Relative Bioavailability of BI 1015550 Following Oral Administration Under Fed and Fasted Conditions in Healthy Male Subjects
Phase: PHASE1
Conditions: Healthy
Sponsor: Boehringer Ingelheim

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Clinical Trial Protocol
TITLE PAGE
Document Number:
c17549115-01
EudraCT No.:
BI Trial No.:
2017-002271-26
1305-0020
BI Investigational
Product:
BI 1015550
Title:
Relative bioavailability of BI 1015550 following oral administration 
under fed and fasted conditions in healthy male subjects
Lay Title:
This study in healthy men tests how food influences the amount of BI 
1015550 in the blood.
Clinical Phase:
I
Trial Clinical Monitor:
Phone: 
Fax:
Principal Investigator:
Phone: 
Fax:
Status:
Final Protocol 
Version and Date:
Version: 1.0 
Date: 11 July 2017
Page 1 of 64
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© 2017 Boehringer Ingelheim International GmbH or one or more of its affiliated companies. All rights reserved.
This document may not - in full or in part - be passed on, reproduced, published or otherwise used without prior written permission

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CLINICAL TRIAL PROTOCOL SYNOPSIS
Name of company:
Tabulated
Trial Protocol
Boehringer Ingelheim
Name of finished product:
Not applicable
Name of active ingredient:
BI 1015550
Protocol date:
Trial number:
Revision date:
Not applicable
11 July 2017
1305-0020
Title of trial:
Relative bioavailability of BI 1015550 following oral administration under fed 
and fasted conditions in healthy male subjects
Principal Investigator:
Trial site:
Clinical phase:
I
Objective:
To investigate the relative bioavailability of BI 1015550 as tablet formulation 
following oral administration under fed and fasted conditions 
Methodology:
Open-label, randomized, single dose, two-period, two-sequence crossover design 
No. of subjects: 
total entered:
each treatment:
12
12 
Diagnosis:
Not applicable
Main criteria
for inclusion:
Healthy male subjects, age of 18 to 55 years, body mass index (BMI) of 18.5 to 
29.9 kg/m2
Test product:
BI 1015550 as tablet formulation 
dose:
 
mode of admin.:
Oral with 240 mL of water following a high fat breakfast (treatment test (T)) and 
after an overnight fast of at least 10 h (treatment reference (R))
Duration of treatment:
2 single doses (treatment R = fasted , treatment T = fed) separated by a washout 
phase of at least 7 days
Criteria for
pharmacokinetics:
Primary endpoints:                    AUC0-tz and Cmax
Secondary endpoints:                AUC0-  
 
 
                                                   

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Name of company:
Tabulated
Trial Protocol
Boehringer Ingelheim
Name of finished product:
Not applicable
Name of active ingredient:
BI 1015550
Protocol date:
Trial number:
Revision date:
Not applicable
11 July 2017
1305-0020
Criteria for safety:
Treatment emergent adverse events (TEAEs) including clinically relevant 
findings from the physical examination, safety laboratory tests including testing 
for fecal occult blood and fecal calprotectin, 12-lead electrocardiogram (ECG), 
vital signs (blood pressure [BP], pulse rate [PR])
Statistical methods:
Descriptive statistics will be calculated for all endpoints. 
Relative bioavailability will be estimated by the ratios of the geometric means 
(test/reference) for the primary and secondary endpoints. Additionally, their two-
sided 90% confidence intervals (CIs) will be provided. This method corresponds 
to the two one-sided t-tests procedure, each at the 5% significance level. Since 
the main focus is on estimation and not testing, an acceptance range is not 
specified. The statistical model will be an ANOVA on the logarithmic scale 
including effects for ‘sequence’, ‘subjects nested within sequences’, ‘period’ and 
‘treatment’. CIs will be calculated based on the residual error from the ANOVA.

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FLOW CHART
Period
Visit
Day
Planned time (relative to drug 
administration 
[h:min]
Approximate clock time  of actual 
day [h:min]
Event and comment
Safety laboratory 
Fecal occult blood and fecal 
calprotectin testing
PK blood
12-lead ECG
Vital signs
Questioning for AEs and 
concomitant therapy9
SCR
1
-21 to -1
Screening 1
x
x
x
x
x
1/2 (two identical periods with a washout of at least 7 days)
2/3
-5 to -1
-120:00
08:00
Ambulatory visit (visit 2 only)
x8
x8
x8
-1
-12:00
20:00
Admission to trial site2
x2,6
x2
1
-03:00
05:00
Allocation to subject number3 (visit 
2 only)
x3
x3
x3
x3
-00:30
07:30
High fat, high calorie breakfast (only 
in treatment T)
0:00
08:00
Drug administration
0:15
08:15
x
0:30
08:30
x
0:45
08:45
x
1:00
09:00
x
1:15
09:15
x
1:30
09:30
x
2:00
10:00
240 mL fluid intake 7
x
3:00
11:00
x
4:00
12:00
240 mL fluid intake, lunch7
x
x
x
x
6:00
14:00
x
8:00
16:00
Snack (voluntary)7
x
10:00
18:00
x
x
11:00
19:00
Dinner
12:00
20:00
x
x
2
24:00
08:00
Discharge5
x
x
x
x
x
34:00
18:00
Ambulatory visit
x
x
3
48:00
08:00
Ambulatory visit
x
x
4
72:00
08:00
Ambulatory visit
x
x
5
96:00
08:00
Ambulatory visit
x
x
6
120:00
08:00
Ambulatory visit
x
x
x
EOT
4
8 to 15
End of trial (EOT) examination4
x
x
x
x
x
1.
Subject must be informed and written informed consent obtained prior to starting any screening procedures. Screening procedures 
include physical examination, check of vital signs, ECG, safety laboratory (including drug screening), fecal occult blood and fecal 
calprotectin testing, 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; subjects should be admitted no later than 10 hours before scheduled drug administration.
3.
The time is approximate; the respective procedure is to be performed and completed within 3 h prior to drug administration and prior to 
predose meal intake.
4.
End of trial examination includes physical examination, vital signs, ECG, safety laboratory, 
 
 recording of AEs and concomitant therapies

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5.
Discharge by the investigator or his designee after confirmation of fitness of the subject
6.
Only urine drug screening and alcohol breath test.
7.
If several actions are indicated at the same time point, the intake of meals/fluid will be the last action.
8.
Safety laboratory, fecal occult blood test and fecal calprotectin testing to be taken and to be medically evaluated within 5 days prior to 
first administration of study drug; these procedures can be omitted, if the screening examination is performed on Days -5 to -1.
9.
AEs and concomitant therapies will be recorded throughout the trial, but will be specifically asked for at the time points indicated in 
the Flow Chart above.

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TABLE OF CONTENTS
TITLE PAGE ......................................................................................................1
CLINICAL TRIAL PROTOCOL SYNOPSIS ................................................2
FLOW CHART...................................................................................................4
TABLE OF CONTENTS ...................................................................................6
ABBREVIATIONS.......................................................................................... 10
1.
INTRODUCTION.................................................................................... 13
 
2.
RATIONALE, OBJECTIVES, AND BENEFIT - RISK 
ASSESSMENT ......................................................................................... 22
2.2
TRIAL OBJECTIVES.......................................................................................22
2.3
BENEFIT - RISK ASSESSMENT ...................................................................22
2.3.1
Procedure-related risks ........................................................................22
3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION.............. 26
3.1
OVERALL TRIAL DESIGN AND PLAN ......................................................26
3.1.1
Administrative structure of the trial...................................................26
3.2
DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE OF 
CONTROL GROUP..........................................................................................27
3.3
SELECTION OF TRIAL POPULATION ......................................................27
3.3.1
Main diagnosis for study entry............................................................27
3.3.2
Inclusion criteria...................................................................................27
3.3.3
Exclusion criteria ..................................................................................28

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3.3.4
Removal of subjects from therapy or assessments.............................29
3.3.4.1
Removal of individual subjects..........................................................29
3.3.4.2
Discontinuation of the trial by the sponsor........................................30
3.3.5
Replacement of subjects .......................................................................30
4.
TREATMENTS........................................................................................ 31
4.1
TREATMENTS TO BE ADMINISTERED....................................................31
4.1.1
Identity of BI investigational product.................................................31
4.1.2
Method of assigning subjects to treatment groups ............................31
4.1.5
Blinding and procedures for unblinding ............................................32
4.1.6
Packaging, labelling, and re-supply ....................................................33
4.1.7
Storage conditions.................................................................................33
4.1.8
Drug accountability ..............................................................................33
4.2
OTHER TREATMENTS, EMERGENCY  PROCEDURES,
RESTRICTIONS ...............................................................................................34
4.2.1
Other treatments and emergency procedures....................................34
4.2.2
Restrictions............................................................................................34
4.2.2.1
Restrictions regarding concomitant treatment ...................................34
4.2.2.2
Restrictions on diet and life style.......................................................34
4.3
TREATMENT COMPLIANCE.......................................................................35
5.
VARIABLES AND THEIR ASSESSMENT ......................................... 36
5.1
EFFICACY - CLINICAL PHARMACOLOGY.............................................36
5.1.1
Endpoints of efficacy.............................................................................36
5.1.2
Assessment of efficacy...........................................................................36
5.2
SAFETY..............................................................................................................36
5.2.1
Endpoints of safety................................................................................36
5.2.2
Assessment of adverse events...............................................................36
5.2.2.1
Definitions of adverse events.............................................................36
5.2.2.2
Adverse event collection and reporting .............................................39
5.2.3
Assessment of safety laboratory parameters......................................41
5.2.4
Electrocardiogram................................................................................44
5.2.5
Assessment of other safety parameters...............................................44
5.2.5.1
Vital signs ..........................................................................................44
5.2.5.2
Medical examinations........................................................................44
5.3
OTHER...............................................................................................................45
5.4
APPROPRIATENESS OF MEASUREMENTS.............................................45
5.5
DRUG CONCENTRATION MEASUREMENTS AND 
PHARMACOKINETICS..................................................................................45
5.5.1
Pharmacokinetic endpoints..................................................................45
5.5.1.1
Primary endpoints..............................................................................45

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5.5.1.2
Secondary endpoint............................................................................46
5.5.2
Methods of sample collection...............................................................46
5.5.2.1
Plasma sampling for pharmacokinetic analysis.................................46
5.5.3
Analytical determinations ....................................................................47
5.5.3.1
Analytical determination of analyte plasma concentration................47
6.
INVESTIGATIONAL PLAN.................................................................. 48
6.1
VISIT SCHEDULE............................................................................................48
6.2
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS ................48
6.2.1
Screening period....................................................................................48
6.2.2
Treatment periods.................................................................................48
6.2.3
End of trial period.................................................................................49
7.
STATISTICAL METHODS AND DETERMINATION OF
SAMPLE SIZE......................................................................................... 50
7.1
STATISTICAL DESIGN – MODEL ...............................................................50
7.1.1
Objectives...............................................................................................50
7.1.2
Endpoints...............................................................................................50
7.1.3
Model......................................................................................................50
7.2
NULL AND ALTERNATIVE HYPOTHESES ..............................................50
7.3
PLANNED ANALYSES....................................................................................50
7.3.1
Primary analyses...................................................................................51
7.3.2
Secondary analyses ...............................................................................52
7.3.3
Safety analyses.......................................................................................52
7.3.4
Interim analyses ....................................................................................53
7.3.5
Pharmacokinetic analyses ....................................................................53
7.4
HANDLING OF MISSING DATA ..................................................................54
7.4.1
Safety......................................................................................................54
7.4.2
Plasma drug concentration - time profiles..........................................54
7.4.3
Pharmacokinetic parameters...............................................................54
7.5
RANDOMISATION ..........................................................................................54
7.6
DETERMINATION OF SAMPLE SIZE ........................................................55
8.
INFORMED CONSENT, DATA PROTECTION, TRIAL
RECORDS ................................................................................................ 57
8.1
STUDY APPROVAL, SUBJECT INFORMATION, AND INFORMED 
CONSENT ..........................................................................................................57
8.2
DATA QUALITY ASSURANCE .....................................................................57
8.3
RECORDS..........................................................................................................58
8.3.1
Source documents .................................................................................58
8.3.2
Direct access to source data and documents.......................................58
8.3.3
Storage period of records.....................................................................58
8.4
EXPEDITED REPORTING OF ADVERSE EVENTS .................................59

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8.5
STATEMENT OF CONFIDENTIALITY.......................................................59
8.5.1
Collection, storage and future use of biological samples and 
corresponding data ...............................................................................59
8.6
COMPLETION OF TRIAL..............................................................................59
9.
REFERENCES......................................................................................... 60
9.1
PUBLISHED REFERENCES...........................................................................60
9.2
UNPUBLISHED REFERENCES.....................................................................61
10. APPENDICES .......................................................................................... 63
11. DESCRIPTION OF GLOBAL AMENDMENT(S).............................. 64

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ABBREVIATIONS
ADME
Absorption, distribution, metabolism, and excretion
AE
Adverse event
AESI
Adverse events of special interest
ANOVA
Analysis of variance
AUC0-∞
Area under the concentration-time curve of the analyte in plasma over the 
time interval from 0 extrapolated to infinity
AUCt1-t2
Area under the concentration-time curve of the analyte in plasma over the 
time interval t1 to t2
AUC0-tz
Area under the concentration-time curve of the analyte in plasma over the 
time interval from 0 to the last quantifiable data point
BA
Bioavailability
BALF
Bronchoalveolar lavage fluid
BI
Boehringer Ingelheim
b.i.d.
Bis in die, twice daily
BLQ
Below limit of quantification
BMI
Body mass index (weight divided by height squared)
BP
Blood pressure
CA
Competent authority
CI
Confidence interval
CL/F
Apparent clearance of the analyte in plasma after extravascular 
administration
Cmax
Maximum measured concentration of the analyte in plasma
Cmin
Minimum measured concentration of the analyte in plasma
CML
Clinical Monitor Local
CNS
Central Nervous System
CRA
Clinical Research Associates
CRF
Case report form
CRO
Contract research organization
CTP
Clinical trial protocol
CTR
Clinical trial report
CV
Arithmetic coefficient of variation
DILI
Drug induced liver injury

Bioequivalence margin
ECG
Electrocardiogram
EDTA
Ethylenediaminetetraacetic acid
EOT
End of trial

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ES
Entered set
F
Absolute bioavailability factor
FDA
Food and Drug Administration
GCP
Good Clinical Practice
gCV
Geometric coefficient of variation
GI
Gastro-intestinal
gMean
Geometric mean
HPC
Human Pharmacology Centre
HPLC-MS/MS
High performance liquid chromatography with tandem mass spectrometry
IEC
Independent Ethics Committee
IPF
Pulmonary fibrosis
IPV
Important protocol violation
IRB
Institutional Review Board
ISF
Investigator site file
z
Terminal rate constant of the analyte in plasma
LI
Linearity index
MedDRA
Medical Dictionary for Regulatory Activities
MoA
Mode of action
MRTpo
Mean residence time of the analyte in the body after oral administration
NOA
Not analysed
NOAEL
No observed adverse effect level
NOP
No peak detectable
NOR
No valid result
NOS
No sample available
PD
Pharmacodynamic(s)
PK
Pharmacokinetic(s)
PKS
Pharmacokinetic set
PR
Pulse rate
QT
Time between start of the Q-wave and the end of the T-wave in an 
electrocardiogram
R
Reference treatment
RDC
Remote Data Capture
REP
Residual effect period
SAE
Serious adverse event
SCR
Screening
SRD
Single-rising dose
SUSAR
Suspected Unexpected Serious Adverse Reaction
T
Test product or treatment

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TCM
Trial Clinical Monitor
TDMAP
Trial Data Management and Analysis Plan
TEAEs
Treatment emergent adverse events
TMF
Trial master file
t1/2
Terminal half-life of the analyte in plasma
tmax
Time from  dosing to the maximum measured concentration of the analyte 
in plasma
tz
Time of last measurable concentration of the analyte in plasma
TS
Treated set
TSAP
Trial statistical analysis plan
Vz/F
Apparent volume of distribution during the terminal phase after
extravascular administration

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1.
INTRODUCTION
BI 1015550 is a potent and selective inhibitor of the Phosphodiesterase 4 (PDE4) enzyme and 
has been shown to have both anti-inflammatory and anti-fibrotic activities. 
 
This trial will 
investigate the effect of food on pharmacokinetics of BI 1015550. 
 
 

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:
 
 
 
 
 
 
 
 

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2.
RATIONALE, OBJECTIVES, AND BENEFIT - RISK 
ASSESSMENT
 
 
 
 
 
 
 
 
 
 
2.2
TRIAL OBJECTIVES
The primary objective of this trial is to investigate the effect of food on the pharmacokinetics
of the oral tablet formulation of BI 1015550 
 by 
investigating the relative bioavailability of TF1 under fed and fasted conditions.
The assessment of safety and tolerability will be an additional objective of this part.
A description of the endpoints to be determined, and the observations along with specific 
information as how to collect the data for that information, is provided in Section 5.
2.3
BENEFIT - RISK ASSESSMENT
Participation in this study is without any (therapeutic) benefit for healthy subjects. Their 
participation in the study, however, is of major importance to the development of BI 1015550 
 The subjects are exposed to the risks of the study procedures and the 
risks related to the exposure to the trial medication.
2.3.1
Procedure-related risks
The use of an indwelling venous catheter for the purpose of blood sampling may be 
accompanied by mild bruising and also, in rare cases, by transient inflammation of the wall of 
the vein. In addition, in rare cases a nerve might be injured while inserting the venous 

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catheter, potentially resulting in paresthesia, reduced sensibility, and/or pain for an indefinite 
period. The same risks apply to venipuncture for blood sampling.
ECG electrodes may cause local and typically transient skin reactions.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION
3.1
OVERALL TRIAL DESIGN AND PLAN
This trial will be performed as a randomized, open-label, single dose, two-period, two-
sequence crossover trial in healthy male subjects in order to compare the test treatment 
(treatment T = fed) to the reference treatment (treatment R = fasted). The subjects will be 
randomly allocated to the two treatment sequences (T-R or R-T).
A total of 12 healthy male subjects are planned to participate in this trial. 
The treatments will be two single oral doses 
 BI 1015550 separated by a washout 
period of at least 7 days between the treatments:
Treatment T:
 tablets of BI 1015550 as Trial Formulation 1 (TF1), fed
Treatment R:
 tablets of BI 1015550 as Trial Formulation 1 (TF1), fasted
For details refer to Section 4.1.
An overview of all relevant trial activities is provided in the Flow Chart. For visit schedules 
and details of trial procedures at selected visits, refer to Sections 6.1 and 6.2, respectively.
3.1.1
Administrative structure of the trial
The trial is sponsored by Boehringer Ingelheim (BI) Pharma GmbH & Co. KG, Germany.
BI has appointed a Trial Clinical Monitor (TCM), responsible for coordinating all required 
activities, in order to 

Manage the trial in accordance with applicable regulations and internal SOPs,

Direct the clinical trial team in the preparation, conduct, and reporting of the trial,

Ensure appropriate training and information of local clinical monitors (CML), Clinical 
Research Associates (CRAs), and participating trial sites.
The trial medication will be provided by the Clinical Trial Supplies Unit (CTSU), BI Pharma 
GmbH & Co. KG, Biberach, Germany. 
 
Safety laboratory tests will be performed by the local laboratory of the trial site 
 
The analyses of BI 1015550 concentrations in plasma will be performed at a suitable contract 
research organization (CRO) under the responsibility of the Department of Drug Metabolism 
and Pharmacokinetics, BI Pharma GmbH & Co. KG, Biberach, Germany. 

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On-site monitoring will be performed by BI or a contract research organization appointed by 
BI.
Data management and statistical evaluation will be done by BI or by a suitable contract 
research organization (CRO) under the responsibility of BI and according to BI SOPs.
Tasks and functions assigned in order to organize, 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.
3.2
DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE OF 
CONTROL GROUP
For relative bioavailability trials, the crossover design is preferred due to its efficiency: since 
each subject serves as his own control, the comparison between treatments is based on a 
comparison within subjects rather than between subjects. This trial design therefore removes 
intersubject variability from the comparison between treatments [cf. R94 1529].
Blinding is not possible because the treatments are distinguishable.
The open-label treatment is not expected to bias results, since the study endpoints are derived 
from measurement of plasma concentrations of the analyte provided by a bioanalytical 
laboratory which is blinded to treatment allocation.
3.3
SELECTION OF TRIAL POPULATION
It is planned that 12 healthy male subjects will enter the study. Subjects will be recruited 
from the volunteers' pool of the trial site. 
 
A log of all subjects enrolled into the trial (i.e. having given informed consent) will be 
maintained in the ISF at the investigational site irrespective of whether they have been treated 
with investigational drug or not.
3.3.1
Main diagnosis for study entry
The study will be performed in healthy subjects.
3.3.2
Inclusion criteria
Subjects will only be included into the trial, if they meet the following criteria:
1. Healthy male subjects according to the assessment of the investigator, based on a 
complete medical history including a physical examination, vital signs (BP, PR), 12-lead 
ECG, and clinical laboratory tests 
2. Age of 18 to 55 years (incl.)

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3. BMI of 18.5 to 29.9 kg/m2 (incl.)
4. Signed and dated written informed consent prior to admission to the study in accordance 
with GCP and local legislation
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) is deviating from 
normal and judged 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 45 to 90 bpm
3. Any laboratory value outside the reference range that the investigator considers to be of 
clinical relevance
4. Any evidence of a concomitant disease judged as clinically relevant by the investigator
5. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, or 
hormonal disorders
6. Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the 
pharmacokinetics of the trial medication (except appendectomy)
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 mood disorders and any signs of suicidality (ideation as well as behavior) in the 
past
8. History of relevant orthostatic hypotension, fainting spells, or blackouts
9. Chronic or relevant acute infections
10. History of relevant allergy or hypersensitivity (including allergy to the trial medication or 
its excipients) 
11. Use of drugs within 30 days prior to administration of trial medication if that might 
reasonably influence the results of the trial (incl. QT/QTc interval prolongation)
12. Participation in another trial where an investigational drug has been administered within 
60 days prior to planned administration of trial medication, or current participation in 
another trial involving administration of investigational drug
13. Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
14. Inability to refrain from smoking on trial days
15. Alcohol abuse (consumption of more than 30 g per day)
16. Drug abuse or positive drug screening
17. Blood donation of  more than 100 mL within 30 days prior to administration of trial 
medication or intended donation during the trial
18. Intention to perform excessive physical activities within one week prior to administration 
of trial medication or during the trial
19. Inability to comply with dietary regimen of trial site

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20. A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are 
repeatedly greater than 450 ms) or any other relevant ECG finding at screening
21. A history of additional risk factors for Torsades de Pointes (such as heart failure, 
hypokalemia, or family history of Long QT Syndrome)
22. Subject is assessed as unsuitable for inclusion by the investigator, for instance, because 
considered not able to understand and comply with study requirements, or has a condition 
that would not allow safe participation in the study 
23. Male subjects who do not agree to minimize the risk of female partners becoming 
pregnant from the first dosing day until two month after the study completion. Acceptable 
methods of contraception comprises barrier contraception and a medically accepted 
contraceptive method for the female partner (intra-uterine device, hormonal contraceptive 
since at least two month)
In addition, the following trial-specific exclusion criteria apply:
24. Positive or missing fecal occult blood test
25. Positive testing for hematuria if confirmed by microscopic urine analysis 
For study restrictions, refer to Section 4.2.2.
3.3.4
Removal of subjects from therapy or assessments
3.3.4.1
Removal of individual subjects
An individual subject is to be removed from the trial if:
1. The subject withdraws consent for trial treatment or trial participation, without the need to 
justify the decision
2. The subject needs to take concomitant drugs that interfere with the investigational  
product or other trial medication
3. The subject is no longer able to participate for other medical reasons (such as surgery, 
adverse events, or diseases)
4. An AE or clinically significant laboratory change or abnormality occurred that the 
investigator judges to warrant discontinuation of treatment. This may include cases of 
sustained symptomatic hypotension (BP <90/50 mmHg) or hypertension (BP >180/100 
mmHg) or of clinically relevant changes in ECG requiring intervention as well as 
unexplained liver enzyme elevations at any time during the trial.
5. The subject shows an elevation of AST and/or ALT ≥3-fold ULN combined with an 
elevation of total bilirubin ≥2-fold ULN (measured in the same blood sample) and/or 
needs to be followed up according to the ‘DILI checklist’ provided in the ISF.
In addition to these criteria, the physician may discontinue subjects at any time based on his 
or her clinical judgment.

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A subject can also be removed from the trial if eligibility criteria are being violated or if the 
subject fails to comply with the protocol (for instance, by non-adherence to dietary rules, or 
non-attendance at study assessments).
If a subject is removed from or withdraws from the trial prior to first administration of trial 
medication, the data of this subject will not be entered in the case report form (CRF) or trial 
database and will not be reported in the clinical trial report (CTR). If a subject is removed 
from or withdraws from the trial after first administration of trial medication, this will be 
documented and the reason for discontinuation must be recorded in the CRF. In this case, the 
data will be included in the CRF/trial database and will be reported in the CTR. At the time 
of discontinuation a complete end of trial examination will be performed if possible and the 
information will be recorded in the CRFs. If the discontinuation occurs before the end of the 
residual effect period (REP) (see Section 5.2.2.2), the discontinued subject should if possible 
be questioned for AEs and concomitant therapies at or after the end of the REP in order to 
ascertain collection of AEs and concomitant therapies throughout the REP, if not contrary to 
any consent withdrawal of the subject. These discontinuations will be discussed in the CTR.
3.3.4.2
Discontinuation of the trial by the sponsor
Boehringer Ingelheim reserves the right to discontinue the trial overall or at a particular trial 
site at any time for any of the following reasons:
1. New toxicological findings or serious adverse events invalidate the earlier positive 
benefit-risk-assessment. More specifically, the trial will be terminated if more than 50% 
of the subjects show drug-related and clinically relevant adverse events of moderate or
severe intensity, or if at least one drug-related serious adverse event is reported.
2. The expected enrolment goals overall or at a particular trial site are not met
3. Violation of GCP, or the CTP by a trial site or investigator, disturbing the appropriate 
conduct of the trial
4. The sponsor decides to discontinue the further development of the investigational 
product.
3.3.5
Replacement of subjects
In case some subjects do not complete the trial, the trial clinical monitor together with the 
trial pharmacokineticist and the trial statistician are to decide if and how many subjects will 
be replaced. A replacement subject will be assigned a unique study subject number, and will 
be assigned to the same treatment as the subject he replaces.

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4.
TREATMENTS
4.1
TREATMENTS TO BE ADMINISTERED
The investigational product has been manufactured by BI Pharma GmbH & Co. KG. 
4.1.1
Identity of BI investigational product
The characteristics of the test product are given below:
Substance:
BI 1015550
Pharmaceutical formulation: Tablet formulation 1 (TF1)
Source:
Boehringer Ingelheim Pharma GmbH & Co. KG, Germany
Unit strength:
Posology:
4-0-0 
Route of administration:
p.o.
Duration of use:
Single dose in treatments T (fed) and R (fasted)
4.1.2
Method of assigning subjects to treatment groups
The randomization list of study subject numbers and assigned treatment sequences will be 
provided to the trial site in advance.
The allocation of subjects to study subject numbers will be performed prior to the first
administration of trial medication in the morning of Day 1 (Visit 2). For this purpose, the 
subjects will be allocated to a study subject number by drawing lots. By the use of the 
randomization list subjects are then assigned to a treatment sequence.
Once a subject number has been assigned, it cannot be reassigned to any other subject.
The randomization procedure is described in Section 7.5.
 
 

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4.1.5
Blinding and procedures for unblinding
No blinding was performed because the treatments are distinguishable from each another.
This Phase I trial will be handled in an open fashion throughout (that is, during the conduct,
including data cleaning and preparation of the analysis). This is considered acceptable 
because the potential for bias seems to be low and does not outweigh practical considerations.

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Emergency envelopes will not be provided, since all subjects receive the same dose of the 
same formulation in this open label design.
PK samples will be labelled in such a way that treatment allocation cannot be derived by the 
analytical site.
4.1.6
Packaging, labelling, and re-supply
Drug supplies will be provided by the Department of Pharmaceutical Development of 
Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
The clinical trial supply consists of containers holding the trial medication which are labelled
with trial identification. The required information according to the German Drug Law as well 
as Annex 13/EU GMP Guideline will be provided on the containers. Containers will be 
labelled with:

BI trial number

Name of product and strengths or identification code

Pharmaceutical dosage form, quantity of dosage units 

Route and mode of administration

Term ‘For Clinical Trial Use’ (domestic language)

Sponsor name and address

Storage conditions

Use-by date

Batch number
The telephone number of the sponsor and name, address and telephone number of the trial 
site are given 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. 
Examples of the labels will be available in the ISF.
No re-supply is planned.
4.1.7
Storage conditions
Drug supplies will be kept in their original packaging and in a secure limited access storage 
area according to the recommended (labelled) storage conditions. Where 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 
local clinical monitor (as provided in the list of contacts) is to be immediately contacted.
4.1.8
Drug accountability
The investigator will receive the investigational drugs delivered by the sponsor when the 
following requirements are fulfilled:

Approval of the trial protocol by the IRB / ethics committee 

Approval/notification of the regulatory authority, e.g. competent authority

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
Availability of the curriculum vitae of the principal investigator

Availability of a signed and dated clinical trial protocol
Only authorized personnel as documented in the form ‘Trial Staff List’ may dispense
medication to trial subjects. The trial medication must be administered in the manner 
specified in the CTP. All unused medication will be disposed locally by the trial site upon 
written authorization by the clinical monitor. Receipt, usage and disposal must be 
documented on the respective forms. Account must be given for any discrepancies. 
The investigator 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 products and trial subjects. The 
investigator will maintain records that document adequately that the subjects were provided 
the doses specified by the CTP, and that reconcile all investigational products received from 
the sponsor. At the time of disposal, the investigator must verify that no remaining supplies 
are in the investigator’s possession.
4.2
OTHER TREATMENTS, EMERGENCY  PROCEDURES,
RESTRICTIONS
4.2.1
Other treatments and emergency procedures
There are no special emergency procedures to be followed. No additional treatment is 
planned. However, in case of adverse events in need of treatment, the investigator can 
authorize 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 medical 
evaluation results have returned to an acceptable level.
4.2.2
Restrictions
4.2.2.1
Restrictions regarding concomitant treatment
In principle, no concomitant therapy is allowed. All concomitant or rescue therapies will be 
recorded (including time of intake on study days) on the appropriate pages of the CRF.
 
4.2.2.2
Restrictions on diet and life style
While admitted to the trial site the subjects are restricted from consuming any other foods or 
drinks than those provided by the staff. Standardized meals will be served at the time points 
described in the Flow Chart. No food is allowed for at least 4 h after drug intake.
From 1 h before drug intake until lunch, fluid intake is restricted to the milk served with 
breakfast in treatment T (see Table 4.1.4: 2), the water administered with the drug, and an 

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additional 240 mL of water at 2 h and 4 h post-dose (mandatory for all subjects). From lunch 
until 24 h post-dose, total fluid intake is restricted to 3000 mL. 
For each study period, alcoholic beverages are not permitted starting 5 days before the first 
administration of trial medication until the last PK sample is collected; grapefruits, Seville 
oranges (sour or bitter oranges) and their juices, and dietary supplements and products
including St. John's wort (Hypericum perforatum) are not allowed from 7 days before the first 
administration until collection of the last PK.
Smoking is not allowed during in-house confinement at the trial site.
Methylxanthine-containing drinks or foods (such as coffee, tea, cola, energy drinks, and 
chocolate) are not allowed from 24 hours before until 24 h after each administration of trial 
medication.
Excessive physical activity (such as competitive sport) should be avoided starting 7 days 
before the first administration of trial medication until the end of trial examination. 
Direct exposure to the sun or exposure to solarium radiation should be avoided during the 
entire study.
4.3
TREATMENT COMPLIANCE
Compliance will be assured by administration of all trial medication in the study center under 
supervision of the investigating physician or a designee. The measured plasma concentrations 
will provide additional confirmation of compliance.
Subjects who are non-compliant (for instance, who do not appear for scheduled visits or 
violate trial restrictions) may be removed from the trial and the CRF will be completed 
accordingly (for further procedures, please see Section 3.3.4.1).

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5.
VARIABLES AND THEIR ASSESSMENT
5.1
EFFICACY - CLINICAL PHARMACOLOGY
5.1.1
Endpoints of efficacy
No efficacy endpoints will be evaluated in this trial.
5.1.2
Assessment of efficacy
Not applicable.
5.2
SAFETY
5.2.1
Endpoints of safety
Safety and tolerability of the investigational drug 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)
 
5.2.2
Assessment of adverse events
5.2.2.1
Definitions of adverse events
Adverse event
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered a medicinal product and which does not necessarily have 
to have a causal relationship with this treatment.
An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
product, whether or not considered related to the medicinal product.
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,

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
requires inpatient hospitalization or 

requires prolongation of existing hospitalization,

results in persistent or significant disability or incapacity, or

is a congenital anomaly/birth defect, 
or 

is deemed serious for any other reason if it is an important medical event when based 
upon appropriate medical judgment which may jeopardize 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 hospitalization or 
development of dependency or abuse. 
AEs considered ‘Always Serious’
Cancers of new histology and exacerbations of existing cancer must be classified as a serious 
event regardless of the duration between discontinuation of the drug and must be reported as 
described in 5.2.2.2, subsections “AE Collection” and “AE reporting to sponsor and 
timelines”.
In accordance with the European Medicines Agency initiative on Important Medical Events, 
Boehringer Ingelheim has set up a list of further 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 given 
above.
The latest list of ‘Always Serious AEs’ can be found in the RDC system. These events should 
always be reported as SAEs as described above.
Adverse events of special interest (AESIs)
The term 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 above.
The following are considered as AESIs in this trial:

Hepatic injury, as defined by the following alterations of hepatic laboratory 
parameters: 
o
an elevation of AST and/or ALT ≥3-fold ULN combined with an elevation of 
total bilirubin ≥2-fold ULN measured in the same blood sample, and/or
o
aminotransferase (ALT, and/or AST) elevations ≥10 fold ULN
These lab findings constitute a hepatic injury alert and the patients showing these lab 
abnormalities need to be followed up according to the ‘DILI checklist’ provided in the ISF. In 
case of clinical symptoms of hepatic injury (icterus, unexplained encephalopathy, 
unexplained coagulopathy, right upper quadrant abdominal pain, etc.) without lab results 

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(ALT, AST, total bilirubin) available, the Investigator should make sure these parameters are 
analyzed, 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.
With the exception of DILI, no AESIs have been defined for this trial.
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
Causal relationship of AEs
Medical judgment should be used to determine the relationship, 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 etiologies 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 diminished).
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.

Additional arguments amongst those stated before, like 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).

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
Disappearance of the event even though the trial drug treatment continues or remains 
unchanged. 
5.2.2.2
Adverse event collection and reporting
AEs 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 as well as the time of onset, end, 
and intensity of these events. 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 careful 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, and intensity of the event as 
well as 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: 
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 or trial database 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 AEs but 
should only report related SAEs and related AESIs of which the investigator
may become aware of by any means of communication, e.g. phone call. Those 
AEs should, however, not be reported in the CRF.

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The Residual Effect Period (REP) for BI 1015550, when measurable drug levels or PD 
effects are still likely to be present, is defined as 
 after the last administration of BI 
1015550. Therefore, all AEs which occurred through the treatment phase and throughout the 
REP will be considered as on treatment; please see Section 7.3.3. Events which occurred after 
the REP will be considered as follow-up events.
AE reporting to 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 via fax immediately (within 24 hours) to the 
sponsor’s unique entry point (country specific contact details will be provided in the ISF). 
The same timeline applies if follow-up information becomes available. In specific occasions 
the Investigator could inform the sponsor upfront via telephone. This does not replace the 
requirement to complete and fax the BI SAE form. 
With receipt of any further information to these events, a follow-up SAE form has to be 
provided. For follow-up information the same rules and timeline apply as for initial 
information.
Information required
For each AE, the investigator should provide the information requested on the appropriate 
CRF pages and the BI SAE form (if applicable). The investigator should determine the causal 
relationship to the trial medication.
The following should also be recorded as an (S)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.
All (S)AEs, including those persisting after individual subject’s end of trial must be followed 
up until they have resolved, have been assessed as ‘chronic’ or ‘stable’, or no further 
information can be obtained.

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Pregnancy
If applicable:
In rare cases, pregnancy might occur in a clinical trial. Once a subject subject has been
enrolled in the clinical trial and has taken trial medication, the investigator must report any
drug exposure during pregnancy in a trial participant immediately (within 24 hours) by means
of Part A of the Pregnancy Monitoring Form to the sponsor’s unique entry point.
Similarly, potential drug exposure during pregnancy must be reported if a partner of a male
trial participant becomes pregnant. This requires a written consent of the pregnant partner.
The outcome of the pregnancy associated with the drug exposure during pregnancy must be
followed up and reported to the sponsor’s unique entry point on the Pregnancy Monitoring
Form for Clinical Trials (Part B).
The ISF will contain the Pregnancy Monitoring Form for Clinical Trials (Part A and 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 Trials 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.
5.2.3
Assessment of safety laboratory parameters
For the assessment of laboratory parameters, blood and urine samples will be collected by the 
trial site at the time points indicated in the Flow Chart after the subjects have fasted for at 
least 10 h. Overnight fasting is not required at the discretion of the investigator or designee
for retests.
The parameters that will be determined are listed in Tables 5.2.3: 1 and 5.2.3: 2. Reference 
ranges will be provided in the ISF, Section 10. 
Manual differential white blood cell count will only be performed if there is an abnormality 
in the automatic blood cell count. In case the urinalysis is positive for erythrocytes, 
leukocytes, nitrite or protein, microscopic examination of the urine sediment will be 
performed. Positive findings of the urine sediment examination will be monitored and if 
needed based on the medical judgment of the investigator an urologist may be consulted.
Fecal occult blood testing will be performed using an immunochemical test kit for 
hemoglobin. Fecal occult blood and calprotectin testing will be performed by the clinical 
laboratory at the time points indicated in the Flow Chart.

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Table 5.2.3: 1
Routine laboratory tests
Functional lab 
group
Test name 
SCR
A1
B2
EOT
Hematology
Hematocrit
Hemoglobin
Red blood cell count (RBC)
Reticulocyte count
White blood cell count (WBC)
Platelet count
Erythrocyte sedimentation rate (ESR)
x
x
x
x
x
x
x
x
x
x
--
x
x
x
x
x
x
--
x
x
x
x
x
x
x
x
x
x
Automatic WBC 
differential 
(relative and absolute)
Neutrophils, eosinophils, basophils, monocytes, 
lymphocytes
x
x
x
x
Manual differential 
WBC (if automatic 
count is not feasible or 
differential WBC is 
abnormal and clinically 
relevant in the opinion of 
the investigator)
Polymorphnuclear neutrophils (segs), band neutrophils 
(stabs), eosinophils, basophils, monocytes, lymphocytes 
Coagulation
Activated partial thromboplastin time (aPTT)
Prothrombin time (Quick’s test and INR)
Fibrinogen
x
x
x
x
x
x
x
x
x
x
x
x
Enzymes
Aspartate transaminase (AST/GOT)
Alanine transaminase (ALT/GPT)
Alkaline phosphatase (AP)
Gamma-glutamyl transferase (GGT)
Glutamate dehydrogenase (GLDH)
Creatine kinase (CK); CK-MB only if CK is elevated 
Lactate dehydrogenase (LDH)
Lipase
Amylase
x
x
x
x
x
x
x
x
x
x
x
x
x
--
x
x
--
--
x
x
x
x
--
x
x
--
--
x
x
x
x
x
x
x
x
x
Hormones
Thyroid stimulating hormone (TSH)
x
--
--
--
Substrates
Plasma glucose
Creatinine 
Total bilirubin 
Direct bilirubin
Total protein
high sensitivity C-Reactive Protein (hsCRP) 
Uric acid 
Total cholesterol 
Triglycerides
Albumin 
x
x
x
x
x
x
x
x
x
x
--
x
x
x
x
x
--
--
--
x
--
x
x
x
x
x
--
--
--
x
x
x
x
x
x
x
x
x
x
x
Electrolytes
Sodium
Potassium
Calcium
Chloride
Inorganic phosphate
x
x
x
x
x
x
x
--
--
x
x
x
--
--
x
x
x
x
x
x
1
A: Days -5 to -1 (Visit 2)
2
B:  Days 2 and 6 (Visit 2/3)

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Table 5.2.3: 1
Routine laboratory tests (cont.)
Functional lab 
group
Test name 
SCR
A1
B2
EOT
Urinalysis (Stix)
Urine nitrite
Urine protein
Urine glucose
Urine ketone
Urobilinogen
Urine bilirubin
Urine erythrocytes
Urine leukocytes
Urine pH
x
x
x
x
x
x
x
x
x
x
x
x
x
x 
x
x
x
x
x
x
x
x
x 
x
x
x
x
x
x
x
x
x
x
x
x
x
Urine sediment 
(microscopic 
examination if 
erythrocytes, leukocytes 
nitrite or protein are 
abnormal in urine)
Only positive findings will be reported (for instance, the 
presence of sediment bacteria, casts in sediment, 
squamous epithelial cells, erythrocytes, leukocytes)
1
A: Days -5 to -1 (Visit 2)
2
B: Days 2 and 6 (Visit 2/3) 
The tests listed in Table 5.2.3: 2 are exclusionary laboratory tests which 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 prior to each treatment period.
Table 5.2.3: 2
Exclusionary laboratory tests
Functional lab group
Test name 
Drug screening (urine)
Amphetamine/MDA
Barbiturates
Benzodiazepine
Cannabis
Cocaine 
Methadone
Methamphetamines/MDMA/XTC
Opiates 
Phencyclidine
Tricyclic antidepressants
Infectious serology (blood)
Hepatitis B surface antigen (qualitative)
Hepatitis B core antibody (qualitative)
Hepatitis C antibodies (qualitative)
HIV-1 and HIV-2 antibody (qualitative)
To encourage compliance with alcoholic restrictions, a breath alcohol test (Alcotest® 7410, 
Dräger AG, Lübeck, Germany) will be performed prior to each treatment period, and may be 
repeated at any time during the study at the discretion of an investigator or designee. The 
results will not be included in the CTR.

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The laboratory tests listed in Table 5.2.3: 1 and 5.2.3: 2 will be performed at 
 
 with the exception of 
the drug screening. This test will be performed at the trial site using e.g. AccuSign® DOA 10 
test.
Laboratory data will be transmitted electronically from the laboratory to the trial site.
5.2.4
Electrocardiogram
Twelve-lead ECGs (I, II, III, aVR, aVL, aVF, V1 - V6) will be recorded using a
computerized electrocardiograph (CardioSoft EKG System, GE Medical Systems, Freiburg,
Germany) at the time points given in the Flow Chart.
All ECGs will be recorded for a 10-sec duration after the subjects have rested for at least 5
min in a supine position. ECG assessment will always precede all other study procedures of 
the same time point (except blood drawing from an intravenous cannula which is already in 
place) to avoid impact of sampling on the ECG quality. 
All ECGs will be stored electronically on the Muse CV Cardiology System (GE Medical 
Systems, Freiburg, Germany). Electrode placement will be performed according to the 
method of Wilson, Goldberger and Einthoven modified by Mason and Likar (hips and 
shoulders instead of ankles and wrists). 
All locally printed ECGs will be evaluated by the investigator or a designee. ECGs may be 
repeated for quality reasons (like alternating current artefacts, muscle movements, electrode 
dislocation) and the repeated ECG will be used for analysis. Additional (unscheduled) ECGs 
may be collected by the investigator for safety reasons. 
Abnormal findings will be reported as AEs (during the trial) or baseline conditions (at 
screening) if judged clinically relevant by the investigator. Any ECG abnormalities will be 
monitored carefully and, if necessary, the subject will be removed from the trial and will 
receive the appropriate medical treatment. 
5.2.5
Assessment of other safety parameters
5.2.5.1
Vital signs
Systolic and diastolic blood pressures (BP) as well as pulse rate (PR) or heart rate (heart rate 
is considered to be equal to pulse rate) will be measured by a blood pressure monitor 
(Dinamap Pro 100, GE Medical Systems, Freiburg, Germany) 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.
5.2.5.2
Medical examinations
At screening, the medical examination will include demographics including height and body 
weight, smoking and alcohol history, relevant medical history and concomitant therapy, 
review of inclusion and exclusion criteria, review of vital signs (BP, PR), 12-lead ECG, 

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laboratory tests, and a physical examination. At the end of trial examination, it will include 
review of vital signs, 12-lead ECG, laboratory tests, and a physical examination.
5.3
OTHER
 
 
 
 
 
 
 
 
 
5.4
APPROPRIATENESS OF MEASUREMENTS
All measurements performed during this trial are standard measurements and will be 
performed in order to monitor subjects’ safety and to determine pharmacokinetic parameters 
in an appropriate way. The scheduled measurements will allow monitoring of changes in vital 
signs, standard laboratory values, and ECG parameters that might occur as a result of 
administration of trial medication. The safety assessments are standard, are accepted for 
evaluation of safety and tolerability of an orally administered drug, and are widely used in 
clinical trials. The pharmacokinetic parameters and measurements outlined in Section 5.5 are
generally used assessments of drug exposure.
5.5
DRUG CONCENTRATION MEASUREMENTS AND 
PHARMACOKINETICS
Date and clock time of drug administration and pharmacokinetic sampling will be recorded. 
Exact time points of plasma sampling will be derived from the study management system 
ClinBase™ and documented in the CRFs by the medical personnel or sent as electronic files
to the trial data manager. The actual sampling times will be used for determination of 
pharmacokinetic parameters.
5.5.1
Pharmacokinetic endpoints
5.5.1.1
Primary endpoints
The following primary endpoints will be determined for BI 1015550:

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
AUC0-tz (area under the concentration-time curve of the analyte in plasma over the 
time interval from 0 to the last quantifiable data point)

Cmax (maximum measured concentration of the analyte in plasma)
5.5.1.2
Secondary endpoint
The following secondary endpoint will be evaluated for BI 1015550:

AUC0-∞(area under the concentration-time curve of the analyte in plasma over the 
time interval from 0 extrapolated to infinity)
 
 
 
5.5.2
Methods of sample collection
5.5.2.1
Plasma sampling for pharmacokinetic analysis
For quantification of analyte plasma concentrations, 2.7 mL of blood will be taken from an 
antecubital or forearm vein into a K3-EDTA (tripotassium ethylenediaminetetraacetic acid)-
anticoagulant blood drawing tube at the times indicated in the Flow Chart. Blood will be 
withdrawn by means of either an indwelling venous catheter or by venipuncture with a metal 
needle.
The EDTA-anticoagulated blood samples will be centrifuged for about 10 min at about 
2000 g to 4000 g and at about 4° to 8 °C. Two plasma aliquots will be obtained and stored in 

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polypropylene tubes. The first aliquot should contain at least 0.5 mL plasma. Plasma aliquots 
will be frozen within 2 hours after blood withdrawal (interim storage of blood/plasma at room 
temperature). For each aliquot the time when the sample was placed in the freezer will be 
documented. Until transfer on dry ice to the analytical laboratory, the aliquots will be stored 
upright at about -20°C or below at the trial site. The second aliquot will be transferred to the 
analytical laboratory after the bioanalyst has acknowledged safe arrival of the first aliquot. At 
the analytical laboratory the plasma samples will be stored at about -20°C or below until 
analysis.
At a minimum, the sample tube labels should list the following information: BI trial number, 
subject number, visit, and planned sampling time. Further information such as “PK”, matrix 
and aliquot number (e.g. 1 or 2/back-up) may also be provided. 
 
 
 
 
 
5.5.3
Analytical determinations
5.5.3.1
Analytical determination of analyte plasma concentration
Concentrations of BI 1015550 in plasma from subjects will be determined by a validated 
HPLC-MS/MS assay (high performance liquid chromatography, tandem mass spectrometry). 
The bioanalyst will be blinded during sample analysis. The analysis will be performed under
the responsibility of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharma 
GmbH & Co. KG, Biberach, Germany at a suitable contract research organization (CRO).

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6.
INVESTIGATIONAL PLAN
6.1
VISIT SCHEDULE
Exact times of measurements outside the permitted time windows will be documented. The 
acceptable time windows for screening and end of trial examination are given in the Flow 
Chart.
Study measurements and assessments scheduled to occur ‘before’ trial medication 
administration on Day 1 are to be performed and completed within a 3 h-period prior to the 
trial drug administration and prior to predose meal intake. 
The acceptable deviation from the scheduled time for post-dose vital signs, ECG and 
laboratory tests will be ± 30 min.
If scheduled in the Flow Chart at the same time as a meal, blood sampling, vital signs and 12-
lead ECG recordings have to be done first. Furthermore, if several measurements including 
venipuncture are scheduled for the same time, venipuncture should be the last of the 
measurements due to its inconvenience to the subject and possible influence on physiological
parameters.
For planned individual plasma concentration 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 determination of pharmacokinetic parameters.
If a subject misses an appointment, it will be rescheduled if possible. The relevance of 
measurements outside the permitted time windows will be assessed no later than at the Report 
Planning Meeting.
6.2
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS
6.2.1
Screening period
After having been informed about the trial, all subjects will give their written informed 
consent in accordance with GCP and local legislation prior to enrolment in the study.
For information regarding laboratory tests (including drug and virus screening, and fecal 
occult blood testing and fecal calprotectin testing), ECG, vital signs, and physical 
examination, refer to Sections 5.2.3 to 5.2.5.
Pharmacogenomic genotyping will be performed in those volunteers whose genotypes are not 
known (for details see Section 5.3).
6.2.2
Treatment periods
Each subject is expected to participate in two treatment periods (Days -1 to Day 6 in each 
period). The treatment periods will be separated by at least 7 days between drug 
administrations. In addition, an ambulatory visit (visit 2) will be necessary within 5 days prior 
to the first study drug administration for safety laboratory, fecal occult blood and fecal
calprotectin testing.

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In the evening of Day -1 of each treatment period study participants will be admitted to the 
trial site and kept under close medical surveillance for at least 24 h following drug 
administration. The subjects will then be allowed to leave the trial site after formal 
assessment and confirmation of their fitness. On all other study days, the study will be 
performed in an ambulatory fashion.
For details on time points and procedures for collection of plasma samples for PK analysis, 
refer to Flow Chart and Section 5.5.2. 
The safety measurements performed during the treatment period are specified in Section 5.2
of this protocol and in the Flow Chart. For details on time points for all other trial procedures, 
refer to the Flow Chart. AEs and concomitant therapy will be assessed continuously from 
screening until the end of trial examination.
6.2.3
End of trial period
For AE assessment, laboratory tests including testing for fecal occult blood and fecal 
calprotectin testing, recording of ECG and vital signs, and physical examination during the 
end of trial period, see Sections 5.2.2 to 5.2.5.
Subjects who discontinue treatment before the end of the planned treatment period should 
undergo the end of trial visit.
All abnormal values (including laboratory parameters) that are judged 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 subject’s end of trial must be followed 
up until they have resolved, have been sufficiently characterized, or no further information 
can be obtained. 
The end of the trial as a whole is defined by the ‘last regular visit completed by last subject’ 
or ‘end date of the last open AE’ or ‘date of the last follow-up test’ or ‘date of an AE has 
been decided as sufficiently followed-up’, whichever is latest.

