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Phase 3 N=1,070 Randomized Double-blind Treatment

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 I

Asthma

Enrolled (actual)
1,070
Serious AEs
2.4%
Results posted
Feb 2014
Primary outcome: Primary: Peak FEV1 Within 3 Hours Post-dose Response — 0.053; 0.289; 0.250; 0.266 Litre — p=<0.0001

Study Design & Population

Study type
Interventional
Phase
Phase 3
Interventions
Placebo (Drug); tiotropium Respimat® low dose (Drug); tiotropium Respimat® high dose (Drug); 50 mcg salmeterol HFA MDI (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Boehringer Ingelheim
Primary completion
Nov 2012

Outcome Measures

OutcomeResultp-value
PRIMARY
Peak FEV1 Within 3 Hours Post-dose Response
0.053; 0.289; 0.250; 0.266 <0.0001 sig
PRIMARY
Trough FEV1 Response
-0.036; 0.148; 0.115; 0.086 <0.0001 sig
PRIMARY
The Responder Rate as Assessed by the ACQ From the Two Twin Trials 205.419 (NCT01172821) and the Present 205.418 (NCT01172808)
57.7; 64.5; 64.3; 66.5 0.0308 sig
SECONDARY
Peak FVC Within 3 Hours Post-dose Response
0.045; 0.219; 0.148; 0.168 <0.0001 sig
SECONDARY
Trough FVC Response
-0.039; 0.086; 0.036; 0.028 0.0001 sig
SECONDARY
FEV1 Area Under Curve 0-3 Hours (AUC0-3h) Response
-0.033; 0.192; 0.163; 0.182 <0.0001 sig
SECONDARY
FVC Area Under Curve 0-3 Hours (AUC0-3h) Response
-0.066; 0.092; 0.041; 0.062 <0.0001 sig
SECONDARY
Trough PEF Response
2.913; 40.819; 36.590; 31.317 <0.0001 sig
SECONDARY
Total Asthma Quality of Life Questionnaire (AQLQs)) Score
5.449; 5.522; 5.519; 5.654 0.2717
SECONDARY
Total Asthma Control Questionnaire (ACQ) Score at the End of the 24-week Treatment Period
1.563; 1.362; 1.431; 1.302 0.0007 sig
SECONDARY
The Responder Rate as Assessed by the ACQ
53.2; 62.5; 66.7; 68.6 0.0377 sig
SECONDARY
Mean Pre-dose Morning PEF (PEF a.m.) Based on the Weekly Mean Response at Week 24
-10.159; 20.432; 13.501; 22.467 <0.0001 sig
SECONDARY
Mean Pre-dose Evening PEF (PEF p.m.) Based on the Weekly Mean Response at Week 24
-9.181; 18.978; 15.188; 19.727 <0.0001 sig
SECONDARY
PEF Variability
-1.400; -1.958; 0.180; -2.300 0.3550
SECONDARY
Mean Pre-dose Morning FEV1 (FEV1 a.m.) Based on the Weekly Mean Response at Week 24
0.021; 0.101; 0.073; 0.117 0.0069 sig
SECONDARY
Mean Pre-dose Evening FEV1 (FEV1 p.m.) Based on the Weekly Mean Response at Week 24
-0.000; 0.065; 0.039; 0.072 0.0363 sig
SECONDARY
Mean Number of Puffs of Rescue Medication During the Entire 24-h Day Based on the Weekly Mean Response at Week 24
-0.962; -1.124; -0.818; -1.416 0.2447
SECONDARY
Asthma Symptom-free Days Based on the Weekly Mean Response at Week 24
0.162; 0.207; 0.157; 0.266 0.1178
SECONDARY
Time to First Severe Asthma Exacerbation From the Two Twin Trials 205.419 (NCT01172821) and the Present 205.418 (NCT01172808)
NA; NA; NA; NA
SECONDARY
Time to First Asthma Exacerbation From the Two Twin Trials 205.419 (NCT01172821) and the Present 205.418 (NCT01172808)
NA; NA; NA; NA

Summary

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.

Eligibility Criteria

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.
  • 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.
  • All patients must have a pre-bronchodilator FEV1 at least 60% and less than or equal to 90% of predicted normal at Visit 1.
  • Variation of absolute FEV1 values of Visit 1 (pre-bronchodilator) as compared to Visit 2 (pre-dose) must be within ± 30%.
  • 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.
  • Patients must be able to use the Respimat® inhaler and metered dose inhaler correctly.
  • 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 con
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01172808). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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