A Study to Compare the Efficacy of Fluticasone Furoate/Vilanterol Inhalation Powder With Usual Inhaled Corticosteroids (ICS)/Long Acting Beta Agonists (LABA) in Persistent Asthma

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02446418
• Collaborator: (none)
• Enrollment: 423
• Locations: 93
• Arms: 2
• Actual Duration (Months): 24.4
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The combination of FF, an ICS and VI, an orally inhaled LABA has been developed as a once-daily combination therapy for the long-term maintenance treatment of asthma in adults and children >=12 years of age. Pivotal phase III studies have demonstrated the safety and efficacy of FF/VI in asthma. However, it is increasingly acknowledged that randomised clinical trials tend to be highly controlled and enrol a more highly selected subject population than is expected to be prescribed the medication post-approval. There is a need for data in a more representative population in close to a 'real life' conditions, where physicians have the ability to choose the best treatment in their view for any individual subject and adapt treatments to subjects' characteristics and response. This multi-center, open-label, randomized, parallel group study will evaluate the efficacy and safety of FF/VI compared with two usual ICS/LABA fixed combination (fluticasone propionate/salmeterol [FP/S] or budesonide/formoterol [BUD/F]) in subjects with persistent asthma, in a "close to real life" settings. FF/VI will be administered once-daily (QD) via ELLIPTA dry powder inhaler (DPI) and FP/S or BUD/F will be administered twice daily (BID) via DISKUS™ and TURBUHALER™ DPI respectively. ELLIPTA is a new powder inhaler designed to be easy to use. The total duration of subject participation will be approximately 6 months (24 weeks). ELLIPTA and DISKUS are registered trademarks of the GSK group of companies. TURBUHALER is a registered trademark of AstraZeneca.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Fluticasone Furoate; Drug: Vilanterol; Drug: Fluticasone propionate; Drug: Salmeterol; Drug: Budesonide; Drug: Formoterol Fumarate	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 423 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A 6-month, Open Label, Randomised, Efficacy Study to Evaluate Fluticasone Furoate (FF, GW685698)/Vilanterol (VI, GW642444) Inhalation Powder Delivered Once Daily Via the Dry Powder Inhaler ELLIPTA™ Compared With Usual ICS/LABA Maintenance Therapy Delivered by Dry Powder Inhaler in Subjects With Persistent Asthma
• Actual Study Start Date: Jul 9, 2015
• Actual Primary Completion Date: Jul 20, 2017
• Actual Study Completion Date: Jul 20, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fluticasone Furoate/Vilanterol Subjects will receive FF/VI 92 micrograms (mcg)/22 mcg or FF/VI 184 mcg/22 mcg as decided by the investigator QD via ELLIPTA DPI for 24 weeks.	Drug: Fluticasone Furoate; FF 92 mcg or 184 mcg blended with lactose administered once daily via ELLIPTA DPI; Drug: Vilanterol; Vilanterol 22 mcg blended with lactose and magnesium stearate administered once daily via ELLIPTA DPI
Active Comparator: FP/S OR BUD/F Subjects will receive FP/S (250 mcg/50 mcg or 500 mcg/50mcg) twice daily via DISKUS or BUD /F (200 mcg/6mcg or 400 mcg/12mcg one or two inhalations) twice daily via TURBUHALER DPI as decided by the investigator for 24 weeks.	Drug: Fluticasone propionate; FP 250 mcg or 500 mcg blended with lactose administered twice daily via DISKUS DPI; Drug: Salmeterol; Salmeterol 50 mcg blended with lactose administered twice daily via DISKUS DPI; Drug: Budesonide; Budesonide 200 mcg or 400 mcg blended with lactose administered twice daily via TURBUHALER DPI; Drug: Formoterol Fumarate; Formoterol Furoate 6 mcg or 12 mcg blended with lactose administered twice daily via TURBUHALER DPI

