An Effectiveness Study Comparing Fluticasone Furoate (FF, GW685698)/Vilanterol (VI, GW642444) With Standard Treatment in Asthma

• ClinicalTrials.gov Identifier: NCT01706198
• Recruitment Status: Completed
• First Posted: October 15, 2012
• Results First Posted: January 24, 2019
• Last Update Posted: January 24, 2019
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Asthma
• Interventions: Drug: fluticasone furoate + vilanterol; Drug: inhaled corticosteroid with or without a long acting beta2-agonist
• Enrollment: 4233

Participant Flow

Recruitment Details	This was a multi-center, randomized, open label study to evaluate the effectiveness of fluticasone furoate (FF)/vilanterol (VI) Inhalation Powder (FF 100 micrograms [mcg]/VI 25 mcg or FF 200 mcg/VI 25 mcg) compared with usual asthma maintenance therapy in participants with asthma in a localized geographical region of United Kingdom.
Pre-assignment Details	A total of 4725 participants were screened of which 4233 participants were randomized to either initiate with FF/VI or continue their usual asthma maintenance therapy in a ratio of 1:1. The total duration of study was approximately 12 months (52 weeks).

Arm/Group Title	Usual Care	FF/VI
Arm/Group Description	Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Period Title: Overall Study
Started	2119	2114
Completed	1946	1920
Not Completed	173	194
Reason Not Completed
Adverse Event	12	15
Protocol Violation	7	5
Other: Subject reached stopping criteria	11	13
Lost to Follow-up	97	93
Physician Decision	23	37
Withdrawal by Subject	23	31

Baseline Characteristics

Arm/Group Title		Usual Care	FF/VI	Total
Arm/Group Description		Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.	Total of all reporting groups
Overall Number of Baseline Participants		2119	2114	4233
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	2119 participants	2114 participants	4233 participants
		49.7 (16.69)	49.9 (16.05)	49.8 (16.37)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	2119 participants	2114 participants	4233 participants
	Female	1241 58.6%	1257 59.5%	2498 59.0%
	Male	878 41.4%	857 40.5%	1735 41.0%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Count of Participants	Number Analyzed	2119 participants	2114 participants	4233 participants
African American/African Heritage		25	40	65
Asian - Central/South Asian Heritage		35	46	81
Asian - East Asian Heritage		4	9	13
Asian - Japanese Heritage		2	0	2
Asian - South East Asian Heritage		9	18	27
Native Hawaiian or Other Pacific Islander		1	1	2
White - Arabic/North African Heritage		6	5	11
White - White/Caucasian/European Heritage		2002	1971	3973
Mixed race		33	23	56
Unknown		2	1	3

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Have Either an Asthma Control Test (ACT) Total Score of >=20 or an Increase From Baseline of >=3 in ACT Total Score at Week 24.
Description	The ACT is a validated self-administered questionnaire utilizing 5 questions to assess asthma control during the past 4 weeks on a 5-point categorical scale (1 to 5). By answering all 5 questions, participants with asthma obtained an ACT score ranging between 5 and 25. Higher scores indicated better control of asthma. An ACT score of <=15 showed poorly controlled asthma; 16 to 19 showed partly controlled asthma and >=20 showed well controlled asthma. The total score was calculated as the sum of the scores from all 5 questions. The primary efficacy analysis (PEA) Population is defined as all Intent-to-Treat (ITT) participants (that is, all participants who were randomized and received at least one prescription of study medication) who have an ACT total score of <20 at Baseline (Day 0). The percentage of responders that is participants with an ACT total score >=20 or an increase from Baseline of >=3 has been presented
Time Frame	Baseline (Day 0) and Week 24

Outcome Measure Data

Analysis Population Description

PEA Population. Only participants with non-missing ACT score were analyzed.

Arm/Group Title	Usual Care	FF/VI
Arm/Group Description:	Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed	1399	1373
Measure Type: Number; Unit of Measure: Percentage of participants
	56	71

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The analysis method was logistic regression adjusted for randomized treatment, asthma maintenance therapy (AMT) at Baseline per randomization stratification, Baseline ACT total score, Baseline ACT total score squared, gender and age.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Adjusted Odds Ratio
	Estimated Value	2.00
	Confidence Interval	(2-Sided) 95%; 1.70 to 2.34
	Estimation Comments	Adjusted odds ratio comparing FF/VI with Usual Care has been presented.

2. Secondary Outcome

Title	Percentage of Participants Who Have Either an ACT Total Score of >=20 or an Increase From Baseline of >=3 in ACT Total Score at Weeks 12, 40 and 52.
Description	The ACT is a validated self-administered questionnaire utilizing 5 questions to assess asthma control during the past 4 weeks on a 5-point categorical scale (1 to 5). By answering all 5 questions, participants with asthma obtained an ACT score ranging between 5 and 25. Higher scores indicated better control of asthma. An ACT score of <=15 showed poorly controlled asthma; 16 to 19 showed partly controlled asthma and >=20 showed well controlled asthma. The total score was calculated as the sum of the scores from all 5 questions. ITT Population comprised of all participants who were randomized and received at least one prescription of study medication. The percentage of responders that is participants with an ACT total score >=20 or an increase from Baseline of >=3 has been presented. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
Time Frame	Baseline (Day 0) and Weeks 12, 40 and 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title		Usual Care	FF/VI
Arm/Group Description:		Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed		2119	2114
Measure Type: Number; Unit of Measure: Percentage of participants
Week 12, n=2032, 2009	Number Analyzed	2032 participants	2009 participants
		62	75
Week 40, n=1938, 1904	Number Analyzed	1938 participants	1904 participants
		60	71
Week 52, n=1922, 1896	Number Analyzed	1922 participants	1896 participants
		58	70

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Logistic regression adjusted for randomized treatment, AMT at Baseline per randomization stratification, Baseline ACT total score, Baseline ACT total score squared, gender and age.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Adjusted Odds Ratio
	Estimated Value	1.92
	Confidence Interval	(2-Sided) 95%; 1.67 to 2.20
	Estimation Comments	Adjusted odds ratio comparing FF/VI with Usual Care for Week 12 has been presented.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Logistic regression adjusted for randomized treatment, AMT at Baseline per randomization stratification, Baseline ACT total score, Baseline ACT total score squared, gender and age.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Adjusted Odds Ratio
	Estimated Value	1.66
	Confidence Interval	(2-Sided) 95%; 1.45 to 1.91
	Estimation Comments	Adjusted odds ratio comparing FF/VI with Usual Care for Week 40 has been presented.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Logistic regression adjusted for randomized treatment, AMT at Baseline per randomization stratification, Baseline ACT total score, Baseline ACT total score squared, gender and age.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Adjusted Odds Ratio
	Estimated Value	1.76
	Confidence Interval	(2-Sided) 95%; 1.54 to 2.02
	Estimation Comments	Adjusted odds ratio comparing FF/VI with Usual Care for Week 52 has been presented.

