Study HZA106829: Efficacy/Safety Study of Fluticasone Furoate/Vilanterol (GW642444) in Adult and Adolescent Asthmatics

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01134042
• Collaborator: (none)
• Enrollment: 587
• Locations: 71
• Arms: 3
• Duration (Months): 16
• Patients Per Site: 8.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of the study is to compare the efficacy and safety of fluticasone furoate/vilanterol (GW642444) inhalation powder administered once daily each evening with fluticasone furoate inhalation powder administered alone once daily each evening in adolescent and adult subjects 12 years of age and older with persistent bronchial asthma over a 24-week period.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Fluticasone Furoate/Vilanterol Inhalation Powder; Drug: Fluticasone Furoate Inhalation Powder; Drug: Fluticasone Propionate Inhalation Powder; Other: Placebo Inhalation Powder 1; Other: Placebo Inhalation Powder 2	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 587 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: HZA106829: A Randomised, Double-blind, Parallel Group, Multicentre Study of Fluticasone Furoate/GW642444 Inhalation Powder, Fluticasone Furoate Inhalation Powder Alone, and Fluticasone Propionate Alone in the Treatment of Persistent Asthma in Adults and Adolescents
• Study Start Date: Jun 1, 2010
• Actual Primary Completion Date: Oct 1, 2011
• Actual Study Completion Date: Oct 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fluticasone Furoate/Vilanterol Fluticasone furoate/vilanterol inhalation powder once daily + Placebo inhalation powder twice daily for 24 weeks	Drug: Fluticasone Furoate/Vilanterol Inhalation Powder; Fluticasone furoate/Vilanterol inhalation powder inhaled orally once daily for 24 weeks; Other: Placebo Inhalation Powder 2; Placebo in Diskus inhaler twice daily
Active Comparator: Fluticasone Furoate Fluticasone furoate inhalation powder once daily + Placebo inhalation powder twice daily for 24 weeks	Drug: Fluticasone Furoate Inhalation Powder; Fluticasone furoate inhalation powder inhaled orally once daily for 24 weeks; Other: Placebo Inhalation Powder 2; Placebo in Diskus inhaler twice daily
Active Comparator: Fluticasone Propionate Fluticasone propionate inhalation powder twice daily + Placebo inhalation powder once daily for 24 weeks	Drug: Fluticasone Propionate Inhalation Powder; Fluticasone propionate inhalation powder inhaled orally twice daily for 24 weeks; Other: Placebo Inhalation Powder 1; Placebo in novel dry powder inhaler once daily

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Clinic Visit Trough (Pre-bronchodilator and Pre-dose) Forced Expiratory Volume in One Second (FEV1) at the End of the 24-week Treatment Period [Baseline and Week 24]

   FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 is defined as the clinic visit (pre-bronchodilator and pre-dose) FEV1 measurement taken at the clinic visit while still on treatment. Pre-dose and pre-rescue albuterol/salbutamol trough FEV1 was measured electronically by spirometry in the evening at the Baseline (BL) through Week 24 clinic visits. The highest of 3 technically acceptable measurements was recorded. BL was the pre-dose value obtained at Visit 3. Change from BL was calculated as the Week 24 value minus the Baseline value. The analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of BL trough FEV1, country, sex, age, and treatment group.The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-BL on-treatment measurement at scheduled clinic visits was used to impute the missing measurements.

2. Change From Baseline in Weighted Mean Serial FEV1 Over 0-24 Hours Post-dose at Week 24 [Baseline and Week 24]

   FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry at the Baseline and Week 24 clinic visits. Weighted mean was calculated using the 24-hour serial FEV1 measurements that included the pre-dose assessment (within 5 minutes prior to dosing) and the post-dose assessments after 5, 15, and 30 minutes and 1, 2, 3, 4, 5, 12, 16, 20, 23, and 24 hours. At each time point, the highest of 3 technically acceptable measurements was recorded. Baseline was the value obtained at Visit 3. Change from Baseline was calculated as the average Week 24 FEV1 value minus the Baseline value.

Secondary Outcome Measures

1. Change From Baseline in the Percentage of Rescue-free and Symptom-free 24-hour Periods at the End of the 24-week Treatment Period [Baseline and Week 24]

   The number of inhalations of rescue bronchodilator, albuterol/salbutamol inhalation aerosol, used during the day and night was recorded by the participants in a daily electronic diary (eDiary). Similarly, asthma symptoms were recorded in a daily eDairy by the participants every day in the morning and evening before taking any rescue or study medication and before the peak expiratory flow measurement. A 24-hour period in which a participant's responses to both the morning and evening assessments indicated no use of rescue medication/symptoms was considered to be rescue free/symptom free. The Baseline value was derived from the last 7 days of the daily eDiary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 24-week Treatment Period minus the Baseline value.