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Asthma Control Test (ACT) Total Score at Week 12 [Baseline and Week 12]

   The ACT is a validated self-completed questionnaire consisting of 5 questions that evaluate asthma control during the past 4 weeks on a 5-point categorical scale. Total scores are calculated from the sum of the scores from the 5 questions and can range from 5 to 25, with higher scores indicating better control. An ACT total score of 5 to 19 suggests that the participant's asthma is unlikely to be well controlled, whilst a score of 20 to 25 suggests that the participant's asthma is likely to be well controlled. Baseline value was the last assessment prior to randomization (Day 0). Change from Baseline was post-dose visit value minus the Baseline value. Least square mean change is presented.

Secondary Outcome Measures

1. Change From Baseline in ACT Total Score at Week 24 [Baseline and Week 24]

   The ACT is a validated self-completed questionnaire consisting of 5 questions that evaluate asthma control on a 5-point categorical scale. Total scores are calculated from the sum of the scores from the 5 questions and can range from 5 to 25, with higher scores indicating better control. An ACT total score of 5 to 19 suggests that the participant's asthma is unlikely to be well controlled, whilst a score of 20 to 25 suggests that the participant's asthma is likely to be well controlled. Baseline value was the last assessment prior to randomization (Day 0). Change from Baseline was post-dose visit value minus the Baseline value. Least square mean change is presented.

2. Percentage of Participants With Correct Use of Device, Defined as Not Making Any Critical or Non-critical Errors, at Week 12, and at Week 24 Independently of the Use at Week 12 [Week 12 and Week 24]

   Participants were asked to read the appropriate package insert for their prescribed inhaler and then the investigator (or suitably qualified designee) demonstrated the proper use of the inhaler. The participant was then asked to self-administer their first dose of study treatment under the supervision of the investigator and any critical and non-critical errors were recorded. Individual instruments for assessing correct inhaler use were provided for each of the three devices used in this study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Informed consent: Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and in this protocol.

• Gender and Age: Male or female subjects aged >=18 and <=75years of age at Screening visit.

Female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin [hCG] test), not lactating, and at least one of the following conditions applies:

Non-reproductive potential defined as: Pre-menopausal females with one of the following - Documented tubal ligation; Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion; Hysterectomy; Documented Bilateral Oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous follicle stimulating hormone [FSH] and estradiol levels consistent with menopause [refer to laboratory reference ranges for confirmatory levels]); Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.

Reproductive potential and agrees to follow one of the options listed below in the GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive Potential (FRP) requirements from 30 days prior to the first dose of study medication and until Week 24.

GSK Modified List of Highly Effective Methods for Avoiding Pregnancy in FRP:

This list does not apply to FRP with same sex partners, when this is their preferred and usual lifestyle or for subjects who are and will continue to be abstinent from penile-vaginal intercourse on a long term and persistent basis: Contraceptive subdermal implant that meets the Standard Operating Procedure (SOP) effectiveness criteria including a <1percent rate of failure per year, as stated in the product label; Intrauterine device or intrauterine system that meets the SOP effectiveness criteria including a <1 percent rate of failure per year, as stated in the product label; Oral Contraceptive, either combined or progestogen alone; Injectable progestogen; Contraceptive vaginal ring; Percutaneous contraceptive patches; Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject; Male condom combined with a vaginal spermicide (foam, gel, film, cream, or suppository); These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception.

• Type of subject: Subjects with documented physician's diagnosis of asthma >=1 year, unsatisfactorily controlled asthma (ACT <20 at Screening and Randomisation visit) treated by ICS alone and intended to be treated by ICS/LABA maintenance therapy; France Only: A subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a Social Security category.

• Current Asthma Therapy: All subjects must be prescribed maintenance therapy and receiving ICS alone without LABA for at least 4 weeks prior to Randomisation visit; Other background asthma medication such as anti-leukotrienes or theophylline is permitted as an alternative to ICS alone, if initiated at least 4 weeks prior to screening visit.

