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

NCT ID: NCT01634152

Last Updated: 2016-01-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 401 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2015-05-31

Brief Summary

The overall purpose of the trial is to evaluate efficacy and safety of tiotropium inhalation solution (2.5 mcg and 5 mcg) delivered via Respimat® inhaler once daily in the evening over 12 weeks, compared to placebo, as add-on controller therapy on top of usual care in children (6 to 11 years old) with severe persistent asthma.

Conditions

Asthma

Study Design

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

Study Groups

Placebo QD

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

2 actuations once daily in the evening

Tiotropium low dose QD

Group Type: EXPERIMENTAL

Tiotropium low dose mcg

Intervention Type: DRUG

2 actuations once daily in the evening

Tiotropium medium dose QD

Group Type: EXPERIMENTAL

Tiotropium high dose

Intervention Type: DRUG

2 actuations once daily in the evening

Interventions

Placebo

2 actuations once daily in the evening

Intervention Type: DRUG

Tiotropium low dose mcg

2 actuations once daily in the evening

Intervention Type: DRUG

Tiotropium high dose

2 actuations once daily in the evening

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. All patients' parent(s) (or legal guardian) must sign and date an informed consent prior to participation in the trial. In addition, an informed assent suitable for this age group has to be obtained from patients. A separate informed consent/assent is required for pharmacogenomic sampling.

2. Male or female patients between 6 and 11 years of age.

3. All patients must have at least a 6-month history of asthma.

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 (partly controlled) at Visit 1 and prior to randomisation at Visit 2 as defined by an Asthma Control Questionnaire (ACQ-IA) mean score >= 1.5.

6. All patients must have a pre-bronchodilator forced expiratory volume in one 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% 15 to 30 minutes after 200 mcg salbutamol/albuterol.

9. Patients must be able to use the Respimat inhaler correctly.

10. Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of electronic diary/peak flow meter (diary compliance of at least 80% is required).

Exclusion Criteria

1. Patients with a significant disease other than asthma.

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

3. Patients with a history of congenital or acquired heart disease, or patients who 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 a malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years.

6. Patients with known active tuberculosis.

7. Patients who have undergone thoracotomy with pulmonary resection.

8. Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the six weeks prior to Visit 1.

9. Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other components of the inhalation solution used with the Respimat inhaler.

10. Pregnant or nursing female patients, including postmenarchal girls with a positive urine pregnancy test at Visit 1.

11. Postmenarchal girls of child-bearing potential not using a highly effective method of birth control.

12. Patients who have been treated with systemic corticosteroids within four weeks prior to Visit 1.

13. Patients who have been treated with systemic beta-adrenergics within four weeks prior to Visit 1.

14. Patients who have been treated with oral beta-blocker medication within four weeks prior to Visit 1 and/or during the screening period.

15. Patients who have been treated with inhaled long-acting anticholinergics or systemic anticholinergic treatment within four weeks prior to Visit 1 and/or during the screening period, or who have been treated with inhaled short-acting anticholinergics within two weeks prior to Visit 1.

16. Patients who have been treated with short-acting theophylline preparations within two weeks prior to Visit 1.

17. Patients who have been treated with 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.

18. Patients who have taken an investigational drug within six half lives according to the investigator's information, or four weeks (whichever is greater) prior to Visit 1 and/or during the screening period.

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

20. Patients with any acute asthma exacerbation or respiratory tract infection 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.

21. Patients requiring six or more puffs of rescue medication per day on more than two 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.

22. Patients who are unable to comply with medication restrictions prior to Visit 1 and/or prior to Visit 2.

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

24. Patients with moderate to severe renal impairment, as defined by a creatinine clearance <50 mL/min/1.73 m2 BSA, as tiotropium is a predominantly renally excreted drug.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 11 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

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Rolling Hills Estates, California, United States

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Denver, Colorado, United States

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North Dartmouth, Massachusetts, United States

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Columbia, Missouri, United States

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Cincinnati, Ohio, United States

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Oklahoma City, Oklahoma, United States

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Charleston, South Carolina, United States

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North Charleston, South Carolina, United States

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Arlington, Texas, United States

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San Antonio, Texas, United States

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Buenos Aires, , Argentina

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Capital Federal, , Argentina

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Capital Federal, , Argentina

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Capital Federal, , Argentina

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Mar del Plata, , Argentina

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Mendoza, , Argentina

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San Miguel de Tucumán, , Argentina

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Herston, Queensland, Australia

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Perth, Western Australia, Australia

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Antwerp, , Belgium

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Bruges, , Belgium

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Namur, , Belgium

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Curitiba, , Brazil

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Goiânia, , Brazil

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Porto Alegre, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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São Paulo, , Brazil

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London, Ontario, Canada

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Sherbrooke, Quebec, Canada

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Jablonec nad Nisou, , Czechia

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Jihlava, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Berlin, , Germany

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Berlin, , Germany

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Bochum, , Germany

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Dresden, , Germany

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Frankfurt, , Germany

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Koblenz, , Germany

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Marburg, , Germany

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Mönchengladbach, , Germany

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Guatemala City, , Guatemala

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Guatemala City, , Guatemala

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Guatemala City, , Guatemala

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Guatemala City, , Guatemala

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Ajka, , Hungary

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Budapest, , Hungary

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Szeged, , Hungary

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Baldone, , Latvia

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Balvi, , Latvia

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Daugavpils, , Latvia

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Jēkabpils, , Latvia

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Ogre, , Latvia

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Rēzekne, , Latvia

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Riga, , Latvia

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Riga, , Latvia

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Šiauliai, , Lithuania

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Tauragė, , Lithuania

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Utena, , Lithuania

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Vilnius, , Lithuania

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Bialystok, , Poland

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Lodz, , Poland

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Lublin, , Poland

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Tarnów, , Poland

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Bucharest, , Romania

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Novosibirsk, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Yaroslavl, , Russia

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Košice, , Slovakia

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Prešov, , Slovakia

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Spišská Nová Ves, , Slovakia

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Chernivtsi, , Ukraine

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Dnipropetrovsk, , Ukraine

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Dnipropetrovsk, , Ukraine

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Donetsk, , Ukraine

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Donetsk, , Ukraine

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Kharkiv, , Ukraine

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Kiev, , Ukraine

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Kryvyi Rih, , Ukraine

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Lviv, , Ukraine

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Odesa, , Ukraine

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Vinnytsia, , Ukraine

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Zaporizhya, , Ukraine

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Zaporizhzhya, , Ukraine

Countries

United States; Argentina; Australia; Belgium; Brazil; Canada; Czechia; Germany; Guatemala; Hungary; Latvia; Lithuania; Poland; Romania; Russia; Slovakia; Ukraine

Other Identifiers

2011-001777-43

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

205.446

Identifier Type: -

Identifier Source: org_study_id