First In Human Study Of Increasing Oral Doses Of PF-04634817

Study Overview
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Brief Summary
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The study will evaluate the hypothesis that at doses and plasma concentrations which affect pharmacodynamic markers of activity at the chemokine receptors, CCR2 and CCR5, the compound is safe and well tolerated. It will also evaluate the hypothesis that the pharmacokinetic profile is robust and consistent with a once or twice a day therapeutic administration.

Official Title
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A Double Blind, Randomized, Placebo Controlled, Dose Escalation Study To Investigate The Pharmacokinetics (In The Fed And Fasted State), Safety And Toleration Of Single Oral Doses Of PF-04634817 In Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-04634817 Placebo
* Drug: PF-04634817
* Drug: PF-04634817
* Drug: PF-04634817
* Drug: PF-04634817
* Drug: PF-04634817
* Drug: PF-04634817
* Drug: PF-04634817
* Drug: PF-04634817
* Drug: PF-04634817
* Drug: PF-04634817 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female (of non-child bearing potential) subjects between 18 and 55 years of age. Body mass index of 17.5 to 30.5 kg/m2 and total body weight > 50kg. Exclusion Criteria: Evidence or history of any clinically significant disease. Treatment with an investigational drug within 30 days of study start Use of prescription and non-prescription medicines within 7 days of study start

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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: PF-04634817 Placebo<br>* Oral solution, placebo, single dose<br>|
| Experimental: Cohort 1, 1mg<br> | Drug: PF-04634817<br>* Oral solution, 1mg, single dose<br>|
| Experimental: Cohort 1, 3mg<br> | Drug: PF-04634817<br>* Oral solution, 3mg, single dose<br>|
| Experimental: Cohort 1, 10mg<br> | Drug: PF-04634817<br>* Oral solution, 10mg, single dose<br>|
| Experimental: Cohort 2, 30mg<br> | Drug: PF-04634817<br>* Oral solution, 30mg, single dose<br>|
| Experimental: Cohort 2, 100mg<br> | Drug: PF-04634817<br>* Oral solution, 100mg, single dose<br>|
| Experimental: Cohort 2, 300mg<br> | Drug: PF-04634817<br>* Oral solution, 300mg, single dose<br>|
| Experimental: Cohort 3, 600mg<br> | Drug: PF-04634817<br>* Oral solution, 600mg, single dose<br>|
| Experimental: Cohort 3, 900mg<br> | Drug: PF-04634817<br>* Oral solution, 900mg, single dose<br>|
| Experimental: Cohort 3, up to 900mg (fed)<br> | Drug: PF-04634817<br>* Oral solution, up to 900mg, single dose after food<br>|
| Placebo Comparator: Cohort 3, placebo (fed)<br> | Drug: PF-04634817 Placebo<br>* Oral solution, placebo, single dose after food<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and toleration: adverse events, supine and standing vital sign measurements, telemetry, 12-lead ECGs, blood and urine tests |  | 0-3 days | 
| Plasma pharmacokinetics: Cmax, Tmax, AUClast, AUCinf, AUC0-24, CL/F, Vz/F and T1/2 |  | 0-4 days | 
| Urinary pharmacokinetics: Aet (mount excreted in urine), Aet% and CLr |  | 0-2 days | 
| p-ERK inhibition in human monocytes |  | 0-3 days | 
| Change in circulating monocytes |  | 0-3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in plasma MCP-1 |  | 0-3 days | 
| MIP 1B stimulated CCR5 receptor internalization |  | 0-3 days | 
| MCP-1 stimulated CCR5 receptor internalization |  | 0-3 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase1, pharmacokinetics, safety, toleration, pharmacodynamics