Pharmacokinetics, Safety and Tolerability of Doses of BI 1015550 in Healthy Chinese Male and Female Subjects (Open-label, Parallel Group Design)
Phase: PHASE1
Conditions: Healthy
Sponsor: Boehringer Ingelheim

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Clinical Trial Protocol
 
Document Number:
c39429830-02
BI Trial No.
1305-0024
BI Investigational
Medicinal Product
BI 1015550
Title
Pharmacokinetics, safety and tolerability of doses of BI 
1015550 in healthy Chinese male and female subjects (open-
label, parallel group design)
Lay Title
A study in healthy Chinese people to test how different doses 
of BI 1015550 are taken up in the body
Clinical Phase
I
Clinical Trial Leader
Phone: 
 Investigator
Current Version, Date
Version 2.0, 16 Mar 2023
Original Protocol Date
29 Jun 2022
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CLINICAL TRIAL PROTOCOL SYNOPSIS
Company name
Boehringer Ingelheim
Original protocol date
29 Jun 2022 
Revision date
16 Mar 2023
BI trial number
1305-0024
Title of trial
Pharmacokinetics, safety and tolerability of doses of BI 1015550 in healthy Chinese 
male and female subjects (open-label, parallel group design)
Investigator 
Trial site
 
Clinical phase
I
Trial rationale
This trial is conducted to investigate the PK and safety of BI 1015550 in Chinese 
healthy subjects.
Trial objectives
To investigate the pharmacokinetics, safety and tolerability following single dose of 
BI 1015550
Trial endpoints
Primary endpoints: AUC0-∞and Cmax of BI 1015550
Secondary endpoint regarding Safety: Occurrence of any treatment-emergent 
adverse event. This is expressed as the percentage of subjects treated with 
investigational drug who experience such an event.
Trial design
Open-label without placebo, single-dose, parallel-group design
Number of subjects 
total entered
Up to 32 subjects including up to 8 subjects for replacement of early 
discontinuation
on each treatment
12 per dose group
Diagnosis
Not applicable
Main inclusion criteria
Healthy Chinese subjects, age of 18 to 55 years (inclusive), body mass index (BMI) 
of 18.5 to 28.0 kg/m2 (inclusive) 

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Test product
BI 1015550
dose
Single doses of 9 mg and 18 mg
mode of 
administration
Oral with 240 mL of water after an overnight fast of at least 10 h
Comparator product
Not applicable
dose
Not applicable
mode of admin.
Not applicable
Duration of treatment
Single dose
Statistical methods
Descriptive statistics will be calculated for all endpoints.

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FLOW CHART
Visit
Day
Planned time (relative to 
drug administration)  
[h:min]
Approximate clock time  of 
actual day [h:min]
Event and comment
Safety laboratory
PK blood
12-lead ECG9
Vital signs (BP, PR)
Questioning for AEs and 
concomitant therapy 6
1
-28 to -1
Screening (SCR)1
xA,1
x
x
2
-1
-12:00
20:00
Admission to trial site2
x5,2
x2
1
-1:00
07:00
Allocation to treatment8 (visit 2 only)
x7, B
x10
x10
x10
x10
0:00
08:00
Drug administration
0:30
08:30
x
0:45
08:45
x
1:00
09:00
x
1:15
09:15
x
1:30
09:30
x
1:45
09:45
x
2:00
10:00
240 mL fluid intake
x
x
2:30
10:30
x
3:00
11:00
x
4:00
12:00
240 mL fluid intake, thereafter lunch3
x
x
x
6:00
14:00
x
8:00
16:00
x
11:00
19:00
Dinner
12:00
20:00
x
x 
2
24:00
08:00
Breakfast3 (voluntary),
discharge from trial site
xB
x
x
x
x
3
48:00
08:00
Ambulatory visit
x
x
4
72:00
08:00
Ambulatory visit
x
x
5
96:00
08:00
Ambulatory visit
x
x
6
120:00
08:00
Ambulatory visit
xB
x
x
7
144:00
08:00
Ambulatory visit
x
x
3
8 to 14
End of study (EoS) examination4
xC
x
x
x
1.
Subject must be informed and written informed consent obtained prior to starting any screening procedures. Screening 
procedures include physical examination, check of vital signs, ECG, safety laboratory (including drug screening), 
demographics (including determination of body height and weight, smoking status and alcohol history), relevant 
medical history, concomitant therapy and review of inclusion/exclusion criteria.
2.
The time is approximate; the procedure is to be performed and completed within the 12 h prior to drug administration.
3.
If several actions are indicated at the same time, the intake of meals will be the last action.
4.
At the end of study (synonym for end of trial), the EoS examination includes physical examination, vital signs, ECG, 
safety laboratory (including pregnancy test in women), recording of AEs and concomitant therapies.
5.
Only urine drug screening and alcohol breath test as well as pregnancy test in women will be done at this time
6.
AEs and concomitant therapies will be recorded throughout the trial, but will be specifically asked for at the times
indicated in the Flow Chart above.
7.
Safety laboratory to be taken and to be medically evaluated within 3 days prior to administration of study drug; this 
safety laboratory assessment can be omitted if the screening examination is performed on Days -3, -2 or -1. Letters A, 
B, and C define different sets of safety laboratory examinations (see Section 5.2.3)
8. 
The time is an approximate. The procedure is to be completed no later than 10 hours prior to drug administration.

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9. 
The ECG recording must be performed in triplicate ECGs at this time. The 3 triplicate ECGs are recorded within 
approximately 1 h. The recordings should be separated by about 5 min intervals. 
10.  Trial measurements and assessments scheduled to occur ‘before’ trial medication administration on Day 1 are to be 
performed and completed within a 3 h-period prior to the trial drug administration.

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TABLE OF CONTENTS
TITLE PAGE ...........................................................................................................................1
CLINICAL TRIAL PROTOCOL SYNOPSIS .....................................................................2
FLOW CHART........................................................................................................................4
TABLE OF CONTENTS ........................................................................................................6
ABBREVIATIONS AND DEFINITIONS...........................................................................10
1.
INTRODUCTION......................................................................................................12
1.1
MEDICAL BACKGROUND ........................................................................12
1.3
RATIONALE FOR PERFORMING THE TRIAL ....................................16
1.4
BENEFIT - RISK ASSESSMENT................................................................17
1.4.1
Benefits..............................................................................................17
1.4.2
Risks ..................................................................................................17
1.4.3
Discussion..........................................................................................20
2.
TRIAL OBJECTIVES AND ENDPOINTS.............................................................21
2.1
MAIN OBJECTIVES, PRIMARY AND SECONDARY ENDPOINTS...21
2.1.1
Main objectives.................................................................................21
2.1.2
Primary endpoints............................................................................21
2.1.3
Secondary endpoints........................................................................21
2.2.2.1
Safety and tolerability ...................................................21
3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION ................................23
3.1
OVERALL TRIAL DESIGN ........................................................................23
3.2
DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE OF 
CONTROL GROUP ......................................................................................23
3.3
SELECTION OF TRIAL POPULATION...................................................23
3.3.1
Main diagnosis for trial entry .........................................................23
3.3.2
Inclusion criteria ..............................................................................24
3.3.3
Exclusion criteria .............................................................................24

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3.3.4
Withdrawal of subjects from treatment or assessments...............25
3.3.4.1
Withdrawal from trial treatment....................................26
3.3.4.2
Withdrawal of consent to trial participation..................26
3.3.4.3
Discontinuation of the trial by the sponsor ...................27
3.3.5
Replacement of subjects ..................................................................27
4.
TREATMENTS..........................................................................................................28
4.1
INVESTIGATIONAL TREATMENTS.......................................................28
4.1.1
Identity of the Investigational Medicinal Products.......................28
4.1.2
Selection of doses in the trial...........................................................28
4.1.3
Method of assigning subjects to treatment groups .......................28
4.1.4
Drug assignment and administration of doses for each subject ..28
4.1.5
Blinding and procedures for unblinding........................................29
4.1.6
Packaging, labelling, and re-supply................................................29
4.1.7
Storage conditions............................................................................29
4.1.8
Drug accountability..........................................................................29
4.2
OTHER TREATMENTS, EMERGENCY PROCEDURES, 
RESTRICTIONS............................................................................................30
4.2.1
Other treatments and emergency procedures...............................30
4.2.2
Restrictions .......................................................................................30
4.2.2.1
Restrictions regarding concomitant treatment...............30
4.2.2.2
Restrictions on diet and life style ..................................30
4.2.2.3
Contraception requirements ..........................................31
4.3
TREATMENT COMPLIANCE ...................................................................31
5.
ASSESSMENTS .........................................................................................................32
5.1
ASSESSMENT OF EFFICACY ...................................................................32
5.2
ASSESSMENT OF SAFETY ........................................................................32
5.2.1
Physical examination .......................................................................32
5.2.2
Vital signs..........................................................................................32
5.2.3
Safety laboratory parameters .........................................................32
5.2.4
Electrocardiogram ...........................................................................35
5.2.5
Other safety parameters..................................................................35
5.2.6
Assessment of adverse events..........................................................36
5.2.6.1
Definitions of adverse events ........................................36
5.2.6.1.1
Adverse event...............................................36
5.2.6.1.2
Serious adverse event...................................36
5.2.6.1.3
AEs considered ‘Always Serious’................36
5.2.6.1.4
Adverse events of special interest ................37
5.2.6.1.5
Intensity (severity) of AEs ...........................38

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5.2.6.1.6
Causal relationship of AEs...........................38
5.2.6.2
Adverse event collection and reporting.........................39
5.2.6.2.1
AE collection................................................39
5.2.6.2.2
AE reporting to the sponsor and timelines...39
5.2.6.2.3
Pregnancy.....................................................40
5.3
DRUG CONCENTRATION MEASUREMENTS AND 
PHARMACOKINETICS ..............................................................................40
5.3.1
Assessment of pharmacokinetics ....................................................40
5.3.2
Methods of sample collection ..........................................................40
5.3.2.1
Blood sampling for pharmacokinetic analysis ..............40
5.4
ASSESSMENT OF BIOMARKERS ............................................................41
5.5
BIOBANKING ...............................................................................................41
5.6
OTHER ASSESSMENTS..............................................................................41
5.6.1
Pharmacogenomic evaluation .........................................................41
5.7
APPROPRIATENESS OF MEASUREMENTS .........................................41
6.
INVESTIGATIONAL PLAN....................................................................................42
6.1
VISIT SCHEDULE........................................................................................42
6.2
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS.............42
6.2.1
Screening period...............................................................................42
6.2.2
Treatment periods............................................................................42
6.2.3
Follow-up period and trial completion...........................................43
7.
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE .....44
7.1
NULL AND ALTERNATIVE HYPOTHESES...........................................44
7.2
PLANNED ANALYSES ................................................................................44
7.2.1
General considerations ....................................................................44
7.2.1.1
Analysis sets..................................................................44
7.2.1.2
Pharmacokinetics...........................................................44
7.2.2
Primary endpoint analyses..............................................................45
7.2.3
Secondary endpoint analyses ..........................................................45
7.2.5
Safety analyses..................................................................................45
7.2.6
Interim analyses ...............................................................................46
7.3
HANDLING OF MISSING DATA...............................................................46
7.3.1
Safety.................................................................................................46

