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Clinical Trial Results:
A Randomized Double-Blind, Double-Dummy, Placebo-Controlled, Parallel-Group, Multicenter, Dose Ranging Study to Evaluate the Efficacy and Safety of GW685698X Inhalation Powder Once Daily and Fluticasone Propionate Inhalation Powder 250mcg Twice Daily compared with Placebo for 8 Weeks in Adolescent and Adult Subjects with Persistent Asthma Symptomatic on Low-Dose Inhaled Corticosteroid Therapy

Summary
EudraCT number	2007-004459-13
Trial protocol	PL EE GR SK DE
Global end of trial date	24 Nov 2008

Results information
Results version number	v1(current)
This version publication date	13 Apr 2016
First version publication date	06 Mar 2015
Other versions

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

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Trial information

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Sponsor protocol code

FFA109685

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)

Yes

EMA paediatric investigation plan number(s)

EMEA-000431-PIP08-07

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?

Yes

Analysis stage

Final

Date of interim/final analysis

16 Jan 2009

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

24 Nov 2008

Was the trial ended prematurely?

Main objective of the trial

The objective of this study was to evaluate the dose response, efficacy and safety of four dosage regimens of GW685698X (100 μg, 200 μg, 300 μg and 400 μg) administered once daily in the evening in adolescent and adult subjects 12 years of age and older with persistent uncontrolled asthma.

Protection of trial subjects

Subjects had to meet all inclusion and none of the exclusion criteria at screening and at end of run-in period to be eligible for randomization to treatment period. During the study, subjects monitored their lung function and recorded asthma symptoms and use of rescue-medication twice daily on an electronic diary. Alert messages to contact the site were programmed should the subject’s asthma deteriorate according to pre-defined criteria. Adverse events were captured at each clinic visit.

Background therapy

Evidence for comparator

Actual start date of recruitment

20 Dec 2007

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 21

Country: Number of subjects enrolled

Slovakia: 18

Country: Number of subjects enrolled

Estonia: 32

Country: Number of subjects enrolled

Germany: 75

Country: Number of subjects enrolled

Greece: 62

Country: Number of subjects enrolled

Canada: 49

Country: Number of subjects enrolled

Korea, Republic of: 132

Country: Number of subjects enrolled

Mexico: 107

Country: Number of subjects enrolled

Philippines: 231

Country: Number of subjects enrolled

Romania: 29

Country: Number of subjects enrolled

Russian Federation: 58

Country: Number of subjects enrolled

South Africa: 56

Country: Number of subjects enrolled

United States: 536

Worldwide total number of subjects

1406

EEA total number of subjects

237

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)

191

Adults (18-64 years)

1125

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Participants (par.) meeting eligibility criteria at the Screening visit completed a 28-day Run-in Period for Baseline safety evaluations and measures of asthma status. Par. were then randomized to an 8-week Treatment Period. 1406 par. were screened, and 622 par. were randomized, out of which 615 par. received at least one dose of study treatment.

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 placebo once daily (OD) in the evening from the dry powder inhaler (DPI) and placebo twice daily (BID) from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol inhalation aerosol to be used as needed throughout the study.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Local use

Dosage and administration details

Twice daily dry powder inhaler

GW685698X 100 µg OD

Arm description

Participants received GW685698X 100 micrograms (µg) OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.

Arm type

Experimental

Investigational medicinal product name

GW685698X

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Local use

Dosage and administration details

100 µg once daily, dry powder inhaler

GW685698X 200 µg OD

Arm description

Participants received GW685698X 200 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.

Arm type

Experimental

Investigational medicinal product name

GW685698X

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Local use

Dosage and administration details

200 µg once daily, dry powder inhaler

GW685698X 300 µg OD

Arm description

Participants received GW685698X 300 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.

Arm type

Experimental

Investigational medicinal product name

GW685698X

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Local use

Dosage and administration details

300 µg once daily, dry powder inhaler

GW685698X 400 µg OD

Arm description

Participants received GW685698X 400 µg OD in the evening from the DPI and placebo BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.

Arm type

Experimental

Investigational medicinal product name

GW685698X

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Local use

Dosage and administration details

400 µg once daily, dry powder inhaler

FP 250 µg BID

Arm description

Participants received fluticasone propionate (FP) 250 µg BID from the DISKUS/ACCUHALER (one inhalation in the morning and one inhalation in the evening) plus placebo OD in the evening from the DPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.

Arm type

Active comparator

Investigational medicinal product name

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder

Routes of administration

Local use

Dosage and administration details

250 µg twice daily, dry powder inhaler

Number of subjects in period 1 ^[1]	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Started	107	105	101	103	99	100
Completed	66	88	87	92	86	81
Not completed	41	17	14	11	13	19
Consent withdrawn by subject	2	3	1	2	1	2
Physician decision	-	1	-	-	2	1
Adverse event, non-fatal	-	3	1	-	2	1
Lost to follow-up	1	-	-	-	1	-
Lack of efficacy	35	10	11	8	7	14
Protocol deviation	3	-	1	1	-	1

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: Participants (par.) meeting eligibility criteria at the Screening visit completed a 28-day Run-in Period for Baseline safety evaluations and measures of asthma status. Par. were then randomized to an 8-week Treatment Period. 1406 par. were screened, and 622 par. were randomized, out of which 615 par. received at least one dose of study treatment.

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Reporting group title

GW685698X 100 µg OD

Reporting group description

Reporting group title

GW685698X 200 µg OD

Reporting group description

Reporting group title

GW685698X 300 µg OD

Reporting group description

Reporting group title

GW685698X 400 µg OD

Reporting group description

Reporting group title

FP 250 µg BID

Reporting group description

Reporting group values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID	Total
Number of subjects	107	105	101	103	99	100	615
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	39.1 ± 16.19	38.3 ± 16.76	38.8 ± 15.97	39.9 ± 15.57	40.7 ± 15.87	39.8 ± 16.7	-
Gender categorical
Units: Subjects
Female	74	72	63	67	64	62	402
Male	33	33	38	36	35	38	213
Race, Customized
Units: Subjects
White	62	64	65	63	56	61	371
Central/South Asian Heritage (HER)	1	1	0	1	0	0	3
Japanese/East Asian HER/South East Asian HER	25	24	23	22	25	23	142
American Indian or Alaska Native	0	1	0	0	0	0	1
American Indian or Alaska Native & White	14	12	13	14	13	13	79
African American / African HER	5	2	0	2	4	3	16
African American / African Heritage & White	0	1	0	0	0	0	1
Native Hawaiian or other Pacific Islander	0	0	0	0	1	0	1
Missing	0	0	0	1	0	0	1

End points

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Reporting group title

Placebo

Reporting group description

Reporting group title

GW685698X 100 µg OD

Reporting group description

Reporting group title

GW685698X 200 µg OD

Reporting group description

Reporting group title

GW685698X 300 µg OD

Reporting group description

Reporting group title

GW685698X 400 µg OD

Reporting group description

Reporting group title

FP 250 µg BID

Reporting group description

Primary: Mean change from Baseline in trough (evening pre-dose and pre- rescue bronchodilator) FEV1 at Week 8

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End point title

Mean change from Baseline in trough (evening pre-dose and pre- rescue bronchodilator) FEV1 at Week 8

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. Pre-dose and pre-rescue bronchodilator (albuterol/salbutamol) trough FEV1 (the measurement of FEV1 performed at the end of the dosing interval) was measured electronically by spirometry in the evening at the Baseline (BL) through Week 8 clinic visits. The highest of 3 technically acceptable measurements was recorded. The Visit 3 FEV1 assessment was used as the BL value. Change from BL in trough FEV1 was calculated as the value at Week 8 minus the value at BL. The analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of BL trough FEV1, country, sex, age, and treatment group. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-BL on-treatment measurement (scheduled/unscheduled visits) was used to impute missing measurements.

End point type

Primary

End point timeframe

Baseline and Week 8

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	106 ^[1]	102 ^[2]	101 ^[3]	102 ^[4]	97 ^[5]	99 ^[6]
Units: Liters
least squares mean (standard error)	-0.065 ± 0.0395	0.142 ± 0.0403	0.173 ± 0.0404	0.228 ± 0.0402	0.215 ± 0.0414	0.16 ± 0.0409

Notes
[1] - Intent-to-Treat (ITT) Population: randomized participants who received >=1 dose of study medication.
[2] - Intent-to-Treat (ITT) Population: randomized participants who received >=1 dose of study medication.
[3] - Intent-to-Treat (ITT) Population: randomized participants who received >=1 dose of study medication.
[4] - Intent-to-Treat (ITT) Population: randomized participants who received >=1 dose of study medication.
[5] - Intent-to-Treat (ITT) Population: randomized participants who received >=1 dose of study medication.
[6] - Intent-to-Treat (ITT) Population: randomized participants who received >=1 dose of study medication.

