Allergen-induced late asthmatic response MedDRA version: 8.1 Level: LLT Classification code 10003567
Conditions
Interventions
Product Name: GSK256066B Diskus
Product Code: GSK256066
Pharmaceutical Form: Inhalation powder, pre-dispensed
Current Sponsor code: GSK256066B
Concentration unit: µg microgram(s)
Concentration type: e
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and females aged 18 to 55 years inclusive. 2. Documented history of bronchial asthma, first diagnosed at least 6 months prior to the screening visit and currently being treated only with intermittent short-acting beta -agonist therapy by inhalation. 3. Pre-bronchodilator FEV1 >75% of predicted at screening. 4. Non-smoking status as verified by urinary cotinine levels below 300 ng/mL cotinine at the screening visit. This can include ex-smokers who have given up smoking for >6 months. 5. Demonstration of a positive wheal and flare reaction (>/= 3 mm relative to negative control) to at least one allergen from a battery of allergens at screening, or within 12 months of study start. 6. Screening allergen challenge demonstrates that the subject experiences both an early and late asthmatic response. 7. Able and willing to give written informed consent to take part in the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Pregnant or nursing females. 2. Women of childbearing potential who are unwilling or unable to use an appropriate method of contraception from at least two weeks prior to the first dose of study medication; and to continue until the final pregnancy test has been performed. 3. Past or present disease, which as judged by the investigator, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease*, haematological disease, neurological disease, endocrine disease or pulmonary disease (including but not confined to chronic bronchitis, emphysema, bronchiectasis or pulmonary fibrosis). 4. Clinically significant abnormalities in safety laboratory analysis at screening including any subject who has greater than “trace urine protein levels” following urinalysis at screening. 5. Subject has known history of hypertension or is hypertensive at screening. 6. Respiratory tract infection and/or exacerbation of asthma within 4 weeks prior to the first dose of study medication. 7. History of life-threatening asthma. 8. History of hay fever. 9. Administration of oral, injectable or dermal steroids within 5 weeks or intranasal and/or inhaled steroids within 1 week of the screening visit. 10. Unable to abstain from other medications including non-steroidal anti-inflammatory drugs (NSAIDs), anti-depressant drugs, anti-histamines and anti-asthma, anti-rhinitis or hay fever medication, other than short acting inhaled beta-agonists and paracetamol (up to 4 g per day) for the treatment of minor ailments eg headache from 48h before the first dose until the follow-up visit. 11. History of being unable to tolerate or complete methacholine, and/or allergen challenge tests. 12. The subject has a screening QTc value of >430msec, PR interval outside the range 120 to 200msec or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T-wave). 13. Subject has a history of atrial arrhythmia or ventricular arrhythmia.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of treatment with repeat inhaled doses of GSK256066 for 14 days on the late asthmatic response (LAR) to inhaled allergen in mild asthmatic subjects compared with placebo;Primary end point(s): Late Asthmatic Response (LAR): minimum FEV1 between 4-10 hours after allergen challenge on Day 14 of each treatment period;Secondary Objective: To evaluate the effect of treatment with repeat inhaled doses of GSK256066 for 14 days on: • bronchial hyper-reactivity in response to methacholine challenge following allergen challenge; • the early asthmatic response (EAR) after allergen challenge; • concentrations of exhaled nitric oxide on Days 1, 7, 14 and 15; • lung function as measured by FEV1 on Days 1, 7 and 14; • safety and tolerability of repeat inhaled doses of GSK256066 in mild asthmatic subjects; • established markers of inflammation; • exploratory markers of inflammation and PDE4 activity; • pharmacokinetics and potential PK/PD relationship on LAR, and exNO. | — |
Countries
United Kingdom
Outcome results
None listed