Asthma
Conditions
Keywords
asthma, allergen challenge, IL-5, eosinophils
Brief summary
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
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
Interventions
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weighted Mean Change From Baseline Over 0-6 Hours in Blood Eosinophils Post-Allergen Challenge on Day 35 | 0-6 hours post allergen challenge, 10-11 hours post treatment, Day 35 | Number of peripheral blood eosinophils measured from blood draws |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weighted Mean Change From Baseline Over 0-6 Hours in Blood Eosinophils Post-Allergen Challenge on Day 14 | 0-6 hours, post allergen challenge, 1 hour post treatment, Day 14 | Number of peripheral blood eosinophils measured from blood draws |
| Weighted Mean Change From Baseline Over 0-6 Hours in Serum IL-5 Post-Allergen Challenge on Day 35 | 0-6 hours post allergen challenge, 10-11 hours post treatment, Day 35 | Amount of serum interleukin (IL)-5 measured from blood draws |
| Weighted Mean Change From Baseline Over 0-6 Hours in Serum IL-5 Post-Allergen Challenge on Day 14 | 0-6 hours post allergen challenge, 1 hour after dosing, Day 14 | Amount of serum IL-5 measured from blood draws |
Countries
United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Population Overall Study Population: participants in all three treatment periods | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Second Treatment Period | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Overall Study Population |
|---|---|
| Age, Continuous | 36.6 years STANDARD_DEVIATION 6.63 |
| Gender Female | 9 Participants |
| Gender Male | 14 Participants |
| Race/Ethnicity, Customized African American | 2 participants |
| Race/Ethnicity, Customized Caucasian | 21 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 14 / 22 | 16 / 23 | 10 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 23 | 1 / 22 |
Outcome results
Primary
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
Time frame: 0-6 hours post allergen challenge, 10-11 hours post treatment, Day 35
Population: Intent-to-Treat (ITT) Population: All participants receiving at least one dose of study medication who had at least one post-randomization efficacy assessment
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Weighted Mean Change From Baseline Over 0-6 Hours in Blood Eosinophils Post-Allergen Challenge on Day 35 | -0.050 Giga Units per Liter (GI/L) |
| FP 100 mcg BID | Weighted Mean Change From Baseline Over 0-6 Hours in Blood Eosinophils Post-Allergen Challenge on Day 35 | -0.040 Giga Units per Liter (GI/L) |
| SFC 50/100 mcg BID | Weighted Mean Change From Baseline Over 0-6 Hours in Blood Eosinophils Post-Allergen Challenge on Day 35 | -0.023 Giga Units per Liter (GI/L) |
Secondary
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
Time frame: 0-6 hours, post allergen challenge, 1 hour post treatment, Day 14
Population: ITT Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Weighted Mean Change From Baseline Over 0-6 Hours in Blood Eosinophils Post-Allergen Challenge on Day 14 | -0.023 Giga Units per Liter (GI/L) |
| FP 100 mcg BID | Weighted Mean Change From Baseline Over 0-6 Hours in Blood Eosinophils Post-Allergen Challenge on Day 14 | -0.022 Giga Units per Liter (GI/L) |
| SFC 50/100 mcg BID | Weighted Mean Change From Baseline Over 0-6 Hours in Blood Eosinophils Post-Allergen Challenge on Day 14 | -0.013 Giga Units per Liter (GI/L) |
Secondary
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
Time frame: 0-6 hours post allergen challenge, 1 hour after dosing, Day 14
Secondary
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
Time frame: 0-6 hours post allergen challenge, 10-11 hours post treatment, Day 35