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7.3.2
Pharmacokinetics.............................................................................46
7.4
RANDOMISATION.......................................................................................46
7.5
DETERMINATION OF SAMPLE SIZE ....................................................46
8.
INFORMED CONSENT, TRIAL RECORDS, DATA PROTECTION, 
PUBLICATION POLICY, AND ADMINISTRATIVE STRUCTURE................47
8.1
TRIAL APPROVAL, SUBJECT INFORMATION, INFORMED 
CONSENT.......................................................................................................47
8.2
DATA QUALITY ASSURANCE .................................................................47
8.3
RECORDS ......................................................................................................48
8.3.1
Source documents ............................................................................48
8.3.2
Direct access to source data and documents..................................49
8.3.3
Storage period of records ................................................................49
8.4
EXPEDITED REPORTING OF ADVERSE EVENTS..............................49
8.5
STATEMENT OF CONFIDENTIALITY AND SUBJECT PRIVACY...49
8.5.1
Collection, storage and future use of biological samples and 
corresponding data ..........................................................................50
8.6
TRIAL MILESTONES..................................................................................50
8.7
ADMINISTRATIVE STRUCTURE OF THE TRIAL...............................50
9.
REFERENCES...........................................................................................................52
9.1
PUBLISHED REFERENCES.......................................................................52
9.2
UNPUBLISHED REFERENCES .................................................................53
10.
APPENDICES ............................................................................................................54
11.
DESCRIPTION OF GLOBAL AMENDMENT(S) ................................................55
11.1
GLOBAL AMENDMENT 1..........................................................................55

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gMean
Geometric mean
HR
Heart rate
IB
Investigator’s brochure
IEC
Independent Ethics Committee
iPD
Important protocol deviation
IPF
Idiopathic Pulmonary Fibrosis
IRB
Institutional Review Board
ISF
Investigator site file
JRS
Japanese Respiratory Society
LATS
Latin America Thoracic Society
LLOQ
Lower limit of quantification
MDA
Methylenedioxyamphetamine
MDMA
Methylenedioxymethamphetamine
MedDRA
Medical Dictionary for Regulatory Activities
PE
Polyethylene
PKS
Pharmacokinetic set
PP
Polypropylene
PR
Pulse rate
QT interval
ECG interval from the start of the QRS complex to the end of the T wave
QTc interval
QT interval corrected for heart rate, e.g. using the method of Fridericia 
(QTcF) or Bazett (QTcB)
REP
Residual effect period
SAE
Serious adverse event
SCR
Screening
SmPC
Summary of Product Characteristics
SOP
Standard operating procedure
SRD
Single-rising dose
SUSAR
Suspected unexpected serious adverse reaction
TMF
Trial master file
t1/2
Terminal half-life of the analyte in plasma
tmax
Time from (last) dosing to the maximum measured concentration of the 
analyte in plasma
TS
Treated set
tz
Time of last measurable concentration of the analyte in plasma
TSAP
Trial statistical analysis plan
ULN
Upper limit of normal

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1.
INTRODUCTION
BI 1015550, a selective inhibitor of the phosphodiesterase 4B (PDE4B) isoenzyme which 
hydrolyzes and inactivates cyclic adenosine monophosphate (cAMP), is being developed by 
Boehringer Ingelheim (BI) for the treatment of idiopathic pulmonary fibrosis (IPF). This 
clinical trial is to investigate safety, tolerability and pharmacokinetics of single oral doses of 
BI 1015550
1.1
MEDICAL BACKGROUND
IPF and other progressive fibrosing ILDs (PF-ILDs) share common pathophysiologic 
characteristics; alveolar epithelial cell injury and subsequent dysregulated repair, 
characterized by excessive deposition of extracellular matrix and loss of normal parenchymal 
architecture and lung function [P11-07084]. In IPF, fibroblasts exhibit unregulated 
proliferation and differentiate into myofibroblasts. The latter is considered the hallmark cell 
in the development and establishment of lung fibrosis [P12-03241]. Several growth factors 
are implicated in the proliferation, migration and transdifferentiation of the fibroblast and 
myofibroblast pool in pulmonary fibrosis.
As of date, nintedanib and pirfenidone are the only drugs registered for the treatment of IPF 
in several countries including China and recommended in the recent ATS/ERS/JRS/ALAT 
Clinical Practice Guideline for the Treatment of Idiopathic Pulmonary Fibrosis [R18-2794]. 
Nintedanib is also approved in the U.S., the European Union, China and many other countries 
for the treatment of other fibrosing ILDs with progressive phenotype.
BI 1015550 is a selective inhibitor of the PDE4 B with broad anti-inflammatory and 
antifibrotic activities. Based on its mode of action, BI 1015550 is hypothesized to have 
complementary activity to current therapies in IPF, as well as improved tolerability compared 
to other marketed PDE-4 inhibitors due to lower affinity for PDE4 D.
For further information please refer to the Investigator’s Brochure (IB) [c02094779].

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1.3
RATIONALE FOR PERFORMING THE TRIAL
The rationale of this trial is to assess the PK, safety and tolerability of BI 1015550 in healthy 
Chinese male and female subjects following single oral administration. The chosen 
population of healthy male and female subjects receiving single oral doses is considered 
adequate to provide the basis for the clinical development program of BI 1015550 in China.

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Table 1.4.2: 1 Overview of trial-related risks for this trial (cont.)
Possible or known 
risks of clinical 
relevance for this 
trial
Summary of data, rationale for the 
risk
Mitigation strategy
Fetal loss, decreased 
fertility
! No teratogenicity was seen in 2 
species in preclinical studies and 
exposure with BI 1015550 via the 
semen is expected to be very low.
! In rats, male and female fertility was 
potentially reduced. Long term 
toxicity studies with BI 1015550 in 
rat and monkey showed no 
microscopic evidence of changes in 
male or female reproductive organs or 
on male spermatogenesis.  For another 
PDE4 inhibitor with comparable 
preclinical findings, clinical data 
showed no effect on male fertility and 
sperm in humans. 
! Fetal loss was increased in female rats 
treated with BI 1015550  
! Efficacy of oral hormonal 
contraceptives can be impacted by 
potential BI 1015550
 
! Only WOCBP that use a highly 
efficient way of birth control are 
allowed to participate. Oral hormonal 
contraceptives are not allowed.
! Repeated pregnancy testing including 
prior first dosing in WOCBP
Discontinuation of treatment in case 
of pregnancy
Weight decrease in 
underweight subjects 
(BMI < 18.5 kg/m2)
! For the marketed PDE4-inhibitors 
apremilast and roflumilast weight loss 
in underweight subjects is an 
identified important risk.
! Presumably caused by increased 
energy expenditure and causing 
predominately loss of body fat
! Inclusion of subjects with BMI> 18.5 
only is routine inclusion criterion in 
Phase I
! The risk after single dose 
administration is considered low
Psychiatric disorders:
! Depression and 
anxiety
! Suicidality
! For the marketed PDE4i depression is 
listed as side effect and they are 
associated with increased risk of 
depression 
with 
some 
patients 
reporting 
suicidal 
ideation 
and 
attempts and also reported cases of 
completed suicide.
! In IPF patients treated with 18mg 
BI 1015550 bid for up to 12 weeks, 
no on-treatment events of suicidal 
ideation or behaviour and no events of 
depression or anxiety were reported.
! The 
risk 
after 
single 
dose 
administration in Phase I (done on 
site) is considered low and will be 
addressed by careful close clinical 
monitoring for AEs and increased 
awareness by the investigator for 
signs and symptoms of depression 
and anxiety as well as for signs and 
symptoms of suicidal ideation and 
behaviour
! Only 
healthy 
subjects 
with 
no 
relevant medical history including 
psychiatric disorders will be enrolled.

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Table 1.4.2: 1 Overview of trial-related risks for this trial (cont.)
Possible or known 
risks 
of 
clinical 
relevance for this 
trial
Summary of data, rationale for the 
risk
Mitigation strategy
Severe 
Infections 
including 
serious, 
opportunistic 
and 
mycobacterium 
tuberculosis 
infections
! Inhibition of the immune response 
due to the anti-inflammatory mode of 
action of BI 1015550 potentially 
increases the risk of infections, 
including Covid-19.
! Serious infections were balanced
between placebo and BI 1015550 in 
Phase II trial.
! Nasopharyngitis was more frequently 
reported under treatment with BI 
1015550 in Phase Ic/II but not in 
Phase I trials and the numbers were 
very small.
Screening procedures for infections 
are defined for this trial. Subjects 
with any relevant chronic or acute 
infections 
including 
human 
immunodeficiency virus (HIV), or 
viral hepatitis are excluded from the 
trial. 
! Treatment of infections should be 
initiated 
promptly 
according 
to 
standards of care.
Major 
Adverse 
Cardiovascular 
Events (MACE) and 
tachyarrhythmia
! Important potential risk for marketed 
PDE4 inhibitor apremilast.
! In preclinical studies with BI 1015550 
no adverse cardiovascular findings 
detected.
! In clinical trials with BI 1015550 no 
relevant findings were observed.
! These risks will be addressed by 
careful safety monitoring and safety 
measures such as
! close clinical monitoring for AEs;
! regular monitoring of vital signs and 
ECG assessments.
Malignancies
! Inhibition of the immune response 
with an immunomodulatory drug may 
potentially impair immune defences 
and thus theoretically decrease 
immune defense against malignancies.
! Subjects with a recent history of 
malignancy within 5 years will be 
excluded from participation in this 
trial.
! Diagnostics and treatment have to be 
initiated according to local standard 
of care.
Gastrointestinal 
disorders (e.g. 
diarrhoea, nausea, 
vomiting, abdominal 
pain)
! Vomiting and diarrhea are important 
dose-limiting side effects of marketed 
oral PDE-4 inhibitors. 
! Diarrhoea was the most frequently 
reported adverse event in Phase II 
with the majority of events being of 
mild intensity.
! Increased awareness of symptoms.
! Careful monitoring of hydration in 
subjects with diarrhoea 
recommended.
! Symptomatic treatment if required
General safety topics
Drug-induced liver
injury (DILI)
! Rare but severe event, standard topic 
of interest for products in 
development thus under constant 
surveillance by sponsors and 
regulators.
! Timely detection, evaluation, and 
follow-up of laboratory alterations in 
selected liver laboratory parameters 
to ensure subjects´ safety. Increased 
awareness and expedited reporting 
(AESI).

