Trial Outcomes & Findings for A Study to Test Different Doses of BI 1358894 and Find Out Whether They Reduce Symptoms in People With Borderline Personality Disorder (NCT NCT04566601)

Last Updated: 2024-01-30

Results Overview

The ZAN-BPD scale reflects the nine DSM-5 criteria and the scale has 4 domain scores that reflect core areas of BPD (i.e., affective, cognitive, impulsive and interpersonal symptoms). The ZAN-BPD scale includes a 5-point rating scale (i.e., 0 = no symptoms to 4 = severe symptoms) for each criterion. The total ZAN-BPD score is the sum of the 4 domain scores and ranges from 0 to 36 where higher scores mean severe symptoms. Least Squares (LS) mean and standard error were estimated by restricted maximum likelihood-based mixed effects model repeated measures (REML-based MMRM) including the fixed categorical covariates of treatment, visit (baseline and Week 1, 2, 4, 6, 8 and 10) and the baseline ZAN-BPD total score strata indicator (\<=18 vs. \>=19), the continuous fixed covariate of baseline ZAN-BPD total score, and treatment-by-visit interaction, as well as baseline-by-visit interaction. LS mean (standard error) for Week 10 are reported.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

390 participants

Primary outcome timeframe

The change from baseline at Week 10 in the total ZAN-BPD score was calculated using the MMRM model which is a longitudinal analyses and it incorporates ZAN-BPD measurements from baseline, Weeks 1, 2, 4, 6, 8 and Week 10.

Results posted on

2024-01-30

Participant Flow

This was a Phase II, 12-week multicenter, multinational, randomised, double-blind, placebo-controlled, parallel-group trial in patients with borderline personality disorder (BPD). Eligible patients with BPD were randomised to receive either BI 1358894 or placebo in a 2.5:1:1:1:2 ratio (placebo or BI 1358894 5 milligram (mg), 25 mg, 75 mg, or 125 mg), for 12 weeks. This trial included a screening period, a 12-week randomised treatment period, and a 4-week follow-up period.

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 Patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 milligram (mg), one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 5mg Patients were administered for 12 weeks once daily, orally one film-coated tablet of 5 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 25mg Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 75mg Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg.	BI 1358894 125mg Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg.
Overall Study STARTED	128	52	53	53	104
Overall Study COMPLETED	95	40	35	40	77
Overall Study NOT COMPLETED	33	12	18	13	27

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 milligram (mg), one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 5mg Patients were administered for 12 weeks once daily, orally one film-coated tablet of 5 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 25mg Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 75mg Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg.	BI 1358894 125mg Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg.
Overall Study Other than listed	13	4	2	1	4
Overall Study Protocol deviation	3	0	1	1	1
Overall Study Technical problems	0	0	1	0	0
Overall Study No reason available	3	2	7	1	5
Overall Study Burden of study procedures	3	0	0	3	1
Overall Study Change of residence	2	2	0	1	2
Overall Study Perceived lack of efficacy	2	0	1	1	2
Overall Study Adverse Event	7	4	6	5	12

Baseline Characteristics

A Study to Test Different Doses of BI 1358894 and Find Out Whether They Reduce Symptoms in People With Borderline Personality Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=128 Participants Patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 milligram (mg), one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 5mg n=52 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 5 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 25mg n=53 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 75mg n=53 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg.	BI 1358894 125mg n=104 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg.	Total n=390 Participants Total of all reporting groups
Age, Continuous	30.4 Years STANDARD_DEVIATION 9.9 • n=5 Participants	29.2 Years STANDARD_DEVIATION 9.6 • n=7 Participants	31.0 Years STANDARD_DEVIATION 11.1 • n=5 Participants	30.6 Years STANDARD_DEVIATION 9.7 • n=4 Participants	29.9 Years STANDARD_DEVIATION 11.2 • n=21 Participants	30.2 Years STANDARD_DEVIATION 10.3 • n=8 Participants
Sex: Female, Male Female	107 Participants n=5 Participants	50 Participants n=7 Participants	48 Participants n=5 Participants	48 Participants n=4 Participants	83 Participants n=21 Participants	336 Participants n=8 Participants
Sex: Female, Male Male	21 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	21 Participants n=21 Participants	54 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	50 Participants n=5 Participants	17 Participants n=7 Participants	25 Participants n=5 Participants	20 Participants n=4 Participants	34 Participants n=21 Participants	146 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	78 Participants n=5 Participants	35 Participants n=7 Participants	28 Participants n=5 Participants	33 Participants n=4 Participants	70 Participants n=21 Participants	244 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	5 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	6 Participants n=21 Participants	15 Participants n=8 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants	7 Participants n=21 Participants	18 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants
Race (NIH/OMB) Black or African American	8 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants	19 Participants n=8 Participants
Race (NIH/OMB) White	112 Participants n=5 Participants	44 Participants n=7 Participants	46 Participants n=5 Participants	46 Participants n=4 Participants	85 Participants n=21 Participants	333 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants	4 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
ZAN-BPD total score at Baseline	16.6 score on a scale STANDARD_DEVIATION 5.0 • n=5 Participants	15.7 score on a scale STANDARD_DEVIATION 5.4 • n=7 Participants	15.8 score on a scale STANDARD_DEVIATION 4.8 • n=5 Participants	16.1 score on a scale STANDARD_DEVIATION 4.6 • n=4 Participants	16.4 score on a scale STANDARD_DEVIATION 5.2 • n=21 Participants	16.3 score on a scale STANDARD_DEVIATION 5.0 • n=8 Participants

PRIMARY outcome

Timeframe: The change from baseline at Week 10 in the total ZAN-BPD score was calculated using the MMRM model which is a longitudinal analyses and it incorporates ZAN-BPD measurements from baseline, Weeks 1, 2, 4, 6, 8 and Week 10.

Population: Full analysis set (FAS) consisted of all patients in TS who had a baseline and at least one evaluable post-baseline measurement for the primary endpoint. Since the MMRM included the measurements from baseline, Week 1, Week 2, Week 4, Week 6, Week 8 and Week 10, number of participants analyzed for the primary endpoint for each arm are the participants who had a ZAN-BPD score value at baseline and one ZAN-BPD score value at one of the post-baseline timepoints up to Week 10.

Outcome measures

Outcome measures
Measure	Placebo n=124 Participants Patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 milligram (mg), one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 5mg n=52 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 5 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 25mg n=52 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 75mg n=52 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg.	BI 1358894 125mg n=102 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg.
Change From Baseline in ZANarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) Total Score at Week 10	-8.7 units on a scale Standard Error 0.5	-8.0 units on a scale Standard Error 0.9	-9.2 units on a scale Standard Error 0.9	-8.9 units on a scale Standard Error 0.8	-9.0 units on a scale Standard Error 0.6

SECONDARY outcome

Timeframe: Baseline and at Week 10.

Population: Full analysis set (FAS) consisted of all patients in TS who had a baseline and at least one evaluable post-baseline measurement for the primary endpoint. Only participants with ZAN-BPD total score at baseline and at Week 10 are reported.

Number of participants with ZAN-BPD response is reported. ZAN-BPD response was defined as ≥30% ZAN-BPD reduction from baseline at Week 10. The ZAN-BPD scale reflects the nine DSM-5 criteria, and the scale has 4 domain scores that reflect core areas of BPD (i.e., affective, cognitive, impulsive and interpersonal symptoms). The ZAN-BPD scale includes a 5-point rating scale (i.e., 0 = no symptoms to 4 = severe symptoms) for each criterion. The total ZAN-BPD score is the sum of the 4 domain scores and ranges from 0 to 36 where higher scores mean severe symptoms.

Outcome measures

Outcome measures
Measure	Placebo n=92 Participants Patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 milligram (mg), one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 5mg n=37 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 5 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 25mg n=33 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 75mg n=41 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg.	BI 1358894 125mg n=74 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg.
ZANarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) Response: Defined as ≥30% ZAN-BPD Reduction From Baseline at Week 10	68 Participants	22 Participants	28 Participants	34 Participants	59 Participants

SECONDARY outcome

Timeframe: Change from baseline in DERS-16 total score at Week 10 was calculated using the MMRM model which is a longitudinal analyses and it incorporates DERS-16 measurements from baseline, Weeks 1, 2, 4, 6, 8 and Week 10.

