Trial Outcomes & Findings for Study to Compare QVM149 and Free Triple Combination of Salmeterol/Fluticasone + Tiotropium (NCT NCT03158311)

Last Updated: 2021-10-08

Results Overview

The AQLQ is a 32-item asthma specific questionnaire designed to measure functional impairments that are most important to patients with asthma, with a recall time of two weeks and each question to be answered on a 7-point scale, where 1=totally limited/problems all the time and 7= not at all limited/no problems. It consists of 4 domains: symptoms, activity limitation, emotional funtion, and emotional stimuli. The overall score is calculated as the mean of 32 items. Higher AQLQ scores indicate better health-related quality of life.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1426 participants

Primary outcome timeframe

Baseline and Week 24

Results posted on

2021-10-08

Participant Flow

Participants took part in 166 investigative sites in 20 countries from 05 Feb 2018 to 19 Jul 2019.

A total of 1917 participants were screened. A 2 week run-in phase preceded the randomized treatment phase of the study. 1821 participants entered the run-in phase. Those participants who met the inclusion criteria entered the randomized treatment phase. Participants were randomized with a randomization ratio of 1:1:1 to three treatment arms.

Participant milestones

Participant milestones
Measure	QVM149 150/50/80 μg QVM149 150/50/80 μg o.d. delivered via Concept1	QVM149 150/50/160 μg QVM149 150/50/160 μg o.d. delivered via Concept1	Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg Salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d. delivered via Respimat®
Overall Study STARTED	474	476	476
Overall Study Full Analysis Set (FAS)	474	476	475
Overall Study Safety Set (SAF)	474	476	475
Overall Study COMPLETED	452	460	448
Overall Study NOT COMPLETED	22	16	28

Reasons for withdrawal

Reasons for withdrawal
Measure	QVM149 150/50/80 μg QVM149 150/50/80 μg o.d. delivered via Concept1	QVM149 150/50/160 μg QVM149 150/50/160 μg o.d. delivered via Concept1	Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg Salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d. delivered via Respimat®
Overall Study Subject/Guardian Decision	10	6	11
Overall Study Adverse Event	5	3	3
Overall Study Techinical Problems	3	1	5
Overall Study Physician Decision	2	3	7
Overall Study Lost to Follow-up	1	1	1
Overall Study Sponsor decision	1	0	0
Overall Study Pregnancy	0	2	0
Overall Study Randomized in error	0	0	1

Baseline Characteristics

Study to Compare QVM149 and Free Triple Combination of Salmeterol/Fluticasone + Tiotropium

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	QVM149 150/50/80 μg n=474 Participants QVM149 150/50/80 μg o.d. delivered via Concept1	QVM149 150/50/160 μg n=476 Participants QVM149 150/50/160 μg o.d. delivered via Concept1	Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg n=476 Participants Salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d. delivered via Respimat®	Total n=1426 Participants Total of all reporting groups
Age, Continuous	51.9 Years STANDARD_DEVIATION 13.58 • n=5 Participants	52.7 Years STANDARD_DEVIATION 13.34 • n=7 Participants	53.1 Years STANDARD_DEVIATION 13.08 • n=5 Participants	52.5 Years STANDARD_DEVIATION 13.33 • n=4 Participants
Sex: Female, Male Female	306 Participants n=5 Participants	289 Participants n=7 Participants	307 Participants n=5 Participants	902 Participants n=4 Participants
Sex: Female, Male Male	168 Participants n=5 Participants	187 Participants n=7 Participants	169 Participants n=5 Participants	524 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	5 Participants n=5 Participants	1 Participants n=7 Participants	10 Participants n=5 Participants	16 Participants n=4 Participants
Race/Ethnicity, Customized Asian	36 Participants n=5 Participants	34 Participants n=7 Participants	33 Participants n=5 Participants	103 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	6 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	14 Participants n=4 Participants
Race/Ethnicity, Customized White	401 Participants n=5 Participants	392 Participants n=7 Participants	391 Participants n=5 Participants	1184 Participants n=4 Participants
Race/Ethnicity, Customized Other	26 Participants n=5 Participants	44 Participants n=7 Participants	39 Participants n=5 Participants	109 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 24

Population: Analysis population included FAS with evaluable AQLQ data at both timepoints. No imputation was used for missing questions or missing total AQLQ score for this analysis. The analysis was performed on observed data only.