Analysis 1

Comparison groups

Placebo v GW685698X 100 µg OD

Number of subjects included in analysis

208

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.207

Confidence interval

level

95%

sides

2-sided

lower limit

0.096

upper limit

0.318

Analysis 2

Comparison groups

Placebo v GW685698X 200 µg OD

Number of subjects included in analysis

207

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.238

Confidence interval

level

95%

sides

2-sided

lower limit

0.127

upper limit

0.349

Analysis 3

Comparison groups

Placebo v GW685698X 300 µg OD

Number of subjects included in analysis

208

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.293

Confidence interval

level

95%

sides

2-sided

lower limit

0.182

upper limit

0.404

Analysis 4

Comparison groups

Placebo v GW685698X 400 µg OD

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.279

Confidence interval

level

95%

sides

2-sided

lower limit

0.167

upper limit

0.392

Analysis 5

Comparison groups

Placebo v FP 250 µg BID

Number of subjects included in analysis

205

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.225

Confidence interval

level

95%

sides

2-sided

lower limit

0.114

upper limit

0.337

Secondary: Mean change from Baseline in daily trough (pre-dose and pre-rescue bronchodilator) evening peak expiratory flow (PEF) averaged over the 8-week Treatment Period

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End point title

Mean change from Baseline in daily trough (pre-dose and pre-rescue bronchodilator) evening peak expiratory flow (PEF) averaged over the 8-week Treatment Period

End point description

PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Trough PEF is defined as the PEF measurement performed at the end of the dosing interval. PEF was measured by the participants using a hand-held electronic peak flow meter each evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. The best of three attempts was recorded by the participants in a daily diary. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline was calculated as the value of the averaged daily evening PEF over the 8-week treatment period minus the value at Baseline. The analysis was performed using an ANCOVA model with covariates of Baseline trough evening PEF, country, sex, age, and treatment group.

End point type

Secondary

End point timeframe

From Baseline up to Week 8

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	107 ^[7]	104 ^[8]	101 ^[9]	102 ^[10]	99 ^[11]	99 ^[12]
Units: Liters per minute
least squares mean (standard error)	-2.8 ± 3.54	9.1 ± 3.6	14.8 ± 3.65	15.1 ± 3.62	21 ± 3.7	18.2 ± 3.69

Notes
[7] - ITT Population. Only those participants available at the specified time points were analyzed.
[8] - ITT Population. Only those participants available at the specified time points were analyzed.
[9] - ITT Population. Only those participants available at the specified time points were analyzed.
[10] - ITT Population. Only those participants available at the specified time points were analyzed.
[11] - ITT Population. Only those participants available at the specified time points were analyzed.
[12] - ITT Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Secondary: Mean change from Baseline in daily morning PEF averaged over the 8-week Treatment Period

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End point title

Mean change from Baseline in daily morning PEF averaged over the 8-week Treatment Period

End point description

PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Trough PEF is defined as the PEF measurement performed at the end of the dosing interval. PEF was measured by the participants using a hand-held electronic peak flow meter each morning prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. The best of three attempts was recorded by the participants in a daily diary. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline was calculated as the value of the averaged daily morning PEF over the 8-week treatment period minus the value at Baseline. The analysis was performed using an ANCOVA model with covariates of Baseline trough morning PEF, country, sex, age, and treatment group.

End point type

Secondary

End point timeframe

From Baseline up to Week 8

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	107 ^[13]	104 ^[14]	101 ^[15]	102 ^[16]	99 ^[17]	99 ^[18]
Units: Liters per minute
least squares mean (standard error)	-4.7 ± 3.78	15.6 ± 3.85	16 ± 3.89	25.5 ± 3.87	26 ± 3.95	25.1 ± 3.94

Notes
[13] - ITT Population. Only those participants available at the specified time points were analyzed.
[14] - ITT Population. Only those participants available at the specified time points were analyzed.
[15] - ITT Population. Only those participants available at the specified time points were analyzed.
[16] - ITT Population. Only those participants available at the specified time points were analyzed.
[17] - ITT Population. Only those participants available at the specified time points were analyzed.
[18] - ITT Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Secondary: Mean change from Baseline in the percentage of symptom-free 24-hour (hr) periods during the 8-week Treatment Period

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End point title

Mean change from Baseline in the percentage of symptom-free 24-hour (hr) periods during the 8-week Treatment Period

End point description

Asthma symptoms were recorded in a daily dairy by the participants every day in the morning and evening before taking any rescue or study medication and before PEF measurement. A 24-hour period in which a participant’s responses to both the morning and evening assessments indicated no symptoms was considered as symptom-free. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 8-week Treatment Period minus the value at Baseline. The analysis was performed using an ANCOVA model with covariates of Baseline, country, sex, age, and treatment group.

End point type

Secondary

End point timeframe

From Baseline up to Week 8

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	107 ^[19]	104 ^[20]	101 ^[21]	102 ^[22]	99 ^[23]	99 ^[24]
Units: Percentage of symptom-free 24-hr periods
least squares mean (standard error)	17.1 ± 2.91	21.3 ± 2.96	19.4 ± 2.99	24.1 ± 2.97	28 ± 3.02	30.4 ± 3.02

Notes
[19] - ITT Population. Only those participants available at the specified time points were analyzed.
[20] - ITT Population. Only those participants available at the specified time points were analyzed.
[21] - ITT Population. Only those participants available at the specified time points were analyzed.
[22] - ITT Population. Only those participants available at the specified time points were analyzed.
[23] - ITT Population. Only those participants available at the specified time points were analyzed.
[24] - ITT Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Secondary: Mean change from Baseline in the percentage of rescue free 24-hour (hr) periods during the 8-week Treatment Period

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End point title

Mean change from Baseline in the percentage of rescue free 24-hour (hr) periods during the 8-week Treatment Period

End point description

The number of inhalations of rescue albuterol/salbutamol inhalation aerosol used during the day and night was recorded by the participants in a daily diary. A 24-hr period in which a participant’s responses to both the morning and evening assessments indicated no use of rescue medication was considered as rescue-free. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 8-week Treatment Period minus the value at Baseline. The analysis was performed using an ANCOVA model with covariates of baseline, country, sex, age, and treatment group.

End point type

Secondary

End point timeframe

From Baseline up to Week 8

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	107 ^[25]	104 ^[26]	101 ^[27]	102 ^[28]	99 ^[29]	99 ^[30]
Units: Percentage of rescue-free 24-hr periods
least squares mean (standard error)	15.6 ± 3.02	25 ± 3.07	23.8 ± 3.12	25 ± 3.1	24.4 ± 3.15	34.5 ± 3.15

Notes
[25] - ITT Population. Only those participants available at the specified time points were analyzed.
[26] - ITT Population. Only those participants available at the specified time points were analyzed.
[27] - ITT Population. Only those participants available at the specified time points were analyzed.
[28] - ITT Population. Only those participants available at the specified time points were analyzed.
[29] - ITT Population. Only those participants available at the specified time points were analyzed.
[30] - ITT Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

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

End point type

Secondary

End point timeframe

From the first dose of study medication up to Week 8/Early Withdrawal

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	107 ^[31]	105 ^[32]	101 ^[33]	103 ^[34]	99 ^[35]	100 ^[36]
Units: Participants	35	10	11	8	7	14

Notes
[31] - ITT Population
[32] - ITT Population
[33] - ITT Population
[34] - ITT Population
[35] - ITT Population
[36] - ITT Population

No statistical analyses for this end point

Secondary: Number of participants with any on-treatment adverse events or serious adverse events throughout the 8-week Treatment Period

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End point title

Number of participants with any on-treatment adverse events or serious adverse events throughout the 8-week Treatment Period

End point description

An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in disability/incapacity; or is a congenital anomaly/birth defect. Medical or scientific judgment should have been exercised in other situations. Refer to the general AE/SAE module for a list of AEs (occurring at a frequency threshold >=3%) and SAEs.

End point type

Secondary

End point timeframe

From the first dose of study medication up to Week 8/Early Withdrawal

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	107 ^[37]	105 ^[38]	101 ^[39]	103 ^[40]	99 ^[41]	100 ^[42]
Units: Participants
Any AE	32	43	33	41	35	42
Any SAE	0	0	0	1	1	0

Notes
[37] - ITT Population
[38] - ITT Population
[39] - ITT Population
[40] - ITT Population
[41] - ITT Population
[42] - ITT Population

No statistical analyses for this end point

Secondary: Number of participants with clinical/visual evidence of oropharyngeal candidiasis

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End point title

Number of participants with clinical/visual evidence of oropharyngeal candidiasis

End point description

A detailed oropharyngeal examination for visual evidence of oral candidiasis was performed for the entire Treatment Period.

End point type

Secondary

End point timeframe

From Baseline up to Week 8/Early Withdrawal

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	107 ^[43]	105 ^[44]	101 ^[45]	103 ^[46]	99 ^[47]	100 ^[48]
Units: Participants
Clinical evidence	0	3	2	4	2	4
No clinical evidence	107	102	99	99	97	96

Notes
[43] - ITT Population
[44] - ITT Population
[45] - ITT Population
[46] - ITT Population
[47] - ITT Population
[48] - ITT Population

No statistical analyses for this end point

Secondary: Percentage of basophils, eosinophils, lymphocytes, monocytes, and total neutrophils in the blood at Baseline and Week 8

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End point title

Percentage of basophils, eosinophils, lymphocytes, monocytes, and total neutrophils in the blood at Baseline and Week 8

End point description

Blood samples were collected for the measurement of basophils, eosinophils, lymphocytes, monocytes, and total neutrophils at Baseline (BL) and Week 8 (W8). The Baseline value was the measurement taken at screening (Visit 1).

End point type

Secondary

End point timeframe

Baseline and Week 8

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	100 ^[49]	103 ^[50]	97 ^[51]	99 ^[52]	94 ^[53]	95 ^[54]
Units: Percentage
arithmetic mean (standard deviation)
Basophils, BL, n=100, 103, 97, 99, 94, 95	0.33 ± 0.159	0.32 ± 0.179	0.35 ± 0.188	0.31 ± 0.155	0.33 ± 0.169	0.34 ± 0.209
Basophils,W8, n=63, 84, 82, 83, 81, 82	0.31 ± 0.182	0.32 ± 0.191	0.38 ± 0.227	0.33 ± 0.165	0.32 ± 0.203	0.35 ± 0.19
Eosinophils, BL, n=100, 103, 97, 99, 94, 95	4.48 ± 3.262	4.05 ± 2.882	4.05 ± 2.981	4.17 ± 2.649	4.2 ± 3.185	4.66 ± 3.393
Eosinophils, W8, n=63, 84, 82, 83, 81, 82	4.78 ± 4.107	3.72 ± 2.518	3.54 ± 2.556	3.53 ± 2.671	3.35 ± 3.063	4.21 ± 3.29
Lymphocytes, BL, n=100, 103, 97, 99, 94, 95	34.05 ± 9.683	33.97 ± 8.817	34.01 ± 9.214	33.7 ± 8.38	31.48 ± 9.075	33.61 ± 9.032
Lymphocytes, W8, n=63, 84, 82, 83, 81, 82	33.51 ± 8.261	32.95 ± 8.183	31.39 ± 8.668	30.97 ± 8.711	27.38 ± 7.585	33.17 ± 7.607
Monocytes, BL, n=100, 103, 97, 99, 94, 95	4.66 ± 1.674	4.52 ± 2.128	4.85 ± 1.939	4.58 ± 1.994	4.47 ± 1.954	4.55 ± 2.19
Monocytes, W8, n=63, 84, 82, 83, 81, 82	4.85 ± 1.798	4.82 ± 3.006	4.92 ± 2.324	4.42 ± 1.833	4.18 ± 2.176	4.59 ± 2.436
Total Neutrophils, BL, n=100, 103, 97, 99, 94, 95	56.46 ± 10.876	57.12 ± 10.016	56.72 ± 9.86	57.22 ± 9.633	59.5 ± 10.248	56.75 ± 10.915
Total Neutrophils, W8, n=63, 84, 82, 83, 81, 82	56.53 ± 9.391	58.17 ± 9.386	59.75 ± 9.513	60.72 ± 9.846	64.75 ± 8.896	57.61 ± 9.681

Notes
[49] - ITT Population. Only those participants available at the specified time points were analyzed.
[50] - ITT Population. Only those participants available at the specified time points were analyzed.
[51] - ITT Population. Only those participants available at the specified time points were analyzed.
[52] - ITT Population. Only those participants available at the specified time points were analyzed.
[53] - ITT Population. Only those participants available at the specified time points were analyzed.
[54] - ITT Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Secondary: Hematocrit at Baseline and Week 8

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End point title

Hematocrit at Baseline and Week 8

End point description

Blood samples were collected for the measurement of Hematocrit at Baseline (BL) and Week 8 (W8). The Baseline value was the measurement taken at screening (Visit 1).

End point type

Secondary

End point timeframe

Baseline and Week 8

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	102 ^[55]	104 ^[56]	96 ^[57]	99 ^[58]	93 ^[59]	95 ^[60]
Units: Proportion of 1
arithmetic mean (standard deviation)
Hematocrit, BL, n=102, 104, 96, 99, 93, 95	0.42 ± 0.041	0.43 ± 0.034	0.42 ± 0.043	0.42 ± 0.035	0.42 ± 0.039	0.42 ± 0.039
Hematocrit, W8, n=62, 84, 82, 83, 81, 81	0.41 ± 0.037	0.42 ± 0.039	0.42 ± 0.043	0.41 ± 0.038	0.42 ± 0.046	0.41 ± 0.055

Notes
[55] - ITT Population. Only those participants available at the specified time points were analyzed.
[56] - ITT Population. Only those participants available at the specified time points were analyzed.
[57] - ITT Population. Only those participants available at the specified time points were analyzed.
[58] - ITT Population. Only those participants available at the specified time points were analyzed.
[59] - ITT Population. Only those participants available at the specified time points were analyzed.
[60] - ITT Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Secondary: Hemoglobin at Baseline and Week 8

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End point title

Hemoglobin at Baseline and Week 8

End point description

Blood samples were collected for the measurement of hemoglobin at Baseline (BL)and Week 8 (W8). The Baseline value was the measurement taken at screening (Visit 1).

End point type

Secondary

End point timeframe

Baseline and Week 8

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	102 ^[61]	104 ^[62]	96 ^[63]	99 ^[64]	93 ^[65]	95 ^[66]
Units: Grams per liter (G/L)
arithmetic mean (standard deviation)
Hemoglobin, BL, n=102, 104, 96, 99, 93, 95	137.64 ± 13.911	139.34 ± 11.908	137.74 ± 14.028	138.08 ± 11.707	138.57 ± 13.393	136.93 ± 14.139
Hemoglobin, W8, n=62, 84, 82, 83, 81, 81	135.09 ± 12.043	136.42 ± 13.342	137.85 ± 13.772	135.3 ± 12.36	138.17 ± 15.05	135.79 ± 18.663

Notes
[61] - ITT Population. Only those participants available at the specified time points were analyzed.
[62] - ITT Population. Only those participants available at the specified time points were analyzed.
[63] - ITT Population. Only those participants available at the specified time points were analyzed.
[64] - ITT Population. Only those participants available at the specified time points were analyzed.
[65] - ITT Population. Only those participants available at the specified time points were analyzed.
[66] - ITT Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Secondary: Platelet count and white blood cell (WBC) count at Baseline and Week 8

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End point title

Platelet count and white blood cell (WBC) count at Baseline and Week 8

End point description

Blood samples were collected for the measurement of platelet count and WBC count at Baseline (BL) and Week 8 (W8). The Baseline value was the measurement taken at screening (Visit 1).

