A Study To Observe Safety And Concentrations Of PF-05297909 And Proteins In Both Blood And Cerebrospinal Fluid After A Single Dose Of PF-05297909 In Healthy Adults

Study Overview
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Brief Summary
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This study is designed to observe the safety and concentrations of PF-05297909 and proteins in both blood and cerebrospinal fluid after a single dose of PF-05297909 in healthy adults.

Official Title
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A Phase 1, Randomized Investigator-And-Subject-Blind, Sponsor Open, Placebo Controlled Two-Part Study To Characterize The Pharmacokinetics And Pharmacodynamics Of Single Doses Of Pf-05297909 In Healthy Adult Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-05297909 25 mg
* Drug: PF-05297909 100 mg
* Drug: PF-05297909 250 mg
* Drug: PF-05297909 525 mg
* Drug: PF-05297909 525 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Healthy adult volunteers: healthy male and/or female subjects of non child bearing 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)

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation<br>Ascending doses in healthy volunteers | Drug: PF-05297909 25 mg<br>* Single oral (PO) dose, PF-05297909 25 mg<br>Drug: PF-05297909 100 mg<br>* Single oral (PO) dose, PF-05297909 100 mg<br>Drug: PF-05297909 250 mg<br>* Single oral (PO) dose, PF-05297909 250 mg<br>Drug: PF-05297909 525 mg<br>* Single oral (PO) dose, PF-05297909 525 mg<br>|
| Experimental: Part 2: CSF PKPD<br>Pharmacokinetic and pharmacodynamic cerebrospinal fluid assessment | Drug: PF-05297909 525 mg<br>* Single oral (PO) dose, 525 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma area under the curve last (AUClast) pharmacokinetic parameter |  | Day 1 to Day 3 | 
| Plasma apparent clearance (CL/F) pharmacokinetic parameter |  | Day 0 to Day 3 | 
| Clinical potency of PF 05297909 for reduction in CSF levels of Abeta40, Abeta42, and/or AbetaX via estimation of the IC50 from a population PK/PD (PPK/PD) model |  | Day 0 to Day 3 | 
| Plasma area under the curve infinity (AUCinf) pharmacokinetic parameter |  | Day 1 to Day 3 | 
| Plasma half-life (t1/2) pharmacokinetic parameter |  | Day 1 to Day 3 | 
| Plasma apparent volume of distribution (Vz/F) pharmacokinetic parameter |  | Day 1 to Day 3 | 
| CSF concentration summary by time point for PF 05297909. |  | Day 1 to Day 3 | 
| Change from baseline in CSF levels of Abeta40 |  | Day 1 to Day 3 | 
| Change from baseline in CSF levels of Abeta42 |  | Day 1 to Day 3 | 
| Change from baseline in CSF levels of AbetaX |  | Day 1 to Day 3 | 
| Change from baseline in CSF levels of sAPPalpha |  | Day 1 to Day 3 | 
| Change from baseline in CSF levels of sAPPbeta. |  | Day 1 to Day 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healthy volunteer, safety, pharmacokinetic, pharmacodynamic