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
- Registration Number
- NCT00988598
- Lead Sponsor
- Pfizer
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 15
- 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.
- Subjects with clinically significant heart disease cannot participate.
- Subjects with a past or current history of seizures cannot participate.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo - PF-04447943 PF-04447943 -
- Primary Outcome Measures
Name Time Method Number of Participants With Laboratory Test Abnormalities 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.
Number of Participants With Vital Signs Abnormalities of Potential Clinical Concern 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.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) 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.
Number of Participants With Electrocardiogram (ECG) Abnormalities of Potential Clinical Concern 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.
- Secondary Outcome Measures
Name Time Method Plasma Concentrations of Donepezil 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 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 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 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 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 Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) 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 plasma concentration time-curve from time zero to end of dosing interval (tau), where dosing interval is 12 hours.
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) 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 plasma concentration time-curve from time zero to end of dosing interval (tau), where dosing interval is 24 hours.
Trial Locations
- Locations (3)
MD Clinical
🇺🇸Hallandale Beach, Florida, United States
Glendale Adventist Medical Center
🇺🇸Glendale, California, United States
University of Florida - Center for Clinical Trials Research
🇺🇸Gainesville, Florida, United States