3. Secondary Outcome

Title	Percentage of Participants With Asthma Control (ACT Total Score >=20) at Weeks 12, 24, 40 and 52.
Description	The ACT is a validated self-administered questionnaire utilizing 5 questions to assess asthma control during the past 4 weeks on a 5-point categorical scale (1 to 5). By answering all 5 questions, participants with asthma obtained an ACT score ranging between 5 and 25. Higher scores indicated better control of asthma. An ACT score of <=15 showed poorly controlled asthma; 16 to 19 showed partly controlled asthma and >=20 showed well controlled asthma. The total score was calculated as the sum of the scores from all 5 questions. The percentage of participants with an ACT total score >=20 has been presented. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
Time Frame	Weeks 12, 24, 40 and 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title		Usual Care	FF/VI
Arm/Group Description:		Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed		2119	2114
Measure Type: Number; Unit of Measure: Percentage of participants
Week 12, n=2032, 2009	Number Analyzed	2032 participants	2009 participants
		46	61
Week 24, n=1957, 1936	Number Analyzed	1957 participants	1936 participants
		46	60
Week 40, n=1938, 1904	Number Analyzed	1938 participants	1904 participants
		45	58
Week 52, n=1922, 1896	Number Analyzed	1922 participants	1896 participants
		44	58

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The analysis method was logistic regression adjusted for randomized treatment, AMT at Baseline per randomization stratification, Baseline ACT total score, gender and age.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Adjusted Odds Ratio
	Estimated Value	2.09
	Confidence Interval	(2-Sided) 95%; 1.82 to 2.40
	Estimation Comments	Adjusted odds ratio comparing FF/VI with Usual Care at Week 12 has been presented.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The analysis method was logistic regression adjusted for randomized treatment, AMT at Baseline per randomization stratification, Baseline ACT total score, gender and age.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Adjusted Odds Ratio
	Estimated Value	1.96
	Confidence Interval	(2-Sided) 95%; 1.70 to 2.25
	Estimation Comments	Adjusted odds ratio comparing FF/VI with Usual Care at Week 24 has been presented.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The analysis method was logistic regression adjusted for randomized treatment, AMT at Baseline per randomization stratification, Baseline ACT total score, gender and age.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Adjusted Odds Ratio
	Estimated Value	1.79
	Confidence Interval	(2-Sided) 95%; 1.56 to 2.06
	Estimation Comments	Adjusted odds ratio comparing FF/VI with Usual Care at Week 40 has been presented.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The analysis method was logistic regression adjusted for randomized treatment, AMT at Baseline per randomization stratification, Baseline ACT total score, gender and age.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Adjusted Odds Ratio
	Estimated Value	1.95
	Confidence Interval	(2-Sided) 95%; 1.69 to 2.24
	Estimation Comments	Adjusted odds ratio comparing FF/VI with Usual Care at Week 52 has been presented.

4. Secondary Outcome

Title	Percentage of Participants Who Have an Increase From Baseline of >=3 in ACT Total Score at Weeks 12, 24, 40 and 52.
Description	The ACT is a validated self-administered questionnaire utilizing 5 questions to assess asthma control during the past 4 weeks on a 5-point categorical scale (1 to 5). By answering all 5 questions, participants with asthma obtained an ACT score ranging between 5 and 25. Higher scores indicated better control of asthma. An ACT score of <=15 showed poorly controlled asthma; 16 to 19 showed partly controlled asthma and >=20 showed well controlled asthma. The total score was calculated as the sum of the scores from all 5 questions. The percentage of participants with an increase in ACT total score >=3 from Baseline has been presented. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
Time Frame	Baseline (Day 0) and Weeks 12, 24, 40 and 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title		Usual Care	FF/VI
Arm/Group Description:		Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed		2119	2114
Measure Type: Number; Unit of Measure: Percentage of participants
Week 12, n=2032, 2009	Number Analyzed	2032 participants	2009 participants
		39	55
Week 24, n=1957, 1936	Number Analyzed	1957 participants	1936 participants
		40	54
Week 40, n=1938, 1904	Number Analyzed	1938 participants	1904 participants
		42	53
Week 52, n=1922, 1896	Number Analyzed	1922 participants	1896 participants
		37	50

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The analysis method was logistic regression adjusted for randomized treatment, AMT at Baseline per randomization stratification, Baseline ACT total score, gender and age.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Adjusted Odds Ratio
	Estimated Value	2.28
	Confidence Interval	(2-Sided) 95%; 1.98 to 2.62
	Estimation Comments	Adjusted odds ratio comparing FF/VI with Usual Care at Week 12 has been presented.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The analysis method was logistic regression adjusted for randomized treatment, AMT at Baseline per randomization stratification, Baseline ACT total score, gender and age.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Adjusted Odds Ratio
	Estimated Value	2.09
	Confidence Interval	(2-Sided) 95%; 1.81 to 2.41
	Estimation Comments	Adjusted odds ratio comparing FF/VI with Usual Care at Week 24 has been presented.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The analysis method was logistic regression adjusted for randomized treatment, AMT at Baseline per randomization stratification, Baseline ACT total score, gender and age.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Adjusted Odds Ratio
	Estimated Value	1.76
	Confidence Interval	(2-Sided) 95%; 1.53 to 2.02
	Estimation Comments	Adjusted odds ratio comparing FF/VI with Usual Care at Week 40 has been presented.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The analysis method was logistic regression adjusted for randomized treatment, AMT at Baseline per randomization stratification, Baseline ACT total score, gender and age.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Adjusted Odds Ratio
	Estimated Value	1.91
	Confidence Interval	(2-Sided) 95%; 1.66 to 2.21
	Estimation Comments	Adjusted odds ratio comparing FF/VI with Usual Care at Week 52 has been presented.

5. Secondary Outcome

Title	Mean Change From Baseline in ACT Total Score at Weeks 12, 24, 40 and 52.
Description	The ACT is a validated self-administered questionnaire utilizing 5 questions to assess asthma control during the past 4 weeks on a 5-point categorical scale (1 to 5). By answering all 5 questions, participants with asthma obtained an ACT score ranging between 5 and 25. Higher scores indicated better control of asthma. An ACT score of <=15 showed poorly controlled asthma; 16 to 19 showed partly controlled asthma and >=20 showed well controlled asthma. The total score was calculated as the sum of the scores from all 5 questions. Baseline value is the value at Visit 2 (Day 0) assessment. Change from Baseline is the value at post-dose visit minus Baseline. The least square mean change in ACT scores has been presented. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
Time Frame	Baseline (Day 0) and Weeks 12, 24, 40 and 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title		Usual Care	FF/VI
Arm/Group Description:		Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed		2119	2114
Least Squares Mean (Standard Error); Unit of Measure: Scores on ACT scale
Week 12, n=2032, 2009	Number Analyzed	2032 participants	2009 participants
		1.77 (0.087)	3.31 (0.087)
Week 24, n=1957, 1936	Number Analyzed	1957 participants	1936 participants
		1.70 (0.093)	3.20 (0.094)
Week 40, n=1938, 1904	Number Analyzed	1938 participants	1904 participants
		1.63 (0.096)	3.00 (0.097)
Week 52, n=1922, 1896	Number Analyzed	1922 participants	1896 participants
		1.49 (0.094)	2.99 (0.095)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	MMRM adjusted for randomized treatment, AMT at Baseline per randomization stratification, Baseline ACT total score, randomized treatment-by-Baseline ACT total score interaction, gender, age, visit and randomized treatment by visit interaction.
	Method	Mixed Model Repeated Measures (MMRM)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.54
	Confidence Interval	(2-Sided) 95%; 1.30 to 1.77
	Estimation Comments	Treatment difference of FF/VI versus Usual Care at Week 12 has been presented.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	MMRM adjusted for randomized treatment, AMT at Baseline per randomization stratification, Baseline ACT total score, randomized treatment-by-Baseline ACT total score interaction, gender, age, visit and randomized treatment by visit interaction.
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.50
	Confidence Interval	(2-Sided) 95%; 1.25 to 1.76
	Estimation Comments	Treatment difference of FF/VI versus Usual Care at Week 24 has been presented.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	MMRM adjusted for randomized treatment, AMT at Baseline per randomization stratification, Baseline ACT total score, randomized treatment-by-Baseline ACT total score interaction, gender, age, visit and randomized treatment by visit interaction.
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.37
	Confidence Interval	(2-Sided) 95%; 1.11 to 1.63
	Estimation Comments	Treatment difference of FF/VI versus Usual Care at Week 40 has been presented.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	MMRM adjusted for randomized treatment, AMT at Baseline per randomization stratification, Baseline ACT total score, randomized treatment-by-Baseline ACT total score interaction, gender, age, visit and randomized treatment by visit interaction.
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.50
	Confidence Interval	(2-Sided) 95%; 1.24 to 1.76
	Estimation Comments	Treatment difference of FF/VI versus Usual Care at Week 52 has been presented.

