Pimavanserin for Aggression

Overseen By Matthew A. Timmins, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Ohio State University

Must not be taking: Antipsychotics, Opiates

Disqualifiers: Bipolar, Schizophrenia, Depression, 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

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the drug pimavanserin (also known as Nuplazid, ACP-103, BVF-036, or BVF-048) can reduce anger outbursts in individuals with impulsive aggression, specifically those with Intermittent Explosive Disorder (IED). Participants will take a single dose of the drug and complete tasks that assess aggression and their perception of hostility in social situations. The trial seeks individuals who currently have or previously had IED and have experienced frequent anger issues. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires participants to be free of anti-psychotic medication for two weeks before starting. If you are on such medications, you will need to stop taking them for this period.

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

Research shows that pimavanserin is usually well-tolerated, though some side effects occur. In previous studies, participants taking pimavanserin reported sleep problems and changes in thinking and memory. Another study found higher rates of restlessness, irritability, and swelling in those on pimavanserin compared to those on a placebo.

Pimavanserin is already used for other conditions, which can offer some reassurance about its safety. However, while these side effects have been observed, they do not affect everyone. Participants in past studies managed the treatment well with careful monitoring. Prospective trial participants should discuss any concerns with the study team to understand the monitoring in place. ^{1 2 3 4 5}

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

Unlike standard treatments for aggression, which often include antipsychotics or mood stabilizers, pimavanserin offers a unique approach by specifically targeting serotonin receptors. This distinct mechanism of action may help manage aggression with potentially fewer side effects, especially those related to movement disorders often seen with traditional antipsychotics. Researchers are excited about pimavanserin because it could provide a more focused and safer option for individuals experiencing aggression, setting it apart from existing therapies.

What evidence suggests that pimavanserin might be an effective treatment for impulsive aggression?

Research has shown that pimavanserin, which participants in this trial may receive, can help reduce aggression and agitation. In a study with Alzheimer's patients, those who took pimavanserin exhibited less agitation and aggressive behavior. This suggests the drug might also help people with Intermittent Explosive Disorder (IED) manage their anger. The drug blocks certain brain receptors related to mood and aggression control. While more research is needed for IED, early results are promising for reducing anger outbursts. ^{1 3 4 6 7}

Who Is on the Research Team?

Emil F. Coccaro

Principal Investigator

Ohio State University

Are You a Good Fit for This Trial?

This trial is for adults aged 21-55 with impulsive aggression or Intermittent Explosive Disorder. They must be in good physical health, not on psychotropic meds for the last four weeks, and able to consent. Women must test negative for pregnancy.

Inclusion Criteria

I am between 21 and 55 years old and can make my own medical decisions.

I haven't taken any anti-psychotic medication for the last two weeks.

Participants with a current (or past) DSM-5 diagnosis of Intermittent Explosive Disorder (IED)

Exclusion Criteria

Clinically significant medical condition

Unwilling/unable to sign informed consent document

Current alcohol/drug use disorder of greater than mild severity

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (virtual)

Baseline Assessment

Participants complete interviews, questionnaires, and a medical evaluation

1 day

1 visit (in-person)

Treatment

Participants receive a single dose of pimavanserin or placebo and complete aggression and social cognition tasks

2 days

2 visits (in-person)

Data Collection

Final online session to ensure all data required by the study protocol is collected

1 day

1 visit (virtual)

Follow-up

Participants are monitored for any adverse effects and overall safety after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pimavanserin
• Placebo

Trial Overview

The study tests if a single dose of Pimavanserin (34 mg), which blocks certain serotonin receptors, can reduce aggressive behavior and alter hostile social cognition in people with anger issues compared to a placebo.

How Is the Trial Designed?

