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| ID | Type | Description | Link |
|---|---|---|---|
| 2009-018005-43 | EudraCT Number | EudraCT |
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| Name | Class |
|---|---|
| Pfizer | INDUSTRY |
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| tiotropium low dose | Experimental | Once daily, delivered with Respimat® inhaler (+ inhalation of placebo HFA MDI twice daily) |
|
| tiotropium high dose | Experimental | Once daily, delivered with Respimat® inhaler (+ inhalation of placebo HFA MDI twice daily) |
|
| 50 mcg salmeterol | Active Comparator | Twice daily, delivered with HFA MDI (+ inhalation of placebo Respimat® inhaler once daily) |
|
| placebo | Placebo Comparator | Once daily, delivered with Respimat® inhaler + twice daily delivered with HFA MDI |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| placebo | Drug | Placebo that represents BI drug |
| |
| placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
| The Responder Rate as Assessed by the ACQ From the Two Twin Trials 205.418 (NCT01172808) and the Present 205.419 (NCT01172821) | 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. | 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
Not provided
Inclusion criteria:
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:
Not provided
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 205.419.01058 Boehringer Ingelheim Investigational Site | Los Angeles | California | United States | |||
| 205.419.01053 Boehringer Ingelheim Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32180164 | Derived | Halpin DMG, Hamelmann EH, Frith PA, Moroni-Zentgraf PM, van Hecke B, Unseld A, Kerstjens HAM, Szefler SJ. Comparative Responses in Lung Function Measurements with Tiotropium in Adolescents and Adults, and Across Asthma Severities: A Post Hoc Analysis. Pulm Ther. 2020 Jun;6(1):131-140. doi: 10.1007/s41030-020-00113-w. Epub 2020 Mar 16. | |
| 31654891 |
Not provided
Not provided
There was 1 patient in the TIO R2.5 and 1 patient in the TIO R5 group randomized but not treated.
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Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Matching Placebo delivered by the Respimat Inhaler resp. MDI (hydrofluoroalkane (HFA 134a) metered inhaler). |
| FG001 | Tio R2.5 | Tiotropium 2.5 microgram (mcg) qd (evening) delivered by the Respimat Inhaler. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
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Not provided
| Drug |
Placebo that represents comparator |
|
| placebo | Drug | Placebo that represents comparator |
|
| tiotropium Respimat® low dose | Drug | IMP |
|
| placebo | Drug | Placebo that represents BI drug |
|
| tiotropium Respimat® high dose | Drug | IMP |
|
| 50 mcg salmeterol HFA MDI | Drug | Active comparator |
|
| placebo | Drug | Placebo that represents comparator |
|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 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. | 24 weeks |
| Total Asthma Control Questionnaire (ACQ) Score | 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. | 24 weeks |
| 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 score ranges from 0 (no impairment) to 6 (maximum impairment). | 24 weeks |
| 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 |
| 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 |
| 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, country, week, baseline, treatment by week, and baseline by week. | Last 7 days before week 24 visit |
| 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 |
| 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 |
| 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 |
| 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 |
| Time to First Severe Asthma Exacerbation From the Two Twin Trials 205.418 (NCT01172808) and the Present 205.419 (NCT01172821) | 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 |
| Time to First Asthma Exacerbation From the Two Twin Trials 205.418 (NCT01172808) and the Present 205.419 (NCT01172821) | 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 |
| Stockton |
| California |
| United States |
| 205.419.01061 Boehringer Ingelheim Investigational Site | Centennial | Colorado | United States |