6. Secondary Outcome

Title	Percentage of Participants in Each ACT Total Score Category (>=20, 16 to 19, <=15) at Weeks 12, 24, 40 and 52.
Description	The ACT is a validated self-administered questionnaire utilizing 5 questions to assess asthma control during the past 4 weeks on a 5-point categorical scale (1 to 5). By answering all 5 questions, participants with asthma obtained an ACT score ranging between 5 and 25. Higher scores indicated better control of asthma. An ACT score of <=15 showed poorly controlled asthma; 16 to 19 showed partly controlled asthma and >=20 showed well controlled asthma. The total score was calculated as the sum of the scores from all 5 questions. The percentage of participants under each ACT total score category that is >=20, 16 to 19 and <=15 has been presented. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).
Time Frame	Weeks 12, 24, 40 and 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title		Usual Care	FF/VI
Arm/Group Description:		Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed		2119	2114
Measure Type: Number; Unit of Measure: Percentage of participants
>=20, Week 12, n=2032, 2009	Number Analyzed	2032 participants	2009 participants
		46	61
16 to 19, Week 12, n=2032, 2009	Number Analyzed	2032 participants	2009 participants
		26	20
<=15, Week 12, n=2032, 2009	Number Analyzed	2032 participants	2009 participants
		28	18
>=20, Week 24, n=1957, 1936	Number Analyzed	1957 participants	1936 participants
		46	60
16 to 19, Week 24, n=1957, 1936	Number Analyzed	1957 participants	1936 participants
		25	20
<=15, Week 24, n=1957, 1936	Number Analyzed	1957 participants	1936 participants
		29	20
>=20, Week 40, n=1938, 1904	Number Analyzed	1938 participants	1904 participants
		45	58
16 to 19, Week 40, n=1938, 1904	Number Analyzed	1938 participants	1904 participants
		24	21
<=15, Week 40, n=1938, 1904	Number Analyzed	1938 participants	1904 participants
		31	21
>=20, Week 52, n=1922, 1896	Number Analyzed	1922 participants	1896 participants
		44	58
16 to 19, Week 52, n=1922, 1896	Number Analyzed	1922 participants	1896 participants
		26	20
<=15, Week 52, n=1922, 1896	Number Analyzed	1922 participants	1896 participants
		30	21

7. Secondary Outcome

Title	Annual Rate of Asthma-related Secondary Care Contacts
Description	All contacts are defined as any encounter the participant may have with a doctor, nurse or other healthcare professionals working as part of the National Health Service (NHS) as identified in the electronic medical records (EMR). Contacts were defined to be asthma-related if the most prominent signs and symptoms that the participant presented were a direct result of the participant's asthma. An asthma-related secondary care contact is defined as an inpatient admission or a specialist outpatient visit or an accident and emergency (A&E) contact. A participant with an A&E contact and subsequent inpatient admission was considered to have had two healthcare contacts. The least square mean annual rate of all asthma-related secondary care contacts along with 95% confidence interval has been presented.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Usual Care	FF/VI
Arm/Group Description:	Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed	2119	2114
Least Squares Mean (95% Confidence Interval); Unit of Measure: Contacts per participant per year
	0.30; (0.25 to 0.34)	0.30; (0.26 to 0.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.786
	Comments	GLM assuming negative binomial distribution (NBD) adjusted for randomized treatment, asthma maintenance therapy at Baseline per randomization stratification, ACT total score at Baseline per randomization stratification, gender and age
	Method	Generalized Linear Model (GLM)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.28
	Estimation Comments	Ratio comparing FF/VI with Usual Care has been presented.

8. Secondary Outcome

Title	Annual Rate of Asthma-related Primary Care Contacts
Description	All contacts are defined as any encounter the participant may have with a doctor, nurse or other healthcare professionals working as part of the NHS as identified in the EMR. Contacts were defined to be asthma-related if the most prominent signs and symptoms that the participant presented were a direct result of the participant's asthma. Asthma-related primary care contacts is defined as the sum of primary care contacts on a given calendar date with either a nurse, General Practitioner or other healthcare professional that can be considered as asthma-related as per Read codes. The least square mean annual rate of all asthma-related primary care contacts along with 95% confidence interval has been presented.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Usual Care	FF/VI
Arm/Group Description:	Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed	2119	2114
Least Squares Mean (95% Confidence Interval); Unit of Measure: Contacts per participant per year
	1.42; (1.36 to 1.47)	1.45; (1.39 to 1.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.461
	Comments	GLM assuming NBD adjusted for randomized treatment, asthma maintenance therapy at Baseline per randomization stratification, ACT total score at Baseline per randomization stratification, gender and age
	Method	Generalized Linear Model (GLM)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.97 to 1.08
	Estimation Comments	Ratio comparing FF/VI with Usual Care has been presented.

9. Secondary Outcome

Title	Number of Participants With Time to First Asthma-related Primary Care Contact
Description	Asthma-related primary care contact is defined as the sum of primary care contacts on a given calendar date with either a nurse, General Practitioner or other healthcare professional that can be considered as asthma-related as per Read codes. Time to first asthma-related primary care contact was measured from the date of randomization (that is, study treatment start date) to the date of first asthma-related primary care contact, or study treatment stop date for participants who completed the study without any asthma-related primary care contacts (censored). Analyses of time to first asthma-related primary care contact was censored at Day 364. The number of participants at risk at Weeks 0, 13, 26, 39 and 52 has been presented. Kaplan Meier method of analysis was used. Study related primary care contacts (that is, contacts scheduled solely due to the participant taking part in clinical trial) were excluded from this analysis.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Usual Care	FF/VI
Arm/Group Description:	Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed	2119	2114
Measure Type: Number; Unit of Measure: Participants
Week 0	2119	2114
Week 13	1621	1599
Week 26	1208	1214
Week 39	907	932
Week 52	479	488

10. Secondary Outcome

Title	Annual Rate of All On-treatment Secondary Care Contacts
Description	A secondary care contact is defined as an inpatient admission or a specialist outpatient visit or an A&E contact. A participant with an A&E contact and subsequent inpatient admission was considered to have had two healthcare contacts. The inpatient admissions recorded at two hospitals on the same day, were counted as a single (inpatient admission) secondary care contact. In the situation where inpatient admission periods overlapped (example, a new inpatient admission was recorded within the dates of an existing inpatient admission period), it was counted as a single (inpatient admission) healthcare contact with start date defined as the earliest inpatient admission date for either of the overlapping admissions and end date defined as the latest discharge date for either of the overlapping admissions. The least square mean annual rate of all on-treatment secondary care contacts along with 95% confidence interval has been summarized.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Usual Care	FF/VI
Arm/Group Description:	Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed	2119	2114
Least Squares Mean (95% Confidence Interval); Unit of Measure: Contacts per participant per year
	5.23; (4.91 to 5.57)	5.17; (4.86 to 5.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.822
	Comments	GLM assuming NBD adjusted for randomized treatment, asthma maintenance therapy at Baseline per randomization stratification, ACT total score at Baseline per randomization stratification, gender and age
	Method	Generalized Linear Model (GLM)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.91 to 1.08
	Estimation Comments	Ratio comparing FF/VI with Usual Care has been presented.

