Evaluation of Tiotropium 2.5 and 5 mcg Once Daily Delivered Via the Respimat® Inhaler Compared to Placebo and Salmeterol HydroFluoroAlkane (HFA) Metered Dose Inhaler (MDI) (50 mcg Twice Daily) in Patient With Moderate Persistent Asthma I

Asthma Clinical Trial

Official title:

A Phase III Randomised, Double-blind, Placebo-controlled, Parallel-group Trial to Evaluate Efficacy and Safety of Tiotropium Inhalation Solution Delivered Via Respimat® Inhaler (2.5 and 5 µg Once Daily) Compared With Placebo and Salmeterol HFA MDI (50 µg Twice Daily) Over 24 Weeks in Moderate Persistent Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01172808
• Other study ID #: 205.418
• Secondary ID: 2009-018004-18
• Status: Completed
• Phase: Phase 3
• First received: July 26, 2010
• Last updated: June 3, 2014
• Start date: August 2010
• Est. completion date: November 2012

Study information

• Verified date: January 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: National Health Surveillance AgencyChina: Food and Drug AdministrationGuatemala: Ministry of Public Health and Social AssistanceIndia: Drugs Controller General of IndiaJapan: Ministry of Health, Labor and WelfareLatvia: State Agency of MedicinesMexico: Federal Commission for Protection Against Health RisksPeru: General Directorate of Pharmaceuticals, Devices, and DrugsPoland: Registration Medicinal Product Medical Device Biocidal ProductRussia: Pharmacological Committee, Ministry of HealthUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The aim of this trial is to evaluate the efficacy and safety of 2.5 and 5 mcg tiotropium over a 24-week treatment period as compared to placebo and salmeterol (50 mcg twice daily). Tiotropium inhalation solution delivered by the Respimat® inhaler will be examined on top of maintenance treatment with inhaled corticosteroid controller medication in patients with moderate persistent asthma. Efficacy and safety will be assessed by measuring effects on lung function, effects on asthma exacerbations, effects on quality of life, effects on asthma control, effects on health care resource utilisation, and number of adverse events.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1071
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion criteria:

1. All patients must sign and date an Informed Consent Form consistent with International Conference on Harmonisation - Good Clinical Practice (ICH-GCP) guidelines and local legislation prior to participation in the trial (i.e. prior to any trial procedures, including any pre-trial washout of medications and medication restrictions for pulmonary function test at Visit 1).

2. Male or female patients aged at least 18 years but not more than 75 years.

3. All patients must have at least a 3 month history of asthma at the time of enrolment into the trial. The diagnosis should be confirmed at Visit 1 by fulfilling inclusion criterion 5.

4. The initial diagnosis of asthma must have been made before the patient's age of 40.

5. The diagnosis of asthma has to be confirmed at Visit 1 with a bronchodilator reversibility (15 minutes after 400 mcg salbutamol (albuterol)) resulting in a Forced Expiratory Volume in one second (FEV1) increase of at least 12% and at least 200mL.

6. All patients must have been on maintenance treatment with a medium, stable dose of inhaled corticosteroids for at least for 4 weeks prior to Visit 1.

7. All patients must be symptomatic at Visit 1 (screening) and prior to randomisation at Visit 2 as defined by an Asthma Control Questionnaire (ACQ) mean score of at least 1.5.

8. All patients must have a pre-bronchodilator FEV1 at least 60% and less than or equal to 90% of predicted normal at Visit 1.

9. Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator) as compared to Visit 2 (pre-dose) must be within ± 30%.

10. Patients must be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment (Visit 0) and who have a smoking history of less than 10 pack years.

11. Patients must be able to use the Respimat® inhaler and metered dose inhaler correctly.

12. Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of electronic diary/peak flow meter.

Exclusion criteria:

1. Patients with a significant disease other than asthma. A significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the trial, or (ii) influence the results of the trial, or (iii) cause concern regarding the patient's ability to participate in the trial.

2. Patients with a clinically relevant abnormal screening (Visit 1) haematology or blood chemistry if the abnormality defines a significant disease as defined in exclusion criterion 1.

3. Patients with a recent history (i.e. six months or less) of myocardial infarction.

4. Patients who have been hospitalised for cardiac failure during the past year.

5. Patients with any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year.

6. Patients with lung diseases other than asthma (e.g. Chronic Obstructive Pulmonary Disease (COPD)).

7. Patients with known active tuberculosis.

8. Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years. Patients with treated basal cell carcinoma are allowed.

9. Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion no. 1.

10. Patients with significant alcohol or drug abuse within the past two years.

11. Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the 6 weeks prior to Visit 1 (screening).

12. Patients with known hypersensitivity to anticholinergic drugs, benzalkonium chloride (BAC), ethylenediamineteraacetic acid (EDTA), salmeterol xinafoate or any other components of the study medication delivery systems.

13. Pregnant or nursing woman.

14. Women of childbearing potential not using a highly effective method of birth control.

15. Patients who have taken an investigational drug within four weeks prior to Visit 1.

16. Patients who have been treated with beta-blocker medication within four weeks prior to Visit 1 and/or during the screening period. Topical cardio-selective beta-blocker eye medications for non-narrow angle glaucoma are allowed.

17. Patients who have been treated with the long-acting anticholinergic tiotropium (Spiriva®) within four weeks prior to Visit 1 and/or during the screening period.

18. Patients who have been treated with oral or patch beta-adrenergics within four weeks prior to Visit 1 and/or during the Screening period.

19. Patients who have been treated with oral corticosteroids within four weeks prior to Visit 1 and/or during the screening period.

20. Patients who have been treated with anti-IgE antibodies, e.g. omalizumab (Xolair®), within 6 months prior to Visit 1 and/or during the screening period.

21. Patients who have been treated with cromone within two weeks prior to Visit 1 and/or during the screening period.

22. Patients who have been treated with methylxanthines or phosphodiesterase 4 inhibitors within two weeks prior to Visit 1 and/or during the screening period.

23. Patients who have been treated with other non-approved and according to international guidelines not recommended "experimental" drugs for routine asthma therapy within four weeks prior to Visit 1 and/or during the screening period.

24. Patients with any asthma exacerbation or any respiratory tract infection iin the four weeks prior to Visit 1 and/or during the screening period.

25. Patients who have previously been randomised in this trial or in the respective twin trial (205.419) or are currently participating in another trial.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Placebo
Placebo that represents comparator
• tiotropium Respimat® low dose
IMP
• Placebo
Placebo that represents comparator
• Placebo
Placebo that represents comparator
• tiotropium Respimat® high dose
IMP
• 50 mcg salmeterol HFA MDI
Active comparator
• Placebo
Placebo that represents BI drug
• Placebo
Placebo that represents BI drug

Locations

Country	Name	City	State
Brazil	205.418.55002 Boehringer Ingelheim Investigational Site	Juiz de Fora
Brazil	205.418.55001 Boehringer Ingelheim Investigational Site	Porto Alegre
Brazil	205.418.55004 Boehringer Ingelheim Investigational Site	Porto Alegre
Brazil	205.418.55005 Boehringer Ingelheim Investigational Site	Porto Alegre
Brazil	205.418.55003 Boehringer Ingelheim Investigational Site	Rio de Janeiro - RJ
China	205.418.86001 Boehringer Ingelheim Investigational Site	Beijing
China	205.418.86005 Boehringer Ingelheim Investigational Site	Beijing
China	205.418.86007 Boehringer Ingelheim Investigational Site	Beijing
China	205.418.86012 Boehringer Ingelheim Investigational Site	Beijing
China	205.418.86014 Boehringer Ingelheim Investigational Site	Changsha
China	205.418.86011 Boehringer Ingelheim Investigational Site	Chengdu
China	205.418.86015 Boehringer Ingelheim Investigational Site	Chengdu
China	205.418.86003 Boehringer Ingelheim Investigational Site	Chongqing
China	205.418.86010 Boehringer Ingelheim Investigational Site	Guangzhou
China	205.418.86013 Boehringer Ingelheim Investigational Site	Kunming
China	205.418.86008 Boehringer Ingelheim Investigational Site	Qingdao
China	205.418.86002 Boehringer Ingelheim Investigational Site	Shanghai
China	205.418.86004 Boehringer Ingelheim Investigational Site	Shenyang
China	205.418.86009 Boehringer Ingelheim Investigational Site	Shenyang
China	205.418.86006 Boehringer Ingelheim Investigational Site	Xi'An
Guatemala	205.418.50203 Boehringer Ingelheim Investigational Site	Guatelama City
Guatemala	205.418.50204 Boehringer Ingelheim Investigational Site	Guatelmala city
Guatemala	205.418.50205 Boehringer Ingelheim Investigational Site	Guatelmala City
Guatemala	205.418.50201 Boehringer Ingelheim Investigational Site	Guatemala City
Guatemala	205.418.50202 Boehringer Ingelheim Investigational Site	Guatemala city
India	205.418.91008 Boehringer Ingelheim Investigational Site	Banglore
India	205.418.91005 Boehringer Ingelheim Investigational Site	Chennai
India	205.418.91004 Boehringer Ingelheim Investigational Site	Coimbatore
India	205.418.91006 Boehringer Ingelheim Investigational Site	Coimbatore
India	205.418.91003 Boehringer Ingelheim Investigational Site	Hyderabad
India	205.418.91009 Boehringer Ingelheim Investigational Site	Jaipur
India	205.418.91002 Boehringer Ingelheim Investigational Site	Nagpur
India	205.418.91007 Boehringer Ingelheim Investigational Site	Pune
India	205.418.91010 Boehringer Ingelheim Investigational Site	Pune
Japan	205.418.81018 Boehringer Ingelheim Investigational Site	Adachi-ku, Tokyo
Japan	205.418.81030 Boehringer Ingelheim Investigational Site	Ako, Hyogo
Japan	205.418.81001 Boehringer Ingelheim Investigational Site	Chiyoda-ku, Tokyo
Japan	205.418.81005 Boehringer Ingelheim Investigational Site	Chuo-ku, Tokyo
Japan	205.418.81025 Boehringer Ingelheim Investigational Site	Chuo-ku, Tokyo
Japan	205.418.81015 Boehringer Ingelheim Investigational Site	Fujioka, Gunma
Japan	205.418.81023 Boehringer Ingelheim Investigational Site	Himeji, Hyogo
Japan	205.418.81007 Boehringer Ingelheim Investigational Site	Hitachi, Ibaraki
Japan	205.418.81009 Boehringer Ingelheim Investigational Site	Iwamizawa, Hokkaido
Japan	205.418.81028 Boehringer Ingelheim Investigational Site	Kanazawa, Ishikawa
Japan	205.418.81011 Boehringer Ingelheim Investigational Site	Kitakami, Iwate
Japan	205.418.81012 Boehringer Ingelheim Investigational Site	Kitakami, Iwate
Japan	205.418.81031 Boehringer Ingelheim Investigational Site	Koga, Ibaraki
Japan	205.418.81016 Boehringer Ingelheim Investigational Site	Koganei, Tokyo
Japan	205.418.81006 Boehringer Ingelheim Investigational Site	Komaki, Aichi
Japan	205.418.81002 Boehringer Ingelheim Investigational Site	Kunitachi, Tokyo
Japan	205.418.81004 Boehringer Ingelheim Investigational Site	Mito, Ibaraki
Japan	205.418.81032 Boehringer Ingelheim Investigational Site	Osaka, Osaka
Japan	205.418.81019 Boehringer Ingelheim Investigational Site	Ota-ku, Tokyo
Japan	205.418.81008 Boehringer Ingelheim Investigational Site	Sapporo, Hokkaido
Japan	205.418.81013 Boehringer Ingelheim Investigational Site	Sendai, Miyagi
Japan	205.418.81014 Boehringer Ingelheim Investigational Site	Sendai, Miyagi
Japan	205.418.81026 Boehringer Ingelheim Investigational Site	Setagaya-ku, Tokyo
Japan	205.418.81024 Boehringer Ingelheim Investigational Site	Takasaki, Gunma
Japan	205.418.81010 Boehringer Ingelheim Investigational Site	Tomakomai, Hokkaido
