Trial Outcomes & Findings for Vahelva Respimat Regulatory Post-marketing Surveillance in Korean Patients With Chronic Obstructive Pulmonary Disease (NCT NCT02864407)

Last Updated: 2022-03-28

Results Overview

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.

Recruitment status

COMPLETED

Target enrollment

3223 participants

Primary outcome timeframe

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.

Results posted on

2022-03-28

Participant Flow

This was an observational prospective, non-interventional, open-label, multi-centre in Korean patients with Chronic Obstructive Pulmonary Disease (COPD).

All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.

Participant milestones

Participant milestones
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
Overall Study STARTED	3223
Overall Study Effectiveness Analysis Set	2105
Overall Study Long-term Safety Analysis Set	813
Overall Study Long-term Effectiveness Analysis Set	767
Overall Study COMPLETED	3100
Overall Study NOT COMPLETED	123

Reasons for withdrawal

Reasons for withdrawal
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
Overall Study Protocol Violation	3
Overall Study Lost to Follow-up	115
Overall Study Not treated with Vahelva® Respimat®	1
Overall Study Were administered Vahelva® Respimat® prior to the consent date	3
Overall Study Consent prior to the contract date	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=3100 Participants Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
Age, Continuous	69.14 Years STANDARD_DEVIATION 9.35 • n=3100 Participants
Sex: Female, Male Female	425 Participants n=3100 Participants
Sex: Female, Male Male	2675 Participants n=3100 Participants
Pre-dose percent predicted forced expiratory volume in one second (FEV1)	57.75 percentage of predicted FEV1 STANDARD_DEVIATION 15.10 • n=418 Participants • 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.

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=3100 Participants Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
Percentage of Subjects With Any Adverse Event, Unexpected Adverse Event, Unexpected Serious Adverse Event, Adverse Event Leading to Discontinuation Any Adverse Event	19.90 percentage of participants Interval 18.51 to 21.35
Percentage of Subjects With Any Adverse Event, Unexpected Adverse Event, Unexpected Serious Adverse Event, Adverse Event Leading to Discontinuation Unexpected Adverse Event	13.65 percentage of participants Interval 12.46 to 14.9
Percentage of Subjects With Any Adverse Event, Unexpected Adverse Event, Unexpected Serious Adverse Event, Adverse Event Leading to Discontinuation Unexpected Serious Adverse Event	3.48 percentage of participants Interval 2.87 to 4.19
Percentage of Subjects With Any Adverse Event, Unexpected Adverse Event, Unexpected Serious Adverse Event, Adverse Event Leading to Discontinuation Adverse Event leading to discontinuation	2.29 percentage of participants Interval 1.79 to 2.88

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=3100 Participants Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
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 Any Adverse Drug Reaction	2.87 percentage of participants Interval 2.31 to 3.52
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 Serious Adverse Drug Reaction	0.16 percentage of participants Interval 0.05 to 0.38
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 Unexpected Adverse Drug Reaction	1.16 percentage of participants Interval 0.81 to 1.6
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 Unexpected Serious Adverse Drug Reaction	0.13 percentage of participants Interval 0.04 to 0.33
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 Adverse Drug Reaction leading to discontinuation	1.32 percentage of participants Interval 0.95 to 1.79

PRIMARY outcome

Timeframe: 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. Percentage of participants with any AE is reported. Percentages were rounded to two decimal places.

Outcome measures

Outcome measures
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=813 Participants Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
Percentage of Subjects With Any Adverse Event (AE) in the Long-term Safety Analysis Set	22.88 percentage of partcipants Interval 20.03 to 25.92

PRIMARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=450 Participants Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
Change From Baseline in Pre-dose Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 24 in the Effectiveness Analysis Set	5.41 percentage of predicted FEV1 Standard Deviation 9.63

PRIMARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=231 Participants Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
Change From Baseline in Pre-dose Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 52 in the Effectiveness Analysis Set	4.91 percentage of predicted FEV1 Standard Deviation 10.00

PRIMARY outcome

Timeframe: 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 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.

