Safety and Efficacy of GW685698X an Inhaled Corticosteroid Once Daily and Twice Daily for the Treatment of Asthma

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00766090
• Collaborator: (none)
• Enrollment: 190
• Locations: 16
• Arm: 1
• Duration (Months): 5
• Patients Per Site: 11.9
• Patients Per Site Per Month: 2.4

Study Details

Study Description

Brief Summary

The purpose of this study is to compare once and twice daily GW685698 in asthma

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: GW685698X	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 190 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multi-Centre, Randomized, Double Blind Cross-over Study to Assess the Non-inferiority of GW685698X 200mcg Once Daily and 100mcg Twice Daily in Adult and Adolescent Patients With Asthma
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GW685698X	Drug: GW685698X; Inhaled Corticosteroid

Outcome Measures

Primary Outcome Measures

1. Trough Forced Expiratory Volume in One Second (FEV1) at Day 28 of the Relevant Treatment Period [Day 28 of the relevant treatment period (up to Study Day 112)]

   Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured electronically by spirometry. Trough FEV1 was the evening pre-dose, pre-rescue bronchodilator FEV1 measurement taken on Day 28 of the relevant treatment period. The analysis was performed using mixed model analysis of covarience (ANCOVA) with fixed effects of treatment, period, sex, and age. Participants were fitted as a random effect, and the period Baseline measurement was included as part of a bivariate response.

Secondary Outcome Measures

1. Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) Throughout the Three 28-day Treatment Periods [From the first dose of the study medication up to Week 16/Early Withdrawal]

   An 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. An 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 was exercised in deciding whether reporting was appropriate in other situations. Refer to the general AE/SAE module for a list of AEs (occuring at a frequency threshold >=3%) and SAEs.

2. 24-hour Urinary Cortisol Excretion at Day 28 of the Relevant Treatment Period [Day 28 of the relevant treatment period (up to Study Day 112)]

   A 24-hour urine sample was collected, and the 24-hour urinary cortisol excretion was analyzed at Day 28 of the relevant treatment period.

3. Number of Participants With Evidence of Oropharyngeal Candidiasis at Day 0 and Day 28 of the Relevant Treatment Period [Day 0 and Day 28 of the relevant treatment period (up to Study Day 112)]

   Detailed oropharyngeal examination for visual evidence of oropharyngeal candidiasis was performed at Day 0 (clinic visits 2, 4, and 6) and Day 28 (clinic visits 3, 5, and 7) of the relevant treatment period.

4. Systolic and Diastolic Blood Pressure at Day 0 and Day 28 of the Relevant Treatment Period [Day 0 and Day 28 of the relevant treatment period (up to Study Day 112)]

   Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at Day 0 (clinic visits 2, 4, and 6) and Day 28 (clinic visits 3, 5, and 7) of the relevant treatment period.

5. Heart Rate at Day 0 and Day 28 of the Relevant Treatment Period [Day 0 and Day 28 of the relevant treatment period (up to Study Day 112)]

   Heart rate was measured at Day 0 (clinic visits 2, 4, and 6) and Day 28 (clinic visits 3, 5, and 7) of the relevant treatment period.

6. Number of Participants Who Withdrew Due to Worsening of Asthma During the Three Treatment Periods [From the first dose of the study medication up to Week 16/Early Withdrawal]

   Participants were withdrawn from the study due to worsening of asthma (lack of efficacy) if they experienced a clinical asthma exacerbation or if clinic FEV1 fell below the FEV1 stability limit, or if during the 7 days immediately preceeding a visit the participant experienced either four or more days in which the PEF had fallen below the PEF stability limit or three or more days in which >=12 inhalations/day of albuterol/salbutamol were used. A clinical asthma exacerbation is defined as the worsening of asthma requiring emergency room visits, hospitalization, or treatment with an asthma medication (inhaled or systemic corticosteroids) other than study medication or rescue salbutamol/albuterol.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Clinical diagnosis of Asthma

• Reversibility ≥ 12% and ≥200mls reversibility of FEV1 within approximately 30-minutes following 2 to 4 puffs of albuterol

• FEV1 between 40-85% predicted

• Currently on short acting beta2 agonist therapy

Key Exclusion Criteria:

• History of life threatening asthma

• Respiratory Infection or oropharyngeal candidiasis

• Asthma exacerbation

• Uncontrolled disease or clinical abnormality

• Allergies

• Taking another Investigational medications or other prohibited medications

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Long Beach	California	United States	90806
2	GSK Investigational Site	Long Beach	California	United States	90808
3	GSK Investigational Site	Torrance	California	United States	90505
4	GSK Investigational Site	Cocoa	Florida	United States	32927
5	GSK Investigational Site	Tallahassee	Florida	United States	32308
6	GSK Investigational Site	Bethesda	Maryland	United States	20814
7	GSK Investigational Site	Columbia	Missouri	United States	65203
8	GSK Investigational Site	Rolla	Missouri	United States	65401
9	GSK Investigational Site	Raleigh	North Carolina	United States	27607
10	GSK Investigational Site	Canton	Ohio	United States	44718
11	GSK Investigational Site	Medford	Oregon	United States	97504
12	GSK Investigational Site	Orangeburg	South Carolina	United States	29118
13	GSK Investigational Site	Austin	Texas	United States	78750
14	GSK Investigational Site	Boerne	Texas	United States	78006
15	GSK Investigational Site	San Antonio	Texas	United States	78229
16	GSK Investigational Site	Waco	Texas	United States	76712

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• Woodcock A, Bleecker ER, Busse WW, Lötvall J, Snowise NG, Frith L, Jacques L, Haumann B, Bateman ED. Fluticasone furoate: once-daily evening treatment versus twice-daily treatment in moderate asthma. Respir Res. 2011 Dec 21;12:160. doi: 10.1186/1465-9921-12-160.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00766090
• Other Study ID Numbers: 112202
• First Posted: Oct 3, 2008
• Last Update Posted: Dec 8, 2016
• Last Verified: Oct 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Asthma

Study Results

Participant Flow

Pre-assignment Detail	Eligible participants (par.) at screening entered a 14-day Run-in Period. Par. were then randomized to 1 of 12 sequences: 6 had placebo and two doses of fluticasone furoate (FF), and 6 had placebo and two doses of fluticasone proprionate (FP) (allocation ratio of 7:2 [FF:FP]). 320 par. were screened and 190 were randomized.

