Study Of Fluticasone Propionate/Salmeterol In Asthmatic Subjects

Study Overview
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Brief Summary
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The aim of the present study is to investigate whether the effects of salmeterol in combination with fluticasone propionate on blood markers of airway inflammation are maintained after chronic dosing and whether the effect is influenced by the time of allergen challenge relative to the time of dosing.

Detailed Description
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A 12-week, randomised, double-blind, placebo-controlled, three-period, cross-over pilot study comparing the effect of salmeterol/fluticasone propionate, fluticasone propionate and placebo on perpheral blood eosinophils and serum IL-5 in response to allergen challenge in asthma subjects when allergen challenge is administered at 1 hour or 11-12 hours post-dose of the dosing interval

Official Title
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A 12-week, Randomised, Double-blind, Placebo-controlled, Three-period, Cross-over Pilot Study Comparing the Effect of Salmeterol/Fluticasone Propionate, Fluticasone Propionate and Placebo on Perpheral Blood Eosinophils and Serum IL-5 in Response to Allergen Challenge in Asthma Subjects When Allergen Challenge is Administered at 1 Hour or 11-12 Hours Post-dose of the Dosing Interval

Conditions
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Asthma

Intervention / Treatment
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* Drug: FP
* Drug: SFC
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent. Outpatient. Male or non-pregnant/non-lactating female. Aged 18-55. Diagnosis of asthma. Pre-bronchodilatory FEV1 > 75% predicted. Using inhaled short-acting beta-2-agonists (SABA) with no inhaled corticosteroids. Judged capable of withholding SABA for at least 6 hours prior to visits. Reversibility of >12% and 200mL or PC20 of <8mg/mL. Demonstration of atopy Exclusion Criteria: History of life-threatening asthma. Use of proscribed asthma medications. Use of anti-histamines or potent inhibitors of CYP3A4. Respiratory tract infection. Asthma exacerbation with 4 weeks of Visit 1. Subjects with exercise induced asthma only. Concurrent respiratory disease. Other clinically significant, uncontrolled condition or disease. Use of any investigational drug within 30 days. Allergic to beta-2-agonists, inhaled corticosteroids or excipients. Positive pregnancy test. Using immunosuppressive medications. Milk protein allergy. Factors likely to interfere with attendance. Current smokers or ex-smokers with a history of >10 pack years. Affiliation wih Investigator site. Medications that may affect the course of asthma or interact with sympathomimetic amines.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1: FP, SFC, Placebo<br>Fluticasone Propionate (FP) 100 micrograms (mcg) twice daily (BID) in the first treatment period: Salmeterol/Fluticasone Propionate Combination (SFC) 50/100 mcg BID in the second treatment period: Placebo in the third treatment period | Drug: FP<br>* Fluticasone Propionate 100 mcg BD<br>Drug: SFC<br>* Salmeterol/Fluticasone Propionate Combination 50/100 mcg BD<br>Drug: Placebo<br>* Matching Placebo<br>|
| Experimental: Sequence 2: Placebo, SFC, FP<br>Placebo in the first treatment period: Salmeterol/Fluticasone Propionate Combination 50/100 mcg BID in the second treatment period: Fluticasone Propionate 100 mcg BID in the third treatment period | Drug: FP<br>* Fluticasone Propionate 100 mcg BD<br>Drug: SFC<br>* Salmeterol/Fluticasone Propionate Combination 50/100 mcg BD<br>Drug: Placebo<br>* Matching Placebo<br>|
| Experimental: Sequence 3: SFC, FP, Placebo<br>Salmeterol/Fluticasone Propionate 50/100 Combination mcg BID in the first treatment period: Fluticasone Propionate 100 mcg BID in the second treatment period: Placebo in the third treatment period | Drug: FP<br>* Fluticasone Propionate 100 mcg BD<br>Drug: SFC<br>* Salmeterol/Fluticasone Propionate Combination 50/100 mcg BD<br>Drug: Placebo<br>* Matching Placebo<br>|
| Experimental: Sequence 4: SFC, Placebo, FP<br>Salmeterol/Fluticasone Propionate Combination 50/100 mcg BID in the first treatment period: Placebo in the second treatment period: Fluticasone Propionate 100 mcg BID in the third treatment period | Drug: FP<br>* Fluticasone Propionate 100 mcg BD<br>Drug: SFC<br>* Salmeterol/Fluticasone Propionate Combination 50/100 mcg BD<br>Drug: Placebo<br>* Matching Placebo<br>|
| Experimental: Sequence 5: FP, Placebo, SFC<br>Fluticasone Propionate 100 mcg BID in the first treatment period: Placebo in the second treatment period: Salmeterol/Fluticasone Propionate Combination 50/100 mcg BID in the third treatment period | Drug: FP<br>* Fluticasone Propionate 100 mcg BD<br>Drug: SFC<br>* Salmeterol/Fluticasone Propionate Combination 50/100 mcg BD<br>Drug: Placebo<br>* Matching Placebo<br>|
| Experimental: Sequence 6: Placebo, FP, SFC<br>Placebo in the first treatment period: Fluticasone Propionate 100 mcg BID in the second treatment period: Salmeterol/Fluticasone Propionate Combination 50/100 mcg BID in the third treatment period | Drug: FP<br>* Fluticasone Propionate 100 mcg BD<br>Drug: SFC<br>* Salmeterol/Fluticasone Propionate Combination 50/100 mcg BD<br>Drug: Placebo<br>* Matching Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weighted Mean Change From Baseline Over 0-6 Hours in Blood Eosinophils Post-Allergen Challenge on Day 35 | Number of peripheral blood eosinophils measured from blood draws | 0-6 hours post allergen challenge, 10-11 hours post treatment, Day 35 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weighted Mean Change From Baseline Over 0-6 Hours in Blood Eosinophils Post-Allergen Challenge on Day 14 | Number of peripheral blood eosinophils measured from blood draws | 0-6 hours, post allergen challenge, 1 hour post treatment, Day 14 | 
| Weighted Mean Change From Baseline Over 0-6 Hours in Serum IL-5 Post-Allergen Challenge on Day 35 | Amount of serum interleukin (IL)-5 measured from blood draws | 0-6 hours post allergen challenge, 10-11 hours post treatment, Day 35 | 
| Weighted Mean Change From Baseline Over 0-6 Hours in Serum IL-5 Post-Allergen Challenge on Day 14 | Amount of serum IL-5 measured from blood draws | 0-6 hours post allergen challenge, 1 hour after dosing, Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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asthma, allergen challenge, IL-5, eosinophils