Single Dose Lipopolysaccharide (LPS) Study In Healthy Volunteers

• ClinicalTrials.gov Identifier: NCT01314885
• Recruitment Status: Completed
• First Posted: March 15, 2011
• Last Update Posted: February 2, 2012
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: November 5, 2010
• First Posted Date: March 15, 2011
• Last Update Posted Date: February 2, 2012
• Study Start Date: January 2011
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 14, 2011): Post LPS sputum neutrophil % is being evaluated at the end of each treatment period to establish the effect of treatment on this endpoint [ Time Frame: 6 hours ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 1, 2012)

• 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. [ Time Frame: 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. [ Time Frame: 1, 4, 6 and 7 hours ]
• Number of participants with adverse events [ Time Frame: Baseline, Day 1 and Day 2 ]
• Change from baseline in ECG parameters [ Time Frame: Baseline, Day 1 and Day 2 ]
• Change from baseline in BP parameters [ Time Frame: Baseline, Day 1 and Day 2 ]
• Change from baseline in lab safety parameters [ Time Frame: Baseline, Day 1 and Day 2 ]

Original Secondary Outcome Measures (submitted: March 14, 2011)

• 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. [ Time Frame: 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. [ Time Frame: 1, 4, 6 and 7 hours ]
• Number of participants with adverse events as a measure of safety and tolerability using 12 lead ECG, BP/pulse rate, and laboratory safety tests. [ Time Frame: Baseline, Day 1 and Day 2 ]
• Measure of phospho p38in sputum. [ Time Frame: 6 hours ]
• Measure of hsp27 in sputum. [ Time Frame: 6 hours ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double (Participant, Investigator)
• Condition: Chronic Obstructive Pulmonary Disease (COPD)

Intervention

• Drug: PF-03715455
  20mg, Inhaled, single dose
• Drug: PH-797804
  30mg, Oral, single dose
• Drug: Placebo for PF-03715455
  Single dose, inhaled, Placebo for PF-03715455
• Drug: Placebo for PH-797804
  Single Dose, Oral, Placebo for PH-797804

Study Arms

• Experimental: PF-03715455
  Intervention: Drug: PF-03715455
• Experimental: PH-797804
  Intervention: Drug: PH-797804
• Placebo Comparator: Placebo for PF-03715455
  Intervention: Drug: Placebo for PF-03715455
• Placebo Comparator: Placebo for PH-797804
  Intervention: Drug: Placebo for PH-797804

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 1, 2012): 39
• Original Estimated Enrollment (submitted: March 14, 2011): 18
• Actual Study Completion Date: December 2011
• Actual Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT01314885
• Other Study ID Numbers: A9111003
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: February 2012