Pimavanserin vs. Quetiapine for Treatment of Parkinson's Psychosis (C-SAPP)

VA Office of Research and Development

Status and phase: Enrolling; Phase 4

Conditions: Parkinson's Disease Psychosis

Treatments: Drug: Quetiapine; Drug: Pimavanserin

Study type: Interventional

Funder types: Other U.S. Federal agency

Identifiers

NCT04373317

2015

Details and patient eligibility

About

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: 358 estimated patients

Sex: All

Ages: 40+ years old

Volunteers: Accepts Healthy Volunteers

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 1 month
• 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 in-person contact with the patient (at least 5 days per week, and at least 4 hours per day that is spent with patient)
• English-speaking

INFORMED OTHER

• Age 18 years or older
• Must have regular in-person contact with the patient (on average at least 5 days per week, and at least 4 hours per day that is spent with patient)
• 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 an antipsychotic, including pimavanserin in the past year, except quetiapine <50 mg/day which has been discontinued for at least 1 month prior to study randomization
• Deep brain stimulation (DBS) surgery occurring within 6 months prior or has had stimulator adjustments in the previous month
• History of a psychotic disorder prior to PD, including schizophrenia and bipolar disorder
• Suspected atypical parkinsonian disorder or dementia with Lewy bodies (DLB)
• Psychosis secondary to other toxic or metabolic disorder
• History of long QT syndrome
• Prolonged QTc [>450ms in men, >470ms in women] at screening
• History of ventricular arrhythmias, 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 prolongs the QTc interval
• Comorbid medical condition determined too severe by SI to allow participation in clinical trial
• Failure to tolerate quetiapine or pimavanserin previously
• Moderate to severe PD dementia (MoCA score <13)
• Currently enrolled in another therapeutic or interventional study
• Nursing home placement at screening or planned placement during the study
• Active suicidality
• Pregnant, or a female of child-bearing potential who is unwilling to use a reliable form of contraception

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

358 participants in 2 patient groups

Pimavanserin 34mg

Active Comparator group

Description:

All participants assigned to pimavanserin will receive the FDA-approved dose of 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.

Treatment:

Drug: Pimavanserin

Quetiapine

Active Comparator group

Description:

Quetiapine extended release will be titrated as shown in the following table. 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 QHSUp-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 QHSUp- or down-titration as appropriate based on psychosis symptoms and tolerability Week 6 call (Visit 06)200 mg quetiapine XR QHSUp- or down-titration as appropriate based on psychosis symptoms and tolerability

Treatment:

Drug: Quetiapine