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

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01340209
First received: April 13, 2011
Last updated: June 4, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: Tiotropium Respimat
Drug: Placebo Respimat
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    The primary endpoint is the number of patients with drug-related adverse events


Secondary Outcome Measures:
  • Trough FEV1 Response [ Time Frame: baseline and week 52 ] [ Designated as safety issue: No ]
    Trough FEV1 response was defined as change from baseline at week 52

  • Trough FVC Response [ Time Frame: baseline and week 52 ] [ Designated as safety issue: No ]
    Trough FVC response was defined as change from baseline at week 52

  • Trough PEF Response [ Time Frame: baseline and week 52 ] [ Designated as safety issue: No ]
    Trough PEF response was defined as change from baseline at week 52

  • Weekly Mean PEFam Response [ Time Frame: baseline and week 52 ] [ Designated as safety issue: No ]
    Weekly mean PEFam response was defined as change from baseline at week 52

  • Weekly Mean PEFpm Response [ Time Frame: baseline and week 52 ] [ Designated as safety issue: No ]
    Weekly mean PEFpm response was defined as change from baseline at week 52

  • Weekly Mean PEF Variability Response [ Time Frame: baseline and week 52 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    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.



Enrollment: 285
Study Start Date: April 2011
Study Completion Date: April 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tiotropium Respimat (low dose)
Tiotropium low dose once daily delivered with Respimat inhaler
Drug: Tiotropium Respimat
Tiotropium low dose once daily delivered with Respimat inhaler
Experimental: Tiotropium Respimat (high dose)
Tiotropium high dose once daily delivered with Respimat inhaler
Drug: Tiotropium Respimat
Tiotropium high dose once daily delivered with Respimat inhaler
Placebo Comparator: Placebo Respimat
Tiotropium placebo once daily delivered with Respimat inhaler
Drug: Placebo Respimat
Tiotropium placebo once daily delivered with Respimat inhaler

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01340209

  Show 55 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Pfizer
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01340209     History of Changes
Other Study ID Numbers: 205.464
Study First Received: April 13, 2011
Results First Received: April 22, 2014
Last Updated: June 4, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Tiotropium
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014