Randomised, Double- Blind, Cross-over Efficacy and Safety Comparison of Three Different Doses of Tiotropium Administered Once Daily Versus Placebo in Patients With Moderate Persistent Asthma.
- Conditions
- Asthma
- Interventions
- Registration Number
- NCT01233284
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
Rationale for the current trial is to evaluate the efficacy and safety of three doses (1.25 µg, 2.5 µg and 5.0 µg ex mouthpiece) of tiotropium inhalation solution in patients with moderate persistent asthma who are still symptomatic despite regular maintenance therapy with inhaled corticosteroids (ICS).
The data collected in the present trial will provide useful information to health care providers and patients regarding the efficacy and safety of a once daily inhalation of three different doses of tiotropium solution delivered by the Respimat® inhaler in addition to inhaled corticosteroids in the treatment of not fully controlled moderate asthma in comparison to placebo. The Pharmacokinetics (PK) of tiotropium is well established in COPD patients. However, there is currently no PK data available for the 3 doses of tiotropium being tested in this trial in patients with moderate persistent asthma. Tiotropium is a once daily drug. Hence, the rationale for blood and urine sampling for PK analysis over 24 hours in a subset of patients is to confirm the PK of the 3 doses in moderate asthma patients. Rationale for the 24-hour pulmonary function test sub-investigation is to demonstrate that a once daily dosing of tiotropium inhalation solution is effective and safe in the treatment of moderate persistent asthma.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 149
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description tiotropium low dose once daily tiotropium bromide 1.25µg once daily once daily, delivered by the Respimat® inhaler tiotropium medium dose once daily tiotropium bromide 2.5µg once daily once daily, delivered by the Respimat® inhaler tiotropium high dose once daily tiotropium bromide high dose once daily once daily, delivered by the Respimat® inhaler Placebo once daily Tiotropium matching Placebo once daily once daily, delivered by the Respimat® inhaler
- Primary Outcome Measures
Name Time Method Forced Expiratory Volume in One Second (FEV1) Peak Within 0-3 Hours Post-dose Response 10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h after drug administration Mixed model repeated measurement (MMRM) results. Response was defined as change from baseline at the end of of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline.
- Secondary Outcome Measures
Name Time Method Trough FEV1 Response Baseline and 4 weeks MMRM results. Response was defined as change from baseline at the end of of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. Trough FEV1 was measured just prior to the last administration of randomised treatment.
FEV1 Area Under the Curve 0-3 Hours (AUC0-3h) Response 10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h after drug administration MMRM results. Response was defined as change from baseline at the end of of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC0-3h was calculated using the trapezoidal rule divided by the observation time (3 hours) to report in litres.
Forced Vital Capacity (FVC) Peak Within 0-3 Hours Post-dose Response 10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h after drug administration MMRM results. Response was defined as change from baseline at the end of of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline.
Trough FVC Response Baseline and 4 weeks MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. Trough FVC was measured just prior to the last administration of randomised treatment.
FVC AUC0-3h Response 10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h after drug administration MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. FVC AUC0-3h was calculated using the trapezoidal rule divided by the observation time (3 hours) to report in litres.
Individual FEV1 Over Time (at Each Timepoint at Visits) Response Baseline and 4 weeks MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline.
Individual FVC Over Time (at Each Timepoint at Visits) Response Baseline and 4 weeks MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline.
Mean Number of Puffs of Rescue Medication During Daytime (Last Week on Treatment, Response Values) Baseline and 4 weeks MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. Weekly means obtained during the last week of each period of randomised treatment will be compared (measured by patients at home using the AM2+ device).
Individual Peak Expiratory Flow (PEF) Over Time (at Each Timepoint at Visits) Response Baseline and 4 weeks MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline.
Mean Pre-dose Morning PEF (PEF a.m.) Response During the Last Week on Treatment Baseline and 4 weeks MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. Weekly means obtained during the last week of each period of randomised treatment will be compared (measured by patients at home using the AM2+ device).
Mean Pre-dose Evening PEF (PEF p.m.) Response During the Last Week on Treatment Baseline and 4 weeks MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. Weekly means obtained during the last week of each period of randomised treatment will be compared (measured by patients at home using the AM2+ device).
PEF Variability Response (Last Week on Treatment) Baseline and 4 weeks MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. PEF variability is the absolute difference between morning and evening PEF value divided by the mean of these two values, expressed as a percent . Weekly means obtained during the last week of each period of randomised treatment will be compared.
Mean Number of Puffs of Rescue Medication During the Whole Day (Last Week on Treatment, Response Values) Baseline and 4 weeks MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. Weekly means obtained during the last week of each period of randomised treatment will be compared (measured by patients at home using the AM2+ device).
Mean Number of Puffs of Rescue Medication During Nighttime (Last Week on Treatment, Response Values) Baseline and 4 weeks MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. Weekly means obtained during the last week of each period of randomised treatment will be compared (measured by patients at home using the AM2+ device).
Mean Number of Night Awakenings During the Last Week on Treatment (Score, Response Values) Baseline and 4 weeks MMRM results. Response was defined as change from baseline at the end of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. Weekly means obtained during the last week of each period of randomised treatment will be compared (measured by patients at home using the AM2+ device).
FEV1 Area Under the Curve Within 24 Hours (h) Response (FEV1 AUC0-12h, FEV1 AUC12-24h, FEV1 AUC0-24h) 10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h, 4h, 11h 50min, 12h 30min, 13h, 14h, 15h, 16h, 18h, 20h, 22h, 23h, 23h 50min after drug administration MMRM results. Response was defined as change from baseline at the end of of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. FEV1 AUC0-12, FEV1 AUC12-24 and FEV1 AUC0-24 were calculated using the trapezoidal rule divided by the observation time (12h resp. 24h) to report in litres.
FVC Area Under the Curve Within 24 Hours (h) Response (FVC AUC0-12h, FVC AUC12-24h, FVC AUC0-24h) 10 minutes (min) before drug administration and 30 min, 1h, 2h, 3h, 4h, 11h 50min, 12h 30min, 13h, 14h, 15h, 16h, 18h, 20h, 22h, 23h, 23h 50min after drug administration MMRM results. Response was defined as change from baseline at the end of of each 4-week treatment period. Means are adjusted for treatment, period, patient and study baseline. FVC AUC0-12, FVC AUC12-24 and FVC AUC0-24 were calculated using the trapezoidal rule divided by the observation time (12h resp. 24h) to report in litres.
Trial Locations
- Locations (19)
205.380.49010 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
205.380.38003 Boehringer Ingelheim Investigational Site
🇺🇦Kharkiv, Ukraine
205.380.38004 Boehringer Ingelheim Investigational Site
🇺🇦Kharkiv, Ukraine
205.380.49009 Boehringer Ingelheim Investigational Site
🇩🇪Mainz, Germany
205.380.38002 Boehringer Ingelheim Investigational Site
🇺🇦Kiev, Ukraine
205.380.49005 Boehringer Ingelheim Investigational Site
🇩🇪Wiesloch, Germany
205.380.49008 Boehringer Ingelheim Investigational Site
🇩🇪Schwerin, Germany
205.380.49004 Boehringer Ingelheim Investigational Site
🇩🇪Hamburg, Germany
205.380.49007 Boehringer Ingelheim Investigational Site
🇩🇪Hannover, Germany
205.380.43001 Boehringer Ingelheim Investigational Site
🇦🇹Schlüsslberg, Austria
205.380.43002 Boehringer Ingelheim Investigational Site
🇦🇹Hallein, Austria
205.380.43004 Boehringer Ingelheim Investigational Site
🇦🇹Linz, Austria
205.380.49001 Boehringer Ingelheim Investigational Site
🇩🇪Wiesbaden, Germany
205.380.49006 Boehringer Ingelheim Investigational Site
🇩🇪Berlin, Germany
205.380.49003 Boehringer Ingelheim Investigational Site
🇩🇪Frankfurt, Germany
205.380.43005 Boehringer Ingelheim Investigational Site
🇦🇹Neumarkt am Wallersee, Austria
205.380.43003 Boehringer Ingelheim Investigational Site
🇦🇹Thalheim bei Wels, Austria
205.380.38005 Boehringer Ingelheim Investigational Site
🇺🇦Ivano-Frankivsk, Ukraine
205.380.38001 Boehringer Ingelheim Investigational Site
🇺🇦Kiev, Ukraine