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

Asthma Clinical Trial

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 500mcg Twice Daily Compared With Placebo for 8 Weeks in Adolescent an

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00603746
• Other study ID #: FFA109684
• Status: Completed
• Phase: Phase 2
• First received: December 27, 2007
• Last updated: March 21, 2017
• Start date: December 2007
• Est. completion date: September 2008

Study information

• Verified date: March 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 Moderate-Dose ICS Therapy

Recruitment information / eligibility

• Status: Completed
• Enrollment: 627
• Est. completion date: September 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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.

• 3. 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%-85% of the predicted normal value during the morning Visit 1 screening period or a best FEV1 of 40%-90% of the predicted normal value during the evening Visit 1 screening period.

• 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 during the screening period.

Re-screening of subjects during the Visit 1 screening period: If a subject does not meet the inclusion criteria based upon FEV1 percent predicted and/or reversibility, the subject may return to the site once within 4 days and repeat the lung function tests.

• 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 >176 = 440mcg exactuator or > 200 =500mcg ex valve]; [fluticasone propionate DPI > 200=500mcg]; [beclomethasone dipropionate DPI > 420 = 840mcg exactuator or > 500 = 1000mcg ex-valve]; [beclomethasone dipropionate HFA Qvar > 160 = 480mcg exactuator or > 200 = 500mcg ex-valve]; [budesonide DPI MDI >400 =1200mcg]; [flunisolide > 1000 = 2000mcg]; [triamcinolone acetonide >1000 =1600mcg]; [mometasone furoate DPI >200 = 440mcg]; [ciclesonide MDI HFA >160 mcg = 320mcg ex-actuator dose / >200mcg = 400mcg 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 subject's asthma status or the subject's 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 subject's asthma status or the subject's 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.

