Download PDF

Clinical Trial Results:
Randomized, Double-Blind Comparison of Advair 100/50 BID vs Salmeterol BID vs Albuterol QID in subjects with ARG/ARG genotype 12 years of Age and Older with Persistent Asthma on Short-Acting Beta2-Agonists Alone

Summary
EudraCT number	2015-004865-10
Trial protocol	Outside EU/EEA
Global end of trial date	23 Jan 2007

Results information
Results version number	v1(current)
This version publication date	28 Dec 2016
First version publication date	28 Dec 2016
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

SFA100062

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom,

Public contact

GSK Response Center, GlaxoSmithKline, 1 866-435-7343,

Scientific contact

GSK Response Center, GlaxoSmithKline, 1 866-435-7343,

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

12 Apr 2007

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

23 Jan 2007

Was the trial ended prematurely?

Main objective of the trial

To evaluate lung function as assessed by AM PEF AUC relative to baseline [AUC(bl)] in subjects who have the B16 Arg/Arg genotype compared with that of subjects who have the B16 Gly/Gly genotype over 16 weeks of treatment with FSC DISKUS 100/50mcg BID. Please note: In the age group population table below, the actual number of adults participants between 18-64 years is 1817. Two participants did not have age information available. Unfortunately, the EU system does not have a way to denote this missing age data, so the 2 participants of unknown age were added to the adult population.

Protection of trial subjects

Non-applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

25 Oct 2004

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Kenya: 116

Country: Number of subjects enrolled

Peru: 135

Country: Number of subjects enrolled

United States: 1960

Worldwide total number of subjects

2211

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

329

Adults (18-64 years)

1819

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

In the results summary Arginine is abbreviated as Arg, and Glycine is abbreviated as Gly

Screening details

The study included a screening period(<= 4 weeks [W]; genotyping of each participant), followed by two 8-W open-label treatment periods (OLTP) (albuterol in OLTP-1; ipratropium bromide [IB] as needed [prn] in OLTP-2) followed by double-blind treatment period of 16 W(fluticasone propionate/salmeterol[FSC] or salmeterol [SM], washout for 2-W (IB prn)

Period 1 title

Double-blinded Treatment Period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

FSC 100/50 microgram (mcg) Arg/Arg

Arm description

Participants received fixed dose combination of fluticasone propionate/salmeterol (FSC) 100/50 mcg twice daily (BID) for 16 weeks. Participants with genotype Arg/Arg were enrolled in this arm

Arm type

Experimental

Investigational medicinal product name

Fluticasone propionate/salmeterol

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

100/50 mcg

FSC 100/50 mcg Arg/Gly

Arm description

Participants received fixed dose combination of FSC 100/50 mcg BID for 16 weeks. Participants with genotype Arg/Gly were enrolled in this arm

Arm type

Experimental

Investigational medicinal product name

Fluticasone propionate/salmeterol

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

100/50 mcg

FSC 100/50 mcg Gly/Gly

Arm description

Participants received fixed dose combination of FSC 100/50 mcg BID for 16 weeks. Participants with genotype Gly/Gly were enrolled in this arm

Arm type

Experimental

Investigational medicinal product name

Fluticasone propionate/salmeterol

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

100/50 mcg

SM 50 mcg Arg/Arg

Arm description

Participants received salmeterol (SM) 50 mcg twice daily (BID) for 16 weeks. Participants with genotype Arg/Arg were enrolled in this arm

Arm type

Active comparator

Investigational medicinal product name

Salmeterol

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

50 mcg

SM 50 mcg Arg/Gly

Arm description

Participants received SM 50 mcg BID for 16 weeks. Participants with genotype Arg/Gly were enrolled in this arm

Arm type

Active comparator

Investigational medicinal product name

Salmeterol

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

50 mcg

SM 50 mcg Gly/Gly

Arm description

Participants received SM 50 mcg BID for 16 weeks. Participants with genotype Gly/Gly were enrolled in this arm

Arm type

Active comparator

Investigational medicinal product name

Salmeterol

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

50 mcg

Number of subjects in period 1 ^[1]	FSC 100/50 microgram (mcg) Arg/Arg	FSC 100/50 mcg Arg/Gly	FSC 100/50 mcg Gly/Gly	SM 50 mcg Arg/Arg	SM 50 mcg Arg/Gly	SM 50 mcg Gly/Gly
Started	89	92	91	90	90	92
Completed	79	84	79	69	74	76
Not completed	10	8	12	21	16	16
Adverse event, serious fatal	-	-	-	-	1	-
Consent withdrawn by subject	-	4	6	6	3	3
Adverse event, non-fatal	3	1	1	1	6	3
Exacerbation	1	-	1	3	-	3
Unknown	4	1	-	2	2	2
Lost to follow-up	1	-	3	4	3	2
Sponsor terminated study	-	-	-	1	-	-
Protocol deviation	1	2	1	4	1	3

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: The worldwide number includes all enrolled participants; baseline information includes ITT population only.

Period 2 title

Washout Period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

FSC 100/50 mcg Arg/Arg

Arm description

Participants received fixed dose combination of fluticasone propionate/salmeterol (FSC) 100/50 mcg twice daily (BID) for 16 weeks. Participants with genotype Arg/Arg were enrolled in this arm

Arm type

Experimental

Investigational medicinal product name

Fluticasone propionate/salmeterol

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

100/50 mcg

FSC 100/50 mcg Arg/Gly

Arm description

Participants received fixed dose combination of FSC 100/50 mcg BID for 16 weeks. Participants with genotype Arg/Gly were enrolled in this arm

Arm type

Experimental

Investigational medicinal product name

Fluticasone propionate/salmeterol

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

100/50 mcg

FSC 100/50 mcg Gly/Gly

Arm description

Participants received fixed dose combination of FSC 100/50 mcg BID for 16 weeks. Participants with genotype Gly/Gly were enrolled in this arm

Arm type

Experimental

Investigational medicinal product name

Fluticasone propionate/salmeterol

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

100/50 mcg

SM 50 mcg Arg/Arg

Arm description

Participants received salmeterol (SM) 50 mcg twice daily (BID) for 16 weeks. Participants with genotype Arg/Arg were enrolled in this arm

Arm type

Active comparator

Investigational medicinal product name

Salmeterol

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

50 mcg

SM 50 mcg Arg/Gly

Arm description

Participants received SM 50 mcg BID for 16 weeks. Participants with genotype Arg/Gly were enrolled in this arm

Arm type

Active comparator

Investigational medicinal product name

Salmeterol

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

50 mcg

SM 50 mcg Gly/Gly

Arm description

Participants received SM 50 mcg BID for 16 weeks. Participants with genotype Gly/Gly were enrolled in this arm

Arm type

Active comparator

Investigational medicinal product name

Salmeterol

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

50 mcg

Number of subjects in period 2	FSC 100/50 mcg Arg/Arg	FSC 100/50 mcg Arg/Gly	FSC 100/50 mcg Gly/Gly	SM 50 mcg Arg/Arg	SM 50 mcg Arg/Gly	SM 50 mcg Gly/Gly
Started	79	84	79	69	74	76
Completed	78	82	79	68	73	76
Not completed	1	2	0	1	1	0
Adverse event, non-fatal	-	1	-	-	-	-
Exacerbation	1	-	-	-	-	-
Unknown	-	-	-	-	1	-
Sponsor terminated study	-	-	-	1	-	-
Protocol deviation	-	1	-	-	-	-

Baseline characteristics

Top of page

Reporting group title

FSC 100/50 microgram (mcg) Arg/Arg

Reporting group description

Participants received fixed dose combination of fluticasone propionate/salmeterol (FSC) 100/50 mcg twice daily (BID) for 16 weeks. Participants with genotype Arg/Arg were enrolled in this arm

Reporting group title

FSC 100/50 mcg Arg/Gly

Reporting group description

Participants received fixed dose combination of FSC 100/50 mcg BID for 16 weeks. Participants with genotype Arg/Gly were enrolled in this arm

Reporting group title

FSC 100/50 mcg Gly/Gly

Reporting group description

Participants received fixed dose combination of FSC 100/50 mcg BID for 16 weeks. Participants with genotype Gly/Gly were enrolled in this arm

Reporting group title

SM 50 mcg Arg/Arg

Reporting group description

Participants received salmeterol (SM) 50 mcg twice daily (BID) for 16 weeks. Participants with genotype Arg/Arg were enrolled in this arm

Reporting group title

SM 50 mcg Arg/Gly

Reporting group description

Participants received SM 50 mcg BID for 16 weeks. Participants with genotype Arg/Gly were enrolled in this arm

Reporting group title

SM 50 mcg Gly/Gly

Reporting group description

Participants received SM 50 mcg BID for 16 weeks. Participants with genotype Gly/Gly were enrolled in this arm

Reporting group values	FSC 100/50 microgram (mcg) Arg/Arg	FSC 100/50 mcg Arg/Gly	FSC 100/50 mcg Gly/Gly	SM 50 mcg Arg/Arg	SM 50 mcg Arg/Gly	SM 50 mcg Gly/Gly	Total
Number of subjects	89	92	91	90	90	92
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	33.8 ± 13.31	31 ± 14.4	33.3 ± 14.33	30 ± 12.02	32.8 ± 14.17	35.2 ± 16.34	-
Gender categorical
Units:
Male	27	33	36	33	32	41	202
Female	62	59	55	57	58	51	342
Race, Customized
The "Other" race category below includes Native Hawaiian, Other Pacific Islander, American Indian and Alaska Native.
Units: Subjects
Arabic/North African	1	0	0	0	0	0	1
Black African American	23	16	12	18	11	16	96
Black African Heritage	6	1	6	14	4	3	34
East and South East Asian	0	0	0	1	3	2	6
Japanese	0	1	1	0	0	0	2
South Asian	0	1	2	0	2	0	5
White/Caucasian	44	57	59	45	54	57	316
Other	15	16	11	12	16	14	84

End points

Top of page

Reporting group title

FSC 100/50 microgram (mcg) Arg/Arg

Reporting group description

Participants received fixed dose combination of fluticasone propionate/salmeterol (FSC) 100/50 mcg twice daily (BID) for 16 weeks. Participants with genotype Arg/Arg were enrolled in this arm

Reporting group title

FSC 100/50 mcg Arg/Gly

Reporting group description

Participants received fixed dose combination of FSC 100/50 mcg BID for 16 weeks. Participants with genotype Arg/Gly were enrolled in this arm

Reporting group title

FSC 100/50 mcg Gly/Gly

Reporting group description

Participants received fixed dose combination of FSC 100/50 mcg BID for 16 weeks. Participants with genotype Gly/Gly were enrolled in this arm

Reporting group title

SM 50 mcg Arg/Arg

Reporting group description

Participants received salmeterol (SM) 50 mcg twice daily (BID) for 16 weeks. Participants with genotype Arg/Arg were enrolled in this arm

Reporting group title

SM 50 mcg Arg/Gly

Reporting group description

Participants received SM 50 mcg BID for 16 weeks. Participants with genotype Arg/Gly were enrolled in this arm

Reporting group title

SM 50 mcg Gly/Gly

Reporting group description

Participants received SM 50 mcg BID for 16 weeks. Participants with genotype Gly/Gly were enrolled in this arm

Reporting group title

FSC 100/50 mcg Arg/Arg

Reporting group description

Participants received fixed dose combination of fluticasone propionate/salmeterol (FSC) 100/50 mcg twice daily (BID) for 16 weeks. Participants with genotype Arg/Arg were enrolled in this arm

Reporting group title

FSC 100/50 mcg Arg/Gly

Reporting group description

Participants received fixed dose combination of FSC 100/50 mcg BID for 16 weeks. Participants with genotype Arg/Gly were enrolled in this arm

Reporting group title

FSC 100/50 mcg Gly/Gly

Reporting group description

Participants received fixed dose combination of FSC 100/50 mcg BID for 16 weeks. Participants with genotype Gly/Gly were enrolled in this arm

Reporting group title

SM 50 mcg Arg/Arg

Reporting group description

Participants received salmeterol (SM) 50 mcg twice daily (BID) for 16 weeks. Participants with genotype Arg/Arg were enrolled in this arm

Reporting group title

SM 50 mcg Arg/Gly

Reporting group description

Participants received SM 50 mcg BID for 16 weeks. Participants with genotype Arg/Gly were enrolled in this arm

Reporting group title

SM 50 mcg Gly/Gly

Reporting group description

Participants received SM 50 mcg BID for 16 weeks. Participants with genotype Gly/Gly were enrolled in this arm

Primary: Mean change from baseline in morning peak expiratory flow (AM/PEF) following the double-blind treatment period.

Top of page

End point title

Mean change from baseline in morning peak expiratory flow (AM/PEF) following the double-blind treatment period.

End point description

AM PEF change from baseline was characterized by the area under the AM PEF curve relative to baseline AUC(bl) over the 16-week double-blind treatment period. Baseline was defined as the average of the AM PEF values recorded on the day of Visit 6 plus the 6 preceding days since AM PEF was measured in the morning (and prior to blinded study drug administration at Randomization [Visit 6]). The PEF measurements were collected via a study-issued Peak Flow Meter. Participants were instructed on proper use of the peak flow meter and on recording the results on the diary card. An analysis of covariance (ANCOVA) model, including terms for genotype, ethnicity stratum and baseline, was used to assess non-inferiority in AM PEF mean change from baseline for the overall 16-week double-blind treatment period. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).(Overall: Baseline to Week 16).

End point type

Primary

End point timeframe

Baseline and Upto 114 days

End point values	FSC 100/50 microgram (mcg) Arg/Arg	FSC 100/50 mcg Arg/Gly	FSC 100/50 mcg Gly/Gly	SM 50 mcg Arg/Arg	SM 50 mcg Arg/Gly	SM 50 mcg Gly/Gly
Number of subjects analysed	87 ^[1]	90 ^[2]	91 ^[3]	86 ^[4]	89 ^[5]	91 ^[6]
Units: Litre/Minute
arithmetic mean (standard error)
Week 1-4 (n=83, 91, 88, 79, 85, 89)	26.9 ± 4.6	19.2 ± 5.95	23.5 ± 4.49	17 ± 3.43	20.6 ± 4.81	11.8 ± 2.91
Week 5-8 (n=80, 88, 84, 75,81, 83)	32.2 ± 5.16	24.6 ± 6.45	27.7 ± 5.12	18.6 ± 4.1	20.6 ± 5.77	13.5 ± 3.77
Week 9-12 (n=76,88,78, 72,76, 79)	37.7 ± 5.48	26.5 ± 6.79	27.7 ± 5.41	22.5 ± 5.91	27.8 ± 6.79	14.8 ± 3.55
Week 13-16 (n=75, 86, 77, 67,73, 75)	38.9 ± 5.66	27 ± 6.83	26.4 ± 5.57	21.7 ± 5.55	28 ± 7.27	12.2 ± 4.04
Overall (n=83, 91, 88, 79, 85, 89)	32.6 ± 4.71	24.9 ± 5.86	25.9 ± 4.77	19.4 ± 3.92	24.6 ± 5.36	12.4 ± 3.05

Notes
[1] - Intent to Treat Population (ITT) (Excluding Investigator 018742)
[2] - Intent to Treat Population (ITT) (Excluding Investigator 018742)
[3] - Intent to Treat Population (ITT) (Excluding Investigator 018742)
[4] - Intent to Treat Population (ITT) (Excluding Investigator 018742)
[5] - Intent to Treat Population (ITT) (Excluding Investigator 018742)
[6] - Intent to Treat Population (ITT) (Excluding Investigator 018742)

Statistical analysis 1

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[7]

P-value

= 0.596

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

3.7

Confidence interval

level

95%

sides

2-sided

lower limit

-10.1

upper limit

17.5

Notes
[7] - Estimation Comments: Week 1 to Week 4

Statistical analysis 2

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[8]

P-value

= 0.579

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

4.4

Confidence interval

level

95%

sides

2-sided

lower limit

-11.1

upper limit

19.8

Notes
[8] - Estimation Comments: Week 5 to Week 8

Statistical analysis 3

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[9]

