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 II
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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 |
- Peak forced expiratory volume in one second (FEV1) response (within 3 hours post dosing) deterined 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 two twin trials 205.418 and 205.419 ) [ 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 ]
- 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: 24 weeks ] [ Designated as safety issue: No ]
- 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 ]
- 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 3 hours 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 ]
- 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 ]
- 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 ]
| Enrollment: | 1032 |
| 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: tiotropium Respimat® high dose
IMP
Drug: placebo
Placebo that represents comparator
|
|
Active Comparator: 50 mcg salmeterol
Twice daily, delivered with HFA MDI (+ inhalation of placebo Respimat® inhaler once daily)
|
Drug: placebo
Placebo that represents BI drug
Drug: 50 mcg salmeterol HFA MDI
Active comparator
|
|
Placebo Comparator: placebo
Once daily, delivered with Respimat® inhaler + twice daily delivered with HFA MDI
|
Drug: placebo
Placebo that represents BI drug
Drug: placebo
Placebo that represents comparator
|
Eligibility| Ages Eligible for Study: | 18 Years to 75 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion criteria:
- 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).
- Male or female patients aged at least 18 years but not more than 75 years.
- 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.
- The initial diagnosis of asthma must have been made before the patient's age of 40.
- 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.
- 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:
- 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.
- 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.
- Patients with a recent history (i.e. six months or less) of myocardial infarction.
- Patients who have been hospitalised for cardiac failure during the past year.
- Patients with any unstable or life-threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year.
- Patients with lung diseases other than asthma (e.g. Chronic Obstructive Pulmonary Disease (COPD)).
- Patients with known active tuberculosis.
- 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.
- 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.
- Patients with significant alcohol or drug abuse within the past two years.
- 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).
- 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.
- Pregnant or nursing woman.
- Women of childbearing potential not using a highly effective method of birth control.
- Patients who have taken an investigational drug within four weeks prior to Visit 1.
- 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.
- 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.
- Patients who have been treated with oral or patch beta-adrenergics within four weeks prior to Visit 1 and/or during the Screening period.
- Patients who have been treated with oral corticosteroids within four weeks prior to Visit 1 and/or during the screening period.
- 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.
- Patients who have been treated with cromone within two weeks prior to Visit 1 and/or during the screening period.
- Patients who have been treated with methylxanthines or phosphodiesterase 4 inhibitors within two weeks prior to Visit 1 and/or during the screening period.
- 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.
- Patients with any asthma exacerbation or any respiratory tract infection iin the four weeks prior to Visit 1 and/or during the screening period.
- Patients who have previously been randomised in this trial or in the respective twin trial (205.418) or are currently participating in another trial.
Contacts and Locations
Show 125 Study Locations| Study Chair: | Boehringer Ingelheim | Boehringer Ingelheim Pharmaceuticals |
More Information
No publications provided
| Responsible Party: | Boehringer Ingelheim Pharmaceuticals |
| ClinicalTrials.gov Identifier: | NCT01172821 History of Changes |
| Other Study ID Numbers: | 205.419, 2009-018005-43 |
| Study First Received: | July 26, 2010 |
| Last Updated: | April 3, 2013 |
| Health Authority: | Brazil: National Health Surveillance Agency China: Food and Drug Administration Colombia: Instituto Nacional de Vigilancia de Medicamentos y Alimentos Germany: Federal Institute for Drugs and Medical Devices India: Drugs Controller General of India Japan: Ministry of Health, Labor and Welfare Mexico: Federal Commission for Protection Against Health Risks Peru: General Directorate of Pharmaceuticals, Devices, and Drugs Poland: Registration Medicinal Product Medical Device Biocidal Product Romania: National Medicines Agency 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 23, 2013