Vahelva Respimat Regulatory Post-marketing Surveillance in Korean Patients With Chronic Obstructive Pulmonary Disease

Study Overview
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Brief Summary
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To monitor the safety profile and effectiveness of Vahelva Respimat in Korean patients with COPD in a routine clinical practice setting

Detailed Description
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Study Design: regulatory PMS study

Official Title
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A Regulatory Required Non Interventional Study to Monitor the Safety and Effectiveness of Once Daily Treatment of Orally Inhaled Vahelva Respimat (Tiotropium + Olodaterol Fixed Dose Combination 2.5µg/2.5µg Per Puff (2 Puffs Comprise One Medicinal Dose)) for Korean Patients With COPD (Chronic Obstructive Pulmonary Disease)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients who have been started on Vahelva Respimat in accordance with the approved label in Korea Age >= 18 years at enrolment Patients who have signed on the data release consent form Exclusion criteria: Patients with hypersensitivity to Vahelva Respimat or to any of the excipients. Patients with a history of hypersensitivity to atropine or its derivatives(e.g. ipratropium, oxitropium, glycopyrronium, clidinium, umeclidinium) Patients with asthma Current participation in other clinical trials

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination)<br>Korean patients with COPD who are newly prescribed with Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination). | Drug: Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination)<br>* The recommended dose for adults is 5 microgram Tiotropium and 5 microgram Olodaterol given as two puffs from the Respimat® inhaler once daily at the same time of the day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Any Adverse Event, Unexpected Adverse Event, Unexpected Serious Adverse Event, Adverse Event Leading to Discontinuation | An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An adverse event could therefore be any unfavourable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An adverse event was assessed as unexpected if not listed in Local Product Information (LPI) and Company Core Data Sheet (CCDS). Percentage of subjects with any Adverse Event, unexpected Adverse Event, unexpected Serious Adverse Event, Adverse Event leading to discontinuation is reported. Percentages were rounded to two decimal places. | From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of Vahelva® Respimat®, up to 52 (±2) weeks+ 28 days. | 
| Percentage of Subjects With Any Adverse Drug Reaction, Serious Adverse Drug Reaction, Unexpected Adverse Drug Reaction, Unexpected Serious Adverse Drug Reaction, Adverse Drug Reaction Leading to Discontinuation | An adverse drug reaction (ADR) was defined as a response to a medicinal product which is noxious and unintended. Response in this context means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility. Adverse reactions may arise from use of the product within or outside the terms of the marketing authorization or from occupational exposure. Conditions of use outside the marketing authorization include off label use, overdose, misuse, abuse and medication errors. Investigator was primarily responsible to assess ADR relatedness. An ADR was assessed as unexpected if not listed in Local Product Information (LPI) and Company Core Data Sheet (CCDS). Percentage of subjects with any Adverse Drug Reaction, serious Adverse Drug Reaction, unexpected Adverse Drug Reaction, unexpected Serious Adverse Drug Reaction, Adverse Drug Reaction leading to discontinuation is reported. Percentages were rounded to two decimal places. | From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of Vahelva® Respimat®, up to 52 (±2) weeks+ 28 days. | 
| Percentage of Subjects With Any Adverse Event (AE) in the Long-term Safety Analysis Set | An adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment. An adverse event could therefore be any unfavourable and unintended sign (e.g. an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Percentage of participants with any AE is reported. Percentages were rounded to two decimal places. | From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of Vahelva® Respimat®, up to 52 (±2) weeks+ 28 days. | 
| Change From Baseline in Pre-dose Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 24 in the Effectiveness Analysis Set | FEV1 is the maximum amount of air that can be forcefully exhaled in one second. It assesses the degree of airway obstruction in a routine test called spirometry, via a spirometer. FEVI was measured before the administration of Vahelva® Respimat® (pre-dose FEV1) at baseline and at Week 24 (±2 weeks). Pre-dose percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.). Change from baseline in pre-dose percent predicted FEV1 to Week 24 was calculated as: pre-dose percent predicted FEV1 value at Week 24 (±2 weeks) - pre-dose percent predicted FEV1 value at baseline. | At baseline (30 days before baseline visit (Visit 1)) and Week 24 (±2 weeks). | 