2. Change From Baseline in the Total Asthma Quality of Life Questionnaire (AQLQ) (+12) Score at Week 12 and Week 24/Early Withdrawal [Baseline, Week 12, and Week 24/Early Withdrawal]

   The AQLQ is a disease-specific, self-administered quality of life questionnaire used to evaluate the impact of asthma treatments on the quality of life of asthma sufferers. The AQLQ for 12 years and older (AQLQ [+12]) is a modified version of the AQLQ for use in asthma patients between the age of 12 and 70. The AQLQ contains 32 items in 4 domains: activity limitation (11 items), symptoms (12 items), emotional function (5 items), and environmental stimuli (4 items). For the 32 items on the questionnaire, the response format consists of a seven-point scale, where a value of 1 indicates "total impairment" and a value of 7 indicates "no impairment." The AQLQ total score is defined as the average of the scores from all 32 questions; thus, the total score ranges from 1 (indicates "total impairment") to 7 (indicates "no impairment"). Baseline was the total score obtained at Visit 3. Change from Baseline was calculated as the total score at Weeks 12 and 24 minus the total score at Baseline.

Other Outcome Measures

1. Clinic Visit 12-hour Post-dose FEV1at Week 24 [Week 24]

   FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. 12-hour post-dose FEV1 measurements were taken electronically by spirometry at the Week 24 clinic visit. The highest of 3 technically acceptable measurements was recorded.

2. Change From Baseline in Weighted Mean Serial FEV1 Over 0 to 4 Hours Post-dose at Week 24 [Baseline and Week 24]

   FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry at Baseline. Weighted mean was calculated using the 4-hour serial FEV1 measurements that included the pre-dose assessment (within 5 minutes prior to dosing) and post-dose assessments after 5, 15, and 30 minutes and 1, 2, 3, and 4 hours. At each time point, the highest of 3 technically acceptable measurements was recorded. Baseline was the value obtained at Visit 3. Change from Baseline was calculated as the average Week 24 FEV1 value minus the Baseline value.

3. Mean Change From Baseline in Daily Morning Trough (AM) and Evening (PM) Peak Expiratory Flow (PEF) Averaged Over the First 12 Weeks and 24 Weeks of the 24-week Treatment Period [From Baseline up to Week 12 and Week 24]

   PEF is a measure of lung function and is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each morning and evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Trough PEF is the PEF measured approximately 24 hours after the last administration of study drug. Change from Baseline (defined as the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily trough AM/PM PEF over 12 weeks and 24 weeks of the 24-week Treatment Period (at Weeks 12 and 24) minus the Baseline value.

4. The Number of Participants Who Withdrew Due to Lack of Efficacy During the 24-week Treatment Period [From the first dose of the study medication up to Week 24/Early Withdrawal]

   The number of participants whose primary reason for withdrawal was lack of efficacy was analyzed.

5. Change From Baseline in the Asthma Control Test (ACT) Scores at Week 12 and Week 24 [Baseline, Week 12, and Week 24/Early Withdrawal]

   The ACT is a 5-item questionnaire developed as a measure of the participant's asthma control. Questions are designed to be self-completed by the participant and include the following: In the past 4 weeks, "How much of the time did your asthma keep you from getting as much done at work, school or at home?", "How often have you had shortness of breath?", "How often did your asthma symptoms wake you up at night or earlier than usual in the morning?", "How often have you used your rescue inhaler or nebulizer medication (such as albuterol)?" and "How would you rate your asthma control"? The ACT total score is defined as the sum of the scores from all 5 questions, provided all questions have been answered; thus, the total score ranges from 5 (poor control of asthma) to 25 (complete control of asthma). A score of 20 or higher indicates well-controlled asthma. Change from Baseline was calculated as the total score at Week 12 and Week 24/Early Withdrawal minus the total score at Baseline.

6. Number of Participants With the Indicated Global Assessment of Change Questionnaire Responses at Weeks 4, 12, and 24 [Week 4, Week 12, and Week 24/Early Withdrawal]

   At the end of Week 4, Week 8, and Week 24/Early Withdrawal, the Global Assessment of Change Questionnaire that assesses changes in asthma symptoms (AS) and rescue medication use (RMU) was completed by the participants. The number of participants who chose the following answers to the questionnaire were determined: much better, somewhat better, a little better, the same, a little worse, somewhat worse, much worse (to assess the changes in asthma symptoms); much less often, somewhat less often, a little less often, the same, a little more often, somewhat more often, much more often (to assess the changes in the frequency of rescue medication use).

7. Number of the Indicated Unscheduled Asthma-related Healthcare Visits During the Treatment Period [From Baseline up to Week 24/Withdrawal Visit]

   All unscheduled asthma-related visits to a physician's office, visits to urgent care, visits to the emergency department, and hospitalizations (ICU=intensive care unit; GW=general ward) associated with severe asthma exacerbations or other asthma-related healthcare issues were recorded.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Outpatient at least 12 years of age

• Both genders; females of childbearing potential must be willing to use birth control method

• Pre-bronchodilator FEV1 of 40-90% predicted

• Reversibility FEV1 of at least 12% and 200mls

• Current asthma therapy that includes an inhaled corticosteroid for at least 12 weeks prior to first visit

Exclusion Criteria:

• History of life-threatening asthma

• Respiratory infection or oral candidiasis

• Asthma exacerbation within 12 weeks

• Concurrent respiratory disease or other disease that would confound study participation or affect subject safety

• Allergies to study drugs, study drugs' excipients, medications related to study drugs

• Taking another investigational medication or medication prohibited for use during this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Bell Gardens	California	United States	90201
2	GSK Investigational Site	Huntington Beach	California	United States	92647
3	GSK Investigational Site	Long Beach	California	United States	90808
4	GSK Investigational Site	Los Angeles	California	United States	90048
5	GSK Investigational Site	Riverside	California	United States	92506
6	GSK Investigational Site	Roseville	California	United States	95661
7	GSK Investigational Site	San Diego	California	United States	92128
8	GSK Investigational Site	Clearwater	Florida	United States	33756
9	GSK Investigational Site	Miami	Florida	United States	33173
10	GSK Investigational Site	Panama City	Florida	United States	32405
11	GSK Investigational Site	Atlanta	Georgia	United States	30342
12	GSK Investigational Site	Normal	Illinois	United States	61761
13	GSK Investigational Site	River Forest	Illinois	United States	60305
14	GSK Investigational Site	Asheville	North Carolina	United States	28801
15	GSK Investigational Site	Cincinnati	Ohio	United States	45231
16	GSK Investigational Site	Oklahoma City	Oklahoma	United States	73103
17	GSK Investigational Site	Oklahoma City	Oklahoma	United States	73112
18	GSK Investigational Site	Lake Oswego	Oregon	United States	97035
19	GSK Investigational Site	Medford	Oregon	United States	97504
20	GSK Investigational Site	Orangeburg	South Carolina	United States	29118
21	GSK Investigational Site	Austin	Texas	United States	78756
22	GSK Investigational Site	El Paso	Texas	United States	79925
23	GSK Investigational Site	Sugar Land	Texas	United States	77479
24	GSK Investigational Site	Cottbus	Brandenburg	Germany	03050
25	GSK Investigational Site	Schwedt	Brandenburg	Germany	16303
26	GSK Investigational Site	Frankfurt	Hessen	Germany	60389
27	GSK Investigational Site	Gelnhausen	Hessen	Germany	63571
28	GSK Investigational Site	Kassel	Hessen	Germany	34121
29	GSK Investigational Site	Ruesselsheim	Hessen	Germany	65428
30	GSK Investigational Site	Hannover	Niedersachsen	Germany	30167
31	GSK Investigational Site	Geesthacht	Schleswig-Holstein	Germany	21502
32	GSK Investigational Site	Luebeck	Schleswig-Holstein	Germany	23552
33	GSK Investigational Site	Hamburg		Germany	20354
34	GSK Investigational Site	Fukuoka		Japan	811-1394
35	GSK Investigational Site	Hiroshima		Japan	732-0052
36	GSK Investigational Site	Hyogo		Japan	672-8048
37	GSK Investigational Site	Ishikawa		Japan	920-8530
38	GSK Investigational Site	Kagawa		Japan	762-0031
39	GSK Investigational Site	Kyoto		Japan	603-8161
40	GSK Investigational Site	Okayama		Japan	712-8064
41	GSK Investigational Site	Okinawa		Japan	901-2132
42	GSK Investigational Site	Shizuoka		Japan	430-8558
43	GSK Investigational Site	Shizuoka		Japan	438-8550
44	GSK Investigational Site	Tokyo		Japan	105-0003
45	GSK Investigational Site	Tokyo		Japan	158-0083
46	GSK Investigational Site	Bialystok		Poland	15-010
47	GSK Investigational Site	Dzialdowo		Poland	13-200
48	GSK Investigational Site	Gdansk		Poland	80-169
49	GSK Investigational Site	Gdansk		Poland	84-462
50	GSK Investigational Site	Gliwice		Poland	44-100
51	GSK Investigational Site	Krakow		Poland	31-202
52	GSK Investigational Site	Piekary Slaskie		Poland	41-940
53	GSK Investigational Site	Sopot		Poland	81-741
54	GSK Investigational Site	Bucharest		Romania	020125
55	GSK Investigational Site	Bucharest		Romania	030317
56	GSK Investigational Site	Iasi		Romania	700115
57	GSK Investigational Site	Oradea		Romania	410176
58	GSK Investigational Site	Ploiesti		Romania	100550
59	GSK Investigational Site	Suceava		Romania	720284
60	GSK Investigational Site	Timisoara		Romania	300310
61	GSK Investigational Site	Ekaterinburg		Russian Federation	620109
62	GSK Investigational Site	Kazan		Russian Federation	420015
63	GSK Investigational Site	Moscow		Russian Federation	115 280
64	GSK Investigational Site	Moscow		Russian Federation	115446
65	GSK Investigational Site	Moscow		Russian Federation	123182
66	GSK Investigational Site	Moscow		Russian Federation	125367
67	GSK Investigational Site	Moscow		Russian Federation	127018
68	GSK Investigational Site	Ryazan,		Russian Federation	390026
69	GSK Investigational Site	Smolensk		Russian Federation	214001
70	GSK Investigational Site	St. Petersburg		Russian Federation	198216
71	GSK Investigational Site	Yaroslavl		Russian Federation

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01134042
• Other Study ID Numbers: 106829
• First Posted: May 31, 2010
• Last Update Posted: Jan 11, 2017
• Last Verified: Nov 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Fluticasone propionate; asthma; vilanterol; GW642444; Fluticasone furoate
• Additional relevant MeSH terms: Asthma; Fluticasone; Xhance

Study Results

Participant Flow

Pre-assignment Detail	Participants (par.) meeting eligibility criteria at the Screening visit entered a 4-week Run-in Period for completion of Baseline (BL) safety evaluations and to obtain BL measures of asthma status. Par. were then randomized to a 24-week Treatment Period. 1206 par. were screened, 587 were randomized, and 586 received >=1 dose of study treatment.

Arm/Group Title	FF 200 µg OD	FF/VI 200/25 µg OD	FP 500 µg BID
Arm/Group Description	Participants received FF 200 microgram (µg) inhalation powder via a Dry Powder Inhaler (DPI) once daily (OD) in the evening plus placebo via the DISKUS/ACCUHALER twice daily (BID), for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received Fluticasone Furoate/Vilanterol (FF/VI) 200/25 µg inhalation powder via a DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received Fluticasone Propionate (FP) 500 µg inhalation powder via the DISKUS/ACCUHALER BID plus placebo via a DPI OD in the evening, for 24 weeks. Additionally participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.
Period Title: Overall Study
STARTED	194	197	195
COMPLETED	146	169	161
NOT COMPLETED	48	28	34

Baseline Characteristics

Arm/Group Title	FF 200 µg OD	FF/VI 200/25 µg OD	FP 500 µg BID	Total
Arm/Group Description	Participants received FF 200 µg inhalation powder via a Dry Powder Inhaler DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FF/VI 200/25 µg inhalation powder via a DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FP 500 µg inhalation powder via the DISKUS/ACCUHALER BID plus placebo via a DPI OD in the evening, for 24 weeks. Additionally participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Total of all reporting groups
Overall Participants	194	197	195	586
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	44.6 (14.33)	46.6 (15.05)	47.3 (14.06)	46.2 (14.51)
Gender (Count of Participants)
Female	113 58.2%	116 58.9%	116 59.5%	345 58.9%
Male	81 41.8%	81 41.1%	79 40.5%	241 41.1%
Race/Ethnicity, Customized (participants) [Number]
African American/African Heritage (HER)	16 8.2%	16 8.1%	19 9.7%	51 8.7%
American Indian or Alaska Native	0 0%	0 0%	1 0.5%	1 0.2%
Japanese/East Asian HER/South East Asian HER	12 6.2%	15 7.6%	13 6.7%	40 6.8%
White	165 85.1%	165 83.8%	162 83.1%	492 84%
African American/African Heritage and White	1 0.5%	1 0.5%	0 0%	2 0.3%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Clinic Visit Trough (Pre-bronchodilator and Pre-dose) Forced Expiratory Volume in One Second (FEV1) at the End of the 24-week Treatment Period
Description	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 is defined as the clinic visit (pre-bronchodilator and pre-dose) FEV1 measurement taken at the clinic visit while still on treatment. Pre-dose and pre-rescue albuterol/salbutamol trough FEV1 was measured electronically by spirometry in the evening at the Baseline (BL) through Week 24 clinic visits. The highest of 3 technically acceptable measurements was recorded. BL was the pre-dose value obtained at Visit 3. Change from BL was calculated as the Week 24 value minus the Baseline value. The analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of BL trough FEV1, country, sex, age, and treatment group.The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-BL on-treatment measurement at scheduled clinic visits was used to impute the missing measurements.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all participants randomized to treatment who received at least one dose of the study medication. Only those participants with non-missing covariates and a post-Baseline FEV1 measurement were analyzed.

Arm/Group Title	FF 200 µg OD	FF/VI 200/25 µg OD	FP 500 µg BID
Arm/Group Description	Participants received FF 200 µg inhalation powder via a Dry Powder Inhaler DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FF/VI 200/25 µg inhalation powder via a DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FP 500 µg inhalation powder via the DISKUS/ACCUHALER BID plus placebo via a DPI OD in the evening, for 24 weeks. Additionally participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.
Measure Participants	186	187	190
Least Squares Mean (Standard Error) [Liters]	0.201 (0.0303)	0.394 (0.0302)	0.183 (0.0300)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FF 200 µg OD, FF/VI 200/25 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.193
	Confidence Interval	(2-Sided) 95%; 0.108 to 0.277
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FF/VI 200/25 µg OD, FP 500 µg BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.210
	Confidence Interval	(2-Sided) 95%; 0.127 to 0.294
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	FF 200 µg OD, FP 500 µg BID
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority is demonstrated if the lower limit of the confidence interval (CI: 0.025, 1-sided significance level) for the mean difference in change from Baseline in clinic visit trough FEV1 of FF 200 µg OD versus FP 500 µg BID was greater than -125 milliliters.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.018
	Confidence Interval	(2-Sided) 95%; -0.066 to 0.102
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Change From Baseline in Weighted Mean Serial FEV1 Over 0-24 Hours Post-dose at Week 24
Description	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry at the Baseline and Week 24 clinic visits. Weighted mean was calculated using the 24-hour serial FEV1 measurements that included the pre-dose assessment (within 5 minutes prior to dosing) and the post-dose assessments after 5, 15, and 30 minutes and 1, 2, 3, 4, 5, 12, 16, 20, 23, and 24 hours. At each time point, the highest of 3 technically acceptable measurements was recorded. Baseline was the value obtained at Visit 3. Change from Baseline was calculated as the average Week 24 FEV1 value minus the Baseline value.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

ITT Population. Weighted mean serial FEV1 was calculated in the subset of participants for whom serial FEV1 at Week 24 was performed.

Arm/Group Title	FF 200 µg OD	FF/VI 200/25 µg OD	FP 500 µg BID
Arm/Group Description	Participants received FF 200 µg inhalation powder via a Dry Powder Inhaler DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FF/VI 200/25 µg inhalation powder via a DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FP 500 µg inhalation powder via the DISKUS/ACCUHALER BID plus placebo via a DPI OD in the evening, for 24 weeks. Additionally participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.
Measure Participants	83	89	86
Least Squares Mean (Standard Error) [Liters]	0.328 (0.0493)	0.464 (0.0470)	0.258 (0.0483)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	FF 200 µg OD, FF/VI 200/25 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.048
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.136
	Confidence Interval	(2-Sided) 95%; 0.001 to 0.270
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	FF/VI 200/25 µg OD, FP 500 µg BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.206
	Confidence Interval	(2-Sided) 95%; 0.073 to 0.339
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in the Percentage of Rescue-free and Symptom-free 24-hour Periods at the End of the 24-week Treatment Period
Description	The number of inhalations of rescue bronchodilator, albuterol/salbutamol inhalation aerosol, used during the day and night was recorded by the participants in a daily electronic diary (eDiary). Similarly, asthma symptoms were recorded in a daily eDairy by the participants every day in the morning and evening before taking any rescue or study medication and before the peak expiratory flow measurement. A 24-hour period in which a participant's responses to both the morning and evening assessments indicated no use of rescue medication/symptoms was considered to be rescue free/symptom free. The Baseline value was derived from the last 7 days of the daily eDiary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 24-week Treatment Period minus the Baseline value.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	FF 200 µg OD	FF/VI 200/25 µg OD	FP 500 µg BID
Arm/Group Description	Participants received FF 200 µg inhalation powder via a Dry Powder Inhaler DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FF/VI 200/25 µg inhalation powder via a DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FP 500 µg inhalation powder via the DISKUS/ACCUHALER BID plus placebo via a DPI OD in the evening, for 24 weeks. Additionally participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.
Measure Participants	193	197	194
Rescue-free 24-hour periods	26.6 (2.45)	38.2 (2.42)	31.9 (2.45)
Symptom-free 24-hour periods	21.0 (2.32)	29.3 (2.29)	24.5 (2.31)

4. Secondary Outcome

Title	Change From Baseline in the Total Asthma Quality of Life Questionnaire (AQLQ) (+12) Score at Week 12 and Week 24/Early Withdrawal
Description	The AQLQ is a disease-specific, self-administered quality of life questionnaire used to evaluate the impact of asthma treatments on the quality of life of asthma sufferers. The AQLQ for 12 years and older (AQLQ [+12]) is a modified version of the AQLQ for use in asthma patients between the age of 12 and 70. The AQLQ contains 32 items in 4 domains: activity limitation (11 items), symptoms (12 items), emotional function (5 items), and environmental stimuli (4 items). For the 32 items on the questionnaire, the response format consists of a seven-point scale, where a value of 1 indicates "total impairment" and a value of 7 indicates "no impairment." The AQLQ total score is defined as the average of the scores from all 32 questions; thus, the total score ranges from 1 (indicates "total impairment") to 7 (indicates "no impairment"). Baseline was the total score obtained at Visit 3. Change from Baseline was calculated as the total score at Weeks 12 and 24 minus the total score at Baseline.
Time Frame	Baseline, Week 12, and Week 24/Early Withdrawal

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Arm/Group Title	FF 200 µg OD	FF/VI 200/25 µg OD	FP 500 µg BID
Arm/Group Description	Participants received FF 200 µg inhalation powder via a Dry Powder Inhaler DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FF/VI 200/25 µg inhalation powder via a DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FP 500 µg inhalation powder via the DISKUS/ACCUHALER BID plus placebo via a DPI OD in the evening, for 24 weeks. Additionally participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.
Measure Participants	194	197	195
Week 12, n=154, 180, 163	0.66 (0.061)	0.74 (0.056)	0.74 (0.059)
Week 24, n=140, 167, 156	0.88 (0.071)	0.93 (0.065)	0.90 (0.068)

5. Other Pre-specified Outcome

Title	Clinic Visit 12-hour Post-dose FEV1at Week 24
Description	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. 12-hour post-dose FEV1 measurements were taken electronically by spirometry at the Week 24 clinic visit. The highest of 3 technically acceptable measurements was recorded.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

ITT Population. 12-hour post-dose FEV1 was analyzed in the subset of participants for whom serial FEV1 at Week 24 was performed.

Arm/Group Title	FF 200 µg OD	FF/VI 200/25 µg OD	FP 500 µg BID
Arm/Group Description	Participants received FF 200 µg inhalation powder via a Dry Powder Inhaler DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FF/VI 200/25 µg inhalation powder via a DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FP 500 µg inhalation powder via the DISKUS/ACCUHALER BID plus placebo via a DPI OD in the evening, for 24 weeks. Additionally participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.
Measure Participants	82	93	87
Mean (Standard Deviation) [Liters]	2.611 (0.8437)	2.683 (0.9758)	2.262 (0.7786)

6. Other Pre-specified Outcome

Title	Change From Baseline in Weighted Mean Serial FEV1 Over 0 to 4 Hours Post-dose at Week 24
Description	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry at Baseline. Weighted mean was calculated using the 4-hour serial FEV1 measurements that included the pre-dose assessment (within 5 minutes prior to dosing) and post-dose assessments after 5, 15, and 30 minutes and 1, 2, 3, and 4 hours. At each time point, the highest of 3 technically acceptable measurements was recorded. Baseline was the value obtained at Visit 3. Change from Baseline was calculated as the average Week 24 FEV1 value minus the Baseline value.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

ITT Population. Weighted mean serial FEV1 was calculated in the subset of participants for whom serial FEV1 at Week 24 was performed.