| 205.419.01066 Boehringer Ingelheim Investigational Site | Denver | Colorado | United States |
| 205.419.01064 Boehringer Ingelheim Investigational Site | Panama City | Florida | United States |
| 205.419.01060 Boehringer Ingelheim Investigational Site | Winter Park | Florida | United States |
| 205.419.01068 Boehringer Ingelheim Investigational Site | Novi | Michigan | United States |
| 205.419.01054 Boehringer Ingelheim Investigational Site | Plymouth | Minnesota | United States |
| 205.419.01062 Boehringer Ingelheim Investigational Site | St Louis | Missouri | United States |
| 205.419.01070 Boehringer Ingelheim Investigational Site | Bozeman | Montana | United States |
| 205.419.01067 Boehringer Ingelheim Investigational Site | Skillman | New Jersey | United States |
| 205.419.01071 Boehringer Ingelheim Investigational Site | Raleigh | North Carolina | United States |
| 205.419.01055 Boehringer Ingelheim Investigational Site | Cincinnati | Ohio | United States |
| 205.419.01065 Boehringer Ingelheim Investigational Site | Portland | Oregon | United States |
| 205.419.01069 Boehringer Ingelheim Investigational Site | Greenville | South Carolina | United States |
| 205.419.01056 Boehringer Ingelheim Investigational Site | Union | South Carolina | United States |
| 205.419.01063 Boehringer Ingelheim Investigational Site | El Paso | Texas | United States |
| 205.419.01051 Boehringer Ingelheim Investigational Site | San Antonio | Texas | United States |
| 205.419.55053 Boehringer Ingelheim Investigational Site | Florianópolis | Brazil |
| 205.419.55054 Boehringer Ingelheim Investigational Site | Porto Alegre | Brazil |
| 205.419.55052 Boehringer Ingelheim Investigational Site | São Paulo | Brazil |
| 205.419.55055 Boehringer Ingelheim Investigational Site | São Paulo | Brazil |
| 205.419.86061 Boehringer Ingelheim Investigational Site | Chengdu | China |
| 205.419.86053 Boehringer Ingelheim Investigational Site | Chongqing | China |
| 205.419.86056 Boehringer Ingelheim Investigational Site | Guangzhou | China |
| 205.419.86062 Boehringer Ingelheim Investigational Site | Guangzhou | China |
| 205.419.86054 Boehringer Ingelheim Investigational Site | Haikou | China |
| 205.419.86059 Boehringer Ingelheim Investigational Site | Kunming | China |
| 205.419.86058 Boehringer Ingelheim Investigational Site | Nanchang | 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 |
| 205.419.86055 Boehringer Ingelheim Investigational Site | Shanghai | China |
| 205.419.86066 Boehringer Ingelheim Investigational Site | Shanghai | China |
| 205.419.86057 Boehringer Ingelheim Investigational Site | Xi'an | China |
| 205.419.86065 Boehringer Ingelheim Investigational Site | Xi'an | China |
| 205.419.86063 Boehringer Ingelheim Investigational Site | Xuzhou | China |
| 205.419.86067 Boehringer Ingelheim Investigational Site | Yangzhou | China |
| 205.419.86068 Boehringer Ingelheim Investigational Site | Yinchuan | China |
| 205.419.57051 Boehringer Ingelheim Investigational Site | Bogotá | Colombia |
| 205.419.57052 Boehringer Ingelheim Investigational Site | Bogotá | Colombia |
| 205.419.57053 Boehringer Ingelheim Investigational Site | Bogotá | Colombia |
| 205.419.57054 Boehringer Ingelheim Investigational Site | Medellín | Colombia |
| 205.419.49061 Boehringer Ingelheim Investigational Site | Bamberg | Germany |
| 205.419.49051 Boehringer Ingelheim Investigational Site | Berlin | Germany |
| 205.419.49052 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 |
| 205.419.49057 Boehringer Ingelheim Investigational Site | Koblenz | Germany |
| 205.419.49056 Boehringer Ingelheim Investigational Site | Lübeck | Germany |
| 205.419.49059 Boehringer Ingelheim Investigational Site | Rüdersdorf | Germany |
| 205.419.49053 Boehringer Ingelheim Investigational Site | Wiesbaden | Germany |
| 205.419.49055 Boehringer Ingelheim Investigational Site | Witten | Germany |
| 205.419.91057 Boehringer Ingelheim Investigational Site | Ahmedabad | India |
| 205.419.91056 Boehringer Ingelheim Investigational Site | Coimbatore | India |
| 205.419.91055 Boehringer Ingelheim Investigational Site | Hyderabad | India |
| 205.419.91051 Boehringer Ingelheim Investigational Site | Jaipur | India |
| 205.419.91058 Boehringer Ingelheim Investigational Site | Jaipur | India |
