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Trial record 1 of 1 for:    01712074
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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

This study has been 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.)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01712074
First Posted: October 23, 2012
Last Update Posted: March 20, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Pfizer
  Purpose
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 Intervention Phase
Alzheimer's Disease Drug: PF-05212377 (SAM-760) Other: Placebo Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • 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:
  • 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:
  • 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.



Enrollment: 186
Study Start Date: November 2012
Study Completion Date: September 2015
Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

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.


Ages Eligible for Study:   60 Years and older   (Adult, Senior)
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
  Contacts and Locations
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


  Show 60 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01712074     History of Changes
Other Study ID Numbers: B2081011
2014-000830-42 ( EudraCT Number )
First Submitted: October 19, 2012
First Posted: October 23, 2012
Results First Submitted: August 26, 2016
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:
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