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
- Conditions
- Asthma
- Interventions
- Drug: PlaceboDrug: 50 mcg salmeterol HFA MDIDrug: tiotropium Respimat® low doseDrug: tiotropium Respimat® high dose
- Registration Number
- NCT01172808
- Lead Sponsor
- Boehringer Ingelheim
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1071
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description tiotropium low dose Placebo Once daily, delivered with Respimat® inhaler (+ inhalation of placebo HFA MDI twice daily) tiotropium low dose tiotropium Respimat® low dose Once daily, delivered with Respimat® inhaler (+ inhalation of placebo HFA MDI twice daily) tiotropium high dose Placebo Once daily, delivered with Respimat® inhaler (+ inhalation of placebo HFA MDI twice daily) 50 mcg salmeterol 50 mcg salmeterol HFA MDI Twice daily, delivered with HFA MDI (+ inhalation of placebo Respimat® inhaler once daily) 50 mcg salmeterol Placebo Twice daily, delivered with HFA MDI (+ inhalation of placebo Respimat® inhaler once daily) placebo Placebo Once daily, delivered with Respimat® inhaler + twice daily delivered with HFA MDI tiotropium high dose tiotropium Respimat® high dose Once daily, delivered with Respimat® inhaler (+ inhalation of placebo HFA MDI twice daily)
- Primary Outcome Measures
Name Time Method Peak FEV1 Within 3 Hours Post-dose Response 24 weeks 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.
Trough FEV1 Response 24 weeks 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.
The Responder Rate as Assessed by the ACQ From the Two Twin Trials 205.419 (NCT01172821) and the Present 205.418 (NCT01172808) 24 weeks 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).
- Secondary Outcome Measures
Name Time Method Peak FVC Within 3 Hours Post-dose Response 24 weeks 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.
Trough FVC Response 24 weeks 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.
FEV1 Area Under Curve 0-3 Hours (AUC0-3h) Response 24 weeks 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.
FVC Area Under Curve 0-3 Hours (AUC0-3h) Response 24 weeks 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.
Trough PEF Response 24 weeks 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.
Total Asthma Quality of Life Questionnaire (AQLQs)) Score 24 weeks 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.
Total Asthma Control Questionnaire (ACQ) Score at the End of the 24-week Treatment Period 24 weeks 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.
The Responder Rate as Assessed by the ACQ 24 weeks 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).
Mean Pre-dose Morning PEF (PEF a.m.) Based on the Weekly Mean Response at Week 24 Baseline and last 7 days before week 24 visit 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.
Mean Pre-dose Evening PEF (PEF p.m.) Based on the Weekly Mean Response at Week 24 Baseline and last 7 days before week 24 visit 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.
PEF Variability Last 7 days before week 24 visit 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.
Mean Pre-dose Morning FEV1 (FEV1 a.m.) Based on the Weekly Mean Response at Week 24 Baseline and last 7 days before week 24 visit 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.
Mean Pre-dose Evening FEV1 (FEV1 p.m.) Based on the Weekly Mean Response at Week 24 Baseline and last 7 days before week 24 visit 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.
Mean Number of Puffs of Rescue Medication During the Entire 24-h Day Based on the Weekly Mean Response at Week 24 Baseline and last 7 days before week 24 visit 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.
Asthma Symptom-free Days Based on the Weekly Mean Response at Week 24 Baseline and last 7 days before week 24 visit 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.
Time to First Severe Asthma Exacerbation From the Two Twin Trials 205.419 (NCT01172821) and the Present 205.418 (NCT01172808) 24 weeks 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).