P-value

= 0.214

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

10.3

Confidence interval

level

95%

sides

2-sided

lower limit

-6

upper limit

26.5

Notes
[9] - Estimation Comments: Week 9 to Week 12

Statistical analysis 4

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[10]

P-value

= 0.165

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

11.7

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

28.3

Notes
[10] - Estimation Comments: Week 13 to Week 16

Statistical analysis 5

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[11]

P-value

= 0.325

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

7.1

Confidence interval

level

95%

sides

2-sided

lower limit

-7.1

upper limit

21.3

Notes
[11] - Estimation Comments: Overall

Statistical analysis 6

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[12]

P-value

= 0.263

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

7.9

Confidence interval

level

95%

sides

2-sided

lower limit

-6

upper limit

21.7

Notes
[12] - Estimation Comments: Week 1 to Week 4

Statistical analysis 7

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[13]

P-value

= 0.334

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

7.6

Confidence interval

level

95%

sides

2-sided

lower limit

-7.9

upper limit

23.2

Notes
[13] - Estimation Comments: Week 5 to Week 8

Statistical analysis 8

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[14]

P-value

= 0.209

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

10.6

Confidence interval

level

95%

sides

2-sided

lower limit

-6

upper limit

27.3

Notes
[14] - Estimation Comments: Week 9 to Week 12

Statistical analysis 9

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[15]

P-value

= 0.227

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

10.5

Confidence interval

level

95%

sides

2-sided

lower limit

-6.5

upper limit

27.4

Notes
[15] - Estimation Comments: Week 13 to Week 16

Statistical analysis 10

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[16]

P-value

= 0.276

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

7.9

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

22.1

Notes
[16] - Estimation Comments: Overall

Statistical analysis 11

Comparison groups

FSC 100/50 mcg Gly/Gly v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[17]

P-value

= 0.541

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

4.2

Confidence interval

level

95%

sides

2-sided

lower limit

-9.2

upper limit

17.6

Notes
[17] - Estimation Comments: Week 1 to Week 4

Statistical analysis 12

Comparison groups

FSC 100/50 mcg Gly/Gly v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[18]

P-value

= 0.668

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

3.3

Confidence interval

level

95%

sides

2-sided

lower limit

-11.7

upper limit

18.3

Notes
[18] - Estimation Comments: Week 5 to Week 8

Statistical analysis 13

Comparison groups

FSC 100/50 mcg Gly/Gly v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[19]

P-value

= 0.965

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-15.6

upper limit

16.3

Notes
[19] - Estimation Comments: Week 9 to Week 12

Statistical analysis 14

Comparison groups

FSC 100/50 mcg Gly/Gly v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[20]

P-value

= 0.878

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-17.5

upper limit

Notes
[20] - Estimation Comments: Week 13 to Week 16

Statistical analysis 15

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[21]

P-value

= 0.91

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-13

upper limit

14.6

Notes
[21] - Estimation Comments: Overall

Statistical analysis 16

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[22]

P-value

= 0.979

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-10.8

upper limit

10.5

Notes
[22] - Estimation Comments: Week 1 to Week 4

Statistical analysis 17

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[23]

P-value

= 0.725

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

2.3

Confidence interval

level

95%

sides

2-sided

lower limit

-10.7

upper limit

15.4

Notes
[23] - Estimation Comments: Week 5 to Week 8

Statistical analysis 18

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[24]

P-value

= 0.858

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.4

Confidence interval

level

17.2%

sides

2-sided

lower limit

-17.2

upper limit

14.3

Notes
[24] - Estimation Comments: Week 9 to Week 12

Statistical analysis 19

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[25]

P-value

= 0.761

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-2.5

Confidence interval

level

95%

sides

2-sided

lower limit

-19.1

upper limit

Notes
[25] - Estimation Comments: Week 13 to Week 16

Statistical analysis 20

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[26]

P-value

= 0.836

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-13

upper limit

10.6

Notes
[26] - Estimation Comments: Overall

Statistical analysis 21

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[27]

P-value

= 0.149

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

7.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.8

upper limit

18.2

Notes
[27] - Estimation Comments: Week 1 to Week 4

Statistical analysis 22

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[28]

P-value

= 0.21

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

8.2

Confidence interval

level

95%

sides

2-sided

lower limit

-4.6

upper limit

Notes
[28] - Estimation Comments: Week 5 to Week 8

Statistical analysis 23

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[29]

P-value

= 0.183

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

10.5

Confidence interval

level

95%

sides

2-sided

lower limit

-5

upper limit

25.9

Notes
[29] - Estimation Comments: Week 9 to Week 12

Statistical analysis 24

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[30]

P-value

= 0.13

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

12.5

Confidence interval

level

95%

sides

2-sided

lower limit

-3.7

upper limit

28.7

Notes
[30] - Estimation Comments: Week 13 to Week 16

Statistical analysis 25

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[31]

P-value

= 0.095

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

9.8

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

21.4

Notes
[31] - Estimation Comments: Overall

Statistical analysis 26

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[32]

P-value

= 0.131

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

7.8

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

Notes
[32] - Estimation Comments: Week 1 to Week 4

Statistical analysis 27

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[33]

P-value

= 0.357

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

5.8

Confidence interval

level

95%

sides

2-sided

lower limit

-6.6

upper limit

18.3

Notes
[33] - Estimation Comments: Week 5 to Week 8

Statistical analysis 28

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[34]

P-value

= 0.123

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

11.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

Notes
[34] - Estimation Comments: Week 9 to Week 12

Statistical analysis29

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[35]

P-value

= 0.06

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

15.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

30.8

Notes
[35] - Estimation Comments: Week 13 to Week 16

Statistical analysis 30

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[36]

P-value

= 0.054

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

11.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

22.3

Notes
[36] - Estimation Comments: Overall

Secondary: Mean change from baseline in the evening peak expiratory flow (PM PEF) following the double-blind treatment period.

Top of page

End point title

Mean change from baseline in the evening peak expiratory flow (PM PEF) following the double-blind treatment period.

End point description

PM PEF change from baseline was characterized by the area under the PM PEF curve relative to baseline AUC(bl) over the 16-week double-blind treatment period. Baseline was defined as the average of the values from the 7 days preceding Visit 6 since these measures were derived from data collected in the evening. . ANCOVA model, including terms for genotype, ethnicity stratum and baseline, was used to assess non-inferiority in PM PEF mean change from baseline for the overall 16-week double-blind treatment period. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).(Overall: Baseline to Week 16).

End point type

Secondary

End point timeframe

Baseline and Upto 114 days

End point values	FSC 100/50 microgram (mcg) Arg/Arg	FSC 100/50 mcg Arg/Gly	FSC 100/50 mcg Gly/Gly	SM 50 mcg Arg/Arg	SM 50 mcg Arg/Gly	SM 50 mcg Gly/Gly
Number of subjects analysed	87 ^[37]	91 ^[38]	90 ^[39]	86 ^[40]	89 ^[41]	91 ^[42]
Units: Litre/Minute
arithmetic mean (standard error)
Week 1-4 (n=83, 91, 88, 79, 86, 88)	21.7 ± 4.52	22.7 ± 4.45	17.1 ± 5.7	15.8 ± 3.34	19.7 ± 5.19	8.7 ± 3.18
Week 5-8 (n=80, 88, 85, 75,82, 82)	27.9 ± 5.46	26.8 ± 4.97	21.6 ± 6.43	20.3 ± 4.5	21.8 ± 5.97	11.7 ± 3.57
Week 9-12 (n=76,88,78, 72, 77,78)	29.7 ± 5.46	26.5 ± 5.19	23.1 ± 6.78	22.9 ± 5.4	33 ± 7.78	11.8 ± 3.88
Week 13-16 (n=75, 86, 77, 69, 74, 75)	31.3 ± 5.65	25.5 ± 5.14	24.7 ± 6.56	21.3 ± 5.1	30.6 ± 8.12	10.7 ± 4.64
Overall n=83, 91, 88, 79,86, 88	26.8 ± 4.75	25 ± 4.57	22.4 ± 5.79	19.3 ± 3.86	26.2 ± 5.89	10.5 ± 3.15

