CSP #2015 - Multicenter, Randomized, Double-blind Comparator Study of Antipsychotics Pimavanserin and Quetiapine for Parkinson''s Disease Psychosis (C-SAPP)
Overview
- Phase
- Phase 4
- Intervention
- Pimavanserin
- Conditions
- Parkinson's Disease Psychosis
- Sponsor
- VA Office of Research and Development
- Enrollment
- 358
- Locations
- 24
- Primary Endpoint
- CGI-I Psychosis
- Status
- Recruiting
- Last Updated
- 8 months ago
Overview
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.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
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
Arms & Interventions
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.
Intervention: Pimavanserin
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
Intervention: Quetiapine
Outcomes
Primary Outcomes
CGI-I Psychosis
Time Frame: 8 Weeks
The Clinical Global Impressions (CGI) scale is a brief, well-established research rating tool used to quantify and track patient progress and treatment response over time. The CGI comprises two measures, one of which is Improvement (CGI-I) from the initiation of treatment. It is scored 1 to 7. The CGI-I is used to assess how much the patient's illness has improved or worsened relative to baseline when the intervention was started (1-Very much improved, 2-Much improved, 3-Minimally improved, 4-No change, 5-Minimally worse, 6-Much worse, 7-Very much worse). The CGI-I can also be used to assess specific domains, including psychosis (this study's primary outcome) and parkinsonism (a secondary outcome). During the 8 weeks, the CGI-I (for psychosis, hereafter simply referred to as the CGI-I) will be administered to all participants at 3 weeks, 5 weeks, and 8 weeks following a CGI-I baseline interview to assess clinical improvement in psychosis.
Secondary Outcomes
- SAPS-PD(8 Weeks)
- MDS-UPDRS III(8 Weeks)
- CGI-I Parkinsonism(8 Weeks)
- Zarit Caregiver Burden Scale(8 Weeks)