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

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Tiotropium high dose QD; Drug: Tiotropium low dose QD; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 403
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tiotropium high dose QD	Drug: Tiotropium high dose QD; 2 actuations once daily in the evening
Experimental: Tiotropium low dose QD	Drug: Tiotropium low dose QD; 2 actuations once daily in the evening
Experimental: Placebo QD	Drug: Placebo; 2 actuations once daily in the evening

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1 Peak (0-3h) Change From Baseline	Change from baseline in peak forced expiratory volume (FEV) in 1 second within the first 3 hours (h) post dosing (FEV1 peak(0-3h)) measured at week 24. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants with available data at the timepoint of interest.	Baseline and 24 Weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough FEV1 Change From Baseline	Change from Baseline in Trough (pre-dose) Forced Expiratory Volume (FEV) in 1 second (FEV1) measured at week 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Baseline and Week 24, Baseline and Week 48.
FEV1 Peak (0-3h) at Week 48 Change From Baseline	Change from baseline in peak forced expiratory volume (FEV) in 1 second within the first 3 hours (h) post dosing (FEV1 peak(0-3h)) measured at week 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants with available data at the timepoint of interest.	Baseline and Week 48.
FEV1 AUC (0-3h) Change From Baseline	Change from baseline of area under the curve (AUC) from 0 to 3 hours for FEV1 (FEV1 AUC (0-3h)) after 24 weeks of treatment. The AUC was calculated by using the trapezoidal rule divided by the observation time (3h). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants with available data at the timepoint of interest.	Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at week 24
FEV1 Change From Baseline at Each Individual Timepoint	FEV1 change from baseline to week 24 at each individual timepoint. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 24 weeks
FVC Peak(0-3h) Change From Baseline	Change from baseline in Maximum forced vital capacity (FVC) measured within the first 3 hours after administration of trial medication (FVC peak(0-3h)) after 24 and 48 Weeks of treatment. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Baseline and Week 24, Baseline and Week 48.
Trough FVC Change From Baseline	Change from baseline in Trough (pre-dose) FVC measured at week 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Baseline and Week 24, Baseline and Week 48
FVC AUC (0-3h) Change From Baseline	Change from baseline of area under the curve (AUC) from 0 to 3 hours for FVC (Forced vital capacity) (FVC AUC (0-3h)) after 24 weeks of treatment. The AUC was calculated by using the trapezoidal rule divided by the observation time (3h). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants with available data at the timepoint of interest.	Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 24 weeks
FVC Change From Baseline at Each Individual Timepoint	FVC change from baseline to week 24 at each individual timepoint. The measured values presented are actually adjusted means The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at Week 24
Use of PRN (Pro re Nata) Rescue Medication Per Day	Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used per day (24 hour period) based on the weekly mean at weeks 24 and 48. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Baseline and Week 24, Baseline and Week 48.
Use of PRN Rescue Medication During Daytime	Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during daytime based on the weekly mean at weeks 24 and 48. Measured values presented are actually adjusted means The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Baseline and Week 24, Baseline and Week 48.
Use of PRN Rescue Medication During Nighttime	Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during nighttime based on the weekly mean at weeks 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Baseline and Week 24, Baseline and Week 48.
Peak Expiratory Flow (PEF) a.m. Change From Baseline	Change from baseline in the morning (a.m.) peak expiratory flow based on the weekly mean at weeks 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Baseline and Week 24, Baseline and Week 48.
PEF p.m. Change From Baseline	Change from baseline in the evening (p.m.) peak expiratory flow based on the weekly mean at weeks 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Baseline and Week 24, Baseline and Week 48.
PEF Variability Change From Baseline	Change from baseline in the peak expiratory flow variability based on the weekly mean at week 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Baseline and Week 24, Baseline and Week 48.
FEV1 a.m Change From Baseline	Change from baseline in morning (a.m.) FEV1 based on the weekly mean at week 24 and 48. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Baseline and Week 24, Baseline and Week 48.
FEV1 p.m. Change From Baseline	Change from baseline in evening (p.m.) FEV1 based on the weekly mean at week 24 and 48. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Baseline and Week 24, Baseline and Week 48.
ACQ-IA Total Score	Interviewer Administered Asthma Control Questionnaire (ACQ-IA) total score after 24 and 48 weeks of treatment. The ACQ-IA is a scale containing 7 questions. Each question has a 7 point scale which ranges from 0 to 6. A score of 0 corresponds to no impairment and a score of 6 corresponds to maximum impairment. ACQ-IA total score is calculated as the mean of the responses to all 7 questions. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Weeks 24 and 48.
