Japan Long-term Safety for Tiotropium Plus Olodaterol

Study Overview
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Brief Summary
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The primary objective of this study is to assess the safety of 52 weeks once daily treatment with orally inhaled tiotropium + olodaterol FDC and olodaterol (delivered by the RESPIMAT Inhaler) in Japanese patients with Chronic Obstructive Pulmonary Disease (COPD).

Official Title
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A Randomised, Double-blind, Parallel-group Study to Assess the Safety and Efficacy of 52 Weeks of Once Daily Treatment of Orally Inhaled Tiotropium + Olodaterol Fixed-dose Combination (2.5µg / 5µg, 5µg / 5µg ) and Olodaterol (5 µg) Delivered by the RESPIMAT Inhaler in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Tiotropium + Olodaterol
* Device: Respimat
* Drug: Tiotropium + Olodaterol
* Drug: Olodaterol
* Device: Respimat
* Device: Respimat


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Diagnosis of chronic obstructive pulmonary disease. Relatively stable airway obstruction with post FEV1< 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 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 are unable to comply with pulmonary medication restrictions Patients with narrow-angle glaucoma or micturition disorder due to prostatic hyperplasia etc.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Tiotropium + Olodaterol (high dose)<br>Tiotropium and Olodaterol FDC solution for inhalation - RESPIMAT | Drug: Tiotropium + Olodaterol<br>* Tiotropium and Olodaterol FDC once daily inhalation<br>Device: Respimat<br>* Respimat inhaler<br>|
| Other: Olodaterol<br>Olodaterol solution for inhalation - RESPIMAT | Drug: Olodaterol<br>* Olodaterol once daily inhalation<br>Device: Respimat<br>* Respimat inhaler<br>|
| Other: Tiotropium + Olodaterol (low dose)<br>Tiotropium and Olodaterol FDC solution for inhalation - RESPIMAT | Drug: Tiotropium + Olodaterol<br>* Tiotropium and Olodaterol FDC once daily inhalation<br>Device: Respimat<br>* Respimat inhaler<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number (%) of Patients With Drug-related AEs | Number (%) of patients with drug-related Adverse Events (AEs). | From first drug administration until 21 days after the last administration, upto 392 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| FEV1 AUC0-3h Response | Forced Expiratory Volume in 1 second Area Under Curve (AUC0-3h) response. FEV1 AUC0-3h was calculated using the trapezoidal rule, divided by the duration (3 h) to report in litres. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. Note: The Mean presented is the unadjusted mean. | Baseline and 1 h, 10 min pre-dose and 30 min, 1 h, 2 h, 3 h post-dose after 52 weeks | 
| Trough FEV1 Response | Trough Forced Expiratory Volume in 1 second Response. The trough was defined as the mean of the 1 h pre-dose and 10 min pre-dose measurements after 52 weeks. Baseline was defined as the mean of the 2 pre-treatment FEV1 values measured on day 1 (-1 hour and -10 minutes) prior to administration of the first dose of study drug. Note: The Mean presented is the unadjusted mean. | Baseline and 1 h, 10 min pre-dose after 52 weeks |