Investigation of Pharmacokinetics and Absolute Oral Bioavailability of BI 1015550 Administered as an Oral Dose With an Intravenous Microtracer Dose of [14C]-BI 1015550 in Healthy Male Volunteers
Phase: PHASE1
Conditions: Healthy
Sponsor: Boehringer Ingelheim



Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 2 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
CLINICAL TRIAL PROTOCOL SYNOPSIS
Company name
Boehringer Ingelheim
Original protocol date
12 December 2022
Revision date
Not applicable
BI trial number
1305-0030
Title of trial
Investigation of pharmacokinetics and absolute oral bioavailability of BI 1015550 
administered as an oral dose with an intravenous microtracer dose of [14C]-BI 
1015550 in healthy male volunteers
Investigator
Trial site
Clinical phase
I
Trial rationale
This trial is intended to examine the absolute oral bioavailability of BI 1015550 as
tablet formulation for oral administration, using an intravenous microtracer 
approach with [14C]-labelled BI 1015550. These data are considered necessary to
further support the understanding of the pharmacokinetics of BI 1015550
Trial objective
To determine the absolute oral bioavailability of BI 1015550
Trial endpoints
Primary endpoints:
AUC0-∞of [14C]-BI 1015550 i.v.
AUC0-∞of BI 1015550 p.o.
Secondary endpoint: 
Oral route: Cmax of BI 1015550 p.o.
Trial design
Non-randomised, open-label, single period, single arm
Number of subjects 
total entered
8
on each treatment
8
Diagnosis
Not applicable
Main inclusion criteria
Healthy male subjects, age of 18 to 65 years (inclusive), body mass index (BMI) of 
18.5 to 29.9 kg/m2 (inclusive)

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 4 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
FLOW CHART
Visit
Day
Planned time (relative to drug 
administration) [h:min]
Approximate clock time of 
actual day [h:min]
Event and comment
Safety laboratory, 12, 13
PK plasma BI 1015550 9
PK plasma [14C]-BI 1015550 9
12-lead ECG 7, 13
Vital signs (BP, PR) 10, 13
Questioning for AEs and 
concomitant therapy 6
1
-21 to 
-2
Screening (SCR)1
xA
x
x
2
-1
Admission to trial site
xB,5,12
x
Dinner
Snack (voluntary)
1
x2
x2
x2
x2
x2
Drug administration
(BI 1015550, 
 tablet, oral)
x
x
x
x
Start of i.v. infusion of BI 
1015550 (C-14)
x11
x
x
x
Stop of i.v. infusion of BI 
1015550 (C-14)
x11
x11
x
240 mL fluid intake
x
x
x
x
x
x
x
240 mL fluid intake, 
thereafter lunch3
x
x
x
x
x
240 mL fluid intake
x
Snack (voluntary)3
x
x
x
x
x
Dinner
x
x
x
2
x
x
xB,12
x
x
x
x
x
x
x
x
3
x
x
x
4
x
x
x
x
x
Breakfast (voluntary)3, discharge 
from trial site
6
Ambulatory visit
xB
x
x
x
8
Ambulatory visit
x
x
x
10
Ambulatory visit
x
x
3
11-
21
End of study (EoS) examination4
XA
x
x
x

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 5 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
A, B
Letters A and B describe different sets of safety laboratory examinations (see Table 5.2.3: 1).
1.
Subject must be informed and written informed consent obtained prior to starting any screening procedures. Screening 
procedures include physical examination, check of vital signs, ECG, safety laboratory (including drug screening), 
demographics (including determination of body height and weight, smoking status and alcohol history), relevant 
medical history, concomitant therapy and review of inclusion/exclusion criteria.
2.
The time is approximate; the procedure is to be performed and completed between waking up and (still prior to) drug 
administration.
3.
If several actions are indicated at the same time, the intake of meals will be the last action.
4.
, 
 
5.
Drug and alcohol screening will be done at this time.
6.
AEs and concomitant therapies will be recorded throughout the trial but will be specifically asked for at the times
indicated in the Flow Chart above. If no particular time is indicated, AEs and concomitant therapies will be checked 
twice daily (morning and evening) until discharge.
7.
12-lead ECG for clinical evaluation by the investigator only. For details of 12-lead ECG, refer to Section 5.2.4. If 
several assessments are planned at the same time, ECG should be performed before vital signs, which will be followed 
by blood samples.
8.
Time window for ambulatory visits is 
9.
For details of PK blood sampling (including samples for the quantification of BI 1015550 concentrations in plasma,
[14C]-BI 1015550, and total radioactivity in plasma), refer to Section 5.3.2. Up to 2.5 h following the administration of 
BI 1015550 tablets, samples should be taken within 
 from the scheduled time; from 
 until discharge,
samples should be taken within +/- 5% of the elapsed time since BI 1015550 tablets were taken. After discharge, 
samples should be taken in line within the time window for ambulatory visits (cf. footnote 8).
10. For details of vital signs evaluation, refer to Section 5.2.2.
11. PK samples will be taken before the start of infusion and after the end of infusion, respectively.
12. PCR testing for SARS-CoV-2 will be performed on Day -1 prior to admission, and on Day 2. PCR testing for SARS-
CoV-2 may be performed additionally as needed based on the current status of the pandemic. SARS-CoV-2 testing on 
Day 2 may take place at any time during this day.
13. Up to 
 following the administration of BI 1015550 tablets, all safety assessments should be done within 
 
of the planned time; from 
until discharge, all safety assessments should be done within +/- 10% of the elapsed 
time since BI 1015550 tablets were taken. After discharge, samples should be taken in line within the time window for 
ambulatory visits (cf. footnote 8).

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 6 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
TABLE OF CONTENTS
TITLE PAGE ......................................................................................................1
CLINICAL TRIAL PROTOCOL SYNOPSIS ................................................2
FLOW CHART...................................................................................................4
TABLE OF CONTENTS ...................................................................................6
ABBREVIATIONS AND DEFINITIONS..................................................... 10
1.
INTRODUCTION.................................................................................... 13
1.1
MEDICAL BACKGROUND............................................................................13
1.2
DRUG PROFILE...............................................................................................13
1.2.1
Clinical Pharmacokinetics....................................................................14
1.2.2
Clinical safety and efficacy...................................................................15
1.2.3
Residual Effect Period..........................................................................17
1.3
RATIONALE FOR PERFORMING THE TRIAL........................................17
1.3.1
Nomenclature ........................................................................................17
1.4
BENEFIT - RISK ASSESSMENT ...................................................................17
1.4.1
Benefits...................................................................................................17
1.4.2
Risks .......................................................................................................17
1.4.3
Discussion...............................................................................................21
2.
TRIAL OBJECTIVES AND ENDPOINTS........................................... 23
2.1
MAIN OBJECTIVES, PRIMARY AND SECONDARY ENDPOINTS ......23
2.1.1
Main objectives......................................................................................23
2.1.2
Primary endpoint(s)..............................................................................23
2.1.3
Secondary endpoint ..............................................................................23
2.2.2.2
Safety and tolerability..............................................................24
3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION.............. 25
3.1
OVERALL TRIAL DESIGN............................................................................25
3.2
DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE OF 
CONTROL GROUP..........................................................................................25
3.3
SELECTION OF TRIAL POPULATION ......................................................26
3.3.1
Main diagnosis for trial entry..............................................................26
3.3.2
Inclusion criteria...................................................................................26
3.3.3
Exclusion criteria ..................................................................................26
3.3.4
Withdrawal of subjects from treatment or assessments ...................28
3.3.4.1
Withdrawal from trial treatment ..............................................28
3.3.4.2
Withdrawal of consent to trial participation ............................29

