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 II
- Conditions
- Asthma
- Interventions
- Drug: tiotropium Respimat® high doseDrug: tiotropium Respimat® low doseDrug: placeboDrug: 50 mcg salmeterol HFA MDI
- Registration Number
- NCT01172821
- 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
- 1032
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description tiotropium low dose tiotropium Respimat® low dose Once daily, delivered with Respimat® inhaler (+ inhalation of placebo HFA MDI twice daily) tiotropium high dose tiotropium Respimat® high 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 placebo Twice daily, delivered with HFA MDI (+ inhalation of placebo Respimat® inhaler once daily) 50 mcg salmeterol 50 mcg salmeterol HFA MDI 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 low dose placebo 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 205.418 (NCT01172808) and the Present 205.419 (NCT01172821) 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.
- 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 and ranges from from 1 (highest intensity) till 7 (no symptoms). Means are adjusted for treatment, centre, week, baseline, treatment by week, and baseline by week.Total Asthma Control Questionnaire (ACQ) Score 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 and ranges from from 0 (no symptoms) till 6 (highest intensity). 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 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, country, 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 205.418 (NCT01172808) and the Present 205.419 (NCT01172821) 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 205.418 (NCT01172808) and the Present 205.419 (NCT01172821) 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 (125)
205.419.01068 Boehringer Ingelheim Investigational Site
🇺🇸Novi, Michigan, United States
205.419.01071 Boehringer Ingelheim Investigational Site
🇺🇸Raleigh, North Carolina, United States
205.419.01056 Boehringer Ingelheim Investigational Site
🇺🇸Union, South Carolina, United States
205.419.01060 Boehringer Ingelheim Investigational Site
🇺🇸Winter Park, Florida, United States
205.419.01066 Boehringer Ingelheim Investigational Site
🇺🇸Denver, Colorado, United States
205.419.01069 Boehringer Ingelheim Investigational Site
🇺🇸Greenville, South Carolina, United States
205.419.01058 Boehringer Ingelheim Investigational Site
🇺🇸Los Angeles, California, United States
205.419.55055 Boehringer Ingelheim Investigational Site
🇧🇷Sao Paulo, Brazil
205.419.01053 Boehringer Ingelheim Investigational Site
🇺🇸Stockton, California, United States
205.419.01061 Boehringer Ingelheim Investigational Site
🇺🇸Centennial, Colorado, United States
205.419.55054 Boehringer Ingelheim Investigational Site
🇧🇷Porto Alegre, Brazil
205.419.01067 Boehringer Ingelheim Investigational Site
🇺🇸Skillman, New Jersey, United States
205.419.81059 Boehringer Ingelheim Investigational Site
🇯🇵Seto, Aichi, Japan
205.419.49053 Boehringer Ingelheim Investigational Site
🇩🇪Wiesbaden, Germany
205.419.81085 Boehringer Ingelheim Investigational Site
🇯🇵Aira, Kagoshima, Japan
205.419.81062 Boehringer Ingelheim Investigational Site
🇯🇵Chuo-ku, Tokyo, Japan
205.419.81064 Boehringer Ingelheim Investigational Site
🇯🇵Iwata, Shizuoka, Japan
205.419.49059 Boehringer Ingelheim Investigational Site
🇩🇪Rüdersdorf, Germany
205.419.81058 Boehringer Ingelheim Investigational Site
🇯🇵Itabashi-ku, Tokyo, Japan
205.419.01062 Boehringer Ingelheim Investigational Site
🇺🇸St. Louis, Missouri, United States
205.419.91055 Boehringer Ingelheim Investigational Site
🇮🇳Hyderabad, India
205.419.49056 Boehringer Ingelheim Investigational Site
🇩🇪Lübeck, Germany
205.419.81075 Boehringer Ingelheim Investigational Site
🇯🇵Kitakyushu, Fukuoka, Japan
205.419.81067 Boehringer Ingelheim Investigational Site
🇯🇵Kyoto, Kyoto, Japan
205.419.81072 Boehringer Ingelheim Investigational Site
