Efficacy and Safety of 2 Doses of Tiotropium Via Respimat Compared to Placebo in Adolescents With Moderate Persistent Asthma

NCT ID: NCT01257230

Last Updated: 2014-09-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 398 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2013-12-31

Brief Summary

The aim of the study is to evaluate efficacy and safety of a 48-week treatment with two doses of tiotropium bromide compared to placebo in adolescent patients with moderate persistent asthma. Efficacy and safety will be assessed by measuring lung function parameters and evaluating the effects on asthma exacerbations, on Quality of life, on health care resource utilisation an on the number of adverse events.

Conditions

Asthma

Study Design

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

Study Groups

placebo

once daily, delivered with Respimat inhaler

Group Type: PLACEBO_COMPARATOR

placebo Respimat

Intervention Type: DRUG

placebo representing comparator

tiotropium low dose

once daily, delivered with Respimat inhaler

Group Type: EXPERIMENTAL

tiotropium Respimat low dose

Intervention Type: DRUG

IMP

tiotropium high dose

once daily, delivered with Respimat inhaler

Group Type: EXPERIMENTAL

tiotropium Respimat high dose

Intervention Type: DRUG

IMP

Interventions

tiotropium Respimat low dose

IMP

Intervention Type: DRUG

placebo Respimat

placebo representing comparator

Intervention Type: DRUG

tiotropium Respimat high dose

IMP

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. All patients and their parents (or legally accepted caregiver) must sign and date an informed consent consistent with ICH-GCP guidelines and local legislation prior to participation in the trial.

2. Male or female patients between 12 and 17 years of age.

3. All patients must have at least a 3 months history of asthma at the time of enrolment into the trial. The diagnosis of asthma has to be confirmed at visit 1 with a bronchodilator reversibility test.

4. All patients must have been on maintenance treatment with inhaled corticosteroids at a stable medium dose for at least 4 weeks before Visit 1.

5. All patients must be symptomatic (partly controlled) at Visit 1 (screening) and at randomisation defined by an Asthma Control Questionnaire (ACQ) mean score of more than or equal to 1.5.

6. All patients must have a pre-bronchodilator FEV1 more than or equal to 60% and less than or equal to 90% of predicted normal at Visit 1. Variation of absolute FEV1 values of Visit 1 as compared to Visit 2 must be within ± 30%.

7. All patients must have an increase in FEV1 of equal or above 12% and 200 mL after 400 µg salbutamol (albuterol) at Visit 1. If patients in the lower age range (e.g., 12 to 14 year olds) exhibit a very small total lung volume, positive reversibility testing might be based solely on the relative (12%) post-bronchodilator response.

8. All patients should be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment.

9. Patients should be able to use the Respimat® inhaler correctly.

10. Patients must be able to perform all trial related procedures including technically acceptable spirometric manoeuvres.

Exclusion Criteria

1. Patients with a significant disease other than asthma.

2. Patients with clinically relevant abnormal screening haematology or blood chemistry

3. Patients with a history of congenital or acquired heart disease, and/or have been hospitalised for cardiac syncope or failure during the past year.

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

5. Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years.

6. Patients with lung diseases other than asthma (e.g. Cystic Fibrosis). In case of ex-premature infants, a history of significant bronchopulmonary dysplasia will be regarded as exclusion criterion.

7. Patients with known active tuberculosis.

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

9. Patients who have undergone thoracotomy with pulmonary resection.

10. 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).

11. Patients with known hypersensitivity to anticholinergic drugs, Benzalkonium chloride (BAC), Ethylenediaminetetraacetic acis (EDTA) or any other components of the tiotropium inhalation solution.

12. Pregnant or nursing adolescent female patients

13. Sexually active female patients of child-bearing 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 long-acting anticholinergics (e.g. tiotropium -Spiriva) within four weeks prior to screening (Visit 1).

16. Patients who are unable to comply with pulmonary medication restrictions prior to randomisation.

17. Patients who have been treated with Anti-IgE treatment (Omalizumab Xolair) within the last 6 months prior to screening.

18. Patients who have been treated with systemic (oral or intravenous) corticosteroids within 4 weeks prior to screening (Visit 1).

19. Patients who have been treated with long-acting theophylline preparations within 2 weeks prior to screening (Visit 1) or during the run-in period

20. Patients who have been treated with other non-approved and according to international guidelines not recommended ¿experimental¿ drugs for routine asthma therapy.

21. Patients with any acute asthma exacerbation or respiratory tract infection in the 4 weeks prior to Visit 1.

22. Patients requiring 10 or more puffs of rescue medication (salbutamol/albuterol) per day on more than 2 consecutive days during the run-in period.

23. Patients who have previously been randomised in this trial or are currently participating in another study.

24. Patients who are being treated with oral beta-blocker medication.

25. Patients with a known narrow-angle glaucoma, or any other disease where anticholinergic treatment is contraindicated.

26. Patients with renal impairment, as defined by a creatinine clearance less than 50 mL/min/1.73 m2 Body Surface Area as calculated by Schwartz formula.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 17 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

205.444.01004 Boehringer Ingelheim Investigational Site

Plymouth, Minnesota, United States

205.444.01005 Boehringer Ingelheim Investigational Site

Columbia, Missouri, United States

205.444.01001 Boehringer Ingelheim Investigational Site

Cincinnati, Ohio, United States

205.444.01014 Boehringer Ingelheim Investigational Site

Oklahoma City, Oklahoma, United States

205.444.01002 Boehringer Ingelheim Investigational Site

Charleston, South Carolina, United States

205.444.01012 Boehringer Ingelheim Investigational Site

Charleston, South Carolina, United States

205.444.01013 Boehringer Ingelheim Investigational Site

El Paso, Texas, United States

205.444.01003 Boehringer Ingelheim Investigational Site

South Burlington, Vermont, United States

205.444.56002 Boehringer Ingelheim Investigational Site

Santiago, , Chile

205.444.56001 Boehringer Ingelheim Investigational Site

Viña del Mar, , Chile

205.444.56003 Boehringer Ingelheim Investigational Site

Viña del Mar, , Chile

205.444.49007 Boehringer Ingelheim Investigational Site

Berlin, , Germany

205.444.49008 Boehringer Ingelheim Investigational Site

Berlin, , Germany

205.444.49001 Boehringer Ingelheim Investigational Site

Bochum, , Germany

205.444.49003 Boehringer Ingelheim Investigational Site

Ettenheim, , Germany

205.444.49006 Boehringer Ingelheim Investigational Site

Koblenz, , Germany

205.444.49005 Boehringer Ingelheim Investigational Site

Rosenheim, , Germany

205.444.36007 Boehringer Ingelheim Investigational Site

Ajka, , Hungary

205.444.36005 Boehringer Ingelheim Investigational Site

Budapest, , Hungary

205.444.36008 Boehringer Ingelheim Investigational Site

Budapest, , Hungary

205.444.36006 Boehringer Ingelheim Investigational Site

Kaposvár, , Hungary

205.444.36001 Boehringer Ingelheim Investigational Site

Miskolc, , Hungary

205.444.36002 Boehringer Ingelheim Investigational Site

Mosdós, , Hungary

205.444.36003 Boehringer Ingelheim Investigational Site

Szeged, , Hungary

205.444.36004 Boehringer Ingelheim Investigational Site

Szigetbecse, , Hungary

205.444.39001 Boehringer Ingelheim Investigational Site

Ancona, , Italy

205.444.39003 Boehringer Ingelheim Investigational Site

Bolzano, , Italy

205.444.39002 Boehringer Ingelheim Investigational Site

Verona, , Italy

205.444.37101 Boehringer Ingelheim Investigational Site

Baldone, , Latvia

205.444.37107 Boehringer Ingelheim Investigational Site

Balvi, , Latvia

205.444.37102 Boehringer Ingelheim Investigational Site

Ogre, , Latvia

205.444.37105 Boehringer Ingelheim Investigational Site

Rēzekne, , Latvia

205.444.37106 Boehringer Ingelheim Investigational Site

Riga, , Latvia

205.444.37103 Boehringer Ingelheim Investigational Site

Talsi, , Latvia

205.444.37104 Boehringer Ingelheim Investigational Site

Tukums, , Latvia

205.444.52002 Boehringer Ingelheim Investigational Site

Guadalajara, , Mexico

205.444.52001 Boehringer Ingelheim Investigational Site

Hermosillo, , Mexico

205.444.52003 Boehringer Ingelheim Investigational Site

Monterrey, , Mexico

205.444.70003 Boehringer Ingelheim Investigational Site

Moscow, , Russia

205.444.70002 Boehringer Ingelheim Investigational Site

Saint Petersburg, , Russia

205.444.70004 Boehringer Ingelheim Investigational Site

Saint Petersburg, , Russia

205.444.70005 Boehringer Ingelheim Investigational Site

Saint Petersburg, , Russia

205.444.70006 Boehringer Ingelheim Investigational Site

Saint Petersburg, , Russia

205.444.70001 Boehringer Ingelheim Investigational Site

Yaroslavl, , Russia

205.444.42104 Boehringer Ingelheim Investigational Site

Košice, , Slovakia

205.444.42106 Boehringer Ingelheim Investigational Site

Martin, , Slovakia

205.444.42101 Boehringer Ingelheim Investigational Site

Nitra, , Slovakia

205.444.42105 Boehringer Ingelheim Investigational Site

Rožňava, , Slovakia

205.444.82003 Boehringer Ingelheim Investigational Site

Guri-si, , South Korea

205.444.82006 Boehringer Ingelheim Investigational Site

Incheon, , South Korea

205.444.82001 Boehringer Ingelheim Investigational Site

Seoul, , South Korea

205.444.82004 Boehringer Ingelheim Investigational Site

Seoul, , South Korea

205.444.34007 Boehringer Ingelheim Investigational Site

Esplugues Del Llobregat, , Spain

205.444.34001 Boehringer Ingelheim Investigational Site

Madrid, , Spain

205.444.34004 Boehringer Ingelheim Investigational Site

Majadahonda (Madrid), , Spain

205.444.34005 Boehringer Ingelheim Investigational Site

Marbella, , Spain

205.444.34006 Boehringer Ingelheim Investigational Site

Sabdadell, , Spain

205.444.34008 Boehringer Ingelheim Investigational Site

Valencia, , Spain

205.444.38008 Boehringer Ingelheim Investigational Site

Dnipropetrovsk, , Ukraine

205.444.38002 Boehringer Ingelheim Investigational Site

Donetsk, , Ukraine

205.444.38005 Boehringer Ingelheim Investigational Site

Kharkiv, , Ukraine

205.444.38003 Boehringer Ingelheim Investigational Site

Kiev, , Ukraine

205.444.38004 Boehringer Ingelheim Investigational Site

Kiev, , Ukraine

205.444.38001 Boehringer Ingelheim Investigational Site

Lviv, , Ukraine

205.444.38010 Boehringer Ingelheim Investigational Site

Zaporizhya, , Ukraine

205.444.38009 Boehringer Ingelheim Investigational Site

Zaporizhzhya, , Ukraine

Countries

United States; Chile; Germany; Hungary; Italy; Latvia; Mexico; Russia; Slovakia; South Korea; Spain; Ukraine

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)

Hamelmann E, Bateman ED, Vogelberg C, Szefler SJ, Vandewalker M, Moroni-Zentgraf P, Avis M, Unseld A, Engel M, Boner AL. Tiotropium add-on therapy in adolescents with moderate asthma: A 1-year randomized controlled trial. J Allergy Clin Immunol. 2016 Aug;138(2):441-450.e8. doi: 10.1016/j.jaci.2016.01.011. Epub 2016 Mar 5.

Reference Type: DERIVED

PMID: 26960245 (View on PubMed)

Other Identifiers

2010-021093-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

205.444

Identifier Type: -

Identifier Source: org_study_id