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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: PF-03715455; Drug: PH-797804; Drug: Placebo for PF-03715455; Drug: Placebo for PH-797804

Detailed Description

Proof of Mechanism

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE1 1YR
    • Pfizer Investigational Site
  • Manchester, United Kingdom, M23 9QZ
    • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PF-03715455	Drug: PF-03715455; 20mg, Inhaled, single dose
EXPERIMENTAL: PH-797804	Drug: PH-797804; 30mg, Oral, single dose
PLACEBO_COMPARATOR: Placebo for PF-03715455	Drug: Placebo for PF-03715455; Single dose, inhaled, Placebo for PF-03715455
PLACEBO_COMPARATOR: Placebo for PH-797804	Drug: Placebo for PH-797804; Single Dose, Oral, Placebo for PH-797804

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (ACTUAL): December 1, 2011
• Study Completion (ACTUAL): December 1, 2011

Study Registration Dates

• First Submitted: November 5, 2010
• First Submitted That Met QC Criteria: March 14, 2011
• First Posted (ESTIMATE): March 15, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): February 2, 2012
• Last Update Submitted That Met QC Criteria: February 1, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: Healthy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: A9111003