Pharmacokinetics of R-BI 1015550 After Single Oral Doses of BI 1015550 in Japanese Healthy Male Subjects (Open-label, Non-randomised, and Parallel Group Design)
Phase: PHASE1
Conditions: Healthy
Sponsor: Boehringer Ingelheim

BI-VQD-12774_40-106_AD-11 (8.0)
Clinical Trial Protocol
TITLE PAGE
Document Number: c42256721-01
BI Trial No.
1305-0038
BI Investigational
Medicinal Product
BI 1015550
Title
Pharmacokinetics of R-BI 1015550 after single oral doses of 
BI 1015550 in Japanese healthy male subjects (open-label, non-
randomised, and parallel group design)
Lay Title
A study to test how different doses of BI 1015550 are taken up in 
the body of healthy Japanese men
Clinical Phase
I
Clinical Trial Leader
             
Telephone: 
, Fax: 
Investigator
Phone:
Fax: 
Current Version, Date
Version 1.0,   05 Aug 2023
Original Protocol Date
05 Aug 2023
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CLINICAL TRIAL PROTOCOL SYNOPSIS
Company name
Boehringer Ingelheim
Original protocol date
05 Aug 2023
Revision date
Not applicable
BI trial number
1305-0038
Title of trial
Pharmacokinetics of R-BI 1015550 after single oral doses of BI 1015550 in 
Japanese healthy male subjects (open-label, non-randomised, and parallel group 
design)
 Investigator
Trial site
Phone:
Fax:
Clinical phase
I
Trial rationale
BI 1015550 undergoes chiral inversion and forms inactive S-enantiomer.
Pharmacokinetics of R-BI 1015550 after single oral doses of BI 1015550 will be 
assessed.
Trial objectives
To investigate pharmacokinetics of R-BI 1015550 after single doses of 
BI 1015550 in healthy Japanese male subjects
Trial endpoints
Primary endpoint: AUC0-∞and Cmax of R-BI 1015550
Trial design
Open-label, non-randomised, and parallel-group design
Number of subjects 
total entered
12
on each treatment
6 per dose group[DG] (6 receiving BI 1015550)
Diagnosis
Not applicable
Main inclusion criteria
Healthy male subjects, age of 18 to 45 years (inclusive), body mass index (BMI) 
of 18.5 to 25.0 kg/m2 (inclusive)
Test product
BI 1015550 film-coated tablet (9 mg and 18 mg)
dose
9 mg (DG 1), 18 mg (DG2)
mode of
administration
Oral approximately 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 laboratory7
PK blood
12-lead ECG
Vital signs (BP, PR,RR)
Questioning for AEs and 
concomitant therapy 8
1
-28 to -1
Screening (SCR)1
xA
x
x
2
-1
-12:00
20:00
Admission to trial site2
x2, 3, C
x2
1
-3:00
6 :00
Allocation to study number4
x4
x4
x4
x4
0:00
9:00
Drug administration
0:30
9:30
x
0:45
9:45
x
1:00
10:00
x
1:15
10:15
x
1:30
10:30
x
1:45
10:45
x
2:00
11:00
240 mL fluid intake5
x
3:00
12:00
x
4:00
13:00
240 mL fluid intake, Lunch5
x
6:00
15:00
x
8:00
17:00
x
x
10:00
19:00
Dinner5
12:00
21:00
x
2
24:00
09:00
Breakfast5
xB
x
x
x
x
3
48:00
09:00
Breakfast5
x
x
4
72:00
09:00
Breakfast5
x
x
5
96:00
09:00
Breakfast5
x
x
6
120:00
09:00
Breakfast5
xB
x
x
7
144:00
09:00
Breakfast5
x
x
3
8
Breakfast(voluntary)5, End of study 
(EoS) examination,6 discharge from 
trial site
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
alcohol breath test, and infection screening except for SARS CoV2 / COVID-19), 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 an approximate. The procedure is to be completed no later than 12 hours prior to drug administration.
3.
Drug screen and alcohol breath test will be performed on admission. Infection screening of SARS CoV2 / COVID-19
will be performed on admission or prior to admission.
4.
The time is approximate; the procedure is to be performed and completed within the 3 h prior to drug administration.
5.
If several actions are indicated at the same time, the intake of meals/fluid will be the last action.
6.
At the end of study (synonym for end of trial), the EoS examination includes physical examination, vital signs, ECG, 
safety laboratory recording of AEs and concomitant therapies, body weight.
7.     Letters A, B, and C define different sets of safety laboratory examinations (see Section 5.2.3)
8. 
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.

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TABLE OF CONTENTS
TITLE PAGE ......................................................................................................1
CLINICAL TRIAL PROTOCOL SYNOPSIS ................................................2
FLOW CHART...................................................................................................3
TABLE OF CONTENTS ...................................................................................4
ABBREVIATIONS AND DEFINITIONS........................................................8
1.
INTRODUCTION.................................................................................... 11
1.1
MEDICAL BACKGROUND............................................................................11
1.3
RATIONALE FOR PERFORMING THE TRIAL........................................15
1.4
BENEFIT - RISK ASSESSMENT ...................................................................15
1.4.1
Benefits...................................................................................................15
1.4.2
Risks .......................................................................................................15
1.4.3
Discussion...............................................................................................19
2.
TRIAL OBJECTIVES AND ENDPOINTS........................................... 20
2.1
MAIN OBJECTIVES, PRIMARY AND SECONDARY ENDPOINTS ......20
2.1.1
Main objectives......................................................................................20
2.1.2
Primary endpoints ................................................................................20
2.1.3
Secondary endpoints.............................................................................20
2.2.2.1
Safety and tolerability..............................................................20
3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION.............. 22
3.1
OVERALL TRIAL DESIGN............................................................................22
3.2
DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE OF 
CONTROL GROUP..........................................................................................22
3.3
SELECTION OF TRIAL POPULATION ......................................................22
3.3.1
Main diagnosis for trial entry..............................................................23
3.3.2
Inclusion criteria...................................................................................23
3.3.3
Exclusion criteria ..................................................................................23

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3.3.4
Withdrawal of subjects from treatment or assessments ...................25
3.3.4.1
Withdrawal from trial treatment ..............................................25
3.3.4.2
Withdrawal of consent to trial participation ............................26
3.3.4.3
Discontinuation of the trial by the sponsor and dose stopping 
criteria ......................................................................................26
3.3.5
Replacement of subjects .......................................................................26
4.
TREATMENTS........................................................................................ 27
4.1
INVESTIGATIONAL TREATMENTS ..........................................................27
4.1.1
Identity of the Investigational Medicinal Products ...........................27
4.1.2
Selection of doses in the trial................................................................27
4.1.3
Method of assigning subjects to treatment groups ............................27
4.1.4
Drug assignment and administration of doses for each subject .......28
4.1.5
Blinding and procedures for unblinding ............................................28
4.1.5.1
Blinding....................................................................................28
4.1.6
Packaging, labelling, and re-supply ....................................................28
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
4.3
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
5.2.4.1
12-lead resting ECG.................................................................35
5.2.5
Other safety parameters.......................................................................36
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’.............................37
5.2.6.1.4 Adverse events of special interest .............................37
5.2.6.1.5 Intensity (severity) of AEs.........................................38
5.2.6.1.6 Causal relationship of AEs ........................................39
5.2.6.2
Adverse event collection and reporting ...................................39

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5.2.6.2.1 AE collection.............................................................39
5.2.6.2.2 AE reporting to the sponsor and timelines ................40
5.2.6.2.3 Pregnancy ..................................................................41
5.3
DRUG CONCENTRATION MEASUREMENTS AND 
PHARMACOKINETICS..................................................................................41
5.3.1
Assessment of pharmacokinetics .........................................................41
5.3.2
Methods of sample collection...............................................................41
5.3.2.1
Blood sampling for pharmacokinetic analysis.........................41
..................................................................................................42
5.4
ASSESSMENT OF BIOMARKERS................................................................42
5.4.1
Pharmacodynamic biomarkers............................................................42
5.4.2
Pharmacogenomic biomarkers............................................................42
5.5
BIOBANKING ...................................................................................................42
5.6
OTHER ASSESSMENTS .................................................................................42
5.6.1
Pharmacogenomic evaluation..............................................................42
5.7
APPROPRIATENESS OF MEASUREMENTS.............................................42
6.
INVESTIGATIONAL PLAN.................................................................. 43
6.1
VISIT SCHEDULE............................................................................................43
6.2
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS ................43
6.2.1
Screening period....................................................................................43
6.2.2
Treatment period ..................................................................................43
6.2.3
Follow-up period and trial completion ...............................................44
7.
STATISTICAL METHODS AND DETERMINATION OF
SAMPLE SIZE......................................................................................... 45
7.1
NULL AND ALTERNATIVE HYPOTHESES ..............................................45
7.2
PLANNED ANALYSES....................................................................................45
7.2.1
General considerations.........................................................................45
7.2.1.1
Analysis sets.............................................................................45
7.2.1.2
Pharmacokinetics.....................................................................45
7.2.2
Primary endpoint analyses...................................................................46
7.2.3
Secondary endpoint analyses ...............................................................46
7.2.5
Safety analyses.......................................................................................46
7.2.6
Interim analyses ....................................................................................47
7.3
HANDLING OF MISSING DATA ..................................................................47
7.3.1
Safety......................................................................................................47
7.3.2
Pharmacokinetics..................................................................................47
7.4
RANDOMISATION ..........................................................................................47
7.5
DETERMINATION OF SAMPLE SIZE ........................................................47

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8.
INFORMED CONSENT, TRIAL RECORDS, DATA 
PROTECTION, PUBLICATION POLICY, AND 
ADMINISTRATIVE STRUCTURE...................................................... 49
8.1
TRIAL APPROVAL, SUBJECT INFORMATION, INFORMED 
CONSENT ..........................................................................................................49
8.2
DATA QUALITY ASSURANCE .....................................................................50
8.3
RECORDS..........................................................................................................50
8.3.1
Source documents .................................................................................50
8.3.2
Direct access to source data and documents.......................................51
8.3.3
Storage period of records.....................................................................51
8.4
EXPEDITED REPORTING OF ADVERSE EVENTS .................................52
8.5
STATEMENT OF CONFIDENTIALITY AND SUBJECT PRIVACY.......52
8.5.1
Collection, storage and future use of biological samples and 
corresponding data ...............................................................................52
8.6
TRIAL MILESTONES .....................................................................................52
8.7
ADMINISTRATIVE STRUCTURE OF THE TRIAL ..................................53
9.
REFERENCES......................................................................................... 54
9.1
PUBLISHED REFERENCES...........................................................................54
9.2
UNPUBLISHED REFERENCES.....................................................................54
10. APPENDIX ............................................................................................... 55
11. DESCRIPTION OF GLOBAL AMENDMENT(S).............................. 56

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ABBREVIATIONS AND DEFINITIONS
ADME
Absorption, distribution, metabolism, and excretion
AE
Adverse event
AESI
Adverse events of special interest
ALAT
Latin American Thoracic Society
ALT
Alanine aminotransferase
AST
Aspartate aminotransferase
ATS
American Thoracic Society
AUC0-∞
Area under the concentration-time curve of the analyte in plasma over the 
time interval from 0 extrapolated to infinity
BI
Boehringer Ingelheim
BMI
Body mass index (weight divided by height squared)
BP
Blood pressure
CA
Competent authority
cAMP
Cyclic adenosine monophosphate
Cmax
Maximum measured concentration of the analyte in plasma
CRF
Case Report Form, paper or electronic (sometimes referred to as ‘eCRF’)
CT Leader
Clinical Trial Leader
CT Manager
Clinical Trial Manager
CTP
Clinical trial protocol
CTR
Clinical trial report
DG
Dose group
DILI
Drug induced liver injury
ECG
Electrocardiogram
ECM
Extracellular matrix
eCRF
Electronic case report form
EDTA
Ethylenediaminetetraacetic acid
EoS
End of Study (synonym for End of Trial) 
ERS
European Respiratory Society
GCP
Good Clinical Practice
gMean
Geometric mean
HIV
Human immunodeficiency virus
HR
Heart rate

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IB
Investigator’s brochure
IC50
half maximal (50%) inhibitory concentration
IEC
Independent Ethics Committee
IFN
Interferon
ILD
Interstitial lung disease
IPD
Important protocol deviation
IRB
Institutional Review Board
ISF
Investigator site file
JRS
Japanese Respiratory Society
LC-MS/MS
liquid chromatography tandem mass spectrometry
LOAEL
Lowest observed adverse effect Level
LPS
Lipopolysaccharide
MDA
Methylenedioxyamphetamine
MDMA
Methylenedioxymethamphetamine
MedDRA
Medical Dictionary for Regulatory Activities
MRD
Multiple-rising dose
NOAEL
no adverse effect level
PDE4B
phosphodiesterase 4B
PDE4D
phosphodiesterase 4D
PDE4i
phosphodiesterase 4 inhibitor
PK
Pharmacokinetic(s)
PKS
Pharmacokinetic set
PopPK
Population Pharmacokinetics
PP
Polypropylene
PPF
progressive pulmonary fibrosis
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
RR
Respiratory rate
RR interval
ECG interval from the peak of the R wave to the peak of the subsequent 
R wave
SAE
Serious adverse event
SCR
Screening
SOP
Standard operating procedure
SRD
Single rising dose
SUSAR
Suspected unexpected serious adverse reaction
TMF
Trial master file
TNF
Tumor Necrosis Factor
t1/2
Terminal half-life of the analyte in plasma

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tmax
Time from (last) dosing to the maximum measured concentration of the 
analyte in plasma
TS
Treated set
TSAP
Trial statistical analysis plan
ULN
Upper limit of normal
Vz
Apparent volume of distribution during the terminal phase after 
intravascular administration
WBC
white blood cell

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1.
INTRODUCTION
BI 1015550, a preferential 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) and 
progressive pulmonary fibrosis (PPF).
1.1
MEDICAL BACKGROUND
IPF and other progressive fibrosing interstitial lung diseases 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 
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 and many other countries for the treatment of other fibrosing ILDs 
with progressive phenotype. Despite the availability of these drugs, the medical need remains 
high in these devastating diseases.

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1.3
RATIONALE FOR PERFORMING THE TRIAL
 
The rationale of this trial is to assess pharmacokinetics of 
R-BI 1015550 following single oral doses in Japanese healthy male subjects. The chosen 
population of healthy male subjects receiving single oral doses is considered adequate to 
provide the basis for the clinical development program of BI 1015550 in Japan.
1.4
BENEFIT - RISK ASSESSMENT
1.4.1
Benefits
Participation in this clinical trial is without any (therapeutic) benefit for healthy subjects. 
Their participation, however, is of major importance for the development of BI 1015550 and 
its use in Japanese patients. 
1.4.2
Risks
Subjects are exposed to risks of trial procedures and risks related to the exposure to the trial 
medication. An overview on trial-related risks is given in Table 1.4.2: 1.
There are no identified risks for BI 1015550, based on the toxicology program or any clinical 

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trials conducted for this product to date. Vasculitis and foetal loss are considered as important 
potential risks based only on nonclinical findings (see section 1.2.1).
Apart from risks related to trial procedures, the risks shown in the table below are hypothetical 
in nature; these are derived from general safety considerations of immunomodulatory drugs 
and from nonclinical and clinical data of compounds with a comparable mode of action. For 
clinical data including adverse events reported during clinical trials with BI 1015550 please 
refer to Section 1.2.
Table 1.4.2: 1
Overview of trial-related risks for this trial 
Possible or known 
risks of clinical 
relevance for this 
trial
Summary of data, rationale for the 
risk
Mitigation strategy
Investigational Medicinal Product BI 1015550: compound/class specific (refer to Section 1.2) 
Vasculitis
Vasculopathy is an established 
nonclinical toxicity of PDE4 inhibitors.
Vasculitis has been shown in both the 
rats and minipigs following oral 
administration of BI 1015550 but not in 
13- or 39-week studies in monkeys.
Vasculitis is listed as an important 
potential risk in the RMP for the 
marketed PDE4- inhibitor apremilast. 
In marketed PDE4 inhibitors, vasculitis 
has not been identified as an adverse drug 
reaction in humans
History of vasculitis is an exclusion 
criterion.
Close clinical monitoring for AEs of 
vasculitis
Weight decrease in 
underweight patients 
(BMI <18.5 kg/m2)
For the marketed PDE4-inhibitors 
apremilast and roflumilast weight loss in 
underweight patients is an identified 
important risk.
Patients who have a BMI 
<18.5 kg/m2 are excluded.
Psychiatric disorders:

Depression and 
anxiety

Suicidality
For the marketed PDE4 inhibitors 
depression is listed as a side effect. They 
are associated with increased risk of 
depression with some patients reporting 
suicidal ideation and/or attempts, with 
some reported cases of completed 
suicide.
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 

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Possible or known 
risks of clinical 
relevance for this 
trial
Summary of data, rationale for the 
risk
Mitigation strategy
High incidence of depression in the ILD 
population per se.
In IPF patients treated with 18 mg 
BI 1015550 bid for up to 12 weeks, no 
on-treatment events of suicidal ideation 
or behavior and no events of depression 
or anxiety were reported
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.
Any lifetime history of suicidal 
behavior (i.e. actual attempt, 
interrupted attempt, aborted attempt, 
or preparatory acts or behavior) at 
screening will be excluded
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
Screening procedures for infections 
are defined for this trial. Patients 
with any relevant chronic or acute 
infections including human 
immunodeficiency virus (HIV), viral 
hepatitis or active tuberculosis are 
excluded from the trial. 
Treatment of infections should be 
initiated promptly according to 
standards of care.
MACE and 
tachyarhythmia
Important potential risk for marketed 
PDE4 inhibitor apremilast
In nonclinical 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
o
close clinical monitoring for 
AEs;
o
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.
Patients with a recent history of 
malignancy within 5 years will be 
excluded from participation in this 
trial except patients with 
appropriately treated basal cell 
carcinoma or in situ squamous cell 
carcinoma of the skin or in situ 
carcinoma of uterine cervix

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Possible or known 
risks of clinical 
relevance for this 
trial
Summary of data, rationale for the 
risk
Mitigation strategy
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.
Gastrointestinal disorders are very 
common or common side effect of the 
approved antifibrotics.
Increased awareness of symptoms.
Careful monitoring of hydration in 
patients with diarrhoea 
recommended.
Symptomatic treatment, e.g. 
loperamide, if required
Reproductive toxicity: 

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 female reproductive organs 
or male spermatogenesis. For another 
PDE4 inhibitor with comparable 
nonclinical findings, clinical data showed 
no effect on male fertility and sperm in 
humans.
In monkeys, a sporadic prolongation in 
menstrual cycles was observed at 
approximately ≥4-fold human exposure 
at 18 mg BI 1015550 bid.
Fetal loss was increased in female rats 
treated with BI 1015550.  
Only male subjects will be screened 
for this study
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 patients´ safety. 
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
o
close clinical monitoring for 
AEs;
o
selection of experienced sites 
and site staff 

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In addition, the following general safety measures will be applied in order to minimize the 
risk to the healthy volunteers: 

Careful dose selection

Subjects will be hospitalised throughout the study from Day -1 to Day 8

Adequate safety monitoring will be performed (e.g., vital signs including ECGs, 
safety laboratory tests, and adverse events). 
The total volume of blood withdrawn per subjects during the entire trial will not exceed 
400 mL. This is less than the volume of a normal blood donation (500 mL). No health-related 
risk to 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.
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.
Considering the medical need for the development of a better tolerated and more effective 
treatment for patients with BI 1015550, the expected benefit outweighs the potential risks.

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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 pharmacokinetics (PK) of R-BI 1015550 in 
Japanese healthy male subjects following oral administration of single BI 1015550 dose of 9 
mg or 18 mg.
2.1.2
Primary endpoints
The following pharmacokinetic parameters will be determined for R-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
Not applicable
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), respiratory rate (RR))

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3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION
3.1
OVERALL TRIAL DESIGN
This single dose trial is designed as open-label to subject, investigator, and sponsor functions 
(refer to Section 4.1.5) and non-randomised within parallel dose groups.
It is planned to include a total of 12 healthy male subjects in the trial. The subjects will be 
assigned to 2 groups consisting of 6 subjects per group (see Table 3.1: 1). 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
Dose group
1
2
Dose
9 mg
18 mg
No. of subjects entered
6
6
No. of subjects receiving active
6
6
The groups will be dosed in parallel. 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 schedules 
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, non-randomised, and
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 single doses to be tested in this trial are those used in the pivotal Phase III trials.
3.3
SELECTION OF TRIAL POPULATION
It is planned that 12 healthy male subjects will enter the trial. Subjects will be recruited by the 
contracted third vendor.
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.

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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.
3.3.2
Inclusion criteria
Subjects will only be included in the trial if they meet the following criteria:
1. Healthy male subjects according to the assessment of the investigator, as based on a 
complete medical history including a physical examination, vital signs (BP, PR, RR), 12-
lead ECG, and clinical laboratory tests 
2. Age of 18 to 45 years (inclusive) 
3. BMI of 18.5 to 25 kg/m2 (inclusive) 
4. Signed and dated written informed consent in accordance with ICH-GCP and local 
legislation prior to admission to the trial
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, RR 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 40 to 90 mmHg, or PR outside the range of 
40 to 99 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
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 or in situ squamous 
cell carcinoma of the skin or in situ carcinoma of uterine cervix

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11. History of relevant allergy or hypersensitivity (including allergy to the trial medication or 
its excipients) 
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 of 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 30 g per day)
17. Drug abuse or positive drug screening
18. Blood donation of more than 400 mL within 12 weeks or 200 mL within 30 days or
plasma donation within 2 weeks prior to 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 male) 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. History of disease that affects the present situation
25. Laboratory test indicative of an ongoing SARS-CoV-2/COVID-19 infection on Day -1 or 
prior to admission, and/ or any clinical symptom suggestive for this disease.
In addition, the following trial-specific exclusion criteria apply:
26. Any lifetime history of suicidal behavior (i.e. actual attempt, interrupted attempt, aborted 
attempt, or preparatory acts or behavior) 
27. History of vasculitis
For restrictions of the trial, refer to Section 4.2.2.

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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).
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 1.2.6), the 
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 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
In addition to these criteria, the investigator may discontinue subjects at any time based on 
his or her clinical judgment.
If new 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.

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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 
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 and dose stopping criteria
Boehringer Ingelheim reserves the right to discontinue the trial at any time for any of the 
following reasons (if reason 4 is 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 product
3. Deviation from GCP, or the CTP, or the contract with BI impairing the appropriate 
conduct of the trial
4. New toxicological findings, serious AEs, or any safety information invalidating the 
earlier positive benefit-risk assessment (see Section 3.3.4.1)
The investigator / trial site will be reimbursed for reasonable expenses incurred in case of 
trial termination (except if item 3 applies).
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. A replacement subject will be assigned a unique trial subject number and will be 
assigned to the same treatment as the subject he 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:
9 mg
Posology:
1-0-0
Mode of administration:
Oral
Duration of use:
Single dose 
The characteristics of the reference product are given below:
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 
4.1.2
Selection of doses in the trial
The doses selected for this trial are the standard clinical dose investigated in the phase 3 
clinical trials (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 willing to participate will be recruited to dose groups 
according to their temporal availability.
As soon as enough subjects are allocated to 1 of 2 dose groups, the following subjects will be 
allocated to remaining 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 

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includes healthy subjects of only Japanese 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 outlined in Table 4.1.4: 1 below.
Table 4.1.4: 1
BI 1015550 treatments, oral administration 
Dose
group
Substance
Pharmaceutical 
form
Unit strength
Number of units
per administration
Total daily
dose
1
BI 1015550 Tablet
9 mg
1 film-coated tablet, single dose
9 mg
2
BI 1015550 Tablet
18 mg
1 film-coated tablet 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 a sitting/standing position. For drug administration, 
the so-called four-eye principle (two-person rule) should be applied. For this, 1 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 except for 
medical examination) or to sleep.
4.1.5
Blinding and procedures for unblinding
4.1.5.1
Blinding
This non-randomised open-label Phase I trial will be handled in an open fashion throughout. 
The treatment assignment will be available to all involved parties. 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 department of Pharmaceutical 
Development of Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany. 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.

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The telephone number of the sponsor and the name, address and telephone number of the trial 
site are provided in the subject information form.
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
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 (CA)

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.
All unused trial 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.

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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 trial days) on the appropriate pages of the CRF.
The use of known PDE-inhibitors such as: theophyllin, theobromin, sildenafil, tadalafil, 
vardenafil, apremilast and roflumilast must be avoided during the whole course of the study. 
Further, the use of known inhibitors and inducers of CYP3A and P-gp activity is not allowed.
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). 
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.
Methylxanthine-containing drinks or foods (such as coffee, tea, cola, energy drinks, or 
chocolate) are not allowed from 4 h before until 4 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. 
Direct exposure to the sun or exposure to solarium radiation should be avoided during the 
entire trial.

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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, and RR), 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 including determination of body 
weight.
5.2.2
Vital signs
Systolic and diastolic BP as well as PR or heart rate (HR) (HR is considered to be equal to 
PR), and RR will be measured at the times indicated in the Flow Chart, after subjects have 
rested for at least 5 min in a supine position. Blood pressures and pulse rate 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 [WBC] /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) and as per 
judgement by the
investigator)
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
A: parameters to be determined at Visit 1 (screening examination) 
B: parameters to be determined at Visit 2 on Day 2 and Day6 (for time points refer to Flow Chart)
C: parameters to be determined at Visit 2 on Day1 and Visit 3 (end of trial examination)

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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
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
Urine sediment 
(microscopic 
examination 
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 on Day 6 (for time points refer to Flow Chart)
C: parameters to be determined at Visit 2 on Day1 and Visit 3 (end of trial examination)
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. It is planned to perform these tests at screening only. 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)
Amphetamine/MDA
Barbiturates
Benzodiazepine
Cannabis
Cocaine 
Methamphetamines/MDMA/Ecstacy
Opiates 
Phencyclidine
Tricyclic antidepressants
Oxycodone
Propoxyphene
Infectious serology (blood)
Hepatitis B surface antigen (qualitative)
Hepatitis B core antibody (qualitative)
Hepatitis C antibodies (qualitative)
HIV-1 and HIV-2 antigen and/or antibody (qualitative)
Syphilis test (RPR, TP antibody method)
Infectious test
SARS CoV2 / COVID-19
To encourage compliance with alcoholic restrictions, a breath alcohol test 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. 
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
5.2.4.1
12-lead resting ECG
Recording
Twelve-lead resting ECGs (I, II, III, aVR, aVL, aVF, V1 - V6) will be recorded using a 
computerised electrocardiograph at the time points given in the Flow Chart. 
To achieve a stable HR 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 recording will always precede all other trial procedures scheduled for 
the same time (except for blood drawing from an intravenous cannula that is already in place) 
to avoid compromising ECG quality.

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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 recorded for safety reasons. 
All ECGs will be stored stored electronically on the local ECG machine. Electrode placement 
will be performed according to the method of Wilson, Goldberger and Einthoven.
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. 
5.2.5
Other safety parameters
Not applicable.
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.
Adverse event report for diarrhea events
In case of events of diarrhoea the following definitions should be followed:
Diarrhoea is defined ≥3 loose/liquid stools per day (WHO definition)
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 

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
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
An event that possibly leads to disability will be handled as ‘deemed serious for any other 
reason’ and, therefore, reported as an SAE.
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 
‘Always Serious AEs’ will be provided upon request. These events should always be reported 
as SAEs as described 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: 

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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. 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), 
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

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.

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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 
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. 

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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 
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.

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5.2.6.2.3
Pregnancy
Once the male subject has been enrolled in the clinical trial and has taken trial medication, 
and if a partner of the male trial participant becomes pregnant, the investigator must report 
any drug exposure during pregnancy in a partner of the male trial participant immediately 
(within 24 hours) by means of Part A of the Pregnancy Monitoring Form to the sponsor’s 
unique entry point, after a written consent of the pregnant partner.
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 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 
, R-
-BI 1015550 concentrations in plasma, 3 mL of 
blood will be drawn from an antecubital or forearm vein into a 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.
Sample handling will be described in detail in a separate lab manual.
Until transfer on dry ice to the analytical laboratory, the plasma samples will be stored at 
approximately -20°C or below at the trial site.
At a minimum, the sample tube labels should list BI trial number, subject number, visit, 
barcode and planned sampling time. Further information such as matrix and analyte may also 
be provided. 
The trial samples will be discarded6 months after the end of the trial.

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5.4
ASSESSMENT OF BIOMARKERS 
Not applicable.
5.4.1
Pharmacodynamic biomarkers
Not applicable.
5.4.2
Pharmacogenomic biomarkers
Not applicable.
5.5
BIOBANKING
Not applicable.
5.6
OTHER ASSESSMENTS
Not applicable.
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, and blood laboratory 
tests will be ± 30 min for the first 24 h after trial drug administration and ± 120 min 
thereafter. Urine laboratory test can be performed between wake-up to the scheduled time.
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 5.2.2 to 5.2.5.
6.2.2
Treatment period
Each subject will receive one dose of trial medication (BI 1015550) at Visit 2.
Trial medication will be taken orally following an overnight fasting of at least 10 hours by 
each subject under direct supervision of the investigator or 
 designee. Details on treatments 
and procedures of administration are described in Section 4.1.4.
Trial participants will be admitted to the trial site in the morning of Day -1 and kept under 
close medical surveillance for at least 24 h following the drug administration. The subjects 

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will then be allowed to leave the trial site after formal EoS assessment by the investigator or 
 designee on Day 8. 
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 
continuously from the time of the 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.
If needed in the opinion of the investigator, additional visits may be scheduled after the EoS
Visit for continued safety monitoring.
If a subject discontinues from the trial, the subject will be followed until the investigator or 
sub-investigator is convinced of the subject’s safety. If follow-up is not possible or comes to 
an end, follow-up should be formally completed after discussion with the sponsor. If a subject 
stop attending trial assessments, the investigator should assess the subject’s status as 
comprehensively as possible and the well-being of the subject should be monitored. 
However, if the subject withdraws from the trial, it is the subject’s choice whether or not to 
participate in further assessments; he or she cannot be compelled.

