Trial Outcomes & Findings for A Study to Test Whether Taking BI 1358894 for 8 Weeks Helps Adults With Post-traumatic Stress Disorder (NCT NCT05103657)

Last Updated: 2024-11-07

Results Overview

CAPS-5 is a 30-item clinician-administered structured interview that can be used to, make current (past month) diagnosis of PTSD and assess PTSD symptoms over the past week. Each of the 20 symptom items in the CAPS-5 is rated from 0 (absent) to 4 (extreme/incapacitating) with a single severity score combining information about frequency/amount and intensity which is yield by summing each item scores and ranges from 0 to 80 with higher scores indicating higher symptom severity. Least Squares (LS) means and confidence intervals were estimated by restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) including the fixed categorical covariates of treatment, and the stratification indicator of presence of significant childhood trauma (yes vs. no), the continuous fixed covariate of baseline CAPS-5 total severity score, time since index event (in years) and the treatment-by-visit interaction. Patient is considered as random. Unstructured covariance matrix was used.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

318 participants

Primary outcome timeframe

The MMRM model is a longitudinal analysis and it incorporated CAPS-5 measurements from baseline, Week 4, and Week 8. MMRM estimates of change from baseline to Week 8 is reported.

Results posted on

2024-11-07

Participant Flow

This was a Phase II, 8-week-treatment, multicentre, randomised, double blind, placebocontrolled, parallel-group trial in patients with Post-Traumatic Stress Disorder (PTSD).

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 received orally, once daily for 8 consecutive weeks film-coated tablets of placebo matching BI 1358894. Placebo matching BI 1358894 was administered with water and in a consistent way, i.e. either with or without food every morning at approximately the same time.	BI 1358894 125 mg Patients received orally, once daily for 8 consecutive weeks 125 milligrams (mg) of BI 1358894. The dosage of 125 milligrams consisted of two film-coated tablets of 50 mg and 1 film-coated tablet of 25 mg. BI 135889 was administered with water and in a consistent way, i.e. either with or without food every morning at approximately the same time.
Overall Study STARTED	160	158
Overall Study Treated	159	157
Overall Study COMPLETED	133	127
Overall Study NOT COMPLETED	27	31

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Patients received orally, once daily for 8 consecutive weeks film-coated tablets of placebo matching BI 1358894. Placebo matching BI 1358894 was administered with water and in a consistent way, i.e. either with or without food every morning at approximately the same time.	BI 1358894 125 mg Patients received orally, once daily for 8 consecutive weeks 125 milligrams (mg) of BI 1358894. The dosage of 125 milligrams consisted of two film-coated tablets of 50 mg and 1 film-coated tablet of 25 mg. BI 135889 was administered with water and in a consistent way, i.e. either with or without food every morning at approximately the same time.
Overall Study Other reasons than listed	9	8
Overall Study Protocol deviation	2	2
Overall Study No reason available	5	4
Overall Study Burden of study procedures	3	1
Overall Study Perceived lack of efficacy	1	1
Overall Study Adverse Event	6	14
Overall Study Not Treated	1	1

Baseline Characteristics

A Study to Test Whether Taking BI 1358894 for 8 Weeks Helps Adults With Post-traumatic Stress Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=159 Participants Patients received orally, once daily for 8 consecutive weeks film-coated tablets of placebo matching BI 1358894. Placebo matching BI 1358894 was administered with water and in a consistent way, i.e. either with or without food every morning at approximately the same time.	BI 1358894 125 mg n=157 Participants Patients received orally, once daily for 8 consecutive weeks 125 milligrams (mg) of BI 1358894. The dosage of 125 milligrams consisted of two film-coated tablets of 50 mg and 1 film-coated tablet of 25 mg. BI 135889 was administered with water and in a consistent way, i.e. either with or without food every morning at approximately the same time.	Total n=316 Participants Total of all reporting groups
Age, Continuous	44.0 Years STANDARD_DEVIATION 12.9 • n=5 Participants	42.8 Years STANDARD_DEVIATION 12.4 • n=7 Participants	43.4 Years STANDARD_DEVIATION 12.6 • n=5 Participants
Sex: Female, Male Female	101 Participants n=5 Participants	111 Participants n=7 Participants	212 Participants n=5 Participants
Sex: Female, Male Male	58 Participants n=5 Participants	46 Participants n=7 Participants	104 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	29 Participants n=5 Participants	35 Participants n=7 Participants	64 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	130 Participants n=5 Participants	122 Participants n=7 Participants	252 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	6 Participants n=5 Participants	10 Participants n=7 Participants	16 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	46 Participants n=5 Participants	26 Participants n=7 Participants	72 Participants n=5 Participants
Race (NIH/OMB) White	102 Participants n=5 Participants	119 Participants n=7 Participants	221 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
CAPS-5 total severity score at baseline	41.3 score on a scale STANDARD_DEVIATION 9.9 • n=5 Participants	42.0 score on a scale STANDARD_DEVIATION 9.6 • n=7 Participants	41.6 score on a scale STANDARD_DEVIATION 9.8 • n=5 Participants

PRIMARY outcome

Timeframe: The MMRM model is a longitudinal analysis and it incorporated CAPS-5 measurements from baseline, Week 4, and Week 8. MMRM estimates of change from baseline to Week 8 is reported.

Population: Full analysis set (FAS): consisted of all patients in the treated set (TS) that had a baseline and at least one evaluable post-baseline measurement for the primary endpoint.

Outcome measures

Outcome measures
Measure	Placebo n=148 Participants Patients received orally, once daily for 8 consecutive weeks film-coated tablets of placebo matching BI 1358894. Placebo matching BI 1358894 was administered with water and in a consistent way, i.e. either with or without food every morning at approximately the same time.	BI 1358894 125 mg n=151 Participants Patients received orally, once daily for 8 consecutive weeks 125 milligrams (mg) of BI 1358894. The dosage of 125 milligrams consisted of two film-coated tablets of 50 mg and 1 film-coated tablet of 25 mg. BI 135889 was administered with water and in a consistent way, i.e. either with or without food every morning at approximately the same time.
Change From Baseline in Clinician-Administered Post Traumatic Stress Disorder (PTSD) Scale for DSM-5 (CAPS-5) Total Severity Score at Week 8	-17.19 units on a scale Interval -19.56 to -14.81	-17.13 units on a scale Interval -19.52 to -14.74

SECONDARY outcome

Timeframe: At baseline and at 8 weeks after start of treatment.

Population: Full analysis set (FAS): consisted of all patients in the treated set (TS) that had a baseline and at least one evaluable post-baseline measurement for the primary endpoint. Only participants with data from baseline and from Week 8 were included in the analysis of this endpoint.

Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (CAPS-5) is a 30-item clinician-administered structured interview that can be used to, make current (past month) diagnosis of PTSD and assess PTSD symptoms over the past week. Each of the 20 symptom items in the CAPS-5 is rated from 0 (absent) to 4 (extreme/incapacitating) with a single severity score combining information about frequency/amount and intensity which is yield by summing each item scores and ranges from 0 to 80 with higher scores indicating higher symptom severity. Number of participants with ≥30% CAPS-5 reduction from baseline at Week 8 is reported.

Outcome measures

Outcome measures
Measure	Placebo n=129 Participants Patients received orally, once daily for 8 consecutive weeks film-coated tablets of placebo matching BI 1358894. Placebo matching BI 1358894 was administered with water and in a consistent way, i.e. either with or without food every morning at approximately the same time.	BI 1358894 125 mg n=129 Participants Patients received orally, once daily for 8 consecutive weeks 125 milligrams (mg) of BI 1358894. The dosage of 125 milligrams consisted of two film-coated tablets of 50 mg and 1 film-coated tablet of 25 mg. BI 135889 was administered with water and in a consistent way, i.e. either with or without food every morning at approximately the same time.
CAPS-5 Response, Defined as ≥30% CAPS-5 Reduction From Baseline at Week 8	77 Participants	77 Participants

SECONDARY outcome

Timeframe: At baseline and at 8 weeks after start of treatment.

Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (CAPS-5) is a 30-item clinician-administered structured interview that can be used to, make current (past month) diagnosis of PTSD and assess PTSD symptoms over the past week. Each of the 20 symptom items in the CAPS-5 is rated from 0 (absent) to 4 (extreme/incapacitating) with a single severity score combining information about frequency/amount and intensity which is yield by summing each item scores and ranges from 0 to 80 with higher scores indicating higher symptom severity. Number of participants with ≥50% CAPS-5 reduction from baseline at Week 8 is reported.

Outcome measures

Outcome measures
Measure	Placebo n=129 Participants Patients received orally, once daily for 8 consecutive weeks film-coated tablets of placebo matching BI 1358894. Placebo matching BI 1358894 was administered with water and in a consistent way, i.e. either with or without food every morning at approximately the same time.	BI 1358894 125 mg n=129 Participants Patients received orally, once daily for 8 consecutive weeks 125 milligrams (mg) of BI 1358894. The dosage of 125 milligrams consisted of two film-coated tablets of 50 mg and 1 film-coated tablet of 25 mg. BI 135889 was administered with water and in a consistent way, i.e. either with or without food every morning at approximately the same time.
CAPS-5 Response, Defined as ≥50% CAPS-5 Reduction From Baseline at Week 8	53 Participants	50 Participants

SECONDARY outcome

Timeframe: The MMRM model is a longitudinal analysis and it incorporated PCL-5 measurements from baseline, Week 4, and Week 8. MMRM estimates of change from baseline to Week 8 is reported.

Population: Full analysis set (FAS): consisted of all patients in the TS that had a baseline and at least one evaluable post-baseline measurement for the primary endpoint.

The PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (PCL-5) is a 20-item patient-reported assessment designed to measure the presence and severity of PTSD symptoms in the past month. Items on the PCL-5 correspond with DSM-5 criteria for PTSD. Each item is rated on a five point Likert scale, from 0 (not at all) to 4 (extremely) yielding a total score from 0-80 with higher scores indicating higher severity of the symptoms. Least Square (LS) means and confidence intervals were estimated by restricted maximum likelihood (REML)-based mixed model repeated measures (MMRM) including the fixed categorical covariates of treatment, and the stratification indicator of presence of significant childhood trauma (yes vs. no), the continuous fixed covariate of baseline CAPS-5 total severity score, time since index event (in years) and the treatment-by-visit interaction. Patient is considered as random. Unstructured covariance matrix was used.

Outcome measures

Outcome measures
Measure	Placebo n=148 Participants Patients received orally, once daily for 8 consecutive weeks film-coated tablets of placebo matching BI 1358894. Placebo matching BI 1358894 was administered with water and in a consistent way, i.e. either with or without food every morning at approximately the same time.	BI 1358894 125 mg n=151 Participants Patients received orally, once daily for 8 consecutive weeks 125 milligrams (mg) of BI 1358894. The dosage of 125 milligrams consisted of two film-coated tablets of 50 mg and 1 film-coated tablet of 25 mg. BI 135889 was administered with water and in a consistent way, i.e. either with or without food every morning at approximately the same time.
Change From Baseline on the PTSD Checklist for DSM-5 (PCL-5) Total Score at Week 8	-19.21 units on a scale Interval -21.8 to -16.61	-18.55 units on a scale Interval -21.12 to -15.98

Adverse Events

Placebo

Serious events: 10 serious events

Other events: 38 other events

Deaths: 1 deaths

BI 1358894 125 mg

Serious events: 12 serious events

Other events: 56 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=159 participants at risk Patients received orally, once daily for 8 consecutive weeks film-coated tablets of placebo matching BI 1358894. Placebo matching BI 1358894 was administered with water and in a consistent way, i.e. either with or without food every morning at approximately the same time.	BI 1358894 125 mg n=157 participants at risk Patients received orally, once daily for 8 consecutive weeks 125 milligrams (mg) of BI 1358894. The dosage of 125 milligrams consisted of two film-coated tablets of 50 mg and 1 film-coated tablet of 25 mg. BI 135889 was administered with water and in a consistent way, i.e. either with or without food every morning at approximately the same time.
Gastrointestinal disorders Nausea	9.4% 15/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	4.5% 7/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
General disorders Fatigue	1.3% 2/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	6.4% 10/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
Investigations Weight increased	1.9% 3/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	7.0% 11/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
Metabolism and nutrition disorders Increased appetite	1.3% 2/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	5.1% 8/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
Nervous system disorders Dizziness	5.0% 8/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	7.6% 12/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
Nervous system disorders Headache	12.6% 20/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	21.7% 34/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Measure	Placebo n=159 participants at risk Patients received orally, once daily for 8 consecutive weeks film-coated tablets of placebo matching BI 1358894. Placebo matching BI 1358894 was administered with water and in a consistent way, i.e. either with or without food every morning at approximately the same time.	BI 1358894 125 mg n=157 participants at risk Patients received orally, once daily for 8 consecutive weeks 125 milligrams (mg) of BI 1358894. The dosage of 125 milligrams consisted of two film-coated tablets of 50 mg and 1 film-coated tablet of 25 mg. BI 135889 was administered with water and in a consistent way, i.e. either with or without food every morning at approximately the same time.
Gastrointestinal disorders Haematochezia	0.00% 0/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	0.64% 1/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
Infections and infestations Appendicitis	0.00% 0/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	0.64% 1/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
Infections and infestations Cellulitis	0.63% 1/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	0.00% 0/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
Infections and infestations Wound infection	0.63% 1/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	0.00% 0/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
Injury, poisoning and procedural complications Toxicity to various agents	0.63% 1/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	0.00% 0/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	0.64% 1/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	0.64% 1/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.63% 1/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	0.64% 1/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial adenocarcinoma	0.00% 0/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	0.64% 1/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
Nervous system disorders Amnesia	0.63% 1/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	0.00% 0/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
Nervous system disorders Encephalopathy	0.00% 0/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	0.64% 1/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
Psychiatric disorders Depression	0.00% 0/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	0.64% 1/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
Psychiatric disorders Panic attack	0.63% 1/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	0.64% 1/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
Psychiatric disorders Suicidal ideation	2.5% 4/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	2.5% 4/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
Psychiatric disorders Suicide attempt	0.63% 1/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	0.64% 1/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
Vascular disorders Deep vein thrombosis	0.63% 1/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	0.00% 0/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.
Vascular disorders Hypertension	0.63% 1/159 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.	0.00% 0/157 • "All-Cause Mortality" "Serious Adverse Events" and "Other Adverse Events": From first administration of BI 1358894 or placebo to last administration of BI 1358894 or placebo + 4 weeks of residual effect period, up to 13 weeks. Treated Set (TS): consisted of all patients that were randomised and had received at least one administration of trial drug. Patients were analysed according to the actual received treatment.