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7.
STATISTICAL METHODS AND DETERMINATION OF
SAMPLE SIZE
7.1
STATISTICAL DESIGN – MODEL
7.1.1
Objectives
The primary objective of this trial is to investigate the relative bioavailability of 
 BI 
1015550 as tablet formulation in the fed state (Test, T) compared to 24 mg BI 1015550 as 
tablet formulation in the fasted state (Reference, R) following oral administration. The trial is 
designed to allow intrasubject comparisons and will be evaluated statistically by use of an 
appropriate linear model.
The secondary objective is the evaluation and comparison of several pharmacokinetic 
parameters between the treatments. The secondary objective(s) will be assessed by 
descriptive statistics.
The assessment of safety and tolerability will be an additional objective of this trial, and will 
be evaluated by descriptive statistics.
7.1.2
Endpoints
Relative bioavailability is to be determined on the basis of the primary and secondary 
pharmacokinetic endpoints (see Section 5.5.1).
Safety and tolerability will be determined on the basis of the parameters specified in Section 
5.2.1.
7.1.3
Model
The statistical model used for the assessments of relative bioavailability is described in 
Section 7.3.2
7.2
NULL AND ALTERNATIVE HYPOTHESES
The relative bioavailability of BI 1015550 under fed and fasted conditions will be estimated 
by the ratios of the geometric means (test/reference) for the primary and secondary PK 
endpoints. Additionally, their two-sided 90% confidence intervals (CIs) will be provided. 
This method corresponds to the two one-sided t-tests procedure, each at the 5% significance 
level. Since the main focus is on estimation and not testing, an acceptance range was not 
specified, that is, no hypothesis will be tested.
7.3
PLANNED ANALYSES
All individual data will be listed.
Adherence to the protocol (such as inclusion/exclusion criteria, times of measurement, 
compliance with intake of trial medication, treatment dispensing errors, prohibited 
concomitant medication, completeness and consistency of data) will be checked. Important 

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protocol violations (IPVs) will be identified no later than in the Report Planning Meeting and 
provided in the TSAP.
The statistical analysis will be based on the following analysis sets.
•
Entered set (ES): This subject set includes all entered and randomized subjects, 
whether treated or not. 
•
Treated set (TS): The treated set includes all subjects who were randomized and 
treated with at least one dose of study drug. The treatment assignment will be 
determined based on the first treatment the subjects received.
•
Pharmacokinetic set (PKS): The PK parameter analysis set (PKS) includes all subjects 
in the Treated Set (TS) who provide at least one primary or secondary PK parameter 
that was not excluded according to the description below. 
Plasma concentration data and parameters of a subject will be included in the statistical 
pharmacokinetic analyses if they are not flagged for exclusion due to a protocol violation 
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.
Relevant protocol violations may be
•
Incorrect trial medication taken, i.e. the subject received at least one dose of trial 
medication the subject was not assigned to
•
Incorrect dose of trial medication taken
•
Use of restricted medications.
Plasma concentrations and/or PK parameters of a subject will be considered as non-
evaluable, if for example
•
The subject experienced emesis that occurred at or before two times median tmax of the 
respective treatment (Median tmax is to be determined excluding the subjects 
experiencing emesis)
•
Missing samples/concentration data at important phases of PK disposition curve
•
Use of restricted comedication
7.3.1
Primary analyses
The primary and secondary parameters (refer to Section 5.5.1) will be calculated according to 
the BI Standard Operating Procedure (SOP) ‘Standards and processes for analyses performed 
within Clinical Pharmacokinetics/Pharmacodynamics’ (001-MCS-36-472).
Point estimates of bioavailability, the ratios of the geometric means (test/reference) for the 
primary and secondary endpoints (see 5.5.1.1, 5.5.1.2), and their two-sided 90% confidence 
intervals (CIs) will be provided.
To this end, the PK endpoints will be log transformed (natural logarithm) prior to fitting the 
ANOVA model on the logarithmic scale. This model will include effects accounting for the 
following sources of variation: ‘sequence’, ‘subjects within sequences’, ‘period’ and 

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‘treatment’. The effect ‘subjects within sequences’ will be considered as random, whereas the 
other effects will be considered as fixed. The model is described by the following equation:
yijkm = + i + sim + j + k + eijkm, where
yijkm = logarithm of response (endpoint, see Section 7.1.3) measured on subject m in 
sequence i receiving treatment k in period j,
= the overall mean,
i = the ith sequence effect, i = 1, 2,
sim = the effect associated with the mth subject in the ith sequence, m=1,…, 6, i=1,2,
j = the jth period effect, j = 1, 2,
k = the kth treatment effect, k = 1, 2,
eijkm = the random error associated with the mth subject in sequence i who received
treatment k in period j.
For each endpoint, the difference between the expected means for log(T)-log(R) will be 
estimated by the difference in the corresponding adjusted means (Least Squares Means), and 
a two-sided 90% confidence interval based on the t-distribution will be computed. These 
quantities will then be back-transformed to the original scale to provide the point estimate 
and 90% CIs for each endpoint.
7.3.2
Secondary analyses
The secondary parameters (refer to Section 5.5.1) will be calculated according to the BI SOP 
‘Standards and processes for analyses performed within Clinical Pharmacokinetics/ 
Pharmacodynamics’ (001-MCS-36-472) and will statistically be assessed using the same 
methods as described for the primary endpoints.
7.3.3
Safety analyses
Safety will be assessed for the endpoints listed in Section 5.2.1. All treated subjects (that is,
all subjects who received at least one dose of study drug), will be included in the safety
analysis. Safety analyses will be descriptive in nature and will be based on BI standards. No 
hypothesis testing is planned.
The analyses will be done by ‘treatment at onset’.
Treatments will be compared in a descriptive way. Tabulations of frequencies/proportions 
will be used for the evaluation of categorical (qualitative) data, and tabulations of descriptive 
statistics will be used to analyze continuous (quantitative) data.

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Measurements (such as ECG, vital signs, or laboratory parameters) or AEs will be assigned to 
treatments (see Section 4.1) based on the actual treatment at the planned time of the 
measurement or on the recorded time of AE onset (concept of treatment emergent AEs).
Therefore, measurements planned or AEs recorded prior to first intake of trial medication will 
be assigned to 'screening', those between first trial medication intake until end of the residual 
effect period (see 5.2.2.2) will be assigned to the treatment period. Events after the residual 
effect period but prior to next intake or end of trial examination will be summarized as 
‘follow-up’. These assignments including the corresponding time intervals will be defined in 
detail in the TSAP.
Additionally, further treatment intervals (analyzing treatments) may be defined in order to 
provide summary statistics for time intervals, such as combined treatments, on-treatment 
totals or periods without treatment effects (such as screening).
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 5.2.2.1) and 
other significant AEs (according to ICH E3) will be listed separately.
Laboratory data will be compared to their reference ranges. Values outside the reference 
range as well as values defined as clinically relevant will be highlighted in the listings. 
Additionally, differences from baseline will be evaluated.
Vital signs or other safety-relevant data observed at screening, baseline, during the course of 
the trial and at the end-of-trial evaluation will be assessed with regard to possible changes 
compared to findings before start of treatment.
Relevant ECG findings will be reported as AEs.
7.3.4
Interim analyses
No interim analysis is planned.
7.3.5
Pharmacokinetic analyses
The pharmacokinetic parameters listed in Section 5.5.1 for BI 1015550 will be calculated 
using validated software programs (preferably Phoenix WinNonlin®) according to the 
relevant SOP of the Sponsor (001-MCS-36-472).
Subjects who are not included in the PKS (refer to Section 7.3) will be reported with their 
individual plasma concentrations and individual pharmacokinetic parameters; however, they 
will not be included in descriptive statistics for plasma concentrations, pharmacokinetic