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 7 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
3.3.4.3
Discontinuation of the trial by the sponsor..............................29
3.3.5
Replacement of subjects .......................................................................29
4.
TREATMENTS........................................................................................ 31
4.1
INVESTIGATIONAL TREATMENTS ..........................................................31
4.1.1
Identity of the Investigational Medicinal Products ...........................31
4.1.2
Selection of doses in the trial................................................................32
4.1.3
Method of assigning subjects to treatment groups ............................32
4.1.4
Drug assignment and administration of doses for each subject .......32
4.1.5
Blinding and procedures for unblinding ............................................33
4.1.6
Packaging, labelling, and re-supply ....................................................33
4.1.7
Storage conditions.................................................................................34
4.1.8
Drug accountability ..............................................................................34
4.2
OTHER TREATMENTS, EMERGENCY PROCEDURES, 
RESTRICTIONS ...............................................................................................35
4.2.1
Other treatments and emergency procedures....................................35
4.2.2
Restrictions............................................................................................35
4.2.2.1
Restrictions regarding concomitant treatment .........................35
4.2.2.2
Restrictions on diet and lifestyle..............................................35
4.2.2.3
Contraception requirements.....................................................36
4.3
TREATMENT COMPLIANCE.......................................................................36
5.
ASSESSMENTS....................................................................................... 37
5.1
ASSESSMENT OF EFFICACY.......................................................................37
5.2
ASSESSMENT OF SAFETY............................................................................37
5.2.1
Physical examination ............................................................................37
5.2.2
Vital signs...............................................................................................37
5.2.3
Safety laboratory parameters..............................................................37
5.2.4
Electrocardiogram................................................................................40
5.2.5
Other safety parameters.......................................................................40
5.2.5.1
Local tolerability......................................................................40
5.2.6
Assessment of adverse events...............................................................40
5.2.6.1
Definitions of adverse events...................................................40
5.2.6.1.1 Adverse event ............................................................40
5.2.6.1.2 Serious adverse event ................................................41
5.2.6.1.3 AEs considered ‘Always Serious’.............................41
5.2.6.1.4 Adverse events of special interest .............................42
5.2.6.1.5 Intensity (severity) of AEs.........................................43
5.2.6.1.6 Causal relationship of AEs ........................................43
5.2.6.2
Adverse event collection and reporting ...................................44
5.2.6.2.1 AE collection.............................................................44
5.2.6.2.2 AE reporting to the sponsor and timelines ................44
5.2.6.2.3 Pregnancy ..................................................................45
5.3
DRUG CONCENTRATION MEASUREMENTS AND 
PHARMACOKINETICS..................................................................................45

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 9 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
8.1
TRIAL APPROVAL, SUBJECT INFORMATION, INFORMED 
CONSENT ..........................................................................................................55
8.2
DATA QUALITY ASSURANCE .....................................................................56
8.3
RECORDS..........................................................................................................56
8.3.1
Source documents .................................................................................56
8.3.2
Direct access to source data and documents.......................................57
8.3.3
Storage period of records.....................................................................57
8.4
EXPEDITED REPORTING OF ADVERSE EVENTS .................................57
8.5
STATEMENT OF CONFIDENTIALITY AND SUBJECT PRIVACY.......58
8.5.1
Collection, storage and future use of biological samples and 
corresponding data ...............................................................................58
8.6
TRIAL MILESTONES .....................................................................................58
8.7
ADMINISTRATIVE STRUCTURE OF THE TRIAL ..................................59
9.
REFERENCES......................................................................................... 61
9.1
PUBLISHED REFERENCES...........................................................................61
9.2
UNPUBLISHED REFERENCES.....................................................................62
10. APPENDICES .......................................................................................... 64
10.1
APPENDIX 1: SEVERE INFECTIONS CONSIDERED AS AESI..............64
10.2
APPENDIX 2: STRONG CYP3A4 INHIBITORS .........................................65
11. DESCRIPTION OF GLOBAL AMENDMENT(S).............................. 66
11.1
GLOBAL AMENDMENT 1 .............................................................................66

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 11 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
ECG
Electrocardiogram
eCRF
Electronic case report form
eDC
Electronic data capture
EoS
End of Study (synonym for End of Trial)
ERS
European Respiratory Society
ESR
Erythrocyte Sedimentation Rate
EU
European Union
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration
GCP
Good Clinical Practice
gCV
Geometric coefficient of variation
GI
Gastro-intestinal
gMean
Geometric mean
HIV
Human Immunodeficiency Virus
IB
Investigator’s brochure
iCF
Intended commercial formulation
ICF
Informed consent form
IEC
Independent Ethics Committee
ILD
Interstitial lung disease
INR
International Normalized Ratio
IPF
Idiopathic pulmonary fibrosis
IPD
Important protocol deviation
IRB
Institutional Review Board
ISF
Investigator site file
JRS
Japanese respiratory society
KMed
Knowledge Management Medicine
K2-EDTA
Dipotassium ethylenediaminetetraacetic acid
MDA
Methylenedioxyamphetamine
MDMA
Methylenedioxymethamphetamine
MedDRA
Medical Dictionary for Regulatory Activities
MRD
Multiple-rising dose
PDE
Phosphodiesterases
PK
Pharmacokinetic(s)
PKS
Pharmacokinetic set
PPF
Progressive pulmonary fibrosis

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 16 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 17 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
Clinical efficacy
In the proof-of-clinical principle Phase II trial, a relevant treatment effect in favour of BI 
1015550 
 was observed on the primary efficacy endpoint, the change from baseline 
in forced vital capacity (FVC) at 12 weeks. Treatment with BI 1015550 prevented a decline 
in FVC in patients with IPF, irrespective of background antifibrotic treatment, in contrast to 
the placebo groups in which a marked decline in FVC was observed. Thus, treatment with BI 
1015550 
 preserved lung function in patients with IPF over 12 weeks.
1.3
RATIONALE FOR PERFORMING THE TRIAL
This trial is intended to examine the absolute oral bioavailability of BI 1015550 as tablet 
formulation for oral administration, using an intravenous microtracer approach with [14C]-
labelled BI 1015550. These data are considered necessary to further support the 
understanding of the pharmacokinetics of BI 1015550.
1.3.1
Nomenclature
In this clinical trial protocol, the following nomenclature is used:
•
[14C]-radioactivity: Radioactivity measured by means of isotope 14C
•
[14C]-BI 1015550: BI 1015550 compound labelled with 14C (“hot” drug 
substance)
•
BI 1015550: non-radioactive compound (“cold” drug substance)
•
BI 1015550 (C-14): Final drug product containing radioactive microtracer, 
mixture of “hot” and “cold” drug substance
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 
thus is expected to be of benefit for future patients receiving this drug.
1.4.2
Risks
Subjects are exposed to risks of trial procedures and risks related to the exposure to the trial 
medication. An overview of 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
trials conducted for this product to date. Vasculitis and foetal loss are considered as important
potential risk based only on non-clinical findings (see Section 1.2).

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 22 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 24 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
2.2.2.2
Safety and tolerability
Safety and tolerability of BI 1015550 will be assessed based on:
!
Adverse events (including clinically relevant findings from the physical examination)
!
Safety laboratory tests
!
12-lead ECG
!
Vital signs (blood pressure, pulse rate)
!
Local tolerability assessed by investigator (based on swelling, induration, heat, 
redness, pain, and other clinically relevant findings reported as AE after intravenous 
infusion)

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 26 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
3.3
SELECTION OF TRIAL POPULATION
It is planned that 8 healthy male subjects will enter the trial. They will be recruited from the 
volunteers' pool of the trial site.
A log of all subjects enrolled into the trial (i.e., who have signed informed consent) will be 
maintained in the ISF, irrespective of whether they have been treated with investigational 
drug or not.
3.3.1
Main diagnosis for trial entry
The trial will be performed in healthy subjects.
Please refer to Section 8.3.1 (Source Documents) for the documentation requirements 
pertaining to the in- and exclusion criteria.
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), 12-lead 
ECG, and clinical laboratory tests 
2. Age of 18 to 65 years (inclusive) 
3. BMI of 18.5 to 29.9 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 or ECG) deviating from 
normal and assessed as clinically relevant by the investigator
2. Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, 
diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the 
range of 40 to 100 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)

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 27 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
7. Diseases of the central nervous system (including but not limited to any kind of seizures 
or stroke), and other relevant neurological or psychiatric disorders (including but not 
limited to major depressive disorder or history of suicide attempts)
8. History of relevant orthostatic hypotension, fainting spells, or blackouts
9. Relevant chronic or acute infections
10. Any documented active or suspected malignancy or history of malignancy within 5 years 
prior to screening, except appropriately treated basal cell carcinoma of the skin or 
squamous cell carcinoma in situ of the skin 
11. History of relevant allergy or hypersensitivity (including allergy to the trial medication or 
its excipients) 
12. Use of drugs within 30 days (or 5 half-lives, whichever is longer) of planned
administration of trial medication that might reasonably influence the results of the trial 
(including drugs that cause QT/QTc interval prolongation, potent CYP3A4 inhibitors, 
selective and non-selective PDE inhibitors, based on investigator judgement, as well as 
vaccination of any kind with or without re-vaccination required during the course of the 
trial)
13. Intake of an investigational drug in another clinical trial within 60 days (or 5 half-lives, 
whichever is longer) 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 5 cigarettes or 1 cigar or 1 pipe per day)
15. Inability to refrain from smoking on specified trial days
16. Average intake of more than 24 units of alcohol per week (1 unit of alcohol equals 
approximately 250 mL of beer, 100 mL of wine, or 35 mL of spirits)
17. Drug abuse or positive drug screening
18. Blood donation of more than 100 mL within 30 days of planned administration of trial 
medication or intended blood donation during the trial
19. Intention to perform excessive physical activities within 4 days prior to the administration 
of trial medication or during the trial
20. Inability to comply with the dietary regimen of the trial site and life-style restrictions of 
the clinical trial protocol
21. A marked prolongation of QT/QTc interval (such as QTc intervals that are repeatedly 
greater than 450 ms in males) 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 

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 28 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
In addition, subjects will not be allowed to participate, if any of the following trial-specific 
criteria apply:
24. A medical history of vasculitis
25. Persistent symptoms of known prior COVID-19 infection and/or laboratory test indicative 
of an ongoing SARS-CoV-2 infection within 4 weeks prior to the administration of trial 
medication
For restrictions of the trial, refer to Section 4.2.2.
3.3.4
Withdrawal of subjects from treatment or assessments
Subjects may withdraw or may be removed from trial treatment or may withdraw consent to 
trial participation as a whole (‘withdrawal of consent’) with very different implications; 
please see Sections 3.3.4.1 and 3.3.4.2 below.
If a subject is removed from or withdraws from the trial prior to the first administration of 
trial medication, the data of this subject will not be entered in the case report form (CRF) and 
will not be reported in the clinical trial report (CTR).
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 1.2.3), the 
discontinued subject should, if possible, be questioned for AEs and concomitant therapies at 
or after the end of the REP, in order to ensure collection of AEs and concomitant therapies 
throughout the REP, if not contrary to any consent withdrawal of the subject.
3.3.4.1
Withdrawal from trial treatment
An individual subject will be withdrawn from trial treatment if:
1. The subject wants to withdraw from trial treatment. The subject will be asked to explain 
the reasons but has the right to refuse to answer
2. The subject has repeatedly shown to be non-compliant with important trial procedures 
and, in the opinion of both, the investigator and sponsor representative, the safety of the 
subject cannot be guaranteed as the subject 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

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 29 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
6. In addition to these criteria, the investigator may discontinue subjects at any time based 
on their clinical judgment.
Even if trial treatment is discontinued, the subject will remain in the trial and, given their
agreement, will undergo the end of study procedures outlined in the Flow Chart and Section 
6.2.3.
If new efficacy or safety information becomes available, Boehringer Ingelheim will review 
the benefit-risk-assessment and, if needed, pause or discontinue the trial treatment for all 
subjects or take any other appropriate action to guarantee the safety of the trial subjects.
3.3.4.2
Withdrawal of consent to trial participation
Subjects may withdraw their consent to trial participation at any time without the need to 
justify the decision. If a subject wants to withdraw consent, the investigator should be 
involved in the discussion with the subject and explain the difference between trial treatment 
discontinuation and withdrawal of consent to trial participation, as well as explain the options 
for continued follow-up after trial treatment discontinuation, please see Section 3.3.4.1 above.
3.3.4.3
Discontinuation of the trial by the sponsor
Boehringer Ingelheim reserves the right to discontinue the trial at any time for any of the 
following reasons (if reasons 4 and/or 5 are met, the trial should be discontinued 
immediately):
1. Failure to meet expected enrolment goals overall or at a particular trial site
2. The sponsor decides to discontinue the further development of the investigational 
products
3. Deviation from GCP, or the CTP, or the contract with BI impairing the appropriate 
conduct of the trial
4. New toxicological findings, serious adverse events, or any safety information invalidating
the earlier positive benefit-risk-assessment (see Section 3.3.4.1)
5. More than 50% of the subjects show drug-related and clinically relevant adverse events of 
moderate or severe intensity, or if more than two subjects have drug-related severe non-
serious adverse events, or if at least one drug-related serious adverse event is reported
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 data from fewer subjects than the required number of subjects are considered evaluable
(including subjects non-evaluable for PK), enrolment of additional subjects (replacement
subjects) will be considered if deemed necessary in order to reach the objective of the trial.
For subjects who withdraw or are withdrawn from treatment or assessments because of a
drug-related adverse event, no additional subjects will be enrolled. The Clinical Trial Leader
together with the Trial Pharmacokineticist and the Trial Statistician are to decide if and how 

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 30 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
many subjects will be enrolled additionally. A replacement subject will be assigned a unique 
trial subject number and will receive all treatments of this single arm. Note that data from the 
subjects to be replaced and data from subjects who withdraw or are withdrawn (after trial 
drug intake) will be included in the safety analysis.

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 31 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
4.
TREATMENTS
4.1
INVESTIGATIONAL TREATMENTS
The investigational product (test product) BI 1015550 (film-coated tablets for oral 
administration) has been manufactured by BI Pharma GmbH & Co. KG. 
Radiolabelled BI 1015550 (C-14) solution for intravenous administration (reference product) 
consists of 
 [14C]-labelled BI 1015550 and 
 unlabelled BI 1015550, manufactured 
by BI Pharma GmbH & Co. KG. The final solution for infusion from both components is 
manufactured by the pharmacy of the trial site (
).
Refer to Section 1.3.1 for nomenclature.

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 34 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
Trial medication will be labelled according to GMP Annex 13 / EU GMP guideline and local 
drug law.
For details of packing and the description of the label, refer to the ISF.
The name, address and telephone number of the trial site are provided in the subject 
information form. The EudraCT number is indicated on the title page of this protocol as well 
as on the subject information and informed consent forms.
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 site’s pharmacy will prepare the dosing units for infusion of BI 1015550 (C-14) (for 
treatment R) and will receive the film-coated tablets of BI 1015550 (for treatment T) from the
sponsor once the below mentioned requirements are fulfilled. The pharmacy will deliver both 
the film-coated tablets (treatment T) and the solution for infusion (treatment R) to the 
investigator upon availability of a valid prescription from the investigator.
!
Approval of the clinical trial protocol by the IRB / ethics committee
!
Availability of a signed and dated clinical trial contract between the sponsor or 
delegate and the investigational site
!
Approval/notification of the regulatory authority, e.g., competent authority
!
Availability of the curriculum vitae of the Principal Investigator
!
Availability of a signed and dated clinical trial protocol
!
Availability of licence for clinical research using radioactive isotopes
Only authorised personnel documented on 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 disposal of remaining trial medication, the 

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 35 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
investigator or designee must verify that no remaining supplies are in the investigator’s 
possession.
All unused medication will be disposed of locally by the trial site upon written authorisation 
of the Clinical Trial Leader. Receipt, usage, and disposal of trial medication must be 
documented on the appropriate forms. Account must be given for any discrepancies.
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. If necessary, short-term use of paracetamol is 
acceptable for symptomatic treatment of AEs. In case of adverse events necessitating
treatment, the required concomitant therapy and medical treatment will be permitted. All 
concomitant or rescue therapies will be recorded (including time of intake on trial days) on 
the appropriate pages of the CRF.
CYP3A4 is regarded as the major enzyme responsible for the metabolism of BI 1015550.
Therefore, potent CYP3A4 inhibitors are specifically restricted in this trial. Refer to 
Appendix 10.2 for a list of potent CYP3A4 inhibitors.
4.2.2.2
Restrictions on diet and lifestyle
While admitted to the trial site, 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 
 after the administration of BI 
1015550 tablet.
From 
 before the administration of BI 1015550 tablet until lunch, fluid intake is restricted 
to the water administered with the drug, and an additional 240 mL of water at 
 
post-dose (mandatory for all subjects). From lunch until 24 h post-dose, total fluid intake is 
restricted to 3000 mL.
Alcoholic beverages are not allowed 48 hours before the administration of BI 1015550 tablet
and during in-house confinement at the site. During the ambulatory phase alcohol 
consumption is restricted to a maximum of 2 units per day (1 unit of alcohol equals 
approximately 250 mL of beer, 100 mL of wine, or 35 mL of spirits).

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 36 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
Green tea, 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 
 before the administration of BI 1015550 tablets until after the last PK 
sample is collected. Consumption of poppy-seed containing products is not permitted within
 prior to drug screening (at Screening visit and on Day -1).
Methylxanthine-containing drinks or foods (such as coffee, tea, cola, energy drinks, or 
chocolate) are not allowed from 
 before until 
 after the administration of BI 1015550 
tablet.
Smoking is not allowed during in-house confinement.
Excessive physical activity (such as competitive sports) should be avoided from 
 
before the administration of trial medication until the end of study examination.
4.2.2.3
Contraception requirements
Not applicable
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).

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 37 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
5.
ASSESSMENTS
5.1
ASSESSMENT OF EFFICACY
Not applicable.
5.2
ASSESSMENT OF SAFETY
5.2.1
Physical examination
At screening, the medical examination will include demographics, height and body weight, 
smoking and alcohol history (alcohol history not mandatory to be entered into CRF or to be 
reported), relevant medical history and concomitant therapy, review of inclusion and 
exclusion criteria, review of vital signs (BP, PR), 12-lead ECG, laboratory tests, and a 
physical examination. At the end of study (end of trial) examination, assessments will include 
the 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 blood pressures (BP) as well as pulse rate (PR) or heart rate (heart rate 
is considered to be equal to pulse rate) will be measured by an automated blood pressure 
monitor at the times indicated in the Flow Chart, after subjects have rested for at least 5 min 
in a supine position. All recordings should be made using the same type of blood pressure 
recording instrument on the same arm, if possible.
5.2.3
Safety laboratory parameters
For the assessment of laboratory parameters, blood and urine samples will be collected by the 
trial site at the times indicated in the Flow Chart after the subjects have fasted for at least 
10 h. For safety laboratory evaluation at the Screening visit, Day -1 and End of Study visit, a 
4 h fast is sufficient, respectively. 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.
SARS-CoV-2 testing will be conducted as specified in the Flow Chart.

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 38 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
Table 5.2.3: 1
Routine laboratory tests
Functional lab group
BI test name [comment/abbreviation]
A
B
Haematology
Haematocrit
Haemoglobin
Red Blood Cell Count/Erythrocytes 
Reticulocytes, absol.
Reticulocytes/Erythrocyte
White Blood Cells/Leucocytes 
Platelet Count/Thrombocytes (quant)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Automatic WBC differential, 
relative 
Neutrophils/Leucocytes; Eosinophils/Leucocytes; 
Basophils/Leucocytes; Monocytes/Leucocytes; 
Lymphocytes/Leucocytes 
X
X
Automatic WBC differential, 
absolute 
Neutrophil, absol.; Eosinophils, absol.; Basophils, absol.; 
Monocytes, absol.; Lymphocytes, absol.
X
X
Manual differential WBC (if 
automatic differential WBC is 
abnormal and according to 
’s lab standards)
Neutr. Poly (segs)/Leucocytes [%]; 
Eosinophils/Leucocytes [%]; Basophils/Leucocytes [%];
Monocytes/Leucocytes [%]; Lymphocytes/Leucocytes [%]
Manual differential red blood 
cell count (if there is an 
abnormality in the blood cell 
count in accordance with 
Clinical laboratory 
 
standard procedures)
Only positive findings will be reported (for instance the 
presence of microcytes)
Coagulation
Activated Partial Thromboplastin Time 
Prothrombin time – INR (International Normalized Ratio)
Fibrinogen
X
X
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
Hormones
Thyroid Stimulating Hormone
X
--
Substrates
Glucose (Serum)
Creatinine 
Bilirubin, Total 
Bilirubin, Direct
Protein, Total
C-Reactive Protein (Quant)  
Uric Acid 
Cholesterol, total 
Triglycerides
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Electrolytes
Sodium
Potassium
Chloride
Calcium
Phosphate (as Phosphorus, Inorganic)
X
X
X
X
X
X
X
X
X
X

