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Clinical Trial Results:
A Randomised Double-Blind, Double-Dummy, Placebo-Controlled, Stratified, Parallel-Group, Multicentre, Dose Ranging Study to Evaluate the Efficacy and Safety of GSK2190915 Tablets Administered Once Daily, Fluticasone Propionate Inhalation Powder 100mcg Twice Daily and Montelukast 10mg Once Daily compared with Placebo for 8 Weeks in Adolescent and Adult Subjects with Persistent Asthma while Treated with Short Acting Beta2-agonist

Summary
EudraCT number	2010-019095-70
Trial protocol	RO BG
Global end of trial date	06 Oct 2011

Results information
Results version number	v1(current)
This version publication date	27 Apr 2016
First version publication date	22 Jul 2015
Other versions

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

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Trial information

Top of page

Sponsor protocol code

LPA112186

ISRCTN number

US NCT number

NCT01147744

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

18 Nov 2011

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

06 Oct 2011

Was the trial ended prematurely?

Main objective of the trial

The primary objective is to evaluate the efficacy, dose response and safety of four doses of GSK 2190915 (10mg, 30mg, 100mg and 300mg)

Protection of trial subjects

A protocol amendment was issued restricting the study to females only following a finding from an interim histopathological assessment of the male reproductive tract from ongoing 6 month rat and 9 month dog toxicology studies. These findings related to testicular toxicity at high exposures of GSK2190915, the clinical significance of which was uncertain.

Background therapy

Evidence for comparator

Actual start date of recruitment

28 Jun 2010

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 96

Country: Number of subjects enrolled

Romania: 53

Country: Number of subjects enrolled

Bulgaria: 105

Country: Number of subjects enrolled

Japan: 84

Country: Number of subjects enrolled

Ukraine: 186

Country: Number of subjects enrolled

United States: 176

Worldwide total number of subjects

700

EEA total number of subjects

254

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)

Adults (18-64 years)

606

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Participants (par.) were screened (Visit 1) for eligibility, which included reversibility testing. Following screening and a 14-days Run-in Period, par. who met the eligibility criteria for randomization to study treatment at Visit 3 were randomy assigned to receive one of seven double-blind treatments for 8 weeks.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants received two tablets of placebo orally plus one dose of fluticasone propionate (FP) matching placebo twice daily (BID) via dry powder inhaler (DPI) in morning and another dose of FP matching placebo via DPI plus one capsule of montelukast matching placebo orally once daily (QD) in evening for the 8-Weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

GSK2190915, 10 mg, QD

Arm description

Participants received one tablet of 10 milligrams (mg) GSK2190915 orally QD and one tablet of placebo orally plus one dose of FP matching placebo BID via DPI in morning and another dose of FP matching placebo via DPI plus one capsule of montelukast matching placebo orally QD in evening for the 8-Weeks.

Arm type

Experimental

Investigational medicinal product name

GSK2190915

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

10 mg (1 tablet once daily morning)

GSK2190915, 30 mg, QD

Arm description

Participants received one tablet of 30 mg GSK2190915 orally QD and one tablet of placebo orally plus one dose of FP matching placebo BID via DPI in morning and another dose of FP matching placebo via DPI plus one capsule of montelukast matching placebo orally QD in evening for the 8-Weeks.

Arm type

Experimental

Investigational medicinal product name

GSK2190915

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

30 mg (1 tablet once daily morning)

GSK2190915, 100 mg, QD

Arm description

Participants received one tablet of 100 mg GSK2190915 orally QD and one tablet of placebo orally plus one dose of FP matching placebo BID via DPI in morning and another dose of FP matching placebo via DPI plus one capsule of montelukast matching placebo orally QD in evening for the 8-Weeks.

Arm type

Experimental

Investigational medicinal product name

GSK2190915

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

100 mg (1 tablet once daily morning)

GSK2190915, 300 mg, QD

Arm description

Participants received one tablet of 100 mg GSK2190915 and one tablet of 200 mg GSK 2190915 orally QD plus one dose of FP matching placebo BID via DPI in morning and another dose of FP matching placebo BID via DPI plus one capsule of montelukast matching placebo orally QD in evening for the 8-Weeks.

Arm type

Experimental

Investigational medicinal product name

GSK2190915

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

300 mg (2 tablets once daily morning)

FP, 100 µg, BID

Arm description

Participants received one dose of FP 100 microgram (µg) BID via DPI plus two tablets of placebo in morning and another dose of FP 100 µg via DPI plus one capsule of montelukast matching placebo orally QD in evening for the 8-Weeks.

Arm type

Active comparator

Investigational medicinal product name

Fluticasone propionate

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Inhalation use

Dosage and administration details

200 µg (100 µg inhaled morning and evening)

Montelukast, 10 mg, QD

Arm description

Participants received two tablets of placebo orally plus one dose of FP matching placebo BID via DPI in morning and another dose of FP matching placebo via DPI plus one capsule of montelukast 10 mg orally QD in evening for the 8-Weeks.

Arm type

Active comparator

Investigational medicinal product name

Montelukast

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

10 mg (1 capsule once daily evening)

Number of subjects in period 1	Placebo	GSK2190915, 10 mg, QD	GSK2190915, 30 mg, QD	GSK2190915, 100 mg, QD	GSK2190915, 300 mg, QD	FP, 100 µg, BID	Montelukast, 10 mg, QD
Started	100	99	100	100	101	103	97
Completed	71	76	82	82	76	83	78
Not completed	29	23	18	18	25	20	19
Consent withdrawn by subject	8	4	2	2	2	5	2
Physician decision	-	1	1	-	-	-	1
Met Protocol-defined Stopping Criteria	1	-	-	-	-	1	-
Adverse event, non-fatal	1	2	3	-	2	1	2
Sponsor decision to amend protocol	7	4	2	5	7	2	6
Lost to follow-up	-	1	-	-	-	-	-
Lack of efficacy	11	11	9	11	13	8	7
Protocol deviation	1	-	1	-	1	3	1

Baseline characteristics

Top of page

Reporting group title

Placebo

Reporting group description

Reporting group title

GSK2190915, 10 mg, QD

Reporting group description

Reporting group title

GSK2190915, 30 mg, QD

Reporting group description

Reporting group title

GSK2190915, 100 mg, QD

Reporting group description

Reporting group title

GSK2190915, 300 mg, QD

Reporting group description

Reporting group title

FP, 100 µg, BID

Reporting group description

Reporting group title

Montelukast, 10 mg, QD

Reporting group description

Reporting group values	Placebo	GSK2190915, 10 mg, QD	GSK2190915, 30 mg, QD	GSK2190915, 100 mg, QD	GSK2190915, 300 mg, QD	FP, 100 µg, BID	Montelukast, 10 mg, QD	Total
Number of subjects	100	99	100	100	101	103	97	700
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	42.3 ± 16.13	40 ± 15.56	43.1 ± 16.17	42.2 ± 14.63	42.2 ± 14.15	41.5 ± 15.16	44.3 ± 14.97	-
Gender categorical
Units: Subjects
Female	88	91	94	92	93	97	89	644
Male	12	8	6	8	8	6	8	56
Race, Customized
Units: Subjects
African American/African Heritage	6	12	10	9	9	7	9	62
American Indian or Alaska Native	0	0	0	2	1	1	0	4
Asian - Japanese Heritage	12	12	12	11	13	12	12	84
Asian - South East Asian Heritage	0	1	0	0	0	0	0	1
White - White/Caucasian/European Heritage	82	74	78	78	78	83	76	549

End points

Top of page

Reporting group title

Placebo

Reporting group description

Reporting group title

GSK2190915, 10 mg, QD

Reporting group description

Reporting group title

GSK2190915, 30 mg, QD

Reporting group description

Reporting group title

GSK2190915, 100 mg, QD

Reporting group description

Reporting group title

GSK2190915, 300 mg, QD

Reporting group description

Reporting group title

FP, 100 µg, BID

Reporting group description

Reporting group title

Montelukast, 10 mg, QD

Reporting group description

Primary: Mean change from Baseline to the end of the 8-Week treatment period in trough FEV1

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End point title

Mean change from Baseline to the end of the 8-Week treatment period in trough FEV1

End point description

Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 is defined as the morning (AM) pre-dose and pre-rescue bronchodilator FEV1 at the clinic visit. Baseline was the pre-dose value obtained at Visit 3. Change from Baseline was calculated as the end of Week 8 value minus the Baseline value. The analysis was performed using an analysis of covariance (ANCOVA) model with covariates of Baseline trough FEV1, age, gender, country and smoking status. The last observation carried forward (LOCF) method was used to impute missing data. Intent-to-Treat (ITT) Population is comprised of all par. randomized to treatment who received at least one dose of double-blind study medication.

End point type

Primary

End point timeframe

Baseline and Week 8

End point values	Placebo	GSK2190915, 10 mg, QD	GSK2190915, 30 mg, QD	GSK2190915, 100 mg, QD	GSK2190915, 300 mg, QD	FP, 100 µg, BID	Montelukast, 10 mg, QD
Number of subjects analysed	98 ^[1]	96 ^[2]	99 ^[3]	100 ^[4]	98 ^[5]	100 ^[6]	95 ^[7]
Units: Liters
least squares mean (standard error)	0.12 ± 0.04	0.18 ± 0.04	0.23 ± 0.04	0.19 ± 0.04	0.19 ± 0.04	0.31 ± 0.04	0.19 ± 0.04

Notes
[1] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[2] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[3] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[4] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[5] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[6] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[7] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.

Statistical Analysis 1

Comparison groups

Placebo v GSK2190915, 10 mg, QD

Number of subjects included in analysis

194

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.326

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.056

Confidence interval

level

95%

sides

2-sided

lower limit

-0.06

upper limit

0.17

Statistical Analysis 2

Comparison groups

Placebo v GSK2190915, 30 mg, QD

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.066

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.104

Confidence interval

level

95%

sides

2-sided

lower limit

-0.01

upper limit

0.22

Statistical Analysis 3

Comparison groups

Placebo v GSK2190915, 100 mg, QD

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.224

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.069

Confidence interval

level

95%

sides

2-sided

lower limit

-0.04

upper limit

0.18

Statistical Analysis 4

Comparison groups

Placebo v GSK2190915, 300 mg, QD

Number of subjects included in analysis

196

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.271

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.062

Confidence interval

level

95%

sides

2-sided

lower limit

-0.05

upper limit

0.17

Statistical Analysis 5

Comparison groups

Placebo v FP, 100 µg, BID

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.189

Confidence interval

level

95%

sides

2-sided

lower limit

0.08

upper limit

0.3

Statistical Analysis 6

Comparison groups

Placebo v Montelukast, 10 mg, QD

Number of subjects included in analysis

193

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.22

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.04

upper limit

0.18

Secondary: Mean change from Baseline in daily PM PEF averaged over the 8-Week treatment period

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End point title

Mean change from Baseline in daily PM PEF averaged over the 8-Week treatment period

End point description

Peak expiratory flow (PEF) is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Change from Baseline was calculated as the value of the averaged PEF daily (pre-dose and pre-rescue bronchodilator) evening (PM) over the 8-Week treatment period minus the Baseline value (defined as the last 7 days prior to randomization of the par.). Analysis was performed using ANCOVA with covariates of Baseline, trough PM PEF, age, gender, country and smoking status.

End point type

Secondary

End point timeframe

From Baseline up to Week 8

End point values	Placebo	GSK2190915, 10 mg, QD	GSK2190915, 30 mg, QD	GSK2190915, 100 mg, QD	GSK2190915, 300 mg, QD	FP, 100 µg, BID	Montelukast, 10 mg, QD
Number of subjects analysed	99 ^[8]	99 ^[9]	99 ^[10]	100 ^[11]	101 ^[12]	101 ^[13]	97 ^[14]
Units: Liters per minute
least squares mean (standard error)	8.01 ± 3.19	7.62 ± 3.19	9.37 ± 3.2	6.21 ± 3.17	10.33 ± 3.15	10.46 ± 3.16	8.53 ± 3.24

Notes
[8] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[9] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[10] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[11] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[12] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[13] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[14] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.

Statistical Analysis 1

Comparison groups

Placebo v GSK2190915, 10 mg, QD

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.932

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.385

Confidence interval

level

95%

sides

2-sided

lower limit

-9.25

upper limit

8.48

Statistical Analysis 2

Comparison groups

Placebo v GSK2190915, 30 mg, QD

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.762

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

1.367

Confidence interval

level

95%

sides

2-sided

lower limit

-7.5

upper limit

10.23

Statistical Analysis 3

Comparison groups

GSK2190915, 100 mg, QD v Placebo

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.689

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.798

Confidence interval

level

95%

sides

2-sided

lower limit

-10.62

upper limit

7.03

Statistical Analysis 4

Comparison groups

Placebo v GSK2190915, 300 mg, QD

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.605

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

2.321

Confidence interval

level

95%

sides

2-sided

lower limit

-6.49

upper limit

11.13

Statistical Analysis 5

Comparison groups

Placebo v FP, 100 µg, BID

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.584

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

2.46

Confidence interval

level

95%

sides

2-sided

lower limit

-6.36

upper limit

11.28

Statistical Analysis 6

Comparison groups

Placebo v Montelukast, 10 mg, QD

Number of subjects included in analysis

196

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.907

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.529

Confidence interval

level

95%

sides

2-sided

lower limit

-8.4

upper limit

9.45

Secondary: Mean change from Baseline in daily trough AM PEF averaged over the 8-Week treatment period

Top of page

End point title

Mean change from Baseline in daily trough AM PEF averaged over the 8-Week treatment period

End point description

The PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Trough AM PEF is defined as the AM pre-dose and pre-rescue bronchodilator at the clinic visit. Change from Baseline was calculated as the value of the averaged PEF daily (pre-dose and pre-rescue bronchodilator) AM over the 8-Week treatment period minus the Baseline value (defined as the last 7 days prior to randomization of the par.). Analysis was performed using ANCOVA with covariates of Baseline, trough AM PEF, age, gender, country and smoking status.

End point type

Secondary

End point timeframe

From Baseline up to Week 8

End point values	Placebo	GSK2190915, 10 mg, QD	GSK2190915, 30 mg, QD	GSK2190915, 100 mg, QD	GSK2190915, 300 mg, QD	FP, 100 µg, BID	Montelukast, 10 mg, QD
Number of subjects analysed	99 ^[15]	99 ^[16]	99 ^[17]	100 ^[18]	101 ^[19]	100 ^[20]	97 ^[21]
Units: Liters per minute
least squares mean (standard error)	11.77 ± 3.28	13.23 ± 3.28	15.52 ± 3.29	8.72 ± 3.26	16.35 ± 3.24	15.25 ± 3.26	17.38 ± 3.32

Notes
[15] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[16] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[17] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[18] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[19] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[20] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[21] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.

Statistical Analysis 1

Comparison groups

Placebo v GSK2190915, 10 mg, QD

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.753

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

1.463

Confidence interval

level

95%

sides

2-sided

lower limit

-7.65

upper limit

10.58

Statistical Analysis 2

Comparison groups

Placebo v GSK2190915, 30 mg, QD

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.419

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

3.75

Confidence interval

level

95%

sides

2-sided

lower limit

-5.36

upper limit

12.87

Statistical Analysis 3

Comparison groups

Placebo v GSK2190915, 100 mg, QD

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.51

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-3.046

Confidence interval

level

95%

sides

2-sided

lower limit

-12.12

upper limit

6.03

Statistical Analysis 4

Comparison groups

Placebo v GSK2190915, 300 mg, QD

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.32

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

4.585

Confidence interval

level

95%

sides

2-sided

lower limit

-4.47

upper limit

13.64

Statistical Analysis 5

Comparison groups

Placebo v FP, 100 µg, BID

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.452

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

3.484

Confidence interval

level

95%

sides

2-sided

lower limit

-5.61

upper limit

12.58

Statistical Analysis 6

Comparison groups

Placebo v Montelukast, 10 mg, QD

Number of subjects included in analysis

196

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.229

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

5.615

Confidence interval

level

95%

sides

2-sided

lower limit

-3.55

upper limit

14.78

Secondary: Mean change from Baseline in the percentage of symptom-free days averaged over the 8-Week treatment period

Top of page

End point title

Mean change from Baseline in the percentage of symptom-free days averaged over the 8-Week treatment period

End point description

Asthma symptoms were recorded in a daily electronic diary (eDiary) by the par. every day in the evening at bedtime and before taking any rescue or study medication and before the assessment of the PEF measurement. Participant’s responses to evening assessments indicated no symptoms were considered to be symptom free. For participants, the symptom free days were assessed during the 8-Week treatment period. Change from Baseline was calculated as the averaged of symptom-free days during the 8-Week treatment period minus the Baseline value (defined as the last 7 days prior to randomization of the par.). Analysis was performed using ANCOVA with covariates of Baseline, age, gender, country and smoking status.

End point type

Secondary

End point timeframe

From Baseline up to Week 8

End point values	Placebo	GSK2190915, 10 mg, QD	GSK2190915, 30 mg, QD	GSK2190915, 100 mg, QD	GSK2190915, 300 mg, QD	FP, 100 µg, BID	Montelukast, 10 mg, QD
Number of subjects analysed	99 ^[22]	99 ^[23]	99 ^[24]	100 ^[25]	101 ^[26]	101 ^[27]	97 ^[28]
Units: Percentage of symptom-free days
least squares mean (standard error)	13.98 ± 2.84	15.15 ± 2.84	18.54 ± 2.84	15.31 ± 2.82	14.06 ± 2.81	22.18 ± 2.81	16.87 ± 2.87

Notes
[22] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[23] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[24] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[25] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[26] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[27] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[28] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.

Statistical Analysis 1

Comparison groups

Placebo v GSK2190915, 10 mg, QD

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.771

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

1.169

Confidence interval

level

95%

sides

2-sided

lower limit

-6.73

upper limit

9.07

Statistical Analysis 2

Comparison groups

Placebo v GSK2190915, 30 mg, QD

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.257

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

4.56

Confidence interval

level

95%

sides

2-sided

lower limit

-3.33

upper limit

12.45

Statistical Analysis 3

Comparison groups

Placebo v GSK2190915, 100 mg, QD

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.741

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

1.326

Confidence interval

level

95%

sides

2-sided

lower limit

-6.54

upper limit

9.19

Statistical Analysis 4

Comparison groups

Placebo v GSK2190915, 300 mg, QD

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.983

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.083

Confidence interval

level

95%

sides

2-sided

lower limit

-7.76

upper limit

7.93

Statistical Analysis 5

Comparison groups

Placebo v FP, 100 µg, BID

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.041

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

8.204

Confidence interval

level

95%

sides

2-sided

lower limit

0.34

upper limit

16.07

Statistical Analysis 6

Comparison groups

Placebo v Montelukast, 10 mg, QD

Number of subjects included in analysis

196

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.475

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

2.891

Confidence interval

level

95%

sides

2-sided

lower limit

-5.05

upper limit

10.83

Secondary: Mean change from Baseline in the percentage of symptom-free nights averaged over the 8-Week treatment period

Top of page

End point title

Mean change from Baseline in the percentage of symptom-free nights averaged over the 8-Week treatment period

End point description

Asthma symptoms were recorded in a daily eDairy by the par. every day in the morning upon rising and before taking any rescue or study medication and before the assessment of the PEF measurement. Participant’s responses to the morning assessments indicated no symptoms were considered to be symptom free. For participants, the symptom free nights were assessed during the 8-Week treatment period. Change from Baseline was calculated as the averaged of symptom-free nights during the 8-Week treatment period minus the Baseline value (defined as the last 7 days prior to randomization of the par.). Analysis was performed using ANCOVA with covariates of Baseline, age, gender, country and smoking status.

End point type

Secondary

End point timeframe

From Baseline up to Week 8

End point values	Placebo	GSK2190915, 10 mg, QD	GSK2190915, 30 mg, QD	GSK2190915, 100 mg, QD	GSK2190915, 300 mg, QD	FP, 100 µg, BID	Montelukast, 10 mg, QD
Number of subjects analysed	99 ^[29]	99 ^[30]	99 ^[31]	100 ^[32]	101 ^[33]	100 ^[34]	97 ^[35]
Units: Percentage of symptom-free nights
least squares mean (standard error)	13.99 ± 2.9	14.83 ± 2.9	16.71 ± 2.9	16.12 ± 2.88	12.21 ± 2.86	19.94 ± 2.88	19.39 ± 2.93

Notes
[29] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[30] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[31] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[32] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[33] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[34] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[35] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.

Statistical Analysis 1

Comparison groups

Placebo v GSK2190915, 10 mg, QD

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.838

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.837

Confidence interval

level

95%

sides

2-sided

lower limit

-7.22

upper limit

8.89

Statistical Analysis 2

Comparison groups

Placebo v GSK2190915, 30 mg, QD

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.508

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

2.715

Confidence interval

level

95%

sides

2-sided

lower limit

-5.33

upper limit

10.76

Statistical Analysis 3

Comparison groups

Placebo v GSK2190915, 100 mg, QD

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.603

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

2.124

Confidence interval

level

95%

sides

2-sided

lower limit

-5.9

upper limit

10.14

Statistical Analysis 4

Comparison groups

Placebo v GSK2190915, 300 mg, QD

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.662

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.781

Confidence interval

level

95%

sides

2-sided

lower limit

-9.78

upper limit

6.22

Statistical Analysis 5

Comparison groups

Placebo v FP, 100 µg, BID

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.146

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

5.949

Confidence interval

level

95%

sides

2-sided

lower limit

-2.08

upper limit

13.98

Statistical Analysis 6

Comparison groups

Placebo v Montelukast, 10 mg, QD

Number of subjects included in analysis

196

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.191

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

5.394

Confidence interval

level

95%

sides

2-sided

lower limit

-2.69

upper limit

13.48

Secondary: Mean change from Baseline in the percentage of rescue-free days averaged over the 8-Week treatment period

Top of page

End point title

Mean change from Baseline in the percentage of rescue-free days averaged over the 8-Week treatment period

End point description

The number of inhalations of rescue salbutamol/albuterol inhalation aerosol used during the day and night was recorded by the par. in a eDiary. The time span during which the par. did not have to take any rescue medication (medication intended to relieve symptoms immediately) was considered to be a rescue-free period. For participants, the rescue-free days were assessed during the 8-Week treatment period. Change from Baseline was calculated as the averaged of rescue-free days during the 8-Week treatment period minus the Baseline value (defined as the last 7 days prior to randomization of the par.). Analysis was performed using ANCOVA with covariates of Baseline, age, gender, country and smoking status.

End point type

Secondary

End point timeframe

From Baseline up to Week 8

End point values	Placebo	GSK2190915, 10 mg, QD	GSK2190915, 30 mg, QD	GSK2190915, 100 mg, QD	GSK2190915, 300 mg, QD	FP, 100 µg, BID	Montelukast, 10 mg, QD
Number of subjects analysed	99 ^[36]	99 ^[37]	99 ^[38]	100 ^[39]	101 ^[40]	101 ^[41]	97 ^[42]
Units: Percentage of rescue-free days
least squares mean (standard error)	16.8 ± 3.1	22.91 ± 3.1	20.91 ± 3.09	18.95 ± 3.08	18.51 ± 3.06	26.39 ± 3.06	23.55 ± 3.13

Notes
[36] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[37] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[38] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[39] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[40] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[41] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[42] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.

Statistical Analysis 1

Comparison groups

Placebo v GSK2190915, 10 mg, QD

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.164

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

6.106

Confidence interval

level

95%

sides

2-sided

lower limit

-2.5

upper limit

14.71

Statistical Analysis 2

Comparison groups

Placebo v GSK2190915, 30 mg, QD

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.349

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

4.106

Confidence interval

level

95%

sides

2-sided

lower limit

-4.49

upper limit

12.7

Statistical Analysis 3

Comparison groups

Placebo v GSK2190915, 100 mg, QD

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.623

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

2.148

Confidence interval

level

95%

sides

2-sided

lower limit

-6.42

upper limit

10.72

Statistical Analysis 4

Comparison groups

Placebo v GSK2190915, 300 mg, QD

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.694

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

1.713

Confidence interval

level

95%

sides

2-sided

lower limit

-6.84

upper limit

10.26

Statistical Analysis 5

Comparison groups

Placebo v FP, 100 µg, BID

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.028

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

9.592

Confidence interval

level

95%

sides

2-sided

lower limit

1.03

upper limit

18.15

Statistical Analysis 6

Comparison groups

Placebo v Montelukast, 10 mg, QD

Number of subjects included in analysis

196

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.125

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

6.75

Confidence interval

level

95%

sides

2-sided

lower limit

-1.89

upper limit

15.38

Secondary: Mean change from Baseline in the percentage of rescue-free nights averaged over the 8-Week treatment period

Top of page

End point title

Mean change from Baseline in the percentage of rescue-free nights averaged over the 8-Week treatment period

End point description

The number of inhalations of rescue salbutamol/albuterol inhalation aerosol used during the day and night was recorded by the par. in a eDiary. The time span during which the par. did not have to take any rescue medication (medication intended to relieve symptoms immediately) was considered to be a rescue-free period. For participants, the rescue-free nights were assessed during the 8-Week treatment period. Change from Baseline was calculated as the averaged of rescue-free nights during the 8-Week treatment period minus the Baseline value (defined as the last 7 days prior to randomization of the par.). Analysis was performed using ANCOVA with covariates of Baseline, age, gender, country and smoking status.

End point type

Secondary

End point timeframe

From Baseline up to Week 8

End point values	Placebo	GSK2190915, 10 mg, QD	GSK2190915, 30 mg, QD	GSK2190915, 100 mg, QD	GSK2190915, 300 mg, QD	FP, 100 µg, BID	Montelukast, 10 mg, QD
Number of subjects analysed	99 ^[43]	99 ^[44]	99 ^[45]	100 ^[46]	101 ^[47]	100 ^[48]	97 ^[49]
Units: Percentage of rescue-free nights
least squares mean (standard error)	16.93 ± 3.04	19.28 ± 3.04	17.36 ± 3.03	19.63 ± 3.02	15.71 ± 3	24.42 ± 3.02	20.54 ± 3.07

Notes
[43] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[44] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[45] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[46] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[47] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[48] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[49] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.

Statistical Analysis 1

Comparison groups

Placebo v GSK2190915, 10 mg, QD

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.585

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

2.346

Confidence interval

level

95%

sides

2-sided

lower limit

-6.09

upper limit

10.78

Statistical Analysis 2

Comparison groups

Placebo v GSK2190915, 30 mg, QD

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.92

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.431

Confidence interval

level

95%

sides

2-sided

lower limit

-8

upper limit

8.86

Statistical Analysis 3

Comparison groups

Placebo v GSK2190915, 100 mg, QD

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.528

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

2.702

Confidence interval

level

95%

sides

2-sided

lower limit

-5.7

upper limit

11.11

Statistical Analysis 4

Comparison groups

Placebo v GSK2190915, 300 mg, QD

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.776

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-1.218

Confidence interval

level

95%

sides

2-sided

lower limit

-9.6

upper limit

7.17

Statistical Analysis 5

Comparison groups

Placebo v FP, 100 µg, BID

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.081

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

7.49

Confidence interval

level

95%

sides

2-sided

lower limit

-0.92

upper limit

15.9

Statistical Analysis 6

Comparison groups

Placebo v Montelukast, 10 mg, QD

Number of subjects included in analysis

196

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.403

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

3.611

Confidence interval

level

95%

sides

2-sided

lower limit

-4.87

upper limit

12.09

Secondary: Mean change from Baseline in day-time asthma symptom score over the 8-Week treatment period

Top of page

End point title

Mean change from Baseline in day-time asthma symptom score over the 8-Week treatment period

End point description

Participants recorded their day-time asthma symptom score in the eDiary each PM at bedtime and before taking any rescue or study medication and before assessing the PEF measurement during the 8-Week treatment period. Day-time asthma symptom scores, as: 0=no asthma symptoms, 1=one episode of short-time asthma symptoms, 2=two or more episodes of short-time asthma symptoms, 3=asthma symptoms occurring during most part of daytime without interference with daily life activities, 4=asthma symptoms occurring during most part of daytime with interference with daily life activities, 5=severe asthma symptoms that disable working or perform normal daily activities. Change from Baseline was calculated as the averaged of day-time asthma symptom score during the 8-Week treatment period minus the Baseline value (defined as the last 7 days prior to randomization of the par.). Analysis was performed using ANCOVA with covariates of Baseline, age, gender, country and smoking status.

End point type

Secondary

End point timeframe

From Baseline up to Week 8

End point values	Placebo	GSK2190915, 10 mg, QD	GSK2190915, 30 mg, QD	GSK2190915, 100 mg, QD	GSK2190915, 300 mg, QD	FP, 100 µg, BID	Montelukast, 10 mg, QD
Number of subjects analysed	99 ^[50]	99 ^[51]	99 ^[52]	100 ^[53]	101 ^[54]	101 ^[55]	97 ^[56]
Units: Day-time symptom scores on a scale
least squares mean (standard error)	-0.34 ± 0.06	-0.34 ± 0.06	-0.5 ± 0.06	-0.36 ± 0.06	-0.34 ± 0.06	-0.43 ± 0.06	-0.41 ± 0.06

Notes
[50] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[51] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[52] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[53] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[54] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[55] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[56] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.

