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

Asthma Clinical Trial

Official title:

A Randomised, Double-blind, Placebo-controlled, Parallel-group Trial 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 48 Weeks in Children (6 to 11 Years Old) With Moderate Persistent Asthma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01634139
• Other study ID #: 205.445
• Secondary ID: 2011-001758-26
• Status: Completed
• Phase: Phase 3
• First received: July 3, 2012
• Last updated: January 6, 2016
• Start date: July 2012
• Est. completion date: December 2015

Study information

• Verified date: January 2016
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Bulgaria: Bulgarian Drug AgencyCanada: Health CanadaGermany: Federal Institute for Drugs and Medical DevicesGuatemala: Ministry of Public Health and Social AssistanceHungary: National Institute of PharmacyLatvia: State Agency of MedicinesLithuania: State Medicine Control Agency - Ministry of HealthNorway: Norwegian Medicines AgencyPortugal: National Pharmacy and Medicines InstituteRomania: National Medicines AgencyRussia: Pharmacological Committee, Ministry of HealthSouth Korea: Ministry of Food and Drug Safety (MFDS)Sweden: Medical Products AgencyUkraine: State Pharmacological Center - Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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 in the evening) over 48 weeks, compared to placebo, in children (6 to 11 years old) with moderate persistent asthma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 403
• Est. completion date: December 2015
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 11 Years

Eligibility

Inclusion criteria:

Inclusion criteria are:

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 at a stable medium dose, either as mono treatment or in combination with another controller medication, for at least 4 weeks before Visit 1. While the LTRA is permitted throughout the trial, the LABA has to be stopped at least 24 hours prior to Visit 1, as no LABAs are permitted during screening and treatment period of this trial.

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:

Exclusion criteria are:

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 hospitalized 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 girl with a positive urine pregnancy test at Visit 1.

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

12. Patients who have been treated with anti-IgE treatment within the last six months prior to Visit 1 and/or during the screening period.

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

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

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

16. 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.

17. Patients who have been treated with long-acting theophylline preparations within four weeks prior to Visit 1 and/or during the screening period or who have been treated with short-acting theophylline preparations within two weeks prior to Visit 1.

18. 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.

19. 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.

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

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

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

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

25. 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Tiotropium low dose QD
2 actuations once daily in the evening
• Tiotropium high dose QD
2 actuations once daily in the evening
• Placebo
2 actuations once daily in the evening

Locations

Country	Name	City	State
Bulgaria	205.445.35901 Boehringer Ingelheim Investigational Site	Sofia
Bulgaria	205.445.35902 Boehringer Ingelheim Investigational Site	Sofia
Bulgaria	205.445.35903 Boehringer Ingelheim Investigational Site	Sofia
Bulgaria	205.445.35904 Boehringer Ingelheim Investigational Site	Sofia
Bulgaria	205.445.35905 Boehringer Ingelheim Investigational Site	Sofia
Canada	205.445.02003 Boehringer Ingelheim Investigational Site	London	Ontario
Canada	205.445.02001 Boehringer Ingelheim Investigational Site	Sherbrooke	Quebec
Germany	205.445.49012 Boehringer Ingelheim Investigational Site	Berlin
Germany	205.445.49015 Boehringer Ingelheim Investigational Site	Berlin
Germany	205.445.49001 Boehringer Ingelheim Investigational Site	Bochum
Germany	205.445.49007 Boehringer Ingelheim Investigational Site	Dresden
Germany	205.445.49004 Boehringer Ingelheim Investigational Site	Ettenheim
Germany	205.445.49009 Boehringer Ingelheim Investigational Site	Koblenz
Germany	205.445.49014 Boehringer Ingelheim Investigational Site	Marburg
Guatemala	205.445.50201 Boehringer Ingelheim Investigational Site	Guatemala
Guatemala	205.445.50202 Boehringer Ingelheim Investigational Site	Guatemala
Guatemala	205.445.50203 Boehringer Ingelheim Investigational Site	Guatemala
Guatemala	205.445.50204 Boehringer Ingelheim Investigational Site	Guatemala
Guatemala	205.445.50205 Boehringer Ingelheim Investigational Site	Guatemala
Hungary	205.445.36003 Boehringer Ingelheim Investigational Site	Ajka
Hungary	205.445.36001 Boehringer Ingelheim Investigational Site	Budapest
Hungary	205.445.36002 Boehringer Ingelheim Investigational Site	Dombovar
Korea, Republic of	205.445.82003 Boehringer Ingelheim Investigational Site	Guri
Korea, Republic of	205.445.82002 Boehringer Ingelheim Investigational Site	Incheon
Korea, Republic of	205.445.82001 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	205.445.82005 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	205.445.82006 Boehringer Ingelheim Investigational Site	Sungnam
Latvia	205.445.37104 Boehringer Ingelheim Investigational Site	Adazi
Latvia	205.445.37101 Boehringer Ingelheim Investigational Site	Baldone
Latvia	205.445.37106 Boehringer Ingelheim Investigational Site	Balvi
Latvia	205.445.37108 Boehringer Ingelheim Investigational Site	Daugavpils
Latvia	205.445.37102 Boehringer Ingelheim Investigational Site	Ogre
Latvia	205.445.37107 Boehringer Ingelheim Investigational Site	Rezekne
Latvia	205.445.37103 Boehringer Ingelheim Investigational Site	Riga
Latvia	205.445.37105 Boehringer Ingelheim Investigational Site	Riga
Lithuania	205.445.37002 Boehringer Ingelheim Investigational Site	Siauliai
Lithuania	205.445.37005 Boehringer Ingelheim Investigational Site	Utena
Lithuania	205.445.37003 Boehringer Ingelheim Investigational Site	Vilnius
Norway	205.445.47002 Boehringer Ingelheim Investigational Site	Oslo
Portugal	205.445.35108 Boehringer Ingelheim Investigational Site	Amadora
Portugal	205.445.35106 Boehringer Ingelheim Investigational Site	Aveiro
Portugal	205.445.35101 Boehringer Ingelheim Investigational Site	Lisboa
Portugal	205.445.35102 Boehringer Ingelheim Investigational Site	Lisboa
Portugal	205.445.35107 Boehringer Ingelheim Investigational Site	Lisboa
Portugal	205.445.35103 Boehringer Ingelheim Investigational Site	Porto
Portugal	205.445.35105 Boehringer Ingelheim Investigational Site	Porto
Romania	205.445.40001 Boehringer Ingelheim Investigational Site	Bucharest
Romania	205.445.40004 Boehringer Ingelheim Investigational Site	Bucharest
Romania	205.445.40003 Boehringer Ingelheim Investigational Site	Cluj Napoca
Russian Federation	205.445.70002 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	205.445.70005 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	205.445.70008 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	205.445.70011 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	205.445.70001 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	205.445.70003 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	205.445.70004 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	205.445.70009 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	205.445.70010 Boehringer Ingelheim Investigational Site	Yaroslavl
Sweden	205.445.46001 Boehringer Ingelheim Investigational Site	Stockholm
Ukraine	205.445.38017 Boehringer Ingelheim Investigational Site	Chernivtsi
Ukraine	205.445.38003 Boehringer Ingelheim Investigational Site	Dnipropetrovsk
Ukraine	205.445.38005 Boehringer Ingelheim Investigational Site	Donetsk
Ukraine	205.445.38011 Boehringer Ingelheim Investigational Site	Donetsk
Ukraine	205.445.38008 Boehringer Ingelheim Investigational Site	Kharkiv
Ukraine	205.445.38004 Boehringer Ingelheim Investigational Site	Kiev
Ukraine	205.445.38012 Boehringer Ingelheim Investigational Site	Kriviy Rig
Ukraine	205.445.38001 Boehringer Ingelheim Investigational Site	Lviv
Ukraine	205.445.38009 Boehringer Ingelheim Investigational Site	Lviv
Ukraine	205.445.38016 Boehringer Ingelheim Investigational Site	Odessa
Ukraine	205.445.38006 Boehringer Ingelheim Investigational Site	Vinnytsya
Ukraine	205.445.38010 Boehringer Ingelheim Investigational Site	Zaporizhya
Ukraine	205.445.38002 Boehringer Ingelheim Investigational Site	Zaporizhzhya
United Kingdom	205.445.44001 Boehringer Ingelheim Investigational Site	London
United States	205.445.01012 Boehringer Ingelheim Investigational Site	Arlington	Texas
United States	205.445.01006 Boehringer Ingelheim Investigational Site	Charleston	South Carolina
United States	205.445.01001 Boehringer Ingelheim Investigational Site	Cincinnati	Ohio
United States	205.445.01002 Boehringer Ingelheim Investigational Site	Columbia	Missouri
United States	205.445.01004 Boehringer Ingelheim Investigational Site	El Paso	Texas
United States	205.445.01010 Boehringer Ingelheim Investigational Site	Oklahoma City	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
Boehringer Ingelheim	Pfizer

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Germany,  Guatemala,  Hungary,  Korea, Republic of,  Latvia,  Lithuania,  Norway,  Portugal,  Romania,  Russian Federation,  Sweden,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peak forced expiratory volume in one second response within 3 hours post dosing (FEV1 peak0-3h response)		after 24 weeks	No
Secondary	Area under the curve from zero to 3 hours of the forced expiratory volume in one second (FEV1) response and area under the curve from zero to 3 hours ofthe forced vital capacity (FVC) response		24 weeks	No
Secondary	Individual in-clinic forced expiratory volume in one second (FEV1) response and forced vital capacity (FVC) response response		24 week	No
Secondary	Asthma control assessed by Asthma Control Questionnaire (ACQ-IA)		24 and 48 week	No
Secondary	Number of responders assessed by Asthma Control Questionnaire (ACQ-IA)		24 and 48 week	No
Secondary	Quality of life assessed by Paediatric Asthma Quality of Life Questionnaire (PAQLQ(S))		24 and 48 week	No
Secondary	Use of rescue medication		24 and 48 week	No
Secondary	Change from baseline in mean weekly pre-dose morning and evening peak expiratory flow (PEF) measured by patients at home		24 and 48 week	No
Secondary	Trough forced expiratory volume in one second (trough FEV1) response		after 24 weeks	No
Secondary	Trough forced expiratory volume in one second (trough FEV1) response		after 48 weeks	No
Secondary	Peak forced vital capacity response within 3 hours post dosing (FVC peak0-3h response)		after 24 and 48 week	No
Secondary	Trough forced vital capacity (trough FVC) response		after 24 and 48 week	No
Secondary	Change from baseline in mean weekly pre-dose morning and evening forced expiratory volume in one second (FEV1) measured by patients at home		24 and 48 week	No
Secondary	Change from baseline in the absolute difference between morning and evening peak expiratory flow (PEF) value divided by the mean of these two values (weekly means will be compared)		24 and 48 week	No
Secondary	Asthma symptoms assessed by the patient's electronic diary		24 and 48 week	No