A Randomized Study To Evaluate The Efficacy And Safety Of An Investigational Drug In Adolescent And Adult Subjects With Asthma Uncontrolled on Low-Dose ICS Therapy.

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00603278
• Collaborator: (none)
• Enrollment: 622
• Locations: 155
• Arms: 2
• Duration (Months): 11
• Patients Per Site: 4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study is designed to determine if the investigational drug is effective and safe in individuals with asthma.

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

Detailed Description

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 Twice Daily compared with Placebo for 8 Weeks in Adolescent and Adult Subjects with Persistent Asthma Symptomatic on Low-Dose ICS Therapy

Study Design

• Study Type: Interventional
• Actual Enrollment: 622 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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 ICS Therapy
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Arm 1	Drug: placebo; placebo
Experimental: Arm 2	Drug: GW685698X; GW685698X

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in Trough (Evening Pre-dose and Pre- Rescue Bronchodilator) FEV1 at Week 8 [Baseline and Week 8]

   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 Baseline value. Change from Baseline in trough FEV1 was calculated as the value at Week 8 minus the value at Baseline. The analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of Baseline trough FEV1, country, sex, age, and treatment group.

Secondary Outcome Measures

1. 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 [From Baseline up to Week 8]

   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.

2. Mean Change From Baseline in Daily Morning PEF Averaged Over the 8-week Treatment Period [From Baseline up to Week 8]

   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.

3. Mean Change From Baseline in the Percentage of Symptom-free 24-hour (hr) Periods During the 8-week Treatment Period [From Baseline up to Week 8]

   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.

4. Mean Change From Baseline in the Percentage of Rescue Free 24-hour (hr) Periods During the 8-week Treatment Period [From Baseline up to Week 8]

   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.

5. Number of Participants Who Withdrew Due to Lack of Efficacy During the 8-Week Treatment Period [From the first dose of study medication up to Week 8/Early Withdrawal]

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

6. Number of Participants With Any On-treatment Adverse Events or Serious Adverse Events Throughout the 8-week Treatment Period [From the first dose of study medication up to Week 8/Early Withdrawal]

   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.

7. Number of Participants With Clinical/Visual Evidence of Oropharyngeal Candidiasis [From Baseline up to Week 8/Early Withdrawal]

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

8. Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in the Blood at Baseline and Week 8 [Baseline and Week 8]

   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).

9. Hematocrit at Baseline and Week 8 [Baseline and Week 8]

   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).

10. Hemoglobin at Baseline and Week 8 [Baseline and Week 8]

    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).

11. Platelet Count and White Blood Cell (WBC) Count at Baseline and Week 8 [Baseline and Week 8]

    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).

12. Red Blood Cells (RBC) Count at Baseline and Week 8 [Baseline and Week 8]

    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).

13. 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 [Baseline and Week 8]

    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).

14. Clinical Chemistry Parameters of Albumin and Total Protein at Baseline and Week 8 [Baseline and Week 8]

    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).

15. 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 [Baseline and Week 8]

    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).

16. Clinical Chemistry Parameters of Direct Bilirubin (DBIL), Total Bilirubin (TBIL), Uric Acid and Creatinine at Baseline and Week 8 [Baseline and Week 8]

    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).

17. Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal [Baseline and Week 8/Early Withdrawal]

    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).

18. Urine Specific Gravity at Baseline and Week 8/Early Withdrawal [Urine specific gravity at Baseline and Week 8/Early Withdrawal]

    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.

19. Urine pH at Baseline and Week 8/Early Withdrawal [Baseline and Week 8/Early Withdrawal]

    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).

20. 24-hour Urinary Cortisol Excretion at Baseline and Week 8 [Baseline and Week 8]

    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.

21. Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 8 [Baseline and Week 8]

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

22. Change From Baseline in Heart Rate at Week 8 [Baseline and Week 8]

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

Eligibility Criteria

Criteria

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

INCLUSION CRITERIA:

Subjects eligible for enrolment in the study must meet all of the following criteria:

• Type of Subject: Outpatient

• Age: 12 years of age or older at Visit 1. For sites in the following countries, subjects recruited will be ≥18 years of age: Bulgaria, Czech Republic, Germany, Greece, Lithuania, New Zealand, Russian Federation, Turkey and any other countries where local regulations or the regulatory status of study medication permit enrolment of adults only.

• Gender: Male or Eligible Female

• To be eligible for entry into the study, females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control, as defined by the following:

• Male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject

• Implants of levonorgestrel

• Injectable progestogen

• Oral contraceptive (either combined estrogen/progestin or progestin only)

• Any intrauterine device (IUD) with a documented failure rate of less than 1% per year.

• Females of childbearing potential who are not sexually active must commit to complete abstinence from intercourse throughout the clinical trial and for a period after the trial to account for elimination of the drug (minimum of six days).

• Double barrier method - spermicide plus a mechanical barrier (e.g., spermicide plus a male condom or a spermicide and female diaphragm).

• NB: For German sites, female subjects must use a method of birth control other than the double barrier method.

• The contraceptive transdermal patch, Ortho Evra (if the subject is less than 198 pounds)

• Female subjects should not be enrolled if they are pregnant, lactating or plan to become pregnant during the time of study participation. A serum pregnancy test is required of all females. This test will be performed at the initial screening visit (Visit 1) and Visit 8. In addition, a urine pregnancy test will be performed on the evening of the double-blind treatment visit, prior to randomization (Visit 3) and at Visits 4 through 7.

• Asthma Diagnosis: Asthma as defined by the National Institutes of Health [National Institutes of Health, 2007].

• Severity of Disease: A best FEV1 of 40%-90% of the predicted normal value during Visit

1. NHANES III predicted values will be used for subjects aged ≥ 12 years and adjustments to predicted values will be made for African American subjects. [Hankinson, 1999].

• Reversibility of Disease: Demonstrated a ≥ 12% and ≥200mL reversibility of FEV1 within approximately 30-minutes following 4 inhalations of albuterol/salbutamol inhalation aerosol (if required, spacers are permitted for reversibility testing only) or one nebulized albuterol/salbutamol solution at the Screening Visit. If a subject fails to demonstrate an increase in FEV1 ≥12% and ≥200mL, then the subject is not eligible for the study and will not be allowed to re-screen.

• Current Anti-Asthma Therapy: Subjects must have been using a 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 one of the following doses: [fluticasone propionate MDI CFC/HFA >220mcg exactuator or ≤250mcg ex valve]; [fluticasone propionate DPI ≤200mcg]; [beclomethasone dipropionate DPI ≤ 420mcg exactuator or ≤ 500mcg ex-valve]; [beclomethasone dipropionate HFA (Qvar) ≤ 160mcg exactuator or ≤ 200mcg ex-valve]; [budesonide DPI MDI ≤400mcg]; [flunisolide ≤ 1000mcg]; [triamcinolone acetonide ≤1000mcg]; [mometasone furoate DPI >200mcg or ≤ 220mcg]; [ciclesonide MDI HFA ≤ 160mcg ex-actuator dose / ≤ 200mcg ex-valve dose].

• Short- Acting Beta2-Agonists: All subjects must be able to replace their current short-acting beta2-agonists with albuterol/salbutamol inhalation aerosol at Visit 1 for use as needed for the duration of the study. The use of spacer devices with metered dose inhaler (MDI) or nebulized albuterol/salbutamol will not be allowed during the study with the exception of their use during reversibility testing at Visit

1. Subjects must be able to withhold all inhaled short-acting beta sympathomimetic bronchodilators for at least 6 hours prior to all study visits.

• Informed Consent: All subjects must be able and willing to give written informed consent to take part in the study.

• Compliance: Subjects must be able to comply with completion of the Daily Diary (includes paper medical conditions diary).

• French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Inclusion Criteria for Randomization

At the end of the run-in period, a subject will be eligible to enter the treatment period of the study if he/she meets the following criteria at Visit 3:

1. Evening pre-dose percent predicted FEV1 of between 40% and 90% of their predicted normal.

2. Any combination of the daily asthma symptom scores (day-time plus night-time) of ≥1 or albuterol/salbutamol use on at least 4 of the last 7 consecutive days of the run-in period (immediately preceding Visit 3).

EXCLUSION CRITERIA:

• History of Life-threatening asthma: Defined for this protocol as an asthma episode that required intubation and/or was associated with hypercapnia, respiratory arrest or hypoxic seizures.

• Respiratory Infection: Culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear that is not resolved within 4 weeks of Visit 1 and led to a change in asthma management, or in the opinion of the Investigator is expected to affect the subjects asthma status or the subjects ability to participate in the study.

• Asthma Exacerbation: Any asthma exacerbation requiring oral corticosteroids within 3 months of Visit 1. A subject must not have had any hospitalization for asthma within 6 months prior to Visit 1.

• Concurrent Diseases/Abnormalities: Historical or current evidence of clinically significant uncontrolled disease including, but not limited to: cardiovascular disease, hepatic disease, renal disease, hematological disease, neurological disease, or pulmonary disease (including, but not confined to chronic bronchitis, emphysema, bronchiectasis with the need of treatment, cystic fibrosis, bronchopulmonary dysplasia, and chronic obstructive pulmonary disease). Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study. The list of additional excluded conditions/diseases includes, but is not limited to the following: congestive heart failure, clinically significant coronary artery disease, stroke within 3 months of Visit 1, poorly controlled peptic ulcer, immunologic compromise, tuberculosis (current or untreated), Addison's disease, uncontrolled thyroid disorder, known aortic aneurysm, clinically significant cardiac arrhythmia, uncontrolled hypertension, hematological, hepatic, or renal disease, current malignancy, cushings disease, uncontrolled diabetes mellitus, recent history of drug or alcohol abuse.

• Oropharyngeal Examination: A subject will not be eligible for the run-in if he/she has clinical visual evidence of oral candidiasis at Visit 1.

• Investigational Medications: A subject must not have participated in a study or used any investigational drug within 30 days prior to Visit 1.

• Drug Allergy: Any adverse reaction including immediate or delayed hypersensitivity to any beta2-agonist, sympathomimetic drug, or any intranasal, inhaled, or systemic corticosteroid therapy. Known or suspected sensitivity to the constituents of the novel dry powder inhaler or DISKUS/ACCUHALER (i.e., lactose or magnesium stearate).

• Milk Protein Allergy: History of severe milk protein allergy.

• Immunosuppressive Medications: A subject must not be using, or require use, of immunosuppressive medications during the study.

NOTE: Immunotherapy for the treatment of allergies is allowed during the study provided that the treatment was initiated prior to Visit 1 and the subject is maintained on a stable regimen throughout the study period.

• Attendance: A subject will not be eligible if he/she or his/her parent or legal guardian has any infirmity, disability, or geographical location which seems likely (in the opinion of the Investigator) to impair compliance with any aspect of this study protocol or scheduled visits to the study center and non-compliant with study medication or procedures (e.g. completion of daily diary). Neurological or psychiatric disease or history of drug or alcohol abuse which in the opinion of the investigator could interfere with the subject's proper completion of the protocol requirements excludes study participation.

• Tobacco Use : Current smoker or a smoking history of 10 pack years or more (e.g. 20 cigarettes/day for 10 years). A subject may not have used tobacco products within the past one year (i.e., cigarettes, cigars, or pipe tobacco).

• Affiliation with Investigator's Site: A subject will not be eligible for this study if he/she is an immediate family member of the participating Investigator, sub-Investigator, study coordinator, or employee of the participating Investigator.

• Corticosteroid Use: Administration of systemic, oral or depot corticosteroids within 12 weeks of Visit 1.

• Potent Cytochrome P450 3A4 (CYP3A4) inhibitors: Patients who are receiving potent CYP3A4 inhibitors within 4 weeks of Visit 1 (e.g., ritonavir, ketoconazole, itraconazole).

Exclusion Criteria for Randomization At the end of the run-in period, a subject will not be eligible to enter the treatment period of the study if they meet any of the following criteria.

1. Clinical Laboratory Abnormalities: Clinically significant abnormal laboratory tests during Visit 1 which are still abnormal upon repeat analysis and are not believed to be due to disease(s) present. Each Investigator will use his/her own discretion in determining the clinical significance of the abnormality. When in doubt, GlaxoSmithKline, or designee, should be notified so that a joint decision can be made.

2. Changes in asthma medication (excluding albuterol/salbutamol inhalation aerosol provided at Visit 1).

3. Occurrence of a culture-documented or suspected bacterial or viral infection of the upper or lower respiratory tract, sinus or middle ear during the run-in period that led to a change in asthma management, or in the opinion of the Investigator is expected to affect the subjects asthma status or the subjects ability to participate in the study.

4. Asthma exacerbation, defined as any worsening of asthma requiring any treatment other than rescue albuterol/salbutamol or regular inhaled corticosteroid use. This includes requiring the use of systemic corticosteroids and / or emergency room visit or hospitalization or a change in subject's regular inhaled corticosteroid dose.

5. A subject will not be eligible for randomization if he/she has an abnormal visual oropharyngeal exam at the randomization Visit 3 (visual clinical evidence of oral candidiasis).

6. Non-compliance with completion of the Daily Diary, defined as: -Completion of AM and PM symptom scores on less than 4 days out of the last 7 days immediately preceding Visit 3.

• Completion of AM and PM rescue use on less than 4 days out of the last 7 days immediately preceding Visit 3.

• Completion of AM and PM PEF measurements on less than 4 days out of the last 7 days immediately preceding Visit 3.

• Recording run-in asthma medication use on less than 4 days out of the last 7 days immediately preceding Visit 3.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Phoenix	Arizona	United States	85028
2	GSK Investigational Site	Fort Smith	Arkansas	United States	72903
3	GSK Investigational Site	Little Rock	Arkansas	United States	72211-3733
4	GSK Investigational Site	Fresno	California	United States	93720
5	GSK Investigational Site	Granada Hills	California	United States	91344
6	GSK Investigational Site	Huntington Beach	California	United States	92647
7	GSK Investigational Site	Long Beach	California	United States	90806
8	GSK Investigational Site	Long Beach	California	United States	90808
9	GSK Investigational Site	Los Angeles	California	United States	90048
10	GSK Investigational Site	Los Angeles	California	United States	90095-1752
11	GSK Investigational Site	Palmdale	California	United States	93551
12	GSK Investigational Site	Riverside	California	United States	92506
13	GSK Investigational Site	Roseville	California	United States	95678
14	GSK Investigational Site	San Diego	California	United States	92120
15	GSK Investigational Site	Torrance	California	United States	90505
16	GSK Investigational Site	Walnut Creek	California	United States	94598
17	GSK Investigational Site	West Covina	California	United States	91790
18	GSK Investigational Site	Colorado Springs	Colorado	United States	80910
19	GSK Investigational Site	Wheat Ridge	Colorado	United States	80033
20	GSK Investigational Site	Bridgeport	Connecticut	United States	06606
21	GSK Investigational Site	Waterbury	Connecticut	United States	06708
22	GSK Investigational Site	Boca Raton	Florida	United States	33487
23	GSK Investigational Site	Cocoa	Florida	United States	32927
24	GSK Investigational Site	Daytona Beach	Florida	United States	32114
25	GSK Investigational Site	Largo	Florida	United States	33770
26	GSK Investigational Site	Miami	Florida	United States	33126
27	GSK Investigational Site	Miami	Florida	United States	33157
28	GSK Investigational Site	Ocala	Florida	United States	34471
29	GSK Investigational Site	West Palm Beach	Florida	United States	33401
30	GSK Investigational Site	Winter Park	Florida	United States	32789
31	GSK Investigational Site	Gainesville	Georgia	United States	30501
32	GSK Investigational Site	Bloomingdale/Illinois	Illinois	United States	60108
33	GSK Investigational Site	Chicago	Illinois	United States	60617
34	GSK Investigational Site	DeKalb	Illinois	United States	60115
35	GSK Investigational Site	Gurnee	Illinois	United States	60031
36	GSK Investigational Site	Evansville	Indiana	United States	47713
37	GSK Investigational Site	Iowa City	Iowa	United States	52240
38	GSK Investigational Site	Lenexa	Kansas	United States	66215
39	GSK Investigational Site	Crescent Springs	Kentucky	United States	41017
40	GSK Investigational Site	Lexington	Kentucky	United States	40536
41	GSK Investigational Site	Metairie	Louisiana	United States	70002
42	GSK Investigational Site	Bangor	Maine	United States	04401
43	GSK Investigational Site	North Dartmouth	Massachusetts	United States	02747
44	GSK Investigational Site	Detroit	Michigan	United States	48221
45	GSK Investigational Site	Taylor	Michigan	United States	48180
46	GSK Investigational Site	Ypsilanti	Michigan	United States	48197
47	GSK Investigational Site	Rochester	Minnesota	United States	55905
48	GSK Investigational Site	Jackson	Mississippi	United States	39202
49	GSK Investigational Site	Rolla	Missouri	United States	65401
50	GSK Investigational Site	St. Louis	Missouri	United States	63141
51	GSK Investigational Site	St. Louis	Missouri	United States	63143
52	GSK Investigational Site	Warrensburg	Missouri	United States	64093
53	GSK Investigational Site	Billings	Montana	United States	59101
54	GSK Investigational Site	Butte	Montana	United States	59701
55	GSK Investigational Site	Missoula	Montana	United States	59808
56	GSK Investigational Site	Las Vegas	Nevada	United States	89107
57	GSK Investigational Site	Clifton/New Jersey	New Jersey	United States	7011
58	GSK Investigational Site	Hillsborough	New Jersey	United States	08844
59	GSK Investigational Site	Red Bank	New Jersey	United States	07701
60	GSK Investigational Site	Skillman	New Jersey	United States	08558
61	GSK Investigational Site	Bronx	New York	United States	10461
62	GSK Investigational Site	East Syracuse	New York	United States	13057
63	GSK Investigational Site	Ithaca	New York	United States	14850
64	GSK Investigational Site	Rockville Center	New York	United States	11570
65	GSK Investigational Site	Greensboro	North Carolina	United States	27401
66	GSK Investigational Site	Greenville	North Carolina	United States	27834
67	GSK Investigational Site	Raleigh	North Carolina	United States	27607
68	GSK Investigational Site	Canton	Ohio	United States	44718
69	GSK Investigational Site	Cincinnati	Ohio	United States	45231
70	GSK Investigational Site	Cleveland	Ohio	United States	44113
71	GSK Investigational Site	Columbus	Ohio	United States	43235
72	GSK Investigational Site	Oklahoma City	Oklahoma	United States	73112
73	GSK Investigational Site	Oklahoma City	Oklahoma	United States	73120
74	GSK Investigational Site	Eugene	Oregon	United States	97401
75	GSK Investigational Site	Medford	Oregon	United States	97504
76	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15243
77	GSK Investigational Site	Bluffton	South Carolina	United States	29910
78	GSK Investigational Site	Charleston	South Carolina	United States	29406
79	GSK Investigational Site	Charleston	South Carolina	United States	29414
80	GSK Investigational Site	Knoxville	Tennessee	United States	37909
81	GSK Investigational Site	Boerne	Texas	United States	78006
82	GSK Investigational Site	Dallas	Texas	United States	75231
83	GSK Investigational Site	Dallas	Texas	United States	75246
84	GSK Investigational Site	Dickinson	Texas	United States	77539
85	GSK Investigational Site	Fort Worth	Texas	United States	76104
86	GSK Investigational Site	Plano	Texas	United States	75093
87	GSK Investigational Site	San Antonio	Texas	United States	78205
88	GSK Investigational Site	San Antonio	Texas	United States	78229
89	GSK Investigational Site	San Antonio	Texas	United States	78233
90	GSK Investigational Site	Waco	Texas	United States	76712
91	GSK Investigational Site	South Burlington	Vermont	United States	05403
92	GSK Investigational Site	Manassas	Virginia	United States	22015
93	GSK Investigational Site	Bellingham	Washington	United States	98225
94	GSK Investigational Site	Spokane	Washington	United States	99204
95	GSK Investigational Site	Spokane	Washington	United States	99207
96	GSK Investigational Site	Bay Roberts	Newfoundland and Labrador	Canada	A0A 1G0
97	GSK Investigational Site	Brampton	Ontario	Canada	L6T 3T1
98	GSK Investigational Site	Mississauga	Ontario	Canada	L5M 2V8
99	GSK Investigational Site	Ottawa	Ontario	Canada	K1Y 4G2
100	GSK Investigational Site	Toronto	Ontario	Canada	M3H 5S4
101	GSK Investigational Site	Quebec City	Quebec	Canada	G1V 4M6
102	GSK Investigational Site	Sainte-Foy	Quebec	Canada	G1V 4G5
103	GSK Investigational Site	Tallinn		Estonia	13419
104	GSK Investigational Site	Tallinn		Estonia	13619
105	GSK Investigational Site	Tartu		Estonia	51014
106	GSK Investigational Site	Schwetzingen	Baden-Wuerttemberg	Germany	68723
107	GSK Investigational Site	Sinsheim	Baden-Wuerttemberg	Germany	74889
108	GSK Investigational Site	Potsdam	Brandenburg	Germany	14469
109	GSK Investigational Site	Geesthacht	Schleswig-Holstein	Germany	21502
110	GSK Investigational Site	Berlin		Germany	10367
111	GSK Investigational Site	Berlin		Germany	10559
112	GSK Investigational Site	Berlin		Germany	10717
113	GSK Investigational Site	Berlin		Germany	10787
114	GSK Investigational Site	Berlin		Germany	10965
115	GSK Investigational Site	Berlin		Germany	12165
116	GSK Investigational Site	Berlin		Germany	13086
117	GSK Investigational Site	Berlin		Germany	13187
118	GSK Investigational Site	Kavala		Greece	65403
119	GSK Investigational Site	Larissa		Greece	41110
120	GSK Investigational Site	N. Efkarpia, Thessaloniki		Greece	564 29
121	GSK Investigational Site	Papagos, Athens		Greece	156 69
122	GSK Investigational Site	Rethymnon, Crete		Greece	74100
123	GSK Investigational Site	Thessaloniki		Greece	57010
124	GSK Investigational Site	Bucheon-Si,		Korea, Republic of
125	GSK Investigational Site	Cheongju, Chungcheongbuk-do		Korea, Republic of	361-711
126	GSK Investigational Site	Gwangju		Korea, Republic of	501-757
127	GSK Investigational Site	Seoul,		Korea, Republic of	120-752
128	GSK Investigational Site	Seoul		Korea, Republic of	110-744
129	GSK Investigational Site	Suwon, Kyonggi-do		Korea, Republic of	443-721
130	GSK Investigational Site	Guadalajara	Jalisco	Mexico	44100
131	GSK Investigational Site	Zapopan	Jalisco	Mexico	45040
132	GSK Investigational Site	Quezon City		Philippines	1100
133	GSK Investigational Site	Quezon City		Philippines	1101
134	GSK Investigational Site	Quezon City		Philippines	1109
135	GSK Investigational Site	Quezon City		Philippines
136	GSK Investigational Site	Gdansk		Poland	80-952
137	GSK Investigational Site	Warszawa		Poland	01-184
138	GSK Investigational Site	Wroclaw		Poland	50-445
139	GSK Investigational Site	Bucharest		Romania	011607
140	GSK Investigational Site	Bucuresti		Romania
141	GSK Investigational Site	Deva		Romania	330084
142	GSK Investigational Site	Targu Mures		Romania	540143
143	GSK Investigational Site	Moscow		Russian Federation	105 077
144	GSK Investigational Site	Moscow		Russian Federation	109240
145	GSK Investigational Site	Moscow		Russian Federation	115 280
146	GSK Investigational Site	Moscow		Russian Federation	129010
147	GSK Investigational Site	Smolensk		Russian Federation	214001
148	GSK Investigational Site	Tomsk		Russian Federation	634001
149	GSK Investigational Site	Bratislava		Slovakia	826 06
150	GSK Investigational Site	Trencin		Slovakia	911 08
151	GSK Investigational Site	Amanzimtoti		South Africa	4126
152	GSK Investigational Site	Bloemfontein		South Africa	9300
153	GSK Investigational Site	Cape Town		South Africa	7500
154	GSK Investigational Site	Claremont		South Africa	7708
155	GSK Investigational Site	Mowbray		South Africa	7700

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

• Bleecker ER, Bateman ED, Busse WW, Woodcock A, Frith L, House KW, Jacques L, Davis AM, Haumann B, Lötvall J. Once-daily fluticasone furoate is efficacious in patients with symptomatic asthma on low-dose inhaled corticosteroids. Ann Allergy Asthma Immunol. 2012 Nov;109(5):353-358.e4. doi: 10.1016/j.anai.2012.08.017.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00603278
• Other Study ID Numbers: FFA109685
• First Posted: Jan 29, 2008
• Last Update Posted: Dec 28, 2016
• Last Verified: Nov 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Adolescents; Adults; Pharmacokinetics; Asthma; GW685698X; Pharmacogenetics
• Additional relevant MeSH terms: Asthma

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily (OD) in the evening from the novel dry powder inhaler (NDPI) 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.	Participants received GW685698X 100 micrograms (µg) OD in the evening from the NDPI 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.	Participants received GW685698X 200 µg OD in the evening from the NDPI 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.	Participants received GW685698X 300 µg OD in the evening from the NDPI 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.	Participants received GW685698X 400 µg OD in the evening from the NDPI 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.	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 NDPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
Period Title: Overall Study
STARTED	107	105	101	103	99	100
COMPLETED	66	88	87	92	86	81
NOT COMPLETED	41	17	14	11	13	19

Baseline Characteristics

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID	Total
Arm/Group Description	Participants received placebo once daily OD in the evening from the NDPI 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 µg OD in the evening from the NDPI 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.	Participants received GW685698X 200 µg OD in the evening from the NDPI 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.	Participants received GW685698X 300 µg OD in the evening from the NDPI 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.	Participants received GW685698X 400 µg OD in the evening from the NDPI 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.	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 NDPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.	Total of all reporting groups
Overall Participants	107	105	101	103	99	100	615
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	39.1 (16.19)	38.3 (16.76)	38.8 (15.97)	39.9 (15.57)	40.7 (15.87)	39.8 (16.70)	39.4 (16.14)
Gender (Count of Participants)
Female	74 69.2%	72 68.6%	63 62.4%	67 65%	64 64.6%	62 62%	402 65.4%
Male	33 30.8%	33 31.4%	38 37.6%	36 35%	35 35.4%	38 38%	213 34.6%
Race/Ethnicity, Customized (Number) [Number]
White	62 57.9%	64 61%	65 64.4%	63 61.2%	56 56.6%	61 61%	371 60.3%
Central/South Asian Heritage (HER)	1 0.9%	1 1%	0 0%	1 1%	0 0%	0 0%	3 0.5%
Japanese/East Asian HER/South East Asian HER	25 23.4%	24 22.9%	23 22.8%	22 21.4%	25 25.3%	23 23%	142 23.1%
American Indian or Alaska Native	0 0%	1 1%	0 0%	0 0%	0 0%	0 0%	1 0.2%
American Indian or Alaska Native & White	14 13.1%	12 11.4%	13 12.9%	14 13.6%	13 13.1%	13 13%	79 12.8%
African American/African HER	5 4.7%	2 1.9%	0 0%	2 1.9%	4 4%	3 3%	16 2.6%
African American/African Heritage & White	0 0%	1 1%	0 0%	0 0%	0 0%	0 0%	1 0.2%
Native Hawaiian or other Pacific Islander	0 0%	0 0%	0 0%	0 0%	1 1%	0 0%	1 0.2%
Missing	0 0%	0 0%	0 0%	1 1%	0 0%	0 0%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in Trough (Evening Pre-dose and Pre- Rescue Bronchodilator) FEV1 at Week 8
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 Baseline value. Change from Baseline in trough FEV1 was calculated as the value at Week 8 minus the value at Baseline. The analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of Baseline trough FEV1, country, sex, age, and treatment group.
Time Frame	Baseline and Week 8

