Study Evaluating TheSafety And Efficacy Of PF-05212377 Or Placebo In Subjects With Alzheimer's Disease With Existing Neuropsychiatric Symptoms On Donepezil

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

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.

Study Overview

• Status: Terminated
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Other: Placebo; Drug: PF-05212377 (SAM-760)

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3S 1M7
      • True North Clinical Research Halifax, Inc.
  • Ontario
    • Chatham, Ontario, Canada, N7L 1C1
      • Chatham-Kent Clinical Trials Research Centre
    • Chatham, Ontario, Canada, N7M 5L9
      • Chatham-Kent Clinical Trials Research Centre
  • Quebec
    • Gatineau, Quebec, Canada, J8T 8J1
      • Recherches Neuro-Hippocampe Inc.
• Chile
  • Ii Region
    • Antofagasta, Ii Region, Chile, 1270244
      • Psicomed Estudios Medicos CIA. LTDA
  • Metropolitana
    • Santiago, Metropolitana, Chile, 7500710
      • BioMedica Research Group
    • Santiago, Metropolitana, Chile, 7560356
      • Especialidades Medicas L Y S
• France
  • La Seyne Sur Mer, France, 83500
    • Espace Sante 2
• Germany
  • Berlin, Germany, 10245
    • Dr. med. Volker Schumann, Arzt fuer Nervenheilkunde
  • Berlin, Germany, 10365
    • Praxis Dr. Franz- Arztehaus am KEH mit Epilepsie-Zentrum
  • Berlin, Germany, 13156
    • Praxis Dr. sc. med. Alexander Schulze
  • Leipzig, Germany, 04107
    • Arzneimittelforschung Leipzig GmbH
  • Nuernberg, Germany, 90402
    • Praxis fuer Neurologie / Psychiatrie Prof. Dr. Steinwachs
• Spain
  • Madrid, Spain, 28049
    • Hospital de Cantoblanco
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Hospital General Universitario de Elche
• United Kingdom
  • Bath, United Kingdom, BA1 3NG
    • The Research Institute for the Care of Older People Centre
  • Cambridge, United Kingdom, CB21 5EF
    • Fulbourn Hospital
  • Chertsey, United Kingdom, KT16 0AE
    • Surrey and Borders Partnership NHS Foundation Trust
  • Northampton, United Kingdom, NN5 6UD
    • Berrywood Hospital
  • Switzerland, United Kingdom, 1217
    • Covance Laboratories
• United States
  • California
    • Costa Mesa, California, United States, 92626
      • ATP Clinical Research, Inc
    • Imperial, California, United States, 92251
      • Sun Valley Research Center
    • Rancho Mirage, California, United States, 92270
      • Desert Valley Research
    • Santa Ana, California, United States, 92705
      • RAA - Apex Aquisition, LLC
  • Connecticut
    • Hamden, Connecticut, United States, 06518
      • Geriatric and Adult Psychiatry LLC
    • New Haven, Connecticut, United States, 06510
      • Yale University
    • New Haven, Connecticut, United States, 06510
      • Yale-New Haven Hospital, Temple Radiology
    • New Haven, Connecticut, United States, 06520
      • Yale University School of Medicine, MRI Research Center (MRI)
  • Florida
    • Boynton Beach, Florida, United States, 33437
      • Diagnostic Centers of America
    • Brooksville, Florida, United States, 34601
      • Meridien Research
    • Deerfield Beach, Florida, United States, 33064
      • Quantum Laboratories
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research Inc
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical
    • Leesburg, Florida, United States, 34748
      • Compass Research LLC-North Clinic
    • Orange City, Florida, United States, 32763
      • Medical Research Group of Central Florida
    • West Palm Beach, Florida, United States, 33407
      • Premiere Research Institute
  • Georgia
    • Alpharetta, Georgia, United States, 30005
      • Institute for Advanced Medical Research
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center for Medical Research
    • Columbus, Georgia, United States, 31904
      • Columbus Research & Wellness Institute, Inc.
  • Louisiana
    • Lake Charles, Louisiana, United States, 70629
      • Lake Charles Clinical Trials
  • Michigan
    • East Lansing, Michigan, United States, 48824
      • Michigan State University
  • Missouri
    • Creve Coeur, Missouri, United States, 63141
      • Millennium Psychiatric Associates, LLC
    • Creve Coeur, Missouri, United States, 63141
      • Metro Imaging (Imaging only)
  • New York
    • New York, New York, United States, 10021
      • Eastside Comprehensive Medical Center, LLC
    • Rochester, New York, United States, 14620
      • University of Rochester Medical Center AD-CARE Program | University of Rochester Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center (MRI Imaging Only)
    • Staten Island, New York, United States, 10305
      • Behavioral Medical Research Of Staten Island
  • Ohio
    • Columbus, Ohio, United States, 43212
      • The Ohio State University (administrative offices only)
    • Columbus, Ohio, United States, 43221
      • The Ohio State University - 2050
  • Pennsylvania
    • Norristown, Pennsylvania, United States, 19403
      • Keystone Clinical Studies, LLC
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Roper St. Francis Healthcare
    • Charleston, South Carolina, United States, 29401
      • Roper Hospital (Imaging Only)
    • Charleston, South Carolina, United States, 29401
      • Roper St. Francis Pharmacy (IP Shipment/Storage)
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic, P.C.
  • Texas
    • Austin, Texas, United States, 78757
      • Senior Adults Speciality Research Inc.
    • Wichita Falls, Texas, United States, 76309
      • Grayline Clinical Drug Trials
  • Vermont
    • Bennington, Vermont, United States, 05201
      • Clinical Neuroscience Research Assoc. d/b/a The Memory Clinic
  • Wisconsin
    • Middleton, Wisconsin, United States, 53562
      • Dean Foundation for Health, Research and Education
    • Waukesha, Wisconsin, United States, 53188
      • Cary J. Kohlenberg, MD, dba, IPC Research
    • Waukesha, Wisconsin, United States, 53226
      • Merrill Hills Manor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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
Placebo Comparator: Placebo	Other: Placebo; Placebo QD
Experimental: 30 mg QD of PF-05212377	Drug: PF-05212377 (SAM-760); 30 mg QD of PF-05212377 (SAM-760)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in ADAS-cog13 Total Score at Week 16	ADAS-cog13 (13-item ADAS cog) is a psychometric instrument that evaluates word recall, ability to follow commands, constructional praxis, naming, ideational praxis, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure of delayed word recall and concentration/ distractibility. The total score of the 13-item scale ranges from 0 to 85, with an increase in score indicating cognitive worsening.	Baseline and Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score at Week 16 (Visit 5)	The NPI evaluates both frequency and severity of 12 neuropsychiatric disturbances including delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, nighttime behaviors, as well as appetite/eating. The NPI total score (for 12 behavioral domains) is calculated as the product of frequency and severity for each domain, and ranges from 0 to 144. An increase in score indicates a worsening of symptoms.	Baseline and Week 16

