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

NCT00988598 | Completed Phase 1 Results

• 1 other identifier: B0401008
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

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.

Conditions

Alzheimer's Disease

Keywords

phase 1 Alzheimer's disease donepezil

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (8)

• 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

  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

Study Arms (2)

PF-04447943

ACTIVE COMPARATOR

Drug: PF-04447943

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

PF-04447943 DRUG

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

PF-04447943

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (3)

Glendale Adventist Medical Center

Glendale, California, 91206, United States

Location

University of Florida - Center for Clinical Trials Research

Gainesville, Florida, 32608, United States

Location

MD Clinical

Hallandale, Florida, 33009, United States

Location

Related Links

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

MeSH Terms

Conditions

Alzheimer Disease

Interventions

6-(4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo(3,4-d)pyrimidin-4-one

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 1, 2009
• First Posted: October 2, 2009
• Study Start: October 26, 2009
• Primary Completion: July 5, 2010
• Study Completion: July 5, 2010
• Last Updated: November 19, 2020
• Results First Posted: November 19, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)