Japan	205.418.81003 Boehringer Ingelheim Investigational Site	Toshima-ku, Tokyo
Japan	205.418.81017 Boehringer Ingelheim Investigational Site	Toshima-ku, Tokyo
Japan	205.418.81022 Boehringer Ingelheim Investigational Site	Yao, Osaka
Japan	205.418.81020 Boehringer Ingelheim Investigational Site	Yokohama, Kanagawa
Japan	205.418.81021 Boehringer Ingelheim Investigational Site	Yokohama, Kanagawa
Latvia	205.418.37004 Boehringer Ingelheim Investigational Site	Daugavpils
Latvia	205.418.37008 Boehringer Ingelheim Investigational Site	Preili
Latvia	205.418.37001 Boehringer Ingelheim Investigational Site	Riga
Latvia	205.418.37002 Boehringer Ingelheim Investigational Site	Riga
Latvia	205.418.37005 Boehringer Ingelheim Investigational Site	Riga
Latvia	205.418.37006 Boehringer Ingelheim Investigational Site	Riga
Latvia	205.418.37007 Boehringer Ingelheim Investigational Site	Riga
Latvia	205.418.37009 Boehringer Ingelheim Investigational Site	Riga
Latvia	205.418.37003 Boehringer Ingelheim Investigational Site	Ventspils
Mexico	205.418.52002 Boehringer Ingelheim Investigational Site	Monterrey
Mexico	205.418.52003 Boehringer Ingelheim Investigational Site	Zapopan
Mexico	205.418.52001 Boehringer Ingelheim Investigational Site	Zona Río
Peru	205.418.51003 Boehringer Ingelheim Investigational Site	Callao
Peru	205.418.51001 Boehringer Ingelheim Investigational Site	Lima
Peru	205.418.51002 Boehringer Ingelheim Investigational Site	Lima
Poland	205.418.48006 Boehringer Ingelheim Investigational Site	Krakow
Poland	205.418.48001 Boehringer Ingelheim Investigational Site	Lodz
Poland	205.418.48005 Boehringer Ingelheim Investigational Site	Lodz
Poland	205.418.48002 Boehringer Ingelheim Investigational Site	Ostrow Wielkopolska
Poland	205.418.48004 Boehringer Ingelheim Investigational Site	Poznan
Poland	205.418.48003 Boehringer Ingelheim Investigational Site	Tczew
Russian Federation	205.418.07007 Boehringer Ingelheim Investigational Site	Gatchina (Leningradskaya oblast)
Russian Federation	205.418.07004 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	205.418.07005 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	205.418.07006 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	205.418.07008 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	205.418.07001 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	205.418.07002 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	205.418.07003 Boehringer Ingelheim Investigational Site	St. Petersburg
United States	205.418.01012 Boehringer Ingelheim Investigational Site	Baltimore	Maryland
United States	205.418.01006 Boehringer Ingelheim Investigational Site	Bellevue	Nebraska
United States	205.418.01016 Boehringer Ingelheim Investigational Site	Boys Town	Nebraska
United States	205.418.01005 Boehringer Ingelheim Investigational Site	Charleston	South Carolina
United States	205.418.01004 Boehringer Ingelheim Investigational Site	Coeur d'Alene	Idaho
United States	205.418.01007 Boehringer Ingelheim Investigational Site	Dallas	Texas
United States	205.418.01010 Boehringer Ingelheim Investigational Site	Easely	South Carolina
United States	205.418.01020 Boehringer Ingelheim Investigational Site	Huntington Beach	California
United States	205.418.01009 Boehringer Ingelheim Investigational Site	Minneapolis	Minnesota
United States	205.418.01002 Boehringer Ingelheim Investigational Site	Mission Viejo	California
United States	205.418.01017 Boehringer Ingelheim Investigational Site	Normal	Illinois
United States	205.418.01013 Boehringer Ingelheim Investigational Site	North Dartmouth	Massachusetts
United States	205.418.01015 Boehringer Ingelheim Investigational Site	North Dartmouth	Massachusetts
United States	205.418.01018 Boehringer Ingelheim Investigational Site	Oklahoma City	Oklahoma
United States	205.418.01003 Boehringer Ingelheim Investigational Site	Omaha	Nebraska
United States	205.418.01014 Boehringer Ingelheim Investigational Site	San Diego	California
United States	205.418.01019 Boehringer Ingelheim Investigational Site	Seattle	Washington
United States	205.418.01008 Boehringer Ingelheim Investigational Site	South Bend	Indiana
United States	205.418.01001 Boehringer Ingelheim Investigational Site	Tacoma	Washington
United States	205.418.01011 Boehringer Ingelheim Investigational Site	Wheat Ridge	Colorado
United States	205.418.01021 Boehringer Ingelheim Investigational Site	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Boehringer Ingelheim	Pfizer