• Subject questionnaires Subjects must be able to complete the questionnaires themselves.

Exclusion Criteria:

• History of Life-threatening asthma: Defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures within the last 6 months before Screening and Randomisation visit.

• Subjects having a severe and unstable asthma, with ACT score < 15 at Visit 1 and at Visit 2, and/or a history of repeated severe exacerbations (3/year) and/or a severe exacerbation in the previous 6 weeks before Visit 1 and Visit 2.

• Chronic obstructive pulmonary disease (COPD) Respiratory Disease: A subject must not have current evidence or diagnosis of chronic obstructive pulmonary disease at Screening visit.

• Current or former cigarette smokers with a history of cigarette smoking of >=10 pack-years at screening [number of pack years = (number of cigarettes per day / 20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)].

• Other diseases/abnormalities: Subjects with historical or current evidence of uncontrolled or clinically significant disease at Screening and Randomisation visit. Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.

• Subjects with a history of adverse reaction including immediate or delayed hypersensitivity to any intranasal, inhaled, or systemic corticosteroid and LABA therapy and to components of the inhalation powder (e.g., lactose, magnesium stearate) at Screening and Randomisation visit. In addition, subjects with a history of severe milk protein allergy that, in the opinion of the Investigator, contraindicates the subject's participation will also be excluded.

• Investigational Medications: A subject must not have used any investigational drug within 30 days prior to Randomisation visit or within five half-lives (t½) of the prior investigational study (whichever is longer of the two), (if unsure discuss with the medical monitor prior to screening).

• Chronic user of systemic corticosteroids: A subject who, in the opinion of the Investigator, is considered to be a chronic user of systemic corticosteroids for respiratory or other indications (if unsure discuss with the medical monitor prior to screening) at Screening visit.

• Subjects treated by the monoclonal antibody omalizumab or mepolizumab at Visit 1. Treatment with omalizumab or mepolizumab is not allowed during the study.

• Subjects involved in other clinical trials at Screening visit.

• Affiliation with Investigator Site: Is an investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the aforementioned that is involved in this study.

• Subjects who plan to move away from the geographical area where the study is being conducted during the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Amiens		France	80090
2	GSK Investigational Site	Angers		France	49000
3	GSK Investigational Site	Avelin		France	59710
4	GSK Investigational Site	Bassussarry		France	64200
5	GSK Investigational Site	Beauzelle		France	31700
6	GSK Investigational Site	Bersee		France	59235
7	GSK Investigational Site	Beziers		France	34500
8	GSK Investigational Site	Biarritz		France	64200
9	GSK Investigational Site	Bourg Des Comptes		France	35890
10	GSK Investigational Site	Broglie		France	27270
11	GSK Investigational Site	Bruay-la-Buissière		France	62700
12	GSK Investigational Site	Bécon les Granits		France	49370
13	GSK Investigational Site	Caen		France	14000
14	GSK Investigational Site	Cannes Cedex		France	06614
15	GSK Investigational Site	Carbon-Blanc		France	33560
16	GSK Investigational Site	Chatellerault		France	86100
17	GSK Investigational Site	Colombey-les-Belles		France	54170
18	GSK Investigational Site	Coulounieix-Chamiers		France	24660
19	GSK Investigational Site	Cournonterral		France	34660
20	GSK Investigational Site	Dessenheim		France	68600
21	GSK Investigational Site	Dijon		France	21000
22	GSK Investigational Site	Dinard		France	35800
23	GSK Investigational Site	Donges		France	44480
24	GSK Investigational Site	Ermont cedex		France	95124
25	GSK Investigational Site	Fleville Devant Nancy		France	54710
26	GSK Investigational Site	Gemenos		France	13420
27	GSK Investigational Site	Gondreville		France	54840
28	GSK Investigational Site	Grenay		France	62160
29	GSK Investigational Site	Guesnain		France	59287
30	GSK Investigational Site	Hatten		France	67690
31	GSK Investigational Site	Hinx		France	40180
32	GSK Investigational Site	La Bouexiere		France	35340
33	GSK Investigational Site	La Fôret Sur Sèvres		France	79380
34	GSK Investigational Site	La Riche		France	37520
35	GSK Investigational Site	Lambersart		France	59130
36	GSK Investigational Site	Laval		France	53000
37	GSK Investigational Site	Le Blanc-Mesnil		France	93150
38	GSK Investigational Site	Limoges		France	87000
39	GSK Investigational Site	Marseille cedex 03		France	13331
40	GSK Investigational Site	Metz-Tessy		France	74370
41	GSK Investigational Site	Montauban cedex		France	82017
42	GSK Investigational Site	Montpellier Cedex 5		France	34295
43	GSK Investigational Site	Montpellier		France	34070
44	GSK Investigational Site	Murs-Erigne		France	49610
45	GSK Investigational Site	Nancy		France	54000
46	GSK Investigational Site	Nantes		France	44200
47	GSK Investigational Site	Nantes		France	44300
48	GSK Investigational Site	Narbonne		France	11100
49	GSK Investigational Site	Nice		France	06000
50	GSK Investigational Site	Obernai		France	67210
51	GSK Investigational Site	Paris		France	75020
52	GSK Investigational Site	Perpignan		France	66000
53	GSK Investigational Site	Rosiers-d'Egletons		France	19300
54	GSK Investigational Site	Rouen		France	76000
55	GSK Investigational Site	Royaumeix		France	54200
56	GSK Investigational Site	Saint Etienne		France	42100
57	GSK Investigational Site	Saint Ouen la Rouerie		France	35460
58	GSK Investigational Site	Saint-Etienne		France	42000
59	GSK Investigational Site	Scorbe Clairvaux		France	86140
60	GSK Investigational Site	Segré		France	49500
61	GSK Investigational Site	Soulac-sur-Mer		France	33780
62	GSK Investigational Site	Strasbourg		France	67000
63	GSK Investigational Site	Thouars		France	79100
64	GSK Investigational Site	Toulon		France	83000
65	GSK Investigational Site	Toulouse cedex 4		France	31077
66	GSK Investigational Site	Toulouse		France	31300
67	GSK Investigational Site	Toul		France	54200
68	GSK Investigational Site	Verzy		France	51380
69	GSK Investigational Site	Vieux Condé		France	59690
70	GSK Investigational Site	Villejuif		France	94800
71	GSK Investigational Site	Wattrelos		France	59150
72	GSK Investigational Site	Witry les Reims		France	51420
73	GSK Investigational Site	Muenchen	Bayern	Germany	80339
74	GSK Investigational Site	Muenchen	Bayern	Germany	81241
75	GSK Investigational Site	Wallerfing	Bayern	Germany	94574
76	GSK Investigational Site	Potsdam	Brandenburg	Germany	14469
77	GSK Investigational Site	Dortmund	Nordrhein-Westfalen	Germany	44263
78	GSK Investigational Site	Rheine	Nordrhein-Westfalen	Germany	48431
79	GSK Investigational Site	Teuchern	Sachsen-Anhalt	Germany	6682
80	GSK Investigational Site	Delitzsch	Sachsen	Germany	04509
81	GSK Investigational Site	Leipzg	Sachsen	Germany	04109
82	GSK Investigational Site	Leipzig	Sachsen	Germany	04103
83	GSK Investigational Site	Leipzig	Sachsen	Germany	04207
84	GSK Investigational Site	Leipzig	Sachsen	Germany	04275
85	GSK Investigational Site	Leipzig	Sachsen	Germany	04357
86	GSK Investigational Site	Geesthacht	Schleswig-Holstein	Germany	21502
87	GSK Investigational Site	Schmoelln	Thueringen	Germany	04626
88	GSK Investigational Site	Berlin		Germany	10119
89	GSK Investigational Site	Berlin		Germany	10717
90	GSK Investigational Site	Berlin		Germany	10787
91	GSK Investigational Site	Berlin		Germany	13156
92	GSK Investigational Site	Berlin		Germany	14059
93	GSK Investigational Site	Magdeburg		Germany	39120