| 205.419.91054 Boehringer Ingelheim Investigational Site | Mumbai | India |
| 205.419.91059 Boehringer Ingelheim Investigational Site | Mysore | India |
| 205.419.91053 Boehringer Ingelheim Investigational Site | Nagpur | India |
| 205.419.81085 Boehringer Ingelheim Investigational Site | Aira, Kagoshima | Japan |
| 205.419.81062 Boehringer Ingelheim Investigational Site | Chuo-ku, Tokyo | Japan |
| 205.419.81073 Boehringer Ingelheim Investigational Site | Fukuoka, Fukuoka | Japan |
| 205.419.81074 Boehringer Ingelheim Investigational Site | Fukuoka, Fukuoka | Japan |
| 205.419.81072 Boehringer Ingelheim Investigational Site | Fukuyama, Hiroshima | Japan |
| 205.419.81069 Boehringer Ingelheim Investigational Site | Habikino, Osaka | Japan |
| 205.419.81071 Boehringer Ingelheim Investigational Site | Hiroshima, Hiroshima | Japan |
| 205.419.81058 Boehringer Ingelheim Investigational Site | Itabashi-ku, Tokyo | Japan |
| 205.419.81064 Boehringer Ingelheim Investigational Site | Iwata, Shizuoka | Japan |
| 205.419.81063 Boehringer Ingelheim Investigational Site | Kanazawa, Ishikawa | Japan |
| 205.419.81054 Boehringer Ingelheim Investigational Site | Kishiwada, Osaka | Japan |
| 205.419.81075 Boehringer Ingelheim Investigational Site | Kitakyushu, Fukuoka | Japan |
| 205.419.81070 Boehringer Ingelheim Investigational Site | Kobe, Hyogo | Japan |
| 205.419.81061 Boehringer Ingelheim Investigational Site | Koto-ku, Tokyo | Japan |
| 205.419.81067 Boehringer Ingelheim Investigational Site | Kyoto, Kyoto | Japan |
| 205.419.81080 Boehringer Ingelheim Investigational Site | Matsusaka, Mie | Japan |
| 205.419.81081 Boehringer Ingelheim Investigational Site | Meguro-ku, Tokyo | Japan |
| 205.419.81060 Boehringer Ingelheim Investigational Site | Minato-ku, Tokyo | Japan |
| 205.419.81077 Boehringer Ingelheim Investigational Site | Minato-ku, Tokyo | Japan |
| 205.419.81056 Boehringer Ingelheim Investigational Site | Morioka, Iwate | Japan |
| 205.419.81055 Boehringer Ingelheim Investigational Site | Naka-gun, Ibaraki | Japan |
| 205.419.81078 Boehringer Ingelheim Investigational Site | Nakano-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 |
| 205.419.81059 Boehringer Ingelheim Investigational Site | Seto, Aichi | Japan |
| 205.419.81082 Boehringer Ingelheim Investigational Site | Shinagawa-ku, Tokyo | Japan |
| 205.419.81065 Boehringer Ingelheim Investigational Site | Shizuoka, Shizuoka | Japan |
| 205.419.81066 Boehringer Ingelheim Investigational Site | Toyota, Aichi | Japan |
| 205.419.81051 Boehringer Ingelheim Investigational Site | Urasoe, Okinawa | 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 |
| 205.419.81079 Boehringer Ingelheim Investigational Site | Yotsukaido, Chiba | Japan |
| 205.419.52051 Boehringer Ingelheim Investigational Site | Mexico City | Mexico |
| 205.419.52052 Boehringer Ingelheim Investigational Site | Mexico City | Mexico |
| 205.419.52053 Boehringer Ingelheim Investigational Site | Monterrey | Mexico |
| 205.419.51051 Boehringer Ingelheim Investigational Site | Lima | Peru |
| 205.419.51052 Boehringer Ingelheim Investigational Site | Lima | Peru |
| 205.419.51053 Boehringer Ingelheim Investigational Site | Lima | Peru |
| 205.419.51054 Boehringer Ingelheim Investigational Site | Lima | Peru |
| 205.419.51055 Boehringer Ingelheim Investigational Site | Lima | Peru |
| 205.419.48052 Boehringer Ingelheim Investigational Site | Bialystok | Poland |
| 205.419.48054 Boehringer Ingelheim Investigational Site | Bydgoszcz | Poland |
| 205.419.48055 Boehringer Ingelheim Investigational Site | Gorzów Wielkopolski | Poland |
| 205.419.48051 Boehringer Ingelheim Investigational Site | Krakow | Poland |
| 205.419.48057 Boehringer Ingelheim Investigational Site | Poznan | Poland |
| 205.419.48058 Boehringer Ingelheim Investigational Site | Sopot | Poland |
| 205.419.48056 Boehringer Ingelheim Investigational Site | Wroclaw | Poland |
| 205.419.48053 Boehringer Ingelheim Investigational Site | Włoszczowa | Poland |
| 205.419.40055 Boehringer Ingelheim Investigational Site | Brasov | Romania |
| 205.419.40056 Boehringer Ingelheim Investigational Site | Brasov | Romania |
| 205.419.40051 Boehringer Ingelheim Investigational Site | Bucharest | Romania |
| 205.419.40052 Boehringer Ingelheim Investigational Site | Bucharest | Romania |
