Evaluation of Tiotropium 5 µg/Day Delivered Via the Respimat® Inhaler Over 48 Weeks in Patients With Severe Persistent Asthma on Top of Usual Care (Study 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 (5 mcg/Day) Over 48 Weeks as add-on Controller Therapy on Top of Usual Care in Patients With Severe Persistent Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00772538
• Other study ID #: 205.416
• Secondary ID: 2008-001413-14
• Status: Completed
• Phase: Phase 3
• First received: October 13, 2008
• Last updated: July 30, 2014
• Start date: October 2008

Study information

• Verified date: July 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Dept of Health and Ageing Therapeutic Goods AdminCanada: Health CanadaDenmark: The Danish Medicines AgencyGermany: Federal Institute for Drugs and Medical DevicesGreat Britain: MHRAItaly: Ethics CommitteeJapan: Ministry of Health, Labor and WelfareNetherlands: Central Committee on Research Involving Human Subjects (CCMO)Russia: Ministry of Health Care and Social Progress of Russian FederationSerbia: Medicines and Medical Devices Agency of Serbia, 11152 BelgradeSouth Africa: Medicines Control CouncilTurkey: Ministry of Health Central Ethics CommitteeUkraine: Ministry of Health Care of Ukraine (MoH of Ukraine)United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The trial is a randomised, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of 5 µg tiotropium over a 48-week treatment period as compared to placebo. Tiotropium inhalation solution delivered by the Respimat® inhaler will be examined as add-on controller therapy on top of usual care in patients with severe persistent asthma.

The primary objective of each trial is to evaluate the long term efficacy of tiotropium over placebo on top of usual care in patients with severe persistent asthma as determined by pulmonary function testing, effects on asthma exacerbations, effects on quality of life, on asthma control and health care resource utilisation. The secondary objective of each trial is to compare the long term safety of tiotropium with placebo in this patient population.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 459
• Est. primary completion date: July 2011
• 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 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 5-year history of asthma at the time of enrolment into the trial and the diagnosis of asthma must have been made before the patient´s age of 40.

4. All patients must have a diagnosis of severe persistent asthma and must be symptomatic despite treatment with high, stable doses of inhaled corticosteroids and a long-acting beta adrenergic agent

5. All patients must have a history of one or more asthma exacerbation in the past year.

6. Patients must have evidence of treated, severe, persistent asthma in postbronchodilatory pulmonary function tests.

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

8. Patients must be able to use the Respimat® inhaler correctly

9. Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of the 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 clinically relevant abnormal screening haematology or blood chemistry.

3. Patients with a recent history (i.e. six months or less) of myocardial infarction, hospitalisation for cardiac failure during the past year, any unstable or life threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year, known active tuberculosis, malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years (treated basal cell carcinoma allowed), lung diseases other than asthma (e.g. COPD), significant alcohol or drug abuse within the past two years, 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.

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

5. Patients using oral corticosteroid medication at stable doses exceeding 5 mg prednisolone or prednisolone equivalent every day or 10 mg prednisolone or prednisolone equivalent every second day.

6. Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other components of the tiotropium inhalation solution.

7. Pregnant or nursing women or women of childbearing potential not using a highly effective method of birth control. Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation/salpingectomy, or post-menopausal for at least two years.

8. Patients who have taken an investigational drug within four weeks or six half-lives (whichever is greater) prior to Visit 1.

9. Patients who have been treated with the long-acting anticholinergic tiotropium (Spiriva®), beta-blocker medication, oral beta-adrenergics, other non-approved and according to international guidelines not recommended ´experimental´ drugs for routine asthma therapy (e.g. TNF-alpha blockers, methotrexate, cyclosporin) within four weeks prior to the Screening Visit (Visit 1) or during the screening period.

10. Patients with any asthma exacerbation or respiratory tract infection in the four weeks prior to the trial.

11. Patients who have previously been randomised in this trial or in the respective twin trial (205.416 versus 205.417) or are currently participating in another trial.

