Efficacy and Safety of 2 Doses of Tiotropium Via Respimat in Adult Patients With Mild Persistent Asthma

NCT ID: NCT01316380

Last Updated: 2015-04-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 465 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2012-04-30

Brief Summary

The aim of this trial is to evaluate the efficacy and safety of 2.5 and 5 mcg tiotropium compared to placebo over 12 week treatment period. Tiotropium inhalation solution will be delivered via Respimat inhaler and will be examined on top of maintenance inhaled corticosteroid treatment in patients with mild persistent asthma. Efficacy and safety will be assessed by measuring the effects on lung functions, effects on lung exacerbations, effects on asthma control and numbers of adverse events.

Conditions

Asthma

Study Design

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

Study Groups

tiotropium 5 mcg

once daily delivered via Respimat inhaler

Group Type: EXPERIMENTAL

tiotropium 5 mcg

Intervention Type: DRUG

To evaluate efficacy and safety of 2.5 and 5 mcg tiotropium versus placebo delivered via Respimat inhaler

tiotropium 2.5 mcg

once daily delivered via Respimat inhaler

Group Type: EXPERIMENTAL

tiotropium 2.5 mcg

Intervention Type: DRUG

To evaluate efficacy and safety of 2.5 and 5 mcg tiotropium versus placebo delivered via Respimat inhaler

placebo

once daily delivered via Respimat inhaler

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

To evaluate efficacy and safety of 2.5 and 5 mcg tiotropium versus placebo delivered via Respimat inhaler

Interventions

placebo

To evaluate efficacy and safety of 2.5 and 5 mcg tiotropium versus placebo delivered via Respimat inhaler

Intervention Type: DRUG

tiotropium 2.5 mcg

To evaluate efficacy and safety of 2.5 and 5 mcg tiotropium versus placebo delivered via Respimat inhaler

Intervention Type: DRUG

tiotropium 5 mcg

To evaluate efficacy and safety of 2.5 and 5 mcg tiotropium versus placebo delivered via Respimat inhaler

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 18 years or more at Visit 0 and 75 years or less at Visit 0.

All patients must have

3. at least a 3 months history of asthma at the time of enrolment into the trial. The initial diagnosis of asthma must have been made before the patient's age of 40;

4. a pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1)= 60% predicted and = 90% of predicted normal at Visit 1. Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator) as compared to Visit 2 (pre-dose) must be within ± 30%.

5. Patient's diagnosis of asthma has to be confirmed at Visit 1 with a bronchodilator reversibility (within 10 minutes pre and 15-30 minutes after 400 µg salbutamol/albuterol) resulting in a FEV1 increase of = 12% and = 200mL. If this is not achieved the reversibility test may be repeated once within two weeks.

6. All patients must be symptomatic despite their current maintenance treatment with low doses of inhaled corticosteroids.

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

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

9. Patients must 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 ((see Appendix 10.3 for calculation).

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

11. Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of the e-Diary/peak flow meter (e-Diary-compliance of at least 80% is required; refer to Section 6.2.1 for instructions).

12. Patients taking a chronic pulmonary medication allowed by the study protocol must be willing to continue this therapy for the entire duration of the study (exception: times of acute disease deterioration).

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) 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 number 1.

3. Patients requiring more than 10 puffs of rescue medication (salbutamol/albuterol MDI) per 24 hours on 2 consecutive days during the screening period.

4. Patients with a recent history (i.e. six months or less) of Acute Coronary Syndrome (STEMI, Non-STEMI and Unstable Angina Pectoris).

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

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

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

8. Patients with known active tuberculosis.

9. 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.

10. 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.

11. Patients with significant alcohol or drug abuse on Investigator's assessment within the past two years.

12. 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).

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

14. Pregnant or nursing woman, including female patients with positive beta-HCG test at Visit 1.

15. Female patients of child-bearing potential not using highly effective method of birth control As defined in ICH (M3).

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 oral or patch beta-adrenergics, systemic, i.e. oral or intravenous corticosteroids, 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 depot corticosteroids within six months prior to Visit 1 and/or during the screening period.

19. Patients who have ever been treated with anti-IgE antibodies.

20. Patients who have been treated with leukotriene modifiers, systemic anticholinergics, cromolyn sodium or nedocromil sodium and methylxanthines or phosphodiesterase 4 inhibitors within two weeks prior to Visit 1 and/or during the screening period.

21. Patients who have been treated with inhaled long acting beta adrenergics and long acting beta adrenergics combination products within four weeks prior to Visit 0 and/or during the screening period.

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

23. Patients who have been treated with other non-approved and according to international guidelines not recommended, experimental drugs for routine asthma therapy (e.g. TNFalpha blockers, methotrexate, cyclosporin) within four weeks prior to Visit 1 and/or during the screening period (period between Visit 1 and Visit 2).

24. Patients with any asthma exacerbation or any respiratory tract infection in the four weeks prior to Visit 1 and/or during the screening period (period between Visit 1 and Visit 2).

25. Current participation 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

205.442.54002 Boehringer Ingelheim Investigational Site

Capital Federal, , Argentina

205.442.54005 Boehringer Ingelheim Investigational Site

Capital Federal, , Argentina

205.442.54003 Boehringer Ingelheim Investigational Site

San Juan Bautista, , Argentina

205.442.43002 Boehringer Ingelheim Investigational Site

Linz, , Austria

205.442.43003 Boehringer Ingelheim Investigational Site

Schlüsslberg, , Austria

205.442.43001 Boehringer Ingelheim Investigational Site

Wels, , Austria

205.442.38502 Boehringer Ingelheim Investigational Site

Rijeka, , Croatia

205.442.38501 Boehringer Ingelheim Investigational Site

Split, , Croatia

205.442.38503 Boehringer Ingelheim Investigational Site

Split, , Croatia

205.442.38504 Boehringer Ingelheim Investigational Site

Zagreb, , Croatia

205.442.37203 Boehringer Ingelheim Investigational Site

Kohtla-Järve, , Estonia

205.442.37201 Boehringer Ingelheim Investigational Site

Rakvere, , Estonia

205.442.37202 Boehringer Ingelheim Investigational Site

Tartu, , Estonia

205.442.50203 Boehringer Ingelheim Investigational Site

Guatemala City, , Guatemala

205.442.50204 Boehringer Ingelheim Investigational Site

Guatemala City, , Guatemala

205.442.50201 Boehringer Ingelheim Investigational Site

Nivel Guatemala, , Guatemala

205.442.50202 Boehringer Ingelheim Investigational Site

Nivel Guatemala, , Guatemala

205.442.50205 Boehringer Ingelheim Investigational Site

Vila Hermosa I, , Guatemala

205.442.36007 Boehringer Ingelheim Investigational Site

Budapest, , Hungary

205.442.36003 Boehringer Ingelheim Investigational Site

Cegléd, , Hungary

205.442.36002 Boehringer Ingelheim Investigational Site

Gödöllö, , Hungary

205.442.36004 Boehringer Ingelheim Investigational Site

Komárom, , Hungary

205.442.36006 Boehringer Ingelheim Investigational Site

Pécs, , Hungary

205.442.36001 Boehringer Ingelheim Investigational Site

Szarvas, , Hungary

205.442.36005 Boehringer Ingelheim Investigational Site

Százhalombatta, , Hungary

205.442.91011 Boehringer Ingelheim Investigational Site

Ahmedabad, , India

205.442.91005 Boehringer Ingelheim Investigational Site

Bangalore, , India

205.442.91009 Boehringer Ingelheim Investigational Site

Banglore, , India

205.442.91002 Boehringer Ingelheim Investigational Site

Coimbatore, , India

205.442.91003 Boehringer Ingelheim Investigational Site

Coimbatore, , India

205.442.91004 Boehringer Ingelheim Investigational Site

Coimbatore, , India

205.442.91008 Boehringer Ingelheim Investigational Site

Hyderabad, , India

205.442.91007 Boehringer Ingelheim Investigational Site

Jaipur, , India

205.442.91001 Boehringer Ingelheim Investigational Site

Nagpur, , India

205.442.91006 Boehringer Ingelheim Investigational Site

Pune, , India

205.442.39007 Boehringer Ingelheim Investigational Site

Acquaviva Delle Fonti (BA), , Italy

205.442.39006 Boehringer Ingelheim Investigational Site

Cagliari, , Italy

205.442.39003 Boehringer Ingelheim Investigational Site

Chieti, , Italy

205.442.39001 Boehringer Ingelheim Investigational Site

Pisa, , Italy

205.442.37101 Boehringer Ingelheim Investigational Site

Baldone, , Latvia

205.442.37103 Boehringer Ingelheim Investigational Site

Daugavpils, , Latvia

205.442.37104 Boehringer Ingelheim Investigational Site

Daugavpils, , Latvia

205.442.37102 Boehringer Ingelheim Investigational Site

Talsi, , Latvia

205.442.48003 Boehringer Ingelheim Investigational Site

Giżycko, , Poland

205.442.48002 Boehringer Ingelheim Investigational Site

Gorzów Wielkopolski, , Poland

205.442.48005 Boehringer Ingelheim Investigational Site

Krakow, , Poland

205.442.48004 Boehringer Ingelheim Investigational Site

Ostrow Wielkopolska, , Poland

205.442.48001 Boehringer Ingelheim Investigational Site

Poznan, , Poland

205.442.42105 Boehringer Ingelheim Investigational Site

Bardejov, , Slovakia

205.442.42107 Boehringer Ingelheim Investigational Site

Humenné, , Slovakia

205.442.42104 Boehringer Ingelheim Investigational Site

Košice, , Slovakia

205.442.42102 Boehringer Ingelheim Investigational Site

Nitra, , Slovakia

205.442.42101 Boehringer Ingelheim Investigational Site

Nové Zámky, , Slovakia

205.442.42108 Boehringer Ingelheim Investigational Site

Poprad, , Slovakia

205.442.42106 Boehringer Ingelheim Investigational Site

Spišská Nová Ves, , Slovakia

205.442.42103 Boehringer Ingelheim Investigational Site

Topoľčany, , Slovakia

205.442.82006 Boehringer Ingelheim Investigational Site

Cheongju-si, , South Korea

205.442.82002 Boehringer Ingelheim Investigational Site

Gangwon-do, , South Korea

205.442.82001 Boehringer Ingelheim Investigational Site

Seoul, , South Korea

205.442.82003 Boehringer Ingelheim Investigational Site

Seoul, , South Korea

205.442.82004 Boehringer Ingelheim Investigational Site

Seoul, , South Korea

205.442.82005 Boehringer Ingelheim Investigational Site

Seoul, , South Korea

Countries

Argentina; Austria; Croatia; Estonia; Guatemala; Hungary; India; Italy; Latvia; Poland; Slovakia; South Korea

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, 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)

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)

Paggiaro P, Halpin DM, Buhl R, Engel M, Zubek VB, Blahova Z, Moroni-Zentgraf P, Pizzichini E. The Effect of Tiotropium in Symptomatic Asthma Despite Low- to Medium-Dose Inhaled Corticosteroids: A Randomized Controlled Trial. J Allergy Clin Immunol Pract. 2016 Jan-Feb;4(1):104-13.e2. doi: 10.1016/j.jaip.2015.08.017. Epub 2015 Nov 7.

Reference Type: DERIVED

PMID: 26563670 (View on PubMed)

Other Identifiers

2010-023112-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

205.442

Identifier Type: -

Identifier Source: org_study_id