A randomised, double-blind, placebo-controlled, four-way crossover, repeat dose study comparing the effect of inhaled fluticasone furoate/GW642444M combination, GW642444M and fluticasone furoate on the allergen-induced asthmatic response in subjects with mild asthma.
- Conditions
- subjects with mild asthmaMedDRA version: 12.1Level: LLTClassification code 10003553Term: Asthma
- Registration Number
- EUCTR2010-019465-28-SE
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 24
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 <35%)
4. Otherwise healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
5. Body mass index within the range 18.5-35.0 kilograms/metre2 (kg/m2).
6. A female subject is eligible to participate if she is of:
• Non-childbearing potential defined as pre-menopausal females with a
documented tubal ligation or hysterectomy; or postmenopausal defined as 12
months of spontaneous amenorrhea [in questionable cases a blood sample with
simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol <
40 pg/ml (<140 pmol/L) is confirmatory]. Females on hormone replacement
therapy (HRT) and whose menopausal status is in doubt will be required to use
one of the contraception methods in Section 8.1 of the protocol, if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow
confirmation of post-menopausal status prior to study enrollment. For most
forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy
and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of
HRT during the study without use of a contraceptive method.
• Child-bearing potential and agrees to use one of the contraception methods
listed in Section 8.1 for an appropriate period of time (as determined by the
product label or investigator) prior to the start of dosing to sufficiently minimize
the risk of pregnancy at that point. Female subjects must agree to use
contraception until 5 terminal half-live post-last dose.
7. Pre-bronchodilator FEV1 >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
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method