12. Patients with a known narrow-angle glaucoma.

Note:

As with other anticholinergic drugs, tiotropium should be used with caution in patients with prostatic hyperplasia or bladder neck obstruction.

As with all predominantly renally excreted drugs, patients with moderate to severe renal impairment (known creatinine clearance of <= 50 mL/min) treated with tiotropium should be monitored closely.

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:
• tiotropium 5mcg/day
Intervention = randomisation: Patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo
• placebo
Matching placebo

Locations

Country	Name	City	State
Australia	205.416.61001 Boehringer Ingelheim Investigational Site	Daw Park	South Australia
Australia	205.416.61003 Boehringer Ingelheim Investigational Site	Nedlands	Western Australia
Australia	205.416.61002 Boehringer Ingelheim Investigational Site	Woodville	South Australia
Canada	205.416.02002 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	205.416.02003 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	205.416.02004 Boehringer Ingelheim Investigational Site	Quebec
Canada	205.416.02001 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Denmark	205.416.45001 Boehringer Ingelheim Investigational Site	Hvidovre
Denmark	205.416.45002 Boehringer Ingelheim Investigational Site	Odense C
Germany	205.416.49002 Boehringer Ingelheim Investigational Site	Berlin
Germany	205.416.49003 Boehringer Ingelheim Investigational Site	Gelnhausen
Germany	205.416.49005 Boehringer Ingelheim Investigational Site	Koblenz
Germany	205.416.49004 Boehringer Ingelheim Investigational Site	Oschersleben
Italy	205.416.39001 Boehringer Ingelheim Investigational Site	Pisa
Italy	205.416.39002 Boehringer Ingelheim Investigational Site	Sesto S. Giovanni (MI)
Japan	205.416.81007 Boehringer Ingelheim Investigational Site	Hachioji, Tokyo
Japan	205.416.81004 Boehringer Ingelheim Investigational Site	Inashiki-gun, Ibaraki
Japan	205.416.81006 Boehringer Ingelheim Investigational Site	Kamogawa, Chiba
Japan	205.416.81012 Boehringer Ingelheim Investigational Site	Maebashi, Gunma
Japan	205.416.81008 Boehringer Ingelheim Investigational Site	Minato-ku, Tokyo
Japan	205.416.81009 Boehringer Ingelheim Investigational Site	Minato-ku, Tokyo
Japan	205.416.81001 Boehringer Ingelheim Investigational Site	Naka-gun, Ibaraki
Japan	205.416.81014 Boehringer Ingelheim Investigational Site	Noda, Chiba
Japan	205.416.81015 Boehringer Ingelheim Investigational Site	Sapporo, Hokkaido
Japan	205.416.81016 Boehringer Ingelheim Investigational Site	Sapporo, Hokkaido
Japan	205.416.81002 Boehringer Ingelheim Investigational Site	Sendai, Miyagi
Japan	205.416.81010 Boehringer Ingelheim Investigational Site	shinagawa-ku, Tokyo
Japan	205.416.81005 Boehringer Ingelheim Investigational Site	Tsukuba, Ibaraki
Japan	205.416.81011 Boehringer Ingelheim Investigational Site	Yokohama, Kanagawa
Japan	205.416.81003 Boehringer Ingelheim Investigational Site	Yonezawa, Yamagata
Netherlands	205.416.31005 Boehringer Ingelheim Investigational Site	Breda
Netherlands	205.416.31001 Boehringer Ingelheim Investigational Site	Groningen
Netherlands	205.416.31004 Boehringer Ingelheim Investigational Site	Helmond
Netherlands	205.416.31003 Boehringer Ingelheim Investigational Site	Zutphen
Russian Federation	205.416.07001 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	205.416.07002 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	205.416.07003 Boehringer Ingelheim Investigational Site	Reutov - Moscow region
Serbia	205.416.38101 Boehringer Ingelheim Investigational Site	Belgrade
Serbia	205.416.38102 Boehringer Ingelheim Investigational Site	Kragujevac
Serbia	205.416.38103 Boehringer Ingelheim Investigational Site	Zemun
South Africa	205.416.27001 Boehringer Ingelheim Investigational Site	Cape Town
South Africa	205.416.27002 Boehringer Ingelheim Investigational Site	Durban
South Africa	205.416.27003 Boehringer Ingelheim Investigational Site	Durban
South Africa	205.416.27004 Boehringer Ingelheim Investigational Site	Pretoria
Turkey	205.416.90001 Boehringer Ingelheim Investigational Site	Istanbul
Turkey	205.416.90002 Boehringer Ingelheim Investigational Site	Izmir
Ukraine	205.416.38002 Boehringer Ingelheim Investigational Site	Kharkov
