A Study to Evaluate Safety, Tolerability, Plasma Drug Levels, and Cognitive Response Following Multiple Doses of a Drug in Healthy Elderly Participants.

Study Overview
=================
Brief Summary
-----------------
Evaluate the safety and tolerability of PF-04447943 after administration of multiple doses in healthy elderly participants. Evaluate plasma drug levels and effects on cognition.

Official Title
-----------------
An Investigator And Subject-Blind Phase 1 Study To Characterize The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Of Multiple Doses Of PF-04447943 Up To An Exposure Cap In Healthy Elderly Subjects

Conditions
-----------------
Healthy, Elderly

Intervention / Treatment
-----------------
* Drug: PF-04447943
* Drug: PF-04447943
* Drug: PF-04447943
* Drug: PF-04447943
* Drug: PF-04447943


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male and/or female subjects. Subjects must be in reasonably good health as determined by the investigator based on medical history, full physical examination (including blood pressure and pulse rate measurement), 12 lead ECG and clinical laboratory tests. Subjects with mild, chronic, stable disease (eg, controlled hypertension, non-insulin dependent diabetes, osteoarthritis may be enrolled if deemed medically prudent by the investigator. Subjects taking daily prescription or non-prescription medications for management of acceptable chronic medical conditions must be on a stable dose. Body Mass Index (BMI) between 18 to 30 kg/m2, inclusive; and a total body weight >50 kg (110 lbs). Creatinine clearance greater than 30 mL/min using the Cockcroft-Gault method. Exclusion Criteria: Subjects with evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, immunologic, or allergic disease. Use of tobacco or any form of nicotine in the past 6 months. Greater than 7 drinks of alcohol per week for women, and greater than 14 drinks of alcohol per week for men.

Ages Eligible for Study
-----------------
Minimum Age: 65 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Subjects will be randomized to receive either experimental drug (n=6) or placebo (n=2). | Drug: PF-04447943<br>* Planned oral dose is PF-04447943, 5 mg q12 hours for 7 days.<br>|
| Experimental: Cohort 2<br>Subjects will be randomized to receive either experimental drug (n=6) or placebo (n=2). | Drug: PF-04447943<br>* Planned oral dose is PF-04447943, 15 mg q12 hours for 7 days.<br>|
| Experimental: Cohort 3a<br>Subjects will be randomized to receive either experimental drug (n=3) or placebo (n=1). | Drug: PF-04447943<br>* Planned oral dose is PF-04447943, 35 mg q12 hours for 7 days. Actual dose may be adjusted based on pharmacokinetic and other data from prior dose cohorts.<br>|
| Experimental: Cohort 3b<br>Subjects will be randomized to receive either experimental drug (n=3) or placebo (n=1). | Drug: PF-04447943<br>* Planned oral dose is PF-04447943, 35 mg q12 hours for 7 days. Actual dose may be adjusted based on pharmacokinetic and other data from prior dose cohorts.<br>|
| Experimental: Cohort 4<br> | Drug: PF-04447943<br>* Planned oral dose is PF-04447943, 35 mg q12 hours for 14 days. Actual dose may be adjusted downward based on pharmacokinetic and other data from prior dose cohorts.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety endpoints include evaluation of adverse events, change from baseline in vital signs, triplicate and single ECGs, and clinical safety laboratory tests |  | For cohorts 1-3, up to 17 days; for cohort 4, up to 24 days. | 
| Pharmacokinetic endpoints include plasma PF-04447943 area udner the curve (AUCt ), maximum plasma concentration (Cmax) and time of maximum plasma concentration (Tmax) |  | For cohorts 1-3, days 1 and 7; for cohort 4, days 1 and 14 | 
| Maximum plasma concentration (Cmax) |  | 1 hour post dose day 4 | 
| Minimum plasma concentration ((Ctrough) |  | For cohorts 1-3, days 2, 3, 4, and 7; for cohort 4, days 2, 3, 4, 12, and 13 | 
| Fraction of the total dose excreted in urine (Fe) and the renal clearance (CLR), and, if the data permit, half-life and the observed exposure accumulation ratio (Ro), and fluctuation index (Cmax: Cmin ratio) following multiple doses |  | For cohorts 1-3, day 7; for cohort 4, day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CogState Phase 1 Battery, to include Detect, Identify, One-Card Learning, Groton Maza Learning, Continuous Paired Associated Learning Test, and Composite Cognitive Score |  | For cohorts 1-3, up to 17 days; for cohort 4, up to 24 days. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
elderly, multi-dose, safety, efficacy