A Study of the Safety and Efficacy of Pimavanserin in Patients With Parkinson's Disease Psychosis

A Multi-Center, Placebo-Controlled, Double-Blind Trial to Examine the Safety and Efficacy of Pimavanserin in the Treatment of Psychosis in Parkinson's Disease

The purpose of this study is to evaluate the safety and efficacy of 40 mg pimavanserin compared to placebo in patients with Parkinson's disease psychosis (PDP).

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease Psychosis
• Intervention / Treatment: Drug: pimavanserin tartrate; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 199
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1G 4G3
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
    • Phoenix, Arizona, United States, 85013
    • Phoenix, Arizona, United States, 85004
    • Tucson, Arizona, United States, 85724
  • California
    • Carson, California, United States, 90746
    • Fountain Valley, California, United States, 92708
    • Fresno, California, United States, 93720
    • Fullerton, California, United States, 92835
    • Irvine, California, United States, 92697
    • La Habra, California, United States, 90631
    • La Jolla, California, United States, 92037
    • Loma Linda, California, United States, 92354
    • Oxnard, California, United States, 93030
    • Pasadena, California, United States, 91105
    • Reseda, California, United States, 91335
    • Sunnyvale, California, United States, 94085
    • Ventura, California, United States, 93003
  • Connecticut
    • Danbury, Connecticut, United States, 06810
  • Florida
    • Boca Raton, Florida, United States, 33486
    • Bradenton, Florida, United States, 34205
    • Naples, Florida, United States, 34102
    • Orlando, Florida, United States, 32806
    • Ormond Beach, Florida, United States, 32174
    • Panama City, Florida, United States, 32405
    • Port Charlotte, Florida, United States, 33980
    • St. Petersburg, Florida, United States, 33713
  • Georgia
    • Augusta, Georgia, United States, 30912
    • Decatur, Georgia, United States, 30033
  • Illinois
    • Elk Grove Village, Illinois, United States, 60007
    • Glenview, Illinois, United States, 60026
  • Kansas
    • Kansas City, Kansas, United States, 66160
  • Kentucky
    • Louisville, Kentucky, United States, 40202
  • Maine
    • Scarborough, Maine, United States, 04074
  • Maryland
    • Baltimore, Maryland, United States, 21287
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
  • Michigan
    • Novi, Michigan, United States, 48377
    • Roseville, Michigan, United States, 48066
    • Traverse City, Michigan, United States, 49684
  • Mississippi
    • Flowood, Mississippi, United States, 39232
  • Missouri
    • St. Louis, Missouri, United States, 63110
  • Montana
    • Missoula, Montana, United States, 59802
  • New Jersey
    • Toms River, New Jersey, United States, 08755
  • New York
    • Albany, New York, United States, 12208
    • Commack, New York, United States, 11725
    • Kingston, New York, United States, 12401
    • New York, New York, United States, 10016
  • North Carolina
    • Durham, North Carolina, United States, 27705
    • Raleigh, North Carolina, United States, 27607
    • Salisbury, North Carolina, United States, 28144
  • Ohio
    • Cincinnati, Ohio, United States, 45219
    • Cleveland, Ohio, United States, 44195
    • Columbus, Ohio, United States, 43210
    • Toledo, Ohio, United States, 43614
  • Pennsylvania
    • Greensburg, Pennsylvania, United States, 15601
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
  • Tennessee
    • Brentwood, Tennessee, United States, 37027
  • Texas
    • Houston, Texas, United States, 77030
  • Utah
    • Salt Lake City, Utah, United States, 84108
  • Virginia
    • Alexandria, Virginia, United States, 22311
    • Roanoke, Virginia, United States, 24018
    • Virginia Beach, Virginia, United States, 23456
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53233

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A clinical diagnosis of Parkinson's disease with a minimum duration of 1 year
• Presence of visual and/or auditory hallucinations, and/or delusions, occurring during the four weeks prior to study screening
• Psychotic symptoms must have developed after Parkinson's disease diagnosis was established
• Subjects that are on anti-Parkinson's medication must be on a stable dose for 1 month prior to Study Day 1 (Baseline) and during the trial
• Subject that has received stereotaxic surgery for subthalamic nucleus deep brain stimulation must be at least 6 months post surgery and the stimulator settings must have been stable for at least 1 month prior to Study Day 1 (Baseline) and must remain stable during the trial
• The subject is willing and able to provide consent
• Caregiver is willing and able to accompany the subject to all visits
• Subject and caregiver are willing and able to adequately communicate in English for the purposes of the primary assessment

Exclusion Criteria:

• Subject has a history of significant psychotic disorders prior to or concomitantly with the diagnosis of Parkinson's disease including, but not limited to, schizophrenia or bipolar disorder
• Subject has received previous ablative stereotaxic surgery (i.e., pallidotomy and thalamotomy) to treat Parkinson's disease
• Subject has current evidence of a serious and or unstable cardiovascular, respiratory, gastrointestinal, renal, hematologic or other medical disorder
• Subject has had a myocardial infarction in last six months
• Subject has any surgery planned during the screening, treatment or follow-up periods

Patients will be evaluated at screening to ensure that all criteria for study participation are met. These evaluations will include specific measures of psychosis severity, delirium, dementia, cardiovascular condition, and pregnancy status. Patients may be excluded from the study based on these assessments (and specifically if it is determined that their baseline health and psychiatric condition do not meet all protocol-specified entry criteria).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; pimavanserin tartrate, 40 mg, tablet, once daily by mouth for 6 weeks	Drug: pimavanserin tartrate; pimavanserin tartrate, 40 mg, tablet, once daily by mouth for 6 weeks; Other Names: ACP-103
Placebo Comparator: 2; placebo, tablet, once daily by mouth for 6 weeks	Drug: placebo; placebo, tablet, once daily by mouth for 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antipsychotic Efficacy	Antipsychotic Efficacy was defined as a decrease in the severity and/or frequency of hallucinations and/or delusions. This is measured as the change from baseline (Day 1) to Day 43 in the Scale for the Assessment of Positive Symptoms 9-item sum score for Parkinson's Disease (SAPS-PD). The possible total score is 0 to 45 and a negative change in score indicates improvement. Analysis Method: Mixed Model Repeated Measures (MMRM)	Each study visit (i.e. Days 1, 15, 29 and 43)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor Symptoms Change From Baseline (Negative = Improvement)	Motor symptoms were measured using the change from baseline to Day 43 in the combined score of the Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living) and Part III (Motor Examination). The possible total score is 0 to 160 and a negative change in score indicates improvement. Analysis Method: Analysis of Covariance (ANCOVA). The UPDRS Parts II+III score was analyzed by constructing 2-sided 95% confidence intervals (CIs) on the difference between the pimavanserin dose group and placebo mean change from baseline. Non-inferiority was concluded if the upper limit of the CI was less than or equal to 5.	Study Days 1 and 43

Collaborators and Investigators

• Sponsor: ACADIA Pharmaceuticals Inc.

Publications and helpful links

General Publications

• Cummings J, Isaacson S, Mills R, Williams H, Chi-Burris K, Corbett A, Dhall R, Ballard C. Pimavanserin for patients with Parkinson's disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet. 2014 Feb 8;383(9916):533-40. doi: 10.1016/S0140-6736(13)62106-6. Epub 2013 Nov 1. Erratum In: Lancet. 2014 Jul 5;384(9937):28.

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: July 30, 2010
• First Submitted That Met QC Criteria: July 30, 2010
• First Posted (Estimate): August 3, 2010

Study Record Updates

• Last Update Posted (Estimate): March 26, 2014
• Last Update Submitted That Met QC Criteria: February 6, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Schizophrenia Spectrum and Other Psychotic Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Psychotic Disorders; Parkinson Disease; Mental Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Antiparkinson Agents; Anti-Dyskinesia Agents; Pimavanserin
• Other Study ID Numbers: ACP-103-020