End point type

Secondary

End point timeframe

Baseline and Week 8

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	101 ^[67]	103 ^[68]	96 ^[69]	99 ^[70]	93 ^[71]	95 ^[72]
Units: 10^9 cells per liter (GI/L)
arithmetic mean (standard deviation)
Platelet count, BL, n=98, 103,93, 98, 89, 94	286.23 ± 57.383	277.29 ± 64.358	290.9 ± 98.801	282.86 ± 70.086	283.01 ± 58.915	285.45 ± 69.22
Platelet count, W8, n=60, 84, 80, 81, 80, 80	275.91 ± 53.705	281.4 ± 66.449	277.73 ± 71.595	287.98 ± 67.053	297.83 ± 76.271	287.6 ± 87.009
WBC, BL, n=101, 103, 96, 99, 93, 95	8.05 ± 2.31	7.9 ± 2.11	7.69 ± 2.086	8.11 ± 2.332	8.23 ± 2.027	8.12 ± 2.141
WBC, W8, n=62, 84, 82, 83, 81, 81	8.02 ± 1.991	8.06 ± 1.894	7.79 ± 2.066	8.2 ± 1.936	9.07 ± 2.054	8.3 ± 3.119

Notes
[67] - ITT Population. Only those participants available at the specified time points were analyzed.
[68] - ITT Population. Only those participants available at the specified time points were analyzed.
[69] - ITT Population. Only those participants available at the specified time points were analyzed.
[70] - ITT Population. Only those participants available at the specified time points were analyzed.
[71] - ITT Population. Only those participants available at the specified time points were analyzed.
[72] - ITT Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Secondary: Red blood cells (RBC) count at Baseline and Week 8

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End point title

Red blood cells (RBC) count at Baseline and Week 8

End point description

Blood samples were collected for the measurement of RBC count at Baseline (BL) and Week 8 (W8). The Baseline value was the measurement taken at screening (Visit 1).

End point type

Secondary

End point timeframe

Baseline and Week 8

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	102 ^[73]	104 ^[74]	96 ^[75]	99 ^[76]	93 ^[77]	95 ^[78]
Units: 10^12 cells per liter (TI/L)
arithmetic mean (standard deviation)
BL, n=102, 104, 96, 99, 93, 95	4.66 ± 0.439	4.68 ± 0.385	4.69 ± 0.539	4.63 ± 0.442	4.64 ± 0.395	4.61 ± 0.412
W8, n=62, 84, 82, 83, 81, 80	4.54 ± 0.483	4.57 ± 0.447	4.62 ± 0.513	4.5 ± 0.458	4.66 ± 0.526	4.52 ± 0.426

Notes
[73] - ITT Population. Only those participants available at the specified time points were analyzed.
[74] - ITT Population. Only those participants available at the specified time points were analyzed.
[75] - ITT Population. Only those participants available at the specified time points were analyzed.
[76] - ITT Population. Only those participants available at the specified time points were analyzed.
[77] - ITT Population. Only those participants available at the specified time points were analyzed.
[78] - ITT Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Secondary: Clinical chemistry parameters of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LD), and gamma glutamyltransferase (GGT) at Baseline and Week 8

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End point title

Clinical chemistry parameters of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LD), and gamma glutamyltransferase (GGT) at Baseline and Week 8

End point description

Blood samples were collected for the measurement of ALP, ALT, AST, LD and GGT at Baseline (BL) and Week 8 (W8). The Baseline value was the measurement taken at Screening (Visit 1).

End point type

Secondary

End point timeframe

Baseline and Week 8

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	106 ^[79]	104 ^[80]	101 ^[81]	102 ^[82]	98 ^[83]	99 ^[84]
Units: International units per liter (IU/L)
arithmetic mean (standard deviation)
ALP, BL, n=106, 104, 101, 102, 98, 99	89.3 ± 58.42	90.5 ± 61.69	83.7 ± 56.68	88 ± 74.76	83.8 ± 40.51	89 ± 57.83
ALP, W8, n=65, 85, 84, 89, 83, 81	88 ± 57.32	82.8 ± 44.87	77.9 ± 40.64	77.9 ± 37.21	81.9 ± 40.05	88.6 ± 53.16
ALT, BL, n=106, 104, 101, 102, 98, 99	22.3 ± 21.25	20 ± 14.75	20.5 ± 15.44	23.4 ± 15.65	20.4 ± 12.7	20.6 ± 15.83
ALT, W8, n=65, 85, 85, 89, 83, 81	20.1 ± 14.37	21 ± 14.01	20.8 ± 11.68	23.3 ± 16.73	22.1 ± 18.46	20.3 ± 14.92
AST, BL, n=106, 103, 100, 102, 97, 99	25.2 ± 30.81	20.8 ± 7.81	24.8 ± 38.56	22.7 ± 10.1	21.2 ± 7.1	21.4 ± 10.18
AST, W8, n=65, 85, 85, 89, 83, 81	21.8 ± 8.77	20.5 ± 7.5	21.4 ± 8.42	22.7 ± 12.58	21.7 ± 8.87	21.4 ± 8.51
LD, BL, n=106, 103, 100, 102, 97, 99	173.2 ± 66.73	167.1 ± 44.88	173.8 ± 129.22	169 ± 54.06	168.6 ± 50.65	167.1 ± 57.95
LD, W8, n=65, 85, 85, 89, 83, 81	157.4 ± 37.93	158.2 ± 29.31	162.5 ± 35.17	160.6 ± 30.45	169.2 ± 31.91	162.4 ± 35.39
GGT, BL, n=106, 104, 101, 102, 98, 99	33.1 ± 54.48	26 ± 20.33	27.6 ± 21.53	35.2 ± 38.16	28.2 ± 18.36	29.5 ± 27.6
GGT, W8, n=65, 85, 85, 89, 83, 81	31.5 ± 44.86	30.1 ± 41.05	29.2 ± 31.63	34.8 ± 39.4	28.3 ± 23.69	28.4 ± 24.14

Notes
[79] - ITT Population. Only those participants available at the specified time points were analyzed.
[80] - ITT Population. Only those participants available at the specified time points were analyzed.
[81] - ITT Population. Only those participants available at the specified time points were analyzed.
[82] - ITT Population. Only those participants available at the specified time points were analyzed.
[83] - ITT Population. Only those participants available at the specified time points were analyzed.
[84] - ITT Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Secondary: Clinical chemistry parameters of albumin and total protein at Baseline and Week 8

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End point title

Clinical chemistry parameters of albumin and total protein at Baseline and Week 8

End point description

Blood samples were collected for the measurement of albumin and total protein at Baseline (BL) and Week 8 (W8). The Baseline value was the measurement taken at Screening (Visit 1).

End point type

Secondary

End point timeframe

Baseline and Week 8

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	106 ^[85]	104 ^[86]	101 ^[87]	102 ^[88]	98 ^[89]	99 ^[90]
Units: Grams per liter (G/L)
arithmetic mean (standard deviation)
Albumin,BL, n=106, 104, 101, 102, 98, 99	45.2 ± 3.43	45.4 ± 3.12	45.4 ± 3.16	45.4 ± 2.71	45.5 ± 2.62	44.9 ± 2.86
Albumin, W8, n=65, 85, 85, 89, 83, 81	44 ± 3.06	44.7 ± 3.08	45.1 ± 2.81	44.6 ± 2.81	45.3 ± 2.91	44.5 ± 3.19
Total protein, BL, n=106, 104, 101, 102, 98, 99	74.1 ± 5.03	73.3 ± 4.16	73.9 ± 4.4	73.7 ± 4.42	74 ± 4.37	73 ± 4.26
Total protein, W8, n=65, 85, 85, 89, 83, 81	72 ± 4.68	72.4 ± 4.31	73.3 ± 5.28	72.5 ± 3.92	73.9 ± 4.02	72.8 ± 4.16

Notes
[85] - ITT Population. Only those participants available at the specified time points were analyzed.
[86] - ITT Population. Only those participants available at the specified time points were analyzed.
[87] - ITT Population. Only those participants available at the specified time points were analyzed.
[88] - ITT Population. Only those participants available at the specified time points were analyzed.
[89] - ITT Population. Only those participants available at the specified time points were analyzed.
[90] - ITT Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Secondary: Clinical chemistry parameters of chloride, calcium, carbon dioxide content/bicarbonate (CO2/BI), cholesterol, glucose, phosphorus inorganic(PI), potassium, sodium, and urea/blood urea nitrogen (BUN) at Baseline and Week 8

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End point title

Clinical chemistry parameters of chloride, calcium, carbon dioxide content/bicarbonate (CO2/BI), cholesterol, glucose, phosphorus inorganic(PI), potassium, sodium, and urea/blood urea nitrogen (BUN) at Baseline and Week 8

End point description

Blood samples were collected for the measurement of chloride, calcium, CO2/BI, cholesterol, glucose, PI, potassium, sodium, and urea/blood urea nitrogen (BUN) at Baseline (BL) and Week 8 (W8). The Baseline value was the measurement taken at screening (Visit 1).

