Clinical trial NCT01314885: Single Dose Lipopolysaccharide (LPS) Study In Healthy Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Keywords: Healthy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-03-15
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: 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: Proof of Mechanism

Eligibility criteria: 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

Primary outcomes:
measure: Post LPS sputum neutrophil % is being evaluated at the end of each treatment period to establish the effect of treatment on this endpoint
timeFrame: 6 hours
Secondary outcomes:
measure: 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.
timeFrame: 6 hours
measure: 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.
timeFrame: 1, 4, 6 and 7 hours
measure: Number of participants with adverse events
timeFrame: Baseline, Day 1 and Day 2
measure: Change from baseline in ECG parameters
timeFrame: Baseline, Day 1 and Day 2
measure: Change from baseline in BP parameters
timeFrame: Baseline, Day 1 and Day 2
measure: Change from baseline in lab safety parameters
timeFrame: Baseline, Day 1 and Day 2
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Pfizer Investigational Site
city: Manchester
country: United Kingdom
facility: Pfizer Investigational Site
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: