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Efficacy and Safety of Tiotropium and Salmeterol in Moderate Persistent Asthma Patients Homozygous for B16-Arg/Arg
This study has been completed.
First Received: July 7, 2006   Last Updated: November 20, 2009   History of Changes
Sponsor: Boehringer Ingelheim Pharmaceuticals
Information provided by: Boehringer Ingelheim Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00350207
  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 II

Study Type: Interventional
Study Design: Treatment, Parallel Assignment
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 ]

Secondary Outcome 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 ]

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:

  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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00350207

  Show 109 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim Pharmaceuticals
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim Pharmaceuticals
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim ( Boehringer Ingelheim, Study Chair )
Study ID Numbers: 205.342
Study First Received: July 7, 2006
Results First Received: August 24, 2009
Last Updated: November 20, 2009
ClinicalTrials.gov Identifier: NCT00350207     History of Changes
Health Authority: Austria: Federal Office for Safety in Health Care;   Belgium: Federal Agency for Medicines and Health Products;   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 and Social Development 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:
Respiratory System Agents
Parasympatholytics
Neurotransmitter Agents
Cholinergic Antagonists
Bronchial Diseases
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Cholinergic Agents
Adrenergic Agonists
Hypersensitivity
Lung Diseases, Obstructive
Respiratory Tract Diseases
Therapeutic Uses
Tiotropium
Salmeterol
Adrenergic beta-Agonists
Immune System Diseases
Asthma
Anti-Asthmatic Agents
Pharmacologic Actions
Autonomic Agents
Lung Diseases
Hypersensitivity, Immediate
Peripheral Nervous System Agents
Bronchodilator Agents
Respiratory Hypersensitivity

ClinicalTrials.gov processed this record on February 08, 2010