Arm/Group Title	FF 200 µg OD	FF/VI 200/25 µg OD	FP 500 µg BID
Arm/Group Description	Participants received FF 200 µg inhalation powder via a Dry Powder Inhaler DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FF/VI 200/25 µg inhalation powder via a DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FP 500 µg inhalation powder via the DISKUS/ACCUHALER BID plus placebo via a DPI OD in the evening, for 24 weeks. Additionally participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.
Measure Participants	83	89	86
Mean (Standard Deviation) [Liters]	0.363 (0.4690)	0.492 (0.5671)	0.256 (0.4679)

7. Other Pre-specified Outcome

Title	Mean Change From Baseline in Daily Morning Trough (AM) and Evening (PM) Peak Expiratory Flow (PEF) Averaged Over the First 12 Weeks and 24 Weeks of the 24-week Treatment Period
Description	PEF is a measure of lung function and is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each morning and evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Trough PEF is the PEF measured approximately 24 hours after the last administration of study drug. Change from Baseline (defined as the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily trough AM/PM PEF over 12 weeks and 24 weeks of the 24-week Treatment Period (at Weeks 12 and 24) minus the Baseline value.
Time Frame	From Baseline up to Week 12 and Week 24

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Arm/Group Title	FF 200 µg OD	FF/VI 200/25 µg OD	FP 500 µg BID
Arm/Group Description	Participants received FF 200 µg inhalation powder via a Dry Powder Inhaler DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FF/VI 200/25 µg inhalation powder via a DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FP 500 µg inhalation powder via the DISKUS/ACCUHALER BID plus placebo via a DPI OD in the evening, for 24 weeks. Additionally participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.
Measure Participants	194	197	195
AM PEF, Week 1 to 12, n=193, 197, 195	15.1 (2.82)	48.1 (2.78)	17.1 (2.80)
AM PEF, Week 1 to 24, n=193, 197, 195	18.2 (2.97)	51.8 (2.94)	18.8 (2.95)
PM PEF, Week 1 to 12, 192, 197, 194	7.5 (2.80)	36.6 (2.75)	12.6 (2.78)
PM PEF, Week 1 to 24, 192, 197, 194	9.1 (2.98)	39.8 (2.93)	13.6 (2.96)

8. Other Pre-specified Outcome

Title	The Number of Participants Who Withdrew Due to Lack of Efficacy During the 24-week Treatment Period
Description	The number of participants whose primary reason for withdrawal was lack of efficacy was analyzed.
Time Frame	From the first dose of the study medication up to Week 24/Early Withdrawal

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	FF 200 µg OD Arm	FF/VI 200/25 µg OD	FP 500 µg BID
Arm/Group Description	Participants received FF 200 µg inhalation powder via a Dry Powder Inhaler DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FF/VI 200/25 µg inhalation powder via a DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FP 500 µg inhalation powder via the DISKUS/ACCUHALER BID plus placebo via a DPI OD in the evening, for 24 weeks. Additionally participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.
Measure Participants	194	197	195
Number [participants]	21 10.8%	6 3%	18 9.2%

9. Other Pre-specified Outcome

Title	Change From Baseline in the Asthma Control Test (ACT) Scores at Week 12 and Week 24
Description	The ACT is a 5-item questionnaire developed as a measure of the participant's asthma control. Questions are designed to be self-completed by the participant and include the following: In the past 4 weeks, "How much of the time did your asthma keep you from getting as much done at work, school or at home?", "How often have you had shortness of breath?", "How often did your asthma symptoms wake you up at night or earlier than usual in the morning?", "How often have you used your rescue inhaler or nebulizer medication (such as albuterol)?" and "How would you rate your asthma control"? The ACT total score is defined as the sum of the scores from all 5 questions, provided all questions have been answered; thus, the total score ranges from 5 (poor control of asthma) to 25 (complete control of asthma). A score of 20 or higher indicates well-controlled asthma. Change from Baseline was calculated as the total score at Week 12 and Week 24/Early Withdrawal minus the total score at Baseline.
Time Frame	Baseline, Week 12, and Week 24/Early Withdrawal

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Arm/Group Title	FF 200 µg OD	FF/VI 200/25 µg OD	FP 500 µg BID
Arm/Group Description	Participants received FF 200 µg inhalation powder via a Dry Powder Inhaler DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FF/VI 200/25 µg inhalation powder via a DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FP 500 µg inhalation powder via the DISKUS/ACCUHALER BID plus placebo via a DPI OD in the evening, for 24 weeks. Additionally participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.
Measure Participants	194	197	195
Week 12, n=164, 183, 169	3.9 (0.29)	4.8 (0.27)	3.9 (0.28)
Week 24, n=147, 170, 162	5.2 (0.30)	5.5 (0.28)	4.7 (0.29)