11. Secondary Outcome

Title	Annual Rate of All On-treatment Primary Care Contacts
Description	All contacts are defined as any encounter the participant may have with a doctor, nurse or other healthcare professionals working as part of the NHS as identified in the EMR. Total primary care contacts is defined as the sum of primary care contacts on a given calendar date with either a nurse, General Practitioner or other healthcare professional. The least square mean annual rate of all on-treatment primary care contacts along with 95% confidence interval has been presented.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Usual Care	FF/VI
Arm/Group Description:	Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed	2119	2114
Least Squares Mean (95% Confidence Interval); Unit of Measure: Contacts per participant per year
	10.61; (10.26 to 10.98)	11.64; (11.25 to 12.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	GLM assuming NBD adjusted for randomized treatment, asthma maintenance therapy at Baseline per randomization stratification, ACT total score at Baseline per randomization stratification, gender and age
	Method	Generalized Linear Model (GLM)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95%; 1.05 to 1.15
	Estimation Comments	Ratio comparing FF/VI with Usual Care has been presented.

12. Secondary Outcome

Title	Number of Participants With Time to First Primary Care Contact
Description	Time to first primary care contact is measured from the date of randomization (that is, study treatment start date) to the date of first primary care contact, or study treatment stop date for participants who completed the study without any primary care contacts (censored). Analyses of time to first primary care contact will be censored at Day 364. The number of participants at risk at Weeks 0, 13, 26, 39 and 52 has been presented. Kaplan Meier method of analysis was used. Study related primary care contacts (that is, contacts scheduled solely due to the participant taking part in clinical trial) were excluded from this analysis.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Usual Care	FF/VI
Arm/Group Description:	Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed	2119	2114
Measure Type: Number; Unit of Measure: Participants
Week 0	2119	2114
Week 13	513	483
Week 26	245	242
Week 39	160	178
Week 52	79	96

13. Secondary Outcome

Title	Mean Annual Rate of Severe Asthma Exacerbations
Description	A severe asthma exacerbation is defined as deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) or antibiotics, and inpatient hospitalization, or emergency department visit due to asthma that required systemic corticosteroids or antibiotics. Least square mean for annual rate of severe asthma exacerbation along with 95% confidence interval has been presented.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Usual Care	FF/VI
Arm/Group Description:	Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed	2119	2114
Least Squares Mean (95% Confidence Interval); Unit of Measure: Exacerbations per participant per year
	0.41; (0.38 to 0.44)	0.40; (0.37 to 0.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.697
	Comments	GLM assuming NBD adjusted for randomized treatment; asthma maintenance therapy and ACT total score at Baseline per randomization stratification; number of severe asthma exacerbations in previous year prior to randomization categorized; gender & age
	Method	Generalized Linear Model (GLM)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.09
	Estimation Comments	Ratio comparing FF/VI with Usual Care has been presented.

14. Secondary Outcome

Title	Time to First Severe Asthma Exacerbation.
Description	A severe asthma exacerbation is defined as deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) or antibiotics, and inpatient hospitalization, or emergency department visit due to asthma that required systemic corticosteroids or antibiotics. The date of a severe asthma exacerbation was defined as the exacerbation onset date. Participants who completed the study without a severe asthma exacerbation were censored. Time to first severe asthma exacerbation was measured from the date of randomization (that is, study treatment start date) to the onset date of first severe asthma exacerbation, or study treatment stop date for participants who completed the study without any severe asthma exacerbations (censored). Analyses of time to first severe asthma exacerbation was censored at Day 364. The number of participants with severe asthma exacerbation has been presented.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Usual Care	FF/VI
Arm/Group Description:	Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed	2119	2114
Measure Type: Number; Unit of Measure: Participants
	654	634

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.504
	Comments	Cox proportional hazards model with randomized treatment, asthma maintenance therapy at Baseline per randomization stratification, ACT total score at Baseline per randomization stratification, gender and age as covariates
	Method	Cox proportional hazards model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.07
	Estimation Comments	A hazard ratio <1 indicated a lower risk with FF/VI compared with Usual Care

15. Secondary Outcome

Title	Mean Number of Salbutamol Inhalers Prescribed for Each Participant Over the 12 Month Treatment Period.
Description	Salbutamol was prescribed as a rescue medication to be used as and when necessary throughout the study. The number of salbutamol inhalers used by each participant during the study was calculated based on the total number of inhalers (adjusted to an equivalence of 200 metered actuations) prescribed. Number of salbutamol inhalers prescribed during the study was derived taking the participants time on study medication into account so it corresponds to 12 months on treatment. The least square mean number of salbutamol inhalers prescribed per participant during the study has been presented. Only participants exposed to study drug for at least 30 days were included in the analysis.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Usual Care	FF/VI
Arm/Group Description:	Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed	2116	2108
Least Squares Mean (Standard Error); Unit of Measure: Mean number of inhalers per participant
	8.0 (0.11)	7.2 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	ANCOVA adjusted for randomized treatment, asthma maintenance therapy at Baseline per randomization stratification, ACT total score at Baseline per randomization stratification, gender,age & number of salbutamol inhalers in year prior to randomization
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.1 to -0.5
	Estimation Comments	Difference of FF/VI versus Usual Care has been presented.

16. Secondary Outcome

Title	Time to Modification of Initial Therapy
Description	Initial therapy is defined as the treatment that the participant was prescribed at randomization. Modification of initial therapy included any change in brand, dose or frequency of inhaler, that is, stepping up in class, dose or frequency, stepping down in class, dose or frequency, switching to another brand of inhaler, switching treatment arm or withdrawal from the study. Time to modification of initial therapy was measured from the date of randomization (that is, exposure start date) to the date of modification of initial therapy or date of treatment termination for participants who completed the study without modifiying initial therapy (censored). The number of participants with modification of initial therapy has been presented.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Usual Care	FF/VI
Arm/Group Description:	Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed	2119	2114
Measure Type: Number; Unit of Measure: Participants
	488	563

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Cox proportional hazards model with randomized treatment, asthma maintenance therapy at Baseline per randomization stratification, ACT total score at Baseline per randomization stratification, gender and age as covariates
	Method	Cox proportional hazards model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.23
	Confidence Interval	(2-Sided) 95%; 1.09 to 1.38
	Estimation Comments	Hazard ratio for FF/VI versus Usual Care has been presented

17. Secondary Outcome

Title	Percentage of Participants Who Have an Increase From Baseline of >=0.5 in Standardized Asthma Quality of Life Questionnaire [AQLQ(S)] Total Score at Week 52.
Description	The AQLQ(S) contained 32 items under the following four domains: activity limitation (11 items), symptoms (12 items), emotional function (5 items) and environmental stimuli (4 items). The response format consisted of a seven-point scale where a value of 1 indicated "total impairment" and a value of 7 indicated "no impairment". The total AQLQ(S) score is the mean of all 32 items in the questionnaire and each individual domain score was calculated as the mean of the items within that domain. Hence, the total and domain scores were each defined on a range from 1 to 7 with higher scores indicating a higher quality of life. Baseline value is the value at Day 0 assessment. Change from Baseline is post dose visit value minus Baseline. The percentage of responders that is, participants with an increase from Baseline of >=0.5 in AQLQ(S) total score has been presented. Only those participants available at the specified time point was analyzed.
Time Frame	Baseline (Day 0) and Week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Usual Care	FF/VI
Arm/Group Description:	Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed	1922	1896
Measure Type: Number; Unit of Measure: Percentage of participants
	43	55

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Logistic regression adjusted for randomized treatment, asthma maintenance therapy at Baseline per randomization stratification, ACT total score at Baseline per randomization stratification, gender, age and Baseline score.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Adjusted Odds Ratio
	Estimated Value	1.79
	Confidence Interval	(2-Sided) 95%; 1.55 to 2.06
	Estimation Comments	Adjusted odds ratio of FF/VI with Usual Care has been presented.

