Evaluation of Tiotropium 2.5 and 5 µg Once Daily Delivered Via the Respimat Inhaler Compared to Placebo in Patient With Moderate to Severe Persistent Asthma

NCT ID: NCT01340209

Last Updated: 2014-07-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 285 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2013-04-30

Brief Summary

The aim of this trial is to evaluate the safety and efficacy of 2.5 and 5 µg tiotropium over a 52-week treatment period as compared to placebo. 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 to severe persistent asthma. Efficacy and safety will be assessed by measuring effects on lung function, effects on asthma exacerbations, effects on asthma control, 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 Respimat (low dose)

Tiotropium low dose once daily delivered with Respimat inhaler

Group Type: EXPERIMENTAL

Tiotropium Respimat

Intervention Type: DRUG

Tiotropium low dose once daily delivered with Respimat inhaler

Tiotropium Respimat (high dose)

Tiotropium high dose once daily delivered with Respimat inhaler

Group Type: EXPERIMENTAL

Tiotropium Respimat

Intervention Type: DRUG

Tiotropium high dose once daily delivered with Respimat inhaler

Placebo Respimat

Tiotropium placebo once daily delivered with Respimat inhaler

Group Type: PLACEBO_COMPARATOR

Placebo Respimat

Intervention Type: DRUG

Tiotropium placebo once daily delivered with Respimat inhaler

Interventions

Tiotropium Respimat

Tiotropium high dose once daily delivered with Respimat inhaler

Intervention Type: DRUG

Placebo Respimat

Tiotropium placebo once daily delivered with Respimat inhaler

Intervention Type: DRUG

Tiotropium Respimat

Tiotropium low dose once daily delivered with Respimat inhaler

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. All patients including the patients under age (under 20 years old) must sign and date an Informed Consent Form consistent with ICH-GCP guidelines and Good Clinical Practice (GCP) 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 (PFT) at Visit 1]. Regarding patients under age, a guardian or a legally authorised representative must also sign and date an Informed Consent Form.

2. Male or female outpatients aged at least 18 years but not more than 75 years at Visit 0.

3. All patients must have at least a 12-week history of asthma at the time of enrolment (Visit 0) 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 (15-30 minutes after 400 µg salbutamol) resulting in a Forced Expiratory Volume in one second (FEV1) increase of at least 12% and at least 200 mL .

6. All patients must have been on maintenance treatment with a medium, stable dose of inhaled corticosteroids (ICS) [alone or in a fixed combination with a Long-acting beta-adrenergic (LABA)] for at least 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. Patients must be never-smokers or ex-smokers who stopped smoking at least one year (52 weeks) prior to enrolment (Visit 0) and who have a smoking history of less than 10 pack years.

10. Patients must be able to use the Respimat inhaler correctly, which is judged at the discretion of the investigator..

11. Patients must be able to perform all trial related procedures including technically acceptable PFTs and use of electronic diary (eDiary)/peak flow meter, which is judged at the discretion of the investigator.

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 no 1.

3. Patients with a recent history (i.e. 6 months or less) of myocardial infarction prior to Visit 0.

4. Patients who have been hospitalised for cardiac failure during the past year prior to Visit 0.

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 prior to Visit 0.

6. Patients with lung diseases other than asthma (e.g. COPD).

7. Patients with known active tuberculosis.

8. Patients with malignancy and/or patients who have undergone resection, radiation therapy or chemotherapy for malignancy within the last 5 years prior to Visit 0. 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, which is judged at the discretion of the investigator, within the past 2 years prior to Visit 0.

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

12. Pregnant or nursing women.

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

14. Patients who have taken an investigational drug within 4 weeks prior to Visit 1.

15. 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.

16. 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.

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

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

19. 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.

20. 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.

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

22. Patients who are currently participating in another trial.

23. Patients with narrow-angle glaucoma and/or micturition disorder due to prostatic hyperplasia.

24. Patients with below 80% of the eDiary completion compliance on Visit 2 (diary compliance of at least 80% is required).

• 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

205.464.81020 Boehringer Ingelheim Investigational Site

Asahikawa, Hokkaido, , Japan

205.464.81031 Boehringer Ingelheim Investigational Site

Atsugi, Kanagawa, , Japan

205.464.81029 Boehringer Ingelheim Investigational Site

Chigasaki, Kanagawa, , Japan

205.464.81011 Boehringer Ingelheim Investigational Site

Chino, Nagano, , Japan

205.464.81050 Boehringer Ingelheim Investigational Site

Chuo-ku, Tokyo, , Japan

205.464.81051 Boehringer Ingelheim Investigational Site

Chuo-ku, Tokyo, , Japan

205.464.81006 Boehringer Ingelheim Investigational Site

Edogawa-ku, Tokyo, , Japan

205.464.81010 Boehringer Ingelheim Investigational Site

Fujisawa, Kanagawa, , Japan

205.464.81016 Boehringer Ingelheim Investigational Site

Fukuoka, Fukuoka, , Japan

205.464.81004 Boehringer Ingelheim Investigational Site

Hanno, Saitama, , Japan

205.464.81040 Boehringer Ingelheim Investigational Site

Himeji, Hyogo, , Japan

205.464.81041 Boehringer Ingelheim Investigational Site

Himeji, Hyogo, , Japan

205.464.81053 Boehringer Ingelheim Investigational Site

Himeji, Hyogo, , Japan

205.464.81007 Boehringer Ingelheim Investigational Site

Hino, Tokyo, , Japan

205.464.81015 Boehringer Ingelheim Investigational Site

Hiroshima, Hiroshima, , Japan

205.464.81002 Boehringer Ingelheim Investigational Site

Hitachinaka, Ibaraki, , Japan

205.464.81048 Boehringer Ingelheim Investigational Site

Iizuka, Fukuoka, , Japan

205.464.81005 Boehringer Ingelheim Investigational Site

Itabashi-ku, Tokyo, , Japan

205.464.81033 Boehringer Ingelheim Investigational Site

Kaga, Ishikawa, , Japan

205.464.81017 Boehringer Ingelheim Investigational Site

Kagoshima, Kagoshima, , Japan

205.464.81023 Boehringer Ingelheim Investigational Site

Kamogawa, Chiba, , Japan

205.464.81024 Boehringer Ingelheim Investigational Site

Kisarazu, Chiba, , Japan

205.464.81047 Boehringer Ingelheim Investigational Site

Kitakyusyu,Fukuoka, , Japan

205.464.81008 Boehringer Ingelheim Investigational Site

Kiyose, Tokyo, , Japan

205.464.81046 Boehringer Ingelheim Investigational Site

Kochi, Kochi, , Japan

205.464.81025 Boehringer Ingelheim Investigational Site

Kodaira, Tokyo, , Japan

205.464.81022 Boehringer Ingelheim Investigational Site

Koshigaya, Saitama, , Japan

205.464.81043 Boehringer Ingelheim Investigational Site

Kurashiki, Okayama, , Japan

205.464.81044 Boehringer Ingelheim Investigational Site

Kure, Hiroshima, , Japan

205.464.81014 Boehringer Ingelheim Investigational Site

Kyoto, Kyoto, , Japan

205.464.81038 Boehringer Ingelheim Investigational Site

Kyoto, Kyoto, , Japan

205.464.81003 Boehringer Ingelheim Investigational Site

Maebashi, Gumma, , Japan

205.464.81042 Boehringer Ingelheim Investigational Site

Matsue, Shimane, , Japan

205.464.81026 Boehringer Ingelheim Investigational Site

Minato-ku, Tokyo, , Japan

205.464.81012 Boehringer Ingelheim Investigational Site

Nagoya, Aichi, , Japan

205.464.81013 Boehringer Ingelheim Investigational Site

Nagoya, Aichi, , Japan

205.464.81034 Boehringer Ingelheim Investigational Site

Nagoya, Aichi, , Japan

205.464.81035 Boehringer Ingelheim Investigational Site

Nagoya, Aichi, , Japan

205.464.81036 Boehringer Ingelheim Investigational Site

Nagoya, Aichi, , Japan

205.464.81037 Boehringer Ingelheim Investigational Site

Nagoya, Aichi, , Japan

205.464.81001 Boehringer Ingelheim Investigational Site

Obihiro, Hokkaido, , Japan

205.464.81018 Boehringer Ingelheim Investigational Site

Obihiro, Hokkaido, , Japan

205.464.81054 Boehringer Ingelheim Investigational Site

Oita, Oita, , Japan

205.464.81055 Boehringer Ingelheim Investigational Site

Oita, Oita, , Japan

205.464.81039 Boehringer Ingelheim Investigational Site

Osaka, Osaka, , Japan

205.464.81049 Boehringer Ingelheim Investigational Site

Saga, Saga, , Japan

205.464.81019 Boehringer Ingelheim Investigational Site

Sapporo, Hokkaido, , Japan

205.464.81021 Boehringer Ingelheim Investigational Site

Sendai, Miyagi, , Japan

205.464.81027 Boehringer Ingelheim Investigational Site

Setagaya-Ku, Tokyo, , Japan

205.464.81028 Boehringer Ingelheim Investigational Site

Setagaya-ku, Tokyo, , Japan

205.464.81045 Boehringer Ingelheim Investigational Site

Toon, Ehime, , Japan

205.464.81009 Boehringer Ingelheim Investigational Site

Yokohama, Kanagawa, , Japan

205.464.81052 Boehringer Ingelheim Investigational Site

Yokohama, Kanagawa, , Japan

205.464.81030 Boehringer Ingelheim Investigational Site

Yokosuka, Kanagawa, , Japan

205.464.81032 Boehringer Ingelheim Investigational Site

Zama, , Japan

Countries

Japan

References

Oba Y, Anwer S, Maduke T, Patel T, Dias S. Effectiveness and tolerability of dual and triple combination inhaler therapies compared with each other and varying doses of inhaled corticosteroids in adolescents and adults with asthma: a systematic review and network meta-analysis. Cochrane Database Syst Rev. 2022 Dec 6;12(12):CD013799. doi: 10.1002/14651858.CD013799.pub2.

Reference Type: DERIVED

PMID: 36472162 (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)

Ohta K, Ichinose M, Tohda Y, Engel M, Moroni-Zentgraf P, Kunimitsu S, Sakamoto W, Adachi M. Long-Term Once-Daily Tiotropium Respimat(R) Is Well Tolerated and Maintains Efficacy over 52 Weeks in Patients with Symptomatic Asthma in Japan: A Randomised, Placebo-Controlled Study. PLoS One. 2015 Apr 20;10(4):e0124109. doi: 10.1371/journal.pone.0124109. eCollection 2015.

Reference Type: DERIVED

PMID: 25894430 (View on PubMed)

Other Identifiers

205.464

Identifier Type: -

Identifier Source: org_study_id