Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
The primary objective of this study is to characterize the pharmacokinetics (i.e. systemic exposure to tiotropium and salmeterol) of tiotropium qd + salmeterol qd or bid versus tiotropium qd and salmeterol bid following 4-week treatment periods in patients with chronic obstructive pulmonary disease (COPD).
Interventions
DRUGTiotropium+Salmeterol
DRUGSalmeterol
DRUGTiotropium
Sponsors
Boehringer Ingelheim
Study design
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
COPD patients of \>= 40 years old with moderate to severe COPD who are current or ex-smokers with a smoking history of at least 10 pack-years
Exclusion criteria
1. Recent history of myocardial infarction, life-threatening cardiac arrhythmia or hospitalisation for cardiac failure 2. History of asthma 3. Malignancy requiring treatment within past 5 years 4. Life-threatening pulmonary obstruction, cystic fibrosis or clinically evident bronchiectasis 5. Known active tuberculosis 6. Pregnant or nusing women 7. Known hypersensitivity to components of the study medication
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area under the concentration-time curve (AUC0-∞ ) of tiotropium in plasma | 16 weeks |
| Maximum measured concentration of tiotropium in plasma (Cmax) | 16 weeks |
| Amount of tiotropium that was eliminated in urine (Ae0-8) from time point 0 to 8 hours post-inhalation | 16 weeks |
| AUC0-∞ of salmeterol in plasma | 16 weeks |
| Cmax salmeterol in plasma | 16 weeks |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| Number of patients with abnormalities in routine blood chemistry, haematology and urinalysis | 16 weeks |
| Trough forced expiratory volume in one second (FEV1) | 16 weeks |
| Trough forced vital capacity (FVC) | 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 |
| Blood pressure (seated) recorded in conjunction with 12-lead ECG recordings pre-dose and following the morning dose of randomized treatment | 20 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 |
Countries
Belgium, Netherlands
Outcome results
None listed