18. Secondary Outcome

Title	Percentage of Participants Who Have an Increase From Baseline of >=0.5 in AQLQ(S) Environmental Stimuli Domain Score at Week 52.
Description	The AQLQ(S) contained 32 items under the following four domains: activity limitation (11 items), symptoms (12 items), emotional function (5 items) and environmental stimuli (4 items). The response format consisted of a seven-point scale where a value of 1 indicated "total impairment" and a value of 7 indicated "no impairment". The total environmental stimuli domain score was calculated as the mean of the items within the environmental stimuli domain. Hence, the environmental stimuli domain scores were each defined on a range from 1 to 7 with higher scores indicating a higher quality of life. Baseline value is the value at Day 0 assessment. Change from Baseline is post dose visit value minus Baseline. The percentage of responders that is, participants with an increase from Baseline of >=0.5 in AQLQ(S) environmental stimuli domain score has been presented. Only those participants available at the specified time point was analyzed.
Time Frame	Baseline (Day 0) and Week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Usual Care	FF/VI
Arm/Group Description:	Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed	1922	1896
Measure Type: Number; Unit of Measure: Percentage of participants
	50	59

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Logistic regression adjusted for randomized treatment, asthma maintenance therapy at Baseline per randomization stratification, ACT total score at Baseline per randomization stratification, gender, age and Baseline score.
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Adjusted Odds Ratio
	Estimated Value	1.51
	Confidence Interval	(2-Sided) 95%; 1.31 to 1.73
	Estimation Comments	Adjusted odds ratio of FF/VI versus Usual Care has been presented.

19. Secondary Outcome

Title	Percentage of Participants With Serious Adverse Event (SAE) of Pneumonia
Description	A serious advent event (SAE) of pneumonia was defined as any SAE in the adverse event special interest (AESI) group of "pneumonia". The incidence of the SAEs of pneumonia for each treatment group is defined as the percentage of participants in that group who have experienced at least one SAE of pneumonia from start date of study treatment to the stop date of exposure + 28 days or date of study discontinuation, whichever is earliest. The percentage of participants with SAE of pneumonia has been presented.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Usual Care	FF/VI
Arm/Group Description:	Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed	2119	2114
Measure Type: Number; Unit of Measure: Percentage of participants
	1	1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority is demonstrated if the upper limit of the two-sided 95% confidence interval for the incidence ratio is less than 2.
Method of Estimation	Estimation Parameter	Incidence ratio
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; 0.8 to 2.7
	Estimation Comments	Incidence ratio was calculated as percentage of participants who had at least one SAE of pneumonia in the FF/VI group divided by the percentage of participants who had at least one SAE of pneumonia in the Usual Care group.

20. Secondary Outcome

Title	Time to First SAE of Pneumonia
Description	An SAE of pneumonia was defined as any SAE in the AESI group of "pneumonia". The date of an event for an SAE of pneumonia was the AE onset date. Participants who do not have an SAE of pneumonia during the first 364 days of the treatment period (start date of exposure to min [end date of exposure + 28 days, date of study discontinuation, start date of exposure + 363]) were censored. Time to first SAE of pneumonia was measured from the date of randomization (that is, study treatment start date) to the onset date of first SAE of pneumonia. The number of participants with first on-treatment SAE of pneumonia has been presented.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Usual Care	FF/VI
Arm/Group Description:	Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed	2119	2114
Measure Type: Number; Unit of Measure: Participants
	16	23

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Usual Care, FF/VI
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.255
	Comments	Cox proportional hazards model with randomized treatment, asthma maintenance therapy at Baseline per randomization stratification, ACT total score at Baseline per randomization stratification, gender and age as covariates.
	Method	Cox proportional hazards model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.45
	Confidence Interval	(2-Sided) 95%; 0.77 to 2.74
	Estimation Comments	Hazard ratio for FF/VI versus Usual Care has been presented.

21. Secondary Outcome

Title	Number of Participants With Fatal SAEs of Pneumonia
Description	All SAEs included in the AESI group of "pneumonia" were considered as an SAE of pneumonia. Fatal SAEs of pneumonia are SAEs that led to death of participants. The number of participants with fatal SAEs of pneumonia has been presented.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Usual Care	FF/VI
Arm/Group Description:	Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed	2119	2114
Measure Type: Number; Unit of Measure: Participants
	3	1

22. Secondary Outcome

Title	Number of Participants With SAEs
Description	An SAE is any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; is a congenital anomaly/birth defect; important medical events which may require medical or surgical intervention for example, invasive or malignant cancers; all events of possible drug-induced liver injury with hyperbilirubinemia. The number of participants with on-treatment SAEs has been summarized.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Usual Care	FF/VI
Arm/Group Description:	Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed	2119	2114
Measure Type: Number; Unit of Measure: Participants
	284	284

23. Secondary Outcome

Title	Number of Participants With Adverse Drug Reactions (ADRs)
Description	An ADR is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, for which there is a reasonable possibility that the untoward occurrence is causally related to the medicinal product. ADRs are a subset of AEs for a given medicinal product.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Usual Care	FF/VI
Arm/Group Description:	Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).	Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
Overall Number of Participants Analyzed	2119	2114
Measure Type: Number; Unit of Measure: Participants
	109	326

