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Evaluation of Tiotropium 2.5 and 5 µg Once Daily Delivered Via the Respimat Inhaler Compared to Placebo in Patient With Moderate to Severe Persistent Asthma

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ClinicalTrials.gov Identifier: NCT01340209
Recruitment Status : Completed
First Posted : April 22, 2011
Results First Posted : July 4, 2014
Last Update Posted : July 4, 2014
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Boehringer Ingelheim

Tracking Information
First Submitted Date  ICMJE April 13, 2011
First Posted Date  ICMJE April 22, 2011
Results First Submitted Date  ICMJE April 22, 2014
Results First Posted Date  ICMJE July 4, 2014
Last Update Posted Date July 4, 2014
Study Start Date  ICMJE April 2011
Actual Primary Completion Date April 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 4, 2014)
Number of Patients With Drug-related Adverse Events [ Time Frame: after the first dose of trial medication and within 30 days after the last dose of trial medication, up to 409 ]
The primary endpoint is the number of patients with drug-related adverse events
Original Primary Outcome Measures  ICMJE
 (submitted: April 21, 2011)
In this trial, no primary endpoints of efficacy are defined because the primary objective of this trial is to evaluate the long term safety of tiotropium (secondary endpoint below) delivered via the Respimat inhaler in the patients with asthma. [ Time Frame: This endpoint has no specific timeframe ]
Change History Complete list of historical versions of study NCT01340209 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 4, 2014)
  • Trough FEV1 Response [ Time Frame: baseline and week 52 ]
    Trough FEV1 response was defined as change from baseline at week 52
  • Trough FVC Response [ Time Frame: baseline and week 52 ]
    Trough FVC response was defined as change from baseline at week 52
  • Trough PEF Response [ Time Frame: baseline and week 52 ]
    Trough PEF response was defined as change from baseline at week 52
  • Weekly Mean PEFam Response [ Time Frame: baseline and week 52 ]
    Weekly mean PEFam response was defined as change from baseline at week 52
  • Weekly Mean PEFpm Response [ Time Frame: baseline and week 52 ]
    Weekly mean PEFpm response was defined as change from baseline at week 52
  • Weekly Mean PEF Variability Response [ Time Frame: baseline and week 52 ]
    Weekly mean PEF variability response was defined as change from baseline at week 52. The PEF variability is the absolute difference between morning and evening PEF value, divided by their mean, expressed as a percent. Response was defined as change from baseline.
  • Weekly Mean Number of Puffs of Rescue Medication During the Whole Day (Response) [ Time Frame: baseline and week 52 ]
    Response of weekly mean number of puffs of rescue medication during the whole day at week 52. Response was defined as change from baseline.
  • Weekly Mean Score of Asthma Symptoms in the Morning (Response) [ Time Frame: baseline and week 52 ]
    Response of weekly mean score of asthma symptoms in the morning at week 52. Response was defined as change from baseline. 5-point verbal rating scale, with answer 1 representing no impairment at all and answer 5 representing the greatest impairment.
  • Weekly Mean Score of Asthma Symptoms During the Day (Response) [ Time Frame: baseline and week 52 ]
    Response of weekly mean score of asthma symptoms during the day at week 52. Response was defined as change from baseline. 5-point verbal rating scale, with answer 1 representing no impairment at all and answer 5 representing the greatest impairment.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 21, 2011)
  • Laboratory data at all visits except Visits 2, 3A, 4A/B, 5A/B, and 6A/B/C during treatment period. Haemoglobin, ¿ Total serum IgE [ Time Frame: 4, 12, 24, 36 and 52 weeks ]
  • 12-lead electrocardiogram (ECG). [ Time Frame: 52 week ]
  • Trough FEV1 response and trough forced vital capacity (FVC) at all visits except Visit 3, 3A, 4A/B, 5A/B, and 6A/B/C of the 52-week treatment period. [ Time Frame: 12, 24, 36 and 52 weeks ]
  • Individual in-clinic peak expiratory flow (PEF) measurements during the 52-week treatment period. [ Time Frame: 12, 24, 36 and 52 weeks ]
  • PEF variability: PEF variability is the absolute difference between morning and evening PEF value divided by the mean of these two values (weekly means will be compared) during the 52-week treatment period. [ Time Frame: up to 52 weeks ]
  • PEF AM/PM: change from baseline in mean weekly morning and pre-dose evening PEF respectively measured by patients at home during the 52-week treatment period. [ Time Frame: up to 52 weeks ]
  • Use of pro re nata (PRN) salbutamol HFA MDI rescue medication during the 52-week treatment period: number of actuations of rescue therapy used per day (i.e. the full 24 hour period, the daytime and the night time; weekly means will be compared). [ Time Frame: up to 52 weeks ]
  • Asthma symptoms as assessed by the patient's eDiary during the 52-week treatment period. Analysis with regard to daytime and nocturnal symptoms will be done. [ Time Frame: up to 52 weeks ]
  • All adverse events [ Time Frame: Day 0 until end of follow up (59 weeks) ]
  • Vital signs: pulse rate (beats/min) and blood pressure (seated, mmHg) recorded not only in conjunction with spirometry but also all records performed at all visits during treatment period. [ Time Frame: 0, 4, 12, 24, 36 and 52 weeks ]
  • Vital status information (dead or alive) of prematurely discontinued patients [ Time Frame: Planned date follow up visit (59 weeks) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of Tiotropium 2.5 and 5 µg Once Daily Delivered Via the Respimat Inhaler Compared to Placebo in Patient With Moderate to Severe Persistent Asthma
Official Title  ICMJE A Phase III Randomised, Double-blind, Placebo-controlled, Parallel-group Trial to Evaluate Safety and Efficacy of Tiotropium Inhalation Solution Delivered Via Respimat Inhaler (2.5 and 5 µg Once Daily) Compared With Placebo Over 52 Weeks in Patients With Moderate to Severe Persistent Asthma
Brief Summary The aim of this trial is to evaluate the safety and efficacy of 2.5 and 5 µg tiotropium over a 52-week treatment period as compared to placebo. Tiotropium inhalation solution delivered by the Respimat inhaler will be examined on top of maintenance treatment with inhaled corticosteroid controller medication in patients with moderate to severe persistent asthma. Efficacy and safety will be assessed by measuring effects on lung function, effects on asthma exacerbations, effects on asthma control, and 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
    Tiotropium high dose once daily delivered with Respimat inhaler
  • Drug: Placebo Respimat
    Tiotropium placebo once daily delivered with Respimat inhaler
  • Drug: Tiotropium Respimat
    Tiotropium low dose once daily delivered with Respimat inhaler
Study Arms  ICMJE
  • Experimental: Tiotropium Respimat (low dose)
    Tiotropium low dose once daily delivered with Respimat inhaler
    Intervention: Drug: Tiotropium Respimat
  • Experimental: Tiotropium Respimat (high dose)
    Tiotropium high dose once daily delivered with Respimat inhaler
    Intervention: Drug: Tiotropium Respimat
  • Placebo Comparator: Placebo Respimat
    Tiotropium placebo once daily delivered with Respimat inhaler
    Intervention: Drug: Placebo Respimat
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: February 6, 2013)
285
Original Estimated Enrollment  ICMJE
 (submitted: April 21, 2011)
280
Actual Study Completion Date  ICMJE April 2013
Actual Primary Completion Date April 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion criteria:

  1. All patients including the patients under age (under 20 years old) must sign and date an Informed Consent Form consistent with ICH-GCP guidelines and Good Clinical Practice (GCP) prior to participation in the trial [i.e. prior to any trial procedures, including any pre-trial washout of medications and medication restrictions for pulmonary function test (PFT) at Visit 1]. Regarding patients under age, a guardian or a legally authorised representative must also sign and date an Informed Consent Form.
  2. Male or female outpatients aged at least 18 years but not more than 75 years at Visit 0.
  3. All patients must have at least a 12-week history of asthma at the time of enrolment (Visit 0) into the trial. The diagnosis should be confirmed at Visit 1 by fulfilling inclusion criterion 5.
  4. The initial diagnosis of asthma must have been made before the patient's age of 40.
  5. The diagnosis of asthma has to be confirmed at Visit 1 with a bronchodilator reversibility (15-30 minutes after 400 µg salbutamol) resulting in a Forced Expiratory Volume in one second (FEV1) increase of at least 12% and at least 200 mL .
  6. All patients must have been on maintenance treatment with a medium, stable dose of inhaled corticosteroids (ICS) [alone or in a fixed combination with a Long-acting beta-adrenergic (LABA)] for at least 4 weeks prior to Visit 1.
  7. 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 at least 1.5.
  8. All patients must have a pre-bronchodilator FEV1 at least 60% and less than or equal to 90% of predicted normal at Visit 1.
  9. Patients must be never-smokers or ex-smokers who stopped smoking at least one year (52 weeks) prior to enrolment (Visit 0) and who have a smoking history of less than 10 pack years.
  10. Patients must be able to use the Respimat inhaler correctly, which is judged at the discretion of the investigator..
  11. Patients must be able to perform all trial related procedures including technically acceptable PFTs and use of electronic diary (eDiary)/peak flow meter, which is judged at the discretion of the investigator.

Exclusion criteria:

  1. Patients with a significant disease other than asthma. A significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the trial, or (ii) influence the results of the trial, or (iii) cause concern regarding the patient's ability to participate in the trial.
  2. Patients with a clinically relevant abnormal screening (Visit 1) haematology or blood chemistry if the abnormality defines a significant disease as defined in exclusion criterion no 1.
  3. Patients with a recent history (i.e. 6 months or less) of myocardial infarction prior to Visit 0.
  4. Patients who have been hospitalised for cardiac failure during the past year prior to Visit 0.
  5. Patients with any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year prior to Visit 0.
  6. Patients with lung diseases other than asthma (e.g. COPD).
  7. Patients with known active tuberculosis.
  8. Patients with malignancy and/or patients who have undergone resection, radiation therapy or chemotherapy for malignancy within the last 5 years prior to Visit 0. Patients with treated basal cell carcinoma are allowed.
  9. Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion no. 1.
  10. Patients with significant alcohol or drug abuse, which is judged at the discretion of the investigator, within the past 2 years prior to Visit 0.
  11. Patients with known hypersensitivity to anticholinergic drugs, benzalkonium chloride (BAC), ethylenediaminetetraacetic acid (EDTA), or any other components of the study medication delivery systems.
  12. Pregnant or nursing women.
  13. Women of childbearing 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 beta-blocker medication within four weeks prior to Visit 1 and/or during the screening period. Topical cardio-selective beta-blocker eye medications for non-narrow angle glaucoma are allowed.
  16. Patients who have been treated with the long-acting anticholinergic tiotropium (Spiriva) within four weeks prior to Visit 1 and/or during the screening period.
  17. Patients who have been treated with oral beta-adrenergics within four weeks prior to Visit 1 and/or during the Screening period.
  18. Patients who have been treated with systemic corticosteroids within four weeks prior to Visit 1 and/or during the screening period.
  19. Patients who have been treated with anti-IgE antibodies, e.g. omalizumab (Xolair®), within 6 months prior to Visit 1 and/or during the screening period.
  20. Patients who have been treated with other 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.
  21. Patients with any asthma exacerbation or any respiratory tract infection in the four weeks prior to Visit 1 and/or during the screening period.
  22. Patients who are currently participating in another trial.
  23. Patients with narrow-angle glaucoma and/or micturition disorder due to prostatic hyperplasia.
  24. Patients with below 80% of the eDiary completion compliance on Visit 2 (diary compliance of at least 80% is required).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Japan
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01340209
Other Study ID Numbers  ICMJE 205.464
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 June 2014

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