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Completed

NCT Number: NCT00988598

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

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.

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Key information

Age range

55 year–85 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Glendale Adventist Medical Center, Glendale, California, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

PF-04447943

Drug

25 mg of PF-04447943 orally every 12 hours for 7 days

Placebo

Drug

25 mg matching placebo to PF-04447943 orally every 12 hours for 7 days

Primary outcomes

  1. Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern

    Time frame: Baseline up to Day 10

    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.

  2. Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern

    Time frame: Baseline up to Day 10

    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.

  3. Number of Participants With Laboratory Test Abnormalities

    Time frame: Baseline up to Day 10

    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.

  4. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Time frame: Baseline up to Day 10

    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 outcomes

  1. 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

  2. Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) 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

    Area under the plasma concentration time-curve from time zero to end of dosing interval (tau), where dosing interval is 12 hours.

  3. 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

  4. 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

  5. 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

  6. Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Donepezil

    Time frame: 0 hours (pre-dose), 0.5, 1, 3, 8, 12 hours post donepezil administration on Day 0(Baseline), Day 7

    Area under the plasma concentration time-curve from time zero to end of dosing interval (tau), where dosing interval is 24 hours.

  7. 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

  8. 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

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study 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

Important dates

Study start
2009
Primary completion
2010
Study completion
2010
First posted
Oct 2, 2009
Registry last updated
Nov 19, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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