End point type

Secondary

End point timeframe

Baseline and Week 8

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	106 ^[91]	104 ^[92]	101 ^[93]	102 ^[94]	98 ^[95]	99 ^[96]
Units: Millimoles per liter (mmol/L)
arithmetic mean (standard deviation)
Chloride, BL, n=106, 104, 101, 102, 98, 99	104.8 ± 3.06	105 ± 2.61	104.7 ± 3.15	104.5 ± 2.34	104.8 ± 3	105 ± 2.41
Chloride, W8, n=65, 85, 85, 89, 83, 81	104.8 ± 2.31	104.3 ± 2.05	104.3 ± 2.36	104.4 ± 2.2	104 ± 2.37	104.4 ± 2.37
Calcium, BL, n=106, 103, 100, 102, 97, 99	2.3 ± 0.12	2.3 ± 0.12	2.3 ± 0.12	2.3 ± 0.1	2.3 ± 0.12	2.3 ± 0.11
Calcium, W8, n=65, 85, 84, 89, 83, 81	2.3 ± 0.12	2.3 ± 0.12	2.3 ± 0.11	2.3 ± 0.11	2.3 ± 0.12	2.3 ± 0.11
CO2/BI, BL, n=106, 103, 100, 102, 97, 99	22.9 ± 2.12	22.5 ± 2.67	22.7 ± 2.4	22.6 ± 2.58	22.6 ± 2.24	22.6 ± 2.15
CO2/BI, W8, n=65, 85, 85, 89, 83, 81	22.4 ± 2.08	22.5 ± 2.4	22.8 ± 2.72	23.1 ± 2.4	22.8 ± 2.58	22.9 ± 2.37
Cholesterol, BL, n=106, 104, 101, 102, 98, 99	5 ± 1.09	5 ± 1.21	4.9 ± 1.07	5.2 ± 1.13	5.2 ± 1.16	5 ± 1.12
Cholesterol, W8, n=65, 85, 85, 89, 83, 81	4.9 ± 1.06	5 ± 1.19	4.9 ± 1.03	5.1 ± 1.08	5.1 ± 1.11	4.9 ± 1.05
Glucose, BL, n=106, 103, 100, 102, 98, 99	5.2 ± 0.94	5.4 ± 1.95	5.1 ± 0.7	5.2 ± 0.84	5.5 ± 2.18	5.5 ± 1.88
Glucose, W8, n=65, 85, 85, 89, 83, 81	5 ± 0.73	5.2 ± 1.66	5.1 ± 1.04	5.2 ± 1.06	5 ± 1.46	5.3 ± 1.85
PI, BL, n=106, 104, 101, 102, 98, 99	1.2 ± 0.2	1.2 ± 0.22	1.2 ± 0.33	1.2 ± 0.19	1.2 ± 0.19	1.1 ± 0.22
PI, W8, n=65, 85, 85, 89, 83, 81	1.3 ± 0.21	1.3 ± 0.17	1.2 ± 0.18	1.2 ± 0.17	1.3 ± 0.26	1.3 ± 0.19
Potassium, BL, n=106, 103, 100, 102, 97, 99	4.2 ± 0.41	4.1 ± 0.45	4.1 ± 0.44	4.2 ± 0.46	4.2 ± 0.38	4.1 ± 0.41
Potassium, W8, n=65, 85, 84, 89, 83, 81	4.2 ± 0.64	4.2 ± 0.53	4.3 ± 0.63	4.2 ± 0.44	4.3 ± 0.66	4.2 ± 0.34
Sodium, BL, n=106, 104, 101, 102, 98, 99	140.7 ± 3.38	140.6 ± 1.91	141 ± 3.13	140.3 ± 2.07	140.7 ± 2.85	140.5 ± 1.76
Sodium, W8, n=65, 85, 85, 89, 83, 81	139.9 ± 2.11	140 ± 1.95	140.3 ± 2.05	140.5 ± 2.15	140.3 ± 2.23	140.2 ± 1.8
BUN, BL, n=106, 104, 101, 102, 98, 99	5.3 ± 1.87	5.1 ± 2.07	5.1 ± 1.9	4.9 ± 1.61	5.2 ± 2.2	5.3 ± 1.78
BUN, W8, n=65, 85, 85, 89, 83, 81	5.2 ± 1.42	4.9 ± 1.47	5 ± 1.61	5 ± 1.68	4.8 ± 1.6	5.2 ± 1.64

Notes
[91] - ITT Population. Only those participants available at the specified time points were analyzed.
[92] - ITT Population. Only those participants available at the specified time points were analyzed.
[93] - ITT Population. Only those participants available at the specified time points were analyzed.
[94] - ITT Population. Only those participants available at the specified time points were analyzed.
[95] - ITT Population. Only those participants available at the specified time points were analyzed.
[96] - ITT Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Secondary: Clinical chemistry parameters of direct bilirubin (DBIL), total bilirubin (TBIL), uric acid and creatinine at Baseline and Week 8

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End point title

Clinical chemistry parameters of direct bilirubin (DBIL), total bilirubin (TBIL), uric acid and creatinine at Baseline and Week 8

End point description

Blood samples were collected for the measurement of DBIL, TBIL, uric acid and creatinine at Baseline (BL) and Week 8 (W8). The Baseline value was the measurement taken at screening (Visit 1).

End point type

Secondary

End point timeframe

Baseline and Week 8

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	106 ^[97]	104 ^[98]	101 ^[99]	102 ^[100]	98 ^[101]	99 ^[102]
Units: Micromoles per liter (µmol/L)
arithmetic mean (standard deviation)
DBIL, BL, n=106, 103, 100, 101, 98, 98	2.1 ± 1.23	2 ± 1.3	1.9 ± 1.09	1.9 ± 1.09	2.1 ± 0.97	1.8 ± 0.9
DBIL, W8, n=65, 65, 85, 89, 83, 81	1.8 ± 0.97	2 ± 1.09	1.9 ± 0.88	1.9 ± 1.18	1.8 ± 0.93	1.7 ± 0.75
TBIL, BL, n=106, 104, 101, 102, 98, 99	10.2 ± 5.39	10.6 ± 6.11	9.4 ± 5.2	9.3 ± 4.65	9.7 ± 5.48	8.9 ± 4.02
TBIL, W8, n=65, 85, 85, 89, 83, 81	8.5 ± 4.38	9.6 ± 6.13	9.2 ± 4.93	8.8 ± 4.14	9.2 ± 4.08	8.4 ± 3.03
Uric acid, BL, n=106, 104, 101, 102, 98, 99	326.7 ± 93.33	323.2 ± 83.6	319.4 ± 94.9	326.7 ± 95.36	323.9 ± 82.3	312.7 ± 85.72
Uric acid, W8, n=65, 85, 85, 89, 83, 81	308.8 ± 89.18	318.3 ± 84.85	319.7 ± 93.76	314.4 ± 94.26	321.1 ± 83.68	311.4 ± 90.62
Creatinine, BL, n=106, 104, 101, 102, 98, 99	77.9 ± 14.57	77.9 ± 18.6	77.8 ± 16.5	75.9 ± 15.04	75.9 ± 18.24	77.7 ± 15.77
Creatinine, W8, n=65, 85, 85, 89, 83, 81	74.4 ± 15.58	74.6 ± 14.95	78.5 ± 16.79	76.9 ± 15.97	76.2 ± 15.18	77.2 ± 16.59

Notes
[97] - ITT Population. Only those participants available at the specified time points were analyzed.
[98] - ITT Population. Only those participants available at the specified time points were analyzed.
[99] - ITT Population. Only those participants available at the specified time points were analyzed.
[100] - ITT Population. Only those participants available at the specified time points were analyzed.
[101] - ITT Population. Only those participants available at the specified time points were analyzed.
[102] - ITT Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Secondary: Number of participants with the indicated result for the indicated urinalysis parameters tested by dipstick at Baseline and Week 8/Early Withdrawal

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End point title

Number of participants with the indicated result for the indicated urinalysis parameters tested by dipstick at Baseline and Week 8/Early Withdrawal

End point description

Urinalysis parameters included: Urine Occult Blood (UOB), Urine Glucose (UG), Urine Ketones (UK), Urine Protein (UP), and Urine Leukocyte Esterase test for detecting White Blood Cell (UWBC). The dipstick was a strip used to detect the presence or absence of these parameters in the urine sample. The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters can be read as negative (Neg), Trace, 1+, 2+, 3+ and 4+, and for UG the result can be read as Neg, Trace, Trace or 1/10 grams per deciliter (G/dL), 1+ or 1/4 G/dL, 3+ or 1 G/dL, indicating proportional concentrations in the urine sample. Data are reported as the number of participants who had neg, Trace, 1+, 2+, 3+ and 4+ levels at Baseline (BL) and Week 8 (W8)/Early Withdrawal (WD). The Baseline value was the measurement taken at screening (Visit 1).