Outcome measures

Outcome measures
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=169 Participants Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
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	6.13 percentage of predicted FEV1 Standard Deviation 9.29

PRIMARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=195 Participants Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
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	4.83 percentage of predicted FEV1 Standard Deviation 10.34

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=480 Participants Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
Change From Baseline in Post Bronchodilator Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 24 in the Effectiveness Analysis Set	3.80 percentage of predicted FEV1 Standard Deviation 8.83

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=230 Participants Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
Change From Baseline in Post Bronchodilator Percent Predicted Forced Expiratory Volume in One Second (FEV1) to Week 52 in the Effectiveness Analysis Set	4.52 percentage of predicted FEV1 Standard Deviation 9.23

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=135 Participants Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
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	5.19 percentage of predicted FEV1 Standard Deviation 8.80

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=200 Participants Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
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	4.36 percentage of predicted FEV1 Standard Deviation 9.16

SECONDARY outcome

Timeframe: At Week 24 (±2 weeks).

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.

Outcome measures

Outcome measures
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=585 Participants Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
Transition Dyspnea Index (TDI) Focal Score at Week 24 in the Effectiveness Analysis Set	-0.18 units on a scale Standard Deviation 0.64

SECONDARY outcome

Timeframe: At Week 52 (±2 weeks).

Outcome measures

Outcome measures
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=137 Participants Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
Transition Dyspnea Index (TDI) Focal Score at Week 52 in the Effectiveness Analysis Set	-0.39 units on a scale Standard Deviation 0.79

SECONDARY outcome

Timeframe: At Week 24 (±2 weeks).

Outcome measures

Outcome measures
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=134 Participants Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
Transition Dyspnea Index (TDI) Focal Score at Week 24 in the Long-term Effectiveness Analysis Set	-0.31 units on a scale Standard Deviation 0.63

SECONDARY outcome

Timeframe: At Week 52 (±2 weeks).

Outcome measures

Outcome measures
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=110 Participants Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
Transition Dyspnea Index (TDI) Focal Score at Week 52 in the Long-term Effectiveness Analysis Set	-0.44 units on a scale Standard Deviation 0.78

SECONDARY outcome

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

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.

Outcome measures

Outcome measures
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=2105 Participants Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
Number of Subjects in Each Category of Overall Evaluation in the Effectiveness Analysis Set Improved	1386 Participants
Number of Subjects in Each Category of Overall Evaluation in the Effectiveness Analysis Set Unchanged	711 Participants
Number of Subjects in Each Category of Overall Evaluation in the Effectiveness Analysis Set Aggravated	8 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=767 Participants Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
Number of Subjects in Each Category of Overall Evaluation in the Long-term Effectiveness Analysis Set Improved	543 Participants
Number of Subjects in Each Category of Overall Evaluation in the Long-term Effectiveness Analysis Set Unchanged	220 Participants
Number of Subjects in Each Category of Overall Evaluation in the Long-term Effectiveness Analysis Set Aggravated	4 Participants
Number of Subjects in Each Category of Overall Evaluation in the Long-term Effectiveness Analysis Set Unassessable	0 Participants

SECONDARY outcome

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

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".

Outcome measures

Outcome measures
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=2105 Participants Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
Effectiveness Rate in the Effectiveness Analysis Set	65.84 percentage of participants Interval 63.77 to 67.87

SECONDARY outcome

Timeframe: 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, 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".

Outcome measures

Outcome measures
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=767 Participants Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
Effectiveness Rate in the Long-term Effectiveness Analysis Set	70.80 percentage of participants Interval 67.44 to 73.99

Adverse Events

Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination)

Serious events: 147 serious events

Other events: 0 other events

Deaths: 12 deaths

Serious adverse events

Serious adverse events
Measure	Vahelva® Respimat® (Tiotropium + Olodaterol Fixed Dose Combination) n=3100 participants at risk Vahelva® Respimat® (Tiotropium + Olodaterol fixed dose combination) was prescribed according to the local label and at the discretion of the treating physician. 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. Each puff contains 2.5 microgram Tiotropium and 2.5 microgram Olodaterol.
Blood and lymphatic system disorders Coagulopathy	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Cardiac disorders Acute myocardial infarction	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Cardiac disorders Angina pectoris	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Cardiac disorders Arteriospasm coronary	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Cardiac disorders Atrial fibrillation	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Cardiac disorders Cardiac failure	0.06% 2/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Cardiac disorders Cor pulmonale	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Cardiac disorders Pericardial effusion	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Cardiac disorders Prinzmetal angina	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Congenital, familial and genetic disorders Atrial septal defect	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Eye disorders Cataract	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Eye disorders Retinal vein occlusion	0.06% 2/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Gastrointestinal disorders Ascites	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Gastrointestinal disorders Colitis ischaemic	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Gastrointestinal disorders Diarrhoea	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Gastrointestinal disorders Haematochezia	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Gastrointestinal disorders Ileus	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Gastrointestinal disorders Ileus paralytic	0.06% 2/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Gastrointestinal disorders Inguinal hernia	0.10% 3/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Gastrointestinal disorders Pancreatitis	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Gastrointestinal disorders Post procedural complication	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
General disorders Asthenia	0.06% 2/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
General disorders Death	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
General disorders Pyrexia	0.06% 2/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Hepatobiliary disorders Cholelithiasis	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Hepatobiliary disorders Hepatic cirrhosis	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Infections and infestations Bronchiolitis	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Infections and infestations Herpes zoster	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Infections and infestations Mycobacterial infection	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Infections and infestations Pneumonia	0.97% 30/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Infections and infestations Pneumonia bacterial	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Infections and infestations Pneumonia influenzal	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Infections and infestations Pulmonary tuberculosis	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Infections and infestations Pyelonephritis acute	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Infections and infestations Sinusitis	0.06% 2/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Infections and infestations Tuberculosis	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Infections and infestations Upper respiratory tract infection	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Infections and infestations Urinary tract infection	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Injury, poisoning and procedural complications Incisional hernia	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Injury, poisoning and procedural complications Radiation pneumonitis	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Injury, poisoning and procedural complications Rib fracture	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Metabolism and nutrition disorders Diabetes mellitus	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Metabolism and nutrition disorders Hyperglycaemic hyperosmolar nonketotic syndrome	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Metabolism and nutrition disorders Hypoglycaemia	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Musculoskeletal and connective tissue disorders Bursitis	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Musculoskeletal and connective tissue disorders Pain in extremity	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myelomonocytic leukaemia	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.10% 3/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatocellular carcinoma	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal cancer	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.06% 2/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant neoplasm progression	0.16% 5/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to central nervous system	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cancer	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell carcinoma	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer	0.06% 2/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of lung	0.06% 2/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thymoma	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Nervous system disorders Bell's palsy	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Nervous system disorders Cerebellar infarction	0.06% 2/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Nervous system disorders Cerebral infarction	0.13% 4/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Nervous system disorders Metabolic encephalopathy	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Nervous system disorders Partial seizures with secondary generalisation	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Psychiatric disorders Delirium	0.06% 2/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Renal and urinary disorders Acute kidney injury	0.10% 3/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Renal and urinary disorders Haematuria	0.06% 2/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Renal and urinary disorders Urinary retention	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Renal and urinary disorders Urinary tract obstruction	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Respiratory, thoracic and mediastinal disorders Bronchiectasis	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.77% 24/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.16% 5/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Respiratory, thoracic and mediastinal disorders Epiglottic cyst	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.23% 7/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.06% 2/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.10% 3/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.13% 4/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Respiratory, thoracic and mediastinal disorders Pulmonary mass	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Skin and subcutaneous tissue disorders Dermatitis exfoliative	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Skin and subcutaneous tissue disorders Leukoplakia	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Vascular disorders Aortic aneurysm	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Vascular disorders Aortic stenosis	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Vascular disorders Hypovolaemic shock	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.
Vascular disorders Peripheral arterial occlusive disease	0.03% 1/3100 • From the signing date on Informed Consent Form (ICF) to 28 days after last administration date of medication, up to 52 (±2) weeks+ 28 days. 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.

Other adverse events

Adverse event data not reported

Additional Information

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Boehringer Ingelheim

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Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER