Trial Outcomes & Findings for Different Doses of BI 1467335 Compared to Placebo in Patients With Clinical Evidence of NASH (NCT NCT03166735)

Last Updated: 2020-06-11

Results Overview

The patient-specific plasma AOC3 activity at time t (24 hours after the last dose in week 12) relative to baseline in percentage was calculated as follows: %AOC3at = \[(AOC3at - AOC3at,back) ⁄ (AOC3abase - AOC3abase,back)\]\*100 With AOC3at the AOC3 activity measured at time t, AOC3at,back the background noise at time t, AOC3abase the AOC3 activity measured at baseline and AOC3abase,back the background noise at baseline. A dose-response relationship was analysed using a non-linear regression model to estimate the daily dosage needed to reach 10% of AOC3 activity (i.e. 90% inhibition) 12 weeks after treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

114 participants

Primary outcome timeframe

Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.

Results posted on

2020-06-11

Participant Flow

This study is a multi-centre, double-blind, parallel-group, randomised, placebo-controlled phase IIa study to investigate safety, tolerability, pharmacodynamics, and pharmacokinetics of different doses of orally administered BI 1467335 (for 12-weeks) compared to placebo in patients with clinical evidence of Non-alcoholic steato-hepatitis (NASH).

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

Participant milestones

Participant milestones
Measure	Placebo Matching placebo taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated placebo tablets were supplied. For blinding reasons, all patients took 5 tablets placebo daily.	BI 1467335 1 Milligram (mg) 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 3 Milligram (mg) 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 6 Milligram (mg) 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 10 Milligram (mg) 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.
Overall Study STARTED	33	16	16	17	32
Overall Study Treated	32	16	16	17	32
Overall Study COMPLETED	32	13	13	16	28
Overall Study NOT COMPLETED	1	3	3	1	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Matching placebo taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated placebo tablets were supplied. For blinding reasons, all patients took 5 tablets placebo daily.	BI 1467335 1 Milligram (mg) 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 3 Milligram (mg) 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 6 Milligram (mg) 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 10 Milligram (mg) 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.
Overall Study Not Treated	1	0	0	0	0
Overall Study follow-up not completed as planned	0	1	1	0	1
Overall Study Withdrawal by Subject	0	0	1	1	2
Overall Study Lost to Follow-up	0	2	1	0	1

Baseline Characteristics

Treated Set (TS): all patients who signed the informed consent and were treated with at least one dose of the trial medication. For 3 patients no AOC3 baseline data was collected.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=32 Participants Matching placebo taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated placebo tablets were supplied. For blinding reasons, all patients took 5 tablets placebo daily.	BI 1467335 1 Milligram (mg) n=16 Participants 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 3 Milligram (mg) n=16 Participants 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 6 Milligram (mg) n=17 Participants 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 10 Milligram (mg) n=32 Participants 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	Total n=113 Participants Total of all reporting groups
Age, Continuous	51.8 years STANDARD_DEVIATION 12.3 • n=32 Participants	52.6 years STANDARD_DEVIATION 13.3 • n=16 Participants	53.9 years STANDARD_DEVIATION 11.5 • n=16 Participants	48.2 years STANDARD_DEVIATION 10.1 • n=17 Participants	49.8 years STANDARD_DEVIATION 14.0 • n=32 Participants	51.1 years STANDARD_DEVIATION 12.5 • n=113 Participants
Sex: Female, Male Female	13 Participants n=32 Participants	10 Participants n=16 Participants	8 Participants n=16 Participants	9 Participants n=17 Participants	18 Participants n=32 Participants	58 Participants n=113 Participants
Sex: Female, Male Male	19 Participants n=32 Participants	6 Participants n=16 Participants	8 Participants n=16 Participants	8 Participants n=17 Participants	14 Participants n=32 Participants	55 Participants n=113 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=32 Participants	5 Participants n=16 Participants	5 Participants n=16 Participants	4 Participants n=17 Participants	8 Participants n=32 Participants	33 Participants n=113 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	21 Participants n=32 Participants	11 Participants n=16 Participants	11 Participants n=16 Participants	13 Participants n=17 Participants	24 Participants n=32 Participants	80 Participants n=113 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=32 Participants	0 Participants n=16 Participants	0 Participants n=16 Participants	0 Participants n=17 Participants	0 Participants n=32 Participants	0 Participants n=113 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=32 Participants	0 Participants n=16 Participants	0 Participants n=16 Participants	0 Participants n=17 Participants	0 Participants n=32 Participants	0 Participants n=113 Participants
Race (NIH/OMB) Asian	1 Participants n=32 Participants	1 Participants n=16 Participants	0 Participants n=16 Participants	0 Participants n=17 Participants	0 Participants n=32 Participants	2 Participants n=113 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=32 Participants	1 Participants n=16 Participants	0 Participants n=16 Participants	0 Participants n=17 Participants	0 Participants n=32 Participants	2 Participants n=113 Participants
Race (NIH/OMB) Black or African American	0 Participants n=32 Participants	0 Participants n=16 Participants	0 Participants n=16 Participants	0 Participants n=17 Participants	0 Participants n=32 Participants	0 Participants n=113 Participants
Race (NIH/OMB) White	30 Participants n=32 Participants	14 Participants n=16 Participants	16 Participants n=16 Participants	17 Participants n=17 Participants	32 Participants n=32 Participants	109 Participants n=113 Participants
Race (NIH/OMB) More than one race	0 Participants n=32 Participants	0 Participants n=16 Participants	0 Participants n=16 Participants	0 Participants n=17 Participants	0 Participants n=32 Participants	0 Participants n=113 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=32 Participants	0 Participants n=16 Participants	0 Participants n=16 Participants	0 Participants n=17 Participants	0 Participants n=32 Participants	0 Participants n=113 Participants
Plasma amine oxidase copper-containing 3 (AOC3) baseline concentration	471.4063 microgram per liter (µg/l) STANDARD_DEVIATION 165.6802 • n=32 Participants • Treated Set (TS): all patients who signed the informed consent and were treated with at least one dose of the trial medication. For 3 patients no AOC3 baseline data was collected.	537.7143 microgram per liter (µg/l) STANDARD_DEVIATION 204.4100 • n=14 Participants • Treated Set (TS): all patients who signed the informed consent and were treated with at least one dose of the trial medication. For 3 patients no AOC3 baseline data was collected.	498.0000 microgram per liter (µg/l) STANDARD_DEVIATION 141.0225 • n=16 Participants • Treated Set (TS): all patients who signed the informed consent and were treated with at least one dose of the trial medication. For 3 patients no AOC3 baseline data was collected.	527.2941 microgram per liter (µg/l) STANDARD_DEVIATION 142.3722 • n=17 Participants • Treated Set (TS): all patients who signed the informed consent and were treated with at least one dose of the trial medication. For 3 patients no AOC3 baseline data was collected.	516.1613 microgram per liter (µg/l) STANDARD_DEVIATION 144.0727 • n=31 Participants • Treated Set (TS): all patients who signed the informed consent and were treated with at least one dose of the trial medication. For 3 patients no AOC3 baseline data was collected.	504.9636 microgram per liter (µg/l) STANDARD_DEVIATION 157.4936 • n=110 Participants • Treated Set (TS): all patients who signed the informed consent and were treated with at least one dose of the trial medication. For 3 patients no AOC3 baseline data was collected.

PRIMARY outcome

Timeframe: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.

Population: Per Protocol Set (PPS): Patients who signed informed consent, were treated with at least one dose of the trial medication, without any important protocol deviations leading to exclusion and who had non-missing baseline and at least one non-missing post-baseline and on-treatment measurement on any primary, secondary or further biomarker endpoint.

Outcome measures

Outcome measures
Measure	Placebo n=30 Participants Matching placebo taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated placebo tablets were supplied. For blinding reasons, all patients took 5 tablets placebo daily.	BI 1467335 1 Milligram (mg) n=12 Participants 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 3 Milligram (mg) n=14 Participants 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 6 Milligram (mg) n=11 Participants 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 10 Milligram (mg) n=24 Participants 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.
Plasma Amine Oxidase Copper-containing 3 (AOC3) Activity After 12 Weeks of Treatment, Relative to Baseline in Percent	102 Percentage relative to baseline Standard Deviation 13.0	24.0 Percentage relative to baseline Standard Deviation 11.9	13.1 Percentage relative to baseline Standard Deviation 10.4	8.27 Percentage relative to baseline Standard Deviation 5.19	2.06 Percentage relative to baseline Standard Deviation 3.62

SECONDARY outcome

Timeframe: Start of treatment till end of treatment + 28 days, up to 113 days.

Population: Treated Set (TS): All patients who signed the informed consent and were treated with at least one dose of the trial medication.

Percentage of participants with drug-related adverse events (AEs). Percentages are calculated using total number of patients per treatment as the denominator.

Outcome measures

Outcome measures
Measure	Placebo n=32 Participants Matching placebo taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated placebo tablets were supplied. For blinding reasons, all patients took 5 tablets placebo daily.	BI 1467335 1 Milligram (mg) n=16 Participants 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 3 Milligram (mg) n=16 Participants 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 6 Milligram (mg) n=17 Participants 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 10 Milligram (mg) n=32 Participants 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.
Percentage of Participants With Drug-related Adverse Events (AEs)	25.0 Percentage of participants	31.3 Percentage of participants	12.5 Percentage of participants	11.8 Percentage of participants	25.0 Percentage of participants

SECONDARY outcome

Timeframe: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.

Alanine aminotransaminase (ALT) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints. The unit of measure is: percentage relative to baseline = \[post baseline (time t)/baseline\]\*100% Statistical analyses description: A Mixed effects Model for Repeated Measurements (MMRM) over time including fixed effects for 'base', 'treatment', 'time', 'base\*time' interaction, and 'treatment\*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Matching placebo taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated placebo tablets were supplied. For blinding reasons, all patients took 5 tablets placebo daily.	BI 1467335 1 Milligram (mg) n=12 Participants 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 3 Milligram (mg) n=13 Participants 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 6 Milligram (mg) n=14 Participants 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 10 Milligram (mg) n=27 Participants 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.
Alanine Aminotransaminase (ALT) After 12 Weeks of Treatment, Relative to Baseline in Percent	92.66 Percentage relative to baseline Standard Error 106.55	97.32 Percentage relative to baseline Standard Error 110.13	87.49 Percentage relative to baseline Standard Error 109.79	80.61 Percentage relative to baseline Standard Error 109.43	77.57 Percentage relative to baseline Standard Error 106.66

SECONDARY outcome

Timeframe: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.

Aspartate aminotransferase (AST) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints. The unit of measure is: percentage relative to baseline = \[post baseline (time t)/baseline\]\*100% Statistical analyses description: A Mixed effects Model for Repeated Measurements (MMRM) over time including fixed effects for 'base', 'treatment', 'time', 'base\*time' interaction, and 'treatment\*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted.

Outcome measures

Outcome measures
Measure	Placebo n=27 Participants Matching placebo taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated placebo tablets were supplied. For blinding reasons, all patients took 5 tablets placebo daily.	BI 1467335 1 Milligram (mg) n=12 Participants 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 3 Milligram (mg) n=13 Participants 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 6 Milligram (mg) n=14 Participants 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 10 Milligram (mg) n=23 Participants 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.
Aspartate Aminotransferase (AST) After 12 Weeks of Treatment, Relative to Baseline in Percent	93.77 Percentage relative to baseline Standard Error 105.91	105.17 Percentage relative to baseline Standard Error 108.93	90.09 Percentage relative to baseline Standard Error 108.72	84.12 Percentage relative to baseline Standard Error 108.34	87.83 Percentage relative to baseline Standard Error 106.26

SECONDARY outcome

Timeframe: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.

Alkaline phosphatase (AP) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints. The unit of measure is: percentage relative to baseline = \[post baseline (time t)/baseline\]\*100% Statistical analyses description: A Mixed effects Model for Repeated Measurements (MMRM) over time including fixed effects for 'base', 'treatment', 'time', 'base\*time' interaction, and 'treatment\*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted.

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Matching placebo taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated placebo tablets were supplied. For blinding reasons, all patients took 5 tablets placebo daily.	BI 1467335 1 Milligram (mg) n=12 Participants 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 3 Milligram (mg) n=13 Participants 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 6 Milligram (mg) n=14 Participants 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 10 Milligram (mg) n=28 Participants 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.
Alkaline Phosphatase (AP) After 12 Weeks of Treatment, Relative to Baseline in Percent	96.62 Percentage relative to baseline Standard Error 102.31	97.58 Percentage relative to baseline Standard Error 103.56	100.52 Percentage relative to baseline Standard Error 103.45	98.47 Percentage relative to baseline Standard Error 103.34	94.71 Percentage relative to baseline Standard Error 102.34

SECONDARY outcome

Timeframe: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.

Gamma-glutamyltransferase (GGT) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints. The unit of measure is: percentage relative to baseline = \[post baseline (time t)/baseline\]\*100% Statistical analyses description: A Mixed effects Model for Repeated Measurements (MMRM) over time including fixed effects for 'base', 'treatment', 'time', 'base\*time' interaction, and 'treatment\*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted.

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Matching placebo taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated placebo tablets were supplied. For blinding reasons, all patients took 5 tablets placebo daily.	BI 1467335 1 Milligram (mg) n=12 Participants 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 3 Milligram (mg) n=13 Participants 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 6 Milligram (mg) n=14 Participants 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 10 Milligram (mg) n=28 Participants 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.
Gamma-glutamyltransferase (GGT) After 12 Weeks of Treatment, Relative to Baseline in Percent	91.37 Percentage relative to baseline Standard Error 105.24	99.42 Percentage relative to baseline Standard Error 108.25	92.44 Percentage relative to baseline Standard Error 108.09	99.51 Percentage relative to baseline Standard Error 107.71	83.70 Percentage relative to baseline Standard Error 105.40

SECONDARY outcome

Timeframe: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.

Caspase-cleaved cytokeratin 18 (CK-18 caspase) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints. The unit of measure is: percentage relative to baseline = \[post baseline (time t)/baseline\]\*100% Statistical analyses description: A MMRM over time including fixed effects for 'base', 'treatment', 'time', 'base\*time' interaction, and 'treatment\*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted.

Outcome measures

Outcome measures
Measure	Placebo n=29 Participants Matching placebo taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated placebo tablets were supplied. For blinding reasons, all patients took 5 tablets placebo daily.	BI 1467335 1 Milligram (mg) n=12 Participants 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 3 Milligram (mg) n=12 Participants 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 6 Milligram (mg) n=14 Participants 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 10 Milligram (mg) n=26 Participants 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.
Caspase-cleaved Cytokeratin 18 (CK-18 Caspase) After 12 Weeks of Treatment, Relative to Baseline in Percent	101.35 Percentage relative to baseline Standard Error 111.15	155.04 Percentage relative to baseline Standard Error 117.61	96.87 Percentage relative to baseline Standard Error 117.54	80.51 Percentage relative to baseline Standard Error 116.32	78.08 Percentage relative to baseline Standard Error 111.59

SECONDARY outcome

Timeframe: Day 1 (baseline), day 15, 29, 43, 57 and 85 (time t) 24 hours after the last dose of BI 1467335.

Population: Per Protocol Set (PPS): patients who signed informed consent, were treated with at least one dose of the trial medication, without any important protocol deviations leading to exclusion and who had non-missing baseline and at least one non-missing post-baseline and on-treatment measurement on any primary, secondary or further biomarker endpoint.

Total cytokeratin 18 (CK-18 total) after 12 weeks of treatment, relative to baseline in percent. Number analyzed lower than N in PPS if there is missing data for specific timepoints. The unit of measure is: percentage relative to baseline = \[post baseline (time t)/baseline\]\*100%. Statistical analyses description: A Mixed effects Model for Repeated Measurements (MMRM) over time including fixed effects for 'base', 'treatment', 'time', 'base\*time' interaction, and 'treatment\*time' interaction was performed. The MMRM estimates for the treatment effects at Week 12 and the corresponding covariance matrix were used to analyse the dose-response relationship using the Multiple contrast test (MCPMod). A test for non-flat dose-response relationship was first performed. If this relationship could be shown, the best fitting model out of a set of candidate models (Sigmoidal Emax, Logistic, Quadratic, Linear, Exponential, Linear logistic, Emax and Betamod) was to be selected and fitted.

Outcome measures

Outcome measures
Measure	Placebo n=28 Participants Matching placebo taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated placebo tablets were supplied. For blinding reasons, all patients took 5 tablets placebo daily.	BI 1467335 1 Milligram (mg) n=11 Participants 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 3 Milligram (mg) n=13 Participants 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 6 Milligram (mg) n=14 Participants 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 10 Milligram (mg) n=26 Participants 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.
Total Cytokeratin 18 (CK-18 Total) After 12 Weeks of Treatment, Relative to Baseline in Percent	92.44 Percentage relative to baseline Standard Error 109.13	128.33 Percentage relative to baseline Standard Error 114.64	99.56 Percentage relative to baseline Standard Error 113.78	94.74 Percentage relative to baseline Standard Error 113.10	81.47 Percentage relative to baseline Standard Error 109.35

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

BI 1467335 1 Milligram (mg)

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

BI 1467335 3 Milligram (mg)

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

BI 1467335 6 Milligram (mg)

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

BI 1467335 10 Milligram (mg)

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Total BI 1467335

Serious events: 2 serious events

Other events: 54 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=32 participants at risk Matching placebo taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated placebo tablets were supplied. For blinding reasons, all patients took 5 tablets placebo daily.	BI 1467335 1 Milligram (mg) n=16 participants at risk 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 3 Milligram (mg) n=16 participants at risk 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 6 Milligram (mg) n=17 participants at risk 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 10 Milligram (mg) n=32 participants at risk 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	Total BI 1467335 n=81 participants at risk All participant who took a dose of BI 1467335.
Gastrointestinal disorders Pancreatitis	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Infections and infestations H1N1 influenza	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Infections and infestations Sinusitis	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).