Statistical Analysis 1

Comparison groups

Placebo v GSK2190915, 10 mg, QD

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.951

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.005

Confidence interval

level

95%

sides

2-sided

lower limit

-0.17

upper limit

0.16

Statistical Analysis 2

Comparison groups

Placebo v GSK2190915, 30 mg, QD

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.043

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.166

Confidence interval

level

95%

sides

2-sided

lower limit

-0.33

upper limit

-0.01

Statistical Analysis 3

Comparison groups

Placebo v GSK2190915, 100 mg, QD

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.734

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.028

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

0.13

Statistical Analysis 4

Comparison groups

Placebo v GSK2190915, 300 mg, QD

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.972

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.003

Confidence interval

level

95%

sides

2-sided

lower limit

-0.16

upper limit

0.16

Statistical Analysis 5

Comparison groups

Placebo v FP, 100 µg, BID

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.238

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.097

Confidence interval

level

95%

sides

2-sided

lower limit

-0.26

upper limit

0.06

Statistical Analysis 6

Comparison groups

Placebo v Montelukast, 10 mg, QD

Number of subjects included in analysis

196

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.36

Method

ANCOVA

Parameter type

Median difference (final values)

Point estimate

-0.075

Confidence interval

level

95%

sides

2-sided

lower limit

-0.24

upper limit

0.09

Secondary: Mean change from Baseline in night-time asthma symptom score over the 8-Week treatment period

Top of page

End point title

Mean change from Baseline in night-time asthma symptom score over the 8-Week treatment period

End point description

Participants recorded their night-time asthma symptom score in the eDiary each AM upon rising and before taking any rescue or study medication and before assessing the PEF measurement during the 8-Week treatment period. Night-time asthma symptom scores, as: 0=no asthma symptoms, 1= one awakening or waking early due to asthma symptoms, 2= two or more awakenings due to asthma symptoms (including waking early), 3= asthma symptoms almost prevented the participant from sleeping, 4= severe asthma symptoms completely prevented from sleeping. Change from Baseline was calculated as the averaged of night-time asthma symptom score during the 8-Week treatment period minus the Baseline value (defined as the last 7 days prior to randomization of the par.). Analysis was performed using ANCOVA with covariates of Baseline, age, gender, country and smoking status.

End point type

Secondary

End point timeframe

From Baseline up to Week 8

End point values	Placebo	GSK2190915, 10 mg, QD	GSK2190915, 30 mg, QD	GSK2190915, 100 mg, QD	GSK2190915, 300 mg, QD	FP, 100 µg, BID	Montelukast, 10 mg, QD
Number of subjects analysed	99 ^[57]	99 ^[58]	99 ^[59]	100 ^[60]	101 ^[61]	100 ^[62]	97 ^[63]
Units: Night-time symptom scores on a scale
least squares mean (standard error)	-0.23 ± 0.05	-0.21 ± 0.05	-0.33 ± 0.05	-0.26 ± 0.05	-0.22 ± 0.05	-0.29 ± 0.05	-0.32 ± 0.05

Notes
[57] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[58] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[59] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[60] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[61] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[62] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[63] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.

Statistical Analysis 1

Comparison groups

Placebo v GSK2190915, 10 mg, QD

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.692

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.028

Confidence interval

level

95%

sides

2-sided

lower limit

-0.11

upper limit

0.17

Statistical Analysis 2

Comparison groups

Placebo v GSK2190915, 30 mg, QD

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.176

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.096

Confidence interval

level

95%

sides

2-sided

lower limit

-0.24

upper limit

0.04

Statistical Analysis 3

Comparison groups

Placebo v GSK2190915, 100 mg, QD

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.768

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.021

Confidence interval

level

95%

sides

2-sided

lower limit

-0.16

upper limit

0.12

Statistical Analysis 4

Comparison groups

Placebo v GSK2190915, 300 mg, QD

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.887

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.01

Confidence interval

level

95%

sides

2-sided

lower limit

-0.13

upper limit

0.15

Statistical Analysis 5

Comparison groups

Placebo v FP, 100 µg, BID

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.471

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.051

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

0.09

Statistical Analysis 6

Comparison groups

Placebo v Montelukast, 10 mg, QD

Number of subjects included in analysis

196

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.248

Method

ANCOVA

Parameter type

Median difference (final values)

Point estimate

-0.083

Confidence interval

level

95%

sides

2-sided

lower limit

-0.22

upper limit

0.06

Secondary: Mean change from Baseline in day-time rescue SABA usage over the 8-Week treatment period

Top of page

End point title

Mean change from Baseline in day-time rescue SABA usage over the 8-Week treatment period

End point description

The number of inhalations of rescue short acting beta2-agonist (SABA), salbutamol/albuterol inhalation aerosol used during the day and night was recorded by the par. in a eDiary. Participants who used salbutamol/albuterol inhalation aerosol at day-time were assessed during the 8-Week treatment period. Change from Baseline was calculated as the averaged number of day-time salbutamol/albuterol inhalation aerosol used during the 8-Week treatment period minus the Baseline value (defined as the last 7 days prior to randomization of the par.). Analysis was performed using ANCOVA with covariates of Baseline, age, gender, country and smoking status.

End point type

Secondary

End point timeframe

From Baseline up to Week 8

End point values	Placebo	GSK2190915, 10 mg, QD	GSK2190915, 30 mg, QD	GSK2190915, 100 mg, QD	GSK2190915, 300 mg, QD	FP, 100 µg, BID	Montelukast, 10 mg, QD
Number of subjects analysed	99 ^[64]	99 ^[65]	99 ^[66]	100 ^[67]	101 ^[68]	101 ^[69]	97 ^[70]
Units: Day-time number of inhalations
least squares mean (standard error)	-0.42 ± 0.07	-0.55 ± 0.07	-0.68 ± 0.07	-0.5 ± 0.07	-0.47 ± 0.07	-0.67 ± 0.07	-0.63 ± 0.07

Notes
[64] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[65] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[66] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[67] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[68] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[69] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[70] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.

