Pimavanserin vs. Quetiapine for the Treatment Parkinson's Psychosis

CSP #2015 - Multicenter, Randomized, Double-blind Comparator Study of Antipsychotics Pimavanserin and Quetiapine for Parkinson''s Disease Psychosis (C-SAPP)

Sponsors

Lead Sponsor: VA Office of Research and Development

Source VA Office of Research and Development
Brief Summary

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. Your individual participation in this research will last approximately 54 weeks.

Overall Status Not yet recruiting
Start Date January 1, 2021
Completion Date July 1, 2024
Primary Completion Date January 1, 2024
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
CGI-I Psychosis 8 Weeks
Secondary Outcome
Measure Time Frame
SAPS-PD 8 Weeks
MDS-UPDRS III 8 Weeks
Zarit Caregiver Burden Scale 8 Weeks
Enrollment 358
Condition
Intervention

Intervention Type: Drug

Intervention Name: Pimavanserin

Description: 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.

Arm Group Label: Pimavanserin 34mg

Intervention Type: Drug

Intervention Name: Quetiapine

Description: Quetiapine, which is a mixed serotonin and dopamine receptor antagonist but also binds to many other brain receptors (e.g., adrenergic, cholinergic, histaminergic receptors), is by far the most commonly used AP for PDP (at least 70% of prescriptions) and does not require special monitoring.

Arm Group Label: Quetiapine

Eligibility

Criteria:

Inclusion Criteria: - Veteran - Diagnosis of idiopathic PD for 2 or more years - 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 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 enrollment - Deep brain stimulation (DBS) surgery occurring within 6 months prior or having unstable stimulator settings 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 - Congestive heart failure - History of stroke within the last 6 months - History of myocardial infarction within the last 6 months - History of long QT syndrome or prolonged QTc [>450ms in men, >470ms in women] at screening/baseline (or baseline, if applicable) - Current uncontrolled serious medical illness - Clinically significant hepatic impairment or severe renal impairment (eGFR <30 mL/min) - Currently taking medications that are significant CYP3A4 inhibitors or inducers - 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 baseline or planned placement during the study - Active suicidality - Pregnancy/Pregnant, or a female of child-bearing potential who is unwilling to use a reliable form of contraception

Gender: All

Minimum Age: 40 Years

Maximum Age: N/A

Healthy Volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Daniel Weintraub, MD Study Chair Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
Overall Contact

Last Name: Daniel Weintraub, MD

Phone: (215) 823-5800

Phone Ext.: 5934

Email: [email protected]

Location
Facility: Contact: Investigator: Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA Daniel Weintraub, MD 215-823-5800 5934 [email protected] Daniel Weintraub, MD Study Chair
Location Countries

United States

Verification Date

September 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Pimavanserin 34mg

Type: Active Comparator

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.

Label: Quetiapine

Type: Active Comparator

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

Acronym C-SAPP
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Intervention Model Description: 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 Purpose: Treatment

Masking: Triple (Participant, Care Provider, Investigator)

Masking Description: 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.

Source: ClinicalTrials.gov