A Study to Evaluate the Effect of GW870086X on Allergen Challenge in Mild Asthmatics

Exclusion Criteria

• •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).
• •Clinically significant abnormalities in safety laboratory analysis at screening.
• •Subject has known history of hypertension or is hypertensive at screening. Hypertension at screening is defined as persistent systolic BP \>140mmHg or diastolic BP \> 90mmHg.
• •Respiratory tract infection and/or exacerbation of asthma within 4 weeks prior to the first dose of study medication.
• •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.
• •Administration of oral, injectable or dermal steroids within 4 weeks or intranasal and/or inhaled steroids within 2 week of the screening visit.
• •The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
• •A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• •A positive test for HIV antibody.
• •History of regular alcohol consumption within 6 months of the study defined as:
• •an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males). One unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine.
• •The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• •Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• •Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. Paracetamol is an exception and will be permitted at daily doses of up to 4 g from screening to follow-up.
• •Has taken Xanthines (including theophylline, but not including caffeine), anticholinergics, cromoglycates and/or long-acting beta-agonists within 1 week prior to screening and is unable to abstain from them throughout the study.
• •Unable to abstain from other medications including non-steroidal anti-inflammatory drugs (NSAIDs), anti-depressant drugs, anti-histamines and anti-asthma (not including steroids), 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 7 days before screening until the follow-up visit.
• •Unable to abstain from medication or supplements that significantly inhibit the cytochrome P450 subfamily enzyme CYP3A4, including ritonavir and ketoconazol from screening and throughout the study.
• •Unable to use the DISKHALER and/or DISKUS device correctly.
• •History of being unable to tolerate or complete methacholine or allergen challenge tests.
• •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%.
• •Subject is undergoing allergen desensitisation therapy.
• •History of sensitivity to any of the study medications (including lactose), or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
• •Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• •Unwillingness or inability to follow the procedures outlined in the protocol.
• •Subjects who are kept due to regulatory or juridical order in an institution.
• •Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
• •Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.