Countries where clinical trial is conducted

United States,  Brazil,  China,  Guatemala,  India,  Japan,  Latvia,  Mexico,  Peru,  Poland,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak FEV1 Within 3 Hours Post-dose Response	Peak forced expiratory volume in one second (FEV1) response within 3 hours post-dose determined at the end of the 24-week treatment. Response was defined as change from baseline (10 minutes before the first dose of trial medication at visit 2). Means are adjusted for treatment, centre, week, baseline, treatment by week, and baseline by week.	24 weeks	No
Primary	Trough FEV1 Response	Trough FEV1 response determined at the end of the 24-week treatment. Response was defined as change from baseline (10 minutes before the first dose of trial medication at visit 2). Means are adjusted for treatment, centre, week, baseline, treatment by week, and baseline by week.	24 weeks	No
Primary	The Responder Rate as Assessed by the ACQ From the Two Twin Trials 205.419 (NCT01172821) and the Present 205.418 (NCT01172808)	The responder rate as assessed by the Asthma Control Questionnaire (ACQ) determined at the end of the 24-week treatment period (on combined data from the two twin trials 205.418 (NCT01172808) and 205.419 (NCT01172821)). A patient was considered to be a responder if he or she was reported with an improvement (decrease) in the ACQ total score of at least 0.5 points.; The ACQ total score was calculated as the mean of the responses to 7 questions and was analysed as an absolute value. The score ranges from 0 (no impairment) to 6 (maximum impairment).	24 weeks	No
Secondary	Peak FVC Within 3 Hours Post-dose Response	Peak forced vital capacity (FVC) response within 3 hours post-dose determined at the end of the 24-week treatment. Response was defined as change from baseline (10 minutes before the first dose of trial medication at visit 2). Means are adjusted for treatment, centre, week, baseline, treatment by week, and baseline by week.	24 weeks	No
Secondary	Trough FVC Response	Trough FVC response determined at the end of the 24-week treatment. Response was defined as change from baseline (10 minutes before the first dose of trial medication at visit 2). Means are adjusted for treatment, country, week, baseline, treatment by week, and baseline by week.	24 weeks	No
Secondary	FEV1 Area Under Curve 0-3 Hours (AUC0-3h) Response	Response was defined as change from baseline (10 minutes before the first dose of trial medication at visit 2) determined at the end of the 24-week treatment. Means are adjusted for treatment, centre, week, baseline, treatment by week, and baseline by week. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.	24 weeks	No
Secondary	FVC Area Under Curve 0-3 Hours (AUC0-3h) Response	Response was defined as change from baseline (10 minutes before the first dose of trial medication at visit 2) determined at the end of the 24-week treatment. Means are adjusted for treatment, country, week, baseline, treatment by week, and baseline by week. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.	24 weeks	No
Secondary	Trough PEF Response	Trough peak expiratory flow (PEF) response determined at the end of the 24-week treatment. Response was defined as change from baseline (10 minutes before the first dose of trial medication at visit 2). Means are adjusted for treatment, centre, week, baseline, treatment by week, and baseline by week.	24 weeks	No
Secondary	Total Asthma Quality of Life Questionnaire (AQLQs)) Score	Total score from the Standardised Asthma Quality of Life Questionnaire (AQLQ(s)) determined at the end of 24-week treatment. The AQLQ(s) contains 32 questions, each question has a 7 point scale from 1 (highest intensity) till 7 (no symptoms). Total score was defined as the sum of all items divided by the number of items. Means are adjusted for treatment, centre, week, baseline, treatment by week, and baseline by week.	24 weeks	No
Secondary	Total Asthma Control Questionnaire (ACQ) Score at the End of the 24-week Treatment Period	Control of asthma as assessed by the ACQ determined at the end of 24-week treatment. The ACQ contains 7 questions, each question has a 7 point scale from 0 (no symptoms) till 6 (highest intensity). Total score was defined as the sum of all items divided by the number of items. Means are adjusted for treatment, centre, week, baseline, treatment by week, and baseline by week.	24 weeks	No
Secondary	The Responder Rate as Assessed by the ACQ	The responder rate as assessed by the Asthma Control Questionnaire (ACQ) determined at the end of the 24-week treatment period. A patient was considered to be a responder if he or she was reported with an improvement (decrease) in ACQ total score of at least 0.5 points. The ACQ total score was calculated as the mean of the responses to 7 questions and was analysed as an absolute value. The score ranges from 0 (no impairment) to 6 (maximum impairment).	24 weeks	No
Secondary	Mean Pre-dose Morning PEF (PEF a.m.) Based on the Weekly Mean Response at Week 24	Weekly means obtained during the last 7 days before week 24 measured by patients at home using the AM3 device. Response was defined as change from baseline. Means are adjusted for treatment, country, week, baseline, treatment by week, and baseline by week.	Baseline and last 7 days before week 24 visit	No
Secondary	Mean Pre-dose Evening PEF (PEF p.m.) Based on the Weekly Mean Response at Week 24	Weekly means obtained during the last 7 days before week 24 measured by patients at home using the AM3 device. Response was defined as change from baseline. Means are adjusted for treatment, country, week, baseline, treatment by week, and baseline by week.	Baseline and last 7 days before week 24 visit	No
Secondary	PEF Variability	PEF daily variability was assesed by patients at home using the AM3 device. PEF variability is the absolute difference between morning and evening PEF value divided by their mean, based on the weekly mean response at week 24. Means are adjusted for treatment, centre, week, baseline, treatment by week, and baseline by week.	Last 7 days before week 24 visit	No
Secondary	Mean Pre-dose Morning FEV1 (FEV1 a.m.) Based on the Weekly Mean Response at Week 24	Weekly means obtained during the last 7 days before week 24 measured by patients at home using the AM3 device. Response was defined as change from baseline. Means are adjusted for treatment, country, week, baseline, treatment by week, and baseline by week.	Baseline and last 7 days before week 24 visit	No
Secondary	Mean Pre-dose Evening FEV1 (FEV1 p.m.) Based on the Weekly Mean Response at Week 24	Weekly means obtained during the last 7 days before week 24 measured by patients at home using the AM3 device. Response was defined as change from baseline. Means are adjusted for treatment, country, week, baseline, treatment by week, and baseline by week.	Baseline and last 7 days before week 24 visit	No
Secondary	Mean Number of Puffs of Rescue Medication During the Entire 24-h Day Based on the Weekly Mean Response at Week 24	Daily use of salbutamol (albuterol) rescue medication as needed during the entire study period. Weekly means obtained during the last 7 days before week 24 measured by patients at home using the AM3 device. Response was defined as change from baseline. Means are adjusted for treatment, country, week, baseline, treatment by week, and baseline by week.	Baseline and last 7 days before week 24 visit	No
Secondary	Asthma Symptom-free Days Based on the Weekly Mean Response at Week 24	Weekly means obtained during the last 7 days before week 24 measured by patients at home using the AM3 device. Response was defined as change from baseline. Means are adjusted for treatment, country, week, baseline, treatment by week, and baseline by week. An asthma symptom-free day was defined as a day with no reported symptoms and no use of rescue medication.	Baseline and last 7 days before week 24 visit	No
Secondary	Time to First Severe Asthma Exacerbation From the Two Twin Trials 205.419 (NCT01172821) and the Present 205.418 (NCT01172808)	Time to first severe asthma exacerbation during the 24-week treatment period on combined data from the two twin trials 205.418 (NCT01172808) and 205.419 (NCT01172821).	24 weeks	No
Secondary	Time to First Asthma Exacerbation From the Two Twin Trials 205.419 (NCT01172821) and the Present 205.418 (NCT01172808)	Time to first asthma exacerbation (including severe, non-severe; symptomatic, asymptomatic; i.e. any exacerbation) during the 24-week treatment period on combined data from the two twin trials 205.418 (NCT01172808) and 205.419 (NCT01172821)	24 weeks	No

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