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• GW685698X
GW685698X

Locations

Country	Name	City	State
Australia	GSK Investigational Site	Adelaide	South Australia
Australia	GSK Investigational Site	Clayton	Victoria
Australia	GSK Investigational Site	Nedlands	Western Australia
Bulgaria	GSK Investigational Site	Pleven
Bulgaria	GSK Investigational Site	Ruse
Bulgaria	GSK Investigational Site	Sofia
Canada	GSK Investigational Site	Ajax	Ontario
Canada	GSK Investigational Site	Bay Roberts	Newfoundland and Labrador
Canada	GSK Investigational Site	Brampton	Ontario
Canada	GSK Investigational Site	Mississauga	Ontario
Canada	GSK Investigational Site	Ottawa	Ontario
Canada	GSK Investigational Site	Quebec City	Quebec
Canada	GSK Investigational Site	Sainte-Foy	Quebec
Canada	GSK Investigational Site	Sherbrooke	Quebec
Canada	GSK Investigational Site	Toronto	Ontario
Chile	GSK Investigational Site	Puente Alto - Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago
Chile	GSK Investigational Site	Valparaiso	Valparaíso
Czech Republic	GSK Investigational Site	Beroun
Czech Republic	GSK Investigational Site	Brno
Czech Republic	GSK Investigational Site	Kutna Hora
Czech Republic	GSK Investigational Site	Tabor
Estonia	GSK Investigational Site	Tallinn
Estonia	GSK Investigational Site	Tartu
France	GSK Investigational Site	Grenoble
France	GSK Investigational Site	Marseille
France	GSK Investigational Site	Montpellier
France	GSK Investigational Site	Nantes
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Gelnhausen	Hessen
Germany	GSK Investigational Site	Hannover	Niedersachsen
Mexico	GSK Investigational Site	Distrito Federal
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Mexico
Mexico	GSK Investigational Site	Mexico
Mexico	GSK Investigational Site	Zapopan	Jalisco
Netherlands	GSK Investigational Site	Amsterdam
Netherlands	GSK Investigational Site	Eindhoven
Netherlands	GSK Investigational Site	Hengelo
Netherlands	GSK Investigational Site	Schiedam
Netherlands	GSK Investigational Site	Utrecht
Peru	GSK Investigational Site	Lima
Peru	GSK Investigational Site	Lima
Poland	GSK Investigational Site	Bialystok
Poland	GSK Investigational Site	Warszawa
Poland	GSK Investigational Site	Wroclaw
Russian Federation	GSK Investigational Site	Irkutsk
Russian Federation	GSK Investigational Site	Kazan
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Tomsk
South Africa	GSK Investigational Site	Amanzimtoti
South Africa	GSK Investigational Site	Bellville
South Africa	GSK Investigational Site	Durban
South Africa	GSK Investigational Site	Mowbray
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Bangkok
United States	GSK Investigational Site	Bangor	Maine
United States	GSK Investigational Site	Bellingham	Washington
United States	GSK Investigational Site	Billings	Montana
United States	GSK Investigational Site	Bloomingdale/Illinois	Illinois
United States	GSK Investigational Site	Bluffton	South Carolina
United States	GSK Investigational Site	Boca Raton	Florida
United States	GSK Investigational Site	Boerne	Texas
United States	GSK Investigational Site	Bridgeport	Connecticut
United States	GSK Investigational Site	Butte	Montana
United States	GSK Investigational Site	Canton	Ohio
United States	GSK Investigational Site	Charleston	South Carolina
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Cleveland	Ohio
United States	GSK Investigational Site	Clifton/New Jersey	New Jersey
United States	GSK Investigational Site	Cocoa	Florida
United States	GSK Investigational Site	Colorado Springs	Colorado
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	Crescent Springs	Kentucky
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Daytona Beach	Florida
United States	GSK Investigational Site	DeKalb	Illinois
United States	GSK Investigational Site	Detroit	Michigan
United States	GSK Investigational Site	Dickinson	Texas
United States	GSK Investigational Site	East Syracuse	New York
United States	GSK Investigational Site	Eugene	Oregon
United States	GSK Investigational Site	Evansville	Indiana
United States	GSK Investigational Site	Fort Smith	Arkansas
United States	GSK Investigational Site	Fort Worth	Texas
United States	GSK Investigational Site	Fresno	California
United States	GSK Investigational Site	Gainesville	Georgia
United States	GSK Investigational Site	Granada Hills	California
United States	GSK Investigational Site	Greensboro	North Carolina
United States	GSK Investigational Site	Greenville	North Carolina
United States	GSK Investigational Site	Gurnee	Illinois
United States	GSK Investigational Site	Hillsborough	New Jersey
United States	GSK Investigational Site	Huntington Beach	California
United States	GSK Investigational Site	Iowa City	Iowa
United States	GSK Investigational Site	Ithaca	New York
United States	GSK Investigational Site	Jackson	Mississippi
United States	GSK Investigational Site	Knoxville	Tennessee
United States	GSK Investigational Site	Largo	Florida
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Lenexa	Kansas
United States	GSK Investigational Site	Little Rock	Arkansas
United States	GSK Investigational Site	Little Silver	New Jersey
United States	GSK Investigational Site	Long Beach	California
United States	GSK Investigational Site	Long Beach	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Manassas	Virginia
United States	GSK Investigational Site	Medford	Oregon
United States	GSK Investigational Site	Metairie	Louisiana
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Missoula	Montana
United States	GSK Investigational Site	Mt. Pleasant	South Carolina
United States	GSK Investigational Site	North Dartmouth	Massachusetts
United States	GSK Investigational Site	Ocala	Florida
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Palmdale	California
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Plano	Texas
United States	GSK Investigational Site	Raleigh	North Carolina
United States	GSK Investigational Site	Riverside	California
United States	GSK Investigational Site	Rochester	Minnesota
United States	GSK Investigational Site	Rockville Center	New York
United States	GSK Investigational Site	Rolla	Missouri
United States	GSK Investigational Site	Roseville	California
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	Skillman	New Jersey
United States	GSK Investigational Site	South Burlington	Vermont
United States	GSK Investigational Site	Spokane	Washington
United States	GSK Investigational Site	Spokane	Washington
United States	GSK Investigational Site	St. Louis	Missouri
United States	GSK Investigational Site	St. Louis	Missouri
United States	GSK Investigational Site	Tampa	Florida
United States	GSK Investigational Site	Taylor	Michigan
United States	GSK Investigational Site	Torrance	California
United States	GSK Investigational Site	Waco	Texas
United States	GSK Investigational Site	Walnut Creek	California
United States	GSK Investigational Site	Warrensburg	Missouri
United States	GSK Investigational Site	Waterbury	Connecticut
United States	GSK Investigational Site	West Covina	California
United States	GSK Investigational Site	West Palm Beach	Florida
United States	GSK Investigational Site	Wheat Ridge	Colorado
United States	GSK Investigational Site	Winter Park	Florida
United States	GSK Investigational Site	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  Chile,  Czech Republic,  Estonia,  France,  Germany,  Mexico,  Netherlands,  Peru,  Poland,  Russian Federation,  South Africa,  Thailand, 

References & Publications (1)

Busse WW, Bleecker ER, Bateman ED, Lötvall J, Forth R, Davis AM, Jacques L, Haumann B, Woodcock A. Fluticasone furoate demonstrates efficacy in patients with asthma symptomatic on medium doses of inhaled corticosteroid therapy: an 8-week, randomised, placebo-controlled trial. Thorax. 2012 Jan;67(1):35-41. doi: 10.1136/thoraxjnl-2011-200308. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline in Trough (Evening Pre-dose and Pre- Rescue Bronchodilator) FEV1 at Week 8	Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcibly exhaled from the lungs 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.	Baseline and Week 8
Secondary	Mean Change From Baseline in Daily Trough (Pre-dose and Pre-rescue Bronchodilator) Evening Peak Expiratory Flow (PEF) Averaged Over the 8-week Treatment Period	PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Trough PEF is defined as the maximal rate (speed) that a person can exhale during a short maximal expiratory effort after a full inspiration. 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.	From Baseline up to Week 8
Secondary	Mean Change From Baseline in Daily Morning PEF Averaged Over the 8-week Treatment Period	PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. Trough PEF is defined as the maximal rate (speed) that a person can exhale during a short maximal expiratory effort after a full inspiration. 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.	From Baseline up to Week 8
Secondary	Mean Change From Baseline in the Percentage of Symptom-free 24-hour (hr) Periods During the 8-week Treatment Period	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.	From Baseline up to Week 8
Secondary	Mean Change From Baseline in the Percentage of Rescue-free 24-hour (hr) Periods During the 8-week Treatment Period	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-hour 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.	From Baseline up to Week 8
Secondary	Number Participants Who Withdrew Due to Lack of Efficacy During the 8-week Treatment Period	The number of participants whose primary reason for withdrawal was lack of efficacy was analyzed.	From the first dose of the study medication up to Week 8/Early Withdrawal
Secondary	Number of Participants With Any On-treatment Adverse Event or Serious Adverse Event Throughout the 8-week Treatment Period	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.	From the first dose of the study medication up to Week 8/Early Withdrawal
Secondary	Number of Participants With Clinical/Visual Evidence of Oropharyngeal Candidiasis	A detailed oropharyngeal examination for visual evidence of oral candidiasis was performed.	From Baseline up to Week 8/Early Withdrawal
Secondary	Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils in the Blood at Baseline and Week 8	Blood samples were collected for the measurement of the percentage of basophils, eosinophils, lymphocytes, monocytes, and total neutrophils in the blood at Baseline (BL) and Week 8 (W8). The Baseline value was the measurement taken at screening (Visit 1).	Baseline and Week 8
Secondary	Hematocrit at Baseline and Week 8	Blood samples were collected for the measurement of hematocrit at Baseline and Week 8. The Baseline value was the measurement taken at screening (Visit 1).	Baseline and Week 8
Secondary	Hemoglobin at Baseline and Week 8	Blood samples were collected for the measurement of hemoglobin at Baseline and Week 8. The Baseline value was the measurement taken at screening (Visit 1).	Baseline and Week 8
Secondary	Platelet Count and White Blood Cell Count at Baseline and Week 8	Blood samples were collected for determining the platelet count and white blood cell (WBC) count at Baseline and Week 8. The Baseline value was the measurement taken at screening (Visit 1).	Baseline and Week 8
Secondary	Red Blood Cell Count at Baseline and Week 8	Blood samples were collected for determining the red blood cell count at Baseline and Week 8. The Baseline value was the measurement taken at screening (Visit1).	Baseline and Week 8
Secondary	Clinical Chemistry Parameters of Alanine Amino Transferase (ALT), Alkaline Phosphatase (ALP), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT), and Lactate Dehydrogenase (LDH) at Baseline and Week 8	Blood samples were collected for the measurement of ALT, ALP, AST, GGT, and LDH at Baseline and Week 8. The Baseline value was the measurement taken at screening (Visit 1).	Baseline and Week 8
Secondary	Clinical Chemistry Parameters of Albumin and Total Protein at Baseline and Week 8	Blood samples were collected for the measurement of albumin and total protein at Baseline and Week 8. The Baseline value was the measurement taken at screening (Visit 1).	Baseline and Week 8
Secondary	Clinical Chemistry Parameters of Calcium, Carbon Dioxide Content/Bicarbonate, Chloride, Cholesterol, Glucose, Phosphorus Inorganic, Potassium, Sodium, and Urea at Baseline and Week 8	Blood samples were collected for the measurement of calcium, carbon dioxide content/bicarbonate (CO2/BI), chloride, cholesterol, glucose, phosphorus inorganic (PI), potassium, sodium, and urea at Baseline and Week 8. The Baseline value was the measurement taken at screening (Visit 1).	Baseline and Week 8
Secondary	Clinical Chemistry Parameters of Creatinine, Direct Bilirubin, Total Bilirubin, and Uric Acid at Baseline and Week 8	Blood samples were collected for the measurement of creatinine, direct bilirubin (DBIL), total bilirubin (TBIL), and uric acid at Baseline and Week 8. The Baseline value was the measurement taken at screening (Visit 1).	Baseline and Week 8
Secondary	Number of Participants With the Indicated Result for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline and Week 8/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 Cells (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; results for urinalysis parameters can be read as 1+, 2+, 3+, Large, Moderate, Negative (Neg), Small, and Trace. 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, 2+ or 1/2 G/dL, 3+ or 1 G/dL, 4+ or 2 or more G/dL, indicating proportional concentrations in the urine sample. Data are reported as the number of participants who had 1+, 2+, 3+, Large, Moderate, Neg, Small, or Trace levels at Baseline (BL) and Week 8 (W8)/Early Withdrawal (EW). The Baseline value was the measurement taken at screening (Visit 1).	Baseline and Week 8/Early Withdrawal
Secondary	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.	Baseline and Week 8/Early Withdrawal
Secondary	Urine pH at 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).	Baseline and Week 8/Early Withdrawal
Secondary	24-hour Urinary Cortisol Excretion at 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.	Baseline and Week 8
Secondary	Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 8	Change from Baseline was calculated as the Week 8 value minus the Baseline value.	Baseline and Week 8
Secondary	Change From Baseline in Heart Rate at Week 8	Change from Baseline was calculated as the Week 8 value minus the Baseline value.	Baseline and Week 8

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