Single Dose Lipopolysaccharide (LPS) Study In Healthy Volunteers

Study Overview
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Brief Summary
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A single dose study with the inhaled anti-inflammatory agent PF-03715455 to establish if it has anti-inflammatory activity following a challenge with LPS. Inhaled LPS invokes an acute inflammatory response in the lung which can be seen in induced sputum. PH-0797804 is an internal control for the study.

Detailed Description
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Proof of Mechanism

Official Title
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Randomized, Double-Blind, Double-Dummy, Placebo-Controlled, 3-Way Crossover Study To Determine The Effects Of Single Inhaled Doses Of PF-03715455 (20 Mg) And PH-797804 (30 Mg) On Induced Sputum Neutrophils Following Inhaled Lipopolysaccharide (LPS) Challenge In Healthy Volunteers

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: PF-03715455
* Drug: PH-797804
* Drug: Placebo for PF-03715455
* Drug: Placebo for PH-797804


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female (of non-child bearing potential) subjects, aged 18-50 years. Subjects whose FEV1 and FVC at screening are both greater than or equal to 80% of their predicted value for age, race, sex and height. Subjects who have normoresponsive airways. Subjects who are able to successfully complete screening sputum inductions. Exclusion Criteria: Subjects who have evidence, on review of pre-study laboratory data and full physical examination, or history of any clinically significant hematological, renal, endocrine, gastrointestinal, dermatological, hepatic, psychiatric, neurologic diseases. Specifically liver function tests and CRP must be within the reference range. Subjects with a medical history of asthma symptomatology (ie, wheeze and/or dyspnea at rest). Subjects who have experienced a respiratory tract infection within the previous 4 weeks or any other infection within 1 week of dosing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-03715455<br> | Drug: PF-03715455<br>* 20mg, Inhaled, single dose<br>|
| Experimental: PH-797804<br> | Drug: PH-797804<br>* 30mg, Oral, single dose<br>|
| Placebo Comparator: Placebo for PF-03715455<br> | Drug: Placebo for PF-03715455<br>* Single dose, inhaled, Placebo for PF-03715455<br>|
| Placebo Comparator: Placebo for PH-797804<br> | Drug: Placebo for PH-797804<br>* Single Dose, Oral, Placebo for PH-797804<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post LPS sputum neutrophil % is being evaluated at the end of each treatment period to establish the effect of treatment on this endpoint |  | 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cell counts, IL-6, MPO, MCP-1, MIP1b are individual endpoints which will be evaluated in sputum however they are collected as a single sample. |  | 6 hours | 
| Post-LPS systemic inflammatory indices: Neutrophil count, IL-6, IL-10, MPO, MCP-1, MIP1b, fibrinogen, CC16 and CRP. These are individual endpoints which will be evaluated in blood however they are collected as a single sample. |  | 1, 4, 6 and 7 hours | 
| Number of participants with adverse events |  | Baseline, Day 1 and Day 2 | 
| Change from baseline in ECG parameters |  | Baseline, Day 1 and Day 2 | 
| Change from baseline in BP parameters |  | Baseline, Day 1 and Day 2 | 
| Change from baseline in lab safety parameters |  | Baseline, Day 1 and Day 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy