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

NCT ID: NCT01277523

Last Updated: 2014-10-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 392 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2013-10-31

Brief Summary

The overall purpose of the trial is to evaluate efficacy and safety of tiotropium inhalation solution delivered via Respimat® inhaler (2.5 mcg and 5 mcg once daily) over 12 weeks, compared to placebo, as add-on controller therapy on top of usual care in adolescents (12 to 17 years old) with severe persistent asthma.

The primary objective of the trial is to demonstrate superiority of tiotropium (5 mcg and possibly 2.5 mcg once daily in the evening) over placebo with regard to the primary pulmonary function endpoint after 12 weeks of treatment.

Secondary objectives are to evaluate efficacy of tiotropium with regard to other endpoints, and to evaluate the safety of tiotropium, compared to placebo, as add-on controller therapy on top of usual care in this patient population.

Conditions

Asthma

Study Design

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

Study Groups

A

Group Type: EXPERIMENTAL

tiotropium low dose

Intervention Type: DRUG

2 actuations once daily

B

Group Type: EXPERIMENTAL

tiotropium high dose

Intervention Type: DRUG

2 actuations once daily

C

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

2 actuations once daily

Interventions

tiotropium high dose

2 actuations once daily

Intervention Type: DRUG

placebo

2 actuations once daily

Intervention Type: DRUG

tiotropium low dose

2 actuations once daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. All patients and their parent(s) (or legally accepted representative) must sign and date respectively an informed assent and an informed consent consistent with International Conference on Harmonisation - Harmonised Tripartite Guideline for Good Clinical Practice (ICH-GCP) guidelines and local legislation prior to the patient's participation in the trial. A separate informed consent/assent is required for pharmacogenomic sampling.

2. Male or female patients between 12 and 17 years of age (at date of informed consent/assent).

3. All patients must have at least a 3-month history of asthma at the time of enrolment into the trial.

4. All patients must have been on maintenance treatment with an inhaled corticosteroid either at stable high dose in combination with another controller medication, OR at stable medium dose in combination with two other controller medications, for at least 4 weeks before Visit 1.

5. 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 = 1.5.

6. All patients must have a pre-bronchodilator Forced Expiratory Volume in 1 second (FEV1) = 60% and = 90% of predicted normal at Visit 1.

7. Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator, considered as 100%) as compared to Visit 2 (pre-dose) must be within ± 30%.

8. All patients must confirm the diagnosis of asthma by bronchodilator reversibility at Visit 1, resulting in an increase in FEV1 of = 12% and = 200 mL 15 to 30 minutes after 400 µg salbutamol (albuterol). If patients in the lower age range (e.g. 12 to 14 year old patients) exhibit a very small total lung volume, positive reversibility testing might be based solely on the relative (=12%) post-bronchodilator response.

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

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 spirometric manoeuvres according to American Thoracic Society/ European Respiratory Society (ATS/ERS) standards and use of the electronic diary/peak flow meter (diary compliance of at least 80% is required).

Exclusion Criteria

1. Significant disease other than asthma.

2. Abnormal haematology or blood chemistry.

3. History of heart disease, and/or hospitalised for cardiac syncope or failure.

4. Any unstable or life-threatening or requiring intervention or cardiac arrhythmia.

5. Malignancy for which the patient has undergone resection, radiation therapy or chemotherapy.

6. Active tuberculosis.

7. Alcohol or drug abuse.

8. Thoracotomy with pulmonary resection.

9. Pulmonary rehabilitation program.

10. Hypersensitivity to anticholinergic drugs, or any components of the study medication delivery system.

11. Pregnant or nursing adolescent female patients.

12. Female patients of child-bearing potential not using a highly effective method of birth control.

13. Investigational drug within four weeks or six half lives prior to Visit 1.

14. Long-acting anticholinergics within four weeks prior to Visit 1.

15. Systemic corticosteroids at a high dose or at a not stable low dose within four weeks prior to Visit 1.

16. Leukotriene modifiers if not stabilised for at least four weeks prior to Visit 1.

17. Long-acting theophylline preparations if not stabilised for at least two weeks prior to Visit 1.

18. Anti Immunoglobulin E (Anti-IgE) treatment if not stabilised for at least six months prior to Visit 1.

19. Cromones if not stabilised within four weeks prior to Visit 1.

20. Oral beta-blocker medication within four weeks prior to Visit 1.

21. Systemic oral or i.v. or s.c. beta-adrenergics within four weeks prior to Visit 1.

22. Other non-approved and according to international guidelines not recommended experimental drugs for routine asthma therapy within four weeks prior to Visit 1.

23. Any acute asthma exacerbation or respiratory tract infection in the four weeks prior to Visit 1and/or in the four weeks prior to Visit 2. In case of an asthma deterioration occurring in the four weeks prior to Visit 1 and/or in the four weeks prior to Visit 2, the visit must be postponed.

24. Randomised in this trial or currently participating in another trial.

25. Narrow-angle glaucoma, or any other disease where anticholinergic treatment is contraindicated.

26. Moderate to severe renal impairment.

27. Patients requiring 10 or more puffs of rescue medication per day on more than 2 consecutive days in the four weeks prior to Visit 1 and/or in the four weeks prior to Visit 2. In case of an asthma deterioration occurring in the four weeks prior to Visit 1 and/or in the four weeks prior to Visit 2, the visit must be postponed.

• 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

205.456.01004 Boehringer Ingelheim Investigational Site

Stockton, California, United States

205.456.01008 Boehringer Ingelheim Investigational Site

Normal, Illinois, United States

205.456.01003 Boehringer Ingelheim Investigational Site

Baltimore, Maryland, United States

205.456.01007 Boehringer Ingelheim Investigational Site

Columbia, Missouri, United States

205.456.01002 Boehringer Ingelheim Investigational Site

Bellevue, Nebraska, United States

205.456.01001 Boehringer Ingelheim Investigational Site

Rockville Centre, New York, United States

205.456.01005 Boehringer Ingelheim Investigational Site

Cincinnati, Ohio, United States

205.456.01006 Boehringer Ingelheim Investigational Site

Summerville, South Carolina, United States

205.456.54002 Boehringer Ingelheim Investigational Site

Capital Federal, , Argentina

205.456.54006 Boehringer Ingelheim Investigational Site

Capital Federal, , Argentina

205.456.54008 Boehringer Ingelheim Investigational Site

Capital Federal, , Argentina

205.456.54005 Boehringer Ingelheim Investigational Site

Mendoza, , Argentina

205.456.54003 Boehringer Ingelheim Investigational Site

San Juan Bautista, , Argentina

205.456.54004 Boehringer Ingelheim Investigational Site

San Miguel de Tucumán, , Argentina

205.456.54009 Boehringer Ingelheim Investigational Site

San Miguel de Tucumán, , Argentina

205.456.61002 Boehringer Ingelheim Investigational Site

Parkville, Victoria, Australia

205.456.61001 Boehringer Ingelheim Investigational Site

Perth, Western Australia, Australia

205.456.35902 Boehringer Ingelheim Investigational Site

Plovdiv, , Bulgaria

205.456.35901 Boehringer Ingelheim Investigational Site

Rousse, , Bulgaria

205.456.35903 Boehringer Ingelheim Investigational Site

Sofia, , Bulgaria

205.456.49008 Boehringer Ingelheim Investigational Site

Berlin, , Germany

205.456.49001 Boehringer Ingelheim Investigational Site

Bochum, , Germany

205.456.49004 Boehringer Ingelheim Investigational Site

Frankfurt, , Germany

205.456.49005 Boehringer Ingelheim Investigational Site

Kehl, , Germany

205.456.49003 Boehringer Ingelheim Investigational Site

Koblenz, , Germany

205.456.49010 Boehringer Ingelheim Investigational Site

Mainz, , Germany

205.456.49007 Boehringer Ingelheim Investigational Site

Neu-Isenburg, , Germany

205.456.49002 Boehringer Ingelheim Investigational Site

Wesel, , Germany

205.456.50201 Boehringer Ingelheim Investigational Site

Guatemala City, , Guatemala

205.456.50203 Boehringer Ingelheim Investigational Site

Guatemala City, , Guatemala

205.456.50204 Boehringer Ingelheim Investigational Site

Guatemala City, , Guatemala

205.456.50205 Boehringer Ingelheim Investigational Site

Guatemala City, , Guatemala

205.456.36005 Boehringer Ingelheim Investigational Site

Budapest, , Hungary

205.456.36002 Boehringer Ingelheim Investigational Site

Debrecen, , Hungary

205.456.36004 Boehringer Ingelheim Investigational Site

Gyula, , Hungary

205.456.36001 Boehringer Ingelheim Investigational Site

Miskolc, , Hungary

205.456.36007 Boehringer Ingelheim Investigational Site

Mosdós, , Hungary

205.456.36006 Boehringer Ingelheim Investigational Site

Nagyatád, , Hungary

205.456.97205 Boehringer Ingelheim Investigational Site

Holon, , Israel

205.456.97203 Boehringer Ingelheim Investigational Site

Petah Tikva, , Israel

205.456.97201 Boehringer Ingelheim Investigational Site

Safed, , Israel

205.456.37101 Boehringer Ingelheim Investigational Site

Baldone, , Latvia

205.456.37104 Boehringer Ingelheim Investigational Site

Balvi, , Latvia

205.456.37103 Boehringer Ingelheim Investigational Site

Rēzekne, , Latvia

205.456.37102 Boehringer Ingelheim Investigational Site

Riga, , Latvia

205.456.37105 Boehringer Ingelheim Investigational Site

Talsi, , Latvia

205.456.52001 Boehringer Ingelheim Investigational Site

Hermosillo Sonora, , Mexico

205.456.52002 Boehringer Ingelheim Investigational Site

Monterrey, , Mexico

205.456.52003 Boehringer Ingelheim Investigational Site

Monterrey, , Mexico

205.456.52004 Boehringer Ingelheim Investigational Site

Nuevo León, , Mexico

205.456.09001 Boehringer Ingelheim Investigational Site

Quezon City, , Philippines

205.456.09002 Boehringer Ingelheim Investigational Site

Quezon City, , Philippines

205.456.35105 Boehringer Ingelheim Investigational Site

Coimbra, , Portugal

205.456.35101 Boehringer Ingelheim Investigational Site

Lisbon, , Portugal

205.456.35102 Boehringer Ingelheim Investigational Site

Lisbon, , Portugal

205.456.35104 Boehringer Ingelheim Investigational Site

Lisbon, , Portugal

205.456.35103 Boehringer Ingelheim Investigational Site

Porto, , Portugal

205.456.27001 Boehringer Ingelheim Investigational Site

Cape Town, , South Africa

205.456.27002 Boehringer Ingelheim Investigational Site

Durban, , South Africa

205.456.38006 Boehringer Ingelheim Investigational Site

Dnipropetrovsk, , Ukraine

205.456.38004 Boehringer Ingelheim Investigational Site

Kharkiv, , Ukraine

205.456.38003 Boehringer Ingelheim Investigational Site

Kiev, , Ukraine

205.456.38010 Boehringer Ingelheim Investigational Site

Kryvyi Rih, , Ukraine

205.456.38009 Boehringer Ingelheim Investigational Site

Kyiv, , Ukraine

205.456.38001 Boehringer Ingelheim Investigational Site

Lviv, , Ukraine

205.456.38007 Boehringer Ingelheim Investigational Site

Lviv, , Ukraine

205.456.38005 Boehringer Ingelheim Investigational Site

Uzhhorod, , Ukraine

205.456.38008 Boehringer Ingelheim Investigational Site

Vinnytsia, , Ukraine

205.456.38002 Boehringer Ingelheim Investigational Site

Zaporizhzhya, , Ukraine

Countries

United States; Argentina; Australia; Bulgaria; Germany; Guatemala; Hungary; Israel; Latvia; Mexico; Philippines; Portugal; South Africa; 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, 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, Bernstein JA, Vandewalker M, Moroni-Zentgraf P, Verri D, Unseld A, Engel M, Boner AL. A randomised controlled trial of tiotropium in adolescents with severe symptomatic asthma. Eur Respir J. 2017 Jan 11;49(1):1601100. doi: 10.1183/13993003.01100-2016. Print 2017 Jan.

Reference Type: DERIVED

PMID: 27811070 (View on PubMed)

Other Identifiers

2010-021778-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

205.456

Identifier Type: -

Identifier Source: org_study_id