of motor symptoms, based on four randomized controlled trials.

A Phase III trial demonstrated that pimavanserin 40mg significantly improved PDP symptoms compared to placebo, with notable improvements in secondary outcomes such as caregiver burden and sleep quality, highlighting its efficacy as a treatment option for PDP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pimavanserin: A Novel Drug Approved to Treat Parkinson's Disease Psychosis. Kitten, AK., Hallowell, SA., Saklad, SR., et al.[2021]

Aripiprazole has been shown to effectively reduce irritability and improve overall behavior in children with autistic disorder, based on data from two randomized controlled trials involving nearly 300 patients.

While aripiprazole is generally well tolerated with mild to moderate side effects, about 30% of patients experienced clinically relevant weight gain; however, it has fewer metabolic effects compared to other atypical antipsychotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging role of aripiprazole for treatment of irritability associated with autistic disorder in children and adolescents. Stachnik, J., Gabay, M.[2021]

Pimavanserin is the first FDA-approved drug specifically for treating hallucinations and delusions in Parkinson's disease psychosis, showing significant improvement in symptoms compared to placebo in a pivotal phase III clinical trial.

The drug works as a potent inverse agonist at serotonin 5-HT2A receptors, with a long half-life of 57 hours, allowing for once-daily dosing and demonstrating a favorable safety profile without impairing motor functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pimavanserin: novel pharmacotherapy for Parkinson's disease psychosis. Sahli, ZT., Tarazi, FI.[2018]

Pimavanserin is a selective inverse agonist of the 5-HT2A receptor and has been shown to be a safe and effective treatment for Parkinson's disease psychosis (PDP), significantly reducing hallucinations and delusions without worsening motor symptoms.

Unlike traditional antipsychotics, which can exacerbate motor dysfunction and carry serious warnings for elderly patients, pimavanserin offers a promising alternative, having received breakthrough therapy status from the FDA due to the urgent need for effective treatments in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pimavanserin. Hunter, NS., Anderson, KC., Cox, A.[2017]

Pimavanserin is effective in treating hallucinations and delusions associated with Parkinson's disease, with 80.5% of patients showing improvement compared to 58.1% in the placebo group, based on data from 616 patients.

Unlike other antipsychotics, pimavanserin does not worsen motor function due to its unique mechanism of action that avoids significant dopamine binding, but it still carries a boxed warning about the risk of death in elderly patients with dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The US Food and Drug Administration's Perspective on the New Antipsychotic Pimavanserin. Mathis, MV., Muoio, BM., Andreason, P., et al.[2022]

Pimavanserin is an atypical antipsychotic that effectively treats hallucinations and delusions in Parkinson's disease without worsening motor symptoms, based on a review of 2 published randomized controlled trials.

While only 1 of the 4 trials showed significant improvement in psychotic symptoms compared to placebo, pimavanserin's selective action on serotonin 5-HT2a receptors suggests it may be a more tolerable treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pimavanserin (Nuplazid™) for the treatment of Parkinson disease psychosis: A review of the literature. Touma, KTB., Touma, DC.[2022]

Aripiprazole is one of the few medications approved in the USA for treating irritability in individuals with autism spectrum disorder (ASD), showing clear benefits in multiple studies compared to placebo.

While effective, aripiprazole can have metabolic side effects, highlighting the importance of monitoring and periodic reassessment of treatment needs for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole for treating irritability associated with autism spectrum disorders. Bartram, LA., Lozano, J., Coury, DL.[2019]

Aripiprazole has been FDA-approved for treating irritability in children and adolescents aged 6-17 with autistic disorder, making it one of only two approved medications for this purpose.

The drug's efficacy, safety, and tolerability were documented in studies that supported its approval, highlighting its potential benefits for managing irritability in individuals with autism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aripiprazole for irritability associated with autistic disorder in children and adolescents aged 6-17 years. Blankenship, K., Erickson, CA., Stigler, KA., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05523895

Study Details | NCT05523895 | Pimavanserin for the ... 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05999240

Pimavanserin for Rigid-compulsive Symptoms in Autism ... This Phase 2 study examines the safety, tolerability, and preliminary efficacy of pimavanserin in individuals with Autism Spectrum Disorder.

3. ctv.veeva.com ctv.veeva.com/study/pimavanserin-for-the-treatment-of-irritability-associated-with-autism-spectrum-disorder

Pimavanserin for the Treatment of Irritability Associated With ... 6-week, randomized, double-blind, fixed-dose, placebo-controlled, parallel group study in children and adolescents (aged 5 to17 years) with autism spectrum ...

4. clinicalresearch.com clinicalresearch.com/en/find-trials/Study/NCT05555615

NCT05555615 ACP-103-069 is a 6-week, randomized, double-blind, fixed-dose, placebo controlled, parallel group study of pimavanserin in children and adolescents with ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05523895/pimavanserin-for-the-treatment-of-irritability-associated-with-autism-spectrum-disorder

Pimavanserin for the Treatment of Irritability Associated ... This study will be conducted as a 6-week, randomized, double-blind, fixed-dose, placebo-controlled, parallel group study in children and ...

6. nuplazidhcp.com nuplazidhcp.com/safety-tolerability-data

Safety and Tolerability Data | NUPLAZID® (pimavanserin) Learn about NUPLAZID® safety data. See Important Safety Information and Full Prescribing Information, including Boxed WARNING.

7. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-long-term-safety-of-pimavanserin-for-treating-irritability-in-children-and-adolescents-with-autism-spectrum-disorder/

Study on the Long-Term Safety of Pimavanserin for ... Pimavanserin is being studied for its long-term safety and tolerability in children and adolescents with irritability associated with Autism Spectrum Disorder ( ...