Time to First Asthma Exacerbation From the Two Twin Trials 205.419 (NCT01172821) and the Present 205.418 (NCT01172808) 24 weeks 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)
Trial Locations
- Locations (114)
205.418.55002 Boehringer Ingelheim Investigational Site
🇧🇷Juiz de Fora, Brazil
205.418.01004 Boehringer Ingelheim Investigational Site
🇺🇸Coeur d'Alene, Idaho, United States
205.418.01013 Boehringer Ingelheim Investigational Site
🇺🇸North Dartmouth, Massachusetts, United States
205.418.01006 Boehringer Ingelheim Investigational Site
🇺🇸Bellevue, Nebraska, United States
205.418.01015 Boehringer Ingelheim Investigational Site
🇺🇸North Dartmouth, Massachusetts, United States
205.418.01016 Boehringer Ingelheim Investigational Site
🇺🇸Boys Town, Nebraska, United States
205.418.01003 Boehringer Ingelheim Investigational Site
🇺🇸Omaha, Nebraska, United States
205.418.55003 Boehringer Ingelheim Investigational Site
🇧🇷Rio de Janeiro - RJ, Brazil
205.418.91008 Boehringer Ingelheim Investigational Site
🇮🇳Banglore, India
205.418.91006 Boehringer Ingelheim Investigational Site
🇮🇳Coimbatore, India
205.418.01005 Boehringer Ingelheim Investigational Site
🇺🇸Charleston, South Carolina, United States
205.418.55001 Boehringer Ingelheim Investigational Site
🇧🇷Porto Alegre, Brazil
205.418.55005 Boehringer Ingelheim Investigational Site
🇧🇷Porto Alegre, Brazil
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
205.418.91004 Boehringer Ingelheim Investigational Site
🇮🇳Coimbatore, India
205.418.81018 Boehringer Ingelheim Investigational Site
🇯🇵Adachi-ku, Tokyo, Japan
205.418.50202 Boehringer Ingelheim Investigational Site
🇬🇹Guatemala city, Guatemala
205.418.91005 Boehringer Ingelheim Investigational Site
🇮🇳Chennai, 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
205.418.37005 Boehringer Ingelheim Investigational Site
🇱🇻Riga, Latvia
205.418.91010 Boehringer Ingelheim Investigational Site
🇮🇳Pune, India
205.418.81001 Boehringer Ingelheim Investigational Site
🇯🇵Chiyoda-ku, Tokyo, Japan
205.418.81025 Boehringer Ingelheim Investigational Site
🇯🇵Chuo-ku, Tokyo, Japan
205.418.81015 Boehringer Ingelheim Investigational Site
🇯🇵Fujioka, Gunma, Japan
205.418.81007 Boehringer Ingelheim Investigational Site
🇯🇵Hitachi, Ibaraki, Japan
205.418.81028 Boehringer Ingelheim Investigational Site
🇯🇵Kanazawa, Ishikawa, Japan
205.418.81004 Boehringer Ingelheim Investigational Site
🇯🇵Mito, Ibaraki, Japan
205.418.81008 Boehringer Ingelheim Investigational Site
🇯🇵Sapporo, Hokkaido, Japan
205.418.81013 Boehringer Ingelheim Investigational Site
🇯🇵Sendai, Miyagi, Japan
205.418.81026 Boehringer Ingelheim Investigational Site
🇯🇵Setagaya-ku, Tokyo, Japan
205.418.81010 Boehringer Ingelheim Investigational Site
🇯🇵Tomakomai, Hokkaido, Japan
205.418.81023 Boehringer Ingelheim Investigational Site
🇯🇵Himeji, Hyogo, Japan
205.418.81011 Boehringer Ingelheim Investigational Site
🇯🇵Kitakami, Iwate, Japan
205.418.81014 Boehringer Ingelheim Investigational Site
🇯🇵Sendai, Miyagi, Japan
205.418.81024 Boehringer Ingelheim Investigational Site
🇯🇵Takasaki, Gunma, Japan
205.418.81021 Boehringer Ingelheim Investigational Site
🇯🇵Yokohama, Kanagawa, 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
205.418.37004 Boehringer Ingelheim Investigational Site
🇱🇻Daugavpils, Latvia
205.418.37008 Boehringer Ingelheim Investigational Site
🇱🇻Preili, Latvia
205.418.81002 Boehringer Ingelheim Investigational Site
🇯🇵Kunitachi, Tokyo, Japan
205.418.81032 Boehringer Ingelheim Investigational Site
🇯🇵Osaka, Osaka, Japan
205.418.81019 Boehringer Ingelheim Investigational Site
🇯🇵Ota-ku, Tokyo, Japan
205.418.81022 Boehringer Ingelheim Investigational Site
🇯🇵Yao, Osaka, Japan
205.418.81020 Boehringer Ingelheim Investigational Site
🇯🇵Yokohama, Kanagawa, Japan
205.418.37006 Boehringer Ingelheim Investigational Site
🇱🇻Riga, Latvia
205.418.37009 Boehringer Ingelheim Investigational Site
🇱🇻Riga, Latvia
205.418.37003 Boehringer Ingelheim Investigational Site
🇱🇻Ventspils, Latvia
205.418.52002 Boehringer Ingelheim Investigational Site
🇲🇽Monterrey, Mexico
205.418.52003 Boehringer Ingelheim Investigational Site
🇲🇽Zapopan, Mexico
205.418.51002 Boehringer Ingelheim Investigational Site
🇵🇪Lima, Peru