Notes
[37] - ITT Population (Excluding Investigator 018742)
[38] - ITT Population (Excluding Investigator 018742)
[39] - ITT Population (Excluding Investigator 018742)
[40] - ITT Population (Excluding Investigator 018742)
[41] - ITT Population (Excluding Investigator 018742)
[42] - ITT Population (Excluding Investigator 018742)

Statistical analysis 1

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[43]

P-value

= 0.943

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-13.1

upper limit

14.1

Notes
[43] - Estimation Comments: Week 1 to Week 4

Statistical analysis 3

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[44]

P-value

= 0.621

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-11.9

upper limit

19.9

Notes
[44] - Estimation Comments: Week 9 to Week 12

Statistical analysis 2

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[45]

P-value

= 0.811

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

1.9

Confidence interval

level

95%

sides

2-sided

lower limit

-13.7

upper limit

17.5

Notes
[45] - Estimation Comments: Week 5 to Week 8

Statistical analysis 4

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[46]

P-value

= 0.463

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

5.9

Confidence interval

level

95%

sides

2-sided

lower limit

-9.9

upper limit

21.6

Notes
[46] - Estimation Comments: Week 13 to Week 16

Statistical analysis 6

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[47]

P-value

= 0.667

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-10.9

upper limit

Notes
[47] - Estimation Comments: overall

Statistical analysis 7

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[48]

P-value

= 0.402

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

5.8

Confidence interval

level

95%

sides

2-sided

lower limit

-7.8

upper limit

19.4

Notes
[48] - Estimation Comments: Week 1 to Week 4

Statistical analysis 9

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[49]

P-value

= 0.427

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

6.6

Confidence interval

level

95%

sides

2-sided

lower limit

-9.7

upper limit

22.9

Notes
[49] - Estimation Comments: Week 9 to Week 12

Statistical analysis 8

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[50]

P-value

= 0.359

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

7.3

Confidence interval

level

95%

sides

2-sided

lower limit

-8.4

upper limit

Notes
[50] - Estimation Comments: Week 5 to Week 8

Statistical analysis 10

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[51]

P-value

= 0.443

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

6.3

Confidence interval

level

95%

sides

2-sided

lower limit

-9.9

upper limit

22.5

Notes
[51] - Estimation Comments: Week 13 to Week 16

Statisticial analysis 11

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[52]

P-value

= 0.433

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

5.6

Confidence interval

level

95%

sides

2-sided

lower limit

-8.4

upper limit

19.6

Notes
[52] - Estimation Comments: Overall

Statistical analysis 12

Comparison groups

FSC 100/50 mcg Arg/Gly v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[53]

P-value

= 0.429

Method

ANCOVA

Parameter type

Median difference (final values)

Point estimate

5.3

Confidence interval

level

95%

sides

2-sided

lower limit

-7.9

upper limit

18.5

Notes
[53] - Estimation Comments: Week 1 to Week 4

Statistical analysis 12

Comparison groups

FSC 100/50 mcg Arg/Gly v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[54]

P-value

= 0.483

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

5.4

Confidence interval

level

95%

sides

2-sided

lower limit

-9.8

upper limit

20.6

Notes
[54] - Estimation Comments: Week 5 to Week 8

Statistical analysis 13

Comparison groups

FSC 100/50 mcg Arg/Gly v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[55]

P-value

= 0.745

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

2.6

Confidence interval

level

95%

sides

2-sided

lower limit

-13.1

upper limit

18.3

Notes
[55] - Estimation Comments: Week 9 to Week 12

Statistical analysis 14

Comparison groups

FSC 100/50 mcg Arg/Gly v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[56]

P-value

= 0.958

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-15.1

upper limit

15.9

Notes
[56] - Week 13 to Week 16

Statistical analysis 15

Comparison groups

FSC 100/50 mcg Arg/Gly v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[57]

P-value

= 0.714

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

2.5

Confidence interval

level

95%

sides

2-sided

lower limit

-11.1

upper limit

16.1

Notes
[57] - Estimation Comments: Overall

Statistical analysis 16

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[58]

P-value

= 0.957

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-11.5

upper limit

10.9

Notes
[58] - Estimation Comments: Week 1 to Week 4

Statistical analysis 17

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[59]

P-value

= 0.741

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

2.3

Confidence interval

level

95%

sides

2-sided

lower limit

-11.2

upper limit

15.7

Notes
[59] - Estimation Comments: Week 5 to Week 8

Statistical analysis 19

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[60]

P-value

= 0.586

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-4.9

Confidence interval

level

95%

sides

2-sided

lower limit

-22.4

upper limit

12.7

Notes
[60] - Estimation Comments: Week 13 to Week 16

Statistical analysis 18

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[61]

P-value

= 0.479

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-6

Confidence interval

level

95%

sides

2-sided

lower limit

-22.8

upper limit

10.7

Notes
[61] - Estimation Comments: Week 9 to Week 12

Statistical analysis 20

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[62]

P-value

= 0.648

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-2.9

Confidence interval

level

95%

sides

2-sided

lower limit

-15.4

upper limit

9.6

Notes
[62] - Estimation Comments: Overall

Statistical analysis 21

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[63]

P-value

= 0.086

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

9.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

20.8

Notes
[63] - Estimation Comments: Week 1 to Week 4

Statistical analysis 22

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[64]

P-value

= 0.094

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

11.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

24.6

Notes
[64] - Estimation Comments: Week 5 to Week 8

Statistical analysis 24

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[65]

P-value

= 0.112

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-3.3

upper limit

31.4

Notes
[65] - Estimation Comments: Week 13 to Week 16

Statistical analysis 23

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[66]

P-value

= 0.097

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-2.6

upper limit

30.5

Notes
[66] - Estimation Comments: Week 9 to Week 12

Statistical analysis 25

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[67]

P-value

= 0.062

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

11.7

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

Notes
[67] - Estimation Comments: Overall

Statistical analysis 26

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[68]

P-value

= 0.068

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

20.7

Notes
[68] - Estimation Comments: Week 1 to Week 4

Statistical analysis 27

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[69]

P-value

= 0.165

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

9.1

Confidence interval

level

95%

sides

2-sided

lower limit

-3.8

upper limit

21.9

Notes
[69] - Estimation Comments: Week 5 to Week 8

Statistical analysis 28

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[70]

P-value

= 0.015

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

3.9

upper limit

36.2

Notes
[70] - Estimation Comments: Week 9 to Week 12

Statistical analysis 29

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[71]

P-value

= 0.028

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

18.9

Confidence interval

level

95%

sides

2-sided

lower limit

2.1

upper limit

35.7

Notes
[71] - Estimation Comments: Week 13 to Week 16

Statistical analysis 30

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[72]

P-value

= 0.017

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

14.6

Confidence interval

level

95%

sides

2-sided

lower limit

2.7

upper limit

26.5

Notes
[72] - Estimation Comments: Overall

Secondary: Mean forced expiratory volume in one second (FEV1) change from baseline over the 16-week double-blind treatment period

Top of page

End point title

Mean forced expiratory volume in one second (FEV1) change from baseline over the 16-week double-blind treatment period

End point description

FEV1 is the amount of air that is forcefully exhaled in one second of the FVC test. FEV1 was performed on all subjects using the spirometry equipment at each site. It was calculated as the last scheduled measurement of pre-dose FEV1 during the 16-week double-blind treatment period. Baseline was defined as the pre-dose FEV1 measure from Randomization (Visit 6). Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles). P-values are from an ANCOVA model with terms for baseline, ethnicity stratum and Arg16Gly genotype. (Overall: Baseline to Week 16).

