Phase 2
Completed N=94
A Randomised, Double- Blind, Placebo Controlled, Cross-over Efficacy and Safety Comparison of Tiotropium 5 µg Once Daily and Tiotropium 2.5 µg Twice Daily for Four Weeks in Patients With Moderate Persistent Asthma
Source: ClinicalTrials.gov NCT01152450 ↗Enrolled (actual)
94
Serious AEs
1.1%
Results posted
Oct 2012
Primary outcomePrimary: Forced Expiratory Volume in One Second (FEV1) Area Under the Curve 0-24 Hours (AUC0-24h) Response — 0.091; 0.241; 0.250 L — p=<0.0001
Summary
Rationale for the current trial is to demonstrate 24 hour bronchodilator efficacy and safety of tiotropium 5 µg administered once daily (in the evening) which is regarded beneficial for the compliance and convenience of the patient in comparison to placebo. Further the rationale is to evaluate efficacy and safety of tiotropium 2.5 µg administered twice daily delivered by the Respimat® inhaler in comparison to placebo and tiotropium 5 µg administered once daily (in the evening) delivered by the Respimat® inhaler in patients with moderate persistent asthma.
Rationale for the pharmacokinetic subinvestigation is to evaluate the 24 hours exposure to tiotropium in patients with moderate persistent asthma when administered 5 µg tiotropium once daily (in the evening) or 2.5 µg tiotropium twice daily.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Forced Expiratory Volume in One Second (FEV1) Area Under the Curve 0-24 Hours (AUC0-24h) Response |
0.091; 0.241; 0.250 | <0.0001 sig |
| SECONDARY Mean Pre-dose Morning Peak Expiratory Flow (PEF a.m.) Response During the Last Week on Treatment |
1.953; 23.281; 24.310 | <0.0001 sig |
| SECONDARY Mean Pre-dose Evening Peak Expiratory Flow (PEF p.m.) Response During the Last Week on Treatment |
-1.560; 28.360; 27.096 | <0.0001 sig |
| SECONDARY FEV1 Area Under the Curve 0-12 Hours (AUC0-12h) Response |
0.048; 0.217; 0.233 | <0.0001 sig |
| SECONDARY FEV1 Area Under the Curve 12-24 Hours (AUC12-24h) Response |
0.135; 0.264; 0.266 | <0.0001 sig |
| SECONDARY Peak FEV1 Within 24 Hours Post-dose Response |
0.337; 0.469; 0.468 | <0.0001 sig |
| SECONDARY Trough FEV1 Response |
0.143; 0.254; 0.275 | 0.0002 sig |
| SECONDARY Trough Forced Vital Capacity (FVC) Response |
0.112; 0.179; 0.168 | 0.0515 |
| SECONDARY FVC Area Under the Curve 0-12 Hours (AUC0-12h) Response |
-0.026; 0.099; 0.074 | <0.0001 sig |
| SECONDARY FVC Area Under the Curve 12-24 Hours (AUC12-24h) Response |
0.032; 0.108; 0.100 | 0.0051 sig |
| SECONDARY Peak FVC Within 24 Hours Post-dose Response |
0.302; 0.380; 0.350 | 0.0042 sig |
| SECONDARY Individual FEV1 Over Time (at Each Timepoint at Visits) Response |
0.143; 0.254; 0.275; 0.132; 0.281; 0.304 | — |
| SECONDARY Individual FVC Over Time (at Each Timepoint at Visits) Response |
0.112; 0.179; 0.168; 0.053; 0.158; 0.130 | — |
| SECONDARY Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response |
19.770; 42.428; 57.897; 12.994; 46.272; 58.436 | — |
| SECONDARY FVC Area Under the Curve 0-24 Hours (AUC0-24h) Response |
0.003; 0.104; 0.087 | <0.0001 sig |
| SECONDARY PEF Area Under the Curve 0-24 Hours (AUC0-24h) Response |
8.589; 38.831; 42.899 | <0.0001 sig |
| SECONDARY PEF Variability Response (Last Week on Treatment) |
0.296; 0.619; 0.685 | 0.6747 |
| SECONDARY Mean Number of Puffs of Rescue Medication During the Whole Day (Last Week on Treatment, Response Values) |
-0.841; -0.917; -1.016 | 0.5906 |
| SECONDARY Mean Number of Puffs of Rescue Medication During Daytime (Last Week on Treatment, Response Values) |
-0.562; -0.564; -0.624 | 0.9797 |
| SECONDARY Mean Number of Puffs of Rescue Medication During Nighttime (Last Week on Treatment, Response Values) |
-0.358; -0.419; -0.432 | 0.4089 |
| SECONDARY Mean Number of Night Awakenings During the Last Week on Treatment (Score, Response Values) |
-0.106; -0.104; -0.102 | 0.9626 |
Eligibility Criteria
Inclusion criteria
- All patients must sign and date an Informed Consent Form consistent with International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use 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 months history of asthma at the time of enrolment into the trial. The diagnosis of asthma has to be confirmed at Visit 1 with a bronchodilator reversibility resulting in a Forced Expiratory Volume in 1 Second (FEV1) increase of equal above 12% and equal above 200mL.
- The initial diagnosis of asthma must have been made before the patient's age of 40.
- All patients must have a diagnosis of moderate persistent asthma and must be symptomatic despite their current maintenance treatment with medium doses of inhaled corticosteroids.
- All patients must have been on maintenance treatment with a medium, stable dose of inhaled corticosteroids (alone or in a fixed combination with a Long Acting Betaadrenergic (LABA) or Short Acting Betaadrenergic (SABA)) for at least 4 weeks prior to Visit 1.
- All patients must be symptomatic at Visit 1 (screening) and Visit 2 as defined by an Asthma Control Questionnaire (ACQ) Score
- All patients must have a pre-bronchodilator FEV1 above equal 60% predicted and below equal 90% of predicted normal at Visit 1. Predicted normal values will be calculated according to the European Coal and Steel Community Guidelines (ECSC).
- All patients must have an increase in FEV1 of equal above 12% and equal above 200 mL 15 minutes after 400 µg salbutamol 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 and who have a smoking history of less than 10 pack years.
- Patients must be able to use the Respimat® inhaler correctly.
- Patients must be able to perform all trial related procedures including technically acceptable pulmonary function tests and use of the e-Diary/peak flow meter.
- Patients taking a chronic pulmonary medication allowed by the study protocol must be willing to continue this therapy for the entire duration of the study (exception: times of acute disease deterioration).
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 hematology or blood chemistry if the abnormality defines a significant disease as defined in exclusion criterion no. 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 Lung 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 significant alcohol or drug abuse within the past two years.
- Patients who
Data sourced from ClinicalTrials.gov (NCT01152450). 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. Informational only — not medical advice.