Outcome measures

Outcome measures
Measure	QVM149 150/50/80 μg n=436 Participants QVM149 150/50/80 μg o.d. delivered via Concept1	QVM149 150/50/160 μg n=453 Participants QVM149 150/50/160 μg o.d. delivered via Concept1	Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg n=435 Participants Salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d. delivered via Respimat®
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total Score	0.715 Score on a scale Standard Error 0.070	0.827 Score on a scale Standard Error 0.069	0.753 Score on a scale Standard Error 0.069

SECONDARY outcome

Timeframe: Baseline, Week 8, Week 16 and Week 24

Population: Analysis population included FAS with FEV1 data at the respective visit. Number analyzed signified number of participants who were evaluable for this outcome measure at specified timepoints.

FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. Trough FEV1 is the mean of two FEV1 values measures taken 15 minutes (min) and 45 min prior to evening dose.

Outcome measures

Outcome measures
Measure	QVM149 150/50/80 μg n=420 Participants QVM149 150/50/80 μg o.d. delivered via Concept1	QVM149 150/50/160 μg n=438 Participants QVM149 150/50/160 μg o.d. delivered via Concept1	Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg n=425 Participants Salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d. delivered via Respimat®
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) Week 8	0.246 Litre (L) Standard Error 0.020	0.309 Litre (L) Standard Error 0.020	0.243 Litre (L) Standard Error 0.020
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) Week 16	0.251 Litre (L) Standard Error 0.020	0.319 Litre (L) Standard Error 0.020	0.253 Litre (L) Standard Error 0.020
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) Week 24	0.248 Litre (L) Standard Error 0.021	0.334 Litre (L) Standard Error 0.021	0.238 Litre (L) Standard Error 0.021

SECONDARY outcome

Timeframe: Baseline, Week 16 and Week 24

Population: Analysis population included FAS with ACQ-7 data at the respective visit. Number analyzed signified number of participants who were evaluable for this measure at specified timepoints. No imputation was used for missing questions or missing total ACQ-7 score for this analysis. The analysis was performed on observed data only

The ACQ-7 measured asthma symptom control and consists of 7 items: 5 on symptom assessment, 1 on rescue medication use and 1 on airway calibre (FEV1 % predicted). All seven items are scored on a 7-point Likert scale, with 0 indicating total control and 6 indicating poor control. The questions are equally weighted and the total score is the mean of the seven items. Higher score indicates worst symptoms. The first 6 questions of the ACQ-7 were completed by the participant while the last question was completed by the study investigator using data from the Master Scope spirometer. A negative change from baseline indicates improvement in lung function.

Outcome measures

Outcome measures
Measure	QVM149 150/50/80 μg n=447 Participants QVM149 150/50/80 μg o.d. delivered via Concept1	QVM149 150/50/160 μg n=454 Participants QVM149 150/50/160 μg o.d. delivered via Concept1	Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg n=447 Participants Salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d. delivered via Respimat®
Change From Baseline in Asthma Control Questionnaire (ACQ-7) Total Score Week 16	-1.043 Score on a scale Standard Error 0.045	-1.098 Score on a scale Standard Error 0.045	-1.020 Score on a scale Standard Error 0.045
Change From Baseline in Asthma Control Questionnaire (ACQ-7) Total Score Week 24	-1.080 Score on a scale Standard Error 0.046	-1.172 Score on a scale Standard Error 0.045	-1.048 Score on a scale Standard Error 0.046

SECONDARY outcome

Timeframe: Baseline and Week 16

The AQLQ is a 32-item asthma specific questionnaire designed to measure functional impairments that are most important to patients with asthma, with a recall time of two weeks and each question to be answered on a 7-point scale, where 1=totally limited/problems all the time and 7= not at all limited/no problems. It consists of 4 domains: symptoms, activity limitation, emotional function and environmental stimuli. The overall score is calculated as the mean of 32 items. Higher AQLQ scores indicate better health-related quality of life.

Outcome measures

Outcome measures
Measure	QVM149 150/50/80 μg n=435 Participants QVM149 150/50/80 μg o.d. delivered via Concept1	QVM149 150/50/160 μg n=442 Participants QVM149 150/50/160 μg o.d. delivered via Concept1	Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg n=429 Participants Salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d. delivered via Respimat®
Change From Baseline in AQLQ Total Score	0.690 Score on a scale Standard Error 0.069	0.755 Score on a scale Standard Error 0.068	0.673 Score on a scale Standard Error 0.069

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Analysis population included FAS with evaluable ACQ-7 data at both timepoints. Missing data imputation was used to perform this analysis. Subjects with missing values were imputed as non-responders (a non-responder was defined as \<0.5 decrease in ACQ-7 score at week 24)