Population: Full analysis set (FAS) consisted of all patients in TS who had a baseline and at least one evaluable post-baseline measurement for the primary endpoint. Since the MMRM included the measurements from baseline, Week 1, Week 2, Week 4, Week 6, Week 8 and Week 10, number of participants analyzed for the primary endpoint for each arm are the participants who had a DERS-16 total score value at baseline and a DERS-16 total score value at one of the post-baseline timepoints up to Week 10.

The DERS is a self-report measure of emotion regulation difficulties. It consists of 16 items that assess non-acceptance of negative emotions, inability to engage in goal-directed behaviors when distressed, difficulties controlling impulsive behaviors when distressed, limited access to emotion regulation strategies perceived as effective, and lack of emotional clarity. Each item is scored from 1 (almost never (0-10%)) to 5 (almost always (91-100%)). Total DERS-16 can range from 16 to 80, with higher scores reflecting greater levels of emotion dysregulation. Least Squares (LS) mean and standard error were estimated by REML-based MMRM including the fixed categorical covariates of treatment, visit (baseline and Week 1, 2, 4, 6, 8 and 10) and the continuous fixed covariate of baseline DERS-16 total score, and treatment-by-visit interaction, as well as baseline-by-visit interaction. Patient was considered as random. LS mean (standard error) for Week 10 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=124 Participants Patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 milligram (mg), one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 5mg n=52 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 5 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 25mg n=52 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 75mg n=52 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg.	BI 1358894 125mg n=102 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg.
Change From Baseline in Difficulties in Emotion Regulation Scale (DERS-16) Total Score at Week 10	-9.77 units on a scale Standard Error 1.4	-9.87 units on a scale Standard Error 2.1	-9.76 units on a scale Standard Error 2.2	-10.56 units on a scale Standard Error 2.1	-8.60 units on a scale Standard Error 1.5

SECONDARY outcome

Timeframe: Change from baseline in STAI-S total score at Week 10 was calculated using the MMRM model which is a longitudinal analyses and it incorporates STAI-S measurements from baseline, Weeks 1, 2, 4, 6, 8 and Week 10.

Population: Full analysis set (FAS) consisted of all patients in TS who had a baseline and at least one evaluable post-baseline measurement for the primary endpoint. Since the MMRM included the measurements from baseline, Week 1, Week 2, Week 4, Week 6, Week 8 and Week 10, number of participants analyzed for the primary endpoint for each arm are the participants who had a STAI-S total score value at baseline and a STAI-S total score value at one of the post-baseline timepoints up to Week 10.

The STAI-S consists of 20 item state anxiety questions that evaluate how respondents feel "right now, at this moment". All items are rated on a weighted score of 1 to 4 scale (e.g. from 'Almost Never to 'Almost Always'); with higher scores indicating greater anxiety. STAI-S score ranges from 20 to 80 where higher scores indicate greater anxiety. Least Squares (LS) mean and standard error were estimated by restricted maximum likelihood-based mixed effects model repeated measures (REML-based MMRM) including the fixed categorical covariates of treatment, visit (baseline and Week 1, 2, 4, 6, 8, 10) and the continuous fixed covariate of baseline STAI-S total score, and treatment-by-visit interaction, as well as baseline-by-visit interaction. Patient was considered as random. LS mean (standard error) for Week 10 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=124 Participants Patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 milligram (mg), one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 5mg n=52 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 5 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 25mg n=52 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 75mg n=52 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg.	BI 1358894 125mg n=102 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg.
Change From Baseline in State-Trait Anxiety Inventory (STAI-S) Total Score at Week 10	-6.64 units on a scale Standard Error 1.2	-8.71 units on a scale Standard Error 1.9	-5.43 units on a scale Standard Error 2.0	-7.00 units on a scale Standard Error 1.8	-5.49 units on a scale Standard Error 1.3

SECONDARY outcome

Timeframe: Change from baseline in PHQ-9 total score at Week 10 was calculated using the MMRM model which is a longitudinal analyses and it incorporates PHQ-9 measurements from baseline, Weeks 1, 2, 4, 6, 8 and Week 10.

Population: Full analysis set (FAS) consisted of all patients in TS who had a baseline and at least one evaluable post-baseline measurement for the primary endpoint. Since the MMRM included the measurements from baseline, Week 1, Week 2, Week 4, Week 6, Week 8 and Week 10, number of participants analyzed for the primary endpoint for each arm are the participants who had a PHQ-9 total score value at baseline and a PHQ-9 total score value at one of the post-baseline timepoints up to Week 10.

The PHQ-9 is a 9-item brief self-reported tool used for screening, diagnosing, monitoring and measuring the severity of depression. PHQ-9 has a maximum total score of 27. Depression Severity is assessed as: none (0-4), mild (5-9), moderate (10-14), moderately severe (15-19), or severe (20-27). Least Squares (LS) mean and standard error were estimated by restricted maximum likelihood-based mixed effects model repeated measures (REML-based MMRM) including the fixed categorical covariates of treatment, visit (baseline and Week 1, 2, 4, 6, 8, 10) and the continuous fixed covariate of baseline PHQ-9 total score, and treatment-by-visit interaction, as well as baseline-by-visit interaction. Patient was considered as random. LS mean (standard error) for Week 10 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=124 Participants Patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 milligram (mg), one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 5mg n=52 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 5 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 25mg n=52 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 75mg n=52 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg.	BI 1358894 125mg n=102 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg.
Change From Baseline in Patient Health Questionnaire (PHQ-9) Total Score at Week 10	-1.30 units on a scale Standard Error 0.6	-3.13 units on a scale Standard Error 0.9	-1.07 units on a scale Standard Error 0.9	-1.57 units on a scale Standard Error 0.9	-1.43 units on a scale Standard Error 0.6

SECONDARY outcome

Timeframe: Change from baseline in CGI-S scale at Week 10 was calculated using the MMRM model which is a longitudinal analyses and it incorporates CGI-S measurements from baseline, Weeks 1, 2, 4, 6, 8 and Week 10.

Population: Full analysis set (FAS) consisted of all patients in TS who had a baseline and at least one evaluable post-baseline measurement for the primary endpoint. Since the MMRM included the measurements from baseline, Week 1, Week 2, Week 4, Week 6, Week 8 and Week 10, number of participants analyzed for the primary endpoint for each arm are the participants who had a CGI-S scale value at baseline and a CGI-S scale value at one of the post-baseline timepoints up to Week 10.

The CGI-S rating scale measures the clinician's impression of the severity of illness exhibited by a participant. The CGI-S only question states "Considering your total clinical experience with this particular population, please choose the response below that best describes how mentally ill the patient was over the past week?", and is rated on the following seven-point scale: 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. Least Squares (LS) mean and standard error were estimated by REML-based MMRM including the fixed categorical covariates of treatment, visit (baseline and Week 1, 2, 4, 6, 8, 10) and the continuous fixed covariate of baseline CGI-S total score, and treatment-by-visit interaction, as well as baseline-by-visit interaction. Patient was considered as random. LS mean (standard error) for Week 10 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=124 Participants Patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 milligram (mg), one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 5mg n=52 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 5 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 25mg n=51 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 75mg n=51 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg.	BI 1358894 125mg n=102 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg.
Change From Baseline in Clinical Global Impression Severity Scale (CGI-S) at Week 10	-1.23 units on a scale Standard Error 0.1	-1.29 units on a scale Standard Error 0.2	-1.47 units on a scale Standard Error 0.2	-1.24 units on a scale Standard Error 0.2	-1.42 units on a scale Standard Error 0.1

SECONDARY outcome

Timeframe: Change from baseline in PGI-S scale at Week 10 was calculated using the MMRM model which is a longitudinal analyses and it incorporates PGI-S measurements from baseline, Weeks 1, 2, 4, 6, 8 and Week 10.

Population: Full analysis set (FAS) consisted of all patients in TS who had a baseline and at least one evaluable post-baseline measurement for the primary endpoint. Since the MMRM included the measurements from baseline, Week 1, Week 2, Week 4, Week 6, Week 8 and Week 10, number of participants analyzed for the primary endpoint for each arm are the participants who had a PGI-S scale value at baseline and a PGI-S scale value at one of the post-baseline timepoints up to Week 10.

The PGI-S measures the patient's impression of the severity of their illness. It is a single item 5-point scale that asks patients to rate the severity of their illness. The PGI-S question states "Please choose the response below that best describes the overall severity of your symptoms of Borderline Personality Disorder at this time. (Select one response)": 1=No symptoms; 2=Mild; 3=Moderate; 4=Severe; 5=Very severe. Least Squares (LS) mean and standard error were estimated by restricted maximum likelihood-based mixed effects model repeated measures (REML-based MMRM) including the fixed categorical covariates of treatment, visit (baseline and Week 1, 2, 4, 6, 8,10) and the continuous fixed covariate of baseline PGI-S total score, and treatment-by-visit interaction, as well as baseline-by-visit interaction. Patient was considered as random. LS means (standard error) for Week 10 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=124 Participants Patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 milligram (mg), one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 5mg n=52 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 5 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 25mg n=50 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 75mg n=52 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg.	BI 1358894 125mg n=102 Participants Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg.
Change From Baseline in Patient Global Impression Severity Scale (PGI-S) at Week 10	-0.61 units on a scale Standard Error 0.1	-0.73 units on a scale Standard Error 0.1	-0.73 units on a scale Standard Error 0.2	-0.64 units on a scale Standard Error 0.1	-0.69 units on a scale Standard Error 0.1

Adverse Events

Placebo

Serious events: 11 serious events

Other events: 75 other events

Deaths: 0 deaths

BI 1358894 5mg

Serious events: 4 serious events

Other events: 32 other events

Deaths: 0 deaths

BI 1358894 25mg

Serious events: 3 serious events

Other events: 40 other events

Deaths: 0 deaths

BI 1358894 75mg

Serious events: 4 serious events

Other events: 34 other events

Deaths: 0 deaths

BI 1358894 125mg

Serious events: 16 serious events

Other events: 61 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=128 participants at risk Patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 milligram (mg), one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 5mg n=52 participants at risk Patients were administered for 12 weeks once daily, orally one film-coated tablet of 5 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 25mg n=53 participants at risk Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 75mg n=53 participants at risk Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg.	BI 1358894 125mg n=104 participants at risk Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg.
Cardiac disorders Myocardial infarction	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.96% 1/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Gastrointestinal disorders Abdominal pain	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Gastrointestinal disorders Cannabinoid hyperemesis syndrome	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Gastrointestinal disorders Nausea	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Gastrointestinal disorders Oesophageal varices haemorrhage	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.96% 1/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Gastrointestinal disorders Vomiting	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
General disorders Death	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.96% 1/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Hepatobiliary disorders Cholelithiasis	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.96% 1/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Hepatobiliary disorders Jaundice cholestatic	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.96% 1/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Immune system disorders Anaphylactic reaction	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.96% 1/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Infections and infestations COVID-19	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Infections and infestations Hepatitis A	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Infections and infestations Pneumonia	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Infections and infestations Wound abscess	0.78% 1/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Injury, poisoning and procedural complications Comminuted fracture	0.78% 1/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Injury, poisoning and procedural complications Forearm fracture	0.78% 1/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Metabolism and nutrition disorders Dehydration	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Metabolism and nutrition disorders Metabolic acidosis	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.78% 1/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.96% 1/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Psychiatric disorders Aggression	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.96% 1/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Psychiatric disorders Confusional state	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Psychiatric disorders Depression	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.96% 1/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Psychiatric disorders Drug abuse	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.96% 1/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Psychiatric disorders Panic attack	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.96% 1/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Psychiatric disorders Post-traumatic stress disorder	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Psychiatric disorders Suicidal behaviour	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.96% 1/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Psychiatric disorders Suicidal ideation	6.2% 8/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	5.8% 3/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	5.8% 6/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Psychiatric disorders Suicide attempt	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.96% 1/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Renal and urinary disorders Calculus urinary	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.96% 1/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.96% 1/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.