🇯🇵Fukuyama, Hiroshima, Japan
205.419.81056 Boehringer Ingelheim Investigational Site
🇯🇵Morioka, Iwate, Japan
205.419.91058 Boehringer Ingelheim Investigational Site
🇮🇳Jaipur, India
205.419.49055 Boehringer Ingelheim Investigational Site
🇩🇪Witten, Germany
205.419.81069 Boehringer Ingelheim Investigational Site
🇯🇵Habikino, Osaka, Japan
205.419.81074 Boehringer Ingelheim Investigational Site
🇯🇵Fukuoka, Fukuoka, Japan
205.419.81071 Boehringer Ingelheim Investigational Site
🇯🇵Hiroshima, Hiroshima, Japan
205.419.81073 Boehringer Ingelheim Investigational Site
🇯🇵Fukuoka, Fukuoka, Japan
205.419.81070 Boehringer Ingelheim Investigational Site
🇯🇵Kobe, Hyogo, Japan
205.419.48051 Boehringer Ingelheim Investigational Site
🇵🇱Krakow, Poland
205.419.48058 Boehringer Ingelheim Investigational Site
🇵🇱Sopot, Poland
205.419.48056 Boehringer Ingelheim Investigational Site
🇵🇱Wroclaw, Poland
205.419.81051 Boehringer Ingelheim Investigational Site
🇯🇵Urasoe, Okinawa, Japan
205.419.81078 Boehringer Ingelheim Investigational Site
🇯🇵Nakano-ku,Tokyo, Japan
205.419.81065 Boehringer Ingelheim Investigational Site
🇯🇵Shizuoka, Shizuoka, Japan
205.419.49057 Boehringer Ingelheim Investigational Site
🇩🇪Koblenz, Germany
205.419.48052 Boehringer Ingelheim Investigational Site
🇵🇱Bialystok, Poland
205.419.48053 Boehringer Ingelheim Investigational Site
🇵🇱Wloszczowa, Poland
205.419.51052 Boehringer Ingelheim Investigational Site
🇵🇪Lima, Peru
205.419.81080 Boehringer Ingelheim Investigational Site
🇯🇵Matsusaka, Mie, Japan
205.419.81063 Boehringer Ingelheim Investigational Site
🇯🇵Kanazawa, Ishikawa, Japan
205.419.81054 Boehringer Ingelheim Investigational Site
🇯🇵Kishiwada, Osaka, Japan
205.419.48054 Boehringer Ingelheim Investigational Site
🇵🇱Bydgoszcz, Poland
205.419.81079 Boehringer Ingelheim Investigational Site
🇯🇵Yotsukaido, Chiba, Japan
205.419.81082 Boehringer Ingelheim Investigational Site
🇯🇵Shinagawa-ku, Tokyo, Japan
205.419.40054 Boehringer Ingelheim Investigational Site
🇷🇴Bucharest, Romania
205.419.48055 Boehringer Ingelheim Investigational Site
🇵🇱Gorzow Wielkopolski, Poland
205.419.91056 Boehringer Ingelheim Investigational Site
🇮🇳Coimbatore, India
205.419.91059 Boehringer Ingelheim Investigational Site
🇮🇳Mysore, India
205.419.52052 Boehringer Ingelheim Investigational Site
🇲🇽Mexico City, Mexico
205.419.51055 Boehringer Ingelheim Investigational Site
🇵🇪Lima, Peru
205.419.86061 Boehringer Ingelheim Investigational Site
🇨🇳Chengdu, China
205.419.86053 Boehringer Ingelheim Investigational Site
🇨🇳Chongqing, China
205.419.86054 Boehringer Ingelheim Investigational Site
🇨🇳Haikou, China
205.419.86064 Boehringer Ingelheim Investigational Site
🇨🇳Nanjing, China
205.419.86051 Boehringer Ingelheim Investigational Site
🇨🇳Shanghai, China
205.419.86052 Boehringer Ingelheim Investigational Site
🇨🇳Shanghai, China
205.419.86057 Boehringer Ingelheim Investigational Site
🇨🇳Xi'An, China
205.419.86063 Boehringer Ingelheim Investigational Site
🇨🇳Xuzhou, China
205.419.86068 Boehringer Ingelheim Investigational Site
🇨🇳Yinchuan, China
205.419.57052 Boehringer Ingelheim Investigational Site
🇨🇴Bogota, Colombia
205.419.81081 Boehringer Ingelheim Investigational Site
🇯🇵Meguro-ku, Tokyo, Japan
205.419.81060 Boehringer Ingelheim Investigational Site
🇯🇵Minato-ku, Tokyo, Japan
205.419.81055 Boehringer Ingelheim Investigational Site
🇯🇵Naka-gun, Ibaraki, Japan
205.419.81077 Boehringer Ingelheim Investigational Site
🇯🇵Minato-ku, Tokyo, Japan
205.419.81084 Boehringer Ingelheim Investigational Site
🇯🇵Oita,Oita, Japan
205.419.81068 Boehringer Ingelheim Investigational Site
🇯🇵Osaka-Sayama, Osaka, Japan
205.419.81053 Boehringer Ingelheim Investigational Site
🇯🇵Sapporo, Hokkaido, Japan
205.419.81057 Boehringer Ingelheim Investigational Site
🇯🇵Sendai, Miyagi, Japan
205.419.81066 Boehringer Ingelheim Investigational Site
🇯🇵Toyota, Aichi, Japan
205.419.81052 Boehringer Ingelheim Investigational Site
🇯🇵Urasoe, Okinawa, Japan
205.419.81076 Boehringer Ingelheim Investigational Site
🇯🇵Urasoe, Okinawa, Japan
205.419.81083 Boehringer Ingelheim Investigational Site
🇯🇵Yokohama, Kanagawa, Japan
205.419.81061 Boehringer Ingelheim Investigational Site
🇯🇵Koto-ku, Tokyo, Japan
205.419.01055 Boehringer Ingelheim Investigational Site
🇺🇸Cincinnati, Ohio, United States
205.419.01065 Boehringer Ingelheim Investigational Site
🇺🇸Portland, Oregon, United States
205.419.55053 Boehringer Ingelheim Investigational Site
🇧🇷Florianopolis, Brazil
205.419.01063 Boehringer Ingelheim Investigational Site
🇺🇸El Paso, Texas, United States
205.419.01051 Boehringer Ingelheim Investigational Site
🇺🇸San Antonio, Texas, United States
205.419.55052 Boehringer Ingelheim Investigational Site
🇧🇷Sao Paulo, Brazil
205.419.86056 Boehringer Ingelheim Investigational Site
🇨🇳Guangzhou, China
205.419.86062 Boehringer Ingelheim Investigational Site
🇨🇳Guangzhou, China
205.419.86059 Boehringer Ingelheim Investigational Site
🇨🇳Kunming, China
205.419.86058 Boehringer Ingelheim Investigational Site
🇨🇳Nanchang, China
205.419.86055 Boehringer Ingelheim Investigational Site
🇨🇳Shanghai, China
205.419.86066 Boehringer Ingelheim Investigational Site
🇨🇳Shanghai, China
205.419.86065 Boehringer Ingelheim Investigational Site
🇨🇳Xi'An, China
205.419.86067 Boehringer Ingelheim Investigational Site
🇨🇳Yangzhou, China
205.419.57051 Boehringer Ingelheim Investigational Site
🇨🇴Bogota, Colombia
205.419.57054 Boehringer Ingelheim Investigational Site
🇨🇴Medelin, Colombia
205.419.57053 Boehringer Ingelheim Investigational Site
🇨🇴Bogota, Colombia
205.419.49061 Boehringer Ingelheim Investigational Site
🇩🇪Bamberg, Germany
205.419.49052 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
205.419.49051 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
205.419.49062 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
205.419.49063 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
205.419.49064 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
205.419.49054 Boehringer Ingelheim Investigational Site
🇩🇪Frankfurt, Germany
205.419.49058 Boehringer Ingelheim Investigational Site
🇩🇪Hamburg, Germany
205.419.52053 Boehringer Ingelheim Investigational Site
🇲🇽Monterrey, Mexico
205.419.40052 Boehringer Ingelheim Investigational Site
🇷🇴Bucharest, Romania
205.419.40060 Boehringer Ingelheim Investigational Site
🇷🇴Bucharest, Romania
205.419.51053 Boehringer Ingelheim Investigational Site
🇵🇪Lima, Peru
205.419.51054 Boehringer Ingelheim Investigational Site
🇵🇪Lima, Peru
205.419.40059 Boehringer Ingelheim Investigational Site
🇷🇴Constanta, Romania
205.419.91057 Boehringer Ingelheim Investigational Site
🇮🇳Ahmedabad, India
205.419.91051 Boehringer Ingelheim Investigational Site
🇮🇳Jaipur, India
205.419.52051 Boehringer Ingelheim Investigational Site
🇲🇽Mexico City, Mexico
205.419.40056 Boehringer Ingelheim Investigational Site
🇷🇴Brasov, Romania
205.419.40057 Boehringer Ingelheim Investigational Site
🇷🇴Iasi, Romania
205.419.51051 Boehringer Ingelheim Investigational Site
🇵🇪Lima, Peru
205.419.40055 Boehringer Ingelheim Investigational Site
🇷🇴Brasov, Romania
205.419.40058 Boehringer Ingelheim Investigational Site
🇷🇴Bucharest, Romania
205.419.91054 Boehringer Ingelheim Investigational Site
🇮🇳Mumbai, India
205.419.91053 Boehringer Ingelheim Investigational Site
🇮🇳Nagpur, India
205.419.40053 Boehringer Ingelheim Investigational Site
🇷🇴Bucharest, Romania
205.419.40051 Boehringer Ingelheim Investigational Site
🇷🇴Bucuresti, Romania
205.419.01070 Boehringer Ingelheim Investigational Site
🇺🇸Bozeman, Montana, United States
205.419.48057 Boehringer Ingelheim Investigational Site
🇵🇱Poznan, Poland
205.419.01064 Boehringer Ingelheim Investigational Site
🇺🇸Panama City, Florida, United States
205.419.01054 Boehringer Ingelheim Investigational Site
🇺🇸Plymouth, Minnesota, United States