Group I: Pimavanserin Experimental Treatment 1 Intervention

One single dose of pimavanserin (34 mg oral)

Group II: Placebo Placebo Group 1 Intervention

One single dose of matching placebo

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?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

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)

Published Research Related to This Trial

In a randomized, double-blind, placebo-controlled trial involving 181 Alzheimer's disease patients, pimavanserin significantly reduced psychotic symptoms, especially in those with more severe symptoms (NPI-NH-PS ≥12), showing an 88.9% responder rate for ≥30% improvement compared to 43.3% for placebo.

Pimavanserin was well-tolerated, with similar rates of adverse events compared to placebo, and fewer patients discontinued treatment due to side effects, indicating it is a safe option for managing psychosis in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pimavanserin in Alzheimer's Disease Psychosis: Efficacy in Patients with More Pronounced Psychotic Symptoms. Ballard, C., Youakim, JM., Coate, B., et al.[2020]

Pimavanserin, a selective serotonin 2A receptor inverse agonist, was evaluated as a PET-radioligand in pigs, showing good brain penetration and binding in areas consistent with 5-HT2AR distribution.

However, the study found that the binding of [(11)C]pimavanserin could not be blocked by known antagonists, indicating high nonspecific binding and suggesting that it may not be selective for the 5-HT2AR in this animal model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(11)C-labeling and preliminary evaluation of pimavanserin as a 5-HT2A receptor PET-radioligand. Andersen, VL., Hansen, HD., Herth, MM., et al.[2016]

Pimavanserin is the first and only medication specifically approved for treating Parkinson's disease psychosis (PDP), which affects up to 60% of Parkinson's patients and is associated with serious risks like increased mortality and nursing home placement.

Unlike traditional atypical antipsychotics, pimavanserin is a selective 5-HT2A inverse agonist that does not worsen motor symptoms or cause other adverse effects related to dopamine receptor blockade, making it a safer option for managing PDP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changing the treatment paradigm for Parkinson's disease psychosis with pimavanserin. Lyons, KE., Pahwa, R., Hermanowicz, N., et al.[2019]

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 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 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 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 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 a unique medication that works by blocking the 5-HT2A serotonin receptors, which helps reduce psychotic symptoms in patients with Parkinson's disease.

It is specifically approved for treating Parkinson's disease psychosis, and the article outlines which patients may benefit from this treatment, potential side effects, and recommended dosing guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can pimavanserin help patients with Parkinson disease psychosis? de la Cruz, J., Canal, C.[2020]

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]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/32729631/

Evaluation of the efficacy of pimavanserin in the treatment ...

Patients with ADP, who show improvement in psychotic symptoms after pimavanserin treatment, also experience an improvement in concomitant agitation and ...

2.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0165032724011613

Comprehensive analysis of adverse events associated with ...

This study reveals potential AEs of pimavanserin, including sleep disorders and cognitive changes, underscoring the importance of careful monitoring and ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02992132

NCT02992132 | Study to Examine the Safety and Efficacy ...

A Double-Blind, Placebo-Controlled Study to Examine the Safety and Efficacy of Pimavanserin for the Treatment of Agitation and Aggression in Alzheimer's ...

4.

nuplazidhcp.com

nuplazidhcp.com/efficacy-data

Efficacy Data - NUPLAZID® (pimavanserin)

NUPLAZID significantly reduced the frequency and/or severity of hallucinations and delusions associated with PD psychosis (Primary Endpoint) · NUPLAZID has been ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7418577/

Pimavanserin for the treatment of psychosis in Alzheimer's ...

This paper describes the outcomes of efficacy and tolerability of pimavanserin vs placebo in a subgroup of patients with severe psychosis associated with AD.

6.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2016/207318Orig1s000MedR.pdf

207318Orig1s000 - accessdata.fda.gov

Safety Results ... Trial to Examine the Safety and Efficacy of ACP-103 in the Treatment of.

7.

psychiatryonline.org

psychiatryonline.org/doi/full/10.1176/appi.ajp.20220519

The Safety of Pimavanserin for Parkinson's Disease and ...

Pimavanserin has not demonstrated substantial evidence of effectiveness for agitation in dementia. In a randomized placebo-controlled trial for ...