Efficacy and Safety of Tiotropium and Salmeterol in Moderate Persistent Asthma Patients Homozygous for B16-Arg/Arg

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”

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.

Intervention(s) in this Clinical Trial

• Drug: Tiotropium bromide
• Drug: Placebo
• Drug: Salmeterol xinafoate

Primary 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
    

Secondary Measures

• Mean Weekly Morning Peak Expiratory Flow at Week 4
  • Time Frame: After 4 weeks of treatment
    
• Mean Weekly Morning Peak Expiratory Flow at Week 8
  • Time Frame: After 8 weeks of treatment
    
• Mean Weekly Morning Peak Expiratory Flow at Week 12
  • Time Frame: After 12 weeks of treatment
    
• Mean Weekly Morning Peak Expiratory Flow at Week 16
  • Time Frame: After 16 weeks of treatment
    
• Mean Weekly Evening Peak Expiratory Flow at Week 4
  • Time Frame: After 4 weeks of treatment
    
• Mean Weekly Evening Peak Expiratory Flow at Week 8
  • Time Frame: After 8 weeks of treatment
    
• Mean Weekly Evening Peak Expiratory Flow at Week 12
  • Time Frame: After 12 weeks of treatment
    
• Mean Weekly Evening Peak Expiratory Flow at Week 16
  • Time Frame: After 16 weeks of treatment
    
• Mean Weekly Morning Forced Expiratory Volume in 1 Second at Week 4
  • Time Frame: After 4 weeks of treatment
    
• Mean Weekly Morning Forced Expiratory Volume in 1 Second at Week 8
  • Time Frame: After 8 weeks of treatment
    
• Mean Weekly Morning Forced Expiratory Volume in 1 Second at Week 12
  • Time Frame: After 12 weeks of treatment
    
• Mean Weekly Morning Forced Expiratory Volume in 1 Second at Week 16
  • Time Frame: After 16 weeks of treatment
    
• Mean Weekly Evening Forced Expiratory Volume in 1 Second at Week 4
  • Time Frame: After 4 weeks of treatment
    
• Mean Weekly Evening Forced Expiratory Volume in 1 Second at Week 8
  • Time Frame: After 8 weeks of treatment
    
• Mean Weekly Evening Forced Expiratory Volume in 1 Second at Week 12
  • Time Frame: After 12 weeks of treatment
    
• Mean Weekly Evening Forced Expiratory Volume in 1 Second at Week 16
  • Time Frame: After 16 weeks of treatment
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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
    
• 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 at Visit 4
  • Time Frame: 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 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 at Visit 4
  • Time Frame: 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
    
• Mini-Asthma Quality of Life Questionnaire (Mini-AQLQ) Overall Score at Visit 3
  • Time Frame: After 6 weeks of treatment
    
• Mini-AQLQ Overall Score at Visit 4
  • Time Frame: After 12 weeks of treatment
    
• Mini-AQLQ Overall Score at Visit 5
  • Time Frame: After 16 weeks of treatment
    
• 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 Visit 4
  • Time Frame: After 12 weeks of treatment
    
• Systolic Blood Pressure as Measured by Spirometry at Visit 5
  • Time Frame: After 16 weeks of treatment
    
• 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 Visit 4
  • Time Frame: After 12 weeks of treatment
    
• Diastolic Blood Pressure as Measured by Spirometry at Visit 5
  • Time Frame: After 16 weeks of treatment
    
• Pulse Rate as Measured by Spirometry at Visit 3
  • Time Frame: After 6 weeks of treatment
    
• Pulse Rate as Measured by Spirometry at Visit 4
  • Time Frame: After 12 weeks of treatment
    
• Pulse Rate as Measured by Spirometry at Visit 5
  • Time Frame: After 16 weeks of treatment
    

Inclusion_Criteria:

• 1. Patients homozygous for arginine at the 16th amino acid position of the beta2 adrenergic receptor (B16 Arg/Arg)
• 2. All patients must sign and date an Informed Consent Form for the study prior to participation in the trial
• 3. Male or female outpatients with at least 18 years of age, but not older than 65 years
• 4. Patients must have a documented history of asthma
• 5. Patients must be current non-smokers or ex-smokers with a cigarette smoking history of <10 pack-years
• 6. Patients must be on a maintenance treatment with inhaled corticosteroids with a total daily dose of 400 - 1000 mcg budesonide or equivalent

Exclusion_Criteria:

• 1. Patients with a significant disease other than asthma
• 2. Patients with a recent history (i.e., six months or less) of myocardial infarction
• 3. Patients who have been hospitalized for heart failure (New York Heart Association class III or IV) within the past year
• 4. Patients with any unstable or life threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year
• 5. 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.
• 6. Patients with a diagnosis of chronic obstructive pulmonary disease (COPD)
• 7. Patients with a history of life threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis
• 8. Patients with known active tuberculosis
• 9. Patients who have undergone thoracotomy with pulmonary resection.
• 10. 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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Boehringer Ingelheim Pharmaceuticals Industry

Overall Clinical Trial Officials and Contacts

Boehringer Ingelheim Study Chair Boehringer Ingelheim Pharmaceuticals  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00350207

Study ID Number: 205.342

ClinicalTrials.gov Identifier: NCT00350207

Health Authority: Austria: Federal Office for Safety in Health Care