End point type

Secondary

End point timeframe

Baseline and Upto 114 days

End point values	FSC 100/50 microgram (mcg) Arg/Arg	FSC 100/50 mcg Arg/Gly	FSC 100/50 mcg Gly/Gly	SM 50 mcg Arg/Arg	SM 50 mcg Arg/Gly	SM 50 mcg Gly/Gly
Number of subjects analysed	87 ^[73]	91 ^[74]	90 ^[75]	86 ^[76]	89 ^[77]	91 ^[78]
Units: Liter
arithmetic mean (standard error)
Visit 7 (Week 4), n=81, 89, 88, 79,84, 84	0.22 ± 0.03	0.22 ± 0.033	0.2 ± 0.037	0.25 ± 0.045	0.13 ± 0.035	0.11 ± 0.032
Visit 8 (Week 8) , n=79, 88, 81,75, 78, 79	0.22 ± 0.031	0.22 ± 0.034	0.23 ± 0.032	0.16 ± 0.032	0.18 ± 0.038	0.07 ± 0.037
Visit 9 (Week 12) , n=78, 84, 79 ,69, 75, 76	0.22 ± 0.031	0.23 ± 0.038	0.22 ± 0.035	0.2 ± 0.038	0.12 ± 0.035	0.07 ± 0.031
Visit 10 (Week 16) , n=77, 83, 79, 66, 73, 75	0.21 ± 0.036	0.23 ± 0.039	0.21 ± 0.042	0.22 ± 0.057	0.08 ± 0.035	0.05 ± 0.033
Endpoint , n=81, 89, 88, 79, 84, 84	0.21 ± 0.034	0.23 ± 0.038	0.2 ± 0.038	0.21 ± 0.049	0.11 ± 0.033	0.05 ± 0.031
Overall , n=81, 89, 88, 79,84, 84	0.22 ± 0.027	0.22 ± 0.033	0.21 ± 0.029	0.21 ± 0.032	0.13 ± 0.029	0.08 ± 0.027

Notes
[73] - ITT (Excluding Investigator 018742)
[74] - ITT (Excluding Investigator 018742)
[75] - ITT (Excluding Investigator 018742)
[76] - ITT (Excluding Investigator 018742)
[77] - ITT (Excluding Investigator 018742)
[78] - ITT (Excluding Investigator 018742)

Statistical analysis 1

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[79]

P-value

= 0.869

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.09

upper limit

0.1

Notes
[79] - Estimation Comments: Visit 7 (Week 4)

Statistical analysis 2

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[80]

P-value

= 0.694

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.07

upper limit

0.11

Notes
[80] - Estimation Comments: Visit 8 (Week 8)

Statistical analysis 3

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[81]

P-value

= 0.925

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.09

upper limit

0.1

Notes
[81] - Estimation Comments: Visit 9 (Week 12)

Statistical analysis 4

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[82]

P-value

= 0.775

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.13

upper limit

0.09

Notes
[82] - Estimation Comments: Visit 10 (Week 16)

Statistical analysis 5

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[83]

P-value

= 0.671

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.13

upper limit

0.08

Notes
[83] - Estimation Comments: Endpoint

Statistical analysis 6

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[84]

P-value

= 0.953

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.08

upper limit

0.09

Notes
[84] - Estimation Comments: Overall

Statistical analysis 7

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[85]

P-value

= 0.484

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.06

upper limit

0.13

Notes
[85] - Estimation Comments: Visit 7 (Week 4)

Statistical analysis 8

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[86]

P-value

= 0.988

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.09

upper limit

0.09

Notes
[86] - Estimation Comments: Visit 8 (Week 8)

Statistical analysis 9

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[87]

P-value

= 0.82

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.09

upper limit

0.11

Notes
[87] - Estimation Comments: Visit 9 (Week 12)

Statistical analysis 10

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[88]

P-value

= 0.883

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

0.12

Notes
[88] - Estimation Comments: Visit 10 (Week 16)

Statistical analysis 11

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[89]

P-value

= 0.894

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.1

upper limit

0.11

Notes
[89] - Estimation Comments: Endpoint

Statistical analysis 12

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[90]

P-value

= 0.679

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.07

upper limit

0.1

Notes
[90] - Estimation Comments: Overall

Statistical analysis 13

Comparison groups

FSC 100/50 mcg Arg/Gly v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[91]

P-value

= 0.581

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.07

upper limit

0.12

Notes
[91] - Estimation Comments: Visit 7 (Week 4)

Statistical analysis 14

Comparison groups

FSC 100/50 mcg Arg/Gly v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[92]

P-value

= 0.678

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.11

upper limit

0.07

Notes
[92] - Estimation Comments: Visit 8 (Week 8)

Statistical analysis 15

Comparison groups

FSC 100/50 mcg Arg/Gly v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[93]

P-value

= 0.891

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.09

upper limit

0.1

Notes
[93] - Estimation Comments: Visit 9 (Week 12)

Statistical analysis 16

Comparison groups

FSC 100/50 mcg Arg/Gly v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[94]

P-value

= 0.66

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.08

upper limit

0.13

Notes
[94] - Estimation Comments: Visit 10 (Week 16)

Statistical analysis 17

Comparison groups

FSC 100/50 mcg Gly/Gly v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[95]

P-value

= 0.565

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.07

upper limit

0.13

Notes
[95] - Estimation Comments: Endpoint

Statistical analysis 18

Comparison groups

FSC 100/50 mcg Arg/Gly v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[96]

P-value

= 0.714

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.07

upper limit

0.1

Notes
[96] - Estimation Comments: Overall

Statistical analysis 19

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[97]

P-value

= 0.041

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.11

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

0.22

Notes
[97] - Estimation Comments: Visit 7 (Week 4)

Statistical analysis 20

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[98]

P-value

= 0.736

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.12

upper limit

0.08

Notes
[98] - Estimation Comments: Visit 8 (Week 8)

Statistical analysis 21

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[99]

P-value

= 0.08

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.01

upper limit

0.19

Notes
[99] - Estimation Comments: Visit 9 (Week 12)

Statistical analysis 22

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[100]

P-value

= 0.022

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.14

Confidence interval

level

95%

sides

2-sided

lower limit

0.02

upper limit

0.26

Notes
[100] - Estimation Comments: Visit 10 (Week 16)

Statistical analysis 23

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[101]

P-value

= 0.055

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.11

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

0.22

Notes
[101] - Estimation Comments: Endpoint

Statistical analysis 24

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[102]

P-value

= 0.076

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.01

upper limit

0.16

Notes
[102] - Estimation Comments: Overall

Statistical analysis 25

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[103]

P-value

= 0.016

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.02

upper limit

0.23

Notes
[103] - Estimation Comments: Visit 7 (Week 4)

Statistical analysis 26

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[104]

P-value

= 0.075

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.01

upper limit

0.19

Notes
[104] - Estimation Comments: Visit 8 (Week 8)

Statistical analysis 27

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[105]

P-value

= 0.007

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.14

Confidence interval

level

95%

sides

2-sided

lower limit

0.04

upper limit

0.23

Notes
[105] - Estimation Comments: Visit 9 (Week 12)

Statistical analysis 28

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[106]

P-value

= 0.003

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.18

Confidence interval

level

95%

sides

2-sided

lower limit

0.06

upper limit

0.3

Notes
[106] - Estimation Comments: Visit 10 (Week 16)

Statistical analysis 29

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[107]

P-value

= 0.004

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.05

upper limit

0.27

Notes
[107] - Estimation Comments: Endpoint

Statistical analysis 30

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[108]

P-value

= 0.003

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.13

Confidence interval

level

95%

sides

2-sided

lower limit

0.04

upper limit

0.21

Notes
[108] - Estimation Comments: Overall

Statistical analysis 31

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[109]

P-value

= 0.712

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.08

upper limit

0.12

Notes
[109] - Estimation Comments: Visit 7 (Week 4)

Statistical analysis 32

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[110]

P-value

= 0.031

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.11

Confidence interval

level

95%

sides

2-sided

lower limit

0.01

upper limit

0.21

Notes
[110] - Estimation Comments: Visit 8 (Week 8)

Statistical analysis 33

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[111]

P-value

= 0.331

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

0.14

Notes
[111] - Estimation Comments: Visit 9 (Week 12)

Statistical analysis 34

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[112]

P-value

= 0.517

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.08

upper limit

0.15

Notes
[112] - Estimation Comments: Visit 10 (Week 16)

Statistical analysis 35

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

equivalence ^[113]

P-value

= 0.311

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

0.16

Notes
[113] - Estimation Comments: Endpoint

Statistical analysis 36

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[114]

P-value

= 0.218

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.03

upper limit

0.13

Notes
[114] - Estimation Comments: Overall

Secondary: Mean change from baseline in percent of symptom-free days

Top of page

End point title

Mean change from baseline in percent of symptom-free days

End point description

A symptom-free day was defined as a day with no symptoms (that is a score of 0, indicated no asthma symptoms during the day or previous night, recorded in the daily diary). Percent of symptom-free days was calculated as the number of symptom-free days divided by the total number of days in the assessment period, multiplied by 100 for each participant. Baseline was defined as the average of the values from the 7 days preceding Visit 6 since these measures were derived from data collected in the evening. P-values are from an ANCOVA model with terms for baseline, ethnicity stratum and Arg16Gly genotype. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles) (Overall: Baseline to Week 16).

End point type

Secondary

End point timeframe

Baseline and Upto 114 days

End point values	FSC 100/50 microgram (mcg) Arg/Arg	FSC 100/50 mcg Arg/Gly	FSC 100/50 mcg Gly/Gly	SM 50 mcg Arg/Arg	SM 50 mcg Arg/Gly	SM 50 mcg Gly/Gly
Number of subjects analysed	87 ^[115]	91 ^[116]	90 ^[117]	86 ^[118]	89 ^[119]	91 ^[120]
Units: Days
arithmetic mean (standard error)
Weeks 1-4, n=80, 90, 87, 78, 86, 87	9.5 ± 2.91	12.5 ± 3.13	16.2 ± 2.99	7.1 ± 3.09	7.7 ± 3.08	6.7 ± 2.84
Weeks 5-8, n=78, 87, 83, 74,82, 82	9 ± 3.11	15.1 ± 3.28	19.5 ± 3.31	9.8 ± 3.7	7.1 ± 3.14	7.3 ± 3.04
Weeks 9-12, n=74, 87, 78, 71,77, 78	11.6 ± 3.32	16.6 ± 3.72	17.4 ± 3.29	11.5 ± 3.82	8.3 ± 2.71	9.3 ± 3.03
Weeks 13-16, n=73, 84, 76, 68,74, 75	11 ± 3.47	15.2 ± 4.03	18.1 ± 3.28	12.2 ± 4.3	8.3 ± 2.8	8.2 ± 3.2
Overall, n=80, 90, 88, 79,86, 88	9.9 ± 2.83	14.6 ± 3.19	18.2 ± 2.88	9.6 ± 3.21	9.1 ± 2.69	8.2 ± 2.69

Notes
[115] - ITT Population (Excluding Investigator 018742)
[116] - ITT Population (Excluding Investigator 018742)
[117] - ITT Population (Excluding Investigator 018742)
[118] - ITT Population (Excluding Investigator 018742)
[119] - ITT Population (Excluding Investigator 018742)
[120] - ITT Population (Excluding Investigator 018742)

Statistical analysis 1

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[121]

P-value

= 0.501

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-2.8

Confidence interval

level

95%

sides

2-sided

lower limit

-11.1

upper limit

5.5

Notes
[121] - Estimation Comments: Week 1 to 4

Statistical analysis 2

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[122]

P-value

= 0.187

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-5.9

Confidence interval

level

95%

sides

2-sided

lower limit

-14.7

upper limit

2.9

Notes
[122] - Estimation Comments: Week 5 to 8

Statistical analysis 3

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[123]

P-value

= 0.383

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-4.1

Confidence interval

level

95%

sides

2-sided

lower limit

-13.5

upper limit

5.2

Notes
[123] - Estimation Comments: Week 9 to 12

Statistical analysis 4

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[124]

P-value

= 0.503

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-3.3

Confidence interval

level

95%

sides

2-sided

lower limit

-13

upper limit

6.4

Notes
[124] - Estimation Comments: Week 13 to 16

Statistical analysis 5

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[125]

P-value

= 0.271

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-4.5

Confidence interval

level

95%

sides

2-sided

lower limit

-12.6

upper limit

3.6

Notes
[125] - Estimation Comments: Overall

Statistical analysis 6

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[126]

P-value

= 0.144

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-6.2

Confidence interval

level

95%

sides

2-sided

lower limit

-14.5

upper limit

2.1

Notes
[126] - Estimation Comments: Week 1 to 4

Statistical analysis 7

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[127]

P-value

= 0.028

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-9.9

Confidence interval

level

95%

sides

2-sided

lower limit

-18.8

upper limit

-1.1

Notes
[127] - Estimation Comments: Week 5 to 8

Statistical analysis 8

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[128]

P-value

= 0.316

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-4.8

Confidence interval

level

95%

sides

2-sided

lower limit

-14.3

upper limit

4.6

Notes
[128] - Estimation Comments: Week 9 to 12

Statistical analysis 9

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[129]

P-value

= 0.208

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-6.3

Confidence interval

level

95%

sides

2-sided

lower limit

-16.2

upper limit

3.6

Notes
[129] - Estimation Comments: Week 13 to 16

Statistical analysis 10

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[130]

P-value

= 0.061

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-7.7

Confidence interval

level

95%

sides

2-sided

lower limit

-15.8

upper limit

0.4

Notes
[130] - Estimation Comments: Overall

Statistical analysis 11

Comparison groups

FSC 100/50 mcg Arg/Gly v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[131]

P-value

= 0.411

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-3.3

Confidence interval

level

95%

sides

2-sided

lower limit

-11.4

upper limit

4.7

Notes
[131] - Estimation Comments: Week 1 to 4

Statistical analysis 12

Comparison groups

FSC 100/50 mcg Arg/Gly v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[132]

P-value

= 0.354

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-4

Confidence interval

level

95%

sides

2-sided

lower limit

-12.6

upper limit

4.5

Notes
[132] - Estimation Comments: Week 5 to 8

Statistical analysis 13

Comparison groups

FSC 100/50 mcg Arg/Gly v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[133]

P-value

= 0.878

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-9.8

upper limit

8.4

Notes
[133] - Estimation Comments: Week 9 to 12

Statistical analysis 14

Comparison groups

FSC 100/50 mcg Arg/Gly v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[134]

P-value

= 0.53

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-3

Confidence interval

level

95%

sides

2-sided

lower limit

-12.6

upper limit

6.5

Notes
[134] - Estimation Comments: Week 13 to 16

Statistical analysis 15

Comparison groups

FSC 100/50 mcg Arg/Gly v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[135]

P-value

= 0.419

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-3.2

Confidence interval

level

95%

sides

2-sided

lower limit

-11

upper limit

4.6

Notes
[135] - Estimation Comments: Overall

Statistical analysis 16

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[136]

P-value

= 0.981

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-8

upper limit

7.8

Notes
[136] - Estimation Comments: Week 1 to Week 4

Statistical analysis 17

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[137]

P-value

= 0.465

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

3.2

Confidence interval

level

95%

sides

2-sided

lower limit

-5.4

upper limit

11.9

Notes
[137] - Estimation Comments: Week 5 to 8

Statistical analysis 18

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[138]

P-value

= 0.342

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

4.2

Confidence interval

level

95%

sides

2-sided

lower limit

-4.4

upper limit

12.7

Notes
[138] - Estimation Comments: Week 9 to 12

Statistical analysis 19

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[139]

P-value

= 0.357

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

4.3

Confidence interval

level

95%

sides

2-sided

lower limit

-4.9

upper limit

13.5

Notes
[139] - Estimation Comments: Week 13 to 16

Statistical analysis 20

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[140]

P-value

= 0.768

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-6.4

upper limit

8.6

Notes
[140] - Estimation Comments: Overall

Statistical analysis 21

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[141]

P-value

= 0.774

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-6.7

upper limit

Notes
[141] - Estimation Comments: Week 1 to Week 4

Statistical analysis 22

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[142]

P-value

= 0.432

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

3.4

Confidence interval

level

95%

sides

2-sided

lower limit

-5.2

upper limit

Notes
[142] - Estimation Comments: Week 5 to 8

Statistical analysis 23

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[143]

P-value

= 0.394

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

3.7

Confidence interval

level

95%

sides

2-sided

lower limit

-4.8

upper limit

12.2

Notes
[143] - Estimation Comments: Week 9 to 12

Statistical analysis 24

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[144]

P-value

= 0.215

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

5.8

Confidence interval

level

95%

sides

2-sided

lower limit

-3.4

upper limit

14.9

Notes
[144] - Estimation Comments: Week 13 to 16

Statistical analysis 25

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[145]

P-value

= 0.583

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-5.4

upper limit

9.5

Notes
[145] - Estimation Comments: Overall

Statistical analysis 26

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[146]

P-value

= 0.749

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-6.4

upper limit

8.9

Notes
[146] - Estimation Comments: Week 1 to 4

Statistical analysis 27

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[147]

P-value

= 0.96

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-8.1

upper limit

8.5

Notes
[147] - Estimation Comments: Week 5 to 8

Statistical analysis 28

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[148]

P-value

= 0.911

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-8.7

upper limit

7.8

Notes
[148] - Estimation Comments: Week 9 to 12

Statistical analysis 29

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[149]

P-value

= 0.747

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

1.5

Confidence interval

level

95%

sides

2-sided

lower limit

-7.4

upper limit

10.3

Notes
[149] - Estimation Comments: Week 13 to 16

Statistical analysis 30

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[150]

P-value

= 0.795

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

8.2

Notes
[150] - Estimation Comments: Overall

Secondary: Mean change from baseline in supplemental ipratropium use over the 16-week double-blind treatment periods

Top of page

End point title

Mean change from baseline in supplemental ipratropium use over the 16-week double-blind treatment periods

End point description

Supplemental ipratropium use was analyzed as the number of puffs taken per day. Baseline was defined as the average of the values from the 7 days preceding Visit 6 since these measures were derived from data collected in the evening.P-values are from an ANCOVA model with terms for baseline, ethnicity stratum and Arg16Gly genotype. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).(Overall: Baseline to Week 16).

End point type

Secondary

End point timeframe

Baseline and Upto 114 days

End point values	FSC 100/50 microgram (mcg) Arg/Arg	FSC 100/50 mcg Arg/Gly	FSC 100/50 mcg Gly/Gly	SM 50 mcg Arg/Arg	SM 50 mcg Arg/Gly	SM 50 mcg Gly/Gly
Number of subjects analysed	87 ^[151]	91 ^[152]	90 ^[153]	86 ^[154]	89 ^[155]	91 ^[156]
Units: Puffs/Day
arithmetic mean (standard error)
Weeks 1-4, n=81, 87, 85, 78, 84, 83	-0.47 ± 0.112	-0.54 ± 0.109	-0.6 ± 0.121	-0.34 ± 0.105	-0.37 ± 0.122	-0.33 ± 0.092
Weeks 5-8, n=78, 83, 81, 74, 81, 78	-0.47 ± 0.113	-0.68 ± 0.119	-0.67 ± 0.131	-0.31 ± 0.118	-0.38 ± 0.131	-0.31 ± 0.095
Weeks 9-12, n=73, 84, 75, 71, 76, 74	-0.49 ± 0.124	-0.69 ± 0.129	-0.53 ± 0.115	-0.42 ± 0.119	-0.53 ± 0.121	-0.41 ± 0.09
Weeks 13-16, n=73, 82, 74, 68, 73, 71	-0.55 ± 0.115	-0.68 ± 0.129	-0.47 ± 0.102	-0.49 ± 0.118	-0.56 ± 0.132	-0.42 ± 0.1
Overall, n=81, 87, 86, 79, 85, 84	-0.49 ± 0.11	-0.63 ± 0.113	-0.6 ± 0.117	-0.36 ± 0.102	-0.45 ± 0.118	-0.35 ± 0.083

Notes
[151] - ITT Population (Excluding Investigator 018742)
[152] - ITT Population (Excluding Investigator 018742)
[153] - ITT Population (Excluding Investigator 018742)
[154] - ITT Population (Excluding Investigator 018742)
[155] - ITT Population (Excluding Investigator 018742)
[156] - ITT Population (Excluding Investigator 018742)

Statistical analysis 1

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[157]

P-value

= 0.516

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.27

upper limit

0.13

Notes
[157] - Estimation Comments: Week 1 to 4

Statistical analysis 2

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[158]

P-value

= 0.702

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.16

upper limit

0.24

Notes
[158] - Estimation Comments: Week 5 to 8

Statistical analysis 3

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[159]

P-value

= 0.614

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.15

upper limit

0.26

Notes
[159] - Estimation Comments: Week 9 to 12

Statistical analysis 4

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[160]

P-value

= 0.75

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.25

upper limit

0.18

Notes
[160] - Estimation Comments: Week 13 to 16

Statistical analysis 5

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Arg/Gly

Number of subjects included in analysis

178

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[161]

P-value

= 0.926

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

0.17

Notes
[161] - Estimation Comments: Overall

Statistical analysis 6

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[162]

P-value

= 0.84

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.22

upper limit

0.18

Notes
[162] - Estimation Comments: Week 1 to 4

Statistical analysis 7

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[163]

P-value

= 0.881

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

0.22

Notes
[163] - Estimation Comments: Week 5 to 8

Statistical analysis 8

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[164]

P-value

= 0.545

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.27

upper limit

0.14

Notes
[164] - Estimation Comments: Week 9 to 12

Statistical analysis 9

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[165]

P-value

= 0.199

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.14

Confidence interval

level

95%

sides

2-sided

lower limit

-0.36

upper limit

0.08

Notes
[165] - Estimation Comments: Week 13 to 16

Statistical analysis 10

Comparison groups

FSC 100/50 microgram (mcg) Arg/Arg v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[166]

P-value

= 0.637

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.04

Confidence interval

level

95%

sides

2-sided

lower limit

-0.22

upper limit

0.14

Notes
[166] - Estimation Comments: Overall

Statistical analysis 11

Comparison groups

FSC 100/50 mcg Arg/Gly v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[167]

P-value

= 0.646

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.15

upper limit

0.24

Notes
[167] - Estimation Comments: Week 1 to 4

Statistical analysis 12

Comparison groups

FSC 100/50 mcg Arg/Gly v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[168]

P-value

= 0.812

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-0.22

upper limit

0.17

Notes
[168] - Estimation Comments: Week 5 to 8

Statistical analysis 13

Comparison groups

FSC 100/50 mcg Arg/Gly v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[169]

P-value

= 0.254

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-0.32

upper limit

0.08

Notes
[169] - Estimation Comments: Week 9 to 12

Statistical analysis 14

Comparison groups

FSC 100/50 mcg Arg/Gly v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[170]

P-value

= 0.316

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.11

Confidence interval

level

95%

sides

2-sided

lower limit

-0.32

upper limit

0.1

Notes
[170] - Estimation Comments: Week 13 to 16

Statistical analysis 15

Comparison groups

FSC 100/50 mcg Arg/Gly v FSC 100/50 mcg Gly/Gly

Number of subjects included in analysis

181

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[171]

P-value

= 0.697

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.21

upper limit

0.14

Notes
[171] - Estimation Comments: Overall

Statistical analysis 16

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[172]

P-value

= 0.607

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.26

upper limit

0.15

Notes
[172] - Estimation Comments: Week 1 to 4

Statistical analysis 17

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[173]

P-value

= 0.997

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.23

upper limit

0.23

Notes
[173] - Estimation comments: week 5 to 8

Statistical analysis 18

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[174]

P-value

= 0.799

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-0.17

upper limit

0.22

Notes
[174] - Estimation Comments: Week 9 to 12

Statistical analysis 19

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[175]

P-value

= 0.614

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.25

upper limit

0.15

Notes
[175] - Estimation Comments: Week 13 to 16

Statistical analysis 20

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[176]

P-value

= 0.914

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

0.17

Notes
[176] - Estimation Comments: Overall

Statistical analysis 21

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[177]

P-value

= 0.573

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.06

Confidence interval

level

95%

sides

2-sided

lower limit

-0.26

upper limit

0.15

Notes
[177] - Estimation Comments: Week 1 to 4

Statistical analysis 22

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Arg/Gly

Number of subjects included in analysis

175

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[178]

