Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT01277523
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01277523
Recruitment Status : Completed
First Posted : January 17, 2011
Results First Posted : October 20, 2014
Last Update Posted : October 20, 2014
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Boehringer Ingelheim

Tracking Information
First Submitted Date  ICMJE January 13, 2011
First Posted Date  ICMJE January 17, 2011
Results First Submitted Date  ICMJE October 14, 2014
Results First Posted Date  ICMJE October 20, 2014
Last Update Posted Date October 20, 2014
Study Start Date  ICMJE January 2011
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 14, 2014)
FEV1 peak0-3 Change From Baseline [ Time Frame: Baseline and 12 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 12. Measured values presented are actually adjusted means.
Original Primary Outcome Measures  ICMJE
 (submitted: January 13, 2011)
Change from baseline at the end of the 12-week treatment period in the highest forced expiratory volume in one second reading observed within 3 hours after administration of the evening dose of each randomised treatment (peak FEV1 response). [ Time Frame: 12 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 14, 2014)
  • Trough FEV1 Change From Baseline [ Time Frame: Baseline and 12 weeks ]
    Change from baseline in Trough (pre-dose) Forced expiratory volume in 1 second (FEV1) measured at week 12. Measured values presented are actually adjusted means.
  • FVC peak0-3 Change From Baseline [ Time Frame: Baseline and 12 weeks ]
    Change from baseline in Maximum forced vital capacity (FVC) measured within the first 3 hours after administration of trial medication (FVC peak0-3h) after 12 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 12 weeks ]
    Change from baseline of area under the curve (AUC) from 0 to 3 hours for FEV1 (FEV1 AUC 0-3h) after 12 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.
  • 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 12 weeks ]
    Change from baseline of area under the curve (AUC) from 0 to 3 hours for FVC (Forced vital capacity) (FVC AUC0-3h) after 12 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.
  • Control of Asthma as Assessed by ACQ6 Score. [ Time Frame: Baseline and 12 weeks ]
    Change from baseline in Asthma Control Questionnaire (ACQ) 6 score measured at week 12 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. ACQ6 score is calculated as the mean of the responses to the first 6 questions of the ACQ6. The measured values presented are actually adjusted means.
  • ACQ6 Score Responders [ Time Frame: 12 weeks ]
    Responder rates based on the ACQ6 score after 12 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. ACQ6 is calculated as the mean of the responses to the first 6 questions of the ACQ6. No statistical testing was performed on ACQ6 responders.
  • Control of Asthma as Assessed by ACQ Total Score [ Time Frame: Baseline and 12 weeks ]
    Change from baseline in Asthma Control Questionnaire (ACQ) total score measured at week 12. 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 is 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: 12 weeks ]
    Responder rates based on the ACQ total score after 12 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 total score responders. 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.
  • Use of PRN Rescue Medication During the Day [ Time Frame: Baseline and 12 weeks ]
    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 12. The measured values presented are actually adjusted means.
  • Use of PRN Rescue Medication During the Daytime [ Time Frame: Baseline and 12 weeks ]
    Change from baseline in the number of puffs of rescue medication (salbutamol/albuterol) used during the daytime based on the weekly mean at week 12. Measured values presented are actually adjusted means.
  • Use of PRN Rescue Medication During the Night-time [ Time Frame: Baseline and 12 weeks ]
    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 12. Measured values presented are actually adjusted means
  • Time to First Severe Asthma Exacerbation During the 12-week Treatment Period. [ Time Frame: 12 weeks ]
    Time in days to first severe asthma exacerbation during the 12 week treatment period. 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 an initiation of treatment with systemic corticosteroids for at least 3 days or, in case of ongoing and pre-existing systemic corticosteroid therapy, requiring at least doubling of previous daily doses of systemic corticosteroids for at least 3 days.
  • Analysis of Time to First Asthma Exacerbation During the 12 Week Treatment Period. [ Time Frame: 12 weeks ]
    Time in days to first asthma exacerbation during the 12 week treatment period. 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.
  • Clinically Relevant Abnormalities for Physical Examination, ECG, Vital Signs and Laboratory Tests [ Time Frame: From first drug administration until 30 days after last drug intake, up to 142 days ]
    Clinically relevant abnormalities for physical examination, ECG, vital signs and laboratory tests. New abnormal findings or worsening of baseline conditions were reported as adverse events.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 13, 2011)
  • Change from baseline at the end of the 12-week treatment period in the trough forced expiratory volume in one second (trough FEV1 response). [ Time Frame: 12 weeks ]
  • Change from baseline at the end of the 12-week treatment period in the highest forced vital capacity reading observed within 3 hours after administration of the evening dose of each randomised treatment. [ Time Frame: 12 weeks ]
  • Change from baseline at the end of the 12-week treatment period in the area under the curve from zero to 3 hours of the trough forced expiratory volume and the forced vital capacity. [ Time Frame: 12 weeks ]
  • The number of responders (improvement of at least 0.5 for the ACQ) as assessed by the Asthma Control Questionnaire (ACQ) determined at the end of the 12-week treatment period. [ Time Frame: 12 weeks ]
  • Number of inhalations of salbutamol (albuterol) rescue medication used per day during the 12-week treatment period. [ Time Frame: 0-12 weeks ]
  • Time to first severe asthma exacerbation during the 12-week treatment period. [ Time Frame: 0-12 weeks ]
  • Time to first asthma exacerbation during the 12-week treatment period. [ Time Frame: 0-12 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 Respimat Compared to Placebo in Adolescents With Severe Persistent Asthma
Official Title  ICMJE A Randomised, Double-blind, Placebo-controlled, Parallel-group Trial to Evaluate Efficacy and Safety of Tiotropium Inhalation Solution Delivered Via Respimat® Inhaler (2.5 mcg and 5 mcg Once Daily) Over 12 Weeks as add-on Controller Therapy on Top of Usual Care in Adolescents (12 to 17 Years Old) With Severe Persistent Asthma
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.

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 high dose
    2 actuations once daily
  • Drug: placebo
    2 actuations once daily
  • Drug: tiotropium low dose
    2 actuations once daily
Study Arms  ICMJE
  • Experimental: A
    Intervention: Drug: tiotropium low dose
  • Experimental: B
    Intervention: Drug: tiotropium high dose
  • Placebo Comparator: C
    Intervention: Drug: placebo
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)
392
Original Estimated Enrollment  ICMJE
 (submitted: January 13, 2011)
192
Actual Study Completion Date  ICMJE October 2013
Actual Primary Completion Date October 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
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 Argentina,   Australia,   Bulgaria,   Germany,   Guatemala,   Hungary,   Israel,   Latvia,   Mexico,   Philippines,   Portugal,   South Africa,   Ukraine,   United States
Removed Location Countries Italy,   Norway
 
Administrative Information
NCT Number  ICMJE NCT01277523
Other Study ID Numbers  ICMJE 205.456
2010-021778-13 ( 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 October 2014

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