Evaluation of Tiotropium 5 µg/Day Delivered Via the Respimat® Inhaler Over 48 Weeks in Patients With Severe Persistent Asthma on Top of Usual Care (Study I)

NCT ID: NCT00772538

Last Updated: 2014-08-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 459 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31

Brief Summary

The trial is a randomised, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of 5 µg tiotropium over a 48-week treatment period as compared to placebo. Tiotropium inhalation solution delivered by the Respimat® inhaler will be examined as add-on controller therapy on top of usual care in patients with severe persistent asthma.

The primary objective of each trial is to evaluate the long term efficacy of tiotropium over placebo on top of usual care in patients with severe persistent asthma as determined by pulmonary function testing, effects on asthma exacerbations, effects on quality of life, on asthma control and health care resource utilisation. The secondary objective of each trial is to compare the long term safety of tiotropium with placebo in this patient population.

Conditions

Asthma

Study Design

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

Study Groups

tiotropium 5mcg/day

patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution

Group Type: EXPERIMENTAL

tiotropium 5mcg/day

Intervention Type: DRUG

Intervention = randomisation: Patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo

placebo

patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo inhalation solution

Group Type: EXPERIMENTAL

placebo

Intervention Type: DRUG

Matching placebo

Interventions

tiotropium 5mcg/day

Intervention = randomisation: Patient to receive double-blind treatment with either 5mcg/day tiotropium inhalation solution or placebo

Intervention Type: DRUG

placebo

Matching placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. All patients must sign and date an Informed Consent Form consistent with 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 5-year history of asthma at the time of enrolment into the trial and the diagnosis of asthma must have been made before the patient´s age of 40.

4. All patients must have a diagnosis of severe persistent asthma and must be symptomatic despite treatment with high, stable doses of inhaled corticosteroids and a long-acting beta adrenergic agent

5. All patients must have a history of one or more asthma exacerbation in the past year.

6. Patients must have evidence of treated, severe, persistent asthma in postbronchodilatory pulmonary function tests.

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

8. Patients must be able to use the Respimat® inhaler correctly

9. Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of the 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 clinically relevant abnormal screening haematology or blood chemistry.

3. Patients with a recent history (i.e. six months or less) of myocardial infarction, hospitalisation for cardiac failure during the past year, any unstable or life threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year, known active tuberculosis, malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years (treated basal cell carcinoma allowed), lung diseases other than asthma (e.g. COPD), significant alcohol or drug abuse within the past two years, 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.

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

5. Patients using oral corticosteroid medication at stable doses exceeding 5 mg prednisolone or prednisolone equivalent every day or 10 mg prednisolone or prednisolone equivalent every second day.

6. Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other components of the tiotropium inhalation solution.

7. Pregnant or nursing women or women of childbearing potential not using a highly effective method of birth control. Female patients will be considered to be of childbearing potential unless surgically sterilised by hysterectomy or bilateral tubal ligation/salpingectomy, or post-menopausal for at least two years.

8. Patients who have taken an investigational drug within four weeks or six half-lives (whichever is greater) prior to Visit 1.

9. Patients who have been treated with the long-acting anticholinergic tiotropium (Spiriva®), beta-blocker medication, oral beta-adrenergics, other non-approved and according to international guidelines not recommended ´experimental´ drugs for routine asthma therapy (e.g. TNF-alpha blockers, methotrexate, cyclosporin) within four weeks prior to the Screening Visit (Visit 1) or during the screening period.

10. Patients with any asthma exacerbation or respiratory tract infection in the four weeks prior to the trial.

11. Patients who have previously been randomised in this trial or in the respective twin trial (205.416 versus 205.417) or are currently participating in another trial.

12. Patients with a known narrow-angle glaucoma.

Note:

As with other anticholinergic drugs, tiotropium should be used with caution in patients with prostatic hyperplasia or bladder neck obstruction.

As with all predominantly renally excreted drugs, patients with moderate to severe renal impairment (known creatinine clearance of <= 50 mL/min) treated with tiotropium should be monitored closely.

