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

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

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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Glendale Adventist Medical Center
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida - Center for Clinical Trials Research
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical

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:

• 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.

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; 25 mg matching placebo to PF-04447943 orally every 12 hours for 7 days
Active Comparator: PF-04447943	Drug: PF-04447943; 25 mg of PF-04447943 orally every 12 hours for 7 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline up to Day 10
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.	Baseline up to Day 10
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.	Baseline up to Day 10
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.	Baseline up to Day 10

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentrations of PF-04447943		0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours after morning dose of PF-04447943 on Day 1, Day 7
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.	0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours after morning dose of PF-04447943 on Day 1, Day 7
Maximum Observed Plasma Concentration (Cmax) of PF-04447943		0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours after morning dose of PF-04447943 on Day 1, Day 7
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04447943		0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours after morning dose of PF-04447943 on Day 1, Day 7
Plasma Concentrations of Donepezil		0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7
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.	0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7
Maximum Observed Plasma Concentration (Cmax) of Donepezil		0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Donepezil		0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7

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): October 26, 2009
• Primary Completion (Actual): July 5, 2010
• Study Completion (Actual): July 5, 2010

Study Registration Dates

• First Submitted: October 1, 2009
• First Submitted That Met QC Criteria: October 1, 2009
• First Posted (Estimate): October 2, 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: phase 1 Alzheimer's disease donepezil
• 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: B0401008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• 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.