Ukraine	205.416.38001 Boehringer Ingelheim Investigational Site	Kiev
Ukraine	205.416.38003 Boehringer Ingelheim Investigational Site	Vinnytsya
United Kingdom	205.416.44003 Boehringer Ingelheim Investigational Site	Brighton
United Kingdom	205.416.44002 Boehringer Ingelheim Investigational Site	Leicester
United Kingdom	205.416.44004 Boehringer Ingelheim Investigational Site	Nottingham
United Kingdom	205.416.44005 Boehringer Ingelheim Investigational Site	Nottingham
United States	205.416.01007 Boehringer Ingelheim Investigational Site	Birmingham	Alabama
United States	205.416.01021 Boehringer Ingelheim Investigational Site	Boys Town	Nebraska
United States	205.416.01011 Boehringer Ingelheim Investigational Site	Cherry Hill	New Jersey
United States	205.416.01001 Boehringer Ingelheim Investigational Site	Cincinnati	Ohio
United States	205.416.01022 Boehringer Ingelheim Investigational Site	Columbia	Missouri
United States	205.416.01019 Boehringer Ingelheim Investigational Site	El Paso	Texas
United States	205.416.01002 Boehringer Ingelheim Investigational Site	Elk Grove Village	Illinois
United States	205.416.01017 Boehringer Ingelheim Investigational Site	Lake Oswego	Oregon
United States	205.416.01003 Boehringer Ingelheim Investigational Site	Lexington	Kentucky
United States	205.416.01012 Boehringer Ingelheim Investigational Site	Los Angeles	California
United States	205.416.01018 Boehringer Ingelheim Investigational Site	Los Angeles	California
United States	205.416.01025 Boehringer Ingelheim Investigational Site	North Dartmouth	Massachusetts
United States	205.416.01024 Boehringer Ingelheim Investigational Site	Oklahoma City	Oklahoma
United States	205.416.01009 Boehringer Ingelheim Investigational Site	Richmond	Virginia
United States	205.416.01016 Boehringer Ingelheim Investigational Site	Riverside	California
United States	205.416.01008 Boehringer Ingelheim Investigational Site	San Diego	California
United States	205.416.01010 Boehringer Ingelheim Investigational Site	Stamford	Connecticut
United States	205.416.01023 Boehringer Ingelheim Investigational Site	Tallahassee	Florida
United States	205.416.01004 Boehringer Ingelheim Investigational Site	Walnut Creek	California
United States	205.416.01014 Boehringer Ingelheim Investigational Site	Wheaton	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Boehringer Ingelheim	Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Denmark,  Germany,  Italy,  Japan,  Netherlands,  Russian Federation,  Serbia,  South Africa,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak Forced Expiratory Volume in 1 Second (FEV1) Response Within 3 Hours Post Dosing (0-3h) After a Treatment Period of 24 Weeks.	Peak FEV1 0-3h response was defined as the difference between the maximum FEV1 measured within the first 3 hours post dosing after a treatment period of 24 weeks and the FEV1 baseline measurement (10 minutes before the first dose of trial medication). Mixed Model Repeated Measure (MMRM) results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit and baseline*visit.	Baseline and 24 weeks	No
Primary	Trough FEV1 Response Determined After a Treatment Period of 24 Weeks.	The trough FEV1 is defined as the pre-dose FEV1 measured 10 minutes before the last administration of randomised treatment. Trough FEV1 response was defined as the difference between the trough FEV1 measured after a treatment period of 24 weeks and the FEV1 baseline measurement. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit and baseline*visit.	Baseline and 24 weeks	No
Primary	Time to First Severe Asthma Exacerbation During the 48-week Treatment of the Pooled Data From the Two Twin Trials 205.416 (NCT00772538) and the Present 205.417 (NCT00776984).	Severe asthma exacerbations were pre-defined as all asthma exacerbations that required treatment with systemic (including oral) corticosteroids for at least 3 days or (in case of ongoing and pre-existing systemic corticosteroid therapy) that required at least a doubling of the previous daily dose of systemic corticosteroids for at least 3 days.	48 weeks	No
Secondary	Peak (Within 3 Hours Post-dosing) Forced Vital Capacity (FVC) Response at the End of the 24-week Treatment Period.	Peak FVC 0-3h response was defined as the difference between the maximum FVC measured within the first 3 hours post dosing after a treatment period of 24 weeks and the FVC baseline measurement (10 minutes before the first dose of trial medication). Mixed Model Repeated Measure (MMRM) results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit and baseline*visit.	Baseline and 24 weeks	No
Secondary	Trough FVC Response at the End of the 24-week Treatment Period.	The trough FVC is defined as the pre-dose FVC measured 10 minutes before the last administration of randomised treatment. Trough FVC response was defined as the difference between the trough FVC measured after a treatment period of 24 weeks and the FVC baseline measurement. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit and baseline*visit.	Baseline and 24 weeks	No
Secondary	FEV1 Area Under the Curve (AUC0-3h) Response at the End of the 24-week Treatment Period.	The AUC0-3h was calculated as area under the curve from zero to 3 hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. The trough value was assigned to zero time. Response was defined as change from baseline in FEV1 AUC0-3h after a treatment period of 24 weeks. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit baseline*visit.	Baseline and 24 weeks	No
Secondary	FVC (AUC0-3h) Response at the End of the 24-week Treatment Period.	The AUC0-3h was calculated as area under the curve from zero to 3 hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. The trough value was assigned to zero time. Response was defined as change from baseline in FVC AUC0-3h after a treatment period of 24 weeks. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit baseline*visit.	Baseline and 24 weeks	No
Secondary	Peak FEV1 0-3h Response at the End of the 48-week Treatment Period.	Peak FEV1 0-3h response was defined as the difference between the maximum FEV1 measured within the first 3 hours post dosing after a treatment period of 48 weeks and the FEV1 baseline measurement (10 minutes before the first dose of trial medication). Mixed Model Repeated Measure (MMRM) results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit and baseline*visit.	Baseline and 48 weeks	No
Secondary	Trough FEV1 Response at the End of the 48-week Treatment Period.	The trough FEV1 is defined as the pre-dose FEV1 measured 10 minutes before the last administration of randomised treatment. Trough FEV1 response was defined as the difference between the trough FEV1 measured after a treatment period of 48 weeks and the FEV1 baseline measurement. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit and baseline*visit.	Baseline and 48 weeks	No
Secondary	AUC0-3h FEV1 Response at the End of the 48-week Treatment Period.	The AUC0-3h was calculated as area under the curve from zero to 3 hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. The trough value was assigned to zero time. Response was defined as change from baseline in FEV1 AUC0-3h after a treatment period of 48 weeks. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit baseline*visit.	Baseline and 48 weeks	No
Secondary	Peak FVC 0-3h Response at the End of the 48-week Treatment Period.	Peak FVC 0-3h response was defined as the difference between the maximum FVC measured within the first 3 hours post dosing after a treatment period of 48 weeks and the FVC baseline measurement (10 minutes before the first dose of trial medication). MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit and baseline*visit.	Baseline and 48 weeks	No
Secondary	Trough FVC Response at the End of the 48-week Treatment Period.	The trough FVC is defined as the pre-dose FVC measured 10 minutes before the last administration of randomised treatment. Trough FVC response was defined as the difference between the trough FVC measured after a treatment period of 48 weeks and the FVC baseline measurement. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit and baseline*visit.	Baseline and 48 weeks	No