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation	Proportion of participants with TEAEs leading to discontinuation over the 12-week double blind treatment period and washout. Adverse events (AEs) occurring following start of treatment or increasing in severity were counted as treatment emergent	Week 4 to Week 18
Proportion of Participants With Laboratory Abnormalities of Potential Clinical Concern During Double Blind Period	Proportion (%) of participants with laboratory abnormalities (without regard to baseline abnormalities) of potential clinical concern over the 12-week double blind treatment period. The following laboratory parameters were analyzed: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, bilirubin, alkaline phosphatase, uric acid, albumin, and total protein; urinalysis (pH, glucose, protein/albumin, hemoglobin/blood, ketones/acetone, nitrites, leukocyte esterase, microscopy [if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase]); others (only at screening or needed: urine drug screen, thyroid panel, Vitamin B12, methylmalonic acid, folate and Hemoglobin A1).	Week 4 to Week 16
Selected ECG Change From Baseline - PR Interval at Week 6 (Visit 3)	The PR interval is the time from the onset of the P wave to the start of the QRS complex (the combination of the Q wave, R wave and S wave, representing ventricular depolarization).	Baseline and Week 6
Selected ECG Change From Baseline - PR Interval at Week 10 (Visit 4)	The PR interval is the time from the onset of the P wave to the start of the QRS complex (the combination of the Q wave, R wave and S wave, representing ventricular depolarization).	Baseline and Week 10
Selected ECG Change From Baseline - PR Interval at Week 16/Early Termination (Visit 5)	The PR interval is the time from the onset of the P wave to the start of the QRS complex (the combination of the Q wave, R wave and S wave, representing ventricular depolarization).	Baseline and Week 16/Early Termination
Percentage of Participant With PR Interval Abnormalities of Potential Clinical Concern	Proportion (%) of participants with PR Interval abnormalities meeting categorical criteria over the 12 week double blind treatment period. The PR interval is the time from the onset of the P wave to the start of the QRS complex (the combination of the Q wave, R wave and S wave, representing ventricular depolarization). Participants with post-baseline PR absolute value>=300 msec , a PR increase of >=25% (for participants with a baseline value>=200 msec), or with an increase >=50% (for participants with a baseline value<200 msec) were counted.	Week 4 to Week 16
Selected ECG Change From Baseline - QRS Complex at Week 6 (Visit 3)	The QRS complex is the combination of the Q wave, R wave and S wave, representing ventricular depolarization.	Baseline and Week 6
Selected ECG Change From Baseline - QRS Complex at Week 10 (Visit 4)	The QRS complex is the combination of the Q wave, R wave and S wave, representing ventricular depolarization.	Baseline and Week 10
Selected ECG Change From Baseline - QRS Complex at Week 16/Early Termination (Visit 5)	The QRS complex is the combination of the Q wave, R wave and S wave, representing ventricular depolarization.	Baseline and Week 16/Early Termination
Proportion of Participants With QRS Complex Abnormalities of Potential Clinical Concern	Proportion (%) of participants with QRS Complex abnormalities meeting categorical criteria over the 12 week double blind treatment period. The QRS complex is the combination of the Q wave, R wave and S wave, representing ventricular depolarization). Participants with post-baseline QRS complex absolute value>=100 msec , a QRS complex increase of >=25% (for participants with a baseline value>=100 msec), or with an increase >=50% (for participants with a baseline value<100 msec) were counted.	Week 4 to Week 16
Selected ECG Change From Baseline - QTcF Interval at Week 6 (Visit 3)	The QTcF interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle, which is corrected for heart rate using Fridericia's formula.	Baseline and Week 6