• 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

205.416.01007 Boehringer Ingelheim Investigational Site

Birmingham, Alabama, United States

205.416.01012 Boehringer Ingelheim Investigational Site

Los Angeles, California, United States

205.416.01018 Boehringer Ingelheim Investigational Site

Los Angeles, California, United States

205.416.01016 Boehringer Ingelheim Investigational Site

Riverside, California, United States

205.416.01008 Boehringer Ingelheim Investigational Site

San Diego, California, United States

205.416.01004 Boehringer Ingelheim Investigational Site

Walnut Creek, California, United States

205.416.01010 Boehringer Ingelheim Investigational Site

Stamford, Connecticut, United States

205.416.01023 Boehringer Ingelheim Investigational Site

Tallahassee, Florida, United States

205.416.01002 Boehringer Ingelheim Investigational Site

Elk Grove Village, Illinois, United States

205.416.01003 Boehringer Ingelheim Investigational Site

Lexington, Kentucky, United States

205.416.01014 Boehringer Ingelheim Investigational Site

Wheaton, Maryland, United States

205.416.01025 Boehringer Ingelheim Investigational Site

North Dartmouth, Massachusetts, United States

205.416.01022 Boehringer Ingelheim Investigational Site

Columbia, Missouri, United States

205.416.01021 Boehringer Ingelheim Investigational Site

Boys Town, Nebraska, United States

205.416.01011 Boehringer Ingelheim Investigational Site

Cherry Hill, New Jersey, United States

205.416.01001 Boehringer Ingelheim Investigational Site

Cincinnati, Ohio, United States

205.416.01024 Boehringer Ingelheim Investigational Site

Oklahoma City, Oklahoma, United States

205.416.01017 Boehringer Ingelheim Investigational Site

Lake Oswego, Oregon, United States

205.416.01019 Boehringer Ingelheim Investigational Site

El Paso, Texas, United States

205.416.01009 Boehringer Ingelheim Investigational Site

Richmond, Virginia, United States

205.416.61001 Boehringer Ingelheim Investigational Site

Daw Park, South Australia, Australia

205.416.61002 Boehringer Ingelheim Investigational Site

Woodville, South Australia, Australia

205.416.61003 Boehringer Ingelheim Investigational Site

Nedlands, Western Australia, Australia

205.416.02001 Boehringer Ingelheim Investigational Site

Toronto, Ontario, Canada

205.416.02002 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

205.416.02003 Boehringer Ingelheim Investigational Site

Montreal, Quebec, Canada

205.416.02004 Boehringer Ingelheim Investigational Site

Québec, Quebec, Canada

205.416.45001 Boehringer Ingelheim Investigational Site

Hvidovre, , Denmark

205.416.45002 Boehringer Ingelheim Investigational Site

Odense C, , Denmark

205.416.49002 Boehringer Ingelheim Investigational Site

Berlin, , Germany

205.416.49003 Boehringer Ingelheim Investigational Site

Gelnhausen, , Germany

205.416.49005 Boehringer Ingelheim Investigational Site

Koblenz, , Germany

205.416.49004 Boehringer Ingelheim Investigational Site

Oschersleben, , Germany

205.416.39001 Boehringer Ingelheim Investigational Site

Pisa, , Italy

205.416.39002 Boehringer Ingelheim Investigational Site

Sesto S. Giovanni (MI), , Italy

205.416.81007 Boehringer Ingelheim Investigational Site

Hachioji, Tokyo, , Japan

205.416.81004 Boehringer Ingelheim Investigational Site

Inashiki-gun, Ibaraki, , Japan

205.416.81006 Boehringer Ingelheim Investigational Site

Kamogawa, Chiba, , Japan

205.416.81012 Boehringer Ingelheim Investigational Site

Maebashi, Gunma, , Japan

205.416.81008 Boehringer Ingelheim Investigational Site

Minato-ku, Tokyo, , Japan

205.416.81009 Boehringer Ingelheim Investigational Site

Minato-ku, Tokyo, , Japan

205.416.81001 Boehringer Ingelheim Investigational Site

Naka-gun, Ibaraki, , Japan

205.416.81014 Boehringer Ingelheim Investigational Site

Noda, Chiba, , Japan

205.416.81015 Boehringer Ingelheim Investigational Site

Sapporo, Hokkaido, , Japan

205.416.81016 Boehringer Ingelheim Investigational Site

Sapporo, Hokkaido, , Japan

205.416.81002 Boehringer Ingelheim Investigational Site

Sendai, Miyagi, , Japan

205.416.81010 Boehringer Ingelheim Investigational Site

Shinagawa-ku, Tokyo, , Japan

205.416.81005 Boehringer Ingelheim Investigational Site

Tsukuba, Ibaraki, , Japan

205.416.81011 Boehringer Ingelheim Investigational Site

Yokohama, Kanagawa, , Japan

205.416.81003 Boehringer Ingelheim Investigational Site

Yonezawa, Yamagata, , Japan

205.416.31005 Boehringer Ingelheim Investigational Site

Breda, , Netherlands

205.416.31001 Boehringer Ingelheim Investigational Site

Groningen, , Netherlands

205.416.31004 Boehringer Ingelheim Investigational Site

Helmond, , Netherlands

205.416.31003 Boehringer Ingelheim Investigational Site

Zutphen, , Netherlands

205.416.07001 Boehringer Ingelheim Investigational Site

Moscow, , Russia

205.416.07002 Boehringer Ingelheim Investigational Site

Moscow, , Russia

205.416.07003 Boehringer Ingelheim Investigational Site

Reutov - Moscow Region, , Russia

205.416.38101 Boehringer Ingelheim Investigational Site

Belgrade, , Serbia

205.416.38102 Boehringer Ingelheim Investigational Site

Kragujevac, , Serbia

205.416.38103 Boehringer Ingelheim Investigational Site

Zemun, , Serbia

205.416.27001 Boehringer Ingelheim Investigational Site

Cape Town, , South Africa

205.416.27002 Boehringer Ingelheim Investigational Site

Durban, , South Africa

205.416.27003 Boehringer Ingelheim Investigational Site

Durban, , South Africa

205.416.27004 Boehringer Ingelheim Investigational Site

Pretoria, , South Africa

205.416.90001 Boehringer Ingelheim Investigational Site

Istanbul, , Turkey (Türkiye)

205.416.90002 Boehringer Ingelheim Investigational Site

Izmir, , Turkey (Türkiye)

205.416.38002 Boehringer Ingelheim Investigational Site

Kharkiv, , Ukraine

205.416.38001 Boehringer Ingelheim Investigational Site

Kiev, , Ukraine

205.416.38003 Boehringer Ingelheim Investigational Site

Vinnytsia, , Ukraine

205.416.44003 Boehringer Ingelheim Investigational Site

Brighton, , United Kingdom

205.416.44002 Boehringer Ingelheim Investigational Site

Leicester, , United Kingdom

205.416.44004 Boehringer Ingelheim Investigational Site

Nottingham, , United Kingdom

205.416.44005 Boehringer Ingelheim Investigational Site

Nottingham, , United Kingdom

Countries

United States; Australia; Canada; Denmark; Germany; Italy; Japan; Netherlands; Russia; Serbia; South Africa; Turkey (Türkiye); Ukraine; United Kingdom

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)

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, Engel M, Dahl R, Paggiaro P, Beck E, Vandewalker M, Sigmund R, Seibold W, Moroni-Zentgraf P, Bateman ED. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med. 2012 Sep 27;367(13):1198-207. doi: 10.1056/NEJMoa1208606. Epub 2012 Sep 2.

Reference Type: DERIVED

PMID: 22938706 (View on PubMed)

Other Identifiers

2008-001413-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

205.416

Identifier Type: -

Identifier Source: org_study_id