A Randomised, Open-label, 4-way Crossover Study to Characterize the Pharmacokinetics, Safety and Efficacy of FDC Tiotropium/Salmeterol, Tiotropium, Salmeterol and a Free Combination of Tiotropium Plus Salmeterol Following 4-week Treatment Periods in Patients With COPD.

简要总结

主要结局

次要结局

• Area under the concentration time curve (AUCt1-t2) of tiotropium and salmeterol in plasma over the time interval t1 to t2 for time intervals 0 to 4, 0 to 6, and 0 to 8 hours after inhalation (AUC0-4, AUC0-6, and AUC0-8)(16 weeks)
• Time from dosing to the maximum concentration of tiotropium and salmeterol in plasma (tmax)(16 weeks)
• Terminal rate constant in plasma (λz)(16 weeks)
• Terminal half-life (t½) of tiotropium and salmeterol in plasma)(16 weeks)
• Mean residence time (MRTih) of tiotropium and salmeterol in the body after inhalational administration(16 weeks)
• Apparent clearance (CL/F) of tiotropium and salmeterol in plasma after extravascular administration)(16 weeks)
• Apparent volume of distribution (Vz/F) during the terminal phase (λz) following an extravascular dose)(16 weeks)
• Amount of tiotropium that is eliminated in urine from the time point t1 to time point t2 (Aet1-t2) (Ae0-2, Ae2-4, Ae4-8, Ae0-8)(16 weeks)
• Fraction of tiotropium eliminated in urine from time point t1 to time point t2 (fet1-t2) (fe0-2, fe2-4, fe4-8, fe0-8)(16 weeks)
• Renal clearance of tiotropium from the time point t1 until the time point t2 (CLR,t1-t2) (CLR,0-2, CLR, 2-4, CLR,4-8, CLR,0-8)(16 weeks)
• All adverse events(20 weeks)
• Blood pressure (seated) recorded in conjunction with 12-lead ECG recordings pre-dose and following the morning dose of randomized treatment(20 weeks)
• Number of patients with abnormalities in routine blood chemistry, haematology and urinalysis(16 weeks)
• Trough forced expiratory volume in one second (FEV1)(16 weeks)
• FEV1 area under the curve 0 to 8 hours (FEV1 AUC0-8h)(16 weeks)
• FVC area under the curve 0 to 8 hours (FVC AUC0-8h)(16 weeks)
• Individual FEV1and FVC measurements at each time point at the end of each 4-week treatment period.(16 weeks)
• Trough forced vital capacity (FVC)(16 weeks)