Single Dose Lipopolysaccharide (LPS) Study In Healthy Volunteers

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

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.

Proof of Mechanism

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