Efficacy and Safety of Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) in Chinese Participants With Inadequately Controlled Asthma

Inclusion criteria:

• Participant must be 18 years or older at the time of signing the informed consent.

• Documented history asthma diagnosis as defined by the Global Initiative for Asthma (GINA) at least one year prior to Visit 0.

• Participants with inadequately controlled asthma (ACQ-6 score >=1.5) despite InhaledCorticosteroids/Long-Acting Beta-2-Agonists (ICS/LABA) maintenance therapy at Visit

• Participants who require daily ICS/LABA for at least 12 weeks prior to Visit 0 withno changes to maintenance asthma medications during the 6 weeks immediately prior toVisit 0 (including no changes to a stable total dose of ICS of greater than [>]250micrograms (mcg) per day fluticasone propionate [FP, or equivalent]).

• A best pre-bronchodilator morning (AM) FEV1 >=30 percent (%) and less than (<) 85%of the predicted normal value at Visit 1. Predicted values will be based upon theEuropean Respiratory Society (ERS) Global Lung Function Initiative.

• Airway reversibility defined as >=12% and >=200 milliliters (mL) increase in FEV1between 20 and 60 minutes following 4 inhalations of albuterol/salbutamol aerosol atVisit 1.

• All participants must be able to replace their current Short-Acting Beta-2-Agonists (SABA) inhaler with albuterol/salbutamol aerosol inhaler at Visit 1 as needed forthe duration of the study. Participants must be judged capable of withholdingalbuterol/salbutamol for at least 6 hours prior to study visits.

• Male or female participants following contraceptive/barrier requirements and itshould be consistent with local regulations regarding the methods of contraceptionfor those participating in clinical studies. A female participant is eligible toparticipate if she is not pregnant or breastfeeding, and one of the followingconditions applies: Is a woman of non-childbearing potential (WONCBP) or a woman ofchildbearing potential (WOCBP) who agrees to follow the contraceptive guidanceduring the study.

• Capable of giving signed informed consent which includes compliance with therequirements and restrictions listed in the informed consent form (ICF) and in thisprotocol.

Exclusion Criteria:

• Chest X-ray documented pneumonia in the 6 weeks prior to Visit 1.

• Any asthma exacerbation requiring a change in maintenance asthma therapy in the 6weeks prior to Visit 1.

• Participants with the diagnosis of chronic obstructive pulmonary disease, as perGlobal Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, includingall of the following:

1. History of exposure to risk factors (especially tobacco smoke, occupationaldusts and chemicals, smoke from home cooking and heating fuels).

2. A post-albuterol/salbutamol FEV1/Forced Vital Capacity (FVC) ratio of <0.70 anda post-albuterol/salbutamol FEV1 of less than or equal to (<=)70% of predictednormal values.

3. Onset of disease >=40 years of age.

• Participants with current evidence of pneumonia, active tuberculosis, lung cancer,significant bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension,interstitial lung diseases or other active pulmonary diseases or abnormalities otherthan asthma.

• Immune suppression (e.g., Human Immunodeficiency virus [HIV], Lupus) or other riskfactors for pneumonia (e.g., neurological disorders affecting control of the upperairway, such as Parkinson's Disease, Myasthenia Gravis). Participants at potentiallyhigh risk (e.g., very low Body Mass Index [BMI], severely malnourished, or very lowFEV1) will only be included at the discretion of the Investigator.

• Participants with historical or current evidence of clinically significantcardiovascular, neurological, psychiatric, renal, hepatic, immunological,gastrointestinal, urogenital, nervous system, musculoskeletal, skin, sensory,endocrine (including uncontrolled diabetes or thyroid disease) or hematologicalabnormalities that are uncontrolled. Significant is defined as any disease that, inthe opinion of the Investigator, would put the safety of the participant at riskthrough participation, or which would affect the efficacy or safety analysis if thedisease/condition exacerbated during the study.

• Unstable liver disease as defined by the presence of ascites, encephalopathy,coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistentjaundice, cirrhosis, known biliary abnormalities (with the exception of Gilbert'ssyndrome or asymptomatic gallstones).