10. Other Pre-specified Outcome

Title	Number of Participants With the Indicated Global Assessment of Change Questionnaire Responses at Weeks 4, 12, and 24
Description	At the end of Week 4, Week 8, and Week 24/Early Withdrawal, the Global Assessment of Change Questionnaire that assesses changes in asthma symptoms (AS) and rescue medication use (RMU) was completed by the participants. The number of participants who chose the following answers to the questionnaire were determined: much better, somewhat better, a little better, the same, a little worse, somewhat worse, much worse (to assess the changes in asthma symptoms); much less often, somewhat less often, a little less often, the same, a little more often, somewhat more often, much more often (to assess the changes in the frequency of rescue medication use).
Time Frame	Week 4, Week 12, and Week 24/Early Withdrawal

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Arm/Group Title	FF 200 µg OD	FF/VI 200/25 µg OD	FP 500 µg BID
Arm/Group Description	Participants received FF 200 µg inhalation powder via a Dry Powder Inhaler DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FF/VI 200/25 µg inhalation powder via a DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FP 500 µg inhalation powder via the DISKUS/ACCUHALER BID plus placebo via a DPI OD in the evening, for 24 weeks. Additionally participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.
Measure Participants	194	197	195
Week 4, AS: Much better, n=174, 191, 180	37 19.1%	58 29.4%	35 17.9%
Week 4, AS: Somewhat better, n=174, 191, 180	47 24.2%	65 33%	49 25.1%
Week 4, AS: A little better, n=174, 191, 180	43 22.2%	34 17.3%	40 20.5%
Week 4, AS: The same, n=174, 191, 180	35 18%	25 12.7%	44 22.6%
Week 4, AS: A little worse, n=174, 191, 180	8 4.1%	7 3.6%	6 3.1%
Week 4, AS: Somewhat worse, n=174, 191, 180	2 1%	2 1%	3 1.5%
Week 4, AS: Much worse, n=174, 191, 180	2 1%	0 0%	3 1.5%
Week 4, RMU: Much less often, n=174, 191, 180	49 25.3%	71 36%	42 21.5%
Week 4, RMU: Somewhat less often, n=174, 191, 180	29 14.9%	48 24.4%	41 21%
Week 4, RMU: A little less often, n=174, 191, 180	42 21.6%	38 19.3%	45 23.1%
Week 4, RMU: The same, n=174, 191, 180	34 17.5%	27 13.7%	37 19%
Week 4, RMU: A little more often, n=174, 191, 180	14 7.2%	4 2%	9 4.6%
Week 4, RMU: Somewhat more often, n=174, 191, 180	5 2.6%	2 1%	3 1.5%
Week 4, RMU: Much more often, n=174, 191, 180	1 0.5%	1 0.5%	3 1.5%
Week 12, AS: Much better, n=162, 183, 165	60 30.9%	78 39.6%	54 27.7%
Week 12, AS: Somewhat better, n=162, 183, 165	43 22.2%	51 25.9%	52 26.7%
Week 12, AS: A little better, n=162, 183, 165	27 13.9%	33 16.8%	34 17.4%
Week 12, AS: The same, n=162, 183, 165	23 11.9%	15 7.6%	16 8.2%
Week 12, AS: A little worse, n=162, 183, 165	8 4.1%	5 2.5%	6 3.1%
Week 12, AS: Somewhat worse, n=162, 183, 165	0 0%	1 0.5%	3 1.5%
Week 12, AS: Much worse, n=162, 183, 165	1 0.5%	0 0%	0 0%
Week 12, RMU: Much less often, n=162, 183, 164	66 34%	90 45.7%	59 30.3%
Week 12, RMU: Somewhat less often, n=162, 183, 164	31 16%	36 18.3%	37 19%
Week 12, RMU: A little less often, n=162, 183, 164	28 14.4%	24 12.2%	40 20.5%
Week 12, RMU: The same, n=162, 183, 164	26 13.4%	24 12.2%	20 10.3%
Week 12, RMU: A little more often, n=162, 183, 164	7 3.6%	8 4.1%	6 3.1%
Week 12, RMU: Somewhat more often, n=162, 183, 164	2 1%	0 0%	1 0.5%
Week 12, RMU: Much more often, n=162, 183, 164	2 1%	1 0.5%	1 0.5%
Week 24, AS: Much better, n=146, 168, 162	64 33%	89 45.2%	62 31.8%
Week 24, AS: Somewhat better, n=146, 168, 162	43 22.2%	37 18.8%	52 26.7%
Week 24, AS: A little better, n=146, 168, 162	22 11.3%	23 11.7%	17 8.7%
Week 24, AS: The same, n=146, 168, 162	11 5.7%	14 7.1%	23 11.8%
Week 24, AS: A little worse, n=146, 168, 162	3 1.5%	4 2%	4 2.1%
Week 24, AS: Somewhat worse, n=146, 168, 162	2 1%	1 0.5%	2 1%
Week 24, AS: Much worse, n=146, 168, 162	1 0.5%	0 0%	2 1%
Week 24, RMU: Much less often, n=146, 168, 162	68 35.1%	87 44.2%	69 35.4%
Week 24, RMU: Somewhat less often, n=150, 187, 18	33 17%	38 19.3%	37 19%
Week 24, RMU: A little less often, n=150, 187, 18	29 14.9%	22 11.2%	26 13.3%
Week 24, RMU: The same, n=146, 168, 162	12 6.2%	16 8.1%	19 9.7%
Week 24, RMU: A little more often, n= 142, 168, 16	1 0.5%	3 1.5%	8 4.1%
Week 24, RMU: Somewhat more often, n=146, 168, 162	3 1.5%	1 0.5%	1 0.5%
Week 24, RMU: Much more often, n=146, 168, 162	0 0%	1 0.5%	2 1%

11. Other Pre-specified Outcome

Title	Number of the Indicated Unscheduled Asthma-related Healthcare Visits During the Treatment Period
Description	All unscheduled asthma-related visits to a physician's office, visits to urgent care, visits to the emergency department, and hospitalizations (ICU=intensive care unit; GW=general ward) associated with severe asthma exacerbations or other asthma-related healthcare issues were recorded.
Time Frame	From Baseline up to Week 24/Withdrawal Visit

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	FF 200 µg OD	FF/VI 200/25 µg OD	FP 500 µg BID
Arm/Group Description	Participants received FF 200 µg inhalation powder via a Dry Powder Inhaler DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FF/VI 200/25 µg inhalation powder via a DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.	Participants received FP 500 µg inhalation powder via the DISKUS/ACCUHALER BID plus placebo via a DPI OD in the evening, for 24 weeks. Additionally participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.
Measure Participants	194	197	195
Number of Home Visits (Day)	0.0 (0.07)	0.0 (0.00)	0.0 (0.00)
Number of Home Visits (Night)	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)
Number of Physician Office/Practice Visits	0.0 (0.10)	0.0 (0.00)	0.1 (0.45)
Number of Urgent Care/Outpatient Clinic Visits	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)
Number of Emergency Room Visits	0.0 (0.07)	0.0 (0.00)	0.0 (0.00)
Number of Inpatient Hospitalization Days (ICU)	0.0 (0.00)	0.0 (0.00)	0.0 (0.00)
Number of Inpatient Hospitalization (GW) Days	0.0 (0.29)	0.0 (0.00)	0.0 (0.00)

Adverse Events

Time Frame	Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 24).
Adverse Event Reporting Description	An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
Arm/Group Title	FF 200 µg OD		FF/VI 200/25 µg OD		FP 500 µg BID
Arm/Group Description	Participants received FF 200 µg inhalation powder via a Dry Powder Inhaler DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.		Participants received FF/VI 200/25 µg inhalation powder via a DPI OD in the evening plus placebo via the DISKUS/ACCUHALER BID, for 24 weeks. Additionally participants were provided with albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.		Participants received FP 500 µg inhalation powder via the DISKUS/ACCUHALER BID plus placebo via a DPI OD in the evening, for 24 weeks. Additionally participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication as needed.
All Cause Mortality
	FF 200 µg OD		FF/VI 200/25 µg OD		FP 500 µg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	FF 200 µg OD		FF/VI 200/25 µg OD		FP 500 µg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/194 (0.5%)		6/197 (3%)		2/195 (1%)
Cardiac disorders
Atrial fibrillation	0/194 (0%)		1/197 (0.5%)		0/195 (0%)
Gastrointestinal disorders
Inguinal hernia	0/194 (0%)		1/197 (0.5%)		0/195 (0%)
Infections and infestations
Pneumonia	0/194 (0%)		1/197 (0.5%)		0/195 (0%)
Injury, poisoning and procedural complications
Limb traumatic amputation	0/194 (0%)		1/197 (0.5%)		0/195 (0%)
Lower limb fracture	0/194 (0%)		0/197 (0%)		1/195 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer	0/194 (0%)		1/197 (0.5%)		0/195 (0%)
Renal and urinary disorders
Haematuria	0/194 (0%)		1/197 (0.5%)		0/195 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/194 (0.5%)		0/197 (0%)		0/195 (0%)
Haemoptysis	0/194 (0%)		0/197 (0%)		1/195 (0.5%)
Other (Not Including Serious) Adverse Events
	FF 200 µg OD		FF/VI 200/25 µg OD		FP 500 µg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/194 (34%)		62/197 (31.5%)		73/195 (37.4%)
Infections and infestations
Nasopharyngitis	27/194 (13.9%)		25/197 (12.7%)		39/195 (20%)
Respiratory tract infection viral	7/194 (3.6%)		7/197 (3.6%)		7/195 (3.6%)
Influenza	8/194 (4.1%)		5/197 (2.5%)		7/195 (3.6%)
Bronchitis	6/194 (3.1%)		7/197 (3.6%)		6/195 (3.1%)
Sinusitis	7/194 (3.6%)		3/197 (1.5%)		4/195 (2.1%)
Pharyngitis	2/194 (1%)		4/197 (2%)		6/195 (3.1%)
Rhinitis	2/194 (1%)		1/197 (0.5%)		7/195 (3.6%)
Nervous system disorders
Headache	13/194 (6.7%)		11/197 (5.6%)		15/195 (7.7%)
Respiratory, thoracic and mediastinal disorders
Cough	6/194 (3.1%)		3/197 (1.5%)		13/195 (6.7%)
Oropharyngeal pain	8/194 (4.1%)		4/197 (2%)		7/195 (3.6%)
Dysphonia	2/194 (1%)		6/197 (3%)		4/195 (2.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.