Evaluation of Tiotropium 2.5 and 5 Mcg Once Daily Delivered Via the Respimat® Inhaler Compared to Placebo and Salmeterol HydroFluoroAlkane (HFA) Metered Dose Inhaler (MDI) (50 Mcg Twice Daily) in Patient With Moderate Persistent Asthma I

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01172808
First received: July 26, 2010
Last updated: April 3, 2013
Last verified: April 2013
  Purpose

The aim of this trial is to evaluate the efficacy and safety of 2.5 and 5 mcg tiotropium over a 24-week treatment period as compared to placebo and salmeterol (50 mcg twice daily). 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 persistent asthma. Efficacy and safety will be assessed by measuring effects on lung function, effects on asthma exacerbations, effects on quality of life, effects on asthma control, effects on health care resource utilisation, and number of adverse events.


Condition Intervention Phase
Asthma
Drug: Placebo
Drug: tiotropium Respimat® low dose
Drug: tiotropium Respimat® high dose
Drug: 50 mcg salmeterol HFA MDI
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
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 Efficacy and Safety of Tiotropium Inhalation Solution Delivered Via Respimat® Inhaler (2.5 and 5 µg Once Daily) Compared With Placebo and Salmeterol HFA MDI (50 µg Twice Daily) Over 24 Weeks in Moderate Persistent Asthma

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim Pharmaceuticals:

Primary Outcome Measures:
  • Peak forced expiratory volume in one second (FEV1) response (within 3 hours post dosing) determined at the end of the 24-week treatment period [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Trough FEV1 response determined at the end of the 24-week treatment period [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • The responder rate as assessed by the Asthma Control Questionnaire (ACQ) determined at the end of the 24-week treatment period (on combined data from the two twin trials 205.418 and 205.419) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to first severe asthma exacerbation during the 24-week treatment period (on combined data from the two twin trials 205.418 and 205.419) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Time to first asthma exacerbation during the 24-week treatment period ( on combined data from the two twin trials 205.418 and 205.419) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Asthma control as assessed by Asthma Control Questionnaire (ACQ) at the end of the 24-week treatment period [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Pre-dose FEV1-a.m. (diary data) means of "last-7-days-before-week 24 visit" [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Pre-dose FEV1-p.m. (diary data)means of "last-7-days-before-week 24 visit" [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • PEF variability (absolute difference between morning and evening PEF value divided by their mean)mean of "last-7-days-before-week 24-visit" [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • The ACQ value at the end of the 24-week treatment period (on combined data from the two twin trials 205.418 and 205.419) [ Time Frame: 4, 8, 16 and 24 weeks ] [ Designated as safety issue: No ]
  • FEV1 (AUC0-3h) at the end of the 24-week treatment period [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • FVC (AUC0-3h) at the end of the 24-week treatment period [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • The responder rate as assessed by the Asthma Control Questionnaire (ACQ) determined at the end of the 24-week treatment period [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Peak (within 3 hours post dosing) FVC at the end of the 24-week treatment period [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Trough (within 3hours post dosing) FVC at the end of the 24-week treatment period [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Trough PEF at the end of the 24-week treatment period [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • AQLQ (S) at the end of the 24-week treatment period [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Mean pre-dose PEF-a.m. ( diary data) means of "last-7-days-before -week 24-visit" [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Mean pre-dose PEF-p.m. (diary data) means of "last-7-days-before-week 24-visit" [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Mean PRN rescue medication use during the "last-7-days-before -week-24-visit" [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Asthma symptoms free days during the "last-7-days -before-week 24-visit" [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Enrollment: 1071
Study Start Date: August 2010
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: tiotropium low dose
Once daily, delivered with Respimat® inhaler (+ inhalation of placebo HFA MDI twice daily)
Drug: Placebo
Placebo that represents comparator
Drug: tiotropium Respimat® low dose
IMP
Experimental: tiotropium high dose
Once daily, delivered with Respimat® inhaler (+ inhalation of placebo HFA MDI twice daily)
Drug: Placebo
Placebo that represents comparator
Drug: tiotropium Respimat® high dose
IMP
Active Comparator: 50 mcg salmeterol
Twice daily, delivered with HFA MDI (+ inhalation of placebo Respimat® inhaler once daily)
Drug: 50 mcg salmeterol HFA MDI
Active comparator
Drug: Placebo
Placebo that represents BI drug
Placebo Comparator: placebo
Once daily, delivered with Respimat® inhaler + twice daily delivered with HFA MDI
Drug: Placebo
Placebo that represents comparator
Drug: Placebo
Placebo that represents BI drug

  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 must sign and date an Informed Consent Form consistent with International Conference on Harmonisation - Good Clinical Practice (ICH-GCP) guidelines and local legislation 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 at Visit 1).
  2. Male or female patients aged at least 18 years but not more than 75 years.
  3. All patients must have at least a 3 month history of asthma at the time of enrolment 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 minutes after 400 mcg salbutamol (albuterol)) resulting in a Forced Expiratory Volume in one second (FEV1) increase of at least 12% and at least 200mL.
  6. All patients must have been on maintenance treatment with a medium, stable dose of inhaled corticosteroids for at least for 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. Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator) as compared to Visit 2 (pre-dose) must be within ± 30%.
  10. Patients must be never-smokers or ex-smokers who stopped smoking at least one year prior to enrolment (Visit 0) and who have a smoking history of less than 10 pack years.
  11. Patients must be able to use the Respimat® inhaler and metered dose inhaler correctly.
  12. Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of electronic diary/peak flow meter.

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 1.
  3. Patients with a recent history (i.e. six months or less) of myocardial infarction.
  4. Patients who have been hospitalised for cardiac failure during the past year.
  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.
  6. Patients with lung diseases other than asthma (e.g. Chronic Obstructive Pulmonary Disease (COPD)).
  7. Patients with known active tuberculosis.
  8. Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years. 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 within the past two years.
  11. Patients who are currently in a pulmonary rehabilitation program or have completed a pulmonary rehabilitation program in the 6 weeks prior to Visit 1 (screening).
  12. Patients with known hypersensitivity to anticholinergic drugs, benzalkonium chloride (BAC), ethylenediamineteraacetic acid (EDTA), salmeterol xinafoate or any other components of the study medication delivery systems.
  13. Pregnant or nursing woman.
  14. Women of childbearing potential not using a highly effective method of birth control.
  15. Patients who have taken an investigational drug within four weeks prior to Visit 1.
  16. 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.
  17. 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.
  18. Patients who have been treated with oral or patch beta-adrenergics within four weeks prior to Visit 1 and/or during the Screening period.
  19. Patients who have been treated with oral corticosteroids within four weeks prior to Visit 1 and/or during the screening period.
  20. 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.
  21. Patients who have been treated with cromone within two weeks prior to Visit 1 and/or during the screening period.
  22. Patients who have been treated with methylxanthines or phosphodiesterase 4 inhibitors within two weeks prior to Visit 1 and/or during the screening period.
  23. 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.
  24. Patients with any asthma exacerbation or any respiratory tract infection iin the four weeks prior to Visit 1 and/or during the screening period.
  25. Patients who have previously been randomised in this trial or in the respective twin trial (205.419) or are currently participating in another trial.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01172808

  Show 114 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim Pharmaceuticals
Pfizer
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim Pharmaceuticals
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01172808     History of Changes
Other Study ID Numbers: 205.418, 2009-018004-18
Study First Received: July 26, 2010
Last Updated: April 3, 2013
Health Authority: Brazil: National Health Surveillance Agency
China: Food and Drug Administration
Guatemala: Ministry of Public Health and Social Assistance
India: Drugs Controller General of India
Japan: Ministry of Health, Labor and Welfare
Latvia: State Agency of Medicines
Mexico: Federal Commission for Protection Against Health Risks
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Poland: Registration Medicinal Product Medical Device Biocidal Product
Russia: Pharmacological Committee, Ministry of Health
United States: Food and Drug Administration

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Salmeterol
Tiotropium
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents

ClinicalTrials.gov processed this record on May 22, 2013