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 39 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
Table 5.2.3: 1
Routine laboratory tests (cont.)
Functional lab group
BI test name [comment/abbreviation]
A
B
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 (examinations will only be 
performed if there is an abnormality in 
urinalysis in accordance with Clinical 
Laboratory, standard procedure)
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) and Visit 3 (end of trial examination)
B: parameters to be determined at Visit 2 on Day -1, Day 2 and Day 6 (for time refer to Flow Chart)
The tests listed in Table 5.2.3: 2 are exclusionary laboratory tests that may be repeated as 
required. The results will not be entered in the CRF/database and will not be reported in the 
CTR. Except for drug screening, it is planned to perform these tests during screening only. 
Drug screening will be performed at screening and on Day -1, prior to the treatment period.
Table 5.2.3: 2
Exclusionary laboratory tests
Functional lab group
Test name 
Drug screening (urine)
Alcohol
Amphetamine/MDA1 including Ecstasy
Barbiturates
Benzodiazepine
Cannabis
Cocaine 
Methadone
Methamphetamines/MDMA2
Opiates 
Phencyclidine
Drug screening (blood)
Tricyclic antidepressants
Infectious serology (blood)
Hepatitis B surface antigen (qualitative)
Hepatitis B core antibody (qualitative)
Hepatitis C antibodies (qualitative)
HIV3-1 and HIV3-2 antibody (qualitative)
1: Methylenedioxyamphetamine
2: Methylenedioxymethamphetamine
3: Human Immunodeficiency Virus
The laboratory tests listed in Tables 5.2.3: 1 and 5.2.3: 2 will be performed at the laboratory 
of 
 
Laboratory data will be transmitted electronically from the laboratory to the trial site.

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 40 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
It is the responsibility of the investigator to evaluate the laboratory reports. Clinically relevant 
abnormal findings as judged by the investigator are to be reported as adverse events (please 
refer to Section 5.2.6). 
In case the criteria for hepatic injury are fulfilled, a number of additional measures will be 
performed (please see Section 5.2.6.1.4). 
5.2.4
Electrocardiogram
Twelve-lead ECGs (I, II, III, aVR, aVL, aVF, V1 - V6) will be recorded using a 
computerised electrocardiograph at the times provided in the Flow Chart. 
To achieve a stable heart rate at rest and to assure high quality recordings, the site personnel 
will be instructed to assure a relaxed and quiet environment, so that all subjects are at 
complete rest.
All ECGs will be recorded for a 10 sec duration after subjects have rested for at least 5 min in 
a supine position. ECG assessment will always precede all other trial procedures scheduled 
for the same time to avoid compromising ECG quality. 
All ECGs will be stored electronically. 
ECG printouts will be provided. All locally printed ECGs will be evaluated by the 
investigator or a designee. Abnormal findings will be reported as AEs (during the trial) or 
baseline conditions (if identified at the screening visit) if assessed to be clinically relevant by 
the investigator. Any ECG abnormalities will be carefully monitored and, if necessary, the 
subject will be removed from the trial and will receive the appropriate medical treatment. 
ECGs may be repeated for quality reasons (for instance, due to alternating current artefacts, 
muscle movements, or electrode dislocation) and the repeated ECG will be used for analysis. 
Additional (unscheduled) ECGs may be collected by the investigator for safety reasons. 
5.2.5
Other safety parameters
5.2.5.1
Local tolerability
Local tolerability will be assessed by the investigator on the basis of swelling, induration, 
heat, redness, pain, and other findings. Local findings assessed as clinically relevant by the 
investigator must be recorded as AE.
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.

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 41 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
An AE can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
product, whether considered related or not.
The following should also be recorded as an AE in the CRF and BI SAE form (if applicable):
!
Worsening of the underlying disease or of other pre-existing conditions 
!
Changes in vital signs, ECG, physical examination, and laboratory test results, if they 
are judged clinically relevant by the investigator
If such abnormalities already pre-exist prior to trial inclusion, they will be considered as 
baseline conditions and should be collected in the eCRF only.
5.2.6.1.2
Serious adverse event
A serious adverse event (SAE) is defined as any AE which fulfils at least one of the 
following criteria:
!
Results in death 
!
Is life-threatening, which refers to an event in which the patient was at risk of death 
at the time of the event; it does not refer to an event that hypothetically might have 
caused death if more severe 
!
Requires inpatient hospitalisation, or prolongation of existing hospitalisation
!
Results in persistent or significant disability or incapacity 
!
Is a congenital anomaly/birth defect 
!
Is deemed serious for any other reason if it is an important medical event when based 
upon appropriate medical judgment which may jeopardise the patient and may 
require medical or surgical intervention to prevent one of the other outcomes listed in 
the above definitions. Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalisation or development of dependency or 
abuse
5.2.6.1.3
AEs considered ‘Always Serious’
In accordance with the European Medicines Agency initiative on Important Medical Events, 
Boehringer Ingelheim has set up a list of AEs, which, by their nature, can always be 
considered to be ‘serious’ even though they may not have met the criteria of an SAE as 
defined above.
The latest list of ‘Always Serious AEs’ can be found in the eDC system, an electronic data 
capture system which allows the entry of trial data at the trial site. A copy of the latest list of 
‘Always Serious AEs’ will be provided upon request. These events should always be reported 
as SAEs as described in Section 5.2.6.2.
Cancers of new histology must be classified as a serious event regardless of the time since 
discontinuation of the trial medication and must be reported as described in 5.2.6.2, 
subsections ‘AE Collection’ and ‘AE reporting to sponsor and timelines’.

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 42 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
5.2.6.1.4
Adverse events of special interest
The term adverse events of special interest (AESI) relates to any specific AE that has been 
identified at the project level as being of particular concern for prospective safety monitoring 
and safety assessment within this trial, e.g., the potential for AEs based on knowledge from 
other compounds in the same class. AESIs need to be reported to the sponsor’s 
Pharmacovigilance Department within the same timeframe that applies to SAEs, please see 
Section 5.2.6.2.2.
The following are considered as AESIs:
!
Potential severe DILI
A potential severe Drug Induced Liver Injury (DILI) that requires follow-up is 
defined by the following alterations of hepatic laboratory parameters: 
o
An elevation of AST (aspartate aminotransferase) and/or ALT (alanine 
aminotransferase) ≥3-fold ULN combined with an elevation of total bilirubin 
≥2-fold ULN measured in the same blood sample, or in samples drawn within 30 
days of each other, or
o
Aminotransferase (ALT, and/or AST) elevations ≥10-fold ULN
These lab findings constitute a hepatic injury alert and the subjects showing these lab 
abnormalities need to be followed up according to the ‘DILI checklist’ provided in the 
eDC. 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.
!
Vasculitis
In this trial protocol vasculitis is defined as any adverse 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. The investigator should monitor for any signs and 
symptoms of vasculitis at all times and specifically as part of the AE questioning. 
In case of (suspected) event of vasculitis, further work-up and management as 
outlined has to be followed, including biopsy, appropriate imaging/angiography, 
laboratory measures (e.g., ESR, additional lab sample for immunological and further 
inflammation markers).
!
Severe infections, serious infections, opportunistic or mycobacterium tuberculosis
infections (refer to Appendix 10.1 for a list of severe infections considered as AESI)

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 43 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
5.2.6.1.5
Intensity (severity) of AEs
The intensity (severity) of the AE should be judged based on the following:
Mild:
Awareness of sign(s) or symptom(s) that is/are easily tolerated
Moderate:
Sufficient discomfort to cause interference with usual activity
Severe:
Incapacitating or causing inability to work or to perform usual activities
5.2.6.1.6
Causal relationship of AEs
Medical judgment should be used to determine whether there is a reasonable possibility of a 
causal relationship between the AE and the given trial treatment, considering all relevant 
factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, 
confounding factors such as concomitant medication, concomitant diseases and relevant 
history.
Arguments that may suggest that there is a reasonable possibility of a causal relationship 
could be:
!
The event is consistent with the known pharmacology of the drug 
!
The event is known to be caused by or attributed to the drug class
!
A plausible time to onset of the event relative to the time of drug exposure
!
Evidence that the event is reproducible when the drug is re-introduced
!
No medically sound alternative aetiologies that could explain the event (e.g., pre-
existing or concomitant diseases, or co-medications)
!
The event is typically drug-related and infrequent in the general population not 
exposed to drugs (e.g., Stevens-Johnson syndrome)
!
An indication of dose-response (i.e., greater effect size if the dose is increased, 
smaller effect size if dose is reduced)
Arguments that may suggest that there is no reasonable possibility of a causal relationship 
could be:
!
No plausible time to onset of the event relative to the time of drug exposure is evident 
(e.g., pre-treatment cases, diagnosis of cancer or chronic disease within days / weeks 
of drug administration; an allergic reaction weeks after discontinuation of the drug 
concerned)
!
Continuation of the event despite the withdrawal of the medication, taking into 
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

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 44 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
5.2.6.2
Adverse event collection and reporting
5.2.6.2.1
AE collection
Upon enrolment into a trial, the subject’s baseline condition is assessed (for instance, by 
documentation of medical history/concomitant diagnoses), and relevant changes from 
baseline are noted subsequently. 
Subjects will be required to report spontaneously any AEs. In addition, each subject will be 
regularly assessed by the medical staff throughout the clinical trial and whenever the 
investigator deems necessary. As a minimum, subjects will be questioned for AEs (and 
concomitant therapies) at the time points indicated in the Flow Chart. Assessment will be 
made using non-specific questions such as ‘How do you feel?’. Specific questions will be 
asked wherever necessary in order to more precisely describe an AE.
A carefully written record of all AEs shall be kept by the investigator in charge of the trial. 
Records of AEs shall include data on the time of onset, end time, intensity of the event, and 
any treatment or action required for the event and its outcome.
The following must be collected and documented on the appropriate CRF(s) by the 
investigator:
!
From signing the informed consent onwards until an individual subject’s end of trial
(the End of Study (EoS) visit): 
o
All AEs (serious and non-serious) and all AESIs 
o
The only exception to this rule are AEs (serious and non-serious) and AESIs 
in Phase I trials in healthy volunteers, when subjects discontinue from the trial 
due to screening failures prior to administration of any trial medication. In 
these cases, the subjects’ data must be collected at trial site but will not be 
entered in the CRF and will not be reported in the CTR.
!
After the individual subject’s end of trial: 
o
The investigator does not need to actively monitor the subject for new AEs but 
should only report any occurrence of cancer and trial treatment related SAEs
and trial treatment related AESIs of which the investigator may become aware 
of by any means of communication, e.g., phone call. Those AEs should be 
reported on the BI SAE form (see Section 5.2.6.2.2), but not on the CRF.
5.2.6.2.2
AE reporting to the sponsor and timelines
The investigator must report SAEs, AESIs, and non-serious AEs which are relevant for the 
reported SAE or AESI, on the BI SAE form to the sponsor’s unique entry point within 
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 

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 45 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
information. All (S)AEs, including those persisting after the individual subject’s end of trial, 
must be followed up until they have resolved, have been sufficiently characterized (e.g., as 
‘chronic’ or ‘stable’), or no further information can be obtained.
5.2.6.2.3
Pregnancy
Potential drug exposure during pregnancy must be reported if a partner of a male trial 
participant becomes pregnant. This requires written consent of the pregnant partner.
Reporting and consenting must be in line with local regulations. The ISF will contain the trial 
specific information and consent for the pregnant partner. The investigator must report any 
drug exposure during pregnancy immediately (within 24 hours) by means of Part A of the
Pregnancy Monitoring Form for Clinical Studies to the sponsor’s unique entry point.
The outcome of the pregnancy associated with the drug exposure during pregnancy must be 
followed up and reported to the sponsor’s unique entry point on the Pregnancy Monitoring 
Form for Clinical Studies (Part B). The ISF will contain the Pregnancy Monitoring Form for 
Clinical Studies (Part A and Part B).
As pregnancy itself is not to be reported as an AE, in the absence of an accompanying SAE 
and/or AESI, only the Pregnancy Monitoring Form for Clinical Studies and not the SAE form 
is to be completed. If there is an SAE and/or AESI associated with the pregnancy, an SAE 
form must be completed in addition.
5.3
DRUG CONCENTRATION MEASUREMENTS AND 
PHARMACOKINETICS
5.3.1
Assessment of pharmacokinetics
For the assessment of pharmacokinetics, blood samples will be collected at the time points 
indicated in the Flow Chart. The actual sampling times will be recorded and used for 
determination of pharmacokinetic parameters. 
5.3.2
Methods of sample collection
5.3.2.1
Blood sampling for pharmacokinetic analysis
For quantification of BI 1015550 concentrations in plasma, 2.7 mL of blood will be required. 
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. 
For quantification of [14C]-BI 1015550 concentrations in plasma, an additional 2 mL of blood 
needs to be collected in a K2-EDTA tube at the times indicated in the Flow Chart.
For quantification of total radioactivity in plasma, 9 mL of blood needs to be collected at pre-
dose and 2 mL of blood needs to be collected in a K2-EDTA tube at all other times indicated 
in the Flow Chart.

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 47 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
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 the 
administration of trial medication. Safety assessments are standard, are accepted for the 
evaluation of safety and tolerability of an orally and intravenously administered drug and are 
widely used in clinical trials. The pharmacokinetic parameters and measurements outlined in 
Section 5.3 are generally used assessments for drug exposure. 

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 48 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
6.
INVESTIGATIONAL PLAN
6.1
VISIT SCHEDULE
The acceptable time windows for screening visit and the end-of-study examination are 
provided in the Flow Chart. Exact times of measurements outside of the permitted time 
windows will be documented.
Study measurements and assessments scheduled to occur ‘before’ trial medication 
administration on Day 1 are to be performed and completed between waking up and (still 
prior to) trial drug administration.
If not stated otherwise in the Flow Chart, the acceptable deviation from the scheduled time 
for vital signs, ECG, and laboratory tests will be 
until 
 after trial drug 
administration and ± 10% of the time window of elapsed time since last medication dosing
thereafter.
If scheduled in the Flow Chart at the same time as a meal, 12-lead ECG recordings, followed 
by vital signs, and blood sampling have to be done first. Furthermore, if several 
measurements including venipuncture are scheduled for the same time, 12-lead ECG 
recordings should be followed by vital signs, and venipuncture should be the last of the 
measurements due to its inconvenience to the subject and possible influence on physiological
parameters but should take place at the scheduled time.
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.
For logistical reasons, ambulatory visits may take place within 
 of the scheduled time.
If a subject misses an appointment, it will be rescheduled if possible. The relevance of 
measurements outside the permitted time windows will be assessed no later than at the Report 
Planning Meeting.
6.2
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS
6.2.1
Screening period
After having been informed about the trial, all subjects will provide written informed consent 
in accordance with GCP and local legislation prior to enrolment in the trial.
For information regarding laboratory tests (including drug and virus screening), ECG, vital 
signs, and physical examination, refer to Sections 5.2.1 to 5.2.5.
From obtaining the subject’s informed consent onwards, AEs and AESIs will be collected 
unless a subject discontinues from the trial due to screening failure prior to the 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. Please refer to Section 5.2.6.2.1.

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 49 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
6.2.3
Follow-up period and trial completion
For AE assessment, laboratory tests, recording of ECG and vital signs, and physical 
examination during the follow-up period, see Section 5.2.
Subjects who discontinue treatment or study procedures before the planned end of trial
should undergo the EoS Visit.
All abnormal values (including laboratory parameters) that are assessed as clinically relevant 
by the investigator will be monitored using the appropriate tests until a return to a medically 
acceptable level is achieved. (S)AEs persisting after a subject’s EoS Visit must be followed 
until they have resolved, have been sufficiently characterised, or no further information can 
be obtained. 
If needed in the opinion of the investigator, additional visits may be scheduled after the EoS 
Visit for continued safety monitoring.

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 51 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
! 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 Section 7.2.1.2). Thus, a subject will be included in the PKS, even if he 
contributes only one PK parameter value 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 drug BI 1015550 will be 
calculated according to the relevant BI internal procedures. 
Plasma concentration data and parameters of a subject will be included in the statistical 
pharmacokinetic (PK) analyses if they are not flagged for exclusion due to a protocol 
deviation relevant to the evaluation of PK (to be decided no later than in the Report Planning 
Meeting) or due to PK non-evaluability (as revealed during data analysis, based on the 
criteria specified below). Exclusion of a subject’s data will be documented in the CTR.
Important protocol deviations may be
!
Incorrect trial medication taken, i.e., the subject received at least one dose of trial
medication the subject was not assigned to
!
Incorrect dose of trial medication taken
!
Incorrect duration of infusion
!
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), 
!
A predose concentration is >5% Cmax value of that subject
!
Missing samples/concentration data at important phases of PK disposition curve
!
The subject did not receive the complete assigned infusion volume
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. 
Descriptive and inferential statistics of PK parameters will be based on the PKS.
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 

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 53 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
7.2.3
Secondary endpoint analyses
The secondary endpoints (refer to Section 2.1.3) will be calculated according to the relevant 
BI internal procedures and will be assessed statistically using the same methods as described 
for the primary endpoints.
7.2.5
Safety analyses 
Safety will be analysed based on the assessments described in Section 2.2.2.2. All treated 
subjects (TS, refer to Section 7.2) will be included in the safety analysis. Safety analyses will 
be descriptive in nature and based on BI standards. No hypothesis testing is planned.
For all analyses, the treatment actually administered (= treatment at onset) to the subject will 
be used (any deviations from the 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 to evaluate categorical (qualitative) data, and tabulations of descriptive statistics 
will be used to analyse continuous (quantitative) data.
Measurements (such as vital signs, or laboratory parameters) or AEs will be assigned to 
treatments (see Section 4.1) based on the actual treatment at the time of the measurement or 
on the recorded time of AE onset (concept of treatment emergent AEs). Therefore, 
measurements performed or AEs recorded prior to first intake of trial medication (test 
treatment) will be assigned to the screening period, those between first trial medication intake 
and beginning of reference treatment will be assigned to test treatment period. Those between 
the start of infusion until the end of REP (see Section 1.2.3) will be assigned to the combined 
test/reference treatment period. Events occurring after the REP but prior to next intake or end 
of 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 of the trial will be reported 
to Pharmacovigilance only and will not be captured in the trial database.
Additionally, further treatment intervals (analysing treatments) may be defined in the TSAP 
in order to provide summary statistics for time intervals, such as combined treatments, on-
treatment totals, or periods without treatment effects (such as screening and follow-up 
intervals).
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). Frequency, severity, and causal relationship of AEs will be tabulated by 
treatment, system organ class, and preferred term. SAEs, AESIs (see Section 5.2.6.1), and 
other significant AEs (according to ICH E3) will be listed separately. 
Previous and concomitant therapies will be presented per treatment group without 
consideration of time intervals and treatment periods.

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 54 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
In general, unless otherwise specified in the TSAP, the last non-missing measurement prior to 
study treatment will be used as baseline for safety variables.
Laboratory data will be compared to their reference ranges. Values outside the reference 
range as well as possibly clinically significant values will be highlighted in the listings. 
Additionally, differences from baseline will be evaluated.
Vital signs or other safety-relevant data will be assessed with regard to possible on-treatment 
changes from baseline.
Relevant ECG findings will be reported as AEs.
7.2.6
Interim analyses
No interim analysis is planned.
7.3
HANDLING OF MISSING DATA
7.3.1
Safety
It is not planned to impute missing values for safety parameters.
7.3.2
Pharmacokinetics
Handling of missing PK data will be performed according to the relevant BI internal 
procedures. 
PK parameters that cannot be reasonably calculated based on the available drug 
concentration-time data will not be imputed.
7.4
RANDOMISATION
This is a non-randomised trial. All subjects will receive the same treatments in the same 
order. 
7.5
DETERMINATION OF SAMPLE SIZE
For this exploratory trial, no prospective calculations of statistical precision or power have
been made. The planned sample size of 8 subjects is considered sufficient to get reliable 
results regarding the trial objectives. This sample size accounts for up to 2 dropouts or non-
evaluable subjects in order to have at least 6 subjects who completed the trial as per protocol.