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Table 1.4.2: 1 Overview of trial-related risks for this trial (cont.)
The total volume of blood withdrawn per subject during the entire trial will not exceed the 
volume of a normal blood donation (500 mL). No health-related risk to healthy subjects is 
expected from withdrawal of this volume of blood.
1.4.3
Discussion
The nature of the target and the mechanism of action of BI 1015550 is well understood.
Based on its mode of action, BI1015550 is hypothesized to have complementary activity to 
current therapies in IPF.
In the context of the unmet medical need and anticipated benefit of BI 1015550, the benefit 
risk evaluation of the compound, based upon the available preclinical and clinical 
information, is favourable.
Possible or known 
risks 
of 
clinical 
relevance for this 
trial
Summary of data, rationale for the 
risk
Mitigation strategy
Trial procedures
Blood Sampling
! As with all blood sampling, there is a 
risk of mild pain, local irritation, or 
bruising (a black or blue mark) at the 
puncture site. Furthermore, there is a 
small risk of light-headedness and/or 
fainting. In rare cases, the puncture 
site can also become infected or 
nerves may be damaged, inducing 
long-lasting 
abnormal 
sensations 
(paraesthesia), impaired sensation of 
touch and persistent pain.
! These risks will be addressed by 
careful safety monitoring and risk 
mitigation measures such as
! close clinical monitoring for AEs;
! selection of experienced sites and 
site staff 

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2.
TRIAL OBJECTIVES AND ENDPOINTS
2.1
MAIN OBJECTIVES, PRIMARY AND SECONDARY ENDPOINTS
2.1.1
Main objectives
The main objectives of this trial are to investigate PK, safety and tolerability of BI 1015550 
in Chinese healthy male and female subjects following oral administration of single doses.
2.1.2
Primary endpoints
The following pharmacokinetic parameters will be determined for BI 1015550:
!
AUC0-∞(area under the concentration-time curve of the analyte in plasma over the 
time interval from 0 extrapolated to infinity)
!
Cmax (maximum measured concentration of the analyte in plasma)
2.1.3
Secondary endpoints
!
The occurrence of any treatment-emergent adverse events, assessed as the percentage 
of subjects treated with investigational drug who experience such an event.
2.2.2.1
Safety and tolerability
Safety and tolerability of BI 1015550 will be assessed based on:
!
AEs (including clinically relevant findings from the physical examination)
!
Safety laboratory tests
!
12-lead ECG
!
Vital signs (blood pressure [BP], pulse rate [PR])

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3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION
3.1
OVERALL TRIAL DESIGN
The trial will be performed as open-label, single dose parallel dose groups.
It is planned to include a total of 24 healthy Chinese male and female subjects in the trial.
The subjects will be assigned to 2 groups, each consisting of 12 subjects with at least 3 
female subjects within each dose group. In case of subjects not completed the trial, up to 8 
replacement will be recruited for whole study, see section 3.3.5. The dose groups to be 
evaluated are outlined in Table 3.1: 1 below. 
Table 3.1: 1
Dose groups receiving BI 1015550
Dose group
1
2
Dose
9 mg
18 mg
No. of subjects entered
12
12
No. of subjects receiving active
12
12
The groups will be dosed sequentially in ascending order of doses. At any time during the 
ongoing study, further dosing will be stopped in case of safety and tolerability concerns based 
on the pre-specified trial-specific stopping criteria (refer to Section 3.3.4.3).
An overview of all relevant trial activities is provided in the Flow Chart. For visit schedule 
and details of trial procedures at selected visits, refer to Sections 6.1 and 6.2, respectively.
3.2
DISCUSSION OF TRIAL
DESIGN, INCLUDING THE CHOICE OF 
CONTROL GROUP
The study will be conducted according to a single-dose, open-label parallel-group design.
The open-label treatment is not expected to bias results, since the trial endpoints are derived 
from measurement of plasma concentrations of the analyte.
The placebo group is not needed since primary objective is to evaluate PK parameters but not 
to evaluate safety
The dose to be tested in this trial is identical to those in the pivotal Phase III trials.
3.3
SELECTION OF TRIAL POPULATION
It is planned that at least 24 healthy male and female subjects (at least 3 female subjects in
each dose group) will enter the trial. Subjects will be recruited from the volunteers' pool of 
the trial site.
A log of all subjects enrolled into the trial (i.e. who have signed informed consent) will be 
maintained in the ISF, irrespective of whether they have been treated with investigational 
drug or not.
3.3.1
Main diagnosis for trial entry
The trial will be performed in healthy subjects.
Please refer to Section 8.3.1 (Source Documents) for the documentation requirements 
pertaining to the in- and exclusion criteria.

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3.3.2
Inclusion criteria
Chinese subjects will only be included in the trial if they meet the following criteria:
1.
Healthy male or female subjects according to the assessment of the investigator, as based 
on a complete medical history including a physical examination, vital signs (BP, PR), 12-
lead ECG, and clinical laboratory tests
2.
Age of 18 to 55 years (inclusive) 
3.
BMI of 18.5 to 28.0 kg/m2 (inclusive)
4.
Signed and dated written informed consent in accordance with ICH-GCP and local 
legislation prior to admission to the trial
5.
Women of childbearing potential (WOCBP) must be ready and able to use highly 
effective methods of birth control. Of note, oral hormonal contraceptives are not 
considered a highly effective method due to potential drug-drug interactions. A list of 
contraception methods meeting these criteria and instructions on the duration of their use 
is provided in the patient information; please refer to section 4.2.2.3.
3.3.3
Exclusion criteria
Subjects will not be allowed to participate, if any of the following general criteria apply:
1.
Any finding in the medical examination (including BP, PR or ECG) deviating from 
normal and assessed as clinically relevant by the investigator
2.
Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, 
diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the 
range of 50 to 90 bpm
3.
Any laboratory value outside the reference range that the investigator considers to be of 
clinical relevance
4.
Any evidence of a concomitant disease assessed as clinically relevant by the investigator
5.
Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or 
hormonal disorders
6.
Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with 
the pharmacokinetics of the trial medication (except appendectomy or simple hernia 
repair)
7.
Diseases of the central nervous system (including but not limited to any kind of seizures 
or stroke), and other relevant neurological or psychiatric disorders (including but not 
limited to major depressive disorder or any history of suicidal ideation or behaviour)
8.
History of relevant orthostatic hypotension, fainting spells, or blackouts
9.
Relevant chronic or acute infections
10. Any documented active or suspected malignancy or history of malignancy within 5 years 
prior to screening, except appropriately treated basal cell carcinoma of the skin in situ 
squamous cell carcinoma of the skin or in situ carcinoma of uterine cervix.
11. History of relevant allergy or hypersensitivity (including allergy to the trial medication or 
its excipients) 

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12. Use of drugs within 30 days of planned administration of trial medication that might 
reasonably influence the results of the trial (including drugs that cause QT/QTc interval
prolongation)
13. Intake of an investigational drug in another clinical trial within 60 days or five t1/2 of 
investigational drug (whichever is longer), prior to the planned administration of 
investigational drug in the current trial, or concurrent participation in another clinical 
trial in which investigational drug is administered
14. Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
15. Inability to refrain from smoking on specified trial days
16. Alcohol abuse (consumption of more than 12 g per day for females and 24 g per day for
males)
17. Drug abuse or positive drug screening
18. Blood donation of more than 100 mL within 30 days of planned administration of trial 
medication or intended blood donation during the trial
19. Intention to perform excessive physical activities within one week prior to the 
administration of trial medication or during the trial
20. Inability to comply with the dietary regimen of the trial site
21. A marked prolongation of QT/QTc interval (such as QTc intervals that are repeatedly 
greater than 450 ms in males or repeatedly greater than 470 ms in females) or any other 
relevant ECG finding at screening
22. A history of additional risk factors for Torsade de Pointes (such as heart failure, 
hypokalaemia, or family history of Long QT Syndrome)
23. Subject is assessed as unsuitable for inclusion by the investigator, for instance, because 
the subject is not considered able to understand and comply with study requirements, or 
has a condition that would not allow safe participation in the study 
24. During COVID-19 pandemic: laboratory test indicative of an ongoing SARS-CoV-2 
infection
25. For female subjects: Positive pregnancy test
26. For female subjects: Lactation, pregnancy, or plans to become pregnant during the trial 
or within 30 days after trial completion
27. Use of any Chinese traditional medicines and drugs (including prescription drug or over 
the counter) within 30 days of planned administration of trial medication.
For restrictions of the trial, refer to Section 4.2.2.
3.3.4
Withdrawal of subjects from treatment or assessments
Subjects may withdraw or may be removed from trial treatment or may withdraw consent to 
trial participation as a whole (‘withdrawal of consent’) with very different implications; 
please see Sections 3.3.4.1 and 3.3.4.2 below.
If a subject is removed from or withdraws from the trial prior to the first administration of 
trial medication, the data of this subject will not be entered in the case report form (CRF) and 
will not be reported in the clinical trial report (CTR).

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If a subject is removed from or withdraws from the trial after the first administration of trial 
medication, this will be documented and the reason for discontinuation must be recorded in 
the CRF; in addition, trial data will be included in the CRF and will be reported in the CTR. 
Following removal or withdrawal, a complete end-of-trial examination should be performed.
If the discontinuation or withdrawal occurs before the end of the REP (see Section 1.2.2), the 
discontinued subject should, if possible, be questioned for AEs and concomitant therapies at 
or after the end of the REP, in order to ensure collection of AEs and concomitant therapies 
throughout the REP, if not contrary to any consent withdrawal of the subject.
3.3.4.1
Withdrawal from trial treatment
An individual subject will be withdrawn from trial treatment if:
1.
The subject wants to withdraw from trial treatment. The subject will be asked to explain 
the reasons but has the right to refuse to answer
2.
The subject has repeatedly shown to be non-compliant with important trial procedures 
and, in the opinion of both, the investigator and sponsor representative, the safety of the 
subject cannot be guaranteed as he / she is not willing or able to adhere to the trial 
requirements in the future.
3.
The subject needs to take concomitant medication that interferes with the investigational 
medicinal product or other trial treatment
4.
The subject can no longer receive trial treatment for medical reasons (such as pregnancy, 
surgery, adverse events (AEs), or diseases)
5.
The subject has an elevation of AST and/or ALT ≥3-fold ULN and an elevation of total 
bilirubin ≥2-fold ULN (measured in the same blood sample) and/or needs to be followed 
up according to the DILI checklist provided in the ISF
28. In addition to these criteria, the investigator may discontinue subjects at any time based 
on his or her clinical judgment.
29. Based on the inclusion criteria (i.e. women of non-childbearing potential) it is highly 
unlikely that a female trial participant becomes pregnant. 
However, if it is known that a subject becomes pregnant during the trial, administration 
of the trial medication is to be stopped immediately, and the subject is to be removed 
from the trial. The subject is to be followed until she has given birth or until the end of 
the pregnancy. The subject’s data are to be collected until the end of the trial (last visit of 
last subject) and reported in the CTR. For reporting of pregnancy and associated events, 
refer to Section 5.2.6.2.3.
30. If new efficacy or safety information becomes available, Boehringer Ingelheim will 
review the benefit-risk-assessment and, if needed, pause or discontinue the trial treatment 
for all subjects or take any other appropriate action to guarantee the safety of the trial 
subjects.
3.3.4.2
Withdrawal of consent to trial participation
Subjects may withdraw their consent to trial participation at any time without the need to 
justify the decision. If a subject wants to withdraw consent, the investigator should be 

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involved in the discussion with the subject and explain the difference between trial treatment 
discontinuation and withdrawal of consent to trial participation, as well as explain the options 
for continued follow-up after trial treatment discontinuation, please see Section 3.3.4.1 above.
3.3.4.3
Discontinuation of the trial by the sponsor
Boehringer Ingelheim reserves the right to discontinue the trial at any time for any of the 
following reasons (if reasons 4 and/or 5 are met, the trial should be discontinued 
immediately):
1.
Failure to meet expected enrolment goals overall or at a particular trial site
2.
The sponsor decides to discontinue the further development of the investigational 
products
3.
Deviation from GCP, or the CTP impairing the appropriate conduct of the trial
4.
New toxicological findings, serious adverse events, or any safety information
invalidating the earlier positive benefit-risk-assessment (see Section 3.3.4.1)
3.3.5
Replacement of subjects
If some subjects do not complete the trial (including subjects non-evaluable for PK), they 
may be replaced if considered necessary to reach the objective of the trial. Subjects who 
withdraw or are withdrawn from treatment or assessments because of a drug-related adverse 
event will not be replaced. The Clinical Trial Leader together with the Trial 
Pharmacokineticist and the Trial Statistician are to decide if and how many subjects will be 
replaced. The total number of replacements may not exceed 4 subjects per dose group. A 
replacement subject will be assigned a unique trial subject number, and will be assigned to 
the same treatment as the subject he or she replaces.

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4.
TREATMENTS
4.1
INVESTIGATIONAL TREATMENTS
4.1.1
Identity of the Investigational Medicinal Products
The characteristics of the test product are given below:
Substance:
BI 1015550
Pharmaceutical formulation:
Film-coated tablets
Source:
BI Pharma GmbH & Co. KG, Germany
Unit strength:
9mg
Posology:
1-0-0
Mode of administration:
Oral
Duration of use:
Single dose
Substance:
BI 1015550
Pharmaceutical formulation:
Film-coated tablets
Source:
BI Pharma GmbH & Co. KG, Germany
Unit strength:
18 mg
Posology:
1-0-0
Mode of administration:
Oral
Duration of use:
Single dose
Excipients include hydroxypropylcellulose, lactose, microcrystalline cellulose type 101, 
croscarmellose sodium, magnesium stearate, ready to use film-coating dry mixture (Opadry ®
pink).
4.1.2
Selection of doses in the trial
The dose selected for this trial is the standard clinical dose (see Section 1.2).
4.1.3
Method of assigning subjects to treatment groups
Prior to the screening visit, subjects will be contacted in writing and informed about the 
planned visit dates. The subjects who are willing to participate will be recruited to dose 
groups according to their temporal availability. 
As soon as enough subjects have been allocated to one of the 2 dose groups, the following 
subject will be allocated to the other dose group. Therefore, the allocation of subjects to dose 
groups is not influenced by trial personnel, but only by the subjects’ temporal availability. As 
the trial includes healthy subjects of only Chinese ethnicity, relevant imbalances between the 
dose groups are not expected.
It is an open-label trial without randomisation.
4.1.4
Drug assignment and administration of doses for each subject
The treatments to be evaluated are summarised in Table 4.1.4: 1 below. 

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Table 4.1.4: 1 Dosage and treatment schedule
Dose
group
Substance
Pharmaceutical
form
Unit 
strength
Number of units 
per administration
Total 
dose
1
BI 1015550
Tablet
9 mg
1 film-coated tablet, single dose
9 mg
2
BI 1015550
Tablet
18 mg
1 film-coated tablets, single 
dose
18 mg
Administration of trial medication will be performed after subjects have fasted overnight; 
fasting is to start no later than 10 h before the scheduled dosing. The investigator (or 
authorised designee) will administer the trial medication as an oral dose together with about 
240 mL of water to subjects who are in an upright position. For drug administration, the so
called four-eye principle (two-person rule) should be applied. For this, one authorised 
employee of the trial site should witness the administration of trial medication, and – if 
applicable – its preparation (e.g. reconstitution), if correct dosage cannot be ensured 
otherwise.
Subjects will be kept under close medical surveillance until 24 h after drug administration. 
During the first 4 h after drug administration, subjects are not allowed to lie down (i.e. no 
declination of the upper body of more than 45 degrees from upright posture) or to sleep.
4.1.5
Blinding and procedures for unblinding
The trial will be conducted in an open-label fashion.
This Phase I trial will be handled in an open fashion throughout (that is, during the conduct, 
including data cleaning and preparation of the analysis). This is considered acceptable 
because the potential for bias is low and does not outweigh practical considerations. 
Emergency envelopes will not be provided, since the treatments of all subjects are known in 
this open-label trial.
4.1.6
Packaging, labelling, and re-supply
The investigational medicinal products will be provided by 
 They 
will be packaged and labelled in accordance with the principles of Good Manufacturing 
Practice (GMP). 
For details of packing and the description of the label, refer to the ISF.
The telephone number of the sponsor and the name, address and telephone number of the trial 
site are provided in the subject information form.
Examples of the labels will be available in the ISF.
No re-supply is planned.
4.1.7
Storage conditions
Drug supplies will be kept in their original packaging and in a secure limited access storage 
area in accordance with the recommended (labelled) storage conditions. If necessary, a 
temperature log must be maintained to make certain that the drug supplies are stored at the 
correct temperature. If the storage conditions are found to be outside the specified range, the 
Clinical Research Associate (as provided in the list of contacts) is to be contacted
immediately.
4.1.8
Drug accountability
The investigator or designee will receive the investigational drugs delivered from the sponsor

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when the following requirements are fulfilled:
!
Approval of the clinical trial protocol by the IRB / ethics committee
!
Approval/notification of the regulatory authority, e.g. competent authority
!
Availability of the curriculum vitae of the Principal Investigator
!
Availability of a signed and dated clinical trial protocol  
Only authorised personnel documented in the form 'Trial Staff List' may dispense 
investigational drugs to trial subjects. Investigational drugs are not allowed to be used outside 
of this protocol.
The investigator or designee must maintain records of the product’s delivery to the trial site, 
the inventory at the site, the use by each subject, and the disposal of unused products.
These records will include dates, quantities, batch / serial numbers, expiry ('use-by') dates, 
and the unique code numbers assigned to the investigational medicinal product and trial 
subjects. The investigator or designee will maintain records that document adequately that the 
subjects were provided the doses specified by the CTP and reconcile all investigational 
medicinal products received from the sponsor. At the time of return of remaining trial 
medication, the investigator or designee must verify that no remaining supplies are in the 
investigator’s possession.
4.2
OTHER TREATMENTS, EMERGENCY PROCEDURES, RESTRICTIONS
4.2.1
Other treatments and emergency procedures
There are no special emergency procedures to be followed. No additional treatment is 
planned. However, if adverse events require treatment, the investigator can authorise 
symptomatic therapy. In those cases, subjects will be treated as necessary and, if required, 
kept under supervision at the trial site or transferred to a hospital until all results of medical 
evaluations are acceptable.
4.2.2
Restrictions
4.2.2.1
Restrictions regarding concomitant treatment
In principle, no concomitant therapy is allowed. All concomitant or rescue therapies will be 
recorded (including time of intake on study days) on the appropriate pages of the CRF.
The use of known PDE-inhibitors such as: theophyllin, theobromin, sildenafil, tadalafil, 
vardenafil and roflumilast must be avoided during the whole course of the study. 
 
4.2.2.2
Restrictions on diet and life style
While admitted to the trial site, the subjects will be instructed not to consume any foods or 
drinks other than those provided by the staff. Standardised meals will be served at the times
indicated in the Flow Chart. No food is allowed for at least 4 h after drug intake.
From 1 h before drug intake until lunch, fluid intake is restricted to the water administered 
with the drug, and an additional 240 mL of water served at 2 h and 4 h post-dose on Day 1 
(mandatory for all subjects).

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Alcoholic beverages, grapefruits, Seville oranges (sour or bitter oranges) and their juices, and 
dietary supplements and products containing St. John's wort (Hypericum perforatum) are not 
permitted from 7 days before the first administration of trial medication until after the last PK 
sample of each trial period is collected.
Poppy-seeds containing foods should not be consumed within 3 days before each admission 
to trial site, in order to avoid false-positive results in the drug screen.
Methylxanthine-containing drinks or foods (such as coffee, tea, cola, energy drinks, or 
chocolate) are not allowed from 24 h before until 24 h after each administration of trial 
medication.
Smoking is not allowed during in-house confinement.
Excessive physical activity (such as competitive sport) should be avoided from 7 days before 
the first administration of trial medication until the end of trial examination.
4.2.2.3
Contraception requirements
If female subjects of child-bearing potential are included in the trial, adequate contraception 
is to be maintained throughout the course of the trial. Of note, oral hormonal contraceptives 
are not considered a highly effective method due to potential drug-drug interactions (see 
Section 3.3.2 for the definition of adequate measures, a list of contraception methods meeting 
these criteria is provided in the subject information).
4.3
TREATMENT COMPLIANCE
Compliance will be assured by administration of all trial medication in the trial centre under 
supervision of the investigating physician or a designee. The measured plasma concentrations 
of trial medication will provide additional confirmation of compliance.
Subjects who are non-compliant (for instance, who do not appear for scheduled visits or 
violate trial restrictions) may be removed from the trial and the CRF will be completed 
accordingly (for further procedures, please see Section 3.3.4.1).

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5.
ASSESSMENTS
5.1
ASSESSMENT OF EFFICACY
Not applicable. No efficacy endpoints will be evaluated in this trial.
5.2
ASSESSMENT OF SAFETY
5.2.1
Physical examination
At screening, the medical examination will include demographics, height and body weight, 
smoking and alcohol history (alcohol history not mandatory to be entered into CRF or to be 
reported),, relevant medical history and concomitant therapy, review of inclusion and 
exclusion criteria, review of vital signs (BP, PR), 12-lead ECG, laboratory tests, and a 
physical examination. At the end of trial examination, it will include review of vital signs, 12-
lead ECG, laboratory tests, and a physical examination.
5.2.2
Vital signs
Systolic and diastolic blood pressures (BP) as well as pulse rate (PR) or heart rate (heart rate 
is considered to be equal to pulse rate) will be measured by a blood pressure monitor at the 
times indicated in the Flow Chart, after subjects have rested for at least 5 min in a sitting
position. All recordings should be made using the same type of blood pressure recording 
instrument on the same arm, if possible.
5.2.3
Safety laboratory parameters
For the assessment of laboratory parameters, blood and urine samples will be collected by the 
trial site at the times indicated in the Flow Chart after the subjects have fasted for at least 
10 h. For retests, at the discretion of the investigator or designee, overnight fasting is not 
required. 
The parameters to be assessed are listed in Tables 5.2.3: 1 and 5.2.3: 2. Reference ranges will 
be provided in the ISF. 
Manual differential white blood cell count or urine sediment examinations will only be 
performed if there is an abnormality in the automatic blood cell count or in the urinalysis, 
respectively. 

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Table 5.2.3: 1 Routine laboratory tests
Functional 
lab 
group
BI test name [comment/abbreviation]
A
B
C
Haematology
Haematocrit
Haemoglobin
Red Blood Cell Count/Erythrocytes 
White Blood Cells/Leucocytes 
Platelet Count/Thrombocytes (quant)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Automatic WBC 
differential, 
relative 
Neutrophils/Leukocytes; Eosinophils/Leukocytes; 
Basophils/ Leukocytes; Monocytes/Leukocytes; 
Lymphocytes/Leukocytes 
X
X
X
Automatic WBC 
differential, 
absolute 
Neutrophil, absol.; Eosinophils, absol.; Basophils, absol.; 
Monocytes, absol.; Lymphocytes, absol.
X
X
X
Manual 
differential WBC 
(if automatic
differential WBC 
is abnormal)
Neut. Poly (segs)/Leukocytes; Neut. Poly (segs), absol.; 
Neutrophils Bands/Leukocytes; Neutrophils Bands, 
absol.; Eosinophils/Leukocytes; Eosinophils, absol.; 
Basophils/ Leukocytes; Basophils, absol.; 
Monocytes/Leukocytes; Monocytes, absol.; 
Lymphocytes/Leukocytes; Lymphocytes, absol.
Coagulation
Activated Partial Thromboplastin Time 
Prothrombin time
Prothrombin time – INR (International Normalization 
Ratio)
Fibrinogen
X
X
X 
X
--
--
--
--
--
--
--
--
Enzymes
AST [Aspartate aminotransferase] /GOT, SGOT 
ALT [Alanine aminotransferase] /GPT, SGPT
Alkaline Phosphatase
Gamma-Glutamyl Transferase 
Creatine Kinase [CK]
Creatine Kinase Isoenzyme MB [only if CK is elevated] 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Hormones
Thyroid Stimulating Hormone 
X
--
--

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Table 5.2.3: 1 Routine laboratory tests (cont.)
Functional 
lab 
group
BI test name [comment/abbreviation]
A
B
C
Substrates
Glucose (Plasma)
Creatinine 
GFR/ CKD-EPI
Bilirubin, Total 
Bilirubin, Direct
Protein, Total
C-Reactive Protein (Quant)  
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Blood
Pregnancy 
#
X
Urine Pregnancy #
X
X
Electrolytes
Sodium
Potassium
X
X
X
X
X
X
Urinalysis (Stix)
Urine Nitrite (qual)
Urine Protein (qual)
Urine Glucose (qual)
Urine Ketone (qual)
Urobilinogen (qual)
Urine Bilirubin (qual)
Urine RBC/Erythrocytes (qual)
Urine WBC/Leucocytes (qual)
Urine pH
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine sediment 
(microscopic 
examination if 
erythrocytes, 
leukocytes nitrite 
or protein are 
abnormal in urine)
Only positive findings will be reported (for instance, the 
presence of sediment bacteria, casts in sediment, 
squamous epithelial cells, erythrocytes, leukocytes)
A: parameters to be determined at Visit 1 (screening examination) 
B: parameters to be determined at Visit 2 (for time points refer to Flow Chart)
C: parameters to be determined at Visit 3 (end of trial examination)
# ß-HCG will be performed at Visit 1, Visit 2 (Day -1) and EoS only. Blood Pregnancy test should be done 
at Visit 1, urine pregnancy test will be done at Visit 2 (Day -1) and EoS.
The tests listed in Table 5.2.3: 2 are exclusionary laboratory tests that may be repeated as 
required. The results will not be entered in the CRF/database and will not be reported in the 
CTR. Except for pregnancy tests and drug screening, it is planned to perform these tests 
during screening only. Pregnancy testing in women will be performed at screening, prior to 
each treatment period, and as part of the end of trial examination. Although only women of 
non-childbearing potential are included in this trial, these tests are performed as 
precautionary measure. Drug screening will be performed at screening and prior to each 
treatment period.

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Table 5.2.3: 2 Exclusionary laboratory tests
Functional lab group
Test name 
Drug screening (urine)
Tetrahydrocannabinol acid)
Cocaine
Methamphetamines
MDMA
Morphine
Ketamine
Infectious serology (blood)
(At screening only)
Hepatitis B surface antigen (qualitative)
Hepatitis B core antibody (qualitative)
Hepatitis C antibodies (qualitative)
HIV-1 and HIV-2 antibody (qualitative)
Pregnancy test (blood/urine)
Beta human chorionic gonadotropin (beta-HCG)
To encourage compliance with alcoholic restrictions, a breath alcohol will be performed prior 
to each treatment period, and may be repeated at any time during the trial at the discretion of 
an investigator or designee. The results will not be included in the CTR.
The laboratory tests listed in Tables 5.2.3: 1 and 5.2.3: 2 will be performed by the local 
laboratory of the trial site or/and at a clinical research organization designated by the sponsor.
It is the responsibility of the Investigator to evaluate the laboratory reports. Clinically 
relevant abnormal findings as judged by the Investigator are to be reported as adverse events 
(please refer to Section 5.2.6). 
In case the criteria for hepatic injury are fulfilled, a number of additional measures will be 
performed (please see Section 5.2.6.1.4). 
5.2.4
Electrocardiogram
Twelve-lead ECGs (I, II, III, aVR, aVL, aVF, V1 - V6) will be recorded using a 
computerised electrocardiograph at the times provided in the Flow Chart. 
To achieve a stable heart rate at rest and to assure high quality recordings, the site personnel 
will be instructed to assure a relaxed and quiet environment, so that all subjects are at 
complete rest.
All ECGs will be recorded for a 10 sec duration after subjects have rested for at least 5 min in 
a supine position. ECG assessment will always precede all other trial procedures scheduled 
for the same time to avoid compromising ECG quality. 
All locally printed ECGs will be evaluated by the investigator or a designee. Abnormal 
findings will be reported as AEs (during the trial) or baseline conditions (if identified at the 
screening visit) if assessed to be clinically relevant by the investigator. Any ECG 
abnormalities will be carefully monitored and, if necessary, the subject will be removed from 
the trial and will receive the appropriate medical treatment. 
ECGs may be repeated for quality reasons (for instance, due to alternating current artefacts, 
muscle movements, or electrode dislocation) and the repeated ECG will be used for analysis. 
Additional (unscheduled) ECGs may be collected by the investigator for safety reasons. 
5.2.5
Other safety parameters
Not applicable.

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5.2.6
Assessment of adverse events
5.2.6.1
Definitions of adverse events
5.2.6.1.1
Adverse event
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered a medicinal product and which does not necessarily have 
to have a causal relationship with this treatment.
An AE can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
product, whether considered related or not.
The following should also be recorded as an AE in the CRF and BI SAE form (if applicable):
!
Worsening of the underlying disease or of other pre-existing conditions 
!
Changes in vital signs, ECG, physical examination, and laboratory test results, if they 
are judged clinically relevant by the investigator
If such abnormalities already pre-exist prior to trial inclusion, they will be considered as 
baseline conditions and should be collected in the eCRF only.
5.2.6.1.2
Serious adverse event
A serious adverse event (SAE) is defined as any AE which fulfils at least one of the 
following criteria:
! Results in death 
! Is life-threatening, which refers to an event in which the patient was at risk of death at 
the time of the event; it does not refer to an event that hypothetically might have 
caused death if more severe 
! Requires inpatient hospitalisation, or prolongation of existing hospitalisation
! Results in persistent or significant disability or incapacity 
! Is a congenital anomaly/birth defect 
! Is deemed serious for any other reason if it is an important medical event when based 
upon appropriate medical judgment which may jeopardise the patient and may 
require medical or surgical intervention to prevent one of the other outcomes listed in 
the above definitions. Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalisation or development of dependency or 
abuse
5.2.6.1.3
AEs considered ‘Always Serious’
In accordance with the European Medicines Agency initiative on Important Medical Events, 
Boehringer Ingelheim has set up a list of AEs, which, by their nature, can always be 
considered to be ‘serious’ even though they may not have met the criteria of an SAE as 
defined above.
The latest list of ‘Always Serious AEs’ can be found in the eDC system, an electronic data 
capture system which allows the entry of trial data at the trial site. A copy of the latest list of 

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‘Always Serious AEs’ will be provided upon request. These events should always be reported 
as SAEs as described in Section 5.2.6.2.
Cancers of new histology must be classified as a serious event regardless of the time since 
discontinuation of the trial medication and must be reported as described in 5.2.6.2, 
subsections AE Collection’ and ‘AE reporting to sponsor and timelines’.
5.2.6.1.4
Adverse events of special interest
The term adverse events of special interest (AESI) relates to any specific AE that has been 
identified at the project level as being of particular concern for prospective safety monitoring 
and safety assessment within this trial, e.g. the potential for AEs based on knowledge from 
other compounds in the same class. AESIs need to be reported to the sponsor’s 
Pharmacovigilance Department within the same timeframe that applies to SAEs, please see 
Section 5.2.6.2.2.
The following are considered as AESIs:
!
Potential severe DILI
A potential severe Drug Induced Liver Injury (DILI) that requires follow-up is 
defined by the following alterations of hepatic laboratory parameters: 
o
An elevation of AST (aspartate aminotransferase) and/or ALT (alanine 
aminotransferase) ≥3-fold ULN combined with an elevation of total bilirubin 
≥2-fold ULN measured in the same blood sample, or in samples drawn within 
30 days of each other, or
o
Aminotransferase (ALT, and/or AST) elevations ≥10-fold ULN
These lab findings constitute a hepatic injury alert and the subjects showing these lab 
abnormalities need to be followed up according to the ‘DILI checklist’ provided in the 
ISF.
In case of clinical symptoms of hepatic injury (icterus, unexplained 
encephalopathy, unexplained coagulopathy, right upper quadrant abdominal pain, 
etc.) without lab results (ALT, AST, total bilirubin) available, the Investigator should 
make sure that these parameters are analysed, if necessary in an unscheduled blood 
test that needs to be sent to central laboratory. Should the results meet the criteria of 
hepatic injury alert, the procedures described in the DILI checklist should be 
followed.
!
Severe or serious infections, opportunistic or mycobacterium tuberculosis infections
The opportunistic infections include pneumocystis jirovecii, Human Polyoma-1 virus 
disease including polyomavirus-associated nephropathy, Cytomegalie Virus, post-
transplant lymphoproliferative disorder (Epstein-Barr-Virus), progressive multifocal 
leucoencephalopathy, 
bartonellosis 
(disseminated 
only), 
blastomycosis, 
toxoplasmosis, coccidioidomycosis, histoplasmosis, aspergillosis (invasive only), 
candidiasis (invasive or pharyngeal), cryptococcosis, other invasive fungi 
(mucormycosis (zygomycosis, rhizopus,
mucor, lichtheimia), scedosporium/ 
pseudallescheria boydii, fusarium), legionellosis, listeria monocytogenes (invasive 
only), tuberculosis, nocardiosis, non-tuberculous mycobacterium, salmonellosis 
(invasive only), HBV reactivation, herpes simplex (invasive only), herpes zoster, 
strongyloides 
(hyperinfection 
syndrome 
and 
disseminated 
forms 
only), 

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paracoccidioides, penicillium marneffei, sporothrix schenckii, cryptosporidium 
species (chronic only), microsporidiosis, leishmaniasis (visceral only), trypanosoma 
cruzi infection (Chagas’ disease) (disseminated only), campylobacteriosis (invasive 
only),  shigellosis (invasive only), vibriosis (invasive due to vibrio vulnificus), 
Hepatitis C progression [R17-2617].
!
Vasculitis events
In this trial protocol vasculitis is defined as any event term included in the MedDRA 
SMQ Vasculitis (broad). This includes clinical and pathological features related to 
primary or secondary vasculitis syndromes and involving any type, size, and location 
of blood vessels.
5.2.6.1.5
Intensity (severity) of AEs
The intensity (severity) of the AE should be judged based on the following:
Mild:
Awareness of sign(s) or symptom(s) that is/are easily tolerated
Moderate:
Sufficient discomfort to cause interference with usual activity
Severe:
Incapacitating or causing inability to work or to perform usual activities
5.2.6.1.6
Causal relationship of AEs
Medical judgment should be used to determine whether there is a reasonable possibility of a 
causal relationship between the AE and the given trial treatment, considering all relevant 
factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, 
confounding factors such as concomitant medication, concomitant diseases and relevant 
history.
Arguments that may suggest that there is a reasonable possibility of a causal relationship 
could be:
!
The event is consistent with the known pharmacology of the drug 
!
The event is known to be caused by or attributed to the drug class
!
A plausible time to onset of the event relative to the time of drug exposure
!
Evidence that the event is reproducible when the drug is re-introduced
!
No medically sound alternative aetiologies that could explain the event (e.g. pre-
existing or concomitant diseases, or co-medications)
!
The event is typically drug-related and infrequent in the general population not 
exposed to drugs (e.g. Stevens-Johnson syndrome)
!
An indication of dose-response (i.e. greater effect size if the dose is increased, smaller 
effect size if dose is reduced)
Arguments that may suggest that there is no reasonable possibility of a causal relationship 
could be:
!
No plausible time to onset of the event relative to the time of drug exposure is evident 
(e.g. pre-treatment cases, diagnosis of cancer or chronic disease within days / weeks 
of drug administration; an allergic reaction weeks after discontinuation of the drug 
concerned)
!
Continuation of the event despite the withdrawal of the medication, taking into 

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account the pharmacological properties of the compound (e.g. after 5 half-lives). Of 
note, this criterion may not be applicable to events whose time course is prolonged 
despite removing the original trigger
!
There is an alternative explanation (e.g. situations where other drugs or underlying 
diseases appear to provide a more likely explanation for the observed event than the 
drug concerned)
!
Disappearance of the event even though the trial drug treatment continues or remains 
unchanged
5.2.6.2
Adverse event collection and reporting
5.2.6.2.1
AE collection
Upon enrolment into a trial, the subject’s baseline condition is assessed (for instance, by 
documentation of medical history/concomitant diagnoses), and relevant changes from 
baseline are noted subsequently. 
Subjects will be required to report spontaneously any AEs. In addition, each subject will be 
regularly assessed by the medical staff throughout the clinical trial and whenever the 
investigator deems necessary. As a minimum, subjects will be questioned for AEs (and 
concomitant therapies) at the time points indicated in the Flow Chart. Assessment will be 
made using non-specific questions such as ‘How do you feel?’. Specific questions will be 
asked wherever necessary in order to more precisely describe an AE.
A carefully written record of all AEs shall be kept by the investigator in charge of the trial. 
Records of AEs shall include data on the time of onset, end time, intensity of the event, and 
any treatment or action required for the event and its outcome.
The following must be collected and documented on the appropriate CRF(s) by the 
investigator:
!
From signing the informed consent onwards until an individual subject’s end of trial
(the End of Study (EoS) visit): 
o
All AEs (serious and non-serious) and all AESIs 
o
The only exception to this rule are AEs (serious and non-serious) and AESIs in 
Phase I trials in healthy volunteers, when subjects discontinue from the trial 
due to screening failures prior to administration of any trial medication. In 
these cases, the subjects’ data must be collected at trial site but will not be 
entered in the CRF and will not be reported in the CTR.
!
After the individual subject’s end of trial: 
o
The investigator does not need to actively monitor the subject for new AEs but 
should only report any occurrence of cancer and trial treatment related SAEs
and trial treatment related AESIs of which the investigator may become aware 
of by any means of communication, e.g. phone call. Those AEs should be 
reported on the BI SAE form (see Section 5.2.6.2.2), but not on the CRF.
5.2.6.2.2
AE reporting to the sponsor and timelines
The Investigator must report SAEs, AESIs, and non-serious AEs which are relevant for the 
reported SAE or AESI, on the BI SAE form to the sponsor’s unique entry point within 

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24 hours of becoming aware of the event, the country specific reporting process will be 
provided in the ISF. The same timeline applies if follow-up information becomes available. 
On specific occasions, the Investigator could inform the sponsor upfront via telephone. This 
does not replace the requirement to complete and send the BI SAE form. 
With receipt of any further information to these events, a follow-up SAE form has to be 
provided. For follow-up information, the same rules and timeline apply as for initial 
information. All (S)AEs, including those persisting after the individual subject’s end of trial, 
must be followed up until they have resolved, have been sufficiently characterized (e.g. as 
‘chronic’ or ‘stable’), or no further information can be obtained.
5.2.6.2.3
Pregnancy
In rare cases, pregnancy might occur in a clinical trial. Once a subject has been enrolled in 
the clinical trial and has taken trial medication, the investigator must report any drug 
exposure during pregnancy in a trial participant immediately (within 24 hours) by means of 
Part A of the Pregnancy Monitoring Form to the sponsor’s unique entry point.
Similarly, potential drug exposure during pregnancy must be reported if a partner of a male 
trial participant becomes pregnant. This requires written consent of the pregnant partner.
Reporting and consenting must be in line with local regulations. The ISF will contain the trial 
specific information and consent for the pregnant partner.
The outcome of the pregnancy associated with the drug exposure during pregnancy must be 
followed up and reported to the sponsor’s unique entry point on the Pregnancy Monitoring 
Form for Clinical Studies (Part B). The ISF will contain the Pregnancy Monitoring Form for 
Clinical Studies (Part A and Part B).
As pregnancy itself is not to be reported as an AE, in the absence of an accompanying SAE 
and/or AESI, only the Pregnancy Monitoring Form for Clinical Studies and not the SAE form 
is to be completed. If there is an SAE and/or AESI associated with the pregnancy, an SAE 
form must be completed in addition.
5.3
DRUG CONCENTRATION MEASUREMENTS AND PHARMACOKINETICS
5.3.1
Assessment of pharmacokinetics
For the assessment of pharmacokinetics, blood samples will be collected at the time points 
indicated in the Flow Chart. The actual sampling times will be recorded and used for 
determination of pharmacokinetic parameters. 
5.3.2
Methods of sample collection
5.3.2.1
Blood sampling for pharmacokinetic analysis
For quantification of BI 1015550 concentrations in plasma, 3 mL of blood will be drawn 
from 
an 
antecubital 
or
forearm 
vein 
into
an 
K2-EDTA 
(dipotassium 
ethylenediaminetetraacetic acid)-anticoagulant blood drawing tube at the times indicated in 
the Flow Chart. Blood will be withdrawn by means of either an indwelling venous catheter or 
by venipuncture with a metal needle.
The EDTA-anticoagulated blood samples will be centrifuged for approximately 10 min at 
approximately 2000 g to 4000 g and at about 4 to 8 °C. 

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Two plasma aliquots will be obtained and stored in polypropylene tubes. The first aliquot 
should contain at least 0.5 mL of plasma. The process from blood collection until transfer of 
plasma aliquots into the freezer should be completed in less than 120 min. Until transfer on 
dry ice to the analytical laboratory, the aliquots will be stored upright at approximately -20°C 
or below at the trial site. The second aliquot will be transferred to the analytical laboratory 
after the bioanalyst has acknowledged safe arrival of the first aliquot. At the analytical 
laboratory, the plasma samples will be stored at approximately -20°C or below until analysis.
At a minimum, the sample tube labels should list BI trial number, subject number, visit, and 
planned sampling time. 
After analysis, the plasma samples may be used for further methodological investigations
(e.g. for stability testing or assessment of metabolites) or to address Health Authority 
questions regarding the results/methodology. However, only data related to the analyte and/or 
its metabolite(s) including anti-drug antibodies (if applicable) will be generated by these 
additional investigations. The trial samples will be discarded after completion of the 
additional investigations but not later than 5 years after the CTR is archived.
5.4
ASSESSMENT OF BIOMARKERS 
Not applicable.
5.5
BIOBANKING
Not applicable.
5.6
OTHER ASSESSMENTS
5.6.1
Pharmacogenomic evaluation
Not applicable.
5.7
APPROPRIATENESS OF MEASUREMENTS
All measurements performed during this trial are standard measurements and will be 
performed in order to monitor subjects’ safety and to determine pharmacokinetic parameters 
in an appropriate way. The scheduled measurements will allow monitoring of changes in vital 
signs, standard laboratory values, and ECG parameters that might occur as a result of 
administration of trial medication. The safety assessments are standard, are accepted for 
evaluation of safety and tolerability of an orally administered drug, and are widely used in 
clinical trials. The pharmacokinetic parameters and measurements outlined in Section 5.3 are 
generally used assessments of drug exposure. 

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6.
INVESTIGATIONAL PLAN
6.1
VISIT SCHEDULE
Exact times of measurements outside the permitted time windows will be documented. The 
acceptable time windows for screening and the end of trial examination are provided in the 
Flow Chart.
Trial measurements and assessments scheduled to occur ‘before’ trial medication 
administration on Day 1 are to be performed and completed within a 3 h-period prior to the 
trial drug administration.
The acceptable deviation from the scheduled time for vital signs, ECG, laboratory tests, and 
AEs/concomitant therapies questioning will be:
± 30 min up to 48 h after drug administration (planned time)
± 120 min after 48 h to the end of study
If several activities are scheduled at the same time point in the Flow Chart, ECG should be 
the first and meal the last activity. Furthermore, if several measurements including 
venipuncture are scheduled for the same time, venipuncture should be the last of the 
measurements due to its inconvenience to the subject and possible influence on physiological
parameters.
For planned blood sampling times, refer to the Flow Chart. While these nominal times should 
be adhered to as closely as possible, the actual sampling times will be recorded and used for 
the determination of pharmacokinetic parameters.
If a subject misses an appointment, it will be rescheduled if possible. The relevance of 
measurements outside the permitted time windows will be assessed no later than at the Report 
Planning Meeting.
6.2
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS
6.2.1
Screening period
After having been informed about the trial, all subjects will provide written informed consent 
in accordance with GCP and local legislation prior to enrolment in the trial.
For information regarding laboratory tests (including drug and virus screening), ECG, vital 
signs, and physical examination, refer to Sections 5.2.1 to 5.2.4.
6.2.2
Treatment periods
Each subject will receive one dose of trial medication at Visit 2.
On the evening of Day -1, trial participants will be admitted to the trial site and kept under 
close medical surveillance for at least 24 h following drug administration. The subjects will 
then be allowed to leave the trial site after formal assessment and confirmation of their 
fitness. On all other trial days, subjects will be treated in an ambulatory fashion.
For details on time points and procedures for collection of plasma samples for PK analysis, 
refer to Flow Chart and Section 5.3.2.
The safety measurements performed during the treatment period are specified in Section 5.2
of this protocol and in the Flow Chart. AEs and concomitant therapy will be assessed 

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continuously from obtaining subject’s written informed consent until the end of trial
examination.
For details on times of all other trial procedures, refer to the Flow Chart.
6.2.3
Follow-up period and trial completion
For AE assessment, laboratory tests, recording of ECG and vital signs, and physical 
examination during the follow-up period, see Section 5.2.
Subjects who discontinue treatment before the end of the planned treatment period should 
undergo the EoS Visit.
If needed in the opinion of the investigator, additional visits may be scheduled after the EoS
Visit for continued safety monitoring.
All abnormal values (including laboratory parameters) that are assessed as clinically relevant 
by the investigator will be monitored using the appropriate tests until a return to a medically 
acceptable level is achieved. (S)AEs persisting after a subject’s EoS Visit must be followed 
until they have resolved, have been sufficiently characterised, or no further information can 
be obtained.

