This is a double-blind, single dose (four inhalations), four-way cross over study in healthy subjects that will assess the systemic pharmacokinetics (PK) and systemic pharmacodynamics (PD) of Fluticasone Furoate, (FF), Umeclidinium, (UMEC) and Vilanterol (VI). Study drug will be delivered through a novel single-step activation dry powder inhaler (NDPI) which has a two strip configuration. The NDPI will be configured with different combinations of each compound and also a new blend of UMEC/VI inhalation powder within a single strip of the NDPI device. Study drug will be administered through the inhaled route to healthy subjects in single doses (four inhalations). Each subject will receive treatment in a randomized order Treatment A FF (400 microgram [µg]) and UMEC (500 µg)/VI (100 µg), Treatment B UMEC (500 µg) and VI (100 µg), Treatment C FF (400 µg) and VI (100 µg) and Treatment D FF (400 µg) and UMEC (500 µg) over four treatment periods. Each treatment period will be separated by a washout of 7 to 21 days. After the four treatment periods, a follow up visit will take place 7 to 21 days following the final dose of study medication and the maximum duration a subject will be involved in the study is eighteen weeks.

Pharmacokinetics will be assessed by the measurement of plasma and urine concentrations of FF, UMEC and VI. Safety and PD will be monitored using blood glucose, serum potassium, heart rate, 12-lead ECGs and clinical laboratory tests. Plasma samples for PK will be collected throughout the study, urine, blood glucose, serum potassium, heart rate, 12-lead ECGs and clinical laboratory tests will be assessed on Day 1 only. AEs will be assessed throughout the study.

Inclusion Criteria:

• Healthy as determined by a responsible and experienced physician, based on a medical evaluation
• Male or female between 18 and 65 years of age
• Body Mass Index (BMI) within the range 19.0 - 33.0 kilogram (kg)/meters (m)^2 (inclusive)
• Average QT interval corrected using Fridericia's (QTcF) formula < 450 millisecond (msec)
• Forced Expiratory Volume in 1 second (FEV1) >=80% predicted and a FEV1/Forced Vital Capacity (FVC) ratio >=0.7
• Subjects who are current non-smokers who have not used any tobacco products in the 6-month period preceding the screening visit
• Alanine transaminase (ALT), alkaline phosphatase and bilirubin <=1.5xupper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)
• A female subject is eligible to participate if she is confirmed postmenopausal or permanently sterilized; or if she is of child-bearing potential and is abstinent or agrees to use contraception prior to start of dosing until the follow up visit
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form

Exclusion Criteria:

• A supine mean heart rate outside the range 40-90 beats per minute (bpm) at screening.
• History of respiratory disease (i.e. history of asthmatic symptoms) in the last 10 years.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening or a positive test for human immunodeficiency virus (HIV) antibody.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones) or a history of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 drinks for males or >7 drinks for females.
• A positive pre-study drug/alcohol screen
• 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) or has had exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• Lactating or pregnant females as determined by positive serum or urine human chorionic gonadotropin (hCG) test at screening or prior to dosing.
• Unable to refrain from the 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 Glaxo SmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. Or the subject is unable to refrain from consumption of red wine, seville oranges, grapefruit or grapefruit juice and pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication and for the duration of the study.
• 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.
• 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.