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 55 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
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), the EU directive 
2001/20/EC, 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 
webpage: 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.
The terms and conditions of the insurance coverage are made available to the investigator and 
the subjects and are stored in the ISF.
8.1
TRIAL APPROVAL, SUBJECT INFORMATION, INFORMED CONSENT
This trial will be initiated only after all required legal documentation has been reviewed and 
approved by the respective Institutional Review Board (IRB / Independent Ethics Committee 
(IEC and competent authority (CA) according to national and international regulations. The 
same applies for the implementation of changes introduced by amendments.
Prior to a subject’s participation in the trial, written informed consent must be obtained from 
each subject (or the subject’s legally accepted representative) according to ICH-GCP and to 
the regulatory and legal requirements of the participating country. Each signature must be 
personally dated by each signatory and the informed consent and any additional subject-
information form retained by the investigator as part of the trial records. A signed copy of the 
informed consent and any additional subject information must be given to each subject or the 
subject’s legally accepted representative.
The subject must be given sufficient time to consider participation in the trial. The 
investigator or delegate obtains written consent of the subject’s own free will with the 
informed consent form after confirming that the subject understands the contents. The 
investigator or 
 delegate must sign (or place a seal on) and date the informed consent form. 
If a trial collaborator has given a supplementary explanation, the trial collaborator also signs 
(or places a seal on) and dates the informed consent.
Re-consenting may become necessary when new relevant information becomes available and 
should be conducted according to the sponsor’s instructions.

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 56 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
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.
Before providing any copy of subjects’ source documents to the sponsor, the investigator 
must ensure that all subject identifiers (e.g., subject’s name, initials, address, phone number, 
and social security number) have properly been removed or redacted to ensure subject 
confidentiality.
If the subject is not compliant with the protocol, any corrective action (e.g., re-training) must 
be documented in the subject file.
For the CRF, data must be derived from source documents, for example:
!
Subject identification: gender, year of birth (in accordance with local laws and 
regulations)
!
Subject participation in the trial (substance, trial number, subject number, date subject 
was informed)

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 57 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
!
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 
contract or the local requirements valid at the time of the end of the trial (whatever is longer).
Sponsor:
The sponsor must retain the essential documents according to the sponsor’s SOPs.
8.4
EXPEDITED REPORTING OF ADVERSE EVENTS
BI is responsible to fulfil their legal and regulatory reporting obligation in accordance with 
regulatory requirements.

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 58 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
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 form 
(ICF)
!
The BI-internal facilities storing biological samples from clinical trial participants as 
well as the external storage facility are qualified for the storage of biological samples 
collected in clinical trials.
!
An appropriate sample and data management system, incl. audit trail for clinical data 
and samples to identify and destroy such samples according to ICF is in place
!
A fit for the purpose documentation (e.g., biomarker proposal, analysis plan and 
report) ensures compliant usage
!
A fit for purpose approach will be used for assay/equipment validation depending on 
the intended use of the biomarker data
!
Samples and/or data may be transferred to third parties and other countries as 
specified in the ICF
8.6
TRIAL MILESTONES
The start of the trial is defined as the date when the first subject in the whole trial signs 
informed consent.
The end of the trial is defined as the date of the last visit of the last subject in the whole trial 
(‘Last Subject Completed’).
Early termination of the trial is defined as the premature termination of the trial due to any 
reason before the end of the trial as specified in this protocol.
Temporary halt of the trial is defined as any unplanned interruption of the trial by the sponsor 
with the intention to resume it.

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 60 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
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 and/or a contract research 
organisation appointed 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.

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 63 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
c39775503
 Assessment of requirement for male contraception. Memo. 09 
June 2022
n00201897
In vitro determination of BI 1015550 protein binding in human and animal 
plasma and in human serum albumin and α1-acid glycoprotein solutions. 
(DM-11-1046).
n00201905
In vitro blood cell partitioning of 14C-BI 1015550 in rat, Göttingen 
minipig, and human blood. (DM-11-1045).
n00261666
BI 1015550: Metabolite profiling in plasma after multiple oral 
administration to healthy volunteers and metabolite exposure 
determination in human and the relevant toxicity species.
n00290709
A fertility and early embryonic development to implantation study of BI 
1015550 by oral gavage in male and female rats. CRL study no. 9001829, 
BI no. 21R070.

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 64 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
10.
APPENDICES
10.1
APPENDIX 1: SEVERE INFECTIONS CONSIDERED AS AESI
The opportunistic infections to be considered as AESI include (R17-2617):
pneumocystis jirovecii, 
Human Polyoma-1 virus disease including polyomavirus-associated nephropathy, 
Cytomegalie Virus, 
posttransplant 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.

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 65 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
10.2
APPENDIX 2: STRONG CYP3A4 INHIBITORS
Strong CYP 3A4 inhibitors:
!
boceprevir
!
ceritinib
!
clarithromycin
!
cobicistat
!
conivaptan
!
diltiazem
!
idelalisib 
!
indinavir
!
itraconazole
!
ketoconazole oral administration
!
LCL161
!
mifepristone
!
mibefradil
!
nefazodone
!
nelfinafir
!
posaconazole
!
ribociclib
!
ritonavir
!
saquinavir
!
telaprevir
!
telithromycin
!
troleandomycin
!
VIEKIRA PAK2
!
voriconazole
Combinations of CYP 3A4 inhibitors:
!
danoprevir/ritonavir
!
elvitegravir/ritonavir
!
indinavir/ritonavir
!
lopinavir/ritonavir
!
paritaprevir/ritonavir/ombitasvir/dasbuvir
!
saquinavir/ritonavir
!
tipranavir/ritonavir

Boehringer Ingelheim
12 Dec 2022
BI Trial No.: 1305-0030
c38933360-01
Trial Protocol
Page 66 of 66
Proprietary confidential information © 2022 Boehringer Ingelheim International GmbH or one or more of its affiliated companies
BI-VQD-11906_40-106_AD-13 (8.0)
11.
DESCRIPTION OF GLOBAL AMENDMENT(S)
This is the original protocol.
11.1
GLOBAL AMENDMENT 1
Date of amendment
EudraCT number
BI Trial number
BI Investigational Medicinal 
Product(s)
Title of protocol
Substantial Global Amendment due to urgent safety reasons 
Substantial Global Amendment 
Non-substantial Global Amendment 
Section to be changed
Description of change
Rationale for change

 
 
 
APPROVAL / SIGNATURE PAGE 
Document Number: 
 
Technical Version Number:
Document Name: 
                                                                                                                 
 
Title: 
                                                                                                                   
Signatures (obtained electronically) 
Meaning of Signature  
Signed by 
Date Signed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
F

FOLQLFDOWULDOSURWRFROYHUVLRQ
,QYHVWLJDWLRQRISKDUPDFRNLQHWLFVDQGDEVROXWHRUDOELRDYDLODELOLW\RI%,
DGPLQLVWHUHGDVDQRUDOGRVHZLWKDQLQWUDYHQRXVPLFURWUDFHUGRVHRI>&@%,
LQKHDOWK\PDOHYROXQWHHUV
$XWKRU&OLQLFDO7ULDO/HDGHU
'HF&(7
$XWKRU7ULDO6WDWLVWLFLDQ
'HF&(7
$XWKRU&OLQLFDO3KDUPDFRNLQHWLFLVW
'HF&(7
$SSURYDO&OLQLFDO3URJUDP
'HF&(7
9HULILFDWLRQ3DSHU6LJQDWXUH
&RPSOHWLRQ
'HF&(7

Boehringer Ingelheim 
Page 2 of 2
Document Number: 
Technical Version Number:
(Continued) Signatures (obtained electronically) 
Meaning of Signature  
Signed by 
Date Signed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
F
