Study In Healthy Subjects To Evaluate The Changes In The Protein sAPP-Alpha In Cerebrospinal Fluid Following A Single Oral Dose Of PF-04995274

Study Overview
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Brief Summary
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The primary purpose of the study is to evaluate the effect of PF-04995274 on cerebrospinal fluid levels of soluble Amyloid precursor protein fragments and Amyloid beta fragments following single oral dose in healthy volunteers. Safety and tolerability of PF-04995274 single dose administration in healthy volunteers will also be assessed as part of the objectives.

Detailed Description
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The purpose of the study is to evaluate the effect of PF-04995274 on CSF levels of s-APP and Abeta fragments following single oral dose in healthy volunteers

Official Title
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A Phase 1 Investigator And Subject-Blind Study In Healthy Subjects To Evaluate The Pharmacodynamic Effects Of Single Doses Of PF-04995274 On Sapp-Alpha Concentrations In Cerebrospinal Fluid Using Serial Sampling Methodology

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-04995274
* Drug: PF-04995274


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For all cohorts, healthy male and/or female subjects of nonchildbearing potential between the ages of 18 and 55 years, inclusive. (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and heart rate measurement, 12 lead ECG and clinical laboratory tests). Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Pregnant or nursing women; women of childbearing potential.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
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 single oral doses of 0.1 mg, 10 mg, 15mg/ 40 mg PF-04995274 or a placebo | Drug: PF-04995274<br>* Subjects will be randomized to receive single oral doses of 0.1 mg, 10 mg, 15mg/ 40 mg PF-04995274 or a placebo<br>|
| Experimental: Cohort 2<br>Subjects will be receive single oral doses of PF-04995274 not exceeding 15mg or a placebo | Drug: PF-04995274<br>* Doses for cohort 2 will be decided based on an Interim analysis of data from cohort 1. The highest dose to be used in Cohort 2 not to exceed 15mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Endpoints (AE's, Vital signs, ECG, Clinical safety laboratory endpoints, Clinical examinations) |  | duration of study | 
| Cmax, Tmax, AUClast, AUCinf, and t1/2 of PF 04995274 and PF-05082547 in plasma, as the data permit |  | upto 5 days post dose | 
| Cmax, Tmax, AUClast, AUCinf, and t1/2 of PF 04995274 and PF-05082547 in cerebrospinal fluid, as the data permit |  | upto 8 hrs post dose | 
| Cmax, Tmax, AUClast, AUCinf, and t1/2 of s-APP alpha and Abeta fragments in cerebrospinal fluid, as the data permit |  | 8 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK/PD model |  | 8 hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healthy volunteers, pharmacokinetics-pharmacodynamics, cerebrospinal fluid, serial sampling