The primary objective of this trial was to establish non-inferiority of lung function response to tiotropium 10 μg, formulated as inhalation powder in the polyethylene hard capsule and delivered via the HandiHaler® 2, compared to tiotropium 18 μg, formulated as inhalation powder in the hard gelatine capsule and delivered via the HandiHaler® (Spiriva®) following single dose inhalation in patients with COPD. A hard polyethylene (PE) capsule with half the strength (tiotropium 5 μg) was included to investigate a dose ordering effect. The secondary objectives were to characterize the pharmacokinetics of tiotropium inhalation powder hard PE capsule (delivered via HandiHaler® 2) and tiotropium inhalation powder hard gelatine capsule (delivered via HandiHaler®) and to compare the safety of the two pharmaceutical formulations.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
121
inhalation powder, hard PE capsule
inhalation powder, hard PE capsule
Tiotropium inhalation powder, hard gelatine capsule
oral inhalation via the blue HandiHaler®
oral inhalation via the grey HandiHaler®
Area under the curve for the time period 0 to 12 hours of forced expiratory volume in one second (FEV1 AUC0-12)
Time frame: pre-dose and 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
Peak FEV1 on each test-day
Peak FEV1 is defined as the maximum FEV1 obtained within the first three hours post dosing
Time frame: pre-dose and 30, 60 minutes, 2 and 3 hours post-dosing
Peak forced vital capacity (FVC)
Time frame: pre-dose and 30, 60 minutes, 2, 3, 4, 6, 8, 10, 12, 14, 22, 23 and 24 hours post-dosing
FVC AUC0-12
Time frame: pre-dose and 30, 60 minutes, 2, 3, 4, 6, 8, 10 and 12 hours post-dosing
FEV1 AUC12-24
Time frame: 12, 14, 22, 23 and 24 hours post-dosing
FEV1 AUC0-24
Time frame: pre-dose and 30, 60 minutes, 2, 3, 4, 6, 8, 10, 12, 14, 22, 23 and 24 hours post-dosing
FVC AUC12-24
Time frame: 12, 14, 22, 23 and 24 hours post-dosing
FVC AUC0-24
Time frame: pre-dose and 30, 60 minutes, 2, 3, 4, 6, 8, 10, 12, 14, 22, 23 and 24 hours post-dosing
Individual FEV1 measurements at each time point
Time frame: pre-dose and 30, 60 minutes, 2, 3, 4, 6, 8, 10, 12, 14, 22, 23 and 24 hours post-dosing
Individual FVC measurements at each time point
Time frame: pre-dose and 30, 60 minutes, 2, 3, 4, 6, 8, 10, 12, 14, 22, 23 and 24 hours post-dosing
AUCt1-t2 (area under the concentration-time curve of the analyte in plasma over the time interval t1 to t2)
Time frame: 5, 15, 30 minutes, 1 and 2 hours following drug administration
Cmax (maximum measured concentration of the analyte in plasma)
Time frame: 5, 15, 30 minutes, 1 and 2 hours following drug administration
tmax (time from dosing to the maximum concentration of the analyte in plasma)
Time frame: 5, 15, 30 minutes, 1 and 2 hours following drug administration
Aet1-t2 (amount of analyte that is eliminated in urine from the time point t1 to time point t2)
Time frame: 0 to 2, 2 to 12 hours after administration
fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2)
Time frame: 0 to 2, 2 to 12 hours after administration
CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2)
Time frame: 0 to 2, 2 to 12 hours after administration
%AUCtz-∞ (percentage of the extrapolated part of the total AUC0-∞)
Time frame: 5, 15, 30 minutes, 1 and 2 hours following drug administration
Number of patients with adverse events
Time frame: up to 13 weeks
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