Pimavanserin vs. Quetiapine for Treatment of Parkinson's Psychosis

NCT ID: NCT04373317

Last Updated: 2025-08-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

358 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-10-24

Study Completion Date

2027-08-24

Brief Summary

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Patients with Parkinson's disease (PD) sometimes experience symptoms affecting their movement, such as slowness, tremor, stiffness, and balance or walking problems. Many patients also have other symptoms not related to movement, called non-motor symptoms, which may affect one's mood or emotions, memory or thinking, or cause one to see or hear things that aren't real (hallucinations) or believe things that aren't true (delusions). Hallucinations or delusions, together called psychosis, occur in up to 60% of PD patients at some point in time. Parkinson's disease psychosis can sometimes be associated with decreased quality of life, increased nursing home placement, increased rate of death, and greater caregiver burden. There are approximately 50,000 Veterans with Parkinson's disease receiving care in the VA, and up to 30,000 (60%) of them will experience psychosis at some point in time.

Quetiapine is an antipsychotic drug approved by the Food and Drug Administration (FDA) that is the most commonly used medication to treat PD psychosis, but more studies are needed to determine if it works for this condition and is also well tolerated and safe. Pimavanserin is a newer antipsychotic drug approved by the Food and Drug Administration (FDA) specifically to treat PD psychosis, but more studies are needed to determine if it works and its safety.

The purpose of this research is to gather additional information on the safety and effectiveness of both Quetiapine and Pimavanserin. By doing this study, the investigators hope to learn which of these medications is the most effective course of treatment for people with PD psychosis.

Enrollment is open to Veterans nationwide, see your VA provider about the possibility of being referred to one of the study's Hub sites. This can be done through contact from your provider to the study's NSC (Tamara Boney at 267-303-9829).

Detailed Description

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CSP #2015 - C-SAPP is a randomized, intent-to-treat, double-blind, two-arm, parallel design, multicenter comparator study. A total of up to approximately 24 Department of Veterans Affairs Medical Centers (VAMCs) will be invited to participate in the study. Veterans age 40 years and older with PD and symptoms of psychosis will be pre-screened for enrollment (consent) using established inclusion/exclusion criteria. Enrolled participants meeting eligibility will be randomized in a blinded fashion to one of two arms (fixed-dose pimavanserin or flexible-dose quetiapine), stratified by cognitive impairment \[per the Montreal Cognitive Assessment (MoCA)\]. Assessments will be collected at multiple time points - baseline, week 3, week 5, and at week 8 after randomization. Assessments of psychosis (CGI-I psychosis), PDP symptoms (SAPS-PD), and nighttime sleep/daytime sleepiness \[per Scales for Outcomes in PD-Sleep Scale nighttime subscale (SCOPA-S NS)/Epworth Sleepiness Scale (ESS)\] will be completed at each in-person visit, while caregiver burden (ZBI), functioning and well-being \[per the Parkinson's Disease Questionnaire-8 (PDQ-8)\] will be assessed at baseline and treatment visits of weeks 5 and 8, parkinsonism (CGI-I parkinsonism) and motor abilities (MDS-UPDRS III) at baseline and week 8, and cognition (MoCA) at screening and week 8. Additional contact by phone/video will occur at weeks 1 and 6. PD medications and side-effects will also be collected. SAEs, and AEs using the Treatment Emergent Symptom Scale (TESS) for guidance, will be continuously monitored at each participant contact (in-person and phone/video). A quality by design (QbD) approach was utilized focusing on its key principles to help prospectively identify important errors that could jeopardize the reliability of the data and safety of study participants.

