Clinical trial NCT00673478: Tiotropium and Salmeterol PK Study in COPD Patients
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2008-05-07
Enrollment: 50
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Area under the concentration-time curve (AUC0-∞ ) of tiotropium in plasma
timeFrame: 16 weeks
measure: Maximum measured concentration of tiotropium in plasma (Cmax)
timeFrame: 16 weeks
measure: Amount of tiotropium that was eliminated in urine (Ae0-8) from time point 0 to 8 hours post-inhalation
timeFrame: 16 weeks
measure: AUC0-∞ of salmeterol in plasma
timeFrame: 16 weeks
measure: Cmax salmeterol in plasma
timeFrame: 16 weeks
Secondary outcomes:
measure: 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)
timeFrame: 16 weeks
measure: Time from dosing to the maximum concentration of tiotropium and salmeterol in plasma (tmax)
timeFrame: 16 weeks
measure: Terminal rate constant in plasma (λz)
timeFrame: 16 weeks
measure: Terminal half-life (t½) of tiotropium and salmeterol in plasma)
timeFrame: 16 weeks
measure: Mean residence time (MRTih) of tiotropium and salmeterol in the body after inhalational administration
timeFrame: 16 weeks
measure: Apparent clearance (CL/F) of tiotropium and salmeterol in plasma after extravascular administration)
timeFrame: 16 weeks
measure: Apparent volume of distribution (Vz/F) during the terminal phase (λz) following an extravascular dose)
timeFrame: 16 weeks
measure: 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)
timeFrame: 16 weeks
measure: Fraction of tiotropium eliminated in urine from time point t1 to time point t2 (fet1-t2) (fe0-2, fe2-4, fe4-8, fe0-8)
timeFrame: 16 weeks
measure: 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)
timeFrame: 16 weeks
measure: All adverse events
timeFrame: 20 weeks
measure: Blood pressure (seated) recorded in conjunction with 12-lead ECG recordings pre-dose and following the morning dose of randomized treatment
timeFrame: 20 weeks
measure: Number of patients with abnormalities in routine blood chemistry, haematology and urinalysis
timeFrame: 16 weeks
measure: Trough forced expiratory volume in one second (FEV1)
timeFrame: 16 weeks
measure: Trough forced vital capacity (FVC)
timeFrame: 16 weeks
measure: FEV1 area under the curve 0 to 8 hours (FEV1 AUC0-8h)
timeFrame: 16 weeks
measure: FVC area under the curve 0 to 8 hours (FVC AUC0-8h)
timeFrame: 16 weeks
measure: Individual FEV1and FVC measurements at each time point at the end of each 4-week treatment period.
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Genk
country: Belgium
facility: 1184.24.32001 Boehringer Ingelheim Investigational Site
city: Hasselt
country: Belgium
facility: 1184.24.32002 Boehringer Ingelheim Investigational Site
city: Heerlen
country: Netherlands
facility: 1184.24.31001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: