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

NCT ID: NCT01172808

Last Updated: 2014-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1071 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2012-11-30

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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

tiotropium low dose

Once daily, delivered with Respimat® inhaler (+ inhalation of placebo HFA MDI twice daily)

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Placebo that represents comparator

tiotropium Respimat® low dose

Intervention Type: DRUG

IMP

tiotropium high dose

Once daily, delivered with Respimat® inhaler (+ inhalation of placebo HFA MDI twice daily)

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Placebo that represents comparator

tiotropium Respimat® high dose

Intervention Type: DRUG

IMP

50 mcg salmeterol

Twice daily, delivered with HFA MDI (+ inhalation of placebo Respimat® inhaler once daily)

Group Type: ACTIVE_COMPARATOR

50 mcg salmeterol HFA MDI

Intervention Type: DRUG

Active comparator

Placebo

Intervention Type: DRUG

Placebo that represents BI drug

placebo

Once daily, delivered with Respimat® inhaler + twice daily delivered with HFA MDI

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo that represents comparator

Placebo

Intervention Type: DRUG

Placebo that represents BI drug

Interventions

Placebo

Placebo that represents comparator

Intervention Type: DRUG

tiotropium Respimat® low dose

IMP

Intervention Type: DRUG

Placebo

Placebo that represents comparator

Intervention Type: DRUG

Placebo

Placebo that represents comparator

Intervention Type: DRUG

tiotropium Respimat® high dose

IMP

Intervention Type: DRUG

50 mcg salmeterol HFA MDI

Active comparator

Intervention Type: DRUG

Placebo

Placebo that represents BI drug

Intervention Type: DRUG

Placebo

Placebo that represents BI drug

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

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

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

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

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

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

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

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

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

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

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

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

Exclusion Criteria

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

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

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

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

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

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

7. Patients with known active tuberculosis.

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

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

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

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

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

13. Pregnant or nursing woman.

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

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

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

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

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

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

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

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

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

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

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

205.418.01020 Boehringer Ingelheim Investigational Site

Huntington Beach, California, United States

205.418.01002 Boehringer Ingelheim Investigational Site

Mission Viejo, California, United States

205.418.01014 Boehringer Ingelheim Investigational Site

San Diego, California, United States

205.418.01011 Boehringer Ingelheim Investigational Site

Wheat Ridge, Colorado, United States

205.418.01004 Boehringer Ingelheim Investigational Site

Coeur d'Alene, Idaho, United States

205.418.01017 Boehringer Ingelheim Investigational Site

Normal, Illinois, 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

205.418.01013 Boehringer Ingelheim Investigational Site