Conditions

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Parkinson's Disease Psychosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Two active treatments will be administered in this RCT, with 1:1 treatment assignment to either quetiapine or pimavanserin. Both active treatments are FDA-approved antipsychotics.
Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
In order to facilitate titrations, study drug will be provided in blister cards with a sufficient number of over-encapsulated drug to bridge participants to their next titration step. Each blister card will contain a one-week supply of study drug. Because dosing will be nightly, and the study will use a combination of quetiapine strengths for all protocol-specified quetiapine doses, participants in both treatment groups will take two identical capsules both of which containing the protocol-specified nightly dose. For example, if a participant is randomized to quetiapine and is up-titrated from 50 to 100 mg ER, this participant will take 2 identical capsules, each containing 50 mg of ER quetiapine. Similarly, participants randomized to pimavanserin will take two capsules every night, one containing a placebo capsule, and the other containing 34 mg of pimavanserin.

Study Groups

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Pimavanserin 34mg

Participants assigned to pimavanserin will receive 34mg (equivalent to 40 mg pimavanserin tartrate) daily without titration; however, because pimavanserin is blinded to quetiapine, participants will undergo sham titration based on tolerability.

Group Type ACTIVE_COMPARATOR

Pimavanserin

Intervention Type DRUG

Fixed-dose Pimavanserin - Pimavanserin is a new antipsychotic agent, and pure 5HT-2A inverse agonist, that was approved by the FDA recently (2016) for the treatment of PDP. It is the only FDA-approved medication for PDP, but is still not the first-line AP used in PD. All participants assigned to pimavanserin will receive the FDA-approved dose of 34 mg (equivalent to 40 mg pimavanserin tartrate) daily without titration up or down; however, because pimavanserin is blinded to quetiapine, participants will undergo sham titration based on tolerability (i.e., overall adverse event profile) and efficacy (i.e., improvement in severity of psychosis).

Quetiapine

Participants assigned to Quetiapine will be titrated from 25mg/day to a maximum of 200mg/day based on tolerability. During the 8-week treatment phase, there is a maximum of 6 weeks for titration.

Titration Schedule

Visit/call Quetiapine Dose (Flexible)Quetiapine Notes Baseline visit (Visit 00)25 mg IR QHSAll participants must be up-titrated to at least 50 mg/day at week 1 Week 1 call (Visit 01)50 mg XR QHS Up-titration Week 3 visit (Visit 03)100 mg XR QHS (requiring two 50-mg quetiapine XR capsules)Up- or down-titration as appropriate based on psychosis symptoms and tolerability Week 5 visit (Visit 05)150 mg quetiapine XR QHS Up- or down-titration as appropriate based on psychosis symptoms and tolerability Week 6 call (Visit 06)200 mg quetiapine XR QHS Up- or down-titration as appropriate based on psychosis symptoms and tolerability

Group Type ACTIVE_COMPARATOR

Quetiapine

Intervention Type DRUG

Flexible-dose Quetiapine - Quetiapine, which is a mixed serotonin and dopamine receptor antagonist, is by far the most commonly used AP for PDP. However, scientific evidence for the efficacy of quetiapine in PDP is almost non-existent as most of the studies were underpowered, had high drop-out rates, and possibly underdosed quetiapine. Quetiapine immediate and extended release will be titrated as shown:

Baseline visit Quetiapine: 25 mg IR QHS, All participants must be up-titrated to 50 mg/day

Week 1 call Quetiapine: 50 mg XR QHS, Up-titration to 50 mg

Week 3 visit Quetiapine: 100 mg XR QHS, Up-titration as appropriate

Week 5 visit Quetiapine: 150 mg XR QHS, Up- or down-titration as appropriate

Week 6 call Quetiapine: 200 mg XR QHS, Up- or down-titration as appropriate

Interventions

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Pimavanserin

Fixed-dose Pimavanserin - Pimavanserin is a new antipsychotic agent, and pure 5HT-2A inverse agonist, that was approved by the FDA recently (2016) for the treatment of PDP. It is the only FDA-approved medication for PDP, but is still not the first-line AP used in PD. All participants assigned to pimavanserin will receive the FDA-approved dose of 34 mg (equivalent to 40 mg pimavanserin tartrate) daily without titration up or down; however, because pimavanserin is blinded to quetiapine, participants will undergo sham titration based on tolerability (i.e., overall adverse event profile) and efficacy (i.e., improvement in severity of psychosis).

