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

A PHASE 2 MULTICENTER, DOUBLE BLIND, PLACEBO CONTROLLED, PARALLEL GROUP STUDY OF PF-04447943 IN SUBJECTS WITH MILD TO MODERATE ALZHEIMER'S DISEASE

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: PF-04447943; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 191
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 3G8
      • Medical Arts Health Research Group
  • Ontario
    • Hamilton, Ontario, Canada, L9C 7N4
      • Hamilton Health Sciences
    • Peterborough, Ontario, Canada, K9H 2P4
      • Kawartha Regional Memory Clinic
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Neuro Rive Sud Clinic
    • Sherbrooke, Quebec, Canada, J1H 1Z1
      • Diex Recherche Inc.
• Chile
  • II Region
    • Antofagasta, II Region, Chile
      • Psicomed Estudios Clínicos
  • RM
    • Providencia, RM, Chile, 7500617
      • Centro Doctora Lissette Duque
    • Santiago, RM, Chile, 7500922
      • Hospital del Salvador
    • Santiago, RM, Chile, 7500710
      • Psicomedica Research Group
    • Santiago, RM, Chile, 7550112
      • Neuroconsult
    • Santiago, RM, Chile, 7560356
      • Especialidades Medicas L Y S
  • Santiago
    • La Florida, Santiago, Chile, 8260094
      • Neuropsicología Ltda.
  • XIV Region
    • Valdivia, XIV Region, Chile, 5090145
      • Hospital Base Valdivia
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Fakultní nemocnice
  • Pardubice, Czechia, 53203
    • Pardubicka krajska nemocnice, a.s.
  • Praha 2, Czechia, 120 00
    • Pragtis, s.r.o.
  • Praha 5, Czechia, 150 08
    • Fakultni nemocnice v Motole
  • Praha 5, Czechia, 15800
    • Psychiatry Trial, s.r.o.
  • Praha 8, Czechia, 180 00
    • Psychiatricka ambulance
  • Praha 8, Czechia, 18000
    • Neurologie - EEG, s.r.o
  • Rychnov nad Kneznou, Czechia, 51601
    • Centrum neurologicke pece, s.r.o.
  • Strakonice, Czechia, 386 01
    • Psychiatricka ambulance
• United States
  • Alabama
    • Northport, Alabama, United States, 35476
      • Neurology Clinic, PC
  • California
    • Costa Mesa, California, United States, 92626
      • ATP Clinical Research, Inc.
    • Glendale, California, United States, 91204
      • Southwestern Research Incorporated
    • Newport Beach, California, United States, 92663
      • Pacific Coast Imaging (for Imaging only)
    • Rancho Mirage, California, United States, 92270
      • The Southwest Institute for Clinical Research, Inc.
    • San Diego, California, United States, 92128
      • Pacific Research Network (Satellite Site)
    • Vista, California, United States, 92081
      • Pacific Research Network, Inc. (Satellite Site)
  • Florida
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
    • Plantation, Florida, United States, 33317
      • Berma Research Group
  • Illinois
    • Joliet, Illinois, United States, 60435
      • Joliet Center for Clinical Research
  • Indiana
    • Fort Wayne, Indiana, United States, 46805
      • Fort Wayne Neurological Center
    • Indianapolis, Indiana, United States, 46260
      • Agewell
  • Kentucky
    • Paducah, Kentucky, United States, 42003
      • Four Rivers Clinical Research, Inc.
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • Lake Charles Clinical Trials, LLC
    • Lake Charles, Louisiana, United States, 70601
      • Advanced MRI
  • Massachusetts
    • Newton, Massachusetts, United States, 02459
      • Neurocare, Inc.
  • New York
    • Cedarhurst, New York, United States, 11516
      • Neurobehavioral Research Inc
    • Staten Island, New York, United States, 10305
      • Behavioral Medical Research Of Staten Island
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Alzheimer's Disease Research Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital, Alzheimer's Disease and Memory Disorders Center
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic, PC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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	Drug: Placebo; matching placebo tablets, every 12 hours for 12 wks
Experimental: PF-04447943	Drug: PF-04447943; tablets, 25 mg every 12 hours for 12 wks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) Score at Baseline	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.	Baseline (Day 1)
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) at 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.	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 70 (ADAS-Cog 70) at Week 3, 6 and 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.	Baseline, Week 3, 6, 9
Clinical Global Impression - Improvement (CGI-I)	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.	Week 3, 6, 9, 12
Neuropsychiatric Inventory (NPI) Total Score at 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.	Baseline
Change From Baseline in Neuropsychiatric Inventory (NPI) Total Score at Week 3, 6, 9 and 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.	Baseline, Week 3, 6, 9, 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Laboratory Test Abnormalities	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.	Baseline up to Week 12
Number of Participants With Pre-defined Criteria for Electrocardiogram (ECG) Abnormalities	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.	Baseline up to Week 12
Number of Participants With Abnormal Physical Examinations and Neurological Examinations	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.	Screening (28 days before Baseline), Week 12
Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS)	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?").	Screening, Baseline, Post-baseline (Week 1 up to 12)
PF-04447943 Plasma Concentration		Pre-dose on Week 1; 0 to 3 hours following cognitive testing at Week 3, 6, 9, 12
Number of Participants With Pre-defined Criteria of Vital Signs Abnormalities	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.	Baseline up to Week 12 for change in supine or standing blood pressure; Week 1, 3, 6, 9, 12 for orthostatic hypotension

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2009
• Primary Completion (Actual): September 22, 2010
• Study Completion (Actual): September 22, 2010

Study Registration Dates

• First Submitted: June 29, 2009
• First Submitted That Met QC Criteria: June 29, 2009
• First Posted (Estimate): June 30, 2009

Study Record Updates

• Last Update Posted (Actual): November 19, 2020
• Last Update Submitted That Met QC Criteria: October 28, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: safety; Alzheimer's disease; efficacy; PF-04447943; plasma concentrations
• 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: B0401005; 2009-012179-82 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.