• Clinically significant Electrocardiogram (ECG) abnormality: Evidence of a clinicallysignificant abnormality in the 12-lead ECG performed during screening. TheInvestigator will determine the clinical significance of each abnormal ECG findingin relation to the participant's medical history and exclude participants who wouldbe at undue risk by participating in the trial. An abnormal and clinicallysignificant finding is defined as a 12-lead tracing that is interpreted as, but notlimited to, any of the following:

1. Atrial Fibrillation with rapid ventricular rate >120 beats per minute (bpm).

2. Sustained or non-sustained ventricular tachycardia.

3. Second degree heart block Mobitz type II and third degree heart block (unlesspacemaker or defibrillator had been inserted).

4. QT interval corrected for heart rate by Fridericia's formula (QTcF) >=500milliseconds (msec) in participants with QRS <120 msec and QTcF >=530 msec inparticipants with QRS >=120 msec.

• Participants with any of the following at Screening (Visit 1):

1. Myocardial infarction or unstable angina in the last 6 months.

2. Unstable or life-threatening cardiac arrhythmia requiring intervention in thelast 3 months.

3. New York Heart Association (NYHA) Class IV Heart failure [American HeartAssociation, 2016].

• Participants with a medical condition such as narrow-angle glaucoma, urinaryretention, prostatic hypertrophy or bladder neck obstruction should only be includedif in the opinion of the Investigator the benefit outweighs the risk and that thecondition would not contraindicate study participation.

• Participants with carcinoma that has not been in complete remission for at least 5years. Participants who have had carcinoma in situ of the cervix, squamous cellcarcinoma and basal cell carcinoma of the skin would not be excluded based on the 5year waiting period if the participant has been considered cured by treatment.

• Participants with a history of psychiatric disease, intellectual deficiency, poormotivation or other conditions that will limit the validity of informed consent toparticipate in the study.

• Participants who are medically unable to withhold their albuterol/salbutamol for the 6-hour period required prior to spirometry testing at each study visit.

• Participants who are:

1. Current smokers (defined as participants who have used inhaled tobacco productswithin the 12 months prior to Visit 1, e.g. cigarettes,electronic-cigarettes/vaping, cigars or pipe tobacco).

2. Former smokers with a smoking history of >=10 pack years (e.g. >=20 cigarettesper day for 10 years).

• Participants with a known or suspected history of alcohol or drug abuse within thelast 2 years.

• A history of allergy or hypersensitivity to any corticosteroid,anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk proteinor magnesium stearate.

• Participants at risk of non-compliance, or unable to comply with the studyprocedures. Any infirmity, disability, or geographic location that would limitcompliance for scheduled visits.

• Study Investigators, sub-Investigators, study coordinators, employees of aparticipating Investigator or study site, or immediate family members of theaforementioned that is involved with this study.

• In the opinion of the Investigator, any participant who is unable to read and/orwould not be able to complete study related materials.

Inclusion criteria for randomization:

• Participants with inadequately controlled asthma (ACQ-6 score >=1.5) at Visit 2.

• A best pre-bronchodilator morning (AM) FEV1 >=30% and <90% of the predicted normalvalue at Visit 2. Predicted values will be based upon the ERS Global Lung FunctionInitiative (Quanjer).

• Liver function tests at Visit 1:

1. Alanine aminotransferase (ALT) <2 times upper limit of normal (ULN).

2. Alkaline phosphatase <=1.5 times ULN.

3. Bilirubin <=1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable ifbilirubin is fractionated and direct bilirubin <35%).

• Compliance with completion of the Electronic diary reporting defined as completionof all questions/assessment on >=4 of the last 7 days during the run-in period.

Exclusion criteria for randomization:

• Occurrence of a culture-documented or suspected bacterial or viral infection of theupper or lower respiratory tract, sinus or middle ear during the run-in period thatled to a change in asthma management or, in the opinion of the Investigator, isexpected to affect the participant's asthma status or the participant's ability toparticipate in the study.

• Evidence of a severe exacerbation during screening or the run-in period, defined asdeterioration of asthma requiring the use of systemic corticosteroids (tablets,suspension, or injection) for at least 3 days or an in-patient hospitalization oremergency department visit due to asthma that required systemic corticosteroids.

• Changes in asthma medication (excluding run-in medication and albuterol/salbutamolinhalation aerosol provided at Visit 1).

• Evidence of clinically significant abnormal laboratory tests during screening orrun-in which are still abnormal upon repeat analysis and are not believed to be dueto disease(s) present. Each Investigator will use his/her own discretion indetermining the clinical significance of the abnormality.