Intervention Type DRUG

Quetiapine

Flexible-dose Quetiapine - Quetiapine, which is a mixed serotonin and dopamine receptor antagonist, is by far the most commonly used AP for PDP. However, scientific evidence for the efficacy of quetiapine in PDP is almost non-existent as most of the studies were underpowered, had high drop-out rates, and possibly underdosed quetiapine. Quetiapine immediate and extended release will be titrated as shown:

Baseline visit Quetiapine: 25 mg IR QHS, All participants must be up-titrated to 50 mg/day

Week 1 call Quetiapine: 50 mg XR QHS, Up-titration to 50 mg

Week 3 visit Quetiapine: 100 mg XR QHS, Up-titration as appropriate

Week 5 visit Quetiapine: 150 mg XR QHS, Up- or down-titration as appropriate

Week 6 call Quetiapine: 200 mg XR QHS, Up- or down-titration as appropriate

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Veteran
* Age 40 years or older
* Diagnosis of Parkinson's Disease consistent with UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria
* Psychosis \[with Neuropsychiatric Inventory (NPI) hallucinations (B) or delusions (A) score 4 or greater\]
* Stable dose of PD medications for at least 2 weeks
* If on an acetylcholinesterase inhibitor (AChEI) initially prescribed at least 3 months prior and stable dose (no dose or medication change) for past month
* Informed other must provide informed consent and agree to attend all study visits. The informed other must be at least 18 years of age and have regular contact with the patient (on average at least 4 days per week and at least 2 hours per day, or at least 3 days per week and at least 4 hours per day, that is with patient) via in-person, video, or telephone
* English-speaking

INFORMED OTHER

* Age 18 years or older
* Must have regular contact with the patient (on average at least 4 days per week, and at least 2 hours per day, or at least 3 days per week and at least 4 hours pr day, that is with patient) via in-person, video, or telephone
* Agree to attend all study visits
* Be able to provide informed consent
* English-speaking

Exclusion Criteria

* Psychosis symptoms severe enough to preclude enrollment in a clinical trial and require prompt clinical care instead
* Treatment with quetiapine \>50 mg/day or pimavanserin in the past 3 months, or quetiapine 50 mg/day or another antipsychotic in the past week prior to study randomization
* Deep brain stimulation (DBS) surgery within 3 months or has had stimulator adjustments in the previous 2 weeks
* History of a psychotic disorder prior to PD, including bipolar disorder, schizophrenia, schizoaffective disorder, and major depressive disorder with psychotic features, if it is thought to be the cause of the current psychosis symptoms
* Suspected atypical parkinsonian disorder or dementia with Lewy bodies (DLB)
* Psychosis secondary to other toxic or metabolic disorder
* History of long QT syndrome
* Documented chart evidence indicating persistent hypoglycemia, hypokalemia, hypomagnesemia that would put patient at increased risk for QTc prolongation.
* History of ventricular arrhythmias, except when treated with an implantable cardioverter defibrillator (ICD) or pacemaker, or untreated or unstable atrial fibrillation/flutter
* Currently taking medications that are moderate or strong CYP3A4 inducers or strong CYP3A4 inhibitors
* Concomitant use of drugs that prolong the QTc interval with a known risk of Torsades de Pointes
* Comorbid medical condition determined too severe by Site Investigator to allow participation in clinical trial
* Failure to tolerate quetiapine or pimavanserin previously
* Severe cognitive impairment (MoCA score \<5)
* Nursing home placement at screening or planned placement during the study, unless approved by study Co-Chairs. Approval will depend upon nursing facility agreement to receive, return, and administer medications or allow participant to self-administer study medications; appropriate IO availability; and transportation availability for study visits.
* Currently enrolled in another therapeutic or interventional study
* Pregnant, or a female of child-bearing potential who is unwilling to use a reliable form of contraception
Minimum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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VA Office of Research and Development

FED

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Daniel Weintraub, MD

Role: STUDY_CHAIR

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

Locations

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Southern Arizona VA Health Care System, Tucson, AZ

Tucson, Arizona, United States

Site Status TERMINATED

VA Loma Linda Healthcare System, Loma Linda, CA

Loma Linda, California, United States

Site Status RECRUITING

VA Palo Alto Health Care System, Palo Alto, CA

Palo Alto, California, United States

Site Status RECRUITING

San Francisco VA Medical Center, San Francisco, CA

San Francisco, California, United States

Site Status ACTIVE_NOT_RECRUITING

VA Greater Los Angeles Healthcare System, West Los Angeles, CA

West Los Angeles, California, United States

Site Status TERMINATED

Rocky Mountain Regional VA Medical Center, Aurora, CO

Aurora, Colorado, United States

Site Status RECRUITING

North Florida/South Georgia Veterans Health System, Gainesville, FL

Gainesville, Florida, United States

Site Status ACTIVE_NOT_RECRUITING

Edward Hines Jr. VA Hospital, Hines, IL

Hines, Illinois, United States

Site Status ACTIVE_NOT_RECRUITING

Lexington VA Medical Center, Lexington, KY

Lexington, Kentucky, United States

Site Status TERMINATED

VA Ann Arbor Healthcare System, Ann Arbor, MI

Ann Arbor, Michigan, United States

Site Status ACTIVE_NOT_RECRUITING

Minneapolis VA Health Care System, Minneapolis, MN

Minneapolis, Minnesota, United States

Site Status RECRUITING

St. Louis VA Medical Center John Cochran Division, St. Louis, MO

St Louis, Missouri, United States

Site Status ACTIVE_NOT_RECRUITING

New Mexico VA Health Care System, Albuquerque, NM

Albuquerque, New Mexico, United States

Site Status TERMINATED

Syracuse VA Medical Center, Syracuse, NY

Syracuse, New York, United States

Site Status TERMINATED

Asheville VA Medical Center, Asheville, NC

Asheville, North Carolina, United States

Site Status TERMINATED

Louis Stokes VA Medical Center, Cleveland, OH

Cleveland, Ohio, United States

Site Status RECRUITING

VA Portland Health Care System, Portland, OR

Portland, Oregon, United States

Site Status RECRUITING

Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Philadelphia MultiService Center, Philadelphia, PA

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Tennessee Valley Healthcare System Nashville Campus, Nashville, TN

Nashville, Tennessee, United States

Site Status TERMINATED

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, United States

Site Status RECRUITING

South Texas Health Care System, San Antonio, TX

San Antonio, Texas, United States

Site Status TERMINATED

Hunter Holmes McGuire VA Medical Center, Richmond, VA

Richmond, Virginia, United States

Site Status TERMINATED

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Seattle, Washington, United States

Site Status ACTIVE_NOT_RECRUITING

Countries

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United States

Central Contacts

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Daniel Weintraub, MD

Role: CONTACT

(215) 823-5800 ext. 5934

John E Duda, MD

Role: CONTACT

(215) 823-5934

Facility Contacts

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Dorothee Cole, MD

Role: primary

909-825-7084 ext. 6049

Sonia Read

Role: backup

9098257084 ext. 2963

Shannon Kilgore, MD

Role: primary

650-858-3999

Cheyenne Murphy

Role: backup

6504935000

Jeanne Feuerstein, MD

Role: primary

720-723-6205

James Ashe, MD

Role: primary

612-725-2000 ext. 5538

Molly Carson

Role: backup

6127252000 ext. 5203

Peijun Chen

Role: primary

216-791-3800 ext. 66804

Aasef Shaikh

Role: backup

2167913800 ext. 65229

Joel Mack, MD

Role: primary

503-220-8262 ext. 54521

Michael Tanaka

Role: backup

5032208262 ext. 57338

Daniel Weintraub, MD

Role: primary

(215) 823-5800 ext. 5934

James Morley, MD

Role: primary

215-823-5934

Philip Danquah

Role: backup

Aliya Sarwar, MD

Role: primary

713-794-7841

Priscilla Bigner

Role: backup

7137947939

Other Identifiers

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2015

Identifier Type: -

Identifier Source: org_study_id

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