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

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.

Time frame: At baseline (30 days before baseline visit (Visit 1)) and Week 24 (±2 weeks).

Population: Effectiveness analysis set included those who signed the informed consent form to participate in this study as subject, visited as per the study schedule, took Vahelva® Respimat® for 22 weeks or more, the cases included in safety evaluation, and were evaluated for the effectiveness including overall evaluation (if the case assessed as 'unassessable' was excluded). Only participants with non-missing values are reported.

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.

Time frame: At baseline (30 days before baseline visit (Visit 1)) and Week 24 (±2 weeks).

Population: Long-term effectiveness analysis set included those subjects in the safety analysis set who took Vahelva® Respimat® for 50 weeks or more. Only participants with non-missing values are reported.

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.

Time frame: At baseline (30 days before baseline visit (Visit 1)) and Week 52 (±2 weeks).

Population: Effectiveness analysis set included those who signed the informed consent form to participate in this study as subject, visited as per the study schedule, took Vahelva® Respimat® for 22 weeks or more, the cases included in safety evaluation, and were evaluated for the effectiveness including overall evaluation (if the case assessed as 'unassessable' was excluded). Only participants with non-missing values are reported.

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.

Time frame: At baseline (30 days before baseline visit (Visit 1)) and Week 52 (±2 weeks).

Population: Long-term effectiveness analysis set included those subjects in the safety analysis set who took Vahelva® Respimat® for 50 weeks or more. Only participants with non-missing values are reported.

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.

Time frame: 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.

Population: Safety analysis set included those who signed the informed consent form to participate in this study as subject, took Vahelva® Respimat® once at least, and were completed follow up by the physician once or more.

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.

Time frame: 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.

Population: Long term safety analysis set included those subjects in the safety analysis set who took Vahelva® Respimat® for 50 weeks or more.

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.

Time frame: 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.

Population: Safety analysis set included those who signed the informed consent form to participate in this study as subject, took Vahelva® Respimat® once at least, and were completed follow up by the physician once or more.

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.

Time frame: At baseline and Week 24 (±2 weeks).

Population: Effectiveness analysis set included those who signed the informed consent form to participate in this study as subject, visited as per the study schedule, took Vahelva® Respimat® for 22 weeks or more, the cases included in safety evaluation, and were evaluated for the effectiveness including overall evaluation (if the case assessed as 'unassessable' was excluded). Only participants with non-missing values are reported.

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.

Time frame: At baseline and Week 24 (±2 weeks).

Population: Long-term effectiveness analysis set included those subjects in the safety analysis set who took Vahelva® Respimat® for 50 weeks or more. Only participants with non-missing values are reported.

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.

Time frame: At baseline and Week 52 (±2 weeks).

Population: Effectiveness analysis set included those who signed the informed consent form to participate in this study as subject, visited as per the study schedule, took Vahelva® Respimat® for 22 weeks or more, the cases included in safety evaluation, and were evaluated for the effectiveness including overall evaluation (if the case assessed as 'unassessable' was excluded). Only participants with non-missing values are reported.

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.

Time frame: At baseline and Week 52 (±2 weeks).

Population: Long-term effectiveness analysis set included those subjects in the safety analysis set who took Vahelva® Respimat® for 50 weeks or more. Only participants with non-missing values are reported.

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.

Time frame: At baseline and at Week 24 (±2 weeks) or at Week 52 (±2 weeks).

Population: Effectiveness analysis set included those who signed the informed consent form to participate in this study as subject, visited as per the study schedule, took Vahelva® Respimat® for 22 weeks or more, the cases included in safety evaluation, and were evaluated for the effectiveness including overall evaluation (if the case assessed as 'unassessable' was excluded).

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.

Time frame: At baseline and at Week 24 (±2 weeks) or at Week 52 (±2 weeks).

Population: Long-term effectiveness analysis set included those subjects in the safety analysis set who took Vahelva® Respimat® for 50 weeks or more.

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.

Time frame: At baseline and at Week 24 (±2 weeks) or at Week 52 (±2 weeks).

Population: Effectiveness analysis set included those who signed the informed consent form to participate in this study as subject, visited as per the study schedule, took Vahelva® Respimat® for 22 weeks or more, the cases included in safety evaluation, and were evaluated for the effectiveness including overall evaluation (if the case assessed as 'unassessable' was excluded).

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.

Time frame: At baseline and at Week 24 (±2 weeks) or at Week 52 (±2 weeks).

Population: Long-term effectiveness analysis set included those subjects in the safety analysis set who took Vahelva® Respimat® for 50 weeks or more.

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.

Time frame: At Week 24 (±2 weeks).

Population: Effectiveness analysis set included those who signed the informed consent form to participate in this study as subject, visited as per the study schedule, took Vahelva® Respimat® for 22 weeks or more, the cases included in safety evaluation, and were evaluated for the effectiveness including overall evaluation (if the case assessed as 'unassessable' was excluded). Only participants with non-missing values are reported.

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.

Time frame: At Week 24 (±2 weeks).

Population: Long-term effectiveness analysis set included those subjects in the safety analysis set who took Vahelva® Respimat® for 50 weeks or more. Only participants with non-missing values are reported.

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.

Time frame: At Week 52 (±2 weeks).

Population: Effectiveness analysis set included those who signed the informed consent form to participate in this study as subject, visited as per the study schedule, took Vahelva® Respimat® for 22 weeks or more, the cases included in safety evaluation, and were evaluated for the effectiveness including overall evaluation (if the case assessed as 'unassessable' was excluded). Only participants with non-missing values are reported.

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.

Time frame: At Week 52 (±2 weeks).

Population: Long-term effectiveness analysis set included those subjects in the safety analysis set who took Vahelva® Respimat® for 50 weeks or more. Only participants with non-missing values are reported.