Tiotropium and Salmeterol PK Study in COPD Patients
Primary Purpose
Pulmonary Disease, Chronic Obstructive
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Tiotropium+Salmeterol
Salmeterol
Tiotropium
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive
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:
- Recent history of myocardial infarction, life-threatening cardiac arrhythmia or hospitalisation for cardiac failure
- History of asthma
- Malignancy requiring treatment within past 5 years
- Life-threatening pulmonary obstruction, cystic fibrosis or clinically evident bronchiectasis
- Known active tuberculosis
- Pregnant or nusing women
- Known hypersensitivity to components of the study medication
Sites / Locations
- 1184.24.32001 Boehringer Ingelheim Investigational Site
- 1184.24.32002 Boehringer Ingelheim Investigational Site
- 1184.24.31001 Boehringer Ingelheim Investigational Site
Outcomes
Primary Outcome Measures
Area under the concentration-time curve (AUC0-∞ ) of tiotropium in plasma
Maximum measured concentration of tiotropium in plasma (Cmax)
Amount of tiotropium that was eliminated in urine (Ae0-8) from time point 0 to 8 hours post-inhalation
AUC0-∞ of salmeterol in plasma
Cmax salmeterol in plasma
Secondary Outcome Measures
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)
Time from dosing to the maximum concentration of tiotropium and salmeterol in plasma (tmax)
Terminal rate constant in plasma (λz)
Terminal half-life (t½) of tiotropium and salmeterol in plasma)
Mean residence time (MRTih) of tiotropium and salmeterol in the body after inhalational administration
Apparent clearance (CL/F) of tiotropium and salmeterol in plasma after extravascular administration)
Apparent volume of distribution (Vz/F) during the terminal phase (λz) following an extravascular dose)
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)
Fraction of tiotropium eliminated in urine from time point t1 to time point t2 (fet1-t2) (fe0-2, fe2-4, fe4-8, fe0-8)
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)
All adverse events
Blood pressure (seated) recorded in conjunction with 12-lead ECG recordings pre-dose and following the morning dose of randomized treatment
Number of patients with abnormalities in routine blood chemistry, haematology and urinalysis
Trough forced expiratory volume in one second (FEV1)
Trough forced vital capacity (FVC)
FEV1 area under the curve 0 to 8 hours (FEV1 AUC0-8h)
FVC area under the curve 0 to 8 hours (FVC AUC0-8h)
Individual FEV1and FVC measurements at each time point at the end of each 4-week treatment period.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00673478
Brief Title
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
2. Study Status
Record Verification Date
April 2014
Overall Recruitment Status
Completed
Study Start Date
May 2008 (undefined)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Disease, Chronic Obstructive
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Tiotropium+Salmeterol
Intervention Type
Drug
Intervention Name(s)
Salmeterol
Intervention Type
Drug
Intervention Name(s)
Tiotropium
Primary Outcome Measure Information:
Title
Area under the concentration-time curve (AUC0-∞ ) of tiotropium in plasma
Time Frame
16 weeks
Title
Maximum measured concentration of tiotropium in plasma (Cmax)
Time Frame
16 weeks
Title
Amount of tiotropium that was eliminated in urine (Ae0-8) from time point 0 to 8 hours post-inhalation
Time Frame
16 weeks
Title
AUC0-∞ of salmeterol in plasma
Time Frame
16 weeks
Title
Cmax salmeterol in plasma
Time Frame
16 weeks
Secondary Outcome Measure Information:
Title
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)
Time Frame
16 weeks
Title
Time from dosing to the maximum concentration of tiotropium and salmeterol in plasma (tmax)
Time Frame
16 weeks
Title
Terminal rate constant in plasma (λz)
Time Frame
16 weeks
Title
Terminal half-life (t½) of tiotropium and salmeterol in plasma)
Time Frame
16 weeks
Title
Mean residence time (MRTih) of tiotropium and salmeterol in the body after inhalational administration
Time Frame
16 weeks
Title
Apparent clearance (CL/F) of tiotropium and salmeterol in plasma after extravascular administration)
Time Frame
16 weeks
Title
Apparent volume of distribution (Vz/F) during the terminal phase (λz) following an extravascular dose)
Time Frame
16 weeks
Title
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)
Time Frame
16 weeks
Title
Fraction of tiotropium eliminated in urine from time point t1 to time point t2 (fet1-t2) (fe0-2, fe2-4, fe4-8, fe0-8)
Time Frame
16 weeks
Title
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)
Time Frame
16 weeks
Title
All adverse events
Time Frame
20 weeks
Title
Blood pressure (seated) recorded in conjunction with 12-lead ECG recordings pre-dose and following the morning dose of randomized treatment
Time Frame
20 weeks
Title
Number of patients with abnormalities in routine blood chemistry, haematology and urinalysis
Time Frame
16 weeks
Title
Trough forced expiratory volume in one second (FEV1)
Time Frame
16 weeks
Title
Trough forced vital capacity (FVC)
Time Frame
16 weeks
Title
FEV1 area under the curve 0 to 8 hours (FEV1 AUC0-8h)
Time Frame
16 weeks
Title
FVC area under the curve 0 to 8 hours (FVC AUC0-8h)
Time Frame
16 weeks
Title
Individual FEV1and FVC measurements at each time point at the end of each 4-week treatment period.
Time Frame
16 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
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:
Recent history of myocardial infarction, life-threatening cardiac arrhythmia or hospitalisation for cardiac failure
History of asthma
Malignancy requiring treatment within past 5 years
Life-threatening pulmonary obstruction, cystic fibrosis or clinically evident bronchiectasis
Known active tuberculosis
Pregnant or nusing women
Known hypersensitivity to components of the study medication
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Organizational Affiliation
Boehringer Ingelheim
Official's Role
Study Chair
Facility Information:
Facility Name
1184.24.32001 Boehringer Ingelheim Investigational Site
City
Genk
Country
Belgium
Facility Name
1184.24.32002 Boehringer Ingelheim Investigational Site
City
Hasselt
Country
Belgium
Facility Name
1184.24.31001 Boehringer Ingelheim Investigational Site
City
Heerlen
Country
Netherlands
12. IPD Sharing Statement
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Tiotropium and Salmeterol PK Study in COPD Patients
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