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. 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 and unscheduled visits) was used to impute missing measurements.

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	106	102	101	102	97	99
Least Squares Mean (Standard Error) [Liters]	-0.065 (0.0395)	0.142 (0.0403)	0.173 (0.0404)	0.228 (0.0402)	0.215 (0.0414)	0.160 (0.0409)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, GW685698X 100 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	0.207
	Confidence Interval	(2-Sided) 95%; 0.096 to 0.318
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, GW685698X 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	0.238
	Confidence Interval	(2-Sided) 95%; 0.127 to 0.349
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, GW685698X 300 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	0.293
	Confidence Interval	(2-Sided) 95%; 0.182 to 0.404
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, GW685698X 400 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	0.279
	Confidence Interval	(2-Sided) 95%; 0.167 to 0.392
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, FP 250 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	0.225
	Confidence Interval	(2-Sided) 95%; 0.114 to 0.337
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

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
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.
Time Frame	From Baseline up to Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	107	104	101	102	99	99
Least Squares Mean (Standard Error) [Liters per minute]	-2.8 (3.54)	9.1 (3.60)	14.8 (3.65)	15.1 (3.62)	21.0 (3.70)	18.2 (3.69)

3. Secondary Outcome

Title	Mean Change From Baseline in Daily Morning PEF Averaged Over the 8-week Treatment Period
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.
Time Frame	From Baseline up to Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	107	104	101	102	99	99
Least Squares Mean (Standard Error) [Liters per minute]	-4.7 (3.78)	15.6 (3.85)	16.0 (3.89)	25.5 (3.87)	26.0 (3.95)	25.1 (3.94)

4. Secondary Outcome

Title	Mean Change From Baseline in the Percentage of Symptom-free 24-hour (hr) Periods During the 8-week Treatment Period
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.
Time Frame	From Baseline up to Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	107	104	101	102	99	99
Least Squares Mean (Standard Error) [Percentage of symptom-free 24-hr periods]	17.1 (2.91)	21.3 (2.96)	19.4 (2.99)	24.1 (2.97)	28.0 (3.02)	30.4 (3.02)

5. Secondary Outcome

Title	Mean Change From Baseline in the Percentage of Rescue Free 24-hour (hr) Periods During the 8-week Treatment Period
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.
Time Frame	From Baseline up to Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	107	104	101	102	99	99
Least Squares Mean (Standard Error) [Percentage of rescue-free 24-hr periods]	15.6 (3.02)	25.0 (3.07)	23.8 (3.12)	25.0 (3.10)	24.4 (3.15)	34.5 (3.15)

6. Secondary Outcome

Title	Number of Participants Who Withdrew Due to Lack of Efficacy During the 8-Week Treatment Period
Description	The number of participants whose primary reason for withdrawal was lack of efficacy was analyzed.
Time Frame	From the first dose of study medication up to Week 8/Early Withdrawal

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	107	105	101	103	99	100
Number [Participants]	35 32.7%	10 9.5%	11 10.9%	8 7.8%	7 7.1%	14 14%

7. Secondary Outcome

Title	Number of Participants With Any On-treatment Adverse Events or Serious Adverse Events Throughout the 8-week Treatment Period
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.
Time Frame	From the first dose of study medication up to Week 8/Early Withdrawal

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	107	105	101	103	99	100
Any AE	32 29.9%	43 41%	33 32.7%	41 39.8%	35 35.4%	42 42%
Any SAE	0 0%	0 0%	0 0%	1 1%	1 1%	0 0%

8. Secondary Outcome

Title	Number of Participants With Clinical/Visual Evidence of Oropharyngeal Candidiasis
Description	A detailed oropharyngeal examination for visual evidence of oral candidiasis was performed for the entire Treatment Period.
Time Frame	From Baseline up to Week 8/Early Withdrawal

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	107	105	101	103	99	100
Clinical evidence	0 0%	3 2.9%	2 2%	4 3.9%	2 2%	4 4%
No clinical evidence	107 100%	102 97.1%	99 98%	99 96.1%	97 98%	96 96%

9. Secondary Outcome

Title	Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in the Blood at Baseline and Week 8
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).
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	100	103	97	99	94	95
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 (0.190)
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)	4.20 (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 (3.290)
Lymphocytes, BL, n=100, 103, 97, 99, 94, 95	34.05 (9.683)	33.97 (8.817)	34.01 (9.214)	33.70 (8.380)	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 (2.190)
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	56.53 (9.391)	58.17 (9.386)	59.75 (9.513)	60.72 (9.846)	64.75 (8.896)	57.61 (9.681)

10. Secondary Outcome

Title	Hematocrit at Baseline and Week 8
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).
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	102	104	96	99	93	95
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)

11. Secondary Outcome

Title	Hemoglobin at Baseline and Week 8
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).
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	102	104	96	99	93	95
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)	135.30 (12.360)	138.17 (15.050)	135.79 (18.663)

12. Secondary Outcome

Title	Platelet Count and White Blood Cell (WBC) Count at Baseline and Week 8
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).
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	101	103	96	99	93	95
Platelet count, BL, n=98, 103,93, 98, 89, 94	286.23 (57.383)	277.29 (64.358)	290.90 (98.801)	282.86 (70.086)	283.01 (58.915)	285.45 (69.220)
Platelet count, W8, n=60, 84, 80, 81, 80, 80	275.91 (53.705)	281.40 (66.449)	277.73 (71.595)	287.98 (67.053)	297.83 (76.271)	287.60 (87.009)
WBC, BL, n=101, 103, 96, 99, 93, 95	8.05 (2.310)	7.90 (2.110)	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)	8.20 (1.936)	9.07 (2.054)	8.30 (3.119)

13. Secondary Outcome

Title	Red Blood Cells (RBC) Count at Baseline and Week 8
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).
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	102	104	96	99	93	95
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)	4.50 (0.458)	4.66 (0.526)	4.52 (0.426)

14. Secondary Outcome

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
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).
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	106	104	101	102	98	99
ALP, BL, n=106, 104, 101, 102, 98, 99	89.3 (58.42)	90.5 (61.69)	83.7 (56.68)	88.0 (74.76)	83.8 (40.51)	89.0 (57.83)
ALP, W8, n=65, 85, 84, 89, 83, 81	88.0 (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)	20.0 (14.75)	20.5 (15.44)	23.4 (15.65)	20.4 (12.70)	20.6 (15.83)
ALT, W8, n=65, 85, 85, 89, 83, 81	20.1 (14.37)	21.0 (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 (10.10)	21.2 (7.10)	21.4 (10.18)
AST, W8, n=65, 85, 85, 89, 83, 81	21.8 (8.77)	20.5 (7.50)	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)	169.0 (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)	26.0 (20.33)	27.6 (21.53)	35.2 (38.16)	28.2 (18.36)	29.5 (27.60)
GGT, W8, n=65, 85, 85, 89, 83, 81	31.5 (44.86)	30.1 (41.05)	29.2 (31.63)	34.8 (39.40)	28.3 (23.69)	28.4 (24.14)

15. Secondary Outcome

Title	Clinical Chemistry Parameters of Albumin and Total Protein at Baseline and Week 8
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).
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	106	104	101	102	98	99
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	44.0 (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 (4.40)	73.7 (4.42)	74.0 (4.37)	73.0 (4.26)
Total protein, W8, n=65, 85, 85, 89, 83, 81	72.0 (4.68)	72.4 (4.31)	73.3 (5.28)	72.5 (3.92)	73.9 (4.02)	72.8 (4.16)

16. Secondary Outcome

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
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).
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	106	104	101	102	98	99
Chloride, BL, n=106, 104, 101, 102, 98, 99	104.8 (3.06)	105.0 (2.61)	104.7 (3.15)	104.5 (2.34)	104.8 (3.00)	105.0 (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 (2.20)	104.0 (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 (0.10)	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 (2.40)	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 (2.40)	22.8 (2.72)	23.1 (2.40)	22.8 (2.58)	22.9 (2.37)
Cholesterol, BL, n=106, 104, 101, 102, 98, 99	5.0 (1.09)	5.0 (1.21)	4.9 (1.07)	5.2 (1.13)	5.2 (1.16)	5.0 (1.12)
Cholesterol, W8, n=65, 85, 85, 89, 83, 81	4.9 (1.06)	5.0 (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 (0.70)	5.2 (0.84)	5.5 (2.18)	5.5 (1.88)
Glucose, W8, n=65, 85, 85, 89, 83, 81	5.0 (0.73)	5.2 (1.66)	5.1 (1.04)	5.2 (1.06)	5.0 (1.46)	5.3 (1.85)
PI, BL, n=106, 104, 101, 102, 98, 99	1.2 (0.20)	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, 98	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)	141.0 (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)	140.0 (1.95)	140.3 (2.05)	140.5 (2.15)	140.3 (2.23)	140.2 (1.80)
BUN, BL, n=106, 104, 101, 102, 98, 99	5.3 (1.87)	5.1 (2.07)	5.1 (1.90)	4.9 (1.61)	5.2 (2.20)	5.3 (1.78)
BUN, W8, n=65, 85, 85, 89, 83, 81	5.2 (1.42)	4.9 (1.47)	5.0 (1.61)	5.0 (1.68)	4.8 (1.60)	5.2 (1.64)

17. Secondary Outcome

Title	Clinical Chemistry Parameters of Direct Bilirubin (DBIL), Total Bilirubin (TBIL), Uric Acid and Creatinine at Baseline and Week 8
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).
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	106	104	101	102	98	99
DBIL, BL, n=106, 103, 100, 101, 98, 98	2.1 (1.23)	2.0 (1.30)	1.9 (1.09)	1.9 (1.09)	2.1 (0.97)	1.8 (0.90)
DBIL, W8, n=65, 65, 85, 89, 83, 81	1.8 (0.97)	2.0 (1.09)	1.9 (0.88)	1.9 (0.88)	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 (5.20)	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 (83.60)	319.4 (94.90)	326.7 (95.36)	323.9 (82.30)	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 (18.60)	77.8 (16.50)	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)

18. Secondary Outcome

Title	Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/Early Withdrawal
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).
Time Frame	Baseline and Week 8/Early Withdrawal

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT Population.

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	102	101	98	99	94	97
UOB, Neg, BL, n=102, 101, 98, 99, 94, 95	96 89.7%	91 86.7%	85 84.2%	90 87.4%	81 81.8%	91 91%
UOB, Trace, BL, n=102, 101, 98, 99, 94, 97	4 3.7%	1 1%	3 3%	4 3.9%	8 8.1%	2 2%
UOB, 1+, BL, n=102, 101, 98, 99, 94, 97	1 0.9%	4 3.8%	6 5.9%	1 1%	1 1%	1 1%
UOB, 2+, BL, n=102, 101, 98, 99, 94, 97	0 0%	1 1%	1 1%	0 0%	0 0%	1 1%
UOB, 3+, BL, n=102, 101, 98, 99, 94, 97	1 0.9%	4 3.8%	3 3%	4 3.9%	4 4%	2 2%
UOB, Neg, W8, n=63, 85, 84, 82, 82, 82	56 52.3%	77 73.3%	77 76.2%	73 70.9%	73 73.7%	72 72%
UOB, Trace, W8, n=63, 85, 84, 82, 82, 82	4 3.7%	3 2.9%	2 2%	3 2.9%	2 2%	4 4%
UOB, 1+, W8, n=63, 85, 84, 82, 82, 82	0 0%	2 1.9%	1 1%	1 1%	3 3%	1 1%
UOB, 2+, W8, n=63, 85, 84, 82, 82, 82	1 0.9%	1 1%	2 2%	1 1%	3 3%	1 1%
UOB, 3+, W8, n=63, 85, 84, 82, 82, 82	2 1.9%	2 1.9%	2 2%	4 3.9%	1 1%	4 4%
UOB, Neg, WD, n=9, 4, 1, 2, 3, 7	9 8.4%	4 3.8%	1 1%	2 1.9%	3 3%	6 6%
UOB, 2+, WD, n=9, 4, 1, 2, 3, 7	0 0%	0 0%	0 0%	0 0%	0 0%	1 1%
UG, Neg, BL, n=102, 101, 98, 99, 94, 97	100 93.5%	98 93.3%	98 97%	98 95.1%	91 91.9%	94 94%
UG, Trace, BL, n=102, 101, 98, 99, 94, 97	1 0.9%	1 1%	0 0%	0 0%	0 0%	0 0%
UG, Trace or 1/10 G/DL, BL, n=102, 101,98,99,94,97	1 0.9%	0 0%	0 0%	0 0%	0 0%	1 1%
UG, 1+ or 1/3 G/DL, BL, n=102, 101, 98, 99, 94, 97	0 0%	0 0%	0 0%	1 1%	1 1%	1 1%
UG, 3+ or 1 G/DL, BL, n=102, 101, 98, 99, 94, 97	0 0%	2 1.9%	0 0%	0 0%	2 2%	1 1%
UG, Neg,W8, n=63, 85, 84, 82, 82, 82	62 57.9%	83 79%	83 82.2%	81 78.6%	82 82.8%	80 80%
UG, Trace, W8, n=63, 85, 84, 82, 82, 82	0 0%	0 0%	1 1%	1 1%	0 0%	0 0%
UG, 1+ or 1/4 G/DL, W8, n=63, 85, 84, 82, 82, 82	1 0.9%	0 0%	0 0%	0 0%	0 0%	0 0%
UG, 3+ or 1 G/DL, W8, n=63, 85, 84, 82, 82, 82	0 0%	2 1.9%	0 0%	0 0%	0 0%	2 2%
UG, Neg, WD, n=9, 4, 1, 2, 3, 7	9 8.4%	4 3.8%	1 1%	2 1.9%	3 3%	7 7%
UK, Neg, BL, n=102, 101, 98, 99, 94, 97	97 90.7%	96 91.4%	96 95%	96 93.2%	90 90.9%	94 94%
UK, Trace, BL, n=102, 101, 98, 99, 94, 97	5 4.7%	2 1.9%	2 2%	3 2.9%	4 4%	1 1%
UK, 1+, BL, n=102, 101, 98, 99, 94, 97	0 0%	2 1.9%	0 0%	0 0%	0 0%	2 2%
UK, 2+, BL, n=102, 101, 98, 99, 94, 97	0 0%	1 1%	0 0%	0 0%	0 0%	0 0%
UK, Neg, W8, n=63, 85, 84, 82, 82, 82	61 57%	80 76.2%	81 80.2%	78 75.7%	75 75.8%	80 80%
UK, Trace, W8, n=63, 85, 84, 82, 82, 82	2 1.9%	5 4.8%	2 2%	4 3.9%	7 7.1%	2 2%
UK, 1+, W8, n=63, 85, 84, 82, 82, 82	0 0%	0 0%	1 1%	0 0%	0 0%	0 0%
UK, Neg, WD, n=9, 4, 1, 2, 3, 7	9 8.4%	4 3.8%	1 1%	2 1.9%	3 3%	7 7%
UP, Neg, BL, n=102, 101, 98, 99, 94, 97	76 71%	78 74.3%	77 76.2%	78 75.7%	70 70.7%	75 75%
UP, Trace, BL, n=102, 101, 98, 99, 94, 97	19 17.8%	14 13.3%	13 12.9%	13 12.6%	17 17.2%	11 11%
UP, 1+, BL, n=102, 101, 98, 99, 94, 97	6 5.6%	6 5.7%	7 6.9%	7 6.8%	6 6.1%	11 11%
UP, 2+, BL, n=102, 101, 98, 99, 94, 97	0 0%	1 1%	1 1%	0 0%	1 1%	0 0%
UP, 3+, BL, n=102, 101, 98, 99, 94, 97	1 0.9%	2 1.9%	0 0%	1 1%	0 0%	0 0%
UP, Neg, W8, n=63, 85, 84, 82, 82, 82	54 50.5%	64 61%	68 67.3%	65 63.1%	63 63.6%	61 61%
UP, Trace, W8, n=63, 85, 84, 82, 82, 82	6 5.6%	14 13.3%	8 7.9%	12 11.7%	17 17.2%	15 15%
UP, 1+, W8, n=63, 85, 84, 82, 82, 82	3 2.8%	5 4.8%	6 5.9%	5 4.9%	2 2%	5 5%
UP, 2+, W8,n=63, 85, 84, 82, 82, 82	0 0%	2 1.9%	1 1%	0 0%	0 0%	0 0%
UP, 3+, W8, n=63, 85, 84, 82, 82, 82	0 0%	0 0%	0 0%	0 0%	0 0%	1 1%
UP, 4+, W8, n=63, 85, 84, 82, 82, 82	0 0%	0 0%	1 1%	0 0%	0 0%	0 0%
UP, Neg, WD, n=9, 4, 1, 2, 3, 7	8 7.5%	4 3.8%	0 0%	1 1%	3 3%	6 6%
UP, Trace, WD, n=9, 4, 1, 2, 3, 7	0 0%	0 0%	1 1%	1 1%	0 0%	0 0%
UP, 1+, WD, n=9, 4, 1, 2, 3, 7	1 0.9%	0 0%	0 0%	0 0%	0 0%	1 1%
UWBC, Neg, BL, n=102, 101, 98, 99, 94, 97	86 80.4%	87 82.9%	82 81.2%	81 78.6%	74 74.7%	88 88%
UWBC, Trace, BL, n=102, 101, 98, 99, 94, 97	2 1.9%	4 3.8%	7 6.9%	3 2.9%	5 5.1%	2 2%
UWBC, 1+, BL, n=102, 101, 98, 99, 94. 97	6 5.6%	5 4.8%	4 4%	7 6.8%	8 8.1%	3 3%
UWBC, 2+, BL, n=102, 101, 98, 99, 94, 97	7 6.5%	3 2.9%	2 2%	8 7.8%	5 5.1%	4 4%
UWBC, 3+, BL, n=102, 101, 98, 99, 94, 97	1 0.9%	2 1.9%	3 3%	0 0%	2 2%	0 0%
UWBC, Neg, W8, n=63, 85, 84, 82, 82, 82	52 48.6%	65 61.9%	71 70.3%	62 60.2%	63 63.6%	69 69%
UWBC, Trace, W8, n=63, 85, 84, 82, 82, 82	3 2.8%	5 4.8%	4 4%	7 6.8%	7 7.1%	3 3%
UWBC, 1+, W8, n=63, 85, 84, 82, 82, 82	7 6.5%	7 6.7%	6 5.9%	7 6.8%	5 5.1%	7 7%
UWBC, 2+, W8, n=63, 85, 84, 82, 82, 82	1 0.9%	7 6.7%	3 3%	5 4.9%	7 7.1%	3 3%
UWBC, 3+, W8, n=63, 85, 84, 82, 82, 82	0 0%	1 1%	0 0%	1 1%	0 0%	0 0%
UWBC, Neg, WD, n=9, 4, 1, 2, 3, 7	9 8.4%	4 3.8%	0 0%	1 1%	3 3%	7 7%
UWBC, 2+, WD, n=9, 4, 1, 2, 3, 7	0 0%	0 0%	1 1%	1 1%	0 0%	0 0%

19. Secondary Outcome

Title	Urine Specific Gravity at Baseline and Week 8/Early Withdrawal
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.
Time Frame	Urine specific gravity at Baseline and Week 8/Early Withdrawal

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	102	104	96	99	94	97
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)	1.0210 (0.00884)	1.0255 (0.00726)
WD, n=9, 4, 1, 2, 3, 7	1.0206 (0.00532)	1.0228 (0.00772)	1.0380 (0)	1.0175 (0.01768)	1.0273 (0.00306)	1.0164 (0.00824)

20. Secondary Outcome

Title	Urine pH at Baseline and Week 8/Early Withdrawal
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).
Time Frame	Baseline and Week 8/Early Withdrawal

Outcome Measure Data

Analysis Population Description

ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	102	104	96	99	94	97
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 (0.370)	6.04 (0.393)
W8, n=62, 84, 82, 83, 82, 82	6.00 (0.458)	6.13 (0.518)	6.10 (0.451)	5.99 (0.397)	6.00 (0.437)	6.01 (0.368)
WD, n=9, 4, 1, 2, 3, 7	6.11 (0.601)	6.13 (0.250)	6.00 (0)	6.00 (0.000)	5.67 (0.289)	5.93 (0.345)

21. Secondary Outcome

Title	24-hour Urinary Cortisol Excretion at Baseline and Week 8
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.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

Urine Cortisol (UC) Population: all participants whose urine samples did not have confounding factors that could affect the interpretation of results.

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	56	69	75	75	72	70
Baseline	68.45	56.80	65.90	64.50	73.40	75.69
Week 8	64.70	60.80	53.00	56.00	62.00	58.39

22. Secondary Outcome

Title	Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 8
Description	Change from Baseline was calculated as the Week 8 value minus the Baseline value.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	107	105	101	103	99	100
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)	0.0 (9.37)	-0.2 (8.05)	1.0 (7.90)

23. Secondary Outcome

Title	Change From Baseline in Heart Rate at Week 8
Description	Change from Baseline was calculated as the Week 8 value minus the Baseline value.
Time Frame	Baseline and Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	GW685698X 100 µg OD	GW685698X 200 µg OD	GW685698X 300 µg OD	GW685698X 400 µg OD	FP 250 µg BID
Arm/Group Description	Participants received placebo once daily 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 inhalation aerosol to be used as needed throughout the study.	Participants received GW685698X 100 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.	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.	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.	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.	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.
Measure Participants	107	105	101	103	99	100
Mean (Standard Deviation) [Beats per minute]	0.8 (10.12)	0.5 (7.65)	-0.4 (8.90)	1.5 (10.92)	0.5 (8.55)	-1.7 (9.68)

Adverse Events

Time Frame	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 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.
Arm/Group Title	Placebo		GW685698X 100 µg OD		GW685698X 200 µg OD		GW685698X 300 µg OD		GW685698X 400 µg OD		FP 250 µg BID
Arm/Group Description	Participants received placebo once daily OD in the evening from the NDPI 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 inhalation aerosol to be used as needed throughout the study.		Participants received GW685698X 100 µg OD in the evening from the NDPI 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.		Participants received GW685698X 200 µg OD in the evening from the NDPI 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.		Participants received GW685698X 300 µg OD in the evening from the NDPI 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.		Participants received GW685698X 400 µg OD in the evening from the NDPI 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.		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 NDPI for 8 weeks. In addition, participants were provided supplemental albuterol/salbutamol aerosol to be used as needed throughout the study.
All Cause Mortality
	Placebo		GW685698X 100 µg OD		GW685698X 200 µg OD		GW685698X 300 µg OD		GW685698X 400 µg OD		FP 250 µg BID
	Affected / at Risk (%)	# Events	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)		/ (NaN)
Serious Adverse Events
	Placebo		GW685698X 100 µg OD		GW685698X 200 µg OD		GW685698X 300 µg OD		GW685698X 400 µg OD		FP 250 µg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/107 (0%)		0/105 (0%)		0/101 (0%)		1/103 (1%)		1/99 (1%)		0/100 (0%)
Cardiac disorders
Myocardial infarction	0/107 (0%)		0/105 (0%)		0/101 (0%)		1/103 (1%)		0/99 (0%)		0/100 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/107 (0%)		0/105 (0%)		0/101 (0%)		0/103 (0%)		1/99 (1%)		0/100 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		GW685698X 100 µg OD		GW685698X 200 µg OD		GW685698X 300 µg OD		GW685698X 400 µg OD		FP 250 µg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/107 (15.9%)		29/105 (27.6%)		18/101 (17.8%)		22/103 (21.4%)		20/99 (20.2%)		32/100 (32%)
Gastrointestinal disorders
Diarrhoea	0/107 (0%)		4/105 (3.8%)		1/101 (1%)		1/103 (1%)		1/99 (1%)		1/100 (1%)
Abdominal pain upper	0/107 (0%)		2/105 (1.9%)		1/101 (1%)		1/103 (1%)		3/99 (3%)		0/100 (0%)
Toothache	0/107 (0%)		1/105 (1%)		1/101 (1%)		0/103 (0%)		0/99 (0%)		3/100 (3%)
Infections and infestations
Nasopharyngitis	8/107 (7.5%)		9/105 (8.6%)		5/101 (5%)		7/103 (6.8%)		4/99 (4%)		7/100 (7%)
Upper respiratory tract infection	3/107 (2.8%)		2/105 (1.9%)		3/101 (3%)		1/103 (1%)		0/99 (0%)		6/100 (6%)
Oral candidiasis	0/107 (0%)		3/105 (2.9%)		1/101 (1%)		3/103 (2.9%)		3/99 (3%)		3/100 (3%)
Sinusitis	1/107 (0.9%)		2/105 (1.9%)		0/101 (0%)		0/103 (0%)		1/99 (1%)		3/100 (3%)
Musculoskeletal and connective tissue disorders
Back pain	0/107 (0%)		1/105 (1%)		1/101 (1%)		3/103 (2.9%)		3/99 (3%)		2/100 (2%)
Nervous system disorders
Headache	6/107 (5.6%)		9/105 (8.6%)		8/101 (7.9%)		8/103 (7.8%)		9/99 (9.1%)		8/100 (8%)
Respiratory, thoracic and mediastinal disorders
Cough	1/107 (0.9%)		2/105 (1.9%)		0/101 (0%)		2/103 (1.9%)		4/99 (4%)		2/100 (2%)
Dysphonia	1/107 (0.9%)		1/105 (1%)		0/101 (0%)		2/103 (1.9%)		2/99 (2%)		4/100 (4%)
Oropharyngeal pain	0/107 (0%)		2/105 (1.9%)		1/101 (1%)		1/103 (1%)		3/99 (3%)		3/100 (3%)

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.