Arm/Group Title	Sequence 1: Placebo, FF 200 µg, FF 100 µg	Sequence 2: Placebo, FF 100 µg, FF 200 µg	Sequence 3: FF 100 µg, Placebo, FF 200 µg	Sequence 4: FF 100 µg, FF 200 µg, Placebo	Sequence 5: FF 200 µg, Placebo, FF 100 µg	Sequence 6: FF 200 µg, FF 100 µg, Placebo	Sequence 7: Placebo, FP 200 µg, FP 100 µg	Sequence 8: Placebo, FP 100 µg, FP 200 µg	Sequence 9: FP 100 µg, Placebo, FP 200 µg	Sequence 10: FP 100 µg, FP 200 µg, Placebo	Sequence 11: FP 200 µg, Placebo, FP 100 µg	Sequence 12: FP 200 µg, FP 100 µg, Placebo
Arm/Group Description	Participants received placebo twice daily (BID), fluticasone furoate (FF) 200 microgram (µg) inhalation powder once daily (OD) in the evening, and FF 100 µg inhalation powder twice daily (BID) in Treatment Periods 1, 2, and 3, respectively. All treatments were administered via a Dry Powder Inhaler (DPI) for 28 days. Each of the 3 treatment periods was separated by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received placebo BID, FF 100 µg inhalation powder BID, and FF 200 µg inhalation powder OD in the evening in Treatment Periods 1, 2, and 3, respectively. All treatments were administered via a Dry Powder Inhaler (DPI) for 28 days. Each of the 3 treatment periods was separated by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FF 100 µg inhalation powder BID, placebo BID, and FF 200 µg inhalation powder OD in the evening in Treatment Periods 1, 2, and 3, respectively. All treatments were administered via a Dry Powder Inhaler (DPI) for 28 days. Each of the 3 treatment periods was separated by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FF 100 µg inhalation powder BID, FF 200 µg inhalation powder OD in the evening, and placebo BID in Treatment Periods 1, 2, and 3, respectively. All treatments were administered via a Dry Powder Inhaler (DPI) for 28 days. Each of the 3 treatment periods was separated by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FF 200 µg inhalation powder OD in the evening, placebo BID, and FF 100 µg inhalation powder BID in Treatment Periods 1, 2, and 3, respectively. All treatments were administered via a Dry Powder Inhaler (DPI) for 28 days. Each of the 3 treatment periods was separated by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FF 200 µg inhalation powder OD in the evening, FF 100 µg inhalation powder BID, and placebo BID in Treatment Periods 1, 2, and 3, respectively. All treatments were administered via a Dry Powder Inhaler (DPI) for 28 days. Each of the 3 treatment periods was separated by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received placebo twice daily (BID), fluticasone propionate (FP) 200 microgram (µg) inhalation powder once daily (OD) in the evening, and FP 100 µg inhalation powder twice daily (BID) in Treatment Periods 1, 2, and 3, respectively. All treatments were administered via a DISKUS inhaler for 28 days. Each of the 3 treatment periods was separated by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received placebo BID, FP 100 µg inhalation powder BID, and FP 200 µg inhalation powder OD in the evening in Treatment Periods 1, 2, and 3, respectively. All treatments were administered via a DISKUS inhaler for 28 days. Each of the 3 treatment periods was separated by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FP 100 µg inhalation powder BID, placebo BID, and FP 200 µg inhalation powder OD in the evening in Treatment Periods 1, 2, and 3, respectively. All treatments were administered via a DISKUS inhaler for 28 days. Each of the 3 treatment periods was separated by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FP 100 µg inhalation powder BID, FP 200 µg inhalation powder OD in the evening, and placebo BID in Treatment Periods 1, 2, and 3, respectively. All treatments were administered via a DISKUS inhaler for 28 days. Each of the 3 treatment periods was separated by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FP 200 µg inhalation powder OD in the evening, placebo BID, and FP 100 µg inhalation powder BID in Treatment Periods 1, 2, and 3, respectively. All treatments were administered via a DISKUS inhaler for 28 days. Each of the 3 treatment periods was separated by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FP 200 µg inhalation powder OD in the evening, FP 100 µg inhalation powder BID, and placebo BID in Treatment Periods 1, 2, and 3, respectively. All treatments were administered via a DISKUS inhaler for 28 days. Each of the 3 treatment periods was separated by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.
Period Title: Treatment Period 1 (28 Days)
STARTED	25	27	23	26	23	23	6	8	7	8	7	7
COMPLETED	22	27	23	25	23	23	6	8	6	8	7	7
NOT COMPLETED	3	0	0	1	0	0	0	0	1	0	0	0
Period Title: Treatment Period 1 (28 Days)
STARTED	22	27	23	25	23	23	6	8	6	8	7	7
COMPLETED	22	27	22	25	23	23	6	8	6	8	7	7
NOT COMPLETED	0	0	1	0	0	0	0	0	0	0	0	0
Period Title: Treatment Period 1 (28 Days)
STARTED	22	27	22	25	23	23	6	8	6	8	7	7
COMPLETED	22	27	21	25	21	23	6	8	6	8	7	7
NOT COMPLETED	0	0	1	0	2	0	0	0	0	0	0	0
Period Title: Treatment Period 1 (28 Days)
STARTED	22	27	21	25	21	23	6	8	6	8	7	7
COMPLETED	22	27	20	25	21	23	6	8	6	8	7	7
NOT COMPLETED	0	0	1	0	0	0	0	0	0	0	0	0
Period Title: Treatment Period 1 (28 Days)
STARTED	22	27	20	25	21	23	6	8	6	8	7	7
COMPLETED	22	26	20	24	20	22	6	8	6	8	7	6
NOT COMPLETED	0	1	0	1	1	1	0	0	0	0	0	1

