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A Brief Study To Evaluate The Safety, Tolerability, And Blood Levels Of Multiple Doses Of PF-044467943 Or Placebo In Combination With Donepezil In Subjects With Mild To Moderate Alzheimer's Disease

Primary Purpose

Alzheimer's Disease

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PF-04447943
Placebo
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer's Disease focused on measuring phase 1 Alzheimer's disease donepezil

Eligibility Criteria

55 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects must have Alzheimer's dementia with a Mini Mental State Examination score between 18-26, inclusive.
  • Subjects must have a reliable caregiver.
  • Subjects must be on Aricept
  • Memantine is allowed if subjects are on a stable dose
  • Subjects must be in reasonably good health, based on medical history, physical examination, vital signs, and ECG, with no serious or unstable disease within the past 3 months.

Exclusion Criteria:

  • Subjects with clinically significant heart disease cannot participate.
  • Subjects with a past or current history of seizures cannot participate.

Sites / Locations

  • Glendale Adventist Medical Center
  • University of Florida - Center for Clinical Trials Research
  • MD Clinical

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

PF-04447943

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern
Criteria for vital signs abnormalities of potential concern included: supine/standing systolic blood pressure (BP) (less than [<] 90 millimeter of mercury [mmHg], maximum [max] decrease and increase of greater than or equal to [>=] 30 mmHg from baseline); diastolic BP (<50 mmHg, maximum decrease and increase of >=20 mmHg from baseline); supine pulse rate <40 beats per minute [bpm] or greater than [>]120 bpm); standing pulse rate <40 bpm or >140 bpm. Baseline is defined as the last pre-dose (PF-04447943) recording at Day 0.
Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern
Criteria for ECG abnormalities of potential clinical concern included: PR interval (>=300 milliseconds [msec], >= 25 percent [%] increase when baseline >200 msec or increase >=50% when baseline less than or equal to [<=] 200 msec); QRS interval (>=200 msec, >= 25% increase when baseline >100 msec or increase >=50% when baseline <=100 msec); QT corrected using Fridericia's formula (QTcF) (>=500 msec, maximum increase between >=30 to <60 msec and >=60 msec). Baseline is defined as the last pre-dose (PF-04447943) recording at Day 0.
Number of Participants With Laboratory Test Abnormalities
Criteria for laboratory tests abnormalities included: hemoglobin, hematocrit (<0.8*lower limit of normal [LLN]); red blood cell count (<0.8*LLN); platelets (<0.5*LLN or >1.75* upper limit of normal [ULN]); leucocytes (<0.6*LLN or >1.5*ULN); lymphocytes, total neutrophils (<0.8*LLN or >1.2*ULN); basophils, eosinophils, monocytes (>1.2*ULN); total bilirubin (>1.5* ULN); aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (>3*ULN); creatinine, blood urea nitrogen (>1.3*ULN); glucose (<0.6*LLN or >1.5*ULN); uric acid (>1.2*ULN); sodium (<0.95*LLN or 1.05*ULN); potassium, calcium, chloride, bicarbonate (<0.9*LLN or 1.1*ULN); albumin, total protein (<0.8*LLN or 1.2*ULN); urine analysis. Total number of participants with any laboratory abnormalities was reported.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Day 10 after last dose that were absent before treatment or that worsened relative to pretreatment state. Any abnormalities related to physical and neurological findings, laboratory tests, vital signs and ECG were reported as adverse events. AEs included SAEs as well as non-serious AEs which occurred during the trial.

Secondary Outcome Measures

Plasma Concentrations of PF-04447943
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-04447943
Area under the plasma concentration time-curve from time zero to end of dosing interval (tau), where dosing interval is 12 hours.
Maximum Observed Plasma Concentration (Cmax) of PF-04447943
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04447943
Plasma Concentrations of Donepezil
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Donepezil
Area under the plasma concentration time-curve from time zero to end of dosing interval (tau), where dosing interval is 24 hours.
Maximum Observed Plasma Concentration (Cmax) of Donepezil
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Donepezil

Full Information

First Posted
October 1, 2009
Last Updated
October 28, 2020
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT00988598
Brief Title
A Brief Study To Evaluate The Safety, Tolerability, And Blood Levels Of Multiple Doses Of PF-044467943 Or Placebo In Combination With Donepezil In Subjects With Mild To Moderate Alzheimer's Disease
Official Title
A PHASE 1, DOUBLE-BLIND, PLACEBO-CONTROLLED, SPONSOR OPEN, RANDOMIZED, MULTIPLE DOSE STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF PF-04447943 IN MILD TO MODERATE ALZHEIMER'S DISEASE SUBJECTS ON STABLE DONEPEZIL THERAPY
Study Type
Interventional

2. Study Status

Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
October 26, 2009 (Actual)
Primary Completion Date
July 5, 2010 (Actual)
Study Completion Date
July 5, 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of the study is to evaluate the safety of PF-04447943 when given in combination with donepezil in subjects who have Alzheimer's Disease. The study will also evaluate the absorption and distribution of both PF-04447943 and donepezil.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
phase 1 Alzheimer's disease donepezil