| 205.419.40053 Boehringer Ingelheim Investigational Site | Bucharest | Romania |
| 205.419.40054 Boehringer Ingelheim Investigational Site | Bucharest | Romania |
| 205.419.40058 Boehringer Ingelheim Investigational Site | Bucharest | Romania |
| 205.419.40060 Boehringer Ingelheim Investigational Site | Bucharest | Romania |
| 205.419.40059 Boehringer Ingelheim Investigational Site | Constanța | Romania |
| 205.419.40057 Boehringer Ingelheim Investigational Site | Iași | Romania |
| Casale TB, Aalbers R, Bleecker ER, Meltzer EO, Zaremba-Pechmann L, de la Hoz A, Kerstjens HAM. Tiotropium Respimat(R) add-on therapy to inhaled corticosteroids in patients with symptomatic asthma improves clinical outcomes regardless of baseline characteristics. Respir Med. 2019 Oct-Nov;158:97-109. doi: 10.1016/j.rmed.2019.09.014. Epub 2019 Sep 30. |
| 31319851 | Derived | Halpin DMG, Meltzer EO, Pisternick-Ruf W, Moroni-Zentgraf P, Engel M, Zaremba-Pechmann L, Casale T, FitzGerald JM. Peak expiratory flow as an endpoint for clinical trials in asthma: a comparison with FEV1. Respir Res. 2019 Jul 18;20(1):159. doi: 10.1186/s12931-019-1119-6. |
| 29174062 | Derived | Casale TB, Bateman ED, Vandewalker M, Virchow JC, Schmidt H, Engel M, Moroni-Zentgraf P, Kerstjens HAM. Tiotropium Respimat Add-on Is Efficacious in Symptomatic Asthma, Independent of T2 Phenotype. J Allergy Clin Immunol Pract. 2018 May-Jun;6(3):923-935.e9. doi: 10.1016/j.jaip.2017.08.037. Epub 2017 Nov 22. |
| 25682232 | Derived | Kerstjens HA, Casale TB, Bleecker ER, Meltzer EO, Pizzichini E, Schmidt O, Engel M, Bour L, Verkleij CB, Moroni-Zentgraf P, Bateman ED. Tiotropium or salmeterol as add-on therapy to inhaled corticosteroids for patients with moderate symptomatic asthma: two replicate, double-blind, placebo-controlled, parallel-group, active-comparator, randomised trials. Lancet Respir Med. 2015 May;3(5):367-76. doi: 10.1016/S2213-2600(15)00031-4. Epub 2015 Feb 12. |
| FG002 | Tio R5 | Tiotropium 5 mcg qd (evening) delivered by the Respimat Inhaler. |
| FG003 | Salmeterol | Salmeterol 50 mcg bid (morning and evening) delivered by the MDI (hydrofluoroalkane (HFA 134a) metered inhaler). |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Treated Set (TS) - all randomised patients who received at least 1 dose of randomised trial medication.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Matching Placebo delivered by the Respimat Inhaler resp. MDI (hydrofluoroalkane (HFA 134a) metered inhaler). |
| BG001 | Tio R2.5 | Tiotropium 2.5 microgram (mcg) qd (evening) delivered by the Respimat Inhaler. |
| BG002 | Tio R5 | Tiotropium 5 mcg qd (evening) delivered by the Respimat Inhaler. |
| BG003 | Salmeterol | Salmeterol 50 mcg bid (morning and evening) delivered by the MDI (hydrofluoroalkane (HFA 134a) metered inhaler). |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Full Analysis Set (FAS) - all treated patients who had baseline data and at least 1 on-treatment efficacy measurement. | Posted | Mean | Standard Error | Litre | 24 weeks |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | FAS | Posted | Mean | Standard Error | Litre | 24 weeks |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | FAS | Posted | Mean | Standard Error | Litre | 24 weeks |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. | FAS | Posted | Mean | Standard Error | Litre | 24 weeks |
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| 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. | FAS | Posted | Mean | Standard Error | Litre | 24 weeks |
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| 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. | FAS | Posted | Mean | Standard Error | Litre | 24 weeks |
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| 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. | FAS | Posted | Mean | Standard Error | Litre/min | 24 weeks |
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| 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 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. | FAS | Posted | Mean | Standard Error | units on a scale | 24 weeks |
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| Secondary | Total Asthma Control Questionnaire (ACQ) Score | 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. | FAS | Posted | Mean | Standard Error | units on a scale | 24 weeks |
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| 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 score ranges from 0 (no impairment) to 6 (maximum impairment). | FAS | Posted | Number | Percentage of participants | 24 weeks |
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| 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 | FAS | Posted | Mean | Standard Error | Litre/min | Baseline and last 7 days before week 24 visit |
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| 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. | FAS | Posted | Mean | Standard Error | Litre/min | Baseline and last 7 days before week 24 visit |
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| 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, country, week, baseline, treatment by week, and baseline by week. | FAS | Posted | Mean | Standard Error | Percentage of Mean PEF | Last 7 days before week 24 visit |
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| 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. | FAS | Posted | Mean | Standard Error | Litre | Baseline and last 7 days before week 24 visit |
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| 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. | FAS | Posted | Mean | Standard Error | Litre | Baseline and last 7 days before week 24 visit |
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| 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. | FAS | Posted | Mean | Standard Error | Number of Puffs | Baseline and last 7 days before week 24 visit |
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| 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. | FAS | Posted | Mean | Standard Error | Days | Baseline and last 7 days before week 24 visit |
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| Primary | The Responder Rate as Assessed by the ACQ From the Two Twin Trials 205.418 (NCT01172808) and the Present 205.419 (NCT01172821) | 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. | FAS of combined data from the two twin trials 205.418 (NCT01172808) and 205.419 (NCT01172821). | Posted | Number | Percentage of participants | 24 weeks |
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| Secondary | Time to First Severe Asthma Exacerbation From the Two Twin Trials 205.418 (NCT01172808) and the Present 205.419 (NCT01172821) | 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) | FAS of combined data from the two twin trials 205.418 (NCT01172808) and 205.419 (NCT01172821) | Posted | Median | 95% Confidence Interval | weeks | 24 weeks |
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| Secondary | Time to First Asthma Exacerbation From the Two Twin Trials 205.418 (NCT01172808) and the Present 205.419 (NCT01172821) | 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) | FAS of combined data from the two twin trials 205.418 (NCT01172808) and 205.419 (NCT01172821) | Posted | Median | 95% Confidence Interval | weeks | 24 weeks |
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24 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Matching Placebo delivered by the Respimat Inhaler resp. MDI (hydrofluoroalkane (HFA 134a) metered inhaler). | 4 | 254 | 102 | 254 | ||
| EG001 | Tio R2.5 | Tiotropium 2.5 microgram (mcg) qd (evening) delivered by the Respimat Inhaler. | 7 | 257 | 89 | 257 | ||
| EG002 | Tio R5 | Tiotropium 5 mcg qd (evening) delivered by the Respimat Inhaler. | 7 | 253 | 87 | 253 | ||
| EG003 | Salmeterol | Salmeterol 50 mcg bid (morning and evening) delivered by the MDI (hydrofluoroalkane (HFA 134a) metered inhaler). | 4 | 266 | 90 | 266 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anal fistula | Gastrointestinal disorders | MEDDRA 15.1 | Systematic Assessment |
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| Colitis | Gastrointestinal disorders | MEDDRA 15.1 | Systematic Assessment |
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| Ileus paralytic | Gastrointestinal disorders | MEDDRA 15.1 | Systematic Assessment |
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| Suprapubic pain | General disorders | MEDDRA 15.1 | Systematic Assessment |
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| Anaphylactic reaction | Immune system disorders | MEDDRA 15.1 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MEDDRA 15.1 | Systematic Assessment |
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| Pyelonephritis | Infections and infestations | MEDDRA 15.1 | Systematic Assessment |
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| Chemical poisoning | Injury, poisoning and procedural complications | MEDDRA 15.1 | Systematic Assessment |
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| Intestinal anastomosis complication | Injury, poisoning and procedural complications | MEDDRA 15.1 | Systematic Assessment |
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| Osteoarthritis | Musculoskeletal and connective tissue disorders | MEDDRA 15.1 | Systematic Assessment |
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| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | MEDDRA 15.1 | Systematic Assessment |
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| Ovarian adenoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 15.1 | Systematic Assessment |
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| Cerebral haemorrhage | Nervous system disorders | MEDDRA 15.1 | Systematic Assessment |
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| Cervicobrachial syndrome | Nervous system disorders | MEDDRA 15.1 | Systematic Assessment |
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| Ectopic pregnancy | Pregnancy, puerperium and perinatal conditions | MEDDRA 15.1 | Systematic Assessment |
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| Benign prostatic hyperplasia | Reproductive system and breast disorders | MEDDRA 15.1 | Systematic Assessment |
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| Parovarian cyst | Reproductive system and breast disorders | MEDDRA 15.1 | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MEDDRA 15.1 | Systematic Assessment |
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| Eosinophilic pneumonia | Respiratory, thoracic and mediastinal disorders | MEDDRA 15.1 | Systematic Assessment |
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| Nasal polyps | Respiratory, thoracic and mediastinal disorders | MEDDRA 15.1 | Systematic Assessment |
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| Sleep apnoea syndrome | Respiratory, thoracic and mediastinal disorders | MEDDRA 15.1 | Systematic Assessment |
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| Hypertension | Vascular disorders | MEDDRA 15.1 | Systematic Assessment |
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| Hypertensive crisis | Vascular disorders | MEDDRA 15.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MEDDRA 15.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MEDDRA 15.1 | Systematic Assessment |
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| Peak expiratory flow rate decreased | Investigations | MEDDRA 15.1 | Systematic Assessment |
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| Asthma | Respiratory, thoracic and mediastinal disorders | MEDDRA 15.1 | Systematic Assessment |
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Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim Pharmaceuticals | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
Not provided
Not provided
| Male |
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| Analyses included the fixed, categorical effects of treatment, centre, week, and treatment-by-week interaction, as well as the covariates of baseline value and baseline value-by-week interaction. Patient was included as a random effect in the model. | Mixed Models Analysis | Adjusted using a restricted maximum likelihood (REML)-based mixed effects model with repeated measures (MMRM). | <0.0001 | Mean Difference (Final Values) | 0.169 | Standard Error of the Mean | 0.027 | 2-Sided | 95 | 0.116 | 0.222 | Tio R5 - Placebo | No | Superiority or Other |
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Salmeterol 50 mcg bid (morning and evening) delivered by the MDI (hydrofluoroalkane (HFA 134a) metered inhaler).
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Salmeterol 50 mcg bid (morning and evening) delivered by the MDI (hydrofluoroalkane (HFA 134a) metered inhaler).
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