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7.
STATISTICAL METHODS AND DETERMINATION OF SAMPLE 
SIZE
7.1
NULL AND ALTERNATIVE HYPOTHESES
It is not planned to test any statistical hypotheses in this trial. 
7.2
PLANNED ANALYSES
7.2.1
General considerations
7.2.1.1
Analysis sets
Statistical analyses will be based on the following analysis sets:
!
Treated set (TS): The treated set includes all subjects who were treated with at least 
one dose of trial drug. The treated set will be used for safety analyses.
!
Pharmacokinetic parameter analysis set (PKS): This set includes all subjects in the 
treated set (TS) who provide at least one PK endpoint that was defined as primary and 
was not excluded due to a protocol deviation relevant to the evaluation of PK or due 
to PK non-evaluability (as specified in the following subsection ‘Pharmacokinetics’).
Thus, a subject will be included in the PKS, even if he/she contributes only one PK 
parameter value to the statistical assessment. Descriptive analyses of PK parameters 
will be based on the PKS.
Descriptions of additional analysis sets may be provided in the TSAP.
Adherence to the protocol will be assessed by the trial team. Important protocol deviation 
(iPD) categories will be suggested in the iPD specification file. iPDs will be identified no 
later than in the Report Planning Meeting, and the iPD categories will be updated as needed.
7.2.1.2
Pharmacokinetics
The pharmacokinetic parameters listed in Section 2.1 and 2.2.2 for drug BI 1015550 will be 
calculated according to the relevant BI internal procedures. 
Plasma concentration data and parameters of a subject will be included in the statistical 
pharmacokinetic (PK) analyses if they are not flagged for exclusion due to a protocol 
deviation relevant to the evaluation of PK (to be decided no later than in the Report Planning 
Meeting) or due to PK non-evaluability (as revealed during data analysis, based on the 
criteria specified below). Exclusion of a subject’s data will be documented in the CTR.
Important protocol deviations may be
!
Incorrect trial medication taken, i.e. the subject received at least one dose of trial
medication the subject was not assigned to
!
Incorrect dose of trial medication taken
!
Use of restricted medications
Plasma concentrations and/or parameters of a subject will be considered as non-evaluable, if 
for example
!
The subject experienced emesis that occurred at or before two times median tmax of the 

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respective treatment (Median tmax is to be determined excluding the subjects 
experiencing emesis), 
!
Missing samples/concentration data at important phases of PK disposition curve
Plasma concentration data and parameters of a subject which are flagged for exclusion will be 
reported with its individual values but will not be included in the statistical analyses. 
Only concentration values within the validated concentration range and actual sampling times 
will be used for the calculation of pharmacokinetic parameters. Concentrations used in the 
pharmacokinetic calculations will be in the same format provided in the bioanalytical report, 
(that is, to the same number of decimal places provided in the bioanalytical report). 
7.2.2
Primary endpoint analyses
The primary endpoints (refer to Section 2.1.2) will be calculated according to BI standards. 
The analysis will be based on the PKS and will be descriptive in nature.
7.2.3
Secondary endpoint analyses
The analysis of secondary safety endpoint will be based on the TS and will be descriptive in 
nature (refer to Section 7.2.5)
7.2.5
Safety analyses 
Safety will be assessed as defined by the endpoints listed in Section 2.1.3 and 2.2.2.1 based 
on the treated set (TS). Safety analyses will be descriptive in nature and based on BI 
standards. No hypothesis testing is planned.
For all analyses, the treatment actually administered (= treatment at onset) to the subject will 
be used (any deviations from the randomised treatment will be discussed in the minutes of the 
Report Planning Meeting).
Treatments will be compared in a descriptive way. Tabulations of frequencies/proportions 
will be used to evaluate categorical (qualitative) data, and tabulations of descriptive statistics 
will be used to analyse continuous (quantitative) data.
Measurements (such as ECG, vital signs, or laboratory parameters) or AEs will be assigned to 
treatments (see Section 4.1) based on the actual treatment at the time of the measurement or 
on the recorded time of AE onset (concept of treatment emergent AEs). Therefore, 
measurements performed or AEs recorded prior to intake of trial medication will be assigned 
to the screening period, those between trial medication intake and end of REP (see Section
1.2.2) will be assigned to the treatment period. Events occurring after the REP but prior to 
trial termination date will be assigned to ’follow-up’. These assignments including the 
corresponding time intervals will be defined in detail in the TSAP. Note that AEs occurring 
after the last per protocol contact but entered before database lock will be reported to 
Pharmacovigilance only and will not be captured in the trial database.
Additionally, further treatment intervals (called analysing treatments) may be defined in the 
TSAP in order to provide summary statistics for other than above periods, such as combined 
treatments, on-treatment totals, or periods without treatment effects (such as screening and 

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post-study intervals).
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). Frequency, severity, and causal relationship of AEs will be tabulated by 
treatment, system organ class, and preferred term. SAEs, AESIs (see Section 5.2.6.1), and 
other significant AEs (according to ICH E3) will be listed separately. 
Previous and concomitant therapies will be presented per treatment group without 
consideration of time intervals and treatment periods.
Laboratory data will be compared to their reference ranges. Values outside the reference 
range as well as possibly clinically significant values will be highlighted in the listings. 
Additionally, differences from baseline will be evaluated.
Vital signs or other safety-relevant data will be assessed with regard to possible on-treatment 
changes from baseline.
Relevant ECG findings will be reported as AEs.
7.2.6
Interim analyses
No interim analysis is planned.
7.3
HANDLING OF MISSING DATA
7.3.1
Safety
It is not planned to impute missing values for safety parameters.
7.3.2
Pharmacokinetics
Handling of missing PK data will be performed according to the relevant BI internal 
procedures. 
PK parameters that cannot be reasonably calculated based on the available drug 
concentration-time data will not be imputed.
7.4
RANDOMISATION
Not applicable.
7.5
DETERMINATION OF SAMPLE SIZE
It is planned to include 12 subjects per dose group, and a total of up to 32 subjects including 
up to 8 replaced subjects in this trial. The planned sample size is not based on a power 
calculation. The size of 12 subjects per dose group is commonly used in studies of the present 
type and is in general considered as sufficient for the exploratory evaluation of single dose 
safety and PK.

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8.
INFORMED CONSENT, TRIAL RECORDS, DATA 
PROTECTION, PUBLICATION POLICY, AND 
ADMINISTRATIVE STRUCTURE
The trial will be carried out in compliance with the protocol, the ethical principles laid down 
in the Declaration of Helsinki, in accordance with the ICH Harmonized Guideline for Good 
Clinical Practice (GCP), relevant BI Standard Operating Procedures (SOPs) and other 
relevant regulations. Investigators and site staff must adhere to these principles. Deviation 
from the protocol, the principles of ICH GCP or applicable regulations will be treated as 
‘protocol deviation’.
Standard medical care (prophylactic, diagnostic, and therapeutic procedures) remains the 
responsibility of the subject’s treating physician.
The investigator will inform the sponsor immediately of any urgent safety measures taken to 
protect the trial subjects against any immediate hazard, as well as of any serious breaches of 
the protocol or of ICH GCP.
The Boehringer Ingelheim transparency and publication policy can be found on the following 
web page: trials.boehringer-ingelheim.com. The rights of the investigator and of the sponsor 
with regard to publication of the results of this trial are described in the investigator contract. 
As a general rule, no trial results should be published prior to finalisation of the CTR.
8.1
TRIAL APPROVAL, SUBJECT INFORMATION, INFORMED CONSENT
This trial will be initiated only after all required legal documentation has been reviewed and 
approved by the respective Institutional Review Board (IRB / Independent Ethics Committee 
(IEC and competent authority (CA) according to national and international regulations. The 
same applies for the implementation of changes introduced by amendments.
Prior to a subject’s participation in the trial, written informed consent must be obtained from 
each subject (or the subject’s legally accepted representative) according to ICH-GCP and to 
the regulatory and legal requirements of the participating country. Each signature must be 
personally dated by each signatory and the informed consent and any additional subject-
information form retained by the investigator as part of the trial records. A signed copy of the 
informed consent and any additional subject information must be given to each subject or the 
subject’s legally accepted representative.
The subject must be given sufficient time to consider participation in the trial. The 
investigator or delegate obtains written consent of the subject’s own free will with the 
informed consent form after confirming that the subject understands the contents. The 
investigator or 
 delegate must sign (or place a seal on) and date the informed consent form. 
If a trial collaborator has given a supplementary explanation, the trial collaborator also signs 
(or places a seal on) and dates the informed consent.
Re-consenting may become necessary when new relevant information becomes available and 
should be conducted according to the sponsor’s instructions.
The consent and re-consenting process should be properly documented in the source 
documentation.
8.2
DATA QUALITY ASSURANCE
A risk-based approach is used for trial quality management. It is initiated by the assessment 

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of critical data and processes for trial subject protection and reliability of the results as well as 
identification and assessment of associated risks. An Integrated Quality and Risk 
Management Plan or alternative plan, in line with the guidance provided by ICH Q9 and 
ICH-GCP E6, for fully outsourced trials, documents the rationale and strategies for risk 
management during trial conduct including monitoring approaches, vendor management and 
other processes focusing on areas of greatest risk. 
Continuous risk review and assessment may lead to adjustments in trial conduct, trial design 
or monitoring approaches. 
A quality assurance audit/inspection of this trial may be conducted by the sponsor, sponsor’s 
designees, or by IRB / IEC or by regulatory authorities. The quality assurance auditor will 
have access to all medical records, the investigator’s trial-related files and correspondence, 
and the informed consent documentation of this clinical trial.
8.3
RECORDS
CRFs for individual subjects will be provided by the sponsor. For drug accountability, refer 
to Section 4.1.8.
8.3.1
Source documents
In accordance with regulatory requirements, the investigator should prepare and maintain 
adequate and accurate source documents and trial records for each trial subject that include 
all observations and other data pertinent to the investigation. Source data as well as reported 
data should follow the ‘ALCOA principles’ and be attributable, legible, contemporaneous, 
original, and accurate. Changes to the data should be traceable (audit trail).
Data reported on the CRF must be consistent with the source data or the discrepancies must 
be explained.
The current medical history of the subject may not be sufficient to confirm eligibility for the 
trial and the investigator may need to request previous medical histories and evidence of any 
diagnostic tests. In this case, the investigator must make at least one documented attempt to 
retrieve previous medical records. If this fails, a verbal history from the subject, documented 
in their medical records, would be acceptable.
Before providing any copy of subjects’ source documents to the sponsor, the investigator 
must ensure that all subject identifiers (e.g., subject’s name, initials, address, phone number, 
and social security number) have properly been removed or redacted to ensure subject 
confidentiality.
If the subject is not compliant with the protocol, any corrective action (e.g. re-training) must 
be documented in the subject file.
For the CRF, data must be derived from source documents, for example:
!
Subject identification: gender, year of birth (in accordance with local laws and 
regulations)
!
Subject participation in the trial (substance, trial number, subject number, date subject 
was informed)
!
Dates of subject’s visits, including dispensing of trial medication
!
Medical history (including trial indication and concomitant diseases, if applicable)
!
Medication history

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!
AEs and outcome events (onset date [mandatory], and end date [if available])
!
SAEs (onset date [mandatory], and end date [if available])
!
Concomitant therapy (start date, changes)
!
Originals or copies of laboratory results and other imaging or testing results, with 
proper documented medical evaluation (in validated electronic format, if available)
!
ECG results (original or copies of printouts)
!
Completion of subject’s participation in the trial (end date; in case of premature 
discontinuation, document the reason for it, if known)
!
Prior to allocation of a subject to a treatment into a clinical trial, there must be 
documented evidence in the source data (e.g. medical records) that the trial participant 
meets all inclusion criteria and does not meet any exclusion criteria. The absence of 
records (either medical records, verbal documented feedback of the subject or testing 
conducted specific for a protocol) to support inclusion/exclusion criteria does not 
make the subject eligible for the clinical trial.
8.3.2
Direct access to source data and documents
The investigator/institution will allow site trial-related monitoring, audits, IRB / IEC review 
and regulatory inspections. Direct access must be provided to the CRF and all source 
documents/data, including progress notes, copies of laboratory and medical test results, which 
must be available at all times for review by the Clinical Research Associate, auditor and 
regulatory inspector (e.g. FDA). They may review all CRFs and informed consents. The 
accuracy of the data will be verified by direct comparison with the source documents 
described in Section 8.3.1. The sponsor will also monitor compliance with the protocol and 
GCP.
8.3.3
Storage period of records
Trial site:
The trial site must retain the source and essential documents (including ISF) according to the 
local requirements valid at the time of the end of the trial (whatever is longer).
Sponsor:
The sponsor must retain the essential documents according to the sponsor’s SOPs.
8.4
EXPEDITED REPORTING OF ADVERSE EVENTS
BI is responsible to fulfil their legal and regulatory reporting obligation in accordance with 
regulatory requirements.
8.5
STATEMENT OF CONFIDENTIALITY AND SUBJECT PRIVACY
Data protection and data security measures are implemented for the collection, storage and 
processing of subject data in accordance with the principles 7 and 12 of the WHO GCP 
handbook.
Individual subject data obtained as a result of this trial is considered confidential and 
disclosure to third parties is prohibited with the following exceptions: 
Personalised treatment data may be given to the subject’s personal physician or to other 
appropriate medical personnel responsible for the subject’s welfare. Data generated at the site 
as a result of the trial need to be available for inspection on request by the participating 
physicians, the sponsor’s representatives, by the IRB / IEC and the regulatory authorities.