End point type

Secondary

End point timeframe

Baseline and Week 8/Early Withdrawal

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	102 ^[103]	101 ^[104]	98 ^[105]	99 ^[106]	94 ^[107]	97 ^[108]
Units: Participants
UOB, Neg, BL, n=102, 101, 98, 99, 94, 97	96	91	85	90	81	91
UOB, Trace, BL, n=102, 101, 98, 99, 94, 97	4	1	3	4	8	2
UOB, 1+, BL, n=102, 101, 98, 99, 94, 97	1	4	6	1	1	1
UOB, 2+, BL, n=102, 101, 98, 99, 94, 97	0	1	1	0	0	1
UOB, 3+, BL, n=102, 101, 98, 99, 94, 97	1	4	3	4	4	2
UOB, Neg, W8, n=63, 85, 84, 82, 82, 82	56	77	77	73	73	72
UOB, Trace, W8, n=63, 85, 84, 82, 82, 82	4	3	2	3	2	4
UOB, 1+, W8, n=63, 85, 84, 82, 82, 82	0	2	1	1	3	1
UOB, 2+, W8, n=63, 85, 84, 82, 82, 82	1	1	2	1	3	1
UOB, 3+, W8, n=63, 85, 84, 82, 82, 82	2	2	2	4	1	4
UOB, Neg, WD, n=9, 4, 1, 2, 3, 7	9	4	1	2	3	6
UOB, 2+, WD, n=9, 4, 1, 2, 3, 7	0	0	0	0	0	1
UG, Neg, BL, n=102, 101, 98, 99, 94, 97	100	98	98	98	91	94
UG, Trace, BL, n=102, 101, 98, 99, 94, 97	1	1	0	0	0	0
UG, Trace or 1/10 G/DL,BL,n=102,101,98,99,94,97	1	0	0	0	0	1
UG, 1+ or 1/3 G/DL, BL, n=102, 101, 98, 99, 94, 97	0	0	0	1	1	1
UG, 3+ or 1 G/DL, BL, n=102, 101, 98, 99, 94, 97	0	2	0	0	2	1
UG, Neg,W8, n=63, 85, 84, 82, 82, 82	62	83	83	81	82	80
UG, Trace, W8, n=63, 85, 84, 82, 82, 82	0	0	1	1	0	0
UG, 1+ or 1/4 G/DL, W8, n=63, 85, 84, 82, 82, 82	1	0	0	0	0	0
UG, 3+ or 1 G/DL, W8, n=63, 85, 84, 82, 82, 82	0	2	0	0	0	2
UG, Neg, WD, n=9, 4, 1, 2, 3, 7	9	4	1	2	3	7
UK, Neg, BL, n=102, 101, 98, 99, 94, 97	97	96	96	96	90	94
UK, Trace, BL, n=102, 101, 98, 99, 94, 97	5	2	2	3	4	1
UK, 1+, BL, n=102, 101, 98, 99, 94, 97	0	2	0	0	0	2
UK, 2+, BL, n=102, 101, 98, 99, 94, 97	0	1	0	0	0	0
UK, Neg, W8, n=63, 85, 84, 82, 82, 82	61	80	81	78	75	80
UK, Trace, W8, n=63, 85, 84, 82, 82, 82	2	5	2	4	7	2
UK, 1+, W8, n=63, 85, 84, 82, 82, 82	0	0	1	0	0	0
UK, Neg, WD, n=9, 4, 1, 2, 3, 7	9	4	1	2	3	7
UP, Neg, BL, n=102, 101, 98, 99, 94, 97	76	78	77	78	70	75
UP, Trace, BL, n=102, 101, 98, 99, 94, 97	19	14	13	13	17	11
UP, 1+, BL, n=102, 101, 98, 99, 94, 97	6	6	7	7	6	11
UP, 2+, BL, n=102, 101, 98, 99, 94, 97	0	1	1	0	1	0
UP, 3+, BL, n=102, 101, 98, 99, 94, 97	1	2	0	1	0	0
UP, Neg, W8, n=63, 85, 84, 82, 82, 82	54	64	68	65	63	61
UP, Trace, W8, n=63, 85, 84, 82, 82, 82	6	14	8	12	17	15
UP, 1+, W8, n=63, 85, 84, 82, 82, 82	3	5	6	5	2	5
UP, 2+, W8,n=63, 85, 84, 82, 82, 82	0	2	1	0	0	0
UP, 3+, W8, n=63, 85, 84, 82, 82, 82	0	0	0	0	0	1
UP, 4+, W8, n=63, 85, 84, 82, 82, 82	0	0	1	0	0	0
UP, Neg, WD, n=9, 4, 1, 2, 3, 7	8	4	0	1	3	6
UP, Trace, WD, n=9, 4, 1, 2, 3, 7	0	0	1	1	0	0
UP, 1+, WD, n=9, 4, 1, 2, 3, 7	1	0	0	0	0	1
UWBC, Neg, BL, n=102, 101, 98, 99, 94, 97	86	87	82	81	74	88
UWBC, Trace, BL, n=102, 101, 98, 99, 94, 97	2	4	7	3	5	2
UWBC, 1+, BL, n=102, 101, 98, 99, 94, 97	6	5	4	7	8	3
UWBC, 2+, BL, n=102, 101, 98, 99, 94, 97	7	3	2	8	5	4
UWBC, 3+, BL, n=102, 101, 98, 99, 94, 97	1	2	3	0	2	0
UWBC, Neg, W8, n=63, 85, 84, 82, 82, 82	52	65	71	62	63	69
UWBC, Trace, W8, n=63, 85, 84, 82, 82, 82	3	5	4	7	7	3
UWBC, 1+, W8, n=63, 85, 84, 82, 82, 82	7	7	6	7	5	7
UWBC, 2+, W8, n=63, 85, 84, 82, 82, 82	1	7	3	5	7	3
UWBC, 3+, W8, n=63, 85, 84, 82, 82, 82	0	1	0	1	0	0
UWBC, Neg, WD, n=9, 4, 1, 2, 3, 7	9	4	0	1	3	7
UWBC, 2+, WD, n=9, 4, 1, 2, 3, 7	0	0	1	1	0	0

Notes
[103] - ITT Population. Only those participants available at the specified time points were analyzed.
[104] - ITT Population. Only those participants available at the specified time points were analyzed.
[105] - ITT Population. Only those participants available at the specified time points were analyzed.
[106] - ITT Population. Only those participants available at the specified time points were analyzed.
[107] - ITT Population. Only those participants available at the specified time points were analyzed.
[108] - ITT Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Secondary: Urine specific gravity at Baseline and Week 8/Early Withdrawal

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End point title

Urine specific gravity at Baseline and Week 8/Early Withdrawal

End point description

Urine samples were collected for the measurement of urine specific gravity by dipstick method at Baseline and at Week 8/Early Withdrawal. The Baseline value was the measurement taken at screening (Visit 1). Specific gravity is a measure of the amount of material dissolved in the urine. Specific gravity is the ratio of the density (mass of a unit volume) of a substance to the density (mass of the same unit volume) of a reference substance. Normal urine has a specific gravity between 1.010 and 1.020.

End point type

Secondary

End point timeframe

Baseline and Week 8/Early Withdrawal

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	102 ^[109]	104 ^[110]	96 ^[111]	99 ^[112]	94 ^[113]	97 ^[114]
Units: ratio
arithmetic mean (standard deviation)
BL, n=102, 101, 98, 99, 94, 97	1.0232 ± 0.00741	1.0227 ± 0.00687	1.0226 ± 0.00718	1.0224 ± 0.00719	1.0225 ± 0.00759	1.0245 ± 0.00679
W8, n=63, 85, 84, 82, 82, 82	1.0225 ± 0.00778	1.0227 ± 0.00714	1.0227 ± 0.00655	1.0223 ± 0.00766	1.021 ± 0.00884	1.0255 ± 0.00726
WD, n=9, 4, 1, 2, 3, 7	1.0206 ± 0.00532	1.0228 ± 0.00772	1.038 ± 0	1.0175 ± 0.01768	1.0273 ± 0.00306	1.0164 ± 0.00824

Notes
[109] - ITT Population. Only those participants available at the specified time points were analyzed.
[110] - ITT Population. Only those participants available at the specified time points were analyzed.
[111] - ITT Population. Only those participants available at the specified time points were analyzed.
[112] - ITT Population. Only those participants available at the specified time points were analyzed.
[113] - ITT Population. Only those participants available at the specified time points were analyzed.
[114] - ITT Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Secondary: Urine pH at Baseline and Week 8/Early Withdrawal

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End point title

Urine pH at Baseline and Week 8/Early Withdrawal

End point description

Urine samples were collected for the measurement of urine pH by dipstick method at Baseline and at Week 8/Early Withdrawal. The Baseline value was the measurement taken at screening (Visit 1). Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).

End point type

Secondary

End point timeframe

Baseline and Week 8/Early Withdrawal

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	102 ^[115]	104 ^[116]	96 ^[117]	99 ^[118]	94 ^[119]	97 ^[120]
Units: scores on a scale
arithmetic mean (standard deviation)
BL, n=102, 104, 96, 99, 94, 97	6.11 ± 0.507	5.98 ± 0.367	6.05 ± 0.455	5.97 ± 0.383	6.01 ± 0.37	6.04 ± 0.393
W8, n=62, 84, 82, 83, 82, 82	6 ± 0.458	6.13 ± 0.518	6.1 ± 0.451	5.99 ± 0.397	6 ± 0.437	6.01 ± 0.368
WD, n=9, 4, 1, 2, 3, 7	6.11 ± 0.601	6.13 ± 0.25	6 ± 0	6 ± 0	5.67 ± 0.289	5.93 ± 0.345

Notes
[115] - ITT Population. Only those participants available at the specified time points were analyzed.
[116] - ITT Population. Only those participants available at the specified time points were analyzed.
[117] - ITT Population. Only those participants available at the specified time points were analyzed.
[118] - ITT Population. Only those participants available at the specified time points were analyzed.
[119] - ITT Population. Only those participants available at the specified time points were analyzed.
[120] - ITT Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Secondary: 24-hour urinary cortisol excretion at Baseline and Week 8

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End point title

24-hour urinary cortisol excretion at Baseline and Week 8

End point description

A 24-hour urine sample was collected for the measurement of 24-hour urinary cortisol excretion at the following scheduled time points: within 7 days prior to Study Visit 3 (Baseline; Week 0) and Study Visit 8 (Week 8). The Baseline value for 24-hour urinary cortisol was taken from Visit 3. Urine Cortisol (UC) Population: all participants whose urine samples did not have confounding factors that could affect the interpretation of results.

End point type

Secondary

End point timeframe

Baseline and Week 8

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	56 ^[121]	69 ^[122]	75 ^[123]	75 ^[124]	72 ^[125]	70 ^[126]
Units: Nanomole per 24 hours (nmol/24hr)
median (full range (min-max))
Baseline	68.45 (12.9 to 261.2)	56.8 (6.8 to 385.4)	65.9 (9.6 to 463.5)	64.5 (20.1 to 311)	73.4 (12.5 to 221.7)	75.69 (17.9 to 384.8)
Week 8	64.7 (7.6 to 200)	60.8 (13.9 to 262.1)	53 (9.2 to 371.5)	56 (5.4 to 340)	62 (7.7 to 294.3)	58.39 (8 to 338.5)

Notes
[121] - UC Population
[122] - UC Population
[123] - UC Population
[124] - UC Population
[125] - UC Population
[126] - UC Population

No statistical analyses for this end point

Secondary: Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Week 8

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End point title

Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Week 8

End point description

Change from Baseline was calculated as the Week 8 value minus the Baseline value.

End point type

Secondary

End point timeframe

Baseline and Week 8

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	107 ^[127]	105 ^[128]	101 ^[129]	103 ^[130]	99 ^[131]	100 ^[132]
Units: Millimeters of mercury (mmHg)
arithmetic mean (standard deviation)
SBP	0.8 ± 9.83	0.3 ± 12.93	-0.2 ± 12.06	0.9 ± 11.51	0.9 ± 10.55	1.1 ± 11.49
DBP	2.1 ± 6.96	0.6 ± 9.19	-0.3 ± 9.18	0 ± 9.37	-0.2 ± 8.05	1 ± 7.9

Notes
[127] - ITT Population. Only those participants available at the specified time points were analyzed.
[128] - ITT Population. Only those participants available at the specified time points were analyzed.
[129] - ITT Population. Only those participants available at the specified time points were analyzed.
[130] - ITT Population. Only those participants available at the specified time points were analyzed.
[131] - ITT Population. Only those participants available at the specified time points were analyzed.
[132] - ITT Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Secondary: Change from Baseline in heart rate at Week 8

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End point title

Change from Baseline in heart rate at Week 8

End point description

Change from Baseline was calculated as the Week 8 value minus the Baseline value.

End point type

Secondary

End point timeframe

Baseline and Week 8

End point values	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Number of subjects analysed	107 ^[133]	105 ^[134]	101 ^[135]	103 ^[136]	99 ^[137]	100 ^[138]
Units: Beats per minute
arithmetic mean (standard deviation)	0.8 ± 10.12	0.5 ± 7.65	-0.4 ± 8.9	1.5 ± 10.92	0.5 ± 8.55	-1.7 ± 9.68

Notes
[133] - ITT Population. Only those participants available at the specified time points were analyzed.
[134] - ITT Population. Only those participants available at the specified time points were analyzed.
[135] - ITT Population. Only those participants available at the specified time points were analyzed.
[136] - ITT Population. Only those participants available at the specified time points were analyzed.
[137] - ITT Population. Only those participants available at the specified time points were analyzed.
[138] - ITT Population. Only those participants available at the specified time points were analyzed.

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the the treatment period (up to Week 8).

Adverse event reporting additional description

SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Placebo

Reporting group description

Reporting group title

GW685698X 100 µg OD

Reporting group description

Reporting group title

GW685698X 200 µg OD

Reporting group description

Reporting group title

GW685698X 300 µg OD

Reporting group description

Reporting group title

GW685698X 400 µg OD

Reporting group description

Reporting group title

FP 250 µg BID

Reporting group description

Serious adverse events	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 107 (0.00%)	0 / 105 (0.00%)	0 / 101 (0.00%)	1 / 103 (0.97%)	1 / 99 (1.01%)	0 / 100 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events
Cardiac disorders
Myocardial infarction
subjects affected / exposed	0 / 107 (0.00%)	0 / 105 (0.00%)	0 / 101 (0.00%)	1 / 103 (0.97%)	0 / 99 (0.00%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 107 (0.00%)	0 / 105 (0.00%)	0 / 101 (0.00%)	0 / 103 (0.00%)	1 / 99 (1.01%)	0 / 100 (0.00%)
occurrences causally related to treatment / all	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

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

Non-serious adverse events	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Total subjects affected by non serious adverse events
subjects affected / exposed	17 / 107 (15.89%)	29 / 105 (27.62%)	18 / 101 (17.82%)	22 / 103 (21.36%)	20 / 99 (20.20%)	32 / 100 (32.00%)
Nervous system disorders
Headache
subjects affected / exposed	6 / 107 (5.61%)	9 / 105 (8.57%)	8 / 101 (7.92%)	8 / 103 (7.77%)	9 / 99 (9.09%)	8 / 100 (8.00%)
occurrences all number	11	14	8	9	13	10
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 107 (0.00%)	4 / 105 (3.81%)	1 / 101 (0.99%)	1 / 103 (0.97%)	1 / 99 (1.01%)	1 / 100 (1.00%)
occurrences all number	0	5	1	1	1	1
Abdominal pain upper
subjects affected / exposed	0 / 107 (0.00%)	2 / 105 (1.90%)	1 / 101 (0.99%)	1 / 103 (0.97%)	3 / 99 (3.03%)	0 / 100 (0.00%)
occurrences all number	0	2	1	1	7	0
Toothache
subjects affected / exposed	0 / 107 (0.00%)	1 / 105 (0.95%)	1 / 101 (0.99%)	0 / 103 (0.00%)	0 / 99 (0.00%)	3 / 100 (3.00%)
occurrences all number	0	1	1	0	0	4
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 107 (0.93%)	2 / 105 (1.90%)	0 / 101 (0.00%)	2 / 103 (1.94%)	4 / 99 (4.04%)	2 / 100 (2.00%)
occurrences all number	1	2	0	2	5	2
Dysphonia
subjects affected / exposed	1 / 107 (0.93%)	1 / 105 (0.95%)	0 / 101 (0.00%)	2 / 103 (1.94%)	2 / 99 (2.02%)	4 / 100 (4.00%)
occurrences all number	1	1	0	2	2	4
Oropharyngeal pain
subjects affected / exposed	0 / 107 (0.00%)	2 / 105 (1.90%)	1 / 101 (0.99%)	1 / 103 (0.97%)	3 / 99 (3.03%)	3 / 100 (3.00%)
occurrences all number	0	2	1	1	5	3
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	0 / 107 (0.00%)	1 / 105 (0.95%)	1 / 101 (0.99%)	3 / 103 (2.91%)	3 / 99 (3.03%)	2 / 100 (2.00%)
occurrences all number	0	2	1	3	7	2
Infections and infestations
Nasopharyngitis
subjects affected / exposed	8 / 107 (7.48%)	9 / 105 (8.57%)	5 / 101 (4.95%)	7 / 103 (6.80%)	4 / 99 (4.04%)	7 / 100 (7.00%)
occurrences all number	9	9	5	7	4	7
Upper respiratory tract infection
subjects affected / exposed	3 / 107 (2.80%)	2 / 105 (1.90%)	3 / 101 (2.97%)	1 / 103 (0.97%)	0 / 99 (0.00%)	6 / 100 (6.00%)
occurrences all number	3	2	4	1	0	6
Oral candidiasis
subjects affected / exposed	0 / 107 (0.00%)	3 / 105 (2.86%)	1 / 101 (0.99%)	3 / 103 (2.91%)	3 / 99 (3.03%)	3 / 100 (3.00%)
occurrences all number	0	4	1	3	3	4
Sinusitis
subjects affected / exposed	1 / 107 (0.93%)	2 / 105 (1.90%)	0 / 101 (0.00%)	0 / 103 (0.00%)	1 / 99 (1.01%)	3 / 100 (3.00%)
occurrences all number	1	3	0	0	1	3

More information

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Were there any global substantial amendments to the protocol? Yes

24 Oct 2007

• Amend once daily GW685698X administration from morning to evening and to amend timing of measures that were impacted by this change • Amend inclusion criterion % predicted normal FEV1 range to account for evening measures

12 Dec 2007

• Amend anti-asthma therapy inclusion criteria. Subjects must have been using an inhaled corticosteroid for at least 8 weeks prior to Visit 1 and maintained on a stable dose of inhaled corticosteroids for four weeks prior to Visit 1 at specified doses

21 Mar 2008

• Adjust the FEV1 entry criteria depending on the time of day the screening period was conducted. A best FEV1 of 40%-85% of the predicted normal value during the Visit 1 screening period if the Visit occurred between 5:00 AM and 12:00 Noon or a best FEV1 of 40%-90% of the predicted normal value during the Visit 1 screening period if the Visit occurred between 5:00 PM and 11:00 PM. • Allow subjects to re-screen for Visit 1 if they failed to meet lung function criteria. • Clarify the exclusion of subjects with upper and lower respiratory tract infections at Visit 1 and Visit 3. Subjects were to be excluded if they had culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that was not resolved within 4 weeks of Visit 1 and that led to a change in asthma management, or in the opinion of the Investigator was expected to affect the subjects asthma status or the subject’s ability to participate in the study. • Allow the use of long acting anti-histamines.

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 in trough (evening pre-dose and pre- rescue bronchodilator) FEV1 at Week 8

Primary: Mean change from Baseline in trough (evening pre-dose and pre- rescue bronchodilator) FEV1 at Week 8

Secondary: Mean change from Baseline in daily trough (pre-dose and pre-rescue bronchodilator) evening peak expiratory flow (PEF) averaged over the 8-week Treatment Period

Secondary: Mean change from Baseline in daily trough (pre-dose and pre-rescue bronchodilator) evening peak expiratory flow (PEF) averaged over the 8-week Treatment Period

Secondary: Mean change from Baseline in daily morning PEF averaged over the 8-week Treatment Period

Secondary: Mean change from Baseline in daily morning PEF averaged over the 8-week Treatment Period

Secondary: Mean change from Baseline in the percentage of symptom-free 24-hour (hr) periods during the 8-week Treatment Period

Secondary: Mean change from Baseline in the percentage of symptom-free 24-hour (hr) periods during the 8-week Treatment Period

Secondary: Mean change from Baseline in the percentage of rescue free 24-hour (hr) periods during the 8-week Treatment Period

Secondary: Mean change from Baseline in the percentage of rescue free 24-hour (hr) periods during 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

Secondary: Number of participants with any on-treatment adverse events or serious adverse events throughout the 8-week Treatment Period

Secondary: Number of participants with any on-treatment adverse events or serious adverse events throughout the 8-week Treatment Period

Secondary: Number of participants with clinical/visual evidence of oropharyngeal candidiasis

Secondary: Number of participants with clinical/visual evidence of oropharyngeal candidiasis

Secondary: Percentage of basophils, eosinophils, lymphocytes, monocytes, and total neutrophils in the blood at Baseline and Week 8

Secondary: Percentage of basophils, eosinophils, lymphocytes, monocytes, and total neutrophils in the blood at Baseline and Week 8

Secondary: Hematocrit at Baseline and Week 8

Secondary: Hematocrit at Baseline and Week 8

Secondary: Hemoglobin at Baseline and Week 8

Secondary: Hemoglobin at Baseline and Week 8

Secondary: Platelet count and white blood cell (WBC) count at Baseline and Week 8

Secondary: Platelet count and white blood cell (WBC) count at Baseline and Week 8

Secondary: Red blood cells (RBC) count at Baseline and Week 8

Secondary: Red blood cells (RBC) count at Baseline and Week 8

Secondary: Clinical chemistry parameters of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LD), and gamma glutamyltransferase (GGT) at Baseline and Week 8

Secondary: Clinical chemistry parameters of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LD), and gamma glutamyltransferase (GGT) at Baseline and Week 8

Secondary: Clinical chemistry parameters of albumin and total protein at Baseline and Week 8

Secondary: Clinical chemistry parameters of albumin and total protein at Baseline and Week 8

Secondary: Clinical chemistry parameters of chloride, calcium, carbon dioxide content/bicarbonate (CO2/BI), cholesterol, glucose, phosphorus inorganic(PI), potassium, sodium, and urea/blood urea nitrogen (BUN) at Baseline and Week 8

Secondary: Clinical chemistry parameters of chloride, calcium, carbon dioxide content/bicarbonate (CO2/BI), cholesterol, glucose, phosphorus inorganic(PI), potassium, sodium, and urea/blood urea nitrogen (BUN) at Baseline and Week 8

Secondary: Clinical chemistry parameters of direct bilirubin (DBIL), total bilirubin (TBIL), uric acid and creatinine at Baseline and Week 8

Secondary: Clinical chemistry parameters of direct bilirubin (DBIL), total bilirubin (TBIL), uric acid and creatinine at Baseline and Week 8

Secondary: Number of participants with the indicated result for the indicated urinalysis parameters tested by dipstick at Baseline and Week 8/Early Withdrawal

Secondary: Number of participants with the indicated result for the indicated urinalysis parameters tested by dipstick at Baseline and Week 8/Early Withdrawal

Secondary: Urine specific gravity at Baseline and Week 8/Early Withdrawal

Secondary: Urine specific gravity at Baseline and Week 8/Early Withdrawal

Secondary: Urine pH at Baseline and Week 8/Early Withdrawal

Secondary: Urine pH at Baseline and Week 8/Early Withdrawal

Secondary: 24-hour urinary cortisol excretion at Baseline and Week 8

Secondary: 24-hour urinary cortisol excretion at Baseline and Week 8

Secondary: Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Week 8

Secondary: Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Week 8

Secondary: Change from Baseline in heart rate at Week 8

Secondary: Change from Baseline in heart rate at Week 8

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information