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Apr 28, 2016
• Statistical Analysis Plan - Aug 21, 2017

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02446418
• Other Study ID Numbers: 116492
• First Posted: May 18, 2015
• Last Update Posted: Jan 14, 2019
• Last Verified: Jun 1, 2018

• Keywords provided by GlaxoSmithKline: dry powder inahler; vilanerol; efficacy; safety; fluticasone furoate; quality of life
• Additional relevant MeSH terms: Asthma; Fluticasone; Xhance; Budesonide; Formoterol Fumarate; Salmeterol Xinafoate

Study Results

Participant Flow

Recruitment Details	A total of 439 participants with persistent asthma were screened. The study was conducted at 63 centers in 2 countries: 43 in France and 20 in Germany from 09 July 2015 to 20 July 2017. Age value being reported for all participants is an approximate age accurate to within + or -1 year.
Pre-assignment Detail	A total of 439 participants were screened for this study and 423 participants were randomized to treatment. Three of the randomized participants did not receive study treatment and were not included in the Intent-To-Treat (ITT) population.

Arm/Group Title	Usual ICS/LABA	FF/VI
Arm/Group Description	Eligible participants received fixed combination inhaled corticosteroid (ICS)/long-acting beta2-agonist (LABA) (Fluticasone propionate [FP]/ Salmeterol [S] 250/50 micrograms [mcg] or 500/50 mcg, 1 inhalation twice daily; or Budesonide [BUD]/ Formoterol [F] 200/6 mcg or 400/12 mcg, 1 or 2 inhalations twice daily) for 24 weeks.	Eligible participants received Fluticasone Furoate (FF)/ Vilanterol (VI) 100 mcg/22 mcg or FF/VI 200 mcg/25 mcg 1 inhalation once daily for 24 weeks.
Period Title: Overall Study
STARTED	210	210
COMPLETED	192	194
NOT COMPLETED	18	16

Baseline Characteristics

Arm/Group Title	Usual ICS/LABA	FF/VI	Total
Arm/Group Description	Eligible participants received fixed combination ICS/LABA (FP/S 250/50 mcg or 500/50 mcg, 1 inhalation twice daily; or BUD/F 200/6 mcg or 400/12 mcg, 1 or 2 inhalations twice daily) for 24 weeks.	Eligible participants received Fluticasone FF/Vilanterol VI 100 mcg/22 mcg or FF/VI 200 mcg/25 mcg 1 inhalation once daily for 24 weeks.	Total of all reporting groups
Overall Participants	210	210	420
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	47.5 (14.99)	49.3 (14.67)	48.4 (14.84)
Sex: Female, Male (Count of Participants)
Female	124 59%	145 69%	269 64%
Male	86 41%	65 31%	151 36%
Race/Ethnicity, Customized (Count of Participants)
African American/African Heritage	3 1.4%	4 1.9%	7 1.7%
Asian - Central/South Asian Heritage	0 0%	1 0.5%	1 0.2%
Asian - East Asian Heritage	2 1%	0 0%	2 0.5%
Asian - South East Asian Heritage	0 0%	1 0.5%	1 0.2%
Native Hawaiian Or Other Pacific Islander	1 0.5%	1 0.5%	2 0.5%
White - Arabic/North African Heritage	8 3.8%	6 2.9%	14 3.3%
White - White/Caucasian/European Heritage	196 93.3%	196 93.3%	392 93.3%
Mixed White Race	0 0%	1 0.5%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Asthma Control Test (ACT) Total Score at Week 12
Description	The ACT is a validated self-completed questionnaire consisting of 5 questions that evaluate asthma control during the past 4 weeks on a 5-point categorical scale. Total scores are calculated from the sum of the scores from the 5 questions and can range from 5 to 25, with higher scores indicating better control. An ACT total score of 5 to 19 suggests that the participant's asthma is unlikely to be well controlled, whilst a score of 20 to 25 suggests that the participant's asthma is likely to be well controlled. Baseline value was the last assessment prior to randomization (Day 0). Change from Baseline was post-dose visit value minus the Baseline value. Least square mean change is presented.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Usual ICS/LABA	FF/VI
Arm/Group Description	Eligible participants received fixed combination ICS/LABA (FP/S 250/50 mcg or 500/50 mcg, 1 inhalation twice daily; or BUD/F 200/6 mcg or 400/12 mcg, 1 or 2 inhalations twice daily) for 24 weeks.	Eligible participants received Fluticasone FF/Vilanterol VI 100 mcg/22 mcg or FF/VI 200 mcg/25 mcg 1 inhalation once daily for 24 weeks.
Measure Participants	188	188
Least Squares Mean (Standard Error) [Scores on a Scale]	2.8 (0.26)	3.6 (0.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual ICS/LABA, FF/VI
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority of fixed combination FF/VI to usual ICS/LABA in inhalation powder was assessed assuming a non-inferiority margin of -1.5.
Statistical Test of Hypothesis	p-Value	0.033
	Comments
	Method	Mixed model repeated measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; 0.1 to 1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		The analysis method was an MMRM adjusted for randomized treatment, visit (Week 6 and Week 12), Baseline ACT total score, randomized treatment-by-visit interaction, Baseline ACT total score-by-visit interaction, gender, age, country and participant fitted as a random factor. The Restricted Maximum Likelihood (REML) estimation approach was used with a default covariance structure of unstructured.

2. Secondary Outcome

Title	Change From Baseline in ACT Total Score at Week 24
Description	The ACT is a validated self-completed questionnaire consisting of 5 questions that evaluate asthma control on a 5-point categorical scale. Total scores are calculated from the sum of the scores from the 5 questions and can range from 5 to 25, with higher scores indicating better control. An ACT total score of 5 to 19 suggests that the participant's asthma is unlikely to be well controlled, whilst a score of 20 to 25 suggests that the participant's asthma is likely to be well controlled. Baseline value was the last assessment prior to randomization (Day 0). Change from Baseline was post-dose visit value minus the Baseline value. Least square mean change is presented.
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	Usual ICS/LABA	FF/VI
Arm/Group Description	Eligible participants received fixed combination ICS/LABA (FP/S 250/50 mcg or 500/50 mcg, 1 inhalation twice daily; or BUD/F 200/6 mcg or 400/12 mcg, 1 or 2 inhalations twice daily) for 24 weeks.	Eligible participants received Fluticasone FF/Vilanterol VI 100 mcg/22 mcg or FF/VI 200 mcg/25 mcg 1 inhalation once daily for 24 weeks.
Measure Participants	184	180
Least Squares Mean (Standard Error) [Scores on a Scale]	3.6 (0.25)	4.0 (0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual ICS/LABA, FF/VI
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority of fixed combination FF/VI to usual ICS/LABA in inhalation powder was assessed assuming a non-inferiority margin of -1.5.
Statistical Test of Hypothesis	p-Value	0.224
	Comments
	Method	Mixed model repeated measures (MMRM)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.3 to 1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		The analysis method was an MMRM adjusted for randomized treatment, visit (Week 6, Week 12, Week 18 and Week 24), Baseline ACT total score, randomized treatment-by-visit interaction, Baseline ACT total score-by visit interaction, gender, age, country and participant fitted as a random factor. The REML estimation approach was used with a default covariance structure of unstructured.

