Efficacy and Safety of Tiotropium and Salmeterol in Moderate Persistent Asthma Patients Homozygous for B16-Arg/Arg
This study has been completed.
Sponsor:
Boehringer Ingelheim Pharmaceuticals
Information provided by:
Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00350207
First received: July 7, 2006
Last updated: May 18, 2012
Last verified: May 2012
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Purpose
This is a 16 week multicentre, multinational, randomised, double-blind, double-dummy, placebo-controlled, parallel group study to evaluate the long-term efficacy and safety of tiotropium compared to salmeterol in moderate persistent asthmatic (GINA step 3) patients homozygous for arginine at the 16th amino acid position of the beta-adrenergic receptor (ADRB2). Following an initial 4-week run-in period on salmeterol MDI patients will be randomised into the 16 week double-blind treatment period in which they receive either tiotropium once daily administered from the Respimat inhaler or salmeterol twice daily administered from the hydrofluoro-alkane Metered Dose Inhaler (MDI), or placebo twice daily. After the 16 week treatment period all patients will receive salmeterol MDI twice daily for four weeks.
The patients perform daily morning and evening peak flow (PEF) and Forced Expiratory Volume in the First Second (FEV1) measurements with an electronic peak flow meter throughout the study. Daily data on asthma control and use of rescue medication are recorded using an electronic diary included in the electronic peak flow meter. On study visits the Mini-Asthma Quality of Life Questionnaire (Elizabeth Juniper) is administered, pulse and blood pressure and pre-dose pulmonary function testing (FEV1 and Forced Vital Capacity) are performed.
| Condition | Intervention | Phase |
|---|---|---|
|
Asthma |
Drug: Tiotropium bromide Drug: Placebo Drug: Salmeterol xinafoate |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Intervention Model: Parallel Assignment Primary Purpose: Treatment |
| Official Title: | A 16-week Randomised, Placebo-controlled, Double-blind, Double-dummy, Parallel-group Study Comparing the Efficacy and Safety of Tiotropium Inhalation Solution Delivered by the Respimat Inhaler (2 Actuations of 2.5 Mcg Once Daily) With That of Salmeterol From the Hydrofluoroalkane Metered Dose Inhaler (2 Actuations of 25 Mcg Twice Daily) in Moderate Persistent Asthma Patients With the B16-Arg/Arg Genotype |
Resource links provided by NLM:
Further study details as provided by Boehringer Ingelheim Pharmaceuticals:
Primary Outcome Measures:
- Change in Mean Weekly Morning Peak Expiratory Flow From Baseline to the End of the Trial [ Time Frame: baseline and after 16 weeks of treatment ]Change from baseline in mean weekly morning peak expiratory flow at 16 weeks. Baseline is defined as the last week prior to the randomisation visit
Secondary Outcome Measures:
- Mean Weekly Morning Peak Expiratory Flow at Week 4 [ Time Frame: After 4 weeks of treatment ]pre-dose
- Mean Weekly Morning Peak Expiratory Flow at Week 8 [ Time Frame: After 8 weeks of treatment ]pre-dose
- Mean Weekly Morning Peak Expiratory Flow at Week 12 [ Time Frame: After 12 weeks of treatment ]pre-dose
- Mean Weekly Morning Peak Expiratory Flow at Week 16 [ Time Frame: After 16 weeks of treatment ]pre-dose
- Mean Weekly Evening Peak Expiratory Flow at Week 4 [ Time Frame: After 4 weeks of treatment ]pre-dose
- Mean Weekly Evening Peak Expiratory Flow at Week 8 [ Time Frame: After 8 weeks of treatment ]pre-dose
- Mean Weekly Evening Peak Expiratory Flow at Week 12 [ Time Frame: After 12 weeks of treatment ]pre-dose
- Mean Weekly Evening Peak Expiratory Flow at Week 16 [ Time Frame: After 16 weeks of treatment ]pre-dose
- Mean Weekly Morning Forced Expiratory Volume in 1 Second at Week 4 [ Time Frame: After 4 weeks of treatment ]pre-dose
- Mean Weekly Morning Forced Expiratory Volume in 1 Second at Week 8 [ Time Frame: After 8 weeks of treatment ]pre-dose
- Mean Weekly Morning Forced Expiratory Volume in 1 Second at Week 12 [ Time Frame: After 12 weeks of treatment ]pre-dose
- Mean Weekly Morning Forced Expiratory Volume in 1 Second at Week 16 [ Time Frame: After 16 weeks of treatment ]pre-dose
- Mean Weekly Evening Forced Expiratory Volume in 1 Second at Week 4 [ Time Frame: After 4 weeks of treatment ]pre-dose
- Mean Weekly Evening Forced Expiratory Volume in 1 Second at Week 8 [ Time Frame: After 8 weeks of treatment ]pre-dose
- Mean Weekly Evening Forced Expiratory Volume in 1 Second at Week 12 [ Time Frame: After 12 weeks of treatment ]pre-dose
- Mean Weekly Evening Forced Expiratory Volume in 1 Second at Week 16 [ Time Frame: After 16 weeks of treatment ]pre-dose
- Mean Weekly Score for Asthma Control Diary Question "Did You Waken up During the Night Due to Asthma" at Week 4 [ Time Frame: After 4 weeks of treatment ]Unit on a scale 1-5. 1: Did not wake up, 2: Woke up once, 3: Woke up 2-5 times, 4: Woke up more than 5 times. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "Did You Waken up During the Night Due to Asthma" at Week 8 [ Time Frame: After 8 weeks of treatment ]Unit on a scale 1-5. 1: Did not wake up, 2: Woke up once, 3: Woke up 2-5 times, 4: Woke up more than 5 times. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "Did You Waken up During the Night Due to Asthma" at Week 12 [ Time Frame: After 12 weeks of treatment ]Unit on a scale 1-5. 1: Did not wake up, 2: Woke up once, 3: Woke up 2-5 times, 4: Woke up more than 5 times. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "Did You Waken up During the Night Due to Asthma" at Week 16 [ Time Frame: After 16 weeks of treatment ]Unit on a scale 1-5. 1: Did not wake up, 2: Woke up once, 3: Woke up 2-5 times, 4: Woke up more than 5 times. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "How Were Your Asthma Symptoms in the Morning" at Week 8 [ Time Frame: After 4 weeks of treatment ]Unit on a scale 1-5. 1: No asthma symptoms, 2: Mild asthma symptoms, 3: Moderate asthma symptoms, 4: Severe asthma symptoms, 5: Very severe asthma symptoms. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "How Were Your Asthma Symptoms This Morning" at Week 8 [ Time Frame: After 8 weeks of treatment ]Unit on a scale 1-5. 1: No asthma symptoms, 2: Mild asthma symptoms, 3: Moderate asthma symptoms, 4: Severe asthma symptoms, 5: Very severe asthma symptoms. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "How Were Your Asthma Symptoms This Morning" at Week 12 [ Time Frame: After 12 weeks of treatment ]Unit on a scale 1-5. 1: No asthma symptoms, 2: Mild asthma symptoms, 3: Moderate asthma symptoms, 4: Severe asthma symptoms, 5: Very severe asthma symptoms. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "How Were Your Asthma Symptoms This Morning" at Week 16 [ Time Frame: After 16 weeks of treatment ]Unit on a scale 1-5. 1: No asthma symptoms, 2: Mild asthma symptoms, 3: Moderate asthma symptoms, 4: Severe asthma symptoms, 5: Very severe asthma symptoms. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "How Were Your Asthma Symptoms During the Day" at Week 4 [ Time Frame: After 4 weeks of treatment ]Unit on a scale 1-5. 1: No asthma symptoms, 2: Mild asthma symptoms, 3: Moderate asthma symptoms, 4: Severe asthma symptoms, 5: Very severe asthma symptoms. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "How Were Your Asthma Symptoms During the Day" at Week 8 [ Time Frame: After 8 weeks of treatment ]Unit on a scale 1-5. 1: No asthma symptoms, 2: Mild asthma symptoms, 3: Moderate asthma symptoms, 4: Severe asthma symptoms, 5: Very severe asthma symptoms. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "How Were Your Asthma Symptoms During the Day" at Week 12 [ Time Frame: After 12 weeks of treatment ]Unit on a scale 1-5. 1: No asthma symptoms, 2: Mild asthma symptoms, 3: Moderate asthma symptoms, 4: Severe asthma symptoms, 5: Very severe asthma symptoms. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "How Were Your Asthma Symptoms During the Day" at Week 16 [ Time Frame: After 16 weeks of treatment ]Unit on a scale 1-5. 1: No asthma symptoms, 2: Mild asthma symptoms, 3: Moderate asthma symptoms, 4: Severe asthma symptoms, 5: Very severe asthma symptoms. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "How Limited Were You in Your Activities Today Because of Your Asthma" at Week 4 [ Time Frame: After 4 weeks of treatment ]Unit on a scale 1-5. 1: Not limited at all, 2: A little limited, 3: Moderately limited, 4: Severely limited, 5: Totally limited. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "How Limited Were You in Your Activities Today Because of Your Asthma" at Week 8 [ Time Frame: After 8 weeks of treatment ]Unit on a scale 1-5. 1: Not limited at all, 2: A little limited, 3: Moderately limited, 4: Severely limited, 5: Totally limited. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "How Limited Were You in Your Activities Today Because of Your Asthma" at Week 12 [ Time Frame: After 12 weeks of treatment ]Unit on a scale 1-5. 1: Not limited at all, 2: A little limited, 3: Moderately limited, 4: Severely limited, 5: Totally limited. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "How Limited Were You in Your Activities Today Because of Your Asthma" at Week 16 [ Time Frame: After 16 weeks of treatment ]Unit on a scale 1-5. 1: Not limited at all, 2: A little limited, 3: Moderately limited, 4: Severely limited, 5: Totally limited. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "How Much Shortness of Breath Did You Experience During the Day" at Week 4 [ Time Frame: After 4 weeks of treatment ]Unit on a scale 1-5. 1: None, 2: A very little, 3: A moderate amount, 4: Quite a lot, 5: A very great deal. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "How Much Shortness of Breath Did You Experience During the Day" at Week 8 [ Time Frame: After 8 weeks of treatment ]Unit on a scale 1-5. 1: None, 2: A very little, 3: A moderate amount, 4: Quite a lot, 5: A very great deal. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "How Much Shortness of Breath Did You Experience During the Day" at Week 12 [ Time Frame: After 12 weeks of treatment ]Unit on a scale 1-5. 1: None, 2: A very little, 3: A moderate amount, 4: Quite a lot, 5: A very great deal. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "How Much Shortness of Breath Did You Experience During the Day" at Week 16 [ Time Frame: After 16 weeks of treatment ]Unit on a scale 1-5. 1: None, 2: A very little, 3: A moderate amount, 4: Quite a lot, 5: A very great deal. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "Did You Experience Wheeze or Cough During the Day" at Week 4 [ Time Frame: After 4 weeks of treatment ]Unit on a scale 1-5. 1: Not at all, 2: A little of the time, 3: A moderate amount of the time, 4: Most of the time, 5: All the time. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "Did You Experience Wheeze or Cough During the Day" at Week 8 [ Time Frame: After 8 weeks of treatment ]Unit on a scale 1-5. 1: Not at all, 2: A little of the time, 3: A moderate amount of the time, 4: Most of the time, 5: All the time. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "Did You Experience Wheeze or Cough During the Day" at Week 12 [ Time Frame: After 12 weeks of treatment ]Unit on a scale 1-5. 1: Not at all, 2: A little of the time, 3: A moderate amount of the time, 4: Most of the time, 5: All the time. 1 is the best value
- Mean Weekly Score for Asthma Control Diary Question "Did You Experience Wheeze or Cough During the Day" at Week 16 [ Time Frame: After 16 weeks of treatment ]Unit on a scale 1-5. 1: Not at all, 2: A little of the time, 3: A moderate amount of the time, 4: Most of the time, 5: All the time. 1 is the best value
- Morning Pre-dose Forced Expiratory Volume in 1 Second as Measured by Spirometry at Visit 3 [ Time Frame: After 6 weeks of treatment ]Morning pre-dose forced expiratory volume in 1 second as measured by spirometry after 6 weeks of treatment
- Morning Pre-dose Forced Expiratory Volume in 1 Second as Measured by Spirometry at Visit 4 [ Time Frame: After 12 weeks of treatment ]Morning pre-dose forced expiratory volume in 1 second as measured by spirometry after 12 weeks of treatment
- Morning Pre-dose Forced Expiratory Volume in 1 Second as Measured by Spirometry at Visit 5 [ Time Frame: After 16 weeks of treatment ]Morning pre-dose forced expiratory volume in 1 second as measured by spirometry after 16 weeks od treatment
- Morning Pre-dose Forced Vital Capacity as Measured by Spirometry at Visit 3 [ Time Frame: After 6 weeks of treatment ]Morning pre-dose forced vital capacity as measured by spirometry after 6 weeks of treatment
- Morning Pre-dose Forced Vital Capacity as Measured by Spirometry at Visit 4 [ Time Frame: After 12 weeks of treatment ]Morning pre-dose forced vital capacity as measured by spirometry after 12 weeks of treatment
- Morning Pre-dose Forced Vital Capacity as Measured by Spirometry at Visit 5 [ Time Frame: After 16 weeks of treatment ]Morning pre-dose forced vital capacity as measured by spirometry after 16 weeks of treatment
- Mini-Asthma Quality of Life Questionnaire (Mini-AQLQ) Overall Score at Visit 3 [ Time Frame: After 6 weeks of treatment ]Mean of the responses to 15 questions from 4 domains: Symptoms (1), Activity Limitations (2), Emotional Function (3), Environmental Stimuli (4). Unit on a scale 1-7. For domain (2): 1: totally limited, 2: extremely limited, 3: very limited, 4: moderate limitation, 5: some limitation, 6: a little limitation, 7: not at all limited. For other domains: 1: all of the time, 2: most of the time, 3: a good bit of the time, 4: some of the time, 5: a little of the time, 6: hardly any of the time, 7: none of the time. 7 is the best value
- Mini-AQLQ Overall Score at Visit 4 [ Time Frame: After 12 weeks of treatment ]Mean of the responses to 15 questions from 4 domains: Symptoms (1), Activity Limitations (2), Emotional Function (3), Environmental Stimuli (4). Unit on a scale 1-7. For domain (2): 1: totally limited, 2: extremely limited, 3: very limited, 4: moderate limitation, 5: some limitation, 6: a little limitation, 7: not at all limited. For other domains: 1: all of the time, 2: most of the time, 3: a good bit of the time, 4: some of the time, 5: a little of the time, 6: hardly any of the time, 7: none of the time. 7 is the best value
- Mini-AQLQ Overall Score at Visit 5 [ Time Frame: After 16 weeks of treatment ]Mean of the responses to 15 questions from 4 domains: Symptoms (1), Activity Limitations (2), Emotional Function (3), Environmental Stimuli (4). Unit on a scale 1-7. For domain (2): 1: totally limited, 2: extremely limited, 3: very limited, 4: moderate limitation, 5: some limitation, 6: a little limitation, 7: not at all limited. For other domains: 1: all of the time, 2: most of the time, 3: a good bit of the time, 4: some of the time, 5: a little of the time, 6: hardly any of the time, 7: none of the time. 7 is the best value
- Systolic Blood Pressure as Measured by Spirometry at Visit 3 [ Time Frame: After 6 weeks of treatment ]Systolic blood pressure as measured by spirometry at 6 weeks
- Systolic Blood Pressure as Measured by Spirometry at Visit 4 [ Time Frame: After 12 weeks of treatment ]Systolic blood pressure as measured by spirometry at 12 weeks
- Systolic Blood Pressure as Measured by Spirometry at Visit 5 [ Time Frame: After 16 weeks of treatment ]Systolic blood pressure as measured by spirometry at 16 weeks
- Diastolic Blood Pressure as Measured by Spirometry at Visit 3 [ Time Frame: After 6 weeks of treatment ]Diastolic blood pressure as measured by spirometry at 6 weeks
- Diastolic Blood Pressure as Measured by Spirometry at Visit 4 [ Time Frame: After 12 weeks of treatment ]Diastolic blood pressure as measured by spirometry at 12 weeks
- Diastolic Blood Pressure as Measured by Spirometry at Visit 5 [ Time Frame: After 16 weeks of treatment ]Diastolic blood pressure as measured by spirometry at 16 weeks
- Pulse Rate as Measured by Spirometry at Visit 3 [ Time Frame: After 6 weeks of treatment ]Pulse rate as measured by spirometry at 6 weeks
- Pulse Rate as Measured by Spirometry at Visit 4 [ Time Frame: After 12 weeks of treatment ]Pulse rate as measured by spirometry at 12 weeks
- Pulse Rate as Measured by Spirometry at Visit 5 [ Time Frame: After 16 weeks of treatment ]Pulse rate as measured by spirometry at 16 weeks
| Enrollment: | 388 |
| Study Start Date: | July 2006 |
| Primary Completion Date: | September 2008 (Final data collection date for primary outcome measure) |
Eligibility| Ages Eligible for Study: | 18 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion_Criteria:
- Patients homozygous for arginine at the 16th amino acid position of the beta2 adrenergic receptor (B16 Arg/Arg)
- All patients must sign and date an Informed Consent Form for the study prior to participation in the trial
- Male or female outpatients with at least 18 years of age, but not older than 65 years
- Patients must have a documented history of asthma
- Patients must be current non-smokers or ex-smokers with a cigarette smoking history of <10 pack-years
- Patients must be on a maintenance treatment with inhaled corticosteroids with a total daily dose of 400 - 1000 mcg budesonide or equivalent
Exclusion_Criteria:
- Patients with a significant disease other than asthma
- Patients with a recent history (i.e., six months or less) of myocardial infarction
- Patients who have been hospitalized for heart failure (New York Heart Association class III or IV) within 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 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 with a diagnosis of chronic obstructive pulmonary disease (COPD)
- Patients with a history of life threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis
- Patients with known active tuberculosis
- Patients who have undergone thoracotomy with pulmonary resection.
- Patients who have completed a pulmonary rehabilitation program in the six weeks prior to visit 1 or patients who are currently in a pulmonary rehabilitation program that will not be maintained throughout the duration of the study.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00350207
Show 109 Study Locations
Show 109 Study LocationsSponsors and Collaborators
Boehringer Ingelheim Pharmaceuticals
Investigators
| Study Chair: | Boehringer Ingelheim | Boehringer Ingelheim Pharmaceuticals |
More Information
Additional Information:
No publications provided by Boehringer Ingelheim Pharmaceuticals
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Boehringer Ingelheim, Study Chair, Boehringer Ingelheim |
| ClinicalTrials.gov Identifier: | NCT00350207 History of Changes |
| Other Study ID Numbers: | 205.342 |
| Study First Received: | July 7, 2006 |
| Results First Received: | August 24, 2009 |
| Last Updated: | May 18, 2012 |
| Health Authority: | Austria: Federal Office for Safety in Health Care Belgium: Federal Agency for Medicines and Health Products, FAMHP Denmark: Danish Medicines Agency Finland: Finnish Medicines Agency France: French Health Products Safety Agency (AFSSAPS) Germany: Federal Institute for Drugs and Medical Devices Great Britain: MHRA Greece: EOF-National Organisation for Medicines Italy: Committee for the clinical experimentation of drug - Company Hospital University Pisana Russia: Ministry of Health of the Russian Federation Slovakia: State Institute for Drug Control South Africa: Medicines Control Council Spain: Spanish Medicines and Healthcare Products Agency Turkey: Ministry of Health Central Ethics Committee 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 Bromides Salmeterol Albuterol Tiotropium Anticonvulsants Central Nervous System Agents |
Therapeutic Uses Pharmacologic Actions Adrenergic beta-2 Receptor Agonists Adrenergic beta-Agonists Adrenergic Agonists Adrenergic Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Bronchodilator Agents Autonomic Agents Peripheral Nervous System Agents Anti-Asthmatic Agents Respiratory System Agents Tocolytic Agents |
ClinicalTrials.gov processed this record on June 18, 2013