Adverse Events

Time Frame	On-treatment serious adverse events (SAEs) and non- serious adverse drug reactions (ADRs) were collected from the start of study treatment and until the follow up contact (Up to Week 52).
Adverse Event Reporting Description	ITT Population comprised of all randomized participants who received at least one prescription of study medication
Arm/Group Title	Usual Care		FF/VI
Arm/Group Description	Participants continued their usual asthma maintenance therapy that is, inhaled corticosteroid without a long acting beta2-agonist or inhaled corticosteroid with long acting beta2-agonist combination (either as a fixed dose combination or an inhaled corticosteroid/long acting beta2-agonist provided in two separate inhalers).		Participants initiated with an appropriate dose of inhaled FF/VI (100 mcg/25 mcg or 200 mcg/25 mcg per actuation) once daily via Novel Dry Powder Inhaler.
All-Cause Mortality
	Usual Care		FF/VI
	Affected / at Risk (%)		Affected / at Risk (%)
Total	27/2119 (1.27%)		15/2114 (0.71%)
Serious Adverse Events
	Usual Care		FF/VI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	284/2119 (13.40%)		284/2114 (13.43%)
Blood and lymphatic system disorders
Anaemia † 1	3/2119 (0.14%)	3	3/2114 (0.14%)	3
Anaemia of chronic disease † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Lymphadenopathy mediastinal † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Microcytic anaemia † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Pancytopenia † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Thrombocytopenia † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Cardiac disorders
Acute coronary syndrome † 1	1/2119 (0.05%)	2	1/2114 (0.05%)	1
Acute myocardial infarction † 1	2/2119 (0.09%)	2	4/2114 (0.19%)	4
Angina pectoris † 1	1/2119 (0.05%)	1	5/2114 (0.24%)	5
Angina unstable † 1	2/2119 (0.09%)	2	0/2114 (0.00%)	0
Arrhythmia † 1	3/2119 (0.14%)	3	2/2114 (0.09%)	2
Arteriosclerosis coronary artery † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Atrial fibrillation † 1	14/2119 (0.66%)	16	7/2114 (0.33%)	7
Atrioventricular block first degree † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Cardiac arrest † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Cardiac failure † 1	0/2119 (0.00%)	0	2/2114 (0.09%)	2
Cardiac failure congestive † 1	2/2119 (0.09%)	2	1/2114 (0.05%)	1
Cardiac ventricular thrombosis † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Coronary artery disease † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Coronary artery thrombosis † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Diastolic dysfunction † 1	2/2119 (0.09%)	2	0/2114 (0.00%)	0
Hypertensive heart disease † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Left ventricular dysfunction † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Left ventricular failure † 1	0/2119 (0.00%)	0	3/2114 (0.14%)	3
Left ventricular hypertrophy † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Myocardial infarction † 1	2/2119 (0.09%)	2	2/2114 (0.09%)	2
Myocardial ischaemia † 1	2/2119 (0.09%)	2	5/2114 (0.24%)	5
Myocarditis † 1	0/2119 (0.00%)	0	2/2114 (0.09%)	2
Palpitations † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Sinus bradycardia † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Sinus node dysfunction † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Tricuspid valve incompetence † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Ventricular extrasystoles † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Ventricular tachycardia † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Congenital, familial and genetic disorders
Branchial cyst † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Endocardial fibroelastosis † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Ear and labyrinth disorders
Deafness † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Tinnitus † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Vertigo † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Vertigo positional † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Endocrine disorders
Adrenal insufficiency † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Hyperparathyroidism † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Hyperthyroidism † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Hypothyroidism † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Inappropriate antidiuretic hormone secretion † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Secondary hypogonadism † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Eye disorders
Angle closure glaucoma † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Cataract † 1	4/2119 (0.19%)	4	6/2114 (0.28%)	6
Conjunctivitis allergic † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Diabetic retinopathy † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Glaucoma † 1	0/2119 (0.00%)	0	4/2114 (0.19%)	4
Ocular hyperaemia † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Retinal detachment † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Gastrointestinal disorders
Abdominal hernia † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Abdominal pain † 1	4/2119 (0.19%)	4	5/2114 (0.24%)	5
Abdominal wall haematoma † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Colitis ischaemic † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Colitis ulcerative † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	2
Constipation † 1	5/2119 (0.24%)	5	1/2114 (0.05%)	1
Diarrhoea † 1	0/2119 (0.00%)	0	4/2114 (0.19%)	4
Diverticulum † 1	0/2119 (0.00%)	0	2/2114 (0.09%)	2
Duodenal ulcer † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Dysphagia † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Gastritis † 1	5/2119 (0.24%)	5	1/2114 (0.05%)	1
Gastrointestinal disorder † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Gastrointestinal haemorrhage † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Gastrooesophageal reflux disease † 1	2/2119 (0.09%)	2	3/2114 (0.14%)	3
Haematemesis † 1	2/2119 (0.09%)	2	0/2114 (0.00%)	0
Incarcerated umbilical hernia † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Intestinal ischaemia † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Intestinal obstruction † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Large intestinal obstruction † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Melaena † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Oesophagitis † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Pancreatitis † 1	1/2119 (0.05%)	1	3/2114 (0.14%)	3
Pancreatitis acute † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Proctalgia † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Rectal haemorrhage † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Umbilical hernia, obstructive † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Upper gastrointestinal haemorrhage † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Vomiting † 1	1/2119 (0.05%)	1	2/2114 (0.09%)	2
General disorders
Chest pain † 1	4/2119 (0.19%)	4	1/2114 (0.05%)	1
Generalised oedema † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Multiple organ dysfunction syndrome † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Non-cardiac chest pain † 1	3/2119 (0.14%)	3	1/2114 (0.05%)	1
Peripheral swelling † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Surgical failure † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Hepatobiliary disorders
Bile duct stone † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Cholecystitis † 1	3/2119 (0.14%)	3	1/2114 (0.05%)	2
Cholelithiasis † 1	1/2119 (0.05%)	1	3/2114 (0.14%)	3
Hepatic cirrhosis † 1	2/2119 (0.09%)	2	1/2114 (0.05%)	1
Hepatic failure † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Hepatic function abnormal † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Jaundice cholestatic † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Immune system disorders
Anaphylactic reaction † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Hypersensitivity † 1	2/2119 (0.09%)	2	0/2114 (0.00%)	0
Mycotic allergy † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Infections and infestations
Abdominal abscess † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Abdominal wall abscess † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Abscess † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Anal abscess † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Appendicitis † 1	2/2119 (0.09%)	2	1/2114 (0.05%)	1
Atypical pneumonia † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Bacteraemia † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Biliary sepsis † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Bronchiolitis † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Candida infection † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Catheter site infection † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Cellulitis † 1	11/2119 (0.52%)	13	7/2114 (0.33%)	8
Chronic hepatitis C † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Diverticulitis † 1	1/2119 (0.05%)	1	3/2114 (0.14%)	3
Empyema † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Encephalitis † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Gastroenteritis † 1	0/2119 (0.00%)	0	2/2114 (0.09%)	2
Genital herpes † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Genital infection † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Infected dermal cyst † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Infected skin ulcer † 1	3/2119 (0.14%)	3	0/2114 (0.00%)	0
Infective exacerbation of chronic obstructive airways disease † 1	0/2119 (0.00%)	0	2/2114 (0.09%)	2
Kidney infection † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Liver abscess † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Localised infection † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Lower respiratory tract infection † 1	7/2119 (0.33%)	7	5/2114 (0.24%)	5
Necrotising fasciitis † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Neutropenic sepsis † 1	1/2119 (0.05%)	1	2/2114 (0.09%)	2
Ophthalmic herpes simplex † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Pelvic inflammatory disease † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Periorbital cellulitis † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Peritonsillar abscess † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Pilonidal cyst † 1	2/2119 (0.09%)	3	1/2114 (0.05%)	1
Pneumonia † 1	13/2119 (0.61%)	14	23/2114 (1.09%)	24
Pneumonia mycoplasmal † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Post procedural infection † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Post procedural sepsis † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Postoperative wound infection † 1	1/2119 (0.05%)	1	2/2114 (0.09%)	2
Pseudomonas infection † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Pyelonephritis † 1	3/2119 (0.14%)	3	1/2114 (0.05%)	1
Respiratory tract infection † 1	0/2119 (0.00%)	0	3/2114 (0.14%)	3
Sepsis † 1	7/2119 (0.33%)	7	3/2114 (0.14%)	3
Sialoadenitis † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Staphylococcal infection † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Subcutaneous abscess † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Tonsillitis † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Upper respiratory tract infection † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Urinary tract infection † 1	4/2119 (0.19%)	4	12/2114 (0.57%)	13
Urosepsis † 1	2/2119 (0.09%)	2	1/2114 (0.05%)	1
Viral infection † 1	2/2119 (0.09%)	2	1/2114 (0.05%)	1
Viral labyrinthitis † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Vulval abscess † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Wound infection † 1	2/2119 (0.09%)	2	1/2114 (0.05%)	1
Injury, poisoning and procedural complications
Accidental overdose † 1	3/2119 (0.14%)	3	2/2114 (0.09%)	2
Ankle fracture † 1	2/2119 (0.09%)	2	8/2114 (0.38%)	8
Brain contusion † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Burns third degree † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Cervical vertebral fracture † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Comminuted fracture † 1	2/2119 (0.09%)	2	0/2114 (0.00%)	0
Corneal abrasion † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Craniocerebral injury † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Facial bones fracture † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Fall † 1	5/2119 (0.24%)	5	6/2114 (0.28%)	6
Femoral neck fracture † 1	2/2119 (0.09%)	2	2/2114 (0.09%)	2
Femur fracture † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Fibula fracture † 1	2/2119 (0.09%)	2	1/2114 (0.05%)	1
Foot fracture † 1	3/2119 (0.14%)	3	3/2114 (0.14%)	3
Foreign body † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Fracture † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Hand fracture † 1	4/2119 (0.19%)	5	1/2114 (0.05%)	1
Head injury † 1	3/2119 (0.14%)	3	1/2114 (0.05%)	1
Humerus fracture † 1	5/2119 (0.24%)	5	2/2114 (0.09%)	2
Intentional overdose † 1	5/2119 (0.24%)	5	5/2114 (0.24%)	5
Intentional product misuse † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Joint dislocation † 1	2/2119 (0.09%)	2	0/2114 (0.00%)	0
Ligament rupture † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	2
Limb crushing injury † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Limb injury † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Meniscus injury † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Overdose † 1	1/2119 (0.05%)	1	2/2114 (0.09%)	2
Pelvic fracture † 1	2/2119 (0.09%)	2	1/2114 (0.05%)	1
Post procedural complication † 1	0/2119 (0.00%)	0	2/2114 (0.09%)	2
Post procedural haematoma † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Post procedural haemorrhage † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Pubis fracture † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Radius fracture † 1	9/2119 (0.42%)	10	4/2114 (0.19%)	4
Rib fracture † 1	1/2119 (0.05%)	1	2/2114 (0.09%)	2
