Previous studies have shown potentially higher exposure to fluticasone furoate in Japanese subjects compared with Caucasian subjects. The reasons for these potential differences are unclear. Therefore this study is being done to look at and compare how fluticasone furoate is processed by the body in healthy Caucasian, Japanese, Korean and Chinese subjects after inhaled and intravenous administration. The data obtained will be used to help in the clinical development of the drug in Japanese and other East Asian populations.

Corticosteroids are a highly effective anti-inflammatory therapy in allergic conditions such as asthma and rhinitis. Fluticasone Furoate (FF) is a novel corticosteroid with potent glucocorticoid activity similar to fluticasone propionate and mometasone furoate. Phase II studies have shown FF to be an effective once daily inhaled steroid for asthma and it is being developed as a potential steroid component in a once daily combination with GW642444M, for once-daily administration for the maintenance treatment of asthma and COPD. FF is approved worldwide (including the US, EU and Japan) as an intranasal steroid for the treatment of allergic rhinitis (VERAMYST™ /AVAMYS™ /ALLERMIST™). Previous inter-study comparisons have indicated potentially higher systemic exposure to FF in Japanese subjects compared with treatment groups that recruited predominantly Caucasian subjects. The reasons for these potential differences are unclear. This study is being performed to evaluate and directly compare the PK and systemic PD effects of FF in healthy Caucasian, Japanese, Korean and Chinese subjects when delivered from the novel dry powder inhaler and intravenously. The data obtained will be used to facilitate clinical development of the FF/GW642444 combination in Japanese and other East Asian populations.

Inclusion Criteria:

• Healthy male or female between 20 and 64 years of age inclusive
• Caucasian, Japanese, Korean or Chinese
• Body mass index (BMI) for Caucasians within the range 18.5-29.0 kg/m2 (inclusive). For East Asians BMI within the range 18.5-24.9 kg/m2 (inclusive) and height 1.55m-1.85m (inclusive)
• Non-smokers
• AST, ALT, alkaline phosphatase and bilirubin </=1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
• No significant abnormality on 12-lead ECG at screening
• No significant abnormality on the Holter ECG at screening
• FEV1 >/= 85% predicted at screening
• Capable of giving written informed consent
• Subjects who are able to use the inhalation device satisfactorily

Exclusion Criteria:

• As a result of screening medical exam, the principal investigator or delegate physician deems the subject unsuitable for the study. Subjects must not have a systolic blood pressure above 145 mmHg or a diastolic pressure above 85 mmHg unless the Investigator confirms that it is satisfactory for their age.
• Any history of breathing problems in adult life
• Pregnant or lactating females
• Subject has been treated for or diagnosed with depression within six months of screening or has a history of significant psychiatric illness
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
• Subjects who have suffered an upper or lower respiratory tract infection within 4 weeks of the screening visit.
• History of sensitivity to any of the study medications, 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.
• History of milk protein allergy.
• 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.
• Subject has taken oral corticosteroids less than 8 weeks before the screening visit.
• Subject has taken inhaled, intranasal or topical steroids less than 4 weeks before the screening visit.
• History of alcohol/drug abuse or dependence within 12 months of the study
• 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.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
• Positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• Positive for HIV antibodies.
• Positive pre-study urine drug screen or when randomly tested during the study.
• Positive carbon monoxide or alcohol breath test at screening or on admission to the Unit.
• Positive urine cotinine test at screening.
• Consumption of seville oranges, pomelos (members of the grapefruit family) or grapefruit juice from 7 days prior to the first dose of study medication.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Subject is mentally or legally incapacitated.

Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.