Secondary	FVC AUC0-3h Response at the End of the 48-week Treatment Period.	The AUC0-3h was calculated as area under the curve from zero to 3 hours using the trapezoidal rule divided by the observation time (3 hours) to report in litres. The trough value was assigned to zero time. Response was defined as change from baseline in FVC AUC0-3h after a treatment period of 48 weeks. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit baseline*visit.	Baseline and 48 weeks	No
Secondary	Mean Pre-dose Morning Peak Expiratory Flow (PEFa.m.) Response (Diary Data) of Last-7-days-before-week-24-visit .	Weekly means obtained during the last 7 days before week 24 visit were compared (measured by patients at home using the asthma monitor device). Response was defined as change from baseline. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit and baseline*visit.	Baseline and last 7 days before week 24 visit	No
Secondary	Mean Pre-dose Evening Peak Expiratory Flow (PEFp.m.) Response (Diary Data) of Last-7-days-before-week 24-visit.	Weekly means obtained during the last 7 days before week 24 visit were compared (measured by patients at home using the asthma monitor device). Response was defined as change from baseline. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit and baseline*visit.	Baseline and last 7 days before week 24 visit	No
Secondary	Mean Pre-dose FEV1 a.m. Response (Diary Data) of Last-7-days-before-week 24-visit.	Weekly means obtained during the last 7 days before week 24 visit were compared (measured by patients at home using the asthma monitor device). Response was defined as change from baseline. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit and baseline*visit.	Baseline and last 7 days before week 24 visit	No
Secondary	Mean Pre-dose FEV1-p.m.Response (Diary Data) of Last-7-days-before-week 24-visit.	Weekly means obtained during the last 7 days before week 24 visit were compared (measured by patients at home using the asthma monitor device). Response was defined as change from baseline. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit and baseline*visit.	Baseline and last 7 days before week 24 visit	No
Secondary	Mean PEF Variability Response (Absolute Difference Between Morning and Evening PEF Value Divided by Their Mean) of Last-7-days-before-week 24-visit.	Weekly means obtained during the last 7 days before week 24 visit were compared (measured by patients at home using the asthma monitor device). The PEF variability is the absolute difference between morning and evening PEF value divided by their mean, expressed as a percent. Response was defined as change from baseline. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit and baseline*visit.	Baseline and last 7 days before week 24 visit	No
Secondary	Time to First Severe Asthma Exacerbation During the 48-week Treatment.	Severe asthma exacerbations were pre-defined as all asthma exacerbations that required treatment with systemic (including oral) corticosteroids for at least 3 days or (in case of ongoing and pre-existing systemic corticosteroid therapy) that required at least a doubling of the previous daily dose of systemic corticosteroids for at least 3 days.	48 weeks	No
Secondary	Number of Asthma Exacerbations Per Patient During the 48-week Treatment Period.	Asthma exacerbations (including severe, non-severe; symptomatic, asymptomatic) were pre-defined as an episode of progressive increase in 1 or more asthma symptoms (e.g. shortness of breath, cough, wheezing, chest tightness or some combination of these symptoms). Additionally, decrease of patients best PEF a.m. of 30 percent or more from the patients mean PEF a.m. for at least 2 consecutive days was considered to be an objective marker of asthma exacerbation.	48 weeks	No
Secondary	Number of Severe Asthma Exacerbations Per Patient During the 48-week Treatment Period.	Severe asthma exacerbations were pre-defined as all asthma exacerbations that required treatment with systemic (including oral) corticosteroids for at least 3 days or (in case of ongoing and pre-existing systemic corticosteroid therapy) that required at least a doubling of the previous daily dose of systemic corticosteroids for at least 3 days.	48 weeks	No
