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

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ClinicalTrials.gov Identifier: NCT01257230
Recruitment Status : Completed
First Posted : December 9, 2010
Results First Posted : August 8, 2014
Last Update Posted : September 5, 2014
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Boehringer Ingelheim

Tracking Information
First Submitted Date  ICMJE December 6, 2010
First Posted Date  ICMJE December 9, 2010
Results First Submitted Date  ICMJE June 12, 2014
Results First Posted Date  ICMJE August 8, 2014
Last Update Posted Date September 5, 2014
Study Start Date  ICMJE December 2010
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 7, 2014)
FEV1 peak0-3 Change From Baseline [ Time Frame: Baseline and 24 weeks ]
Change from baseline in peak Forced expiratory volume in 1 second within the first 3 hours post dosing (FEV1 peak0-3) measured at week 24. Note, the measured values presented are actually adjusted means.
Original Primary Outcome Measures  ICMJE
 (submitted: December 8, 2010)
Peak Forced expiratory Flow in 1 second resonse within 3 hours post dosing (FEV1 peak0-3 response) [ Time Frame: 24 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 27, 2014)
  • Trough FEV1 Change From Baseline [ Time Frame: Baseline and 24 weeks ]
    Change from baseline in Trough (pre-dose) Forced expiratory volume in 1 second (FEV1) measured at week 24. The measured values presented are actually adjusted means.
  • FVC peak0-3 Change From Baseline [ Time Frame: Baseline and 24 weeks ]
    Change from baseline in Maximum forced vital capacity (FVC) measured within the first 3 h after administration of trial medication (FVC peak0-3h) after 24 weeks of treatment. The measured values presented are actually adjusted means.
  • Trough FVC Change From Baseline [ Time Frame: Baseline and 24 weeks ]
    Change from baseline of Trough (pre-dose) forced vital capacity (FVC) measured 10 min before the administration of trial medication after 24 weeks of treatment. The measured values presented are actually adjusted means..
  • FEV1 AUC (0-3h) Change From Baseline [ Time Frame: Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 24 weeks ]
    Change from baseline of area under the curve (AUC) from 0 to 3 h 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). The measured values presented are actually adjusted means.
  • FVC AUC (0-3h) Change From Baseline [ Time Frame: Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 24 weeks ]
    Change from baseline of area under the curve (AUC) from 0 to 3 h for FVC (FVC AUC0-3h) after 24 weeks of treatment. The AUC was calculated by using the trapezoidal rule divided by the observation time (3h). The measured values presented are actually adjusted means.
  • FEF25-75 Change From Baseline [ Time Frame: Baseline and 10 mins before drug administration and 30 mins, 1 hour (h), 2h, 3h after drug administration at 24 weeks ]
    Change from baseline in mean forced expiratory flow between 25% and 75% of the FVC (FEF25-75%), also known as maximum mid-expiratory flow, at individual time points after 24 weeks of treatment. The measured values presented are actually adjusted means.
  • Use of PRN Rescue Medication During the Daytime [ Time Frame: Baseline and Week 24 ]
    Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during the daytime based on the weekly mean at week 24. The measured values presented are actually adjusted means.
  • Use of PRN Rescue Medication During the Night-time [ Time Frame: Baseline and week 24 ]
    Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during the night-time based on the weekly mean at week 24. The measured values presented are actually adjusted means.
  • Use of PRN Rescue Medication During the Day [ Time Frame: Baseline and week 24 ]
    Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during the day (24 hour period) based on the weekly mean at week 24. The measured values presented are actually adjusted means.
  • Control of Asthma as Assessed by ACQ Total Score [ Time Frame: Baseline and week 24 ]
    Change from baseline in Asthma Control Questionnaire (ACQ) total score measured at week 24. The ACQ 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 total score was calculated as the mean of the responses to all 7 questions. The measured values presented are actually adjusted means.
  • ACQ Total Score Responders [ Time Frame: Week 24 ]
    Responder rates based on the ACQ total score after 24 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) The ACQ 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.
  • Control of Asthma as Assessed by ACQ6 [ Time Frame: Baseline and week 24 ]
    Change from baseline in AQC6 score at week 24. The ACQ6 score is calculated as the mean of the responses to the first 6 questions of the ACQ. The ACQ 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. The measured values presented are actually adjusted means.
  • ACQ6 Responders [ Time Frame: Week 24 ]
    Responder rates based on the ACQ6 after 24 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) The ACQ6 score is calculated as the mean of the responses to the first 6 questions of the ACQ. The ACQ 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.
  • Time to First Severe Asthma Exacerbation During the 48 Week Treatment Period [ Time Frame: 48 weeks ]
    The median time to first severe asthma exacerbation was not calculable, so the number of patients who experienced a severe asthma exacerbation are presented for the measured values. A severe asthma exacerbation was defined as a subgroup of all asthma exacerbations that required treatment with systemic corticosteroid for at least 3 days.
  • Time to First Asthma Exacerbation During the 48 Week Treatment Period [ Time Frame: Week 48 ]
    The median time to first asthma exacerbation was not calculable, so the number of patients who experienced an asthma exacerbation are presented for the measured values.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 8, 2010)
  • Trough FEV1at 12 weeks [ Time Frame: 12weeks ]
  • Peak forced vital capacity within 3 hours post dosing (FVC peak0-3), and trough FVC at 12 weeks [ Time Frame: 12 weeks ]
  • FEV1 (AUC0-3) and FVC (AUC0-3) (AUC = Area Under the Curve) [ Time Frame: 12 weeks ]
  • mean forced expiratory flow between 25% and 75% of the FVC (FEF25-75) at week 12 [ Time Frame: 12 weeks ]
  • Use of PRN rescue medication (salbutamol/albuterol) [ Time Frame: weekly means for 48 weeks ]
  • Control of asthma as assessed by the Asthma Control Questionnaire (ACQ) at week 12 [ Time Frame: 12 weeks ]
  • Time to first severe asthma exacerbation; time to first asthma exacerbation [ Time Frame: 48 weeks ]
  • Trough FEV1 at 24 weeks [ Time Frame: 24 weeks ]
  • Trough FEV1 at 48 weeks [ Time Frame: 48 weeks ]
  • Peak forced vital capacity within 3 hours post dsing (FVC peal0-3), and trough FVC at 24 weeks [ Time Frame: 24 weeks ]
  • Peak forced vital capacity within 3 hours post dosing (FVC peak0-3), and trogh FVC at 48 weeks [ Time Frame: 48 weeks ]
  • FEV1 (AUC0-3) and FVC (AUC0-3) at week 24 [ Time Frame: 24 weeks ]
  • FEV1 (AUC0-3) and FVC (AUC0-3) at week 48 [ Time Frame: 48 weeks ]
  • Control of asthma as assessed by the Asthma Control Questionnaire (ACQ) at week 48 [ Time Frame: 48 weeks ]
  • Control of asthma as assessed by the Asthma Control Questionnaire (ACQ) at week 24 [ Time Frame: 24 weeks ]
  • mean forced expiratory flow between 25% and 75% of the FVC (FEF25-75) at week 24 [ Time Frame: 24 weeks ]
  • mean forced expiratory flow between 25% and 75% of the FVC (FEF25-75) at week 48 [ Time Frame: 48 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of 2 Doses of Tiotropium Via Respimat Compared to Placebo in Adolescents With Moderate Persistent Asthma
Official Title  ICMJE A Phase III, Randomised, Double Blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety Over 48 Weeks of Orally Inhaled Tiotropium Bromide (2.5 and 5 µg Once Daily ) Delivered by the Respimat® Inhaler in Adolescents (12 to 17 Years Old) With Moderate Persistent Asthma.
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Condition  ICMJE Asthma
Intervention  ICMJE
  • Drug: tiotropium Respimat low dose
    IMP
  • Drug: placebo Respimat
    placebo representing comparator
  • Drug: tiotropium Respimat high dose
    IMP
Study Arms  ICMJE
  • Placebo Comparator: placebo
    once daily, delivered with Respimat inhaler
    Intervention: Drug: placebo Respimat
  • Experimental: tiotropium low dose
    once daily, delivered with Respimat inhaler
    Intervention: Drug: tiotropium Respimat low dose
  • Experimental: tiotropium high dose
    once daily, delivered with Respimat inhaler
    Intervention: Drug: tiotropium Respimat high dose
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 23, 2013)
398
Original Estimated Enrollment  ICMJE
 (submitted: December 8, 2010)
243
Actual Study Completion Date  ICMJE December 2013
Actual Primary Completion Date December 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 12 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Chile,   Germany,   Hungary,   Italy,   Korea, Republic of,   Latvia,   Mexico,   Russian Federation,   Slovakia,   Spain,   Ukraine,   United States
Removed Location Countries Norway
 
Administrative Information
NCT Number  ICMJE NCT01257230
Other Study ID Numbers  ICMJE 205.444
2010-021093-11 ( EudraCT Number: EudraCT )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Boehringer Ingelheim
Study Sponsor  ICMJE Boehringer Ingelheim
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
PRS Account Boehringer Ingelheim
Verification Date August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP