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Completed

NCT Number: NCT00350207

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

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.

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Key information

Conditions

Asthma Bronchial Diseases Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Lung Diseases Lung Diseases, Obstructive Respiratory Hypersensitivity Respiratory Tract Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

205.342.43002 Boehringer Ingelheim Investigational Site, Graz, Austria

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Tiotropium Bromide

Drug

Placebo

Drug

Salmeterol xinafoate

Drug

Primary outcomes

  1. 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 outcomes

  1. Mean Weekly Morning Peak Expiratory Flow at Week 4

    Time frame: After 4 weeks of treatment

    Mean weekly morning peak expiratory flow at week 4, pre-dose

  2. Mean Weekly Morning Peak Expiratory Flow at Week 8

    Time frame: After 8 weeks of treatment

    Mean weekly morning peak expiratory flow at week 8, pre-dose

  3. Mean Weekly Morning Peak Expiratory Flow at Week 12

    Time frame: After 12 weeks of treatment

    Mean weekly morning peak expiratory flow at week 12, pre-dose

  4. Mean Weekly Morning Peak Expiratory Flow at Week 16

    Time frame: After 16 weeks of treatment

    Mean weekly morning peak expiratory flow at week 16, pre-dose

  5. Mean Weekly Evening Peak Expiratory Flow at Week 4

    Time frame: After 4 weeks of treatment

    Mean weekly evening peak expiratory flow at week 4, pre-dose

  6. Mean Weekly Evening Peak Expiratory Flow at Week 8

    Time frame: After 8 weeks of treatment

    Mean weekly evening peak expiratory flow at week 8, pre-dose

  7. Mean Weekly Evening Peak Expiratory Flow at Week 12

    Time frame: After 12 weeks of treatment

    Mean weekly evening peak expiratory flow at week 12, pre-dose

  8. Mean Weekly Evening Peak Expiratory Flow at Week 16

    Time frame: After 16 weeks of treatment

    Mean weekly evening peak expiratory flow at week 16, pre-dose

  9. 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 4, pre-dose

  10. 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 8, pre-dose

  11. 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 12, pre-dose

  12. Mean Weekly Morning Forced Expiratory Volume in 1 Second at Week 16

    Time frame: After 16 weeks of treatment

    Mean weekly morning forced expiratory volume in 1 second at week 16, pre-dose

  13. 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 4, pre-dose

  14. 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 8, pre-dose

  15. 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 12, pre-dose

  16. Mean Weekly Evening 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 16, pre-dose

  17. Mean Weekly Score for Asthma Control Diary Question "Did You Wake 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, 5: Was awake all night. 1 is the best value

  18. Mean Weekly Score for Asthma Control Diary Question "Did You Wake 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, 5: Was awake all night. 1 is the best value

  19. Mean Weekly Score for Asthma Control Diary Question "Did You Wake 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, 5: Was awake all night. 1 is the best value

  20. Mean Weekly Score for Asthma Control Diary Question "Did You Wake 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, 5: Was awake all night. 1 is the best value

  21. Mean Weekly Score for Asthma Control Diary Question "How Were Your Asthma Symptoms in the Morning" 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

  22. 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

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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

  28. 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

  29. 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

  30. 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

  31. 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

  32. 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

  33. 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

  34. 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

  35. 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

  36. 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

  37. 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

  38. 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

  39. 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

  40. 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

  41. 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

  42. 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

  43. 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

  44. 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

  45. 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

  46. 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

  47. 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

  48. 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

  49. 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

  50. Systolic Blood Pressure in Conjunction With Spirometry at Visit 3

    Time frame: After 6 weeks of treatment

    Systolic blood pressure collected in conjunction with spirometry at 6 weeks

  51. Systolic Blood Pressure in Conjunction With Spirometry at Visit 4

    Time frame: After 12 weeks of treatment

    Systolic blood pressure collected in conjunction with spirometry at 12 weeks

  52. Systolic Blood Pressure in Conjunction With Spirometry at Visit 5

    Time frame: After 16 weeks of treatment

    Systolic blood pressure collected in conjunction with spirometry at 16 weeks

  53. Diastolic Blood Pressure in Conjunction With Spirometry at Visit 3

    Time frame: After 6 weeks of treatment

    Diastolic blood pressure collected in conjunction with spirometry at 6 weeks

  54. Diastolic Blood Pressure in Conjunction With Spirometry at Visit 4

    Time frame: After 12 weeks of treatment

    Diastolic blood pressure collected in conjunction with spirometry at 12 weeks

  55. Diastolic Blood Pressure in Conjunction With Spirometry at Visit 5

    Time frame: After 16 weeks of treatment

    Diastolic blood pressure collected in conjunction with spirometry at 16 weeks

  56. Pulse Rate in Conjunction With Spirometry at Visit 3

    Time frame: After 6 weeks of treatment

    Pulse rate collected in conjunction with spirometry at 6 weeks

  57. Pulse Rate in Conjunction With Spirometry at Visit 4

    Time frame: After 12 weeks of treatment

    Pulse rate collected in conjunction with spirometry at 12 weeks

  58. Pulse Rate in Conjunction With Spirometry at Visit 5

    Time frame: After 16 weeks of treatment

    Pulse rate collected in conjunction with spirometry at 16 weeks

  59. Mean PEF Variability at Week 4

    Time frame: After 4 weeks of treatment

    PEF (Peak expiratory flow) variability is defined as the difference between the highest morning PEF value and the highest evening PEF value of one day divided by the arithmetic mean of these two PEF values and multiplied by 100%

  60. Mean PEF Variability at Week 8

    Time frame: After 8 weeks of treatment

    PEF (Peak expiratory flow) variability is defined as the difference between the highest morning PEF value and the highest evening PEF value of one day divided by the arithmetic mean of these two PEF values and multiplied by 100%

  61. Mean PEF Variability at Week 12

    Time frame: After 12 weeks of treatment

    PEF (Peak expiratory flow) variability is defined as the difference between the highest morning PEF value and the highest evening PEF value of one day divided by the arithmetic mean of these two PEF values and multiplied by 100%

  62. Mean PEF Variability at Week 16

    Time frame: After 16 weeks of treatment

    PEF (Peak expiratory flow) variability is defined as the difference between the highest morning PEF value and the highest evening PEF value of one day divided by the arithmetic mean of these two PEF values and multiplied by 100%

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study 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

Important dates

Study start
2006
Primary completion
2008
First posted
Jul 10, 2006
Registry last updated
Dec 24, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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