Statistical Analysis 1

Comparison groups

Placebo v GSK2190915, 10 mg, QD

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.209

Method

ANCOVA

Parameter type

Median difference (final values)

Point estimate

-0.131

Confidence interval

level

95%

sides

2-sided

lower limit

-0.33

upper limit

0.07

Statistical Analysis 2

Comparison groups

Placebo v GSK2190915, 30 mg, QD

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.011

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.264

Confidence interval

level

95%

sides

2-sided

lower limit

-0.47

upper limit

-0.06

Statistical Analysis 3

Comparison groups

Placebo v GSK2190915, 100 mg, QD

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.464

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.076

Confidence interval

level

95%

sides

2-sided

lower limit

-0.28

upper limit

0.13

Statistical Analysis 4

Comparison groups

Placebo v GSK2190915, 300 mg, QD

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.662

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.045

Confidence interval

level

95%

sides

2-sided

lower limit

-0.25

upper limit

0.16

Statistical Analysis 5

Comparison groups

Placebo v FP, 100 µg, BID

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.018

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.245

Confidence interval

level

95%

sides

2-sided

lower limit

-0.45

upper limit

-0.04

Statistical Analysis 6

Comparison groups

Placebo v Montelukast, 10 mg, QD

Number of subjects included in analysis

196

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.047

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.207

Confidence interval

level

95%

sides

2-sided

lower limit

-0.41

upper limit

Secondary: Mean change from Baseline in night-time rescue SABA usage over the 8-Week treatment period

Top of page

End point title

Mean change from Baseline in night-time rescue SABA usage over the 8-Week treatment period

End point description

The numbers of inhalations of rescue SABA, salbutamol/albuterol inhalation aerosol used during the day and night was recorded by the par. in a eDiary. Participants who used salbutamol/albuterol inhalation aerosol at night-time were assessed during the 8-Week treatment period. Change from Baseline was calculated as the averaged number of night-time salbutamol/albuterol inhalation aerosol used during the 8-Week treatment period minus the Baseline value (defined as the last 7 days prior to randomization of the par.). Analysis was performed using ANCOVA with covariates of Baseline, age, gender, country and smoking status.

End point type

Secondary

End point timeframe

From Baseline up to Week 8

End point values	Placebo	GSK2190915, 10 mg, QD	GSK2190915, 30 mg, QD	GSK2190915, 100 mg, QD	GSK2190915, 300 mg, QD	FP, 100 µg, BID	Montelukast, 10 mg, QD
Number of subjects analysed	99 ^[71]	99 ^[72]	99 ^[73]	100 ^[74]	101 ^[75]	100 ^[76]	97 ^[77]
Units: Night-time number of inhalations
least squares mean (standard error)	-0.3 ± 0.07	-0.4 ± 0.07	-0.44 ± 0.07	-0.42 ± 0.07	-0.3 ± 0.07	-0.47 ± 0.07	-0.46 ± 0.07

Notes
[71] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[72] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[73] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[74] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[75] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[76] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.
[77] - ITT Population. Only those par. with analyzable data at the indicated time point were assessed.

Statistical Analysis 1

Comparison groups

Placebo v GSK2190915, 10 mg, QD

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.098

Confidence interval

level

95%

sides

2-sided

lower limit

-0.28

upper limit

0.09

Statistical Analysis 2

Comparison groups

GSK2190915, 30 mg, QD v Placebo

Number of subjects included in analysis

198

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.145

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.138

Confidence interval

level

95%

sides

2-sided

lower limit

-0.32

upper limit

0.05

Statistical Analysis 3

Comparison groups

Placebo v GSK2190915, 100 mg, QD

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.19

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.123

Confidence interval

level

95%

sides

2-sided

lower limit

-0.31

upper limit

0.06

Statistical Analysis 4

Comparison groups

Placebo v GSK2190915, 300 mg, QD

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.98

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.002

Confidence interval

level

95%

sides

2-sided

lower limit

-0.19

upper limit

0.18

Statistical Analysis 5

Comparison groups

Placebo v FP, 100 µg, BID

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.07

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.171

Confidence interval

level

95%

sides

2-sided

lower limit

-0.36

upper limit

0.01

Statistical Analysis 6

Comparison groups

Placebo v Montelukast, 10 mg, QD

Number of subjects included in analysis

196

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.095

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.158

Confidence interval

level

95%

sides

2-sided

lower limit

-0.34

upper limit

0.03

Secondary: Number of participants who withdrew due to lack of efficacy during the 8-Week treatment period

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End point title

Number of participants who withdrew due to lack of efficacy during the 8-Week treatment period

End point description

The participants who met any of the following withdrawal criteria were considered to be withdrawn due to lack of efficacy: 1) Clinic FEV1 below stability limit calculated at Visit 3. 2) More than three days between two consecutive visits, PEF has fallen below stability limit calculated at Visit 3. 3) Use of 12 or more inhalations of SABA per day for more than two days between consecutive visits. 4) Asthma exacerbation defined as worsening requiring any treatment other than study medication or rescue medication. This included requiring the use of systemic or inhaled corticosteroids and /or emergency room visit or hospitalization for the treatment of asthma. The stability limit was calculated as best pre-salbutamol/albuterol FEV1 at Visit 3 x 80 percent (%).

End point type

Secondary

End point timeframe

8 Weeks

End point values	Placebo	GSK2190915, 10 mg, QD	GSK2190915, 30 mg, QD	GSK2190915, 100 mg, QD	GSK2190915, 300 mg, QD	FP, 100 µg, BID	Montelukast, 10 mg, QD
Number of subjects analysed	100 ^[78]	99 ^[79]	100 ^[80]	100 ^[81]	101 ^[82]	103 ^[83]	97 ^[84]
Units: Participants	11	11	9	11	13	8	7

Notes
[78] - ITT Population
[79] - ITT Population
[80] - ITT Population
[81] - ITT Population
[82] - ITT Population
[83] - ITT Population
[84] - ITT Population

Statistical Analysis 1

Comparison groups

Placebo v GSK2190915, 10 mg, QD

Number of subjects included in analysis

199

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 1

Method

Fisher exact

Confidence interval

Statistical Analysis 2

Comparison groups

Placebo v GSK2190915, 30 mg, QD

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.814

Method

Fisher exact

Confidence interval

Statistical Analysis 3

Comparison groups

Placebo v GSK2190915, 100 mg, QD

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 1

Method

Fisher exact

Confidence interval

Statistical Analysis 4

Comparison groups

Placebo v GSK2190915, 300 mg, QD

Number of subjects included in analysis

201

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.828

Method

Fisher exact

Confidence interval

Statistical Analysis 5

Comparison groups

Placebo v FP, 100 µg, BID

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.477

Method

Fisher exact

Confidence interval

Statistical Analysis 6

Comparison groups

Placebo v Montelukast, 10 mg, QD

Number of subjects included in analysis

197

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.46

Method

Fisher exact

Confidence interval

Adverse events

Top of page

Timeframe for reporting adverse events

Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug until the follow-up contact (up to Week 9).

Adverse event reporting additional description

SAEs and non-serious AEs were reported for members of the ITT population, comprised of all participants who were randomized to treatment, and received at least one dose of double-blind study medication.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

14.1

Reporting group title

Placebo

Reporting group description

Reporting group title

GSK2190915, 10 mg, QD

Reporting group description

Reporting group title

GSK2190915, 30 mg, QD

Reporting group description

Reporting group title

GSK2190915, 100 mg, QD

Reporting group description

Reporting group title

GSK2190915, 300 mg, QD

Reporting group description

Participants received one tablet of 100 mg GSK2190915 and one tablet of 200 mg GSK2190915 orally QD plus one dose of FP matching placebo BID via DPI in morning and another dose of FP matching placebo BID via DPI plus one capsule of montelukast matching placebo orally QD in evening for the 8-Weeks.

Reporting group title

FP, 100 µg, BID

Reporting group description

Reporting group title

Montelukast, 10 mg, QD

Reporting group description

Serious adverse events	Placebo	GSK2190915, 10 mg, QD	GSK2190915, 30 mg, QD	GSK2190915, 100 mg, QD	GSK2190915, 300 mg, QD	FP, 100 µg, BID	Montelukast, 10 mg, QD
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 100 (0.00%)	1 / 99 (1.01%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	1 / 103 (0.97%)	0 / 97 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Cartilage injury
subjects affected / exposed	0 / 100 (0.00%)	0 / 99 (0.00%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	1 / 103 (0.97%)	0 / 97 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Joint dislocation
subjects affected / exposed	0 / 100 (0.00%)	1 / 99 (1.01%)	0 / 100 (0.00%)	0 / 100 (0.00%)	0 / 101 (0.00%)	0 / 103 (0.00%)	0 / 97 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Small intestinal obstruction
subjects affected / exposed	0 / 100 (0.00%)	0 / 99 (0.00%)	0 / 100 (0.00%)	1 / 100 (1.00%)	0 / 101 (0.00%)	0 / 103 (0.00%)	0 / 97 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Placebo	GSK2190915, 10 mg, QD	GSK2190915, 30 mg, QD	GSK2190915, 100 mg, QD	GSK2190915, 300 mg, QD	FP, 100 µg, BID	Montelukast, 10 mg, QD
Total subjects affected by non serious adverse events
subjects affected / exposed	10 / 100 (10.00%)	13 / 99 (13.13%)	6 / 100 (6.00%)	9 / 100 (9.00%)	9 / 101 (8.91%)	14 / 103 (13.59%)	15 / 97 (15.46%)
Nervous system disorders
Headache
subjects affected / exposed	3 / 100 (3.00%)	7 / 99 (7.07%)	2 / 100 (2.00%)	4 / 100 (4.00%)	4 / 101 (3.96%)	9 / 103 (8.74%)	9 / 97 (9.28%)
occurrences all number	3	7	2	4	4	9	9
Infections and infestations
Nasopharyngitis
subjects affected / exposed	5 / 100 (5.00%)	6 / 99 (6.06%)	3 / 100 (3.00%)	2 / 100 (2.00%)	5 / 101 (4.95%)	5 / 103 (4.85%)	5 / 97 (5.15%)
occurrences all number	5	6	3	2	5	5	5
Pharyngitis
subjects affected / exposed	2 / 100 (2.00%)	0 / 99 (0.00%)	1 / 100 (1.00%)	3 / 100 (3.00%)	0 / 101 (0.00%)	0 / 103 (0.00%)	1 / 97 (1.03%)
occurrences all number	2	0	1	3	0	0	1

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

13 Oct 2010

The amendment restricted the study to females only following a finding from an interim histopathological assessment of the male reproductive tract from ongoing 6 month rat and 9 month dog toxicology studies. These findings related to testicular toxicity at high exposures of GSK2190915, the clinical significance of which was uncertain.

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

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Mean change from Baseline to the end of the 8-Week treatment period in trough FEV1

Primary: Mean change from Baseline to the end of the 8-Week treatment period in trough FEV1

Secondary: Mean change from Baseline in daily PM PEF averaged over the 8-Week treatment period

Secondary: Mean change from Baseline in daily PM PEF averaged over the 8-Week treatment period

Secondary: Mean change from Baseline in daily trough AM PEF averaged over the 8-Week treatment period

Secondary: Mean change from Baseline in daily trough AM PEF averaged over the 8-Week treatment period

Secondary: Mean change from Baseline in the percentage of symptom-free days averaged over the 8-Week treatment period

Secondary: Mean change from Baseline in the percentage of symptom-free days averaged over the 8-Week treatment period

Secondary: Mean change from Baseline in the percentage of symptom-free nights averaged over the 8-Week treatment period

Secondary: Mean change from Baseline in the percentage of symptom-free nights averaged over the 8-Week treatment period

Secondary: Mean change from Baseline in the percentage of rescue-free days averaged over the 8-Week treatment period

Secondary: Mean change from Baseline in the percentage of rescue-free days averaged over the 8-Week treatment period

Secondary: Mean change from Baseline in the percentage of rescue-free nights averaged over the 8-Week treatment period

Secondary: Mean change from Baseline in the percentage of rescue-free nights averaged over the 8-Week treatment period

Secondary: Mean change from Baseline in day-time asthma symptom score over the 8-Week treatment period

Secondary: Mean change from Baseline in day-time asthma symptom score over the 8-Week treatment period

Secondary: Mean change from Baseline in night-time asthma symptom score over the 8-Week treatment period

Secondary: Mean change from Baseline in night-time asthma symptom score over the 8-Week treatment period

Secondary: Mean change from Baseline in day-time rescue SABA usage over the 8-Week treatment period

Secondary: Mean change from Baseline in day-time rescue SABA usage over the 8-Week treatment period

Secondary: Mean change from Baseline in night-time rescue SABA usage over the 8-Week treatment period

Secondary: Mean change from Baseline in night-time rescue SABA usage over the 8-Week treatment period

Secondary: Number of participants who withdrew due to lack of efficacy during the 8-Week treatment period

Secondary: Number of participants who withdrew due to lack of efficacy during the 8-Week treatment period

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