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8.5.1
Collection, storage and future use of biological samples and corresponding data
Measures are in place to comply with the applicable rules for the collection, storage and 
future use of biological samples and clinical data, in particular
!
Sample and data usage have to be in accordance with the informed consent
!
The BI-internal facilities storing biological samples from clinical trial participants as 
well as the external storage facility are qualified for the storage of biological samples 
collected in clinical trials.
!
An appropriate sample and data management system, incl. audit trail for clinical data 
and samples to identify and destroy such samples according to ICF is in place
!
A fit for the purpose documentation (e.g. biomarker proposal, analysis plan and 
report) ensures compliant usage
!
A fit for purpose approach will be used for assay/equipment validation depending on 
the intended use of the biomarker data
!
Samples and/or data may be transferred to third parties and other countries as 
specified in the ICF
8.6
TRIAL MILESTONES
The start of the trial is defined as the date when the first subject in the whole trial signs 
informed consent.
The end of the trial is defined as the date of the last visit of the last subject in the whole trial 
(‘Last Subject Completed’).
Early termination of the trial is defined as the premature termination of the trial due to any 
reason before the end of the trial as specified in this protocol.
Temporary halt of the trial is defined as any unplanned interruption of the trial by the sponsor 
with the intention to resume it.
Suspension of the trial is defined as an interruption of the trial based on a Health Authority 
request.
8.7
ADMINISTRATIVE STRUCTURE OF THE TRIAL
The trial is sponsored by Boehringer Ingelheim (BI).
Relevant documentation on the participating (Principal) Investigators (e.g. their curricula 
vitae) will be filed in the ISF.
BI has appointed a Clinical Trial Leader (CTL), responsible for coordinating all required trial 
activities, in order to 
!
Manage the trial in accordance with applicable regulations and internal SOPs
!
Direct the clinical trial team in the preparation, conduct, and reporting of the trial
!
Ensure appropriate training and information of local Clinical Trial Mangers (CTM), 
Clinical Research Associates (CRAs), and investigators of participating trial sites
The trial medication will be provided by the 
 
Safety laboratory tests will be performed by the local laboratory of the trial site.

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Analyses of BI 1015550 concentrations in plasma will be performed at a CRO –
or an appropriate CRO with validated bioanalytical method. On-site monitoring will be 
performed by BI or a contract research organisation appointed by BI.
Data management and statistical evaluation will be done by BI or a contract research 
organisation according to BI SOPs.
Tasks and functions assigned in order to organise, manage, and evaluate the trial are defined 
according to BI SOPs. A list of responsible persons and relevant local information can be 
found in the ISF.

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9.
REFERENCES 
9.1
PUBLISHED REFERENCES
P06-08316
Giembycz MA, An update and appraisal of the cilomilast phase III clinical 
development programme for chronic obstructive pulmonary disease. Br J 
Clin Pharmacol; 2006; 62(2); 138-152.
P11-07084
An official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary 
Fibrosis: Evidence-based Guidelines for Diagnosis and Management. 
Am J Respir Crit Care Med 2011, 183:6, 788-824.
P12-03241
King TE, Pardo A, Selman M. Idiopathic pulmonary fibrosis. 
Lancet 2011. 378: 1949-1961
R10-1555
Daxas (roflumilast) in chronic obstructive pulmonary disease, NDA 22-
522, FDA Advisory Committee briefing document presented to: 
Pulmonary-Allergy Drugs Advisory Committee (briefing book, April 7, 
2010).http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMate
rials/Drugs/Pulmonary-AllergyDrugsAdvisoryCommittee/ucm207376.htm 
(access date: 23 November 2010) ; Jersey City: Forest Research Institute; 
2010.
R10-1559
Giembycz MA. Life after PDE4: overcoming adverse events with dual 
specificity phosphodiesterase inhibitors. Curr Opin Pharmacol 2005; 
5:238-244.
R14-1795
Otezla (apremilast) tablets, for oral use (Celgene) (U.S. prescribing 
information, revised: 3/2014).
R17-0915
Roflumilast 500 mcg tablets (Forest Research Institute):
pharmacology/toxicology NDA/BLA review and evaluation, application 
number: 022522Orig1s000. Source: 
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022522Orig1s0
00PharmR.pdf (access date: 13 March 2017) ; Department of Health and 
Human Services, Public Health Service, Food and Drug Administration, 
Center for Drug Evaluation and Research; 2011.
R17-0919
Otezla (apremilast) (Celgene): pharmacology/toxicology NDA/BLA 
review and evaluation, application number: 205437Orig1s000. Source: 
http://www.accessdata.fda.gov/drugsatfda_docs/nda/2014/205437Orig1s0
00PharmR.pdf (access date: 13 March 2017); Department of Health and 
Human Services, Public Health Service, Food and Drug Administration, 
Center for Drug Evaluation and Research; 2014.
R17-1427
Otezla 10 mg, 20 mg, 30 mg film-coated tablets, Otezla 30 mg film-coated 
tablets (Celgene) (summary for product characteristics, manufacturer 
responsible for batch release, conditions or restrictions regarding supply 
and use, other conditions and requirements of the marketing authorisation, 
conditions or restrictions with regard to the safe and effective use of the 
medicinal product, labelling and package leaflet (first published 
16/02/2015). Source: https://ec.europa.eu/health/documents/community-
register/2015/20150115130395/anx _130395_en.pdf (access date: 19 April 
2017); 2015.

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R17-2617
Winthrop KL, Novosad SA, Baddley JW, Calabrese L, Chiller T, 
Polgreen P, et al. Opportunistic infections and biologic therapies in 
immune-mediated inflammatory diseases: consensus recommendations for 
infection reporting during clinical trials and postmarketing surveillance.
Ann Rheum Dis; 2015, 74; 2107-2116.
R18-2794
Raghu G, Remy-Jardin M, Myers JL, Richeldi L, Ryerson CJ, Lederer DJ, 
et al, American Thoracic Society, European Respiratory Society, Japanese 
Respiratory Society, Latin American Thoracic Society.
Diagnosis of idiopathic pulmonary fibrosis: an official 
ATS/ERS/JRS/ALAT clinical practice guideline. Am J Respir Crit Care 
Med 2018; 198(5); e44-e68.
9.2
UNPUBLISHED REFERENCES
c02094779
BI 1015550 - Investigator’s Brochure, current version
c02191718
Safety, tolerability and pharmacokinetics of multiple rising oral doses of 
BI 1015550 powder for oral solution in healthy male volunteers q.d. or bid 
for 14 days (a randomised, double-blind, placebo-controlled within dose 
groups Phase I trial). 1305.2.
c22991937
 Safety, tolerability, and 
pharmacokinetics of single (Part 1) and multiple rising oral doses (Part 2) 
of BI 1015550 in healthy male subjects. 1305-0011. Clinical Trial Report, 
15 November 2018.
c24902949
. Relative bioavailability of a 
single oral dose of BI 1015550 when administered alone or in combination 
with multiple oral doses of itraconazole in healthy male subjects. 1305-
0015. Clinical Trial Report, 15 March 2019
c25085412
Safety, tolerability, and pharmacokinetics of multiple rising oral doses of 
BI 1015550 in patients with idiopathic pulmonary fibrosis (IPF) on no 
background anti-fibrotic therapy. 1305-0012. Clinical Trial Report, 13 Jan 
2020
c36151567
A Phase I, open-label, non-randomized, single-dose, single-arm, single 
period study to investigate the metabolism and pharmacokinetics of [C-
14]-labelled BI 1015550 after oral administration in healthy male subjects. 
1305-0016. Clinical Trial Report, 28 Feb 2022
c37065416
A randomised, double-blind, placebo-controlled parallel group study in 
IPF patients over 12 weeks evaluating efficacy, safety and tolerability of 
BI 1015550 taken orally. 1305-0013. Clinical Trial Report
U10-3777
BI 137882 – Investigator’s Brochure, 11 February 2011
U11-2788
 Safety, tolerability and pharmacokinetics of single rising 
doses of BI 137882 in healthy male volunteers (A randomised, single-
blind, placebo–controlled Phase I study. Clinical Trial Report, 28 
December 2011

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10.
APPENDICES
Not applicable.

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occur ‘before’ trial medication 
administration on Day 1 are to be performed 
and completed within a 3 h-period prior to 
the trial drug administration.
Rationale for change
Time collecting points clarified.
Section to be changed
Table 1.4.2: 1 Overview of trial-related risks for 
this trial
Description of change
Updated the text as following (See text in bold):
•
An exception This is also applicable for
Paxlovid in the treatment of Covid-19: if 
treatment with Paxlovid is needed trial 
medication needs to be paused
Rationale for change
Clarification. Paxlovid is a type of CYP3A 
inhibitors and should be avoided in this trial.
Section to be changed
4.1.8 Drug accountability
Description of change
Updated the text as following (See text in bold):
•
At the time of disposal return of remaining trial 
medication, the investigator or designee must 
verify that no remaining supplies are in the 
investigator’s possession.
•
All unused medication will be disposed of 
locally by the trial site upon written 
authorisation of the Clinical Trial Leader. 
Receipt, usage and disposal of trial medication 
must be documented on the appropriate forms. 
Account must be given for any discrepancies.
Rationale for change
Clarification. The remaining trial medication can’t 
be disposed at local site in this trial, so the 
remaining trial medication will be returned to 
Sponsor and the description about remaining 
medication disposal at local site was no longer 
required. This revision has been clarified in the 
Protocol Administrative Letter (date: on 8 Nov 
2022) and approved by site Ethic Committee on 10 
Dec 2022 .
Section to be changed
5.2.2 Vital signs
Description of change
Updated the text as following (See text in bold):
•
…after subjects have rested for at least 5 min in 
a supine sitting position. All recordings should 
be made using the same type of blood pressure 
recording instrument on the same arm, if 
possible.
Rationale for change
Adapted to match the wording in section
4.1.4: …during the first 4h after drug 

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administration, subjects are not allowed to lie down 
(i.e. no declination of the upper body of more than 
45 degrees from upright posture) or to sleep. This 
revision has been clarified in the Protocol 
Administrative Letter (date: on 1 Feb 2023) and 
approved by site Ethic Committee on 6 Feb 2023.
Section to be changed
Table 5.2.3: 1 Routine laboratory tests: Footnote
Description of change
Updated the text as following (See text in bold):
# ß-HCG will be performed at Visit 1, Visit 2 (Day 
1 -1) and EoS only. Blood Pregnancy test should be 
done at Visit 1, urine pregnancy test will be done at 
Visit 2 (Day 1 -1) and EoS.
Rationale for change
Adapted to match description in the Flow Chart
Section to be changed
6.2.2 Treatment periods
Description of change
Updated the text as following (See text in bold):
•
On the evening of Day -1, trial participants will 
be admitted to the trial site and kept under close 
medical surveillance for at least 4824h 
following drug administration
Rationale for change
Updated to keep consistency with Flow Chart. This 
revision has been clarified in the Protocol 
Administrative Letter (date: on 1 Feb 2023) and 
approved by site Ethic Committee on 6 Feb 2023.