205.418.07004 Boehringer Ingelheim Investigational Site
🇷🇺Moscow, Russian Federation
205.418.01020 Boehringer Ingelheim Investigational Site
🇺🇸Huntington Beach, California, United States
205.418.01017 Boehringer Ingelheim Investigational Site
🇺🇸Normal, Illinois, United States
205.418.86005 Boehringer Ingelheim Investigational Site
🇨🇳Beijing, China
205.418.86007 Boehringer Ingelheim Investigational Site
🇨🇳Beijing, China
205.418.01002 Boehringer Ingelheim Investigational Site
🇺🇸Mission Viejo, California, United States
205.418.86001 Boehringer Ingelheim Investigational Site
🇨🇳Beijing, China
205.418.86014 Boehringer Ingelheim Investigational Site
🇨🇳Changsha, China
205.418.86002 Boehringer Ingelheim Investigational Site
🇨🇳Shanghai, China
205.418.01001 Boehringer Ingelheim Investigational Site
🇺🇸Tacoma, Washington, United States
205.418.86011 Boehringer Ingelheim Investigational Site
🇨🇳Chengdu, China
205.418.86013 Boehringer Ingelheim Investigational Site
🇨🇳Kunming, China
205.418.86008 Boehringer Ingelheim Investigational Site
🇨🇳Qingdao, China
205.418.86009 Boehringer Ingelheim Investigational Site
🇨🇳Shenyang, China
205.418.01021 Boehringer Ingelheim Investigational Site
🇺🇸Winston-Salem, North Carolina, United States
205.418.01018 Boehringer Ingelheim Investigational Site
🇺🇸Oklahoma City, Oklahoma, United States
205.418.86012 Boehringer Ingelheim Investigational Site
🇨🇳Beijing, China
205.418.86004 Boehringer Ingelheim Investigational Site
🇨🇳Shenyang, China
205.418.86006 Boehringer Ingelheim Investigational Site
🇨🇳Xi'An, China
205.418.81030 Boehringer Ingelheim Investigational Site
🇯🇵Ako, Hyogo, Japan
205.418.81009 Boehringer Ingelheim Investigational Site
🇯🇵Iwamizawa, Hokkaido, Japan
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
205.418.81003 Boehringer Ingelheim Investigational Site
🇯🇵Toshima-ku, Tokyo, Japan
205.418.37001 Boehringer Ingelheim Investigational Site
🇱🇻Riga, Latvia
205.418.37002 Boehringer Ingelheim Investigational Site
🇱🇻Riga, Latvia
205.418.48006 Boehringer Ingelheim Investigational Site
🇵🇱Krakow, Poland
205.418.48005 Boehringer Ingelheim Investigational Site
🇵🇱Lodz, Poland
205.418.51003 Boehringer Ingelheim Investigational Site
🇵🇪Callao, Peru
205.418.51001 Boehringer Ingelheim Investigational Site
🇵🇪Lima, Peru
205.418.48001 Boehringer Ingelheim Investigational Site
🇵🇱Lodz, Poland
205.418.48003 Boehringer Ingelheim Investigational Site
🇵🇱Tczew, Poland
205.418.07002 Boehringer Ingelheim Investigational Site
🇷🇺St. Petersburg, Russian Federation
205.418.07005 Boehringer Ingelheim Investigational Site
🇷🇺Moscow, Russian Federation
205.418.01014 Boehringer Ingelheim Investigational Site
🇺🇸San Diego, California, United States
205.418.01007 Boehringer Ingelheim Investigational Site
🇺🇸Dallas, Texas, 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
205.418.01012 Boehringer Ingelheim Investigational Site
🇺🇸Baltimore, Maryland, United States
205.418.01011 Boehringer Ingelheim Investigational Site
🇺🇸Wheat Ridge, Colorado, United States
205.418.01009 Boehringer Ingelheim Investigational Site
🇺🇸Minneapolis, Minnesota, United States
205.418.01010 Boehringer Ingelheim Investigational Site
🇺🇸Easely, South Carolina, United States
205.418.55004 Boehringer Ingelheim Investigational Site
🇧🇷Porto Alegre, Brazil
205.418.81005 Boehringer Ingelheim Investigational Site
🇯🇵Chuo-ku, Tokyo, Japan
205.418.81017 Boehringer Ingelheim Investigational Site
🇯🇵Toshima-ku, Tokyo, Japan
205.418.37007 Boehringer Ingelheim Investigational Site
🇱🇻Riga, Latvia
205.418.52001 Boehringer Ingelheim Investigational Site
🇲🇽Zona Río, Mexico
205.418.48002 Boehringer Ingelheim Investigational Site
🇵🇱Ostrow Wielkopolska, Poland
205.418.48004 Boehringer Ingelheim Investigational Site
🇵🇱Poznan, Poland
205.418.07007 Boehringer Ingelheim Investigational Site
🇷🇺Gatchina (Leningradskaya oblast), Russian Federation
205.418.07008 Boehringer Ingelheim Investigational Site
🇷🇺Moscow, Russian Federation
205.418.07001 Boehringer Ingelheim Investigational Site
🇷🇺St. Petersburg, Russian Federation
205.418.07006 Boehringer Ingelheim Investigational Site
🇷🇺Moscow, Russian Federation
205.418.07003 Boehringer Ingelheim Investigational Site
🇷🇺St. Petersburg, Russian Federation