Clinical trial NCT01712074: Study Evaluating TheSafety And Efficacy Of PF-05212377 Or Placebo In Subjects With Alzheimer's Disease With Existing Neuropsychiatric Symptoms On Donepezil
Official title: A Randomized, 18-week, Placebo-controlled, Double-blind, Parallel Group Study Of The Safety And Efficacy Of Pf-05212377 (Sam-760) In Subjects With Mild-to-moderate Alzheimer's Disease With Existing Neuropsychiatric Symptoms On A Stable Daily Dose Of Donepezil
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Alzheimer's Disease
Keywords: Randomized
Double Blind
Safety and Efficacy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-10-23
Enrollment: 186
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate safety and efficacy of PF-05212377 in subjects with mild-to-moderate Alzheimer's Disease with existing neuropsychiatric symptoms on a stable dose of Donepezil. The 4-week run-in will minimize placebo effect. The 12-week treatment period is considered the minimum length necessary to reliably evaluate the effect PF-05212377 on cognition and and neuropsychiatric symptoms in this population. The 2-week washout will allow to monitor re-emergence of neuropsychiatric and cognitive symptoms.


Eligibility criteria: Inclusion Criteria:

* Clinical diagnosis of probable AD with supportive brain imaging documentation
* Have existing neuropsychiatric symptoms as defined by a score equal or greater than 10 on the NPI at screening, arising from item scores equal or greater than 2 (frequency X severity) on at least 2 domains.
* Has been on donepezil (stable dose of 5 mg or 10 mg) for at least four months, with no intent to change such for the duration of the study.

Exclusion Criteria:

* Demonstrate extreme agitation, physical aggression or violence to themselves, their caregiver, or others, and/or an inability to complete the ADAS-cog assessment at Screening.
* Have major structural brain disease other than Alzheimer's Disease
* Other severe acute or chronical medical or psychiatric condition or laboratory abnormality

Primary outcomes:
measure: Change From Baseline in ADAS-cog13 Total Score at Week 16
timeFrame: Baseline and Week 16
Secondary outcomes:
measure: Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score at Week 16 (Visit 5)
timeFrame: Baseline and Week 16
Other outcomes:
measure: Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation
timeFrame: Week 4 to Week 18
measure: Proportion of Participants With Laboratory Abnormalities of Potential Clinical Concern During Double Blind Period
timeFrame: Week 4 to Week 16
measure: Selected ECG Change From Baseline - PR Interval at Week 6 (Visit 3)
timeFrame: Baseline and Week 6
measure: Selected ECG Change From Baseline - PR Interval at Week 10 (Visit 4)
timeFrame: Baseline and Week 10
measure: Selected ECG Change From Baseline - PR Interval at Week 16/Early Termination (Visit 5)
timeFrame: Baseline and Week 16/Early Termination
measure: Percentage of Participant With PR Interval Abnormalities of Potential Clinical Concern
timeFrame: Week 4 to Week 16
measure: Selected ECG Change From Baseline - QRS Complex at Week 6 (Visit 3)
timeFrame: Baseline and Week 6
measure: Selected ECG Change From Baseline - QRS Complex at Week 10 (Visit 4)
timeFrame: Baseline and Week 10
measure: Selected ECG Change From Baseline - QRS Complex at Week 16/Early Termination (Visit 5)
timeFrame: Baseline and Week 16/Early Termination
measure: Proportion of Participants With QRS Complex Abnormalities of Potential Clinical Concern
timeFrame: Week 4 to Week 16
measure: Selected ECG Change From Baseline - QTcF Interval at Week 6 (Visit 3)
timeFrame: Baseline and Week 6
measure: Selected ECG Change From Baseline - QTcF Interval at Week 10 (Visit 4)
timeFrame: Baseline and Week 10
measure: Selected ECG Change From Baseline - QTcF Interval at Week 16/Early Termination (Visit 5)
timeFrame: Baseline and Week 16/Early Termination
measure: Proportion of Participants With QTcF Interval Abnormalities of Potential Clinical Concern
timeFrame: Week 4 to Week 16
measure: Blood Pressure (BP) Changes From Baseline - Week 6 (Visit 3)
timeFrame: Baseline and Week 6
measure: Pulse Rate Changes From Baseline - Week 6 (Visit 3)
timeFrame: Baseline and Week 6
measure: BP Changes From Baseline - Week 10 (Visit 4)
timeFrame: Baseline and Week 10
measure: Pulse Rate Changes From Baseline - Week 10 (Visit 4)
timeFrame: Baseline and Week 10
measure: BP Changes From Baseline - Week 16/Early Termination (Visit 5)
timeFrame: Baseline and Week 16/Early Termination
measure: Pulse Rate Changes From Baseline - Week 16/Early Termination (Visit 5)
timeFrame: Baseline and Week 16/Early Termination
measure: Proportion of Participants With Post-Baseline Vital Signs Abnormalities of Potential Clinical Concern
timeFrame: Week 4 to Week 16
measure: Participants in Each Category of C-CASA Mapped From the C-SSRS Responses
timeFrame: From Screening to Week 18/Early Termination
Locations:
city: Costa Mesa
country: United States
facility: ATP Clinical Research, Inc
state: California
city: Imperial
country: United States
facility: Sun Valley Research Center
state: California
city: Rancho Mirage
country: United States
facility: Desert Valley Research
state: California
city: Santa Ana
country: United States
facility: RAA - Apex Aquisition, LLC
state: California
city: Hamden
country: United States
facility: Geriatric and Adult Psychiatry LLC
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: New Haven
country: United States
facility: Yale-New Haven Hospital, Temple Radiology
state: Connecticut
city: New Haven
country: United States
facility: Yale University School of Medicine, MRI Research Center (MRI)
state: Connecticut
city: Boynton Beach
country: United States
facility: Diagnostic Centers of America
state: Florida
city: Brooksville
country: United States
facility: Meridien Research
state: Florida
city: Deerfield Beach
country: United States
facility: Quantum Laboratories
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research Inc
state: Florida
city: Hallandale Beach
country: United States
facility: MD Clinical
state: Florida
city: Leesburg
country: United States
facility: Compass Research LLC-North Clinic
state: Florida
city: Orange City
country: United States
facility: Medical Research Group of Central Florida
state: Florida
city: West Palm Beach
country: United States
facility: Premiere Research Institute
state: Florida
city: Alpharetta
country: United States
facility: Institute for Advanced Medical Research
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Columbus
country: United States
facility: Columbus Research & Wellness Institute, Inc.
state: Georgia
city: Lake Charles
country: United States
facility: Lake Charles Clinical Trials
state: Louisiana
city: East Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Creve Coeur
country: United States
facility: Metro Imaging (Imaging only)
state: Missouri
city: Creve Coeur
country: United States
facility: Millennium Psychiatric Associates, LLC
state: Missouri
city: New York
country: United States
facility: Eastside Comprehensive Medical Center, LLC
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center AD-CARE Program | University of Rochester Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center (MRI Imaging Only)
state: New York
city: Staten Island
country: United States
facility: Behavioral Medical Research of Staten Island
state: New York
city: Columbus
country: United States
facility: The Ohio State University (administrative offices only)
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University - 2050
state: Ohio
city: Norristown
country: United States
facility: Keystone Clinical Studies, LLC
state: Pennsylvania
city: Charleston
country: United States
facility: Roper Hospital (Imaging Only)
state: South Carolina
city: Charleston
country: United States
facility: Roper St. Francis Healthcare
state: South Carolina
city: Charleston
country: United States
facility: Roper St. Francis Pharmacy (IP Shipment/Storage)
state: South Carolina
city: Cordova
country: United States
facility: Neurology Clinic, P.C.
state: Tennessee
city: Austin
country: United States
facility: Senior Adults Speciality Research Inc.
state: Texas
city: Wichita Falls
country: United States
facility: Grayline Clinical Drug Trials
state: Texas
city: Bennington
country: United States
facility: Clinical Neuroscience Research Assoc. d/b/a The Memory Clinic
state: Vermont
city: Middleton
country: United States
facility: Dean Foundation for Health, Research and Education
state: Wisconsin
city: Waukesha
country: United States
facility: Cary J. Kohlenberg, MD, dba, IPC Research
state: Wisconsin
city: Waukesha
country: United States
facility: Merrill Hills Manor
state: Wisconsin
city: Halifax
country: Canada
facility: True North Clinical Research Halifax, Inc.
state: Nova Scotia
city: Chatham
country: Canada
facility: Chatham-kent Clinical Trials Research Centre
state: Ontario
city: Chatham
country: Canada
facility: Chatham-Kent Clinical Trials Research Centre
state: Ontario
city: Gatineau
country: Canada
facility: Recherches Neuro-Hippocampe Inc.
state: Quebec
city: Antofagasta
country: Chile
facility: Psicomed Estudios Medicos CIA. LTDA
state: Ii Region
city: Santiago
country: Chile
facility: Biomedica Research Group
state: Metropolitana
city: Santiago
country: Chile
facility: Especialidades Medicas L Y S
state: Metropolitana
city: La Seyne Sur Mer
country: France
facility: Espace Sante 2
city: Berlin
country: Germany
facility: Dr. med. Volker Schumann, Arzt fuer Nervenheilkunde
city: Berlin
country: Germany
facility: Praxis Dr. Franz- Arztehaus am KEH mit Epilepsie-Zentrum
city: Berlin
country: Germany
facility: Praxis Dr. sc. med. Alexander Schulze
city: Leipzig
country: Germany
facility: Arzneimittelforschung Leipzig Gmbh
city: Nuernberg
country: Germany
facility: Praxis fuer Neurologie / Psychiatrie Prof. Dr. Steinwachs
city: Elche
country: Spain
facility: Hospital General Universitario De Elche
state: Alicante
city: Madrid
country: Spain
facility: Hospital de Cantoblanco
city: Bath
country: United Kingdom
facility: The Research Institute for the Care of Older People Centre
city: Cambridge
country: United Kingdom
facility: Fulbourn Hospital
city: Chertsey
country: United Kingdom
facility: Surrey and Borders Partnership NHS Foundation Trust
city: Northampton
country: United Kingdom
facility: Berrywood Hospital
city: Switzerland
country: United Kingdom
facility: Covance Laboratories
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Fullerton T, Binneman B, David W, Delnomdedieu M, Kupiec J, Lockwood P, Mancuso J, Miceli J, Bell J. A Phase 2 clinical trial of PF-05212377 (SAM-760) in subjects with mild to moderate Alzheimer's disease with existing neuropsychiatric symptoms on a stable daily dose of donepezil. Alzheimers Res Ther. 2018 Apr 5;10(1):38. doi: 10.1186/s13195-018-0368-9.