Study of Biomarkers of Airway Inflammation (0000-128)

A Randomized Clinical Trial to Assess the Effects of Inhaled Fluticasone on Sputum Neutrophils After Low-dose Inhaled Endotoxin Challenge in Healthy Subjects

This study will evaluate the effects of inhaled fluticasone on cell counts and inflammatory mediators measured in sputum of healthy volunteers following exposure to inhaled lipopolysaccharide.

Study Overview

• Status: Completed
• Conditions: Airway Inflammation
• Intervention / Treatment: Drug: Comparator: Placebo to fluticasone; Drug: Comparator: Lipopolysaccharide (LPS); Drug: Comparator: albuterol; Drug: fluticasone propionate

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 1

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:

• Female subjects who can have children must have a negative pregnancy test at screening and agree to use two methods of birth control throughout the study
• Male subjects with female partner(s) who can have children agree to use an acceptable method of birth control throughout the study
• Subject is a nonsmoker
• Subject is in generally good health
• Subject is willing to comply with the diet, alcohol, and caffeine study restrictions

Exclusion Criteria:

• Subject is a nursing mother
• Subject has taken oral corticosteroids within 8 weeks or inhaled/nasal corticosteroids within 4 weeks of screening
• Subject has nasal polyps, recent nasal surgery, or an ongoing upper or lower respiratory tract infection
• Subject has a recent history of allergic rhinitis at screening
• Subject has any respiratory disease at screening
• Subject has daily phlegm or a chronic cough
• Subject is unable to refrain from the use of any prescription or non-prescription drugs or herbal remedies during the study
• Subject consumes excessive amounts of alcohol or caffeine
• Subject has had major surgery, or donated or lost 1 unit of blood within 4 weeks of screening
• Subject has a history of stroke, seizures, or major neurological disorders
• Subject regularly uses illicit drugs or has a history of drug/alcohol abuse
• Subject received a vaccination within 3 weeks of screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 1; Placebo	Drug: Comparator: Placebo to fluticasone; Single dose of placebo to fluticasone (9 x 0 mcg) by metered dose inhaler in one of three treatment periods; Drug: Comparator: Lipopolysaccharide (LPS); 20,000 EU LPS by inhalation 1 hour postdose of fluticasone or placebo in each of three treatment periods; Drug: Comparator: albuterol; Albuterol two 100 mcg inhalations by metered dose inhaler prior to sputum induction at screening, twice during each of the three treatment periods, and at the post-study follow up visit.
Active Comparator: 2; Fluticasone 440 mcg	Drug: Comparator: Lipopolysaccharide (LPS); 20,000 EU LPS by inhalation 1 hour postdose of fluticasone or placebo in each of three treatment periods; Drug: Comparator: albuterol; Albuterol two 100 mcg inhalations by metered dose inhaler prior to sputum induction at screening, twice during each of the three treatment periods, and at the post-study follow up visit.; Drug: fluticasone propionate; Single dose of fluticasone 440 mcg (2 x 220 mcg) or 1980 mcg (9 x 220 mcg) by metered dose inhaler in two of three treatment periods
Active Comparator: 3; Fluticasone 1980 mcg	Drug: Comparator: Lipopolysaccharide (LPS); 20,000 EU LPS by inhalation 1 hour postdose of fluticasone or placebo in each of three treatment periods; Drug: Comparator: albuterol; Albuterol two 100 mcg inhalations by metered dose inhaler prior to sputum induction at screening, twice during each of the three treatment periods, and at the post-study follow up visit.; Drug: fluticasone propionate; Single dose of fluticasone 440 mcg (2 x 220 mcg) or 1980 mcg (9 x 220 mcg) by metered dose inhaler in two of three treatment periods

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Sputum percent neutrophils	6 hours following inhaled LPS challenge

Secondary Outcome Measures

Outcome Measure	Time Frame
Sputum absolute neutrophils (per mL)	6 hours following inhaled LPS challenge
Sputum levels of IL1beta and IL8	6 hours following inhaled LPS challenge
Sputum mRNA expression levels of CD14 and IL1beta	6 hours following inhaled LPS challenge

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): September 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: March 25, 2009
• First Submitted That Met QC Criteria: March 25, 2009
• First Posted (Estimate): March 26, 2009

Study Record Updates

• Last Update Posted (Estimate): July 23, 2015
• Last Update Submitted That Met QC Criteria: July 22, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: Sputum inflammatory biomarkers
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Adrenergic Agonists; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Fluticasone; Xhance; Albuterol
• Other Study ID Numbers: 0000-128; 2009_565