Pimavanserin vs. Quetiapine for Treatment of Parkinson's Psychosis

Official title

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

Overview

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

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.

Interventions

• Drug 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, participan
• 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

Primary outcome measures

• CGI-I Psychosis [Time frame: 8 Weeks]

Secondary outcome measures (4)

• SAPS-PD [Time frame: 8 Weeks]
• MDS-UPDRS III [Time frame: 8 Weeks]
• CGI-I Parkinsonism [Time frame: 8 Weeks]
• Zarit Caregiver Burden Scale [Time frame: 8 Weeks]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 24 centers

• Southern Arizona VA Health Care System, Tucson, AZ — Tucson
• VA Loma Linda Healthcare System, Loma Linda, CA — Loma Linda
• VA Palo Alto Health Care System, Palo Alto, CA — Palo Alto
• San Francisco VA Medical Center, San Francisco, CA — San Francisco
• VA Greater Los Angeles Healthcare System, West Los Angeles, CA — West Los Angeles
• Rocky Mountain Regional VA Medical Center, Aurora, CO — Aurora
• North Florida/South Georgia Veterans Health System, Gainesville, FL — Gainesville
• Edward Hines Jr. VA Hospital, Hines, IL — Hines
• … and 16 more centers

Identifiers

NCT: NCT04373317 · 2015

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