Other adverse events

Other adverse events
Measure	Placebo n=32 participants at risk Matching placebo taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated placebo tablets were supplied. For blinding reasons, all patients took 5 tablets placebo daily.	BI 1467335 1 Milligram (mg) n=16 participants at risk 1 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 3 Milligram (mg) n=16 participants at risk 3 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 6 Milligram (mg) n=17 participants at risk 6 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	BI 1467335 10 Milligram (mg) n=32 participants at risk 10 milligram (mg) BI 1467335 taken daily for 12 weeks. Tablets taken orally with water in the morning, fasted, 1 hour before breakfast. Film-coated tablets were supplied as 1 mg and 5 mg dose strengths. For blinding reasons, all patients took 5 tablets verum or placebo daily.	Total BI 1467335 n=81 participants at risk All participant who took a dose of BI 1467335.
Injury, poisoning and procedural complications Tooth fracture	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Injury, poisoning and procedural complications Vascular procedure complication	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Investigations Blood creatine phosphokinase increased	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Investigations Blood glucose increased	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Investigations Gamma-glutamyltransferase increased	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Investigations Lipase increased	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	2.5% 2/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Investigations Weight increased	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Metabolism and nutrition disorders Decreased appetite	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	2.5% 2/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Metabolism and nutrition disorders Hyperlipidaemia	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Metabolism and nutrition disorders Hypertriglyceridaemia	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Musculoskeletal and connective tissue disorders Back pain	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	12.5% 2/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	4.9% 4/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	11.8% 2/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	2.5% 2/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Anogenital warts	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Nervous system disorders Disturbance in attention	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Nervous system disorders Dizziness	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	12.5% 2/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	9.4% 3/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	7.4% 6/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Nervous system disorders Headache	12.5% 4/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	18.8% 3/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	23.5% 4/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 2/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	11.1% 9/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Nervous system disorders Sciatica	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Nervous system disorders Tension headache	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Psychiatric disorders Anxiety	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	2.5% 2/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Renal and urinary disorders Nephrolithiasis	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	2.5% 2/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Respiratory, thoracic and mediastinal disorders Dry throat	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	2.5% 2/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	2.5% 2/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Respiratory, thoracic and mediastinal disorders Paranasal sinus discomfort	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Respiratory, thoracic and mediastinal disorders Sinus pain	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Skin and subcutaneous tissue disorders Rash	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 2/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	2.5% 2/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Vascular disorders Orthostatic hypotension	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Vascular disorders Subclavian steal syndrome	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Ear and labyrinth disorders Vertigo	6.2% 2/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	2.5% 2/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Eye disorders Vision blurred	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Gastrointestinal disorders Abdominal discomfort	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Gastrointestinal disorders Abdominal pain	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	3.7% 3/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Gastrointestinal disorders Abdominal pain lower	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Gastrointestinal disorders Abdominal pain upper	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Gastrointestinal disorders Diarrhoea	9.4% 3/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	11.8% 2/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	9.4% 3/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	8.6% 7/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Gastrointestinal disorders Dry mouth	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	2.5% 2/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Gastrointestinal disorders Dyspepsia	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 2/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	3.7% 3/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Gastrointestinal disorders Flatulence	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	2.5% 2/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Gastrointestinal disorders Nausea	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	25.0% 4/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	15.6% 5/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	12.3% 10/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Gastrointestinal disorders Pouchitis	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Gastrointestinal disorders Toothache	6.2% 2/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Gastrointestinal disorders Vomiting	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	12.5% 2/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	2.5% 2/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
General disorders Asthenia	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
General disorders Chest pain	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
General disorders Early satiety	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
General disorders Fatigue	9.4% 3/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	15.6% 5/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	7.4% 6/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
General disorders Influenza like illness	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
General disorders Pain	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 2/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	2.5% 2/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Hepatobiliary disorders Hepatic pain	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Immune system disorders Hypersensitivity	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	3.7% 3/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Infections and infestations Bronchitis	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Infections and infestations Gastroenteritis	6.2% 2/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Infections and infestations Gastroenteritis bacterial	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Infections and infestations Influenza	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	12.5% 2/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	2.5% 2/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Infections and infestations Nasopharyngitis	9.4% 3/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	18.8% 3/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	12.5% 2/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	15.6% 5/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	13.6% 11/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Infections and infestations Otitis media	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Infections and infestations Rhinitis	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Infections and infestations Sinusitis	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	2.5% 2/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Infections and infestations Tooth abscess	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Infections and infestations Tooth infection	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Infections and infestations Upper respiratory tract infection	6.2% 2/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	2.5% 2/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Infections and infestations Urinary tract infection	6.2% 2/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	12.5% 2/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	3.7% 3/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Infections and infestations Viral upper respiratory tract infection	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Injury, poisoning and procedural complications Concussion	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	6.2% 1/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	3.1% 1/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	2.5% 2/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Injury, poisoning and procedural complications Post-traumatic neck syndrome	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/16 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	5.9% 1/17 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	0.00% 0/32 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).	1.2% 1/81 • start of treatment till end of treatment + 28 days, up to 113 days. Adverse events are reported based on the Treated Set (all patients who signed the informed consent and were treated with at least one dose of the trial medication).

Additional Information

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Boehringer Ingelheim

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Email: [email protected]

Results disclosure agreements

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