Skull fracture † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Skull fractured base † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Soft tissue injury † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Spinal fracture † 1	1/2119 (0.05%)	1	2/2114 (0.09%)	2
Subarachnoid haemorrhage † 1	0/2119 (0.00%)	0	2/2114 (0.09%)	2
Subdural haematoma † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Thermal burn † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Toxicity to various agents † 1	1/2119 (0.05%)	1	2/2114 (0.09%)	2
Ulna fracture † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Upper limb fracture † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Wound secretion † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Wrist fracture † 1	3/2119 (0.14%)	3	5/2114 (0.24%)	5
Investigations
Blood potassium decreased † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Electrocardiogram QT prolonged † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
International normalised ratio abnormal † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Liver function test abnormal † 1	7/2119 (0.33%)	7	11/2114 (0.52%)	11
Renal function test abnormal † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Metabolism and nutrition disorders
Dehydration † 1	2/2119 (0.09%)	2	1/2114 (0.05%)	1
Diabetes mellitus † 1	3/2119 (0.14%)	3	3/2114 (0.14%)	3
Diabetic ketoacidosis † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Electrolyte imbalance † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Glucose tolerance impaired † 1	2/2119 (0.09%)	2	0/2114 (0.00%)	0
Gout † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Hypercalcaemia † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Hyperglycaemia † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Hyperkalaemia † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Hypokalaemia † 1	1/2119 (0.05%)	1	4/2114 (0.19%)	4
Hyponatraemia † 1	2/2119 (0.09%)	2	0/2114 (0.00%)	0
Malnutrition † 1	2/2119 (0.09%)	2	0/2114 (0.00%)	0
Metabolic acidosis † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Type 2 diabetes mellitus † 1	13/2119 (0.61%)	13	12/2114 (0.57%)	12
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Arthritis † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Back pain † 1	8/2119 (0.38%)	9	3/2114 (0.14%)	3
Bursitis † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Fibromyalgia † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Intervertebral disc protrusion † 1	3/2119 (0.14%)	3	0/2114 (0.00%)	0
Metatarsalgia † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Muscular weakness † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Musculoskeletal chest pain † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Musculoskeletal pain † 1	2/2119 (0.09%)	2	0/2114 (0.00%)	0
Osteoarthritis † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Osteopenia † 1	0/2119 (0.00%)	0	2/2114 (0.09%)	2
Osteoporosis † 1	1/2119 (0.05%)	1	5/2114 (0.24%)	5
Palindromic rheumatism † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Polymyalgia rheumatica † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Rhabdomyolysis † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Rheumatoid arthritis † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acinic cell carcinoma of salivary gland † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Acute myeloid leukaemia † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Adenoma benign † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
B-cell lymphoma recurrent † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Basal cell carcinoma † 1	2/2119 (0.09%)	6	4/2114 (0.19%)	4
Bladder cancer † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Bladder transitional cell carcinoma † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Brain cancer metastatic † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Brain neoplasm † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Breast cancer † 1	2/2119 (0.09%)	2	2/2114 (0.09%)	2
Breast cancer metastatic † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Central nervous system lymphoma † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Chondrosarcoma † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Colon cancer † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Colorectal cancer metastatic † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Endometrial adenocarcinoma † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Gastrointestinal carcinoma † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Gastrointestinal stromal tumour † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Hepatocellular carcinoma † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Invasive ductal breast carcinoma † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Lentigo maligna † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Lung cancer metastatic † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Lung neoplasm malignant † 1	0/2119 (0.00%)	0	2/2114 (0.09%)	2
Malignant melanoma † 1	0/2119 (0.00%)	0	2/2114 (0.09%)	2
Malignant melanoma in situ † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Metastases to central nervous system † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Metastases to liver † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Metastases to lung † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Metastatic renal cell carcinoma † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Neoplasm malignant † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Oesophageal carcinoma † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Penile squamous cell carcinoma † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Phyllodes tumour † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Precursor B-lymphoblastic lymphoma † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Prostate cancer † 1	4/2119 (0.19%)	4	3/2114 (0.14%)	3
Renal cancer † 1	1/2119 (0.05%)	1	2/2114 (0.09%)	2
Renal cancer recurrent † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Renal neoplasm † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Squamous cell carcinoma † 1	1/2119 (0.05%)	1	2/2114 (0.09%)	2
Thyroid cancer † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Ureteric cancer † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Nervous system disorders
Amnesia † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Anosmia † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Carpal tunnel syndrome † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Cerebrovascular accident † 1	0/2119 (0.00%)	0	5/2114 (0.24%)	5
Cerebrovascular disorder † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Dementia † 1	1/2119 (0.05%)	1	2/2114 (0.09%)	2
Dizziness † 1	2/2119 (0.09%)	2	0/2114 (0.00%)	0
Drug withdrawal convulsions † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Epilepsy † 1	2/2119 (0.09%)	2	1/2114 (0.05%)	1
Haemorrhage intracranial † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Haemorrhagic stroke † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Headache † 1	4/2119 (0.19%)	4	2/2114 (0.09%)	2
Ischaemic stroke † 1	1/2119 (0.05%)	1	3/2114 (0.14%)	3
Migraine † 1	2/2119 (0.09%)	2	5/2114 (0.24%)	5
Multiple sclerosis † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Multiple sclerosis relapse † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Neuralgia † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Neuropathy peripheral † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Paraesthesia † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Parkinson's disease † 1	2/2119 (0.09%)	2	0/2114 (0.00%)	0
Radiculopathy † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Sciatica † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Seizure † 1	0/2119 (0.00%)	0	5/2114 (0.24%)	5
Sensory disturbance † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Spinal cord compression † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Status epilepticus † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Subdural hygroma † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Syncope † 1	2/2119 (0.09%)	2	3/2114 (0.14%)	3
Transient ischaemic attack † 1	0/2119 (0.00%)	0	2/2114 (0.09%)	2
Trigeminal neuralgia † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
VIth nerve paralysis † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Vascular dementia † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Vertebral artery dissection † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Vocal cord paralysis † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Pregnancy, puerperium and perinatal conditions
Abortion missed † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Abortion spontaneous † 1	0/2119 (0.00%)	0	2/2114 (0.09%)	2
Unintended pregnancy † 1	3/2119 (0.14%)	3	3/2114 (0.14%)	3
Unwanted pregnancy † 1	2/2119 (0.09%)	2	2/2114 (0.09%)	2
Product Issues
Device dislocation † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Psychiatric disorders
Alcohol withdrawal syndrome † 1	0/2119 (0.00%)	0	2/2114 (0.09%)	3
Alcoholism † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Antisocial personality disorder † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Bipolar disorder † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Confusional state † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Delusion † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Depressed mood † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Depression † 1	2/2119 (0.09%)	2	4/2114 (0.19%)	4
Depression suicidal † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Eating disorder † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Hypomania † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Persistent depressive disorder † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Post-traumatic stress disorder † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Psychotic disorder † 1	1/2119 (0.05%)	1	2/2114 (0.09%)	2
Schizoaffective disorder † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Suicidal ideation † 1	2/2119 (0.09%)	2	3/2114 (0.14%)	3
Suicide attempt † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Renal and urinary disorders
Acute kidney injury † 1	9/2119 (0.42%)	9	6/2114 (0.28%)	6
Chronic kidney disease † 1	5/2119 (0.24%)	5	3/2114 (0.14%)	3
Haematuria † 1	2/2119 (0.09%)	2	1/2114 (0.05%)	1
Hydronephrosis † 1	0/2119 (0.00%)	0	2/2114 (0.09%)	2
Loin pain haematuria syndrome † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Nephrolithiasis † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Renal colic † 1	1/2119 (0.05%)	1	2/2114 (0.09%)	2
Renal impairment † 1	3/2119 (0.14%)	3	3/2114 (0.14%)	3
Ureteric obstruction † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Urinary retention † 1	4/2119 (0.19%)	4	2/2114 (0.09%)	2
Reproductive system and breast disorders
Menorrhagia † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Oedema genital † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Ovarian cyst † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Ovarian cyst torsion † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Pelvic pain † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Prostatitis † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Uterine haemorrhage † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Asthma † 1	30/2119 (1.42%)	34	24/2114 (1.14%)	30
Atelectasis † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Bronchiectasis † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Chronic obstructive pulmonary disease † 1	5/2119 (0.24%)	6	1/2114 (0.05%)	1
Emphysema † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Epistaxis † 1	3/2119 (0.14%)	3	1/2114 (0.05%)	1
Interstitial lung disease † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Pharyngeal inflammation † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Pickwickian syndrome † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Pleurisy † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Pneumonia aspiration † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Pulmonary embolism † 1	2/2119 (0.09%)	2	2/2114 (0.09%)	2
Pulmonary eosinophilia † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Pulmonary oedema † 1	2/2119 (0.09%)	2	0/2114 (0.00%)	0
Reflux laryngitis † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Respiratory arrest † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Respiratory failure † 1	2/2119 (0.09%)	2	2/2114 (0.09%)	2
Sleep apnoea syndrome † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Skin and subcutaneous tissue disorders
Decubitus ulcer † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Dermatitis † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Eczema † 1	2/2119 (0.09%)	2	1/2114 (0.05%)	1
Rash † 1	0/2119 (0.00%)	0	3/2114 (0.14%)	3
Skin necrosis † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Skin ulcer † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Surgical and medical procedures
Abortion induced † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Vascular disorders
Angiodysplasia † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Aortic stenosis † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Circulatory collapse † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Deep vein thrombosis † 1	2/2119 (0.09%)	2	5/2114 (0.24%)	6
Essential hypertension † 1	1/2119 (0.05%)	1	1/2114 (0.05%)	1
Haematoma † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Hypertension † 1	2/2119 (0.09%)	2	0/2114 (0.00%)	0
Hypotension † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Raynaud's phenomenon † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
Superior vena cava occlusion † 1	0/2119 (0.00%)	0	1/2114 (0.05%)	1
Temporal arteritis † 1	1/2119 (0.05%)	1	0/2114 (0.00%)	0
1 Term from vocabulary, MedDRA 19.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	3%
	Usual Care		FF/VI
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2119 (0.00%)		0/2114 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

• Name/Title: GSK Response Center
• Organization: GlaxoSmithKline
• Phone: 866-435-7343

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Svedsater H, Jones R, Bosanquet N, Jacques L, Lay-Flurrie J, Leather DA, Vestbo J, Collier S, Woodcock A. Patient-reported outcomes with initiation of fluticasone furoate/vilanterol versus continuing usual care in the Asthma Salford Lung Study. Respir Med. 2018 Aug;141:198-206. doi: 10.1016/j.rmed.2018.06.003. Epub 2018 Jun 6.

Jacques L, Bakerly ND, New JP, Svedsater H, Lay-Flurrie J, Leather DA. Effectiveness of fluticasone furoate/vilanterol versus fluticasone propionate/salmeterol on asthma control in the Salford Lung Study. J Asthma. 2019 Jul;56(7):748-757. doi: 10.1080/02770903.2018.1490751. Epub 2018 Oct 16.

Woodcock A, Vestbo J, Bakerly ND, New J, Gibson JM, McCorkindale S, Jones R, Collier S, Lay-Flurrie J, Frith L, Jacques L, Fletcher JL, Harvey C, Svedsater H, Leather D; Salford Lung Study Investigators. Effectiveness of fluticasone furoate plus vilanterol on asthma control in clinical practice: an open-label, parallel group, randomised controlled trial. Lancet. 2017 Nov 18;390(10109):2247-2255. doi: 10.1016/S0140-6736(17)32397-8. Epub 2017 Sep 10. Erratum in: Lancet. 2017 Nov 18;390(10109):e40. Lancet. 2018 Feb 3;391(10119):430.

Woodcock A, Bakerly ND, New JP, Gibson JM, Wu W, Vestbo J, Leather D. The Salford Lung Study protocol: a pragmatic, randomised phase III real-world effectiveness trial in asthma. BMC Pulm Med. 2015 Dec 10;15:160. doi: 10.1186/s12890-015-0150-8.

New JP, Bakerly ND, Leather D, Woodcock A. Obtaining real-world evidence: the Salford Lung Study. Thorax. 2014 Dec;69(12):1152-4. doi: 10.1136/thoraxjnl-2014-205259. Epub 2014 Mar 6. Erratum in: Thorax. 2015 Oct;70(10):1008.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01706198
• Other Study ID Numbers: 115150
• First Submitted: October 4, 2012
• First Posted: October 15, 2012
• Results First Submitted: December 6, 2017
• Results First Posted: January 24, 2019
• Last Update Posted: January 24, 2019