3. Secondary Outcome

Title	Percentage of Participants With Correct Use of Device, Defined as Not Making Any Critical or Non-critical Errors, at Week 12, and at Week 24 Independently of the Use at Week 12
Description	Participants were asked to read the appropriate package insert for their prescribed inhaler and then the investigator (or suitably qualified designee) demonstrated the proper use of the inhaler. The participant was then asked to self-administer their first dose of study treatment under the supervision of the investigator and any critical and non-critical errors were recorded. Individual instruments for assessing correct inhaler use were provided for each of the three devices used in this study.
Time Frame	Week 12 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	Usual ICS/LABA	FF/VI
Arm/Group Description	Eligible participants received fixed combination ICS/LABA (FP/S 250/50 mcg or 500/50 mcg, 1 inhalation twice daily; or BUD/F 200/6 mcg or 400/12 mcg, 1 or 2 inhalations twice daily) for 24 weeks.	Eligible participants received Fluticasone FF/Vilanterol VI 100 mcg/22 mcg or FF/VI 200 mcg/25 mcg 1 inhalation once daily for 24 weeks.
Measure Participants	210	210
Week 12; n= 195, 197	93 44.3%	94 44.8%
Week 24; n= 191, 192	96 45.7%	97 46.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual ICS/LABA, FF/VI
	Comments	Week 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.820
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Adjusted Odds Ratio
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95%; 0.47 to 2.62
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		The analysis method was logistic regression adjusted for randomized treatment, correct use of inhaler device at Baseline, gender, age and country.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Usual ICS/LABA, FF/VI
	Comments	Week 24
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.566
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Adjusted Odds Ratio
	Estimated Value	1.41
	Confidence Interval	(2-Sided) 95%; 0.43 to 4.60
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		The analysis method was logistic regression adjusted for randomized treatment, correct use of inhaler device at Baseline, gender, age and country.

Adverse Events

Time Frame	On-treatment serious adverse events (SAEs) and non-serious adverse drug reactions were collected from start of study treatment up to Week 24
Adverse Event Reporting Description	On-treatment SAEs and non-serious adverse drug reactions were collected for the Safety Population comprised of all enrolled participants who received at least one dose of study medication (either FF/VI or usual ICS/LABA) and considered as-treated.
Arm/Group Title	Usual ICS/LABA		FF/VI
Arm/Group Description	Eligible participants received fixed combination ICS/LABA (FP/S 250/50 mcg or 500/50 mcg, 1 inhalation twice daily; or BUD/F 200/6 mcg or 400/12 mcg, 1 or 2 inhalations twice daily) for 24 weeks.		Eligible participants received Fluticasone FF/Vilanterol VI 100 mcg/22 mcg or FF/VI 200 mcg/25 mcg 1 inhalation once daily for 24 weeks.
All Cause Mortality
	Usual ICS/LABA		FF/VI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/210 (0%)		0/209 (0%)
Serious Adverse Events
	Usual ICS/LABA		FF/VI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/210 (1.9%)		3/209 (1.4%)
Gastrointestinal disorders
Abdominal pain	1/210 (0.5%)	1	0/209 (0%)	0
Infections and infestations
Chronic sinusitis	1/210 (0.5%)	1	0/209 (0%)	0
Erysipelas	1/210 (0.5%)	1	0/209 (0%)	0
Labyrinthitis	0/210 (0%)	0	1/209 (0.5%)	1
Ovarian abscess	0/210 (0%)	0	1/209 (0.5%)	1
Nervous system disorders
Epilepsy	1/210 (0.5%)	1	0/209 (0%)	0
Reproductive system and breast disorders
Adnexa uteri pain	0/210 (0%)	0	1/209 (0.5%)	1
Skin and subcutaneous tissue disorders
Skin ulcer	1/210 (0.5%)	1	0/209 (0%)	0
Vascular disorders
Varicose vein ruptured	0/210 (0%)	0	1/209 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Usual ICS/LABA		FF/VI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/210 (0%)		0/209 (0%)

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.