This is a single-centre, randomised, double-blind, four-period, incomplete block, crossover study, with 8 days repeat dosing of intranasal Fluticasone Propionate (25, 50, 100, 200ug) and/or placebo in the Vienna Challenge Chamber in subjects with allergic rhinitis.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
59
Corticosteriod, with anti-inflammatory effects
Placebo comparator
GSK Investigational Site
Vienna, Austria
Weighted Mean Total Nasal Symptom Score (TNSS) at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge [PSC]) in the Vienna Challenge Chamber (VCC)
The TNSS (score of 0-12), defined as the sum of the symptom scores for nasal obstruction, rhinorrhea, nasal itch, and sneeze (each scored on 0-3 scale \[0=none, 1=mild, 2=moderate, 3=severe\]) was measured at pre-challenge, and then every 15 minutes from 0.25 to 4 hours PSC. In the VCC, aerosolized allergen is administered in a sealed chamber to evaluate the efficacy of antihistamines/other treatments. Weighted mean TNSS was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.
Time frame: Day 8 of each study period (Periods 1-4); up to Day 158
Weighted Mean Nasal Airflow at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge)
Allergic rhinitis decreases the passage of air through the nose (nasal airflow) by increasing the nasal airway resistance. Rhinomanometry is used as an objective measurement of airway resistance. Nasal airflow was measured using active anterior rhinomanometry at pre-challenge, and then every 30 minutes from 0.5 to 4 hours post start of VCC. Weighted mean nasal airflow was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.
Time frame: Day 8 of each study period (Periods 1-4); up to Day 158
Weighted Mean Nasal Secretion at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge)
Nasal secretion was measured by weighing tissues used by participants. Wet tissue weight assessments were made pre-challenge, and then every 30 minutes from 0.5 to 4 hours post start of challenge chamber throughout the study. Weighted mean nasal secretion was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.
Time frame: Day 8 of each study period (Periods 1-4); up to Day 158
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Weighted Mean Eye Symptom Score at 2-5 Hours Post-dose (1-4 Hours Post-start of Challenge)
The eye symptom score (total score of 0 \[none\] to 9 \[severe\]) was calculated as the sum of the symptom scores for watery eyes, itchy eyes, and red eyes, each of which was scored on a categorical scale from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), and was measured at pre-challenge, and then every 15 minutes from 0.25 to 4 hours post-start of challenge chamber. Weighted mean eye symptom score was calculated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.
Time frame: Day 8 of each study period (Periods 1-4); up to Day 158
Weighted Mean Global Symptom Score (GSS) at 5 Hours Post-dose (1-4 Hours Post-start of Challenge)
GSS (total score=0-30) is calculated as the sum of sneeze, nasal itch, rhinorrhea, nasal obstruction, cough, itchy throat, itchy ears, watery eyes, itchy eyes, and red eyes SSs, each of which was scored on a categorical scale from 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe), as was measured at pre-challenge, and then every 15 mins from 0.25 to 4 hours post-start of challenge chamber. Weighted mean global symptom score was evaluated by dividing the value of the area under the response time curve between 1 and 4 hours (calculated by trapezoidal rule) by the time interval of available data.
Time frame: Day 8 of each study period (Periods 1-4); up to Day 158
Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: CCL2
AROS Applied Biotechnology (AB) analyzed the nasal epithelial scrapings of participants and generated TaqMan (type of chemistry developed by AB to detect polymerase chain reaction \[PCR\] products) messenger ribonucleic acid (mRNA) biomarker expression data for CCL2, a steroid-responsive gene. Preliminary analysis of the mRNA abundance data was performed by Discovery Statistics. mRNA abundance data were normalized to the scores of GAPDH and 18S housekeeping genes. B-actin was not used. CCL2 data are presented by period to show the treatment-by-period interaction. ng, nanograms.
Time frame: Day 1 (pre-dose) and Day 8 of each study period (Periods 1-4); up to Day 158
Glucocorticoid (GC) Receptor Biomarker Levels in Nasal Epithelial Scraping Samples: 18S, B-actin, DUSP_1_T1, FKBP5, GAPDH, GILZ, PLAU, PTGS2, and RGS2
AROS Applied Biotechnology (AB) analyzed the nasal epithelial scrapings of participants and generated TaqMan (type of chemistry developed by AB to detect polymerase chain reaction \[PCR\] products) messenger ribonucleic acid (mRNA) biomarker expression data for 7 steroid-responsive genes (DUSP\_1\_TI, FKBP5, GILZ, PLAU, CCL2, PTGS2, and RGS2) and 3 housekeeping reference genes (GAPDH, 18S, and b-actin). Preliminary analysis of the mRNA abundance data was performed by Discovery Statistics. mRNA abundance data were normalized to the scores of GAPDH and 18S housekeeping genes. B-actin was not used.
Time frame: Day 1 (pre-dose) and Day 8 of each study period (Periods 1-4); up to Day 158