Study to Examine the Safety and Efficacy of Pimavanserin for the Treatment of Agitation and Aggression in Alzheimer's Disease (SERENE)

A Double-Blind, Placebo-Controlled Study to Examine the Safety and Efficacy of Pimavanserin for the Treatment of Agitation and Aggression in Alzheimer's Disease

To evaluate the efficacy of pimavanserin compared with placebo in treatment of agitation and aggression after 12 weeks of treatment

Study Overview

• Status: Terminated
• Conditions: Agitation and Aggression in Alzheimer's Disease
• Intervention / Treatment: Drug: Pimavanserin 34 mg; Drug: Pimavanserin 20 mg; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 2

Contacts and Locations

Study Locations

• Chile
  • Antofagasta, Chile, 1270244
  • Santiago, Chile, 7500710
  • Santiago, Chile, 7560356
  • Los Rios
    • Valdivia, Los Rios, Chile, 5090000
• France
  • Paris, France, 75010
  • Saint-Herblain, France, 44800
  • Strasbourg, France, 67200
  • Villeurbanne, France, 69100
  • Cedex 9
    • Toulouse, Cedex 9, France, 31059
• Spain
  • Córdoba, Spain, 14011
  • Elche, Spain, 03203
  • Madrid, Spain, 28044
  • Palma de Mallorca, Spain, 07010
  • Pamplona, Spain, 31014
  • Santa Coloma De Gramenet, Spain, 08921
  • Terrassa, Spain, 08221
  • Zaragoza, Spain, 50012
  • Vizcaya
    • Algorta, Vizcaya, Spain, 48993
• United Kingdom
  • Bath, United Kingdom, BA1 3NG
  • Isleworth, United Kingdom, TW7 6AF
  • Manchester, United Kingdom, M21 9UN
  • Northampton, United Kingdom, NN5 6UD
  • Wiltshire
    • Swindon, Wiltshire, United Kingdom, SN3 6BW
• United States
  • California
    • Costa Mesa, California, United States, 92626
    • Fresno, California, United States, 93710
    • Fullerton, California, United States, 92835
    • Los Angeles, California, United States, 90073
    • Pasadena, California, United States, 91105
    • San Diego, California, United States, 92103
  • Connecticut
    • Danbury, Connecticut, United States, 06810
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
  • Florida
    • Boca Raton, Florida, United States, 33486
    • Deerfield Beach, Florida, United States, 33064
    • Miami, Florida, United States, 33137
    • Naples, Florida, United States, 34102
  • Georgia
    • Atlanta, Georgia, United States, 30322
  • Maine
    • Bangor, Maine, United States, 04401
  • Massachusetts
    • Quincy, Massachusetts, United States, 02169
  • Michigan
    • Clinton Township, Michigan, United States, 48035
  • Mississippi
    • Flowood, Mississippi, United States, 39232
    • Jackson, Mississippi, United States, 39216
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
    • Marlton, New Jersey, United States, 08053
    • Toms River, New Jersey, United States, 08755
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
  • North Carolina
    • Charlotte, North Carolina, United States, 28270
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
  • Oregon
    • Medford, Oregon, United States, 97504
  • Pennsylvania
    • Jenkintown, Pennsylvania, United States, 19046
    • Norristown, Pennsylvania, United States, 19401
    • Willow Grove, Pennsylvania, United States, 19090
  • South Carolina
    • Charleston, South Carolina, United States, 29401
  • Tennessee
    • Nashville, Tennessee, United States, 37212
  • Texas
    • DeSoto, Texas, United States, 75115
  • Utah
    • Salt Lake City, Utah, United States, 84124
  • Washington
    • Spokane, Washington, United States, 99202

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female, 50 years of age or older

2. Can understand the nature of the trial and protocol requirements and provide signed informed consent

   • from patient, if deemed competent to provide consent
   • from an appropriate person (e.g. patient's Legally Authorized Representative (LAR) with the patient's assent) if patient is deemed not competent to provide informed consent.
3. Has a diagnosis of probable AD according to the National Institute on Aging-Alzheimer's Association (NIA-AA) guidelines
4. Meets criteria for agitation according to the International Psychogeriatric Association (IPA) guidelines
5. Lives at home or in an assisted living or care facility (but has the capacity to visit the clinic as an outpatient). Subjects must have been at their current location for at least 3 weeks prior to Screening and plan to remain at the same location for the duration of the trial.
6. Has a designated study partner/caregiver who is in contact with the patient at least 3 times a week on 3 separate days
7. Female patients must be of non-childbearing potential or must agree to use an acceptable method of contraception or abstinence , for at least 1 month prior to randomization, during the study, and 1 month following completion of the study
8. The patient and caregiver are willing and able to participate in all schedule evaluations and complete all required tests

Exclusion Criteria:

1. The agitation/aggression is attributable to concomitant medications, environmental conditions, substance abuse, or active medical or psychiatric condition
2. Patient is receiving skilled nursing care for any medical condition other than dementia
3. Treatment with an antipsychotic medication within 2 weeks of Baseline visit or 5 half lives, whichever is longer
4. Patient or study partner/caregiver has a medical condition (e.g., hearing, vision impairments) that would impair the ability to perform the study assessments.
5. Has had a myocardial infarction within the last six months
6. Has a history or symptoms of long QT syndrome
7. Has a history of a significant psychotic disorder before or during the diagnosis of probable Alzheimer's disease (including, but not limited to schizophrenia or bipolar disorder)
8. Patient is bedridden or has any significant medical condition that is unstable and would place the patient at undue risk from study drug or study procedures 9. Has a sensitivity to pimavanserin or its excipients

10. Has previously participated in a clinical study with pimavanserin

11. Has a Global Clinician Assessment of Suicidality (GCAS) score of 3 or 4 based on Investigator's assessment of behavior within the last 3 months at Screening or since last visit at Baseline

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: Pimavanserin 34 mg; Drug- pimavanserin tartrate, 34 mg, taken as two 17 mg tablets, once daily by mouth	Drug: Pimavanserin 34 mg; Pimavanserin 34 mg, tablet, taken as two 17 mg tablets, once daily by mouth
Experimental: Pimavanserin 20 mg; Drug- pimavanserin tartrate, 20 mg, taken as two 10 mg tablets, once daily by mouth	Drug: Pimavanserin 20 mg; Pimavanserin 20 mg, tablet, taken as two 10 mg tablets, once daily by mouth
Placebo Comparator: Placebo; Placebo, taken as two tablets, once daily by mouth	Other: Placebo; Placebo, taken as two tablets, once daily by mouth

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohen-Mansfield Agitation Inventory (CMAI)	The Cohen-Mansfield Agitation Inventory (CMAI) is a 29-item scale to assess agitation. Each item is rated on a 7-point scale of frequency, from least (1) to most frequent (7). Items are summed to calculate the CMAI total score. The CMAI total score has a range of 29-203 points; higher scores indicate more severe agitation	Baseline to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Zarit Burden Interview	The Zarit Burden Interview (ZBI) assess the stresses experienced by caregivers of patients with dementia. It assesses 22 questions about the impact of the patient's disabilities on the caregiver's life, each rated from least (0) to most (4) frequent. Items are summed to calculate the ZBI total score. The ZBI total score ranges from 0 to 88; higher scores denoting more stresses experienced by caregivers.	Baseline to 12 weeks

Collaborators and Investigators

• Sponsor: ACADIA Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (Actual): January 25, 2018
• Study Completion (Actual): February 16, 2018

Study Registration Dates

• First Submitted: December 12, 2016
• First Submitted That Met QC Criteria: December 13, 2016
• First Posted (Estimate): December 14, 2016

Study Record Updates

• Last Update Posted (Actual): March 28, 2019
• Last Update Submitted That Met QC Criteria: March 7, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Neurodegenerative Diseases; Dyskinesias; Psychomotor Disorders; Dementia; Tauopathies; Aggression; Psychomotor Agitation; Alzheimer Disease; 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-103-032; 2016-001127-32 (EudraCT Number)

Plan for Individual participant data (IPD)

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