A Study to Characterize Pharmacokinetics of Tiotropium + Olodaterol Fixed-dose Combination in Japanese Patients With COPD.

Pulmonary Disease, Chronic Obstructive Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01703845
• Other study ID #: 1237.24
• Status: Completed
• Phase: Phase 1
• First received: October 8, 2012
• Last updated: June 19, 2015
• Start date: October 2012
• Est. completion date: March 2013

Study information

• Verified date: June 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: March 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion criteria:

1. Diagnosis of chronic obstructive pulmonary disease

2. Relatively stable airway obstruction with post FEV1=<30% of predicted normal and< 80% predicted normal and post FEV1/FVC <70%

3. Male or female Japanese patients, 40 years of age or older

4. Smoking history of more than 10 pack years

Exclusion criteria:

1. Significant disease other than COPD

2. Clinically relevant abnormal lab values

3. History of asthma

4. Diagnosis of thyrotoxicosis

5. Diagnosis of paroxysmal tachycardia

6. A marked baseline prolongation of QT/QTc interval

7. A history of additional risk factors for Torsade de Pointes (TdP)

8. History of myocardial infarction within 1 year of screening visit

9. Unstable or life-threatening cardiac arrhythmia

10. Hospitalization for heart failure within the past year

11. Known active tuberculosis

12. Malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years

13. History of life-threatening pulmonary obstruction

14. History of cystic fibrosis

15. Clinically evident bronchiectasis

16. History of significant alcohol or drug abuse

17. Thoracotomy with pulmonary resection

18. Oral ß-adrenergics

19. Oral corticosteroid medication at unstable doses

20. Regular use of daytime oxygen therapy for more than one hour per day

21. Pulmonary rehabilitation program in the six weeks prior to the screening visit

22. Investigational drug within one month or six half lives (whichever is greater) prior to screening visit

23. Known hypersensitivity to ß-adrenergic drugs, anticholinergics, BAC, EDTA

24. Pregnant or nursing women

25. Women of childbearing potential not using a highly effective method of birth control

26. Patients who have previously been randomized in this study or are currently participating in another study

27. Patients who are unable to comply with pulmonary medication restrictions

28. Patients with narrow-angle glaucoma or micturition disorder due to prostatic hyperplasia etc

29. Patients being treated with medications that prolong the QT/QTc interval

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Tiotropium (high dose) + Olodaterol
Tiotropium + Olodaterol solution for inhalation
• Tiotropium (low dose) + Olodaterol
Tiotropium + Olodaterol solution for inhalation

Locations

Country	Name	City	State
Japan	1237.24.24001 Boehringer Ingelheim Investigational Site	Toshima-ku, Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21	No
Primary	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.	15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21	No
Primary	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.	15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21	No
Primary	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.	15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3 and 4 hours (h) following drug administration on day 21	No
Primary	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.	from 0 to 4 hours following drug administration on day 21	No
Primary	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.	from 0 to 4 hours following drug administration on day 21	No
Primary	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.	from 0 to 4 hours following drug administration on day 21	No
Primary	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.	15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21	No
Primary	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.	15 min pre-dose and 5, 10, 20, 40 min, 1 and 2 h following drug administration on day 21	No
Primary	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.	15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21	No
Primary	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.	15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, 4 hours following drug administration on day 21	No
Primary	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.	from 0 to 4 hours following drug administration on day 21	No
Primary	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.	from 0 to 4 hours following drug administration on day 21	No
Primary	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).	from 0 to 4 hours following drug administration on day 21	No
Secondary	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.	up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose	No
Secondary	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.	up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose	No

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