| Change From Baseline in Pre-dose Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 52 in the Effectiveness Analysis Set | FEV1 is the maximum amount of air that can be forcefully exhaled in one second. It assesses the degree of airway obstruction in a routine test called spirometry, via a spirometer. FEVI was measured before the administration of Vahelva® Respimat® (pre-dose FEV1) at baseline and at Week 52 (±2 weeks). Pre-dose percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.). Change from baseline in pre-dose percent predicted Forced Expiratory Volume in one second (FEV1) to Week 52 was calculated as: pre-dose percent predicted FEV1 value at Week 52 (±2 weeks) - pre-dose percent predicted FEV1 value at baseline. | At baseline (30 days before baseline visit (Visit 1)) and Week 52 (±2 weeks). | 
| Change From Baseline in Pre-dose Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 24 in the Long-term Effectiveness Analysis Set | FEV1 is the maximum amount of air that can be forcefully exhaled in one second. It assesses the degree of airway obstruction in a routine test called spirometry, via a spirometer. FEVI was measured before the administration of Vahelva® Respimat® (pre-dose FEV1) at baseline and at Week 24 (±2 weeks). Pre-dose percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.). Change from baseline in pre-dose percent predicted Forced Expiratory Volume in one second (FEV1) to Week 24 was calculated as: pre-dose percent predicted FEV1 value at Week 24 (±2 weeks) - pre-dose percent predicted FEV1 value at baseline. | At baseline (30 days before baseline visit (Visit 1)) and Week 24 (±2 weeks). | 
| Change From Baseline in Pre-dose Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 52 in the Long-term Effectiveness Analysis Set | FEV1 is the maximum amount of air that can be forcefully exhaled in one second. It assesses the degree of airway obstruction in a routine test called spirometry, via a spirometer. FEVI was measured before the administration of Vahelva® Respimat® (pre-dose FEV1) at baseline and at Week 52 (±2 weeks). Pre-dose percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.). Change from baseline in pre-dose percent predicted Forced Expiratory Volume in one second (FEV1) to Week 52 was calculated as: pre-dose percent predicted FEV1 value at Week 52 (±2 weeks) - pre-dose percent predicted FEV1 value at baseline. | At baseline (30 days before baseline visit (Visit 1)) and Week 52 (±2 weeks). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Post Bronchodilator Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 24 in the Effectiveness Analysis Set | FEV1 is the maximum amount of air that can be forcefully exhaled in one second. FEVI was measured via a spirometer after the administration of the bronchodilator (Vahelva® Respimat®) at baseline and at Week 24 (±2 weeks). Post bronchodilator percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.). Change from baseline in post bronchodilator percent predicted FEV1 to Week 24 was calculated as: post bronchodilator percent predicted FEV1 value at Week 24 (±2 weeks) - post bronchodilator percent predicted FEV1 value at baseline. | At baseline and Week 24 (±2 weeks). | 
| Change From Baseline in Post Bronchodilator Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 52 in the Effectiveness Analysis Set | FEV1 is the maximum amount of air that can be forcefully exhaled in one second. FEVI was measured via a spirometer after the administration of the bronchodilator (Vahelva® Respimat®) at baseline and at Week 52 (±2 weeks). Post bronchodilator percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.). Change from baseline in post bronchodilator percent predicted FEV1 to Week 52 was calculated as: post bronchodilator percent predicted FEV1 value at Week 52 (±2 weeks) - post bronchodilator percent predicted FEV1 value at baseline. | At baseline and Week 52 (±2 weeks). | 
| Change From Baseline in Post Bronchodilator Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 24 in the Long-term Effectiveness Analysis Set | FEV1 is the maximum amount of air that can be forcefully exhaled in one second. FEVI was measured via a spirometer after the administration of the bronchodilator (Vahelva® Respimat®) at baseline and at Week 24 (±2 weeks). Post bronchodilator percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.). Change from baseline in post bronchodilator percent predicted FEV1 to Week 24 was calculated as: post bronchodilator percent predicted FEV1 value at Week 24 (±2 weeks) - post bronchodilator percent predicted FEV1 value at baseline. | At baseline and Week 24 (±2 weeks). | 
| Change From Baseline in Post Bronchodilator Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 52 in the Long-term Effectiveness Analysis Set | FEV1 is the maximum amount of air that can be forcefully exhaled in one second. FEVI was measured via a spirometer after the administration of the bronchodilator (Vahelva® Respimat®) at baseline and at Week 52 (±2 weeks). Post bronchodilator percent predicted FEV1 was calculated by converting the spirometer reading to a percentage of what would be predicted as normal FEV1 based on a several personal factors (e.g. sex, age, etc.). Change from baseline in post bronchodilator percent predicted FEV1 to Week 52 was calculated as: post bronchodilator percent predicted FEV1 value at Week 52 (±2 weeks) - post bronchodilator percent predicted FEV1 value at baseline. | At baseline and Week 52 (±2 weeks). | 
| Transition Dyspnea Index (TDI) Focal Score at Week 24 in the Effectiveness Analysis Set | Transition dyspnea index (TDI) is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline. TDI consists of 3 individual components: functional impairment, magnitude of task, and magnitude of effort. Each component was rated by 7 grades from -3 (major deterioration) to +3 (major improvement), and were sum up to form a TDI focal score from -9 to +9, with higher scores indicating better outcomes. | At Week 24 (±2 weeks). | 
| Transition Dyspnea Index (TDI) Focal Score at Week 52 in the Effectiveness Analysis Set | Transition dyspnea index (TDI) is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline. TDI consists of 3 individual components: functional impairment, magnitude of task, and magnitude of effort. Each component was rated by 7 grades from -3 (major deterioration) to +3 (major improvement), and were sum up to form a TDI focal score from -9 to +9, with higher scores indicating better outcomes. | At Week 52 (±2 weeks). | 
| Transition Dyspnea Index (TDI) Focal Score at Week 24 in the Long-term Effectiveness Analysis Set | Transition dyspnea index (TDI) is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline. TDI consists of 3 individual components: functional impairment, magnitude of task, and magnitude of effort. Each component was rated by 7 grades from -3 (major deterioration) to +3 (major improvement), and were sum up to form a TDI focal score from -9 to +9, with higher scores indicating better outcomes. | At Week 24 (±2 weeks). | 
| Transition Dyspnea Index (TDI) Focal Score at Week 52 in the Long-term Effectiveness Analysis Set | Transition dyspnea index (TDI) is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline. TDI consists of 3 individual components: functional impairment, magnitude of task, and magnitude of effort. Each component was rated by 7 grades from -3 (major deterioration) to +3 (major improvement), and were sum up to form a TDI focal score from -9 to +9, with higher scores indicating better outcomes. | At Week 52 (±2 weeks). | 
| Number of Subjects in Each Category of Overall Evaluation in the Effectiveness Analysis Set | Overall evaluation (improved, unchanged or aggravated) was performed by investigator and was based on overall clinical assessment including change from baseline in effectiveness assessment (pre-dose percent predicted Forced Expiratory Volume in one second (FEV1), post bronchodilator percent predicted Forced Expiratory Volume in one second (FEV1), Transition dyspnea index (TDI)) after 24 weeks or 52 weeks of treatment. Improved, unchanged, aggravated are defined as below: Improved : If determined as there is any effect of maintaining or improving symptoms; Unchanged : If symptoms have not been changed compared with before and not determined as there is any effect of maintaining symptoms; Aggravated : If symptoms are worse than before administration. Number of subject in each category of overall evaluation (improved, unchanged or aggravated) is reported. | At baseline and at Week 24 (±2 weeks) or at Week 52 (±2 weeks). | 
| Number of Subjects in Each Category of Overall Evaluation in the Long-term Effectiveness Analysis Set | Overall evaluation (improved, unchanged or aggravated) was performed by investigator and was based on overall clinical assessment including change from baseline in effectiveness assessment (pre-dose percent predicted Forced Expiratory Volume in one second (FEV1), post bronchodilator percent predicted Forced Expiratory Volume in one second (FEV1), Transition dyspnea index (TDI)) after 24 weeks or 52 weeks of treatment. Improved, unchanged, aggravated are defined as below: Improved : If determined as there is any effect of maintaining or improving symptoms; Unchanged : If symptoms have not been changed compared with before and not determined as there is any effect of maintaining symptoms; Aggravated : If symptoms are worse than before administration. Number of subject in each category of overall evaluation (improved, unchanged or aggravated) is reported. | At baseline and at Week 24 (±2 weeks) or at Week 52 (±2 weeks). | 
| Effectiveness Rate in the Effectiveness Analysis Set | Overall evaluation (Improved, unchanged or aggravated) by investigator was based on overall clinical assessment including change from baseline in effectiveness assessment (pre-dose percent predicted Forced Expiratory Volume in one second (FEV1), post bronchodilator percent predicted Forced Expiratory Volume in one second (FEV1), Transition dyspnea index (TDI)) after 24 weeks or 52 weeks of treatment. 'Improved' was assessed as Effective, 'Unchanged, Aggravated' were assessed as Invalid. | At baseline and at Week 24 (±2 weeks) or at Week 52 (±2 weeks). | 
| Effectiveness Rate in the Long-term Effectiveness Analysis Set | Overall evaluation (Improved, unchanged, aggravated or unassessable) by investigator was based on overall clinical assessment including change from baseline in effectiveness assessment (pre-dose percent predicted Forced Expiratory Volume in one second (FEV1), post bronchodilator percent predicted Forced Expiratory Volume in one second (FEV1), Transition dyspnea index (TDI)) after 24 weeks or 52 weeks of treatment. 'Improved' was assessed as Effective, 'Unchanged, Aggravated' were assessed as Invalid. | At baseline and at Week 24 (±2 weeks) or at Week 52 (±2 weeks). |