North Dartmouth, Massachusetts, United States

205.418.01015 Boehringer Ingelheim Investigational Site

North Dartmouth, Massachusetts, United States

205.418.01009 Boehringer Ingelheim Investigational Site

Minneapolis, Minnesota, United States

205.418.01006 Boehringer Ingelheim Investigational Site

Bellevue, Nebraska, United States

205.418.01016 Boehringer Ingelheim Investigational Site

Boys Town, Nebraska, United States

205.418.01003 Boehringer Ingelheim Investigational Site

Omaha, Nebraska, United States

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

205.418.01005 Boehringer Ingelheim Investigational Site

Charleston, South Carolina, United States

205.418.01010 Boehringer Ingelheim Investigational Site

Easely, South Carolina, United States

205.418.01007 Boehringer Ingelheim Investigational Site

Dallas, Texas, United States

205.418.01019 Boehringer Ingelheim Investigational Site

Seattle, Washington, United States

205.418.01001 Boehringer Ingelheim Investigational Site

Tacoma, Washington, United States

205.418.55002 Boehringer Ingelheim Investigational Site

Juiz de Fora, , Brazil

205.418.55001 Boehringer Ingelheim Investigational Site

Porto Alegre, , Brazil

205.418.55004 Boehringer Ingelheim Investigational Site

Porto Alegre, , Brazil

205.418.55005 Boehringer Ingelheim Investigational Site

Porto Alegre, , Brazil

205.418.55003 Boehringer Ingelheim Investigational Site

Rio de Janeiro - RJ, , Brazil

205.418.86001 Boehringer Ingelheim Investigational Site

Beijing, , China

205.418.86005 Boehringer Ingelheim Investigational Site

Beijing, , China

205.418.86007 Boehringer Ingelheim Investigational Site

Beijing, , China

205.418.86012 Boehringer Ingelheim Investigational Site

Beijing, , China

205.418.86014 Boehringer Ingelheim Investigational Site

Changsha, , China

205.418.86011 Boehringer Ingelheim Investigational Site

Chengdu, , China

205.418.86015 Boehringer Ingelheim Investigational Site

Chengdu, , China

205.418.86003 Boehringer Ingelheim Investigational Site

Chongqing, , China

205.418.86010 Boehringer Ingelheim Investigational Site

Guangzhou, , China

205.418.86013 Boehringer Ingelheim Investigational Site

Kunming, , China

205.418.86008 Boehringer Ingelheim Investigational Site

Qingdao, , China

205.418.86002 Boehringer Ingelheim Investigational Site

Shanghai, , China

205.418.86004 Boehringer Ingelheim Investigational Site

Shenyang, , China

205.418.86009 Boehringer Ingelheim Investigational Site

Shenyang, , China

205.418.86006 Boehringer Ingelheim Investigational Site

Xi'an, , China

205.418.50203 Boehringer Ingelheim Investigational Site

Guatelama City, , Guatemala

205.418.50204 Boehringer Ingelheim Investigational Site

Guatelmala City, , Guatemala

205.418.50205 Boehringer Ingelheim Investigational Site

Guatelmala City, , Guatemala

205.418.50201 Boehringer Ingelheim Investigational Site

Guatemala City, , Guatemala

205.418.50202 Boehringer Ingelheim Investigational Site

Guatemala City, , Guatemala

205.418.91008 Boehringer Ingelheim Investigational Site

Banglore, , India

205.418.91005 Boehringer Ingelheim Investigational Site

Chennai, , India

205.418.91004 Boehringer Ingelheim Investigational Site

Coimbatore, , India

205.418.91006 Boehringer Ingelheim Investigational Site

Coimbatore, , India

205.418.91003 Boehringer Ingelheim Investigational Site

Hyderabad, , India

205.418.91009 Boehringer Ingelheim Investigational Site

Jaipur, , India

205.418.91002 Boehringer Ingelheim Investigational Site

Nagpur, , India

205.418.91007 Boehringer Ingelheim Investigational Site

Pune, , India

205.418.91010 Boehringer Ingelheim Investigational Site

Pune, , India

205.418.81018 Boehringer Ingelheim Investigational Site

Adachi-ku, Tokyo, , Japan

205.418.81030 Boehringer Ingelheim Investigational Site

Ako, Hyogo, , Japan

205.418.81001 Boehringer Ingelheim Investigational Site

Chiyoda-ku, Tokyo, , Japan

205.418.81005 Boehringer Ingelheim Investigational Site

Chuo-ku, Tokyo, , Japan

205.418.81025 Boehringer Ingelheim Investigational Site

Chuo-ku, Tokyo, , Japan

205.418.81015 Boehringer Ingelheim Investigational Site

Fujioka, Gunma, , Japan

205.418.81023 Boehringer Ingelheim Investigational Site

Himeji, Hyogo, , Japan

205.418.81007 Boehringer Ingelheim Investigational Site

Hitachi, Ibaraki, , Japan

205.418.81009 Boehringer Ingelheim Investigational Site

Iwamizawa, Hokkaido, , Japan

205.418.81028 Boehringer Ingelheim Investigational Site

Kanazawa, Ishikawa, , Japan

205.418.81011 Boehringer Ingelheim Investigational Site

Kitakami, Iwate, , Japan

205.418.81012 Boehringer Ingelheim Investigational Site

Kitakami, Iwate, , Japan

205.418.81031 Boehringer Ingelheim Investigational Site

Koga, Ibaraki, , Japan

205.418.81016 Boehringer Ingelheim Investigational Site

Koganei, Tokyo, , Japan

205.418.81006 Boehringer Ingelheim Investigational Site

Komaki, Aichi, , Japan

205.418.81002 Boehringer Ingelheim Investigational Site

Kunitachi, Tokyo, , Japan

205.418.81004 Boehringer Ingelheim Investigational Site

Mito, Ibaraki, , Japan

205.418.81032 Boehringer Ingelheim Investigational Site

Osaka, Osaka, , Japan

205.418.81019 Boehringer Ingelheim Investigational Site

Ota-ku, Tokyo, , Japan

205.418.81008 Boehringer Ingelheim Investigational Site

Sapporo, Hokkaido, , Japan

205.418.81013 Boehringer Ingelheim Investigational Site

Sendai, Miyagi, , Japan

205.418.81014 Boehringer Ingelheim Investigational Site

Sendai, Miyagi, , Japan

205.418.81026 Boehringer Ingelheim Investigational Site

Setagaya-ku, Tokyo, , Japan

205.418.81024 Boehringer Ingelheim Investigational Site

Takasaki, Gunma, , Japan

205.418.81010 Boehringer Ingelheim Investigational Site

Tomakomai, Hokkaido, , Japan

205.418.81003 Boehringer Ingelheim Investigational Site

Toshima-ku, Tokyo, , Japan

205.418.81017 Boehringer Ingelheim Investigational Site

Toshima-ku, Tokyo, , Japan

205.418.81022 Boehringer Ingelheim Investigational Site

Yao, Osaka, , Japan

205.418.81020 Boehringer Ingelheim Investigational Site

Yokohama, Kanagawa, , Japan

205.418.81021 Boehringer Ingelheim Investigational Site

Yokohama, Kanagawa, , Japan

205.418.37004 Boehringer Ingelheim Investigational Site

Daugavpils, , Latvia

205.418.37008 Boehringer Ingelheim Investigational Site

Preiļi, , Latvia

205.418.37001 Boehringer Ingelheim Investigational Site

Riga, , Latvia

205.418.37002 Boehringer Ingelheim Investigational Site

Riga, , Latvia

205.418.37005 Boehringer Ingelheim Investigational Site

Riga, , Latvia

205.418.37006 Boehringer Ingelheim Investigational Site

Riga, , Latvia

205.418.37007 Boehringer Ingelheim Investigational Site

Riga, , Latvia

205.418.37009 Boehringer Ingelheim Investigational Site

Riga, , Latvia

205.418.37003 Boehringer Ingelheim Investigational Site

Ventspils, , Latvia

205.418.52002 Boehringer Ingelheim Investigational Site

Monterrey, , Mexico

205.418.52003 Boehringer Ingelheim Investigational Site

Zapopan, , Mexico

205.418.52001 Boehringer Ingelheim Investigational Site

Zona Río, , Mexico

205.418.51003 Boehringer Ingelheim Investigational Site

Callao, , Peru

205.418.51001 Boehringer Ingelheim Investigational Site

Lima, , Peru

205.418.51002 Boehringer Ingelheim Investigational Site

Lima, , Peru

205.418.48006 Boehringer Ingelheim Investigational Site

Krakow, , Poland

205.418.48001 Boehringer Ingelheim Investigational Site

Lodz, , Poland

205.418.48005 Boehringer Ingelheim Investigational Site

Lodz, , Poland

205.418.48002 Boehringer Ingelheim Investigational Site

Ostrow Wielkopolska, , Poland

205.418.48004 Boehringer Ingelheim Investigational Site

Poznan, , Poland

205.418.48003 Boehringer Ingelheim Investigational Site

Tczew, , Poland

205.418.07007 Boehringer Ingelheim Investigational Site

Gatchina (Leningradskaya Oblast), , Russia

205.418.07004 Boehringer Ingelheim Investigational Site

Moscow, , Russia

205.418.07005 Boehringer Ingelheim Investigational Site

Moscow, , Russia

205.418.07006 Boehringer Ingelheim Investigational Site

Moscow, , Russia

205.418.07008 Boehringer Ingelheim Investigational Site

Moscow, , Russia

205.418.07001 Boehringer Ingelheim Investigational Site

Saint Petersburg, , Russia

205.418.07002 Boehringer Ingelheim Investigational Site

Saint Petersburg, , Russia

205.418.07003 Boehringer Ingelheim Investigational Site

Saint Petersburg, , Russia

Countries

United States; Brazil; China; Guatemala; India; Japan; Latvia; Mexico; Peru; Poland; Russia

References

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.

Reference Type: DERIVED

PMID: 32180164 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31654891 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31319851 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29174062 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25682232 (View on PubMed)

Other Identifiers

2009-018004-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

205.418

Identifier Type: -

Identifier Source: org_study_id