subjects with mild asthma MedDRA version: 12.1 Level: LLT Classification code 10003553 Term: Asthma
Conditions
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and females aged 18 to 65 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. AST, ALT, alkaline phosphatase and bilirubin = 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 40 MlU/ml and estradiol 70% of predicted at screening. 8. Subjects who are current non-smokers who have not used any tobacco products in the 6-month period preceding the screening visit and have a pack history of = 10 pack years. [number of pack years = (number of cigarettes per day/20) x number of years smoked] 9. Demonstration of a positive wheal and flare reaction (= 3 mm relative to negative control) to at least one allergen from a battery of allergens (including house dust mite, grass pollen and cat hair) on skin prick testing at screening, or within 12 months of study start. 10. Methacholine challenge PC20< 8 mg/mL at screening. 11. Screening allergen challenge demonstrates that the subject experiences both an early and late asthmatic response. The early asthmatic response must include a fall in FEV1 of = 20% from the post saline value, on at least one occasion, between 5 and 30 minutes after the final concentration of allergen. The late asthmatic response must include a fall in FEV1 of = 15% from the post saline value, on at least three occasions, two of which mus
Exclusion criteria
Exclusion criteria: 1. Past or present disease, which as judged by the investigator or medical monitor, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, gastrointestinal disease, 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). 2. Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) 3. Clinically significant abnormalities in safety laboratory analysis at screening. 4. Subject is hypertensive at screening. Hypertension at screening is defined as persistent systolic BP >150 mmHg or diastolic BP > 90mmHg. Subject with controlled hypertension may be included. 5. Respiratory tract infection and/or exacerbation of asthma within 4 weeks prior to the first dose of study medication. 6. History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnoea, respiratory arrest and/or hypoxic seizures. 7. Symptomatic with hay fever at screening or predicted to have symptomatic hayfever during days 14-22 of a treatment period of the study. 8. Administration of oral or injectable steroids within 5 weeks of screening or intranasal and/or inhaled steroids within 4 weeks of the screening visit. 9. Unable to abstain from other medications including non-steroidal anti-inflammatory drugs (NSAIDs), anti-depressant drugs, anti-asthma anti-rhinitis or hay fever medication, other than antihypertensive medication and paracetamol (up to 4 g per day) for the treatment of minor ailments e.g. headache from 14 days before screening until the follow-up visit. 10. Unable to abstain from short acting beta agonists as described in the concomitant medications and non-drug therapies section. 11. Unable to abstain from antihistamines as described in the concomitant medications and non-drug therapies section. 12. If, after 2 concurrent administrations of saline during the allergen challenge at screening the subjects still have a fall in FEV1 of greater than 10%. 13. The subject has participated in a study with a new molecular entity during the previous 3 months or has participated in 4 or more clinical studies in the previous 12 months prior to the first dosing day. 14. History of milk protein allergy. 15. History of being unable to tolerate or complete allergen challenge tests. 16. Subject is undergoing allergen desensitisation therapy. 17. A known hypersensitivity to corticosteroids. 18. Any adverse reaction including immediate or delayed hypersensitivity to any ß2-agonist or sympathomimetic drug, or known or suspected sensitivity to the constituents of GW642444M inhalation powder (e.g., lactose, magnesium stearate). 19. There is a risk of non-compliance with study procedures. 20. History of blood donation (500 mL) within 3 months of starting the clinical study. 21. Subject is mentally or legally incapacitated. 22. Consumption of seville oranges, pummelos (members of the grapefruit family) or grapefruit juice from 14 days prior to the first dose of study medication. 23. The subject regularly drinks more than 28 units of alcohol in a week if male, or 21 units per week if female. In general one unit of alcohol is defined as a medium (125 ml) glass of wine, half a pint (250 ml) of beer or one mea
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To evaluate the bronchoprotective effect of treatment with repeat inhaled doses of inhaled fluticasone furoate (GW685698)/GW642444M combination 100mcg/25 mcg, on the late asthmatic response to inhaled allergen at 1 hour post-dose in mild asthmatic subjects compared with placebo. - To evaluate the bronchoprotective effect of treatment with repeat inhaled doses of inhaled fluticasone furoate (GW685698)/GW642444M combination 100mcg/25 mcg on the early asthmatic response to inhaled allergen at 1 hour post-dose in mild asthmatic subjects compared with fluticasone furoate 100mcg and GW642444M 25mcg.;Secondary Objective: - To evaluate the bronchoprotective effect of treatment with repeat inhaled doses of FF 100mcg and GW642444M 25mcg on the LAR at 1h post-dose vs placebo. - To evaluate the bronchoprotective effect of treatment with repeat inhaled doses of inhaled fluticasone furoate(GW685698)/GW642444M combination 100mcg/25 mcg, FF100mcg and GW642444M 25mcg on the early asthmatic response to inhaled allergen at 1 hour post-dose in mild asthmatic subjects compared with placebo. - To evaluate the effect of treatment with repeat inhaled doses of inhaled fluticasone furoate(GW685698)/GW642444M combination 100mcg/25 mcg, GW642444M 25mcg and fluticasone furoate 100mcg for 21 days on bronchial hyper-reactivity as measured by methacholine challenge on day 22 compared with placebo in mild asthmatic subjects. view protocol section 2.2 for further information on secondary objectives ;Primary end point(s): - Late Asthmatic Response (LAR): minimum FEV1 and weighted mean FEV1 between 4-10 hours following the 1 hour post treatment allergen challenge on Day 21 of treatment with fluticasone furoate (GW685698)/GW642444M combination compared with placebo. - Early Asthmatic Response (EAR): minimum FEV1 and weighted mean FEV1 between 0- 2 hours following the 1 hour post treatment allergen challenge on Day 21 of treatment with fluticasone furoate (GW685698)/GW642444M combina | — |
Countries
Sweden
Outcome results
None listed