Clinical trial NCT01703845: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2012-10-11
Enrollment: 32
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Cmax,ss (Olodaterol)
timeFrame: 15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21
measure: AUCt1-t2,ss (Olodaterol)
timeFrame: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21
measure: AUC0-tz,ss (Olodaterol)
timeFrame: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21
measure: Tmax,ss (Olodaterol)
timeFrame: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3 and 4 hours (h) following drug administration on day 21
measure: Aet1-t2,ss (Olodaterol)
timeFrame: from 0 to 4 hours following drug administration on day 21
measure: fe t1-t2,ss (Olodaterol)
timeFrame: from 0 to 4 hours following drug administration on day 21
measure: CLR,t1-t2,ss (Olodaterol)
timeFrame: from 0 to 4 hours following drug administration on day 21
measure: Cmax,ss (Tiotropium)
timeFrame: 15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21
measure: AUCt1-t2,ss (Tiotropium)
timeFrame: 15 min pre-dose and 5, 10, 20, 40 min, 1 and 2 h following drug administration on day 21
measure: AUC0-tz,ss (Tiotropium)
timeFrame: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21
measure: Tmax,ss (Tiotropium)
timeFrame: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, 4 hours following drug administration on day 21
measure: Aet1-t2,ss (Tiotropium)
timeFrame: from 0 to 4 hours following drug administration on day 21
measure: fe t1-t2,ss (Tiotropium)
timeFrame: from 0 to 4 hours following drug administration on day 21
measure: CLR,t1-t2,ss (Tiotropium)
timeFrame: from 0 to 4 hours following drug administration on day 21
Secondary outcomes:
measure: Number of Participants With Adverse Events (Including Assessment Based on Physical Examination)
timeFrame: up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose
measure: Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG
timeFrame: up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose
Other outcomes:
Locations:
city: Toshima-ku, Tokyo
country: Japan
facility: 1237.24.24001 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: