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A Study Of PF-04447943 Compared To Placebo In Subjects With Mild To Moderate Alzheimer's Disease

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.
 
ClinicalTrials.gov Identifier: NCT00930059
Recruitment Status : Completed
First Posted : June 30, 2009
Results First Posted : November 19, 2020
Last Update Posted : November 19, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
The purpose of this study is to evaluate the effects of PF-04447943 compared to placebo on cognitive, behavioral and overall symptoms of Alzheimer's disease; evaluate the safety and tolerability of PF-0444793 compared to placebo; and determine the levels of PF-04447943 in the plasma over the course of the study.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Drug: PF-04447943 Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 191 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A PHASE 2 MULTICENTER, DOUBLE BLIND, PLACEBO CONTROLLED, PARALLEL GROUP STUDY OF PF-04447943 IN SUBJECTS WITH MILD TO MODERATE ALZHEIMER'S DISEASE
Actual Study Start Date : September 10, 2009
Actual Primary Completion Date : September 22, 2010
Actual Study Completion Date : September 22, 2010

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: PF-04447943 Drug: PF-04447943
tablets, 25 mg every 12 hours for 12 wks

Placebo Comparator: Placebo Drug: Placebo
matching placebo tablets, every 12 hours for 12 wks




Primary Outcome Measures :
  1. Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) Score at Baseline [ Time Frame: Baseline (Day 1) ]
    ADAS-cog is a structured scale assessing the severity of cognitive impairment in Alzheimer's disease. It comprises of following 11 items (range): word recall (0-10), naming objects and fingers (0-5), following commands (0-5), constructional praxis (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-12), recall of test instructions (0-5), spoken language ability (0-5), word-finding difficulty (0-5), comprehension of spoken language (0-5). Total ADAS-cog 70 score was sum of all items and ranged from 0 (least impairment) to 70 (most severe impairment), higher score indicating worse cognition.

  2. Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) at Week 12 [ Time Frame: Baseline, Week 12 ]
    ADAS-cog is a structured scale assessing the severity of cognitive impairment in Alzheimer's disease. It comprises of following 11 items (range): word recall (0-10), naming objects and fingers (0-5), following commands (0-5), constructional praxis (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-12), recall of test instructions (0-5), spoken language ability (0-5), word-finding difficulty (0-5), comprehension of spoken language (0-5). Total ADAS-cog 70 score was sum of all items and ranged from 0 (least impairment) to 70 (most severe impairment), higher score indicating worse cognition.


Secondary Outcome Measures :
  1. Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) at Week 3, 6 and 9 [ Time Frame: Baseline, Week 3, 6, 9 ]
    ADAS-cog is a structured scale assessing the severity of cognitive impairment in Alzheimer's disease. It comprises of following 11 items (range): word recall (0-10), naming objects and fingers (0-5), following commands (0-5), constructional praxis (0-5), ideational praxis (0-5), orientation (0-8), word recognition (0-12), recall of test instructions (0-5), spoken language ability (0-5), word-finding difficulty (0-5), comprehension of spoken language (0-5). Total ADAS-cog 70 score was sum of all items and ranged from 0 (least impairment) to 70 (most severe impairment), higher score indicating worse cognition.

  2. Clinical Global Impression - Improvement (CGI-I) [ Time Frame: Week 3, 6, 9, 12 ]
    CGI-I is a 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale.

  3. Neuropsychiatric Inventory (NPI) Total Score at Baseline [ Time Frame: Baseline ]
    NPI total score evaluates disturbances in 12 behavioral domains: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating and night time behavior. NPI total score ranged from 0 (minimum severity) to 144 (maximum severity); higher score indicates greater behavioral disturbances.

  4. Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Week 3, 6, 9 and 12 [ Time Frame: Baseline, Week 3, 6, 9, 12 ]
    NPI total score evaluates disturbances in 12 behavioral domains: delusions, hallucinations, agitation/aggression, depression/dysphoria, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability/lability, motor disturbance, appetite/eating and night time behavior. NPI total score ranged from 0 (minimum severity) to 144 (maximum severity); higher score indicates greater behavioral disturbances.


Other Outcome Measures:
  1. Number of Participants With Laboratory Test Abnormalities [ Time Frame: Baseline up to Week 12 ]
    Criteria for laboratory test abnormality: a) Hematology: white blood cells (WBC) <0.6*lower limit of normal (LLN)/>1.5*upper limit of normal (ULN), hemoglobin, hematocrit, red blood cells (RBC), lymphocytes <0.8*LLN, total neutrophils <0.8*LLN/ >1.2*ULN, basophils, eosinophils, monocytes >1.2*ULN; b) Liver Function: total bilirubin >1.5*ULN, aspartate aminotransferase (AT), alanine AT[>0.3*ULN, total protein, albumin <0.8*LLN/ >1.2*ULN; c) Renal Function: creatinine >1.3*ULN, uric acid >1.2*ULN; d) Electrolytes: sodium <0.95*LLN/ >1.05*ULN, potassium, chloride, bicarbonate <0.9*LLN/ >1.1*ULN; e) Clinical Chemistry: glucose <0.6*LLN/ >1.5*ULN, glycosylated hemoglobin >1.3*ULN; f) Urinalysis: ketones, protein, blood/hemoglobin, urine glucose >=1, RBC, WBC >=6, hyaline casts >1; g) Hormones: tetraiodothyronine (T4), triiodothyronine (T3) and thyroid stimulating hormone (TSH) <0.8*LLN/1.2*ULN.

  2. Number of Participants With Pre-defined Criteria for Electrocardiogram (ECG) Abnormalities [ Time Frame: Baseline up to Week 12 ]
    Criteria for ECG (12-lead) abnormalities were as follow: 1) PR interval: greater than and equal to (>=) 300 milliseconds (msec), 2) PR interval: maximum increase from baseline >=25 percent (%) (if baseline PR interval greater than [>] 100 msec) or >=50% (if baseline PR interval less than or equal to [<=] 100 msec); 3) QRS complex: >=200 msec, 4) QRS complex: maximum increase from baseline >=25% or >=50%; 5) QT interval >=500 msec; 6) QT interval corrected using Bazett's formula (QTcB): 450 to less than (<) 480 msec, 7) QTcB: 480 to <500 msec, 8) QTcB: >=500 msec, 10) QTcB: 30 to <60 msec increase from baseline, 11) QTcB: >=60 msec increase from baseline; 9) QT interval corrected using the Fridericia's formula (QTcF): 450 to <480 msec, 10) QTcF: 480 to < 500 msec, 11) QTcF: >=500 msec, 12) QTcF: 30 to <60 msec increase from baseline, 13) QTcF: change>=60 msec increase from baseline.

  3. Number of Participants With Abnormal Physical Examinations and Neurological Examinations [ Time Frame: Screening (28 days before Baseline), Week 12 ]
    The complete physical and neurological examination included examination of abdomen, ears, extremities, eyes, general, head, heart, lungs, lymph nodes, mouth, musculoskeletal, neck, nose, ocular fundi, pulse, skin, throat, thyroid, and others. Abnormality was judged by investigator.

  4. Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Screening, Baseline, Post-baseline (Week 1 up to 12) ]
    C-SSRS assessed whether participant experienced the following: suicidal behavior which includes suicide attempt, interrupted attempt, aborted attempt, and preparatory acts towards imminent suicidal behavior (response of "Yes" on "preparatory acts or behavior"); suicidal ideation (response of "Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent); self-injurious behavior (SIB), intent unknown (response of "Yes" on "Has subject engaged in Non-suicidal Self-Injurious Behavior?").

  5. PF-04447943 Plasma Concentration [ Time Frame: Pre-dose on Week 1; 0 to 3 hours following cognitive testing at Week 3, 6, 9, 12 ]
  6. Number of Participants With Pre-defined Criteria of Vital Signs Abnormalities [ Time Frame: Baseline up to Week 12 for change in supine or standing blood pressure; Week 1, 3, 6, 9, 12 for orthostatic hypotension ]
    Pre-defined criteria vital signs abnormalities included maximum increase or decrease of greater than or equal to (>=) 30 millimeters of mercury (mmHg) from baseline for supine systolic blood pressure (SBP); maximum increase or decrease of >=20 mmHg from baseline for supine diastolic BP (DBP); maximum increase or decrease of >=30 mmHg from baseline for standing SBP; maximum increase or decrease of >=20 mmHg from baseline for standing DBP. Orthostatic hypotension was defined as a drop of more than 10 mmHg in diastolic BP or a drop of more than 20 mmHg in systolic BP within 3 minutes of standing from the supine position.



Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Mild to moderate Alzheimer's disease (MMSE 14-26)
  • Good general health (such controlled conditions as Type 2 diabetes and hypertension allowed)

Exclusion Criteria:

  • Use of acetylcholinesterase inhibitors (donepezil, rivastigmine, or galantamine) or memantine within 12 weeks of the start of the study
  • Significant cardiovascular disease in the past 6 months
  • Illness other than Alzheimer's disease that could contribute to cognitive impairment
  • History of stroke or seizure disorder

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): NCT00930059


Locations
Show Show 44 study locations
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00930059    
Other Study ID Numbers: B0401005
2009-012179-82 ( EudraCT Number )
First Posted: June 30, 2009    Key Record Dates
Results First Posted: November 19, 2020
Last Update Posted: November 19, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Keywords provided by Pfizer:
Alzheimer's disease
PF-04447943
efficacy
safety
plasma concentrations
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