Selected ECG Change From Baseline - QTcF Interval at Week 10 (Visit 4)	The QTcF interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle, which is corrected for heart rate using Fridericia's formula.	Baseline and Week 10
Selected ECG Change From Baseline - QTcF Interval at Week 16/Early Termination (Visit 5)	The QTcF interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle, which is corrected for heart rate using Fridericia's formula.	Baseline and Week 16/Early Termination
Proportion of Participants With QTcF Interval Abnormalities of Potential Clinical Concern	Proportion (%) of participants with QTcF Interval abnormalities meeting categorical criteria over the 12-week double blind treatment period. The QTcF interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle, which is corrected for heart rate using Fridericia's formula. Participants with a post-baseline QTcF absolute value of 450 - <480, 480 - <500, or >=500 mec, or with a post-baseline QTcF increase of 30 - <60 or >=60 msec were counted.	Week 4 to Week 16
Blood Pressure (BP) Changes From Baseline - Week 6 (Visit 3)	The BP changes from baseline at Week 6 (Visit 3) including supine systolic BP, standing systolic BP, standing systolic BP, supine diastolic BP, standing diastolic BP.	Baseline and Week 6
Pulse Rate Changes From Baseline - Week 6 (Visit 3)	The pulse rate changes from baseline at Week 6 (Visit 3) including supine pulse rate, and standing pulse rate.	Baseline and Week 6
BP Changes From Baseline - Week 10 (Visit 4)	The BP changes from baseline at Week 10 (Visit 4) including supine systolic BP, standing systolic BP, standing systolic BP, supine diastolic BP, standing diastolic BP.	Baseline and Week 10
Pulse Rate Changes From Baseline - Week 10 (Visit 4)	The pulse rate changes from baseline at Week 10 (Visit 4) including supine pulse rate, and standing pulse rate.	Baseline and Week 10
BP Changes From Baseline - Week 16/Early Termination (Visit 5)	The BP changes from baseline at Week 16/Early Termination (Visit 5) including supine systolic BP, standing systolic BP, standing systolic BP, supine diastolic BP, standing diastolic BP.	Baseline and Week 16/Early Termination
Pulse Rate Changes From Baseline - Week 16/Early Termination (Visit 5)	The pulse rate changes from baseline at Week 16/Early Termination (Visit 5) including supine pulse rate, and standing pulse rate.	Baseline and Week 16/Early Termination
Proportion of Participants With Post-Baseline Vital Signs Abnormalities of Potential Clinical Concern	Proportion (%) of participants with vital signs abnormalities (absolute and change from baseline) meeting categorical criteria over the 12-week double blind treatment period were counted. Vital signs data included blood pressure (BP) and pulse rate.	Week 4 to Week 16
Participants in Each Category of C-CASA Mapped From the C-SSRS Responses	Participants in each category of the Columbia Classification Algorithm of Suicide Assessment (C-CASA) mapped from the Columbia-Suicide Severity Rating Scale (C-SSRS) responses were reported. C-CASA Event Code: <1> Completed suicide; <2> Suicide attempt; <3> Preparatory acts towards imminent suicidal behavior; <4> Suicidal Ideation; <7> Self-injurious behavior, no suicidal intent. The suicidality assessments were performed at Screening, Week 0 (Visit 1), Week 4 (Visit 2), Week 6, (Visit 3), Week 10 (Visit 4), Week 16 (Visit 5), and Week 18 (Visit 6). Only participants falling any category of C-CASA events were listed below.	From Screening to Week 18/Early Termination

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• 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.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: October 19, 2012
• First Submitted That Met QC Criteria: October 19, 2012
• First Posted (Estimate): October 23, 2012

Study Record Updates

• Last Update Posted (Actual): March 20, 2017
• Last Update Submitted That Met QC Criteria: January 30, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Safety and Efficacy; Randomized; Double Blind
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: B2081011; 2014-000830-42 (EudraCT Number)