Other adverse events

Other adverse events
Measure	Placebo n=128 participants at risk Patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 milligram (mg), one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 5mg n=52 participants at risk Patients were administered for 12 weeks once daily, orally one film-coated tablet of 5 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 25 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 25mg n=53 participants at risk Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894. In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and two film-coated tablets of placebo matching BI 1358894 50 mg.	BI 1358894 75mg n=53 participants at risk Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and one film-coated tablet of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=75 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg and one film-coated tablet of placebo matching BI 1358894 50 mg.	BI 1358894 125mg n=104 participants at risk Patients were administered for 12 weeks once daily, orally one film-coated tablet of 25 milligram (mg) of BI 1358894 and two film-coated tablets of 50 milligram (mg) of BI 1358894 (total BI 1358894 dose=125 mg). In order to maintain blinding in regard to each treatment group since BI 1358894 tablets (5 mg, 25 mg, 50 mg) are different sizes, patients were also administered for 12 weeks once daily, orally one film-coated tablet of placebo matching BI 1358894 5 mg.
Gastrointestinal disorders Constipation	1.6% 2/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	3.8% 2/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	9.4% 5/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.96% 1/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Gastrointestinal disorders Diarrhoea	7.8% 10/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	7.7% 4/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	5.7% 3/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	5.7% 3/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	3.8% 4/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Gastrointestinal disorders Dyspepsia	0.78% 1/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	3.8% 2/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	5.7% 3/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Gastrointestinal disorders Nausea	13.3% 17/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	9.6% 5/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	9.4% 5/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	3.8% 2/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	6.7% 7/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
General disorders Fatigue	8.6% 11/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	11.5% 6/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	11.3% 6/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	8.7% 9/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
General disorders Pyrexia	1.6% 2/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	7.7% 4/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	5.7% 3/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	3.8% 2/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.96% 1/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Infections and infestations COVID-19	12.5% 16/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	5.8% 3/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	11.3% 6/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	6.7% 7/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Infections and infestations Influenza	6.2% 8/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	5.8% 3/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	6.7% 7/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Infections and infestations Nasopharyngitis	7.8% 10/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	5.8% 3/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	5.7% 3/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	13.2% 7/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	8.7% 9/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Infections and infestations Pharyngitis	1.6% 2/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	5.8% 3/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Investigations Weight increased	0.00% 0/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	5.7% 3/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	4.8% 5/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Metabolism and nutrition disorders Hyperinsulinaemia	0.78% 1/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	5.7% 3/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Metabolism and nutrition disorders Increased appetite	3.1% 4/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	7.7% 8/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Nervous system disorders Disturbance in attention	3.9% 5/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	5.8% 3/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	3.8% 2/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	7.5% 4/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Nervous system disorders Dizziness	7.0% 9/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	11.5% 6/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	9.4% 5/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	13.2% 7/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	7.7% 8/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Nervous system disorders Headache	25.0% 32/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	34.6% 18/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	43.4% 23/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	28.3% 15/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	31.7% 33/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Nervous system disorders Somnolence	3.1% 4/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	5.8% 3/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	9.4% 5/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	11.3% 6/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	3.8% 4/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Psychiatric disorders Anxiety	7.0% 9/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	11.5% 6/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	5.7% 3/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	5.7% 3/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	2.9% 3/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Psychiatric disorders Initial insomnia	3.9% 5/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	5.7% 3/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Psychiatric disorders Insomnia	7.8% 10/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	9.6% 5/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	9.4% 5/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	7.5% 4/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	5.8% 6/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Psychiatric disorders Intentional self-injury	5.5% 7/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	3.8% 2/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	3.8% 2/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	2.9% 3/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Reproductive system and breast disorders Dysmenorrhoea	2.3% 3/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	9.4% 5/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	3.8% 4/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Respiratory, thoracic and mediastinal disorders Cough	5.5% 7/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 1/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	3.8% 2/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	1.9% 2/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.0% 9/128 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	5.8% 3/52 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	0.00% 0/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	3.8% 2/53 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.	3.8% 4/104 • From first dose of study drug administration until the last dose of study drug administration + 4 weeks of residual effect period, up to 17 weeks. Treated set (TS) consisted of all patients who were randomised and that received at least 1 administration of trial medication. Patients were analysed according to the actual received treatment.

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