ACQ-IA Responder Analysis	Responder categories based on the ACQ-IA total score after 24 and 48 weeks of treatment. Analysis was performed using the following categories and definitions: responder (change from trial baseline ≤-0.5), no change (-0.5 <change from trial baseline <0.5) and worsening (change from trial baseline ≥0.5). No statistical testing was performed for ACQ-IA total score responders. The ACQ-IA is a scale containing 7 questions, each question has a 7-point scale which ranges from 0 to 6; a score of 0 corresponds to no impairment and a score of 6 corresponds to maximum impairment.	Weeks 24 and 48
PAQLQ(S) Total Score	Standardised Paediatric Asthma Quality of Life Questionnaire (PAQLQ(S)) total score at weeks 24 and 48. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). Total Score is calculated as mean of all 23 questions. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Weeks 24 and 48.
PAQLQ(S) Symptom Domain Score	PAQLQ(S) symptom domain score at weeks 24 and 48. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). The individual domain score was calculated as the mean of the items in the domain. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Weeks 24 and 48.
PAQLQ(S) Activity Limitation Domain Score	PAQLQ(S) activity limitation domain score at weeks 24 and 48. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). The individual domain score is calculated as the mean of the items in this domain. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Weeks 24 and 48.
PAQLQ(S) Emotional Function Domain Score	PAQLQ(S) emotional function domain score at weeks 24 and 48. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control). The individual domain score is calculated as the mean of the items in this domain. The measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Weeks 24 and 48.
Responders in PAQLQ(S) at Weeks 24 and 48	Responders in PAQLQ(S) at weeks 24 and 48. Analysis was performed using the following categories and definitions: responder (change from trial baseline ≥0.5), no change (-0.5 <change from trial baseline <0.5) and worsening (change from trial baseline ≤-0.5). No statistical testing was performed for PAQLQ(S) total score responders. The PAQLQ(S) is 23 questions on a 7-point scale, ranging from 1 (worst control) to 7 (best control).	Weeks 24 and 48.
Change From Baseline in Nighttime Awakenings	Change from baseline in nighttime awakenings based on the weekly mean at weeks 24 and 48. Nighttime awakenings was assessed by the question "Did you wake up during the night due to your asthma?" from the e-diary. Scores range from 1 (did not wake up) to 5 (was awake all night). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Baseline and Week 24, Baseline and Week 48.
Change From Baseline in Morning Asthma Symptoms	Change from baseline in morning asthma symptoms based on the weekly mean at weeks 24 and 48. Morning asthma symptoms was assessed by the question "how were your asthma symptoms this morning?" from the e-diary. Scores range from 1 (no asthma symptoms) to 5 (very severe asthma symptoms). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Baseline and Week 24, Baseline and Week 48.
Change From Baseline in Daytime Asthma Symptoms	Change from baseline in daytime asthma symptoms based on the weekly mean at weeks 24 and 48. Daytime asthma symptoms was assessed by the question "how were your asthma symptoms during the day?" from the e-diary. Scores range from 1 (no asthma symptoms) to 5 (very severe asthma symptoms). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Baseline and Week 24, Baseline and Week 48.
Change From Baseline in Daytime Activity Limitations	Change from baseline in daytime activity limitations based on the weekly mean at weeks 24 and 48. Daytime activity limitations was assessed by the question "how limited were you in your activities today because of your asthma?" from the e-diary. Scores range from 1 (not limited) to 5 (totally limited). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Baseline and Week 24, Baseline and Week 48.
Change From Baseline in Daytime Experiences of Shortness of Breath	Change from baseline in daytime experiences of shortness of breath based on the weekly mean at weeks 24 and 48. Daytime experiences of shortness of breath was assessed by the question "how much shortness of breath did you experience during the day" from the e-diary. Scores range from 1 (none) to 5 (a very great deal). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Baseline and Week 24, Baseline and Week 48.
Change From Baseline in Daytime Experiences of Wheeze or Cough	Change from baseline in daytime experiences of wheeze or cough based on the weekly mean at weeks 24 and 48. Daytime experiences of wheeze or cough was assessed by the question "did you experience wheeze or cough during the day?" from the e-diary. Scores range from 1 (not at all) to 5 (all the time). Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Baseline and Week 24, Baseline and Week 48.
Change From Baseline in Asthma Symptom-free Days	Change from baseline in asthma symptom-free days based on the weekly mean at weeks 24 and 48. A day was considered as an asthma symptom-free day if there were no symptoms reported via the e-Diary (electronic diary) and no use of rescue medication reported via the eDiary during that day. Measured values presented are actually adjusted means. The number of participants analysed displays the number of participants included in the statistical model whereas the N's for each timepoint display the number of participants with available data at that timepoint.	Baseline and Week 24, Baseline and Week 48.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Collaborators: Pfizer

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: July 3, 2012
• First Submitted That Met QC Criteria: July 3, 2012
• First Posted (Estimate): July 6, 2012

Study Record Updates

• Last Update Posted (Estimate): July 12, 2016
• Last Update Submitted That Met QC Criteria: June 2, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide
• Other Study ID Numbers: 205.445; 2011-001758-26 (EudraCT Number: EudraCT)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No