Secondary	Number of Patients With at Least One Asthma Exacerbation During the 48-week Treatment Period.	Asthma exacerbations (including severe, non-severe; symptomatic, asymptomatic) were pre-defined as an episode of progressive increase in 1 or more asthma symptoms (e.g. shortness of breath, cough, wheezing, chest tightness or some combination of these symptoms). Additionally, decrease of patients best PEF a.m. of 30 percent or more from the patients mean PEF a.m. for at least 2 consecutive days was considered to be an objective marker of asthma exacerbation.	48 weeks	No
Secondary	Number of Patients With at Least One Severe Asthma Exacerbation During the 48-week Treatment Period.	Severe asthma exacerbations were pre-defined as all asthma exacerbations that required treatment with systemic (including oral) corticosteroids for at least 3 days or (in case of ongoing and pre-existing systemic corticosteroid therapy) that required at least a doubling of the previous daily dose of systemic corticosteroids for at least 3 days.	48 weeks	No
Secondary	Time to First Hospitalisation for Asthma Exacerbation During the 48-week Treatment Period.	Asthma exacerbations (including severe, non-severe; symptomatic, asymptomatic) were pre-defined as an episode of progressive increase in 1 or more asthma symptoms (e.g. shortness of breath, cough, wheezing, chest tightness or some combination of these symptoms). Additionally, decrease of patients best PEF a.m. of 30 percent or more from the patients mean PEF a.m. for at least 2 consecutive days was considered to be an objective marker of asthma exacerbation.	48 weeks	No
Secondary	Number of Hospitalisations for Asthma Exacerbations Per Patient During the 48-week Treatment Period.		48 weeks	No
Secondary	Number of Patients With at Least One Hospitalisation for Asthma Exacerbation During the 48-week Treatment Period.		48 weeks	No
Secondary	Quality of Life as Assessed by Standardised Asthma Quality of Life Questionnaire (AQLQ(S)) at the End of the 24-week Treatment Period.	The AQLQ(S) total score was calculated as the mean of the responses to 32 questions for the domains Symptoms, Activity Limitations, Emotional Function and Environmental Stimuli and was analysed as an absolute value. The AQLQ(S) total score ranges from 1 (worst controlled) to 7 (best). MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit and baseline*visit.	24 weeks	No
Secondary	AQLQ(S) Total Score at the End of the 48-week Treatment Period.	The AQLQ(S) total score was calculated as the mean of the responses to 32 questions for the domains Symptoms, Activity Limitations, Emotional Function and Environmental Stimuli and was analysed as an absolute value. The AQLQ(S) total score ranges from 1 (worst controlled) to 7 (best). MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit and baseline*visit.	48 weeks	No
Secondary	Asthma Control as Assessed by Asthma Control Questionnaire (ACQ) at the End of the 24-week Treatment Period.	For the ACQ, the 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). MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit and baseline*visit.	24 weeks	No
Secondary	ACQ at the End of the 48-week Treatment Period.	For the ACQ, the 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). MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit and baseline*visit.	48 weeks	No
Secondary	Asthma Symptom Free Days Response During the Last-7-days-before-week-24-visit .	Weekly means obtained during the last 7 days before week 24 visit were compared (measured by patients at home using the asthma monitor device). The response is defined as the change of the weekly mean from the baseline weekly mean. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit and baseline*visit.	Baseline and last 7 days before week 24 visit	No
Secondary	Mean Pro Re Nata (as Needed, PRN) Rescue Medication Use Response During the Last-7-days-before-week-24-visit .	Weekly means obtained during the last 7 days before week 24 visit were compared. The response is defined as the change of the weekly mean from the baseline weekly mean. The use of PRN salbutamol (albuterol rescue medication) is determined by the number of puffs of rescue therapy used per day. MMRM results. Means are adjusted for treatment, centre, visit, baseline, treatment*visit and baseline*visit.	Baseline and last 7 days before week 24 visit	No

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