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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.
Any confidence intervals computed are to be interpreted in the perspective of the exploratory 
character of the trial; i.e., confidence intervals are considered as interval estimates for effects.
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 treatment assignment will be determined based on the first 
treatment the subjects received. 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 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 contributes only one PK parameter value for one 
period to the statistical assessment. Descriptive and model-based 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 BI 1015550 will be 
calculated according to the relevant BI internal procedure. 
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 dose of trial medication taken

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
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 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 as 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 as specified in Section 2.1.2 will be derived according to BI standards. 
The analysis will be based on the PKS and will be descriptive in nature.
7.2.3
Secondary endpoint analyses
No secondary endpoint analysis will be performed.
7.2.5
Safety analyses
Safety will be assessed as defined by the endpoints listed in Section 2.1.2 and 2.2.2 based on 
the treated set (TS). Safety analyses will be descriptive in nature and will be based on BI 
standards. 
For all analyses the treatment actually administered (= treatment at onset) to the subject will 
be used (any deviations from the assigned 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 for the evaluation of categorical (qualitative) data, and tabulations of descriptive 
statistics will be used to analyse continuous (quantitative) data.
Measurements (such as ECGs, 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, 

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measurements performed or AEs recorded prior to intake of trial medication will be assigned 
to the screening period, those between the trial medication intake and end of REP (see 
Section 1.2.6) 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.
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 dose 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 formal 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 
procedure. 
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 a total of 12 subjects in this trial and a total of up to 20 subjects 
including up to 8 replaced subjects in this trial. The planned sample size is not based on a 

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power calculation. The size of 6 subjects per dose group (6 on active treatment) is commonly 
used in single dose studies of the present type and is in general considered as sufficient for 
the exploratory evaluation of single dose safety and pharmacokinetics.

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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 responsible Institutional Review Board (IRB) / Independent Ethics 
Committee (IEC) and 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 investigator or delegate must give a full explanation to trial subjects based on the subject 
information form. A language understandable to the subject should be chosen and technical 
terms and expressions avoided, if possible.
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.

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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 
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.

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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

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(s) 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.

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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.
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.

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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. The investigators will have access to the BI web portal 
Clinergize to access documents provided by the sponsor.
BI has appointed a Clinical Trial Leader (CT Leader), 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 Managers
(CT Managers), 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.
Analyses of BI 1015550 concentrations in plasma will be performed at 
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 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
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
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.
R10-1559
Giembycz MA. Life after PDE4: overcoming adverse events with dual 
specificity phosphodiesterase inhibitors. Curr Opin Pharmacol 2005; 5:238-
244.
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.
9.2
UNPUBLISHED REFERENCES
c02094779
BI 1015550 - Investigator’s Brochure, current version
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
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

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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.
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
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
n00293932
[14C]BI 1015550: 
Metabolite 
profiling 
and 
tentative 
metabolite
identification in humans. Draft report.
c28747743
Safety, tolerability and pharmacokinetics of single rising oral doses of
BI 1015550 in healthy Japanese male subjects (double-blind, randomised, 
placebo-controlled, parallel group design). 1305-0017.
c40607236
The effect of multiple oral doses of BI 1015550 on metabolism of
midazolam administered orally in healthy male subjects (open-label, two-
period fixed sequence design trial). 1305-0033.
10.
APPENDIX
Not applicable.

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11.
DESCRIPTION OF GLOBAL AMENDMENT(S)
This is the original protocol.

 
 
 
 
APPROVAL / SIGNATURE PAGE 
 
Document Number: 
 
Technical Version Number:
 
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Title: 
 
 
 
 
                                                                                                                   
 
Signatures (obtained electronically) 
 
Meaning of Signature  
Signed by 
Date Signed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Pharmacokinetics of R-BI 1015550 after single oral doses of BI 1015550 in Japanese
healthy male subjects (open-label, non-randomised, and parallel group design)
Author-Clinical Trial Leader
07 Aug 2023 09:18 CEST
Author-Trial Statistician
07 Aug 2023 14:28 CEST
Approval-Clinical Program 
07 Aug 2023 15:37 CEST
Verification-Paper Signature
Completion
08 Aug 2023 08:12 CEST

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