P-value

= 0.673

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.28

upper limit

0.18

Notes
[178] - Estimation Comments: Week 5 to 8

Statistical analysis 23

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[179]

P-value

= 0.439

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.27

upper limit

0.12

Notes
[179] - Estimation Comments: Week 9 to 12

Statistical analysis 24

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[180]

P-value

= 0.087

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.17

Confidence interval

level

95%

sides

2-sided

lower limit

-0.38

upper limit

0.03

Notes
[180] - Estimation Comments: Week 13 to 16

Statistical analysis 25

Comparison groups

SM 50 mcg Arg/Arg v SM 50 mcg Gly/Gly

Number of subjects included in analysis

177

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[181]

P-value

= 0.347

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.09

Confidence interval

level

95%

sides

2-sided

lower limit

-0.26

upper limit

0.09

Notes
[181] - Estimation Comments: Overall

Statistical analysis 26

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[182]

P-value

= 0.959

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.19

Notes
[182] - Estimation Comments: Week 1 to 4

Statistical analysis 27

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[183]

P-value

= 0.66

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.05

Confidence interval

level

95%

sides

2-sided

lower limit

-0.27

upper limit

0.17

Notes
[183] - Estimation Comments: Week 5 to 8

Statistical analysis 28

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[184]

P-value

= 0.291

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.29

upper limit

0.09

Notes
[184] - Estimation Comments: Week 9 to 12

Statistical analysis 29

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[185]

P-value

= 0.21

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.12

Confidence interval

level

95%

sides

2-sided

lower limit

-0.32

upper limit

0.07

Notes
[185] - Estimation Comments: Week 13 to 16

Statistical analysis 30

Comparison groups

SM 50 mcg Arg/Gly v SM 50 mcg Gly/Gly

Number of subjects included in analysis

180

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[186]

P-value

= 0.391

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.08

Confidence interval

level

95%

sides

2-sided

lower limit

-0.25

upper limit

0.1

Notes
[186] - Estimation Comments: Overall

Adverse events

Top of page

Timeframe for reporting adverse events

AEs and SAEs were collected from the time the first dose of study medication until the follow up contact (Up to 240 days)

Adverse event reporting additional description

SAEs and non-serious AEs were collected in members of the Safety Population, comprised of all participants who received at least one dose of study medication.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

9.1

Reporting group title

FSC100/50

Reporting group description

Reporting group 1 description

Reporting group title

Salmeterol

Reporting group description

Reporting group 2 description

Serious adverse events	FSC100/50	Salmeterol
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 272 (0.00%)	2 / 272 (0.74%)
number of deaths (all causes)	0	1
number of deaths resulting from adverse events	0	0
Reproductive system and breast disorders
Ovarian cyst ruptured
subjects affected / exposed	0 / 272 (0.00%)	1 / 272 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 272 (0.00%)	1 / 272 (0.37%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 1

Frequency threshold for reporting non-serious adverse events: 3%

Non-serious adverse events	FSC100/50	Salmeterol
Total subjects affected by non serious adverse events
subjects affected / exposed	63 / 272 (23.16%)	65 / 272 (23.90%)
Nervous system disorders
Headache
subjects affected / exposed	36 / 272 (13.24%)	30 / 272 (11.03%)
occurrences all number	85	70
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal pain
subjects affected / exposed	11 / 272 (4.04%)	7 / 272 (2.57%)
occurrences all number	13	7
Infections and infestations
Nasopharyngitis
subjects affected / exposed	21 / 272 (7.72%)	18 / 272 (6.62%)
occurrences all number	28	20
Upper respiratory tract infection
subjects affected / exposed	8 / 272 (2.94%)	12 / 272 (4.41%)
occurrences all number	9	13

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

17 Nov 2004

• Updated sponsor contact information • Removed the limitation for methacholine challenge testing only on subject ≥18 years of age • Added historical PC20 <8mg/ml as acceptable • Added exclusion criterion of exercise induced bronchospasm • Modified time intervals for anti-asthma medications • Clarified use of corticosteroids in the Exclusion Criteria • Added an exclusion criterion for peanut and soybean food allergy • Added AM PEF stability limits • Added a requirement to obtain vital signs data during MADR testing • Removed Appendices 5 and 7 • Corrected administrative and typographical errors

14 Jun 2005

• Clarifications in the Protocol Summary, Open-Label Treatment periods (continuation criteria added at Visit 2) • Study population (number of screened subjects) • Section 5, Inclusion criteria numbers 3, 6, and 7 regarding pregnancy testing, historical reversibility, and pre-study anti-asthma medication use required for participation • Section 5, Exclusion Criteria numbers 4, 5, 6, 9, and 10 regarding exercise induced bronchospasm, prohibited anti-asthma medications, prohibited concurrent medications, respiratory tract infection and antibiotic use • Section 6 Study Assessments, Rescreening (use of historical reversibility), Visit 2 continuation criteria added, premature discontinuation visit (open-label and washout periods), methacholine challenge testing (manual), albuterol and ipratropium bromide use (during open-label, randomization, and washout periods) • Section 7. Dosage and Administration to include the washout period • Section 8. Concomitant Medications, permitted and prohibited medications to agree with Section 5, inclusion and exclusion criteria ENTIAL RM2007/00065/00 • Section 9. Subject Completion to include a discontinuation visit and Withdrawal to include screen and open-label, washout failures (data collection) • Section 11. Data Analysis and Statistical Considerations, Other Comparisons of Interest and Sample Size Considerations modified; • Corrections of administrative and reference errors.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Clinical trials

Clinical Trial Results:
Randomized, Double-Blind Comparison of Advair 100/50 BID vs Salmeterol BID vs Albuterol QID in subjects with ARG/ARG genotype 12 years of Age and Older with Persistent Asthma on Short-Acting Beta2-Agonists Alone

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Mean change from baseline in morning peak expiratory flow (AM/PEF) following the double-blind treatment period.

Primary: Mean change from baseline in morning peak expiratory flow (AM/PEF) following the double-blind treatment period.

Secondary: Mean change from baseline in the evening peak expiratory flow (PM PEF) following the double-blind treatment period.

Secondary: Mean change from baseline in the evening peak expiratory flow (PM PEF) following the double-blind treatment period.

Secondary: Mean forced expiratory volume in one second (FEV1) change from baseline over the 16-week double-blind treatment period

Secondary: Mean forced expiratory volume in one second (FEV1) change from baseline over the 16-week double-blind treatment period

Secondary: Mean change from baseline in percent of symptom-free days

Secondary: Mean change from baseline in percent of symptom-free days

Secondary: Mean change from baseline in supplemental ipratropium use over the 16-week double-blind treatment periods

Secondary: Mean change from baseline in supplemental ipratropium use over the 16-week double-blind treatment periods

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: Randomized, Double-Blind Comparison of Advair 100/50 BID vs Salmeterol BID vs Albuterol QID in subjects with ARG/ARG genotype 12 years of Age and Older with Persistent Asthma on Short-Acting Beta2-Agonists Alone

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Mean change from baseline in morning peak expiratory flow (AM/PEF) following the double-blind treatment period.

Primary: Mean change from baseline in morning peak expiratory flow (AM/PEF) following the double-blind treatment period.

Secondary: Mean change from baseline in the evening peak expiratory flow (PM PEF) following the double-blind treatment period.

Secondary: Mean change from baseline in the evening peak expiratory flow (PM PEF) following the double-blind treatment period.

Secondary: Mean forced expiratory volume in one second (FEV1) change from baseline over the 16-week double-blind treatment period

Secondary: Mean forced expiratory volume in one second (FEV1) change from baseline over the 16-week double-blind treatment period

Secondary: Mean change from baseline in percent of symptom-free days

Secondary: Mean change from baseline in percent of symptom-free days

Secondary: Mean change from baseline in supplemental ipratropium use over the 16-week double-blind treatment periods

Secondary: Mean change from baseline in supplemental ipratropium use over the 16-week double-blind treatment periods

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Randomized, Double-Blind Comparison of Advair 100/50 BID vs Salmeterol BID vs Albuterol QID in subjects with ARG/ARG genotype 12 years of Age and Older with Persistent Asthma on Short-Acting Beta2-Agonists Alone