Outcome measures

Outcome measures
Measure	QVM149 150/50/80 μg n=447 Participants QVM149 150/50/80 μg o.d. delivered via Concept1	QVM149 150/50/160 μg n=454 Participants QVM149 150/50/160 μg o.d. delivered via Concept1	Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg n=447 Participants Salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d. delivered via Respimat®
Percentage of Patients Achieving the Minimally Clinically Important Difference (MCID) Decrease From Baseline ACQ-7 ≥ 0.5	393 Participants	387 Participants	375 Participants

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Analysis population included FAS with evaluable AQLQ data at both timepoints. Missing data imputation was used to perform this analysis. Subjects with missing values were imputed as non-responders (a non-responder was defined as \<0.5 increase in AQLQ score at week 24)

The AQLQ is a 32-item asthma specific questionnaire designed to measure functional impairments that are most important to patients with asthma, with a recall time of two weeks and each question to be answered on a 7-point scale, where 1=totally limited/problems all the time and 7= not at all limited/no problems. It consists of 4 domains: symptoms, activity limitation, emotional function and environmental stimuli. The overall score is calculated as the mean of 32 items. Higher AQLQ scores indicate better health-related quality of life. An improvement of 0.5 points in AQLQ score is considered to be the minimally clinically important difference in asthma.

Outcome measures

Outcome measures
Measure	QVM149 150/50/80 μg n=444 Participants QVM149 150/50/80 μg o.d. delivered via Concept1	QVM149 150/50/160 μg n=454 Participants QVM149 150/50/160 μg o.d. delivered via Concept1	Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg n=441 Participants Salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d. delivered via Respimat®
Percentage of Patients Achieving the Minimally Clinically Important Difference (MCID) Change From Baseline AQLQ ≥ 0.5	318 Participants	333 Participants	299 Participants

SECONDARY outcome

Timeframe: Baseline, Week 8, Week 16 and Week 24

Population: Analysis population included FAS with FVC data at the respective visit. Number analyzed signified number of participants who were evaluable for this measure at specified timepoints.

FVC is the total volume of air exhaled during a expiratory maneuvre. It was assessed by performing a spirometry assessment.

Outcome measures

Outcome measures
Measure	QVM149 150/50/80 μg n=420 Participants QVM149 150/50/80 μg o.d. delivered via Concept1	QVM149 150/50/160 μg n=438 Participants QVM149 150/50/160 μg o.d. delivered via Concept1	Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg n=425 Participants Salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d. delivered via Respimat®
Change From Baseline in Forced Vital Capacity (FVC) Week 8	0.216 Litre (L) Standard Error 0.021	0.272 Litre (L) Standard Error 0.021	0.219 Litre (L) Standard Error 0.021
Change From Baseline in Forced Vital Capacity (FVC) Week 16	0.221 Litre (L) Standard Error 0.021	0.275 Litre (L) Standard Error 0.021	0.217 Litre (L) Standard Error 0.021
Change From Baseline in Forced Vital Capacity (FVC) Week 24	0.214 Litre (L) Standard Error 0.022	0.280 Litre (L) Standard Error 0.022	0.186 Litre (L) Standard Error 0.022

SECONDARY outcome

Timeframe: Baseline, Week 8, Week 16 and Week 24

Population: Analysis population included FAS with FEF25-75 data at the respective visit. Number analyzed signified number of participants who were evaluable for this measure at specified timepoints.

Forced expiratory flow during the mid (25 - 75%) portion of the FVC. It was assessed by performing spirometric assessment.

Outcome measures

Outcome measures
Measure	QVM149 150/50/80 μg n=420 Participants QVM149 150/50/80 μg o.d. delivered via Concept1	QVM149 150/50/160 μg n=438 Participants QVM149 150/50/160 μg o.d. delivered via Concept1	Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg n=425 Participants Salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d. delivered via Respimat®
Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75) Week 8	0.290 Litres/second (L/s) Standard Error 0.027	0.332 Litres/second (L/s) Standard Error 0.027	0.270 Litres/second (L/s) Standard Error 0.027
Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75) Week 16	0.291 Litres/second (L/s) Standard Error 0.028	0.355 Litres/second (L/s) Standard Error 0.027	0.297 Litres/second (L/s) Standard Error 0.027
Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75) Week 24	0.290 Litres/second (L/s) Standard Error 0.028	0.375 Litres/second (L/s) Standard Error 0.028	0.286 Litres/second (L/s) Standard Error 0.028

Adverse Events

QVM149 150/50/80 μg

Serious events: 14 serious events

Other events: 245 other events

Deaths: 0 deaths

QVM149 150/50/160 µg

Serious events: 18 serious events

Other events: 246 other events

Deaths: 0 deaths

Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg

Serious events: 19 serious events

Other events: 241 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Serious adverse events
Measure	QVM149 150/50/80 μg n=474 participants at risk QVM149 150/50/80 µg o.d. delivered via Concept1	QVM149 150/50/160 µg n=476 participants at risk QVM149 150/50/160 μg o.d. delivered via Concept1	Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg n=475 participants at risk Salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d. delivered via Respimat®
Infections and infestations Pilonidal cyst	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Blood and lymphatic system disorders Lymphadenopathy	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Cardiac disorders Atrioventricular block second degree	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Cardiac disorders Myocardial infarction	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Cardiac disorders Supraventricular tachycardia	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Cardiac disorders Tachycardia	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Endocrine disorders Goitre	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Abdominal hernia	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Colitis	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Large intestine polyp	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Pancreatitis acute	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
General disorders Hyperpyrexia	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
General disorders Non-cardiac chest pain	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Hepatobiliary disorders Cholecystitis	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Hepatobiliary disorders Cholelithiasis	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Infections and infestations Atypical pneumonia	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Infections and infestations Bronchiolitis	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Infections and infestations Cellulitis	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Infections and infestations Diverticulitis	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Infections and infestations H1N1 influenza	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Infections and infestations Hepatitis viral	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Infections and infestations Lung infection	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Infections and infestations Pneumonia	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	1.1% 5/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Infections and infestations Postoperative abscess	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Infections and infestations Rectal abscess	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Infections and infestations Viral upper respiratory tract infection	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Injury, poisoning and procedural complications Contusion	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Injury, poisoning and procedural complications Intentional product misuse	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.42% 2/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Injury, poisoning and procedural complications Meniscus injury	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Investigations Hepatic enzyme increased	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fibroadenoma of breast	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Large intestine benign neoplasm	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Respiratory tract neoplasm	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Nervous system disorders Carotid artery stenosis	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Nervous system disorders Guillain-Barre syndrome	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.

Other adverse events
Measure	QVM149 150/50/80 μg n=474 participants at risk QVM149 150/50/80 µg o.d. delivered via Concept1	QVM149 150/50/160 µg n=476 participants at risk QVM149 150/50/160 μg o.d. delivered via Concept1	Salmeterol/Fluticasone 50/500 μg Plus Tiotropium 5 μg n=475 participants at risk Salmeterol/fluticasone 50/500 μg b.i.d. delivered via Accuhaler® plus tiotropium 5 μg o.d. delivered via Respimat®
Blood and lymphatic system disorders Anaemia	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.42% 2/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Blood and lymphatic system disorders Haemolysis	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Blood and lymphatic system disorders Lymphadenitis	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Cardiac disorders Angina pectoris	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Cardiac disorders Atrioventricular block first degree	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Cardiac disorders Bundle branch block left	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Cardiac disorders Cardiac failure	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Cardiac disorders Cardiac failure chronic	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Cardiac disorders Coronary artery disease	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Cardiac disorders Palpitations	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.42% 2/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Cardiac disorders Sinus tachycardia	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.42% 2/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.42% 2/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Cardiac disorders Supraventricular tachycardia	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Ear and labyrinth disorders Deafness	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Ear and labyrinth disorders Tinnitus	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Endocrine disorders Hypothyroidism	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Endocrine disorders Thyroid cyst	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Eye disorders Blepharitis	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Eye disorders Cataract	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Eye disorders Conjunctivitis allergic	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.42% 2/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Eye disorders Eye disorder	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Eye disorders Eye pruritus	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Eye disorders Maculopathy	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Eye disorders Panophthalmitis	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Eye disorders Vision blurred	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Abdominal discomfort	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Abdominal distension	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Abdominal hernia	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Abdominal pain	0.63% 3/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.42% 2/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Abdominal pain upper	0.42% 2/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Aphthous ulcer	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Chronic gastritis	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Colitis	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Constipation	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Diarrhoea	0.42% 2/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	1.1% 5/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.84% 4/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Dry mouth	0.63% 3/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	1.1% 5/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Duodenitis	0.00% 0/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Dyspepsia	0.42% 2/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.63% 3/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Enteritis	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.00% 0/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Gastritis	0.84% 4/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.84% 4/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.21% 1/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.21% 1/474 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.42% 2/476 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.	0.42% 2/475 • Adverse events were collected starting on or after the time of first administration of study drug but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration, up to maximum duration of 203 days. Any sign or symptom that occurs during the study treatment but not later than 7 days (30 days in case of a Serious Adverse Events) after the last administration. Analysis performed on the safety set population. Safety Set consisted of all participants who received at least one dose of study medication during this study.