A Study of the Safety and Efficacy of Pimavanserin (ACP-103) in Patients With Parkinson's Disease Psychosis

A Multi-Center, Placebo-Controlled, Double-Blind Trial to Examine the Safety and Efficacy of ACP-103 in the Treatment of Psychosis in Parkinson's Disease

This study will evaluate the safety and efficacy of two dose levels of pimavanserin (ACP-103) compared to placebo in patients with Parkinson's disease psychosis.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease Psychosis
• Intervention / Treatment: Drug: Pimavanserin tartrate (ACP-103); Drug: Pimavanserin tartrate (ACP-103); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 298
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Pleven, Bulgaria, 5800
  • Rousse, Bulgaria, 7003
  • Sofia, Bulgaria, 1113
  • Varna, Bulgaria, 9010
• France
  • Clermont ferrand, France, 63003
  • Marseille, France, 13385
  • Nantes, France, 44093
  • Pessac, France, 33604
  • Strasbourg, France, 67091
  • Toulouse, France, 35059
• India
  • Bangalore, India, 560034
  • Hyderabad, India, 500003
  • Karnataka, India, 575001
  • Mangalore, India, 575002
  • Mumbai, India, 400016
  • Mumbai, India, 400036
  • New Dalhi, India, 110060
  • Pune, India, 411004
  • Pune, India, 411030
  • Tamil Nadu, India, 600006
  • Tamil Nadu, India, 625020
  • Visakhapatnam, India, 530001
• Russian Federation
  • Kazan, Russian Federation, 420061
  • Kirov, Russian Federation, 610014
  • Moscow, Russian Federation, 125284
  • Samara, Russian Federation, 443095
  • Smolensk, Russian Federation, 214018
  • St. Petersburg, Russian Federation, 194044
• Ukraine
  • Kharkiv, Ukraine, 61068
  • Kiev, Ukraine, 04080
  • Kiev, Ukraine, 04114
  • Lugansk, Ukraine, 91045
  • Lviv, Ukraine, 79010
  • Vinnytsia, Ukraine, 21005
• United Kingdom
  • Barnsley, United Kingdom, S75 2EP
  • Blackburn, United Kingdom, BB3 2HH
  • Brighton, United Kingdom, BN2 5BE
  • Dorset, United Kingdom, BH23 2JX
  • London, United Kingdom, NW3 2PF
  • Newcastle upon Tyne, United Kingdom, NE4 6BE
  • North Shields, United Kingdom, NE29 8NH
  • Salford, United Kingdom, M6 8HD
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
    • Phoenix, Arizona, United States, 85013
  • California
    • Berkeley, California, United States, 94705
    • Carson, California, United States, 90746
    • Fountain Valley, California, United States, 92708
    • Irvine, California, United States, 92697
    • Sunnyvale, California, United States, 94805
  • Connecticut
    • Danbury, Connecticut, United States, 06810
    • Fairfield, Connecticut, United States, 06824
  • Florida
    • Boca Raton, Florida, United States, 33486
    • Gainesville, Florida, United States, 32610
    • Jacksonville, Florida, United States, 32209
    • Miami, Florida, United States, 33136
    • Pompano Beach, Florida, United States, 33060
    • Port Charlotte, Florida, United States, 33952
    • Saint Petersburg, Florida, United States, 33701
    • Sarasota, Florida, United States, 34239
    • Tampa, Florida, United States, 33606
  • Georgia
    • Augusta, Georgia, United States, 30912
  • Illinois
    • Springfield, Illinois, United States, 62794
  • Maine
    • Scarborough, Maine, United States, 04074
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
  • Michigan
    • Southfield, Michigan, United States, 48034
    • Traverse City, Michigan, United States, 49684
  • New Jersey
    • Toms River, New Jersey, United States, 08755
  • New York
    • Kingston, New York, United States, 12401
    • Rochester, New York, United States, 14618
  • North Carolina
    • Asheville, North Carolina, United States, 28806
    • Salisbury, North Carolina, United States, 28144
  • Ohio
    • Columbus, Ohio, United States, 43210
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
  • Tennessee
    • Brentwood, Tennessee, United States, 37027
  • Texas
    • San Antonio, Texas, United States, 78258
  • Virginia
    • Richmond, Virginia, United States, 23229
  • Washington
    • Kirkland, Washington, United States, 98034
    • Spokane, Washington, United States, 99204

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 38 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 PD diagnosis was established
• Subject must be on stable dose of anti-Parkinson's medication 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

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2; Pimavanserin tartrate (ACP-103), 10 mg, tablet, once daily by mouth, 6 weeks	Drug: Pimavanserin tartrate (ACP-103); 10 mg, tablet, once daily by mouth, 6 weeks; Drug: Pimavanserin tartrate (ACP-103); 40 mg, tablet, once daily by mouth, 6 weeks
Experimental: 3; Pimavanserin tartrate (ACP-103), 40 mg, tablet, once daily by mouth, 6 weeks	Drug: Pimavanserin tartrate (ACP-103); 10 mg, tablet, once daily by mouth, 6 weeks; Drug: Pimavanserin tartrate (ACP-103); 40 mg, tablet, once daily by mouth, 6 weeks
Placebo Comparator: 1; Placebo tablet, once daily by mouth, 6 weeks	Drug: Placebo; tablet, once daily by mouth, 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 42 in the Scale for the Assessment of Positive Symptoms - Hallucinations and Delusions scales (SAPS-H+D) score for the ITT Analysis Set. The possible total score is 0 to 100 and a negative change in score indicates improvement. Analysis Method: Analysis of Covariance (ANCOVA) and missing data was imputed using Last Observation Carried Forward (LOCF) method.	Each study visit (i.e. Days 1, 8, 15, 29 and 42)

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 (Day 1) to Day 42 in the combined score of the Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living) and Part III (Motor Examination) using the per-protocol (PP) analysis set. The possible total score is 0 to 160 and a negative change in score indicates improvement. Analysis Method: ANCOVA, and missing data was imputed using LOCF. The UPDRS Parts II+III score was analyzed by constructing 2-sided 95% confidence intervals (CIs) on the difference between each 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.	Each study visit (i.e. Days 1, 8, 15, 29 and 42)

Collaborators and Investigators

• Sponsor: ACADIA Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: May 22, 2007
• First Submitted That Met QC Criteria: May 22, 2007
• First Posted (Estimate): May 24, 2007

Study Record Updates

• Last Update Posted (Actual): May 17, 2017
• Last Update Submitted That Met QC Criteria: April 18, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Parkinson's disease, psychotic disorders
• 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-103-012

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No