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PF-04447943
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
PF-04447943
Intervention Description
25 mg of PF-04447943 orally every 12 hours for 7 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
25 mg matching placebo to PF-04447943 orally every 12 hours for 7 days
Primary Outcome Measure Information:
Title
Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern
Description
Criteria for vital signs abnormalities of potential concern included: supine/standing systolic blood pressure (BP) (less than [<] 90 millimeter of mercury [mmHg], maximum [max] decrease and increase of greater than or equal to [>=] 30 mmHg from baseline); diastolic BP (<50 mmHg, maximum decrease and increase of >=20 mmHg from baseline); supine pulse rate <40 beats per minute [bpm] or greater than [>]120 bpm); standing pulse rate <40 bpm or >140 bpm. Baseline is defined as the last pre-dose (PF-04447943) recording at Day 0.
Time Frame
Baseline up to Day 10
Title
Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern
Description
Criteria for ECG abnormalities of potential clinical concern included: PR interval (>=300 milliseconds [msec], >= 25 percent [%] increase when baseline >200 msec or increase >=50% when baseline less than or equal to [<=] 200 msec); QRS interval (>=200 msec, >= 25% increase when baseline >100 msec or increase >=50% when baseline <=100 msec); QT corrected using Fridericia's formula (QTcF) (>=500 msec, maximum increase between >=30 to <60 msec and >=60 msec). Baseline is defined as the last pre-dose (PF-04447943) recording at Day 0.
Time Frame
Baseline up to Day 10
Title
Number of Participants With Laboratory Test Abnormalities
Description
Criteria for laboratory tests abnormalities included: hemoglobin, hematocrit (<0.8*lower limit of normal [LLN]); red blood cell count (<0.8*LLN); platelets (<0.5*LLN or >1.75* upper limit of normal [ULN]); leucocytes (<0.6*LLN or >1.5*ULN); lymphocytes, total neutrophils (<0.8*LLN or >1.2*ULN); basophils, eosinophils, monocytes (>1.2*ULN); total bilirubin (>1.5* ULN); aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (>3*ULN); creatinine, blood urea nitrogen (>1.3*ULN); glucose (<0.6*LLN or >1.5*ULN); uric acid (>1.2*ULN); sodium (<0.95*LLN or 1.05*ULN); potassium, calcium, chloride, bicarbonate (<0.9*LLN or 1.1*ULN); albumin, total protein (<0.8*LLN or 1.2*ULN); urine analysis. Total number of participants with any laboratory abnormalities was reported.
Time Frame
Baseline up to Day 10
Title
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Day 10 after last dose that were absent before treatment or that worsened relative to pretreatment state. Any abnormalities related to physical and neurological findings, laboratory tests, vital signs and ECG were reported as adverse events. AEs included SAEs as well as non-serious AEs which occurred during the trial.
Time Frame
Baseline up to Day 10
Secondary Outcome Measure Information:
Title
Plasma Concentrations of PF-04447943
Time Frame
0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours after morning dose of PF-04447943 on Day 1, Day 7
Title
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-04447943
Description
Area under the plasma concentration time-curve from time zero to end of dosing interval (tau), where dosing interval is 12 hours.
Time Frame
0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours after morning dose of PF-04447943 on Day 1, Day 7
Title
Maximum Observed Plasma Concentration (Cmax) of PF-04447943
Time Frame
0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours after morning dose of PF-04447943 on Day 1, Day 7
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04447943
Time Frame
0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours after morning dose of PF-04447943 on Day 1, Day 7
Title
Plasma Concentrations of Donepezil
Time Frame
0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7
Title
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Donepezil
Description
Area under the plasma concentration time-curve from time zero to end of dosing interval (tau), where dosing interval is 24 hours.
Time Frame
0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7
Title
Maximum Observed Plasma Concentration (Cmax) of Donepezil
Time Frame
0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7
Title
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Donepezil
Time Frame
0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects must have Alzheimer's dementia with a Mini Mental State Examination score between 18-26, inclusive. Subjects must have a reliable caregiver. Subjects must be on Aricept Memantine is allowed if subjects are on a stable dose Subjects must be in reasonably good health, based on medical history, physical examination, vital signs, and ECG, with no serious or unstable disease within the past 3 months. Exclusion Criteria: Subjects with clinically significant heart disease cannot participate. Subjects with a past or current history of seizures cannot participate.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Glendale Adventist Medical Center
City
Glendale
State/Province
California
ZIP/Postal Code
91206
Country
United States
Facility Name
University of Florida - Center for Clinical Trials Research
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32608
Country
United States
Facility Name
MD Clinical
City
Hallandale Beach
State/Province
Florida
ZIP/Postal Code
33009
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing 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.
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B0401008&StudyName=A%20Brief%20Study%20To%20Evaluate%20The%20Safety%2C%20Tolerability%2C%20And%20Blood%20Levels%20Of%20Multiple%20Doses%20Of%20PF-044467943%20Or%20Placebo%20In%20Combination%20W
Description
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A Brief Study To Evaluate The Safety, Tolerability, And Blood Levels Of Multiple Doses Of PF-044467943 Or Placebo In Combination With Donepezil In Subjects With Mild To Moderate Alzheimer's Disease

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