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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

Tracking Information
First Submitted Date  ICMJE October 19, 2012
First Posted Date  ICMJE October 23, 2012
Results First Submitted Date  ICMJE August 26, 2016
Results First Posted Date  ICMJE March 20, 2017
Last Update Posted Date March 20, 2017
Study Start Date  ICMJE November 2012
Actual Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 30, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 19, 2012)
Change from Baseline (Week 4) to 12 weeks after the start of double-blind study medication on the ADAS-cog13 total score (Week 16) [ Time Frame: Week 16 ]
Change History Complete list of historical versions of study NCT01712074 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 30, 2017)
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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 19, 2012)
Change from baseline (Week 4) to 12 weeks after the start of double-blind study medication on the NPI total score (Week 16). [ Time Frame: Week 16 ]
Current Other Pre-specified Outcome Measures
 (submitted: January 30, 2017)
  • 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
  • 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).
  • 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).
  • 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).
  • 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).
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study Evaluating TheSafety And Efficacy Of PF-05212377 Or Placebo In Subjects With Alzheimer's Disease With Existing Neuropsychiatric Symptoms On Donepezil
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer's Disease
Intervention  ICMJE
  • Drug: PF-05212377 (SAM-760)
    30 mg QD of PF-05212377 (SAM-760)
  • Other: Placebo
    Placebo QD
Study Arms  ICMJE
  • Experimental: 30 mg QD of PF-05212377
    Intervention: Drug: PF-05212377 (SAM-760)
  • Placebo Comparator: Placebo
    Intervention: Other: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 29, 2016)
186
Original Estimated Enrollment  ICMJE
 (submitted: October 19, 2012)
342
Actual Study Completion Date  ICMJE September 2015
Actual Primary Completion Date September 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Chile,   France,   Germany,   Spain,   United Kingdom,   United States
Removed Location Countries Australia
 
Administrative Information
NCT Number  ICMJE NCT01712074
Other Study ID Numbers  ICMJE B2081011
2014-000830-42 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP