Back to resultsA Study to Characterize Pharmacokinetics of Tiotropium + Olodaterol Fixed-dose Combination in Japanese Patients With COPD.
Primary Purpose
Pulmonary Disease, Chronic Obstructive
Status
Completed
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Tiotropium (high dose) + Olodaterol
Tiotropium (low dose) + Olodaterol
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive
Eligibility Criteria
Inclusion criteria:
- Diagnosis of chronic obstructive pulmonary disease
- Relatively stable airway obstruction with post FEV1=<30% of predicted normal and< 80% predicted normal and post FEV1/FVC <70%
- Male or female Japanese patients, 40 years of age or older
- Smoking history of more than 10 pack years
Exclusion criteria:
- Significant disease other than COPD
- Clinically relevant abnormal lab values
- History of asthma
- Diagnosis of thyrotoxicosis
- Diagnosis of paroxysmal tachycardia
- A marked baseline prolongation of QT/QTc interval
- A history of additional risk factors for Torsade de Pointes (TdP)
- History of myocardial infarction within 1 year of screening visit
- Unstable or life-threatening cardiac arrhythmia
- Hospitalization for heart failure within the past year
- Known active tuberculosis
- Malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years
- History of life-threatening pulmonary obstruction
- History of cystic fibrosis
- Clinically evident bronchiectasis
- History of significant alcohol or drug abuse
- Thoracotomy with pulmonary resection
- Oral ß-adrenergics
- Oral corticosteroid medication at unstable doses
- Regular use of daytime oxygen therapy for more than one hour per day
- Pulmonary rehabilitation program in the six weeks prior to the screening visit
- Investigational drug within one month or six half lives (whichever is greater) prior to screening visit
- Known hypersensitivity to ß-adrenergic drugs, anticholinergics, BAC, EDTA
- Pregnant or nursing women
- Women of childbearing potential not using a highly effective method of birth control
- Patients who have previously been randomized in this study or are currently participating in another study
- Patients who are unable to comply with pulmonary medication restrictions
- Patients with narrow-angle glaucoma or micturition disorder due to prostatic hyperplasia etc
- Patients being treated with medications that prolong the QT/QTc interval
Sites / Locations
- 1237.24.24001 Boehringer Ingelheim Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Tiotropium + Olodaterol (high dose)
Tiotropium + Olodaterol (low dose)
Arm Description
Tiotropium and Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT
Tiotropium and Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT
Outcomes
Primary Outcome Measures
Cmax,ss (Olodaterol)
Maximum measured concentration of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
AUCt1-t2,ss (Olodaterol)
Area under the concentration-time curve of olodaterol in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (AUCt1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
AUC0-tz,ss (Olodaterol)
Area under the concentration-time curve of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Tmax,ss (Olodaterol)
Time from dosing to the maximum concentration of Olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Aet1-t2,ss (Olodaterol)
Amount of olodaterol that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
fe t1-t2,ss (Olodaterol)
Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
CLR,t1-t2,ss (Olodaterol)
Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Cmax,ss (Tiotropium)
Maximum measured concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
AUCt1-t2,ss (Tiotropium)
Area under the concentration-time curve of tiotropium in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 2 hours at steady state (AUCt1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
AUC0-tz,ss (Tiotropium)
Area under the concentration-time curve of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Tmax,ss (Tiotropium)
Time from dosing to the maximum concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Aet1-t2,ss (Tiotropium)
Amount of tiotropium that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
fe t1-t2,ss (Tiotropium)
Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
CLR,t1-t2,ss (Tiotropium)
Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Plasma concentration of tiotropium could not be quantified up to 4 hours for Tiotropium + Olodaterol (2.5μg/5μg).
Secondary Outcome Measures
Number of Participants With Adverse Events (Including Assessment Based on Physical Examination)
Outcome data show are the number of patients with an adverse event including the assessment based on physical examination.
Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG
Outcome data show are the number of participants with clinically relevant abnormalities reported as an adverse event (AE) related to the vital signs (pulse rate and blood pressure in supine position), clinical laboratory (routine blood chemistry, haematology, and urinalysis) tests and ECG (12-lead holter monitoring Electrocardiography). Relevant findings or worsening of baseline conditions were reported as adverse events.
There were no clinically relevant abnormalities reported as an AE related to the vital signs and ECG.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01703845
Brief Title
A Study to Characterize Pharmacokinetics of Tiotropium + Olodaterol Fixed-dose Combination in Japanese Patients With COPD.
Official Title
A Randomised, Open-label, Parallel-group Trial to Assess Pharmacokinetics and Safety of Tiotropium + Olodaterol Fixed-dose Combination (2.5 µg/ 5 µg, 5 µg/ 5 µg) Delivered by the RESPIMAT Inhaler After 3 Weeks Once Daily Treatment in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
March 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
Brief Summary
The primary objective of this study is to assess pharmacokinetics of tiotropium + olodaterol fixed-dose combination (2.5 µg/ 5 µg, 5 µg/ 5 µg) delivered by the RESPIMAT inhaler after 3 weeks once daily treatment in Japanese patients with 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 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
32 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tiotropium + Olodaterol (high dose)
Arm Type
Experimental
Arm Description
Tiotropium and Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT
Arm Title
Tiotropium + Olodaterol (low dose)
Arm Type
Experimental
Arm Description
Tiotropium and Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT
Intervention Type
Drug
Intervention Name(s)
Tiotropium (high dose) + Olodaterol
Intervention Description
Tiotropium + Olodaterol solution for inhalation
Intervention Type
Drug
Intervention Name(s)
Tiotropium (low dose) + Olodaterol
Intervention Description
Tiotropium + Olodaterol solution for inhalation
Primary Outcome Measure Information:
Title
Cmax,ss (Olodaterol)
Description
Maximum measured concentration of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time Frame
15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21
Title
AUCt1-t2,ss (Olodaterol)
Description
Area under the concentration-time curve of olodaterol in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (AUCt1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time Frame
15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21
Title
AUC0-tz,ss (Olodaterol)
Description
Area under the concentration-time curve of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time Frame
15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21
Title
Tmax,ss (Olodaterol)
Description
Time from dosing to the maximum concentration of Olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time Frame
15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3 and 4 hours (h) following drug administration on day 21
Title
Aet1-t2,ss (Olodaterol)
Description
Amount of olodaterol that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time Frame
from 0 to 4 hours following drug administration on day 21
Title
fe t1-t2,ss (Olodaterol)
Description
Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time Frame
from 0 to 4 hours following drug administration on day 21
Title
CLR,t1-t2,ss (Olodaterol)
Description
Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time Frame
from 0 to 4 hours following drug administration on day 21
Title
Cmax,ss (Tiotropium)
Description
Maximum measured concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time Frame
15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21
Title
AUCt1-t2,ss (Tiotropium)
Description
Area under the concentration-time curve of tiotropium in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 2 hours at steady state (AUCt1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time Frame
15 min pre-dose and 5, 10, 20, 40 min, 1 and 2 h following drug administration on day 21
Title
AUC0-tz,ss (Tiotropium)
Description
Area under the concentration-time curve of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time Frame
15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21
Title
Tmax,ss (Tiotropium)
Description
Time from dosing to the maximum concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time Frame
15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, 4 hours following drug administration on day 21
Title
Aet1-t2,ss (Tiotropium)
Description
Amount of tiotropium that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time Frame
from 0 to 4 hours following drug administration on day 21
Title
fe t1-t2,ss (Tiotropium)
Description
Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Time Frame
from 0 to 4 hours following drug administration on day 21
Title
CLR,t1-t2,ss (Tiotropium)
Description
Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Plasma concentration of tiotropium could not be quantified up to 4 hours for Tiotropium + Olodaterol (2.5μg/5μg).
Time Frame
from 0 to 4 hours following drug administration on day 21
Secondary Outcome Measure Information:
Title
Number of Participants With Adverse Events (Including Assessment Based on Physical Examination)
Description
Outcome data show are the number of patients with an adverse event including the assessment based on physical examination.
Time Frame
up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose
Title
Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG
Description
Outcome data show are the number of participants with clinically relevant abnormalities reported as an adverse event (AE) related to the vital signs (pulse rate and blood pressure in supine position), clinical laboratory (routine blood chemistry, haematology, and urinalysis) tests and ECG (12-lead holter monitoring Electrocardiography). Relevant findings or worsening of baseline conditions were reported as adverse events.
There were no clinically relevant abnormalities reported as an AE related to the vital signs and ECG.
Time Frame
up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria:
Diagnosis of chronic obstructive pulmonary disease
Relatively stable airway obstruction with post FEV1=<30% of predicted normal and< 80% predicted normal and post FEV1/FVC <70%
Male or female Japanese patients, 40 years of age or older
Smoking history of more than 10 pack years
Exclusion criteria:
Significant disease other than COPD
Clinically relevant abnormal lab values
History of asthma
Diagnosis of thyrotoxicosis
Diagnosis of paroxysmal tachycardia
A marked baseline prolongation of QT/QTc interval
A history of additional risk factors for Torsade de Pointes (TdP)
History of myocardial infarction within 1 year of screening visit
Unstable or life-threatening cardiac arrhythmia
Hospitalization for heart failure within the past year
Known active tuberculosis
Malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years
History of life-threatening pulmonary obstruction
History of cystic fibrosis
Clinically evident bronchiectasis
History of significant alcohol or drug abuse
Thoracotomy with pulmonary resection
Oral ß-adrenergics
Oral corticosteroid medication at unstable doses
Regular use of daytime oxygen therapy for more than one hour per day
Pulmonary rehabilitation program in the six weeks prior to the screening visit
Investigational drug within one month or six half lives (whichever is greater) prior to screening visit
Known hypersensitivity to ß-adrenergic drugs, anticholinergics, BAC, EDTA
Pregnant or nursing women
Women of childbearing potential not using a highly effective method of birth control
Patients who have previously been randomized in this study or are currently participating in another study
Patients who are unable to comply with pulmonary medication restrictions
Patients with narrow-angle glaucoma or micturition disorder due to prostatic hyperplasia etc
Patients being treated with medications that prolong the QT/QTc interval
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
1237.24.24001 Boehringer Ingelheim Investigational Site
City
Toshima-ku, Tokyo
Country
Japan
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com/
Description
Related Info
Learn more about this trial
A Study to Characterize Pharmacokinetics of Tiotropium + Olodaterol Fixed-dose Combination in Japanese Patients With COPD.
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