Pimavanserin for Autism

Recruiting at 1 trial location

Overseen By Suvekcha Bhattachan, MA

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: New York State Psychiatric Institute

Must not be taking: Serotonin reuptake inhibitors, Antipsychotics

Disqualifiers: Severe psychiatric conditions, Substance abuse, others

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: 5

Duration: 2 days

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This Phase 2 study examines the safety, tolerability, and preliminary efficacy of pimavanserin in individuals with Autism Spectrum Disorder. Male or female participants aged 16 to 40 years of age will be randomized to receive single doses of either placebo or pimavanserin in this randomized, placebo-controlled, cross-over designed study, followed by open label extension.

Do I have to stop taking my current medications for the trial?

The trial requires participants to continue their current medications and not make any changes to them during the study.

What data supports the effectiveness of the drug Pimavanserin for treating autism?

Pimavanserin is effective in treating hallucinations and delusions in Parkinson's disease psychosis, showing significant improvement in symptoms without worsening motor functions. Its unique action on serotonin receptors might suggest potential benefits for other conditions involving similar symptoms, like autism. ^{1 2 3 4 5}

How is the drug Pimavanserin unique for treating autism?

Pimavanserin is unique because it is a selective serotonin 2A receptor inverse agonist and antagonist, originally approved for treating hallucinations and delusions in Parkinson's disease psychosis, which may offer a novel approach for autism treatment by targeting serotonin pathways differently than other autism therapies. ^{1 2 6 7 8}

Research Team

Matthew Mosconi, PhD

Principal Investigator

University of Kansas Center for Autism Research and Training

Jeremy Veenstra-VanderWeele, MD

Principal Investigator

New York State Psychiatric Institute

Eligibility Criteria

This trial is for individuals aged 16-40 with Autism Spectrum Disorder, as confirmed by a licensed psychiatrist or psychologist and supported by ADOS-2. Participants must have repetitive behavior severity of moderate or above, an IQ over 70, speak English, and live with someone who can report on their behalf. They should be stable on current medications/therapies and able to take oral medication.

Inclusion Criteria

I agree to not change my current medications or treatments during the study.

Participant must have a non-verbal IQ of greater than or equal to 70 as determined by the 4-subtest Wechsler Abbreviated Scale of Intelligence

Parent, primary caregiver, or other adult informant must speak and understand English in order to complete study measures

Exclusion Criteria

I tested positive for drugs but can stop using cannabis if I have a prescription.

Participant has met DSM-5 criteria for a substance abuse disorder within the last 6 months prior to Screening, except for disorders related to caffeine or nicotine

Participant has laboratory evidence of hypothyroidism at Screening, as measured by thyroid stimulating hormone (TSH) and reflex free thyroxine (T4). If TSH is abnormal and the reflex free T4 is normal, the Participant may be enrolled

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive single doses of either placebo or pimavanserin in a randomized, placebo-controlled, cross-over design

2 days

2 visits (in-person)

Open-Label Extension

Participants take pimavanserin 34 mg for six weeks

6 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Pimavanserin

Trial Overview The study tests the safety and potential effectiveness of Pimavanserin Tartrate (34 Mg) compared to a placebo in treating rigid-compulsive symptoms in those with Autism Spectrum Disorder. It's a randomized, cross-over design where participants will receive both treatments at different times followed by an open label extension.

Participant Groups

Group I: Pimavanserin tartrate Experimental Treatment 1 Intervention

Pimavanserin 34 mg white to off-white capsules.

Group II: Placebo Placebo Group 1 Intervention

Placebo to Pimavanserin tartrate

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?

New York State Psychiatric Institute

Lead Sponsor

Trials

481

Recruited

154,000+

Research Foundation for Mental Hygiene, Inc.

Collaborator

Trials

68

Recruited

21,100+

University of Kansas Medical Center

Collaborator

Trials

527

Recruited

181,000+

Weill Medical College of Cornell University

Collaborator

Trials

1,103

Recruited

1,157,000+

ACADIA Pharmaceuticals Inc.

Industry Sponsor

Trials

49

Recruited

11,700+

Founded

1993

Headquarters

San Diego, USA

Known For

Neurological Disorders

Top Products

Nuplazid (pimavanserin), Daybue (trofinetide)

Findings from Research

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]

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]

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]

In a study involving 12 adults with Tourette syndrome, pimavanserin treatment led to a statistically significant reduction in tic severity, with a 12% decrease in the Yale Global Tic Severity Scale score after 8 weeks, although this improvement may not be clinically significant.

Pimavanserin was found to be safe, with no serious adverse events reported, and it also showed positive effects on non-motor symptoms and quality of life, suggesting potential benefits that merit further investigation in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study to Evaluate Pimavanserin for the Treatment of Motor and Behavioral Symptoms of Tourette Syndrome. Billnitzer, A., Jankovic, J.[2022]

Compound 7-16, a novel derivative of pimavanserin, showed significantly higher antagonist and inverse agonist activity at the 5-HT2A receptor compared to pimavanserin, indicating its potential for greater efficacy in treating Parkinson's disease psychosis.

In addition to its enhanced potency, compound 7-16 demonstrated a better safety profile with a wider therapeutic window and improved pharmacokinetics, making it a promising candidate for further development as an anti-PDP agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving the treatment of Parkinson's disease: Structure-based development of novel 5-HT2A receptor antagonists/inverse agonists. Ma, M., Yang, Y., Du, G., et al.[2022]

In a chart review of 26 patients with Parkinson's disease and related conditions, nearly 50% found Pimavanserin (Pim) helpful for managing psychotic symptoms, with 12 patients continuing treatment after 6 weeks.

While some patients experienced adverse effects leading to discontinuation, the overall safety profile suggests that intolerance was not directly related to the medication itself.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pimavanserin for Psychotic Symptoms in People With Parkinsonism: A Second Chart Review. Friedman, JH.[2018]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Pimavanserin: First Global Approval. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Pimavanserin: A Novel Drug Approved to Treat Parkinson's Disease Psychosis. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Pimavanserin: novel pharmacotherapy for Parkinson's disease psychosis. [2018]

5. Spain pubmed.ncbi.nlm.nih.gov

Pimavanserin. [2017]

6. United States pubmed.ncbi.nlm.nih.gov

Pilot Study to Evaluate Pimavanserin for the Treatment of Motor and Behavioral Symptoms of Tourette Syndrome. [2022]

7. France pubmed.ncbi.nlm.nih.gov

Improving the treatment of Parkinson's disease: Structure-based development of novel 5-HT2A receptor antagonists/inverse agonists. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Pimavanserin for Psychotic Symptoms in People With Parkinsonism: A Second Chart Review. [2018]