Baseline Characteristics

Arm/Group Title	FF 200 µg, FF 100 µg, and Placebo Via DPI	FP 200 µg, FP 100 µg, and Placebo Via DISKUS	Total
Arm/Group Description	Participants received FF 200 µg inhalation powder OD in the evening, FF 100 µg inhalation powder BID, and placebo BID in one of the three treatment periods. All treatments were administered via a Dry Powder Inhaler (DPI) for 28 days. Each of the 3 treatment periods was separated by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FP 200 µg inhalation powder OD in the evening, FP 100 µg inhalation powder BID, and placebo BID in one of the three treatment periods. All treatments were administered via a DISKUS for 28 days. Each of the 3 treatment periods was separated by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Total of all reporting groups
Overall Participants	147	43	190
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	31.4 (15.30)	35.2 (16.03)	32.3 (15.51)
Gender (Count of Participants)
Female	87 59.2%	21 48.8%	108 56.8%
Male	60 40.8%	22 51.2%	82 43.2%
Race/Ethnicity, Customized (participants) [Number]
African American/African Heritage (HER)	50 34%	20 46.5%	70 36.8%
American Indian (AI) or Alaska Native (AN)	1 0.7%	0 0%	1 0.5%
Japanese/East Asian HER/South East Asian HER	2 1.4%	1 2.3%	3 1.6%
Native Hawaiian or other Pacific Islander	1 0.7%	0 0%	1 0.5%
White	90 61.2%	22 51.2%	112 58.9%
African American/African HER & AI or AN & White	1 0.7%	0 0%	1 0.5%
African American/African Heritage & White	2 1.4%	0 0%	2 1.1%

Outcome Measures

1. Primary Outcome

Title	Trough Forced Expiratory Volume in One Second (FEV1) at Day 28 of the Relevant Treatment Period
Description	Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. FEV1 was measured electronically by spirometry. Trough FEV1 was the evening pre-dose, pre-rescue bronchodilator FEV1 measurement taken on Day 28 of the relevant treatment period. The analysis was performed using mixed model analysis of covarience (ANCOVA) with fixed effects of treatment, period, sex, and age. Participants were fitted as a random effect, and the period Baseline measurement was included as part of a bivariate response.
Time Frame	Day 28 of the relevant treatment period (up to Study Day 112)

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all participants randomized to treatment who received at least one dose of study medication

Arm/Group Title	Placebo	FF 200 µg OD	FF 100 µg BID	FP 200 µg OD	FP 100 µg BID
Arm/Group Description	Participants received placebo BID via the Dry Powder Inhaler (DPI) or the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FF 200 µg inhalation powder OD in the evening from the DPI for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FF 100 µg inhalation powder BID from the DPI for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FP 200 µg inhalation powder OD PM from the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FP 100 µg inhalation powder BID from the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.
Measure Participants	187	140	142	42	43
Least Squares Mean (Standard Error) [Liters]	2.605 (0.0434)	2.714 (0.0444)	2.703 (0.0443)	2.693 (0.0535)	2.737 (0.0533)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, FF 200 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.108
	Confidence Interval	(2-Sided) 95%; 0.064 to 0.153
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, FF 100 µg BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.098
	Confidence Interval	(2-Sided) 95%; 0.054 to 0.142
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, FP 200 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.020
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.087
	Confidence Interval	(2-Sided) 95%; 0.014 to 0.161
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	FF 200 µg OD, FF 100 µg BID
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was demonstrated if the lower limit of the confidence interval (0.025, 1-sided significance level) for the mean difference in trough FEV1 of FF 200 µg OD versus FF 100 µg BID was greater than -110 milliliters.
Statistical Test of Hypothesis	p-Value	0.641
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.011
	Confidence Interval	(2-Sided) 95%; -0.035 to 0.056
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, FP 100 µg BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.132
	Confidence Interval	(2-Sided) 95%; 0.059 to 0.205
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) Throughout the Three 28-day Treatment Periods
Description	An 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. An 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 was exercised in deciding whether reporting was appropriate in other situations. Refer to the general AE/SAE module for a list of AEs (occuring at a frequency threshold >=3%) and SAEs.
Time Frame	From the first dose of the study medication up to Week 16/Early Withdrawal

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	FF 200 µg OD	FF 100 µg BID	FP 200 µg OD	FP 100 µg BID
Arm/Group Description	Participants received placebo BID via the Dry Powder Inhaler (DPI) or the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FF 200 µg inhalation powder OD in the evening from the DPI for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FF 100 µg inhalation powder BID from the DPI for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FP 200 µg inhalation powder OD PM from the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FP 100 µg inhalation powder BID from the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.
Measure Participants	187	140	142	42	43
Any AE	26 17.7%	22 51.2%	26 13.7%	2 NaN	3 NaN
Any SAE	0 0%	0 0%	0 0%	0 NaN	0 NaN

3. Secondary Outcome

Title	24-hour Urinary Cortisol Excretion at Day 28 of the Relevant Treatment Period
Description	A 24-hour urine sample was collected, and the 24-hour urinary cortisol excretion was analyzed at Day 28 of the relevant treatment period.
Time Frame	Day 28 of the relevant treatment period (up to Study Day 112)

Outcome Measure Data

Analysis Population Description

Urine Cortisol (UC) Population: participants who had both a Baseline urine sample and at least one urine sample from the end of a treatment period that did not have confounding factors that could affect the interpretation of results

Arm/Group Title	Placebo	FF 200 µg OD	FF 100 µg BID	FP 200 µg OD	FP 100 µg BID
Arm/Group Description	Participants received placebo BID via the Dry Powder Inhaler (DPI) or the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FF 200 µg inhalation powder OD in the evening from the DPI for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FF 100 µg inhalation powder BID from the DPI for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FP 200 µg inhalation powder OD PM from the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FP 100 µg inhalation powder BID from the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.
Measure Participants	153	118	116	35	39
Geometric Mean (Geometric Coefficient of Variation) [Nanomoles per 24 hours]	53.94 (66.423)	40.25 (92.316)	45.13 (87.181)	56.16 (94.259)	47.56 (84.896)

4. Secondary Outcome

Title	Number of Participants With Evidence of Oropharyngeal Candidiasis at Day 0 and Day 28 of the Relevant Treatment Period
Description	Detailed oropharyngeal examination for visual evidence of oropharyngeal candidiasis was performed at Day 0 (clinic visits 2, 4, and 6) and Day 28 (clinic visits 3, 5, and 7) of the relevant treatment period.
Time Frame	Day 0 and Day 28 of the relevant treatment period (up to Study Day 112)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	FF 200 µg OD	FF 100 µg BID	FP 200 µg OD	FP 100 µg BID
Arm/Group Description	Participants received placebo BID via the Dry Powder Inhaler (DPI) or the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FF 200 µg inhalation powder OD in the evening from the DPI for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FF 100 µg inhalation powder BID from the DPI for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FP 200 µg inhalation powder OD PM from the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FP 100 µg inhalation powder BID from the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.
Measure Participants	187	140	142	42	43
Day 0: Yes, n=187, 140, 142, 42, 43	0 0%	0 0%	0 0%	0 NaN	0 NaN
Day 0: No, n=187, 140, 142, 42, 43	187 127.2%	140 325.6%	142 74.7%	42 NaN	43 NaN
Day 28: Yes, n=178, 139, 140, 42, 42	0 0%	0 0%	0 0%	0 NaN	0 NaN
Day 28: No, n=178, 139, 140, 42, 42	178 121.1%	139 323.3%	140 73.7%	42 NaN	42 NaN

5. Secondary Outcome

Title	Systolic and Diastolic Blood Pressure at Day 0 and Day 28 of the Relevant Treatment Period
Description	Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at Day 0 (clinic visits 2, 4, and 6) and Day 28 (clinic visits 3, 5, and 7) of the relevant treatment period.
Time Frame	Day 0 and Day 28 of the relevant treatment period (up to Study Day 112)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	FF 200 µg OD	FF 100 µg BID	FP 200 µg OD	FP 100 µg BID
Arm/Group Description	Participants received placebo BID via the Dry Powder Inhaler (DPI) or the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FF 200 µg inhalation powder OD in the evening from the DPI for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FF 100 µg inhalation powder BID from the DPI for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FP 200 µg inhalation powder OD PM from the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FP 100 µg inhalation powder BID from the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.
Measure Participants	187	140	142	42	43
SBP: Day 0, n=187, 140, 142, 42, 43	120.1 (12.08)	118.3 (11.96)	119.5 (12.28)	122.1 (13.55)	121.3 (12.10)
SBP: Day 28, n=178, 139, 140, 42, 42	119.6 (12.76)	120.5 (13.31)	120.6 (12.71)	120.4 (11.92)	120.1 (10.58)
DBP: Day 0, n=187, 140, 142, 42, 43	75.8 (8.26)	74.6 (7.69)	76.0 (8.03)	77.5 (9.98)	76.6 (8.73)
DBP: Day 28, n=178, 139, 140, 42, 42	75.8 (8.45)	74.9 (8.12)	76.4 (7.97)	76.0 (7.81)	75.7 (8.90)

6. Secondary Outcome

Title	Heart Rate at Day 0 and Day 28 of the Relevant Treatment Period
Description	Heart rate was measured at Day 0 (clinic visits 2, 4, and 6) and Day 28 (clinic visits 3, 5, and 7) of the relevant treatment period.
Time Frame	Day 0 and Day 28 of the relevant treatment period (up to Study Day 112)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	FF 200 µg OD	FF 100 µg BID	FP 200 µg OD	FP 100 µg BID
Arm/Group Description	Participants received placebo BID via the Dry Powder Inhaler (DPI) or the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FF 200 µg inhalation powder OD in the evening from the DPI for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FF 100 µg inhalation powder BID from the DPI for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FP 200 µg inhalation powder OD PM from the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FP 100 µg inhalation powder BID from the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.
Measure Participants	187	140	142	42	43
Day 0, n=187, 140, 142, 42, 43	77.0 (9.53)	76.4 (9.27)	77.6 (8.71)	74.5 (9.22)	75.8 (8.12)
Day 28, n=178, 139, 140, 42, 42	76.6 (8.79)	76.9 (9.32)	77.7 (9.47)	74.7 (7.96)	74.6 (8.49)

7. Secondary Outcome

Title	Number of Participants Who Withdrew Due to Worsening of Asthma During the Three Treatment Periods
Description	Participants were withdrawn from the study due to worsening of asthma (lack of efficacy) if they experienced a clinical asthma exacerbation or if clinic FEV1 fell below the FEV1 stability limit, or if during the 7 days immediately preceeding a visit the participant experienced either four or more days in which the PEF had fallen below the PEF stability limit or three or more days in which >=12 inhalations/day of albuterol/salbutamol were used. A clinical asthma exacerbation is defined as the worsening of asthma requiring emergency room visits, hospitalization, or treatment with an asthma medication (inhaled or systemic corticosteroids) other than study medication or rescue salbutamol/albuterol.
Time Frame	From the first dose of the study medication up to Week 16/Early Withdrawal

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	FF 200 µg, FF 100 µg, and Placebo Via DPI	FP 200 µg, FP 100 µg, and Placebo Via DISKUS
Arm/Group Description	Participants received FF 200 µg inhalation powder OD in the evening, FF 100 µg inhalation powder BID, and placebo BID in one of the three treatment periods. All treatments were administered via a Dry Powder Inhaler (DPI) for 28 days. Each of the 3 treatment periods was separated by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.	Participants received FP 200 µg inhalation powder OD in the evening, FP 100 µg inhalation powder BID, and placebo BID in one of the three treatment periods. All treatments were administered via a DISKUS for 28 days. Each of the 3 treatment periods was separated by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.
Measure Participants	147	43
Number [participants]	5 3.4%	1 2.3%

Adverse Events

Time Frame	Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of the study medication up to Week 16/Early Withdrawal.
Adverse Event Reporting 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 study medication.
Arm/Group Title	Placebo		FF 200 µg OD		FF 100 µg BID		FP 200 µg OD		FP 100 µg BID
Arm/Group Description	Participants received placebo BID via the Dry Powder Inhaler (DPI) or the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.		Participants received FF 200 µg inhalation powder OD in the evening from the DPI for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.		Participants received FF 100 µg inhalation powder BID from the DPI for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.		Participants received FP 200 µg inhalation powder OD PM from the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.		Participants received FP 100 µg inhalation powder BID from the DISKUS inhaler for 28 days during one of the 3 treatment periods. Each treatment period was followed by a washout period of 14 days. Participants were provided supplemental albuterol/salbutamol (inhalation aerosol) to be used as needed throughout the study.
All Cause Mortality
	Placebo		FF 200 µg OD		FF 100 µg BID		FP 200 µg OD		FP 100 µg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		FF 200 µg OD		FF 100 µg BID		FP 200 µg OD		FP 100 µg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/187 (0%)		0/140 (0%)		0/142 (0%)		0/42 (0%)		0/43 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		FF 200 µg OD		FF 100 µg BID		FP 200 µg OD		FP 100 µg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/187 (1.1%)		7/140 (5%)		7/142 (4.9%)		0/42 (0%)		0/43 (0%)
Infections and infestations
Upper respiratory tract infection	2/187 (1.1%)		7/140 (5%)		7/142 (4.9%)		0/42 (0%)		0/43 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.