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

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ClinicalTrials.gov Identifier: NCT01712074
Recruitment Status : Terminated (The study was terminated October 23, 2015 as pre-specified, interim analysis futility criteria were met. The termination was not due to safety concerns.)
First Posted : October 23, 2012
Results First Posted : March 20, 2017
Last Update Posted : March 20, 2017
Sponsor:
Information provided by (Responsible Party):
Pfizer

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.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: PF-05212377 (SAM-760) Other: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 186 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : November 2012
Actual Primary Completion Date : September 2015
Actual Study Completion Date : September 2015

Resource links provided by the National Library of Medicine

Drug Information available for: Donepezil

Arm Intervention/treatment
Experimental: 30 mg QD of PF-05212377 Drug: PF-05212377 (SAM-760)
30 mg QD of PF-05212377 (SAM-760)

Placebo Comparator: Placebo Other: Placebo
Placebo QD




Primary Outcome Measures :
  1. Change From Baseline in ADAS-cog13 Total Score at Week 16 [ Time Frame: Baseline and 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.


Secondary Outcome Measures :
  1. Change From Baseline in the Neuropsychiatric Inventory (NPI) Total Score at Week 16 (Visit 5) [ Time Frame: Baseline and Week 16 ]
    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.


Other Outcome Measures:
  1. Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation [ Time Frame: Week 4 to Week 18 ]
    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

  2. Proportion of Participants With Laboratory Abnormalities of Potential Clinical Concern During Double Blind Period [ Time Frame: Week 4 to Week 16 ]

    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).


  3. Selected ECG Change From Baseline - PR Interval at Week 6 (Visit 3) [ Time Frame: Baseline and Week 6 ]
    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).

  4. Selected ECG Change From Baseline - PR Interval at Week 10 (Visit 4) [ Time Frame: Baseline and Week 10 ]
    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).

  5. Selected ECG Change From Baseline - PR Interval at Week 16/Early Termination (Visit 5) [ Time Frame: Baseline and Week 16/Early Termination ]
    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).

  6. Percentage of Participant With PR Interval Abnormalities of Potential Clinical Concern [ Time Frame: Week 4 to Week 16 ]
    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.

  7. Selected ECG Change From Baseline - QRS Complex at Week 6 (Visit 3) [ Time Frame: Baseline and Week 6 ]
    The QRS complex is the combination of the Q wave, R wave and S wave, representing ventricular depolarization.

  8. Selected ECG Change From Baseline - QRS Complex at Week 10 (Visit 4) [ Time Frame: Baseline and Week 10 ]
    The QRS complex is the combination of the Q wave, R wave and S wave, representing ventricular depolarization.

  9. Selected ECG Change From Baseline - QRS Complex at Week 16/Early Termination (Visit 5) [ Time Frame: Baseline and Week 16/Early Termination ]
    The QRS complex is the combination of the Q wave, R wave and S wave, representing ventricular depolarization.

  10. Proportion of Participants With QRS Complex Abnormalities of Potential Clinical Concern [ Time Frame: Week 4 to Week 16 ]
    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.

  11. Selected ECG Change From Baseline - QTcF Interval at Week 6 (Visit 3) [ Time Frame: Baseline and Week 6 ]
    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.

  12. Selected ECG Change From Baseline - QTcF Interval at Week 10 (Visit 4) [ Time Frame: Baseline and Week 10 ]
    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.

  13. Selected ECG Change From Baseline - QTcF Interval at Week 16/Early Termination (Visit 5) [ Time Frame: Baseline and Week 16/Early Termination ]
    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.

  14. Proportion of Participants With QTcF Interval Abnormalities of Potential Clinical Concern [ Time Frame: Week 4 to Week 16 ]

    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.


  15. Blood Pressure (BP) Changes From Baseline - Week 6 (Visit 3) [ Time Frame: Baseline and Week 6 ]
    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.

  16. Pulse Rate Changes From Baseline - Week 6 (Visit 3) [ Time Frame: Baseline and Week 6 ]
    The pulse rate changes from baseline at Week 6 (Visit 3) including supine pulse rate, and standing pulse rate.

  17. BP Changes From Baseline - Week 10 (Visit 4) [ Time Frame: Baseline and Week 10 ]
    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.

  18. Pulse Rate Changes From Baseline - Week 10 (Visit 4) [ Time Frame: Baseline and Week 10 ]
    The pulse rate changes from baseline at Week 10 (Visit 4) including supine pulse rate, and standing pulse rate.

  19. BP Changes From Baseline - Week 16/Early Termination (Visit 5) [ Time Frame: Baseline and Week 16/Early Termination ]
    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.

  20. Pulse Rate Changes From Baseline - Week 16/Early Termination (Visit 5) [ Time Frame: Baseline and Week 16/Early Termination ]
    The pulse rate changes from baseline at Week 16/Early Termination (Visit 5) including supine pulse rate, and standing pulse rate.

  21. Proportion of Participants With Post-Baseline Vital Signs Abnormalities of Potential Clinical Concern [ Time Frame: Week 4 to Week 16 ]
    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.

  22. Participants in Each Category of C-CASA Mapped From the C-SSRS Responses [ Time Frame: From Screening to Week 18/Early Termination ]

    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.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01712074


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

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01712074     History of Changes
Other Study ID Numbers: B2081011
2014-000830-42 ( EudraCT Number )
First Posted: October 23, 2012    Key Record Dates
Results First Posted: March 20, 2017
Last Update Posted: March 20, 2017
Last Verified: January 2017
Keywords provided by Pfizer:
Randomized
Double Blind
Safety and Efficacy
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Donepezil
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents