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
- Conditions
- Asthma
- Interventions
- Registration Number
- NCT01152450
- Lead Sponsor
- Boehringer Ingelheim
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 94
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Tiotropium daily dose q.d. Tiotropium 5 µg q.d. two actuations delivered via Respimat® inhaler Placebo Placebo N/A (two actuations of placebo) delivered via Respimat® inhaler Tiotropium half daily dose b.i.d. Tiotropium 2.5 µg b.i.d two actuations delivered via Respimat® inhaler
- Primary Outcome Measures
Name Time Method Forced Expiratory Volume in One Second (FEV1) Area Under the Curve 0-24 Hours (AUC0-24h) Response 10 minutes (min) prior to first dose (baseline) and -10 min, 30 min, 60 min, 2 hours (h) , 3 h, 4 h , 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose at week 4 Mixed Model Repeated Measure (MMRM) results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measurements performed in relation to evening dosing. AUC0-24h calculated using the trapezoidal rule divided by the observation time (24 hours) to report in litres.
- Secondary Outcome Measures
Name Time Method Mean Pre-dose Morning Peak Expiratory Flow (PEF a.m.) Response During the Last Week on Treatment Baseline and during week 4 of each treatment period MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured by patients at home using the AM2+ device.
Mean Pre-dose Evening Peak Expiratory Flow (PEF p.m.) Response During the Last Week on Treatment Baseline and during week 4 of each treatment period MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured by patients at home using the AM2+ device.
FEV1 Area Under the Curve 0-12 Hours (AUC0-12h) Response 10 min prior to first dose (baseline) and -10 min, 30 min, 60 min, 2 h, 3 h, 4 h and 11 h 50 min related to evening dose at week 4 MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-12h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.
FEV1 Area Under the Curve 12-24 Hours (AUC12-24h) Response 10 min prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose at week 4 MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC12-24h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.
Peak FEV1 Within 24 Hours Post-dose Response Baseline and 4 weeks MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following the evening trial-drug inhalation at the end of each 4 week period of randomised treatment.
Trough FEV1 Response Baseline and 4 weeks MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Trough FEV1 is defined as FEV1 value (performed at 10 minutes prior to the evening trial-drug inhalation) at the end of each 4 week period of randomised treatment.
Trough Forced Vital Capacity (FVC) Response Baseline and 4 weeks MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Trough FVC is defined as FVC value (performed at 10 minutes prior to the evening trial-drug inhalation) at the end of each 4 week period of randomised treatment.
FVC Area Under the Curve 0-12 Hours (AUC0-12h) Response 10 min prior to first dose (baseline) and -10 min, 30 min, 60 min, 2 h, 3 h, 4 h and 11 h 50 min related to evening dose at week 4 MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following each dosing determined at the end of each 4 week treatment period. AUC0-12h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.
FVC Area Under the Curve 12-24 Hours (AUC12-24h) Response 10 min prior to first dose (baseline) and 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose at week 4 MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following each dosing determined at the end of each 4 week treatment period. AUC12-24h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.
Peak FVC Within 24 Hours Post-dose Response Baseline and 4 weeks MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following each dosing determined at the end of each 4 week treatment period.
Individual FEV1 Over Time (at Each Timepoint at Visits) Response Baseline and 4 weeks MMRM results. Response was defined as change from baseline. 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. Means are adjusted for treatment, period, patient and study baseline.
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. Means are adjusted for treatment, period, patient and study baseline.
FVC Area Under the Curve 0-24 Hours (AUC0-24h) Response 10 min prior to first dose (baseline) and -10 min, 30 min, 60 min, 2 h, 3 h, 4 h , 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose at week 4 MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. AUC0-24h calculated using the trapezoidal rule divided by the observation time (24 hours) to report in litres.
PEF Area Under the Curve 0-24 Hours (AUC0-24h) Response 10 min prior to first dose (baseline) and -10 min, 30 min, 60 min, 2 h, 3 h, 4 h , 11 h 50 min, 12 h 30 min, 13 h, 14 h, 15 h, 16 h, 18 h, 20 h, 22 h, 23 h, and 23 h 50 min related to evening dose at week 4 MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. AUC0-24h calculated using the trapezoidal rule divided by the observation time (24 hours) to report in litres/min.
PEF Variability Response (Last Week on Treatment) Baseline and during week 4 MMRM results. Response was defined as change from baseline. 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 during week 4 MMRM results. Response was defined as change from baseline. 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.
Mean Number of Puffs of Rescue Medication During Daytime (Last Week on Treatment, Response Values) Baseline and during week 4 MMRM results. Response was defined as change from baseline. 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.
Mean Number of Puffs of Rescue Medication During Nighttime (Last Week on Treatment, Response Values) Baseline and during week 4 MMRM results. Response was defined as change from baseline. 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.
Mean Number of Night Awakenings During the Last Week on Treatment (Score, Response Values) Baseline and during week 4 MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Assessed by the patient's electronic diary (eDiary incorporated in the AM2+ device), obtained during the last week of each period of randomised treatment.
Trial Locations
- Locations (15)
205.420.37101 Boehringer Ingelheim Investigational Site
🇱🇻Riga, Latvia
205.420.37103 Boehringer Ingelheim Investigational Site
🇱🇻Riga, Latvia
205.420.43001 Boehringer Ingelheim Investigational Site
🇦🇹Wels, Austria
205.420.42002 Boehringer Ingelheim Investigational Site
🇨🇿Brno, Czechia
205.420.49001 Boehringer Ingelheim Investigational Site
🇩🇪Mannheim, Germany
205.420.42001 Boehringer Ingelheim Investigational Site
🇨🇿Kyjov, Czechia
205.420.43002 Boehringer Ingelheim Investigational Site
🇦🇹Linz, Austria
205.420.43004 Boehringer Ingelheim Investigational Site
🇦🇹Schlüsslberg, Austria
205.420.43003 Boehringer Ingelheim Investigational Site
🇦🇹Thalheim bei Wels, Austria
205.420.37201 Boehringer Ingelheim Investigational Site
🇪🇪Kohtla-Järve, Estonia
205.420.37202 Boehringer Ingelheim Investigational Site
🇪🇪Tallinn, Estonia
205.420.49002 Boehringer Ingelheim Investigational Site
🇩🇪Großhansdorf, Germany
205.420.49004 Boehringer Ingelheim Investigational Site
🇩🇪Hannover, Germany
205.420.49003 Boehringer Ingelheim Investigational Site
🇩🇪Schwerin, Germany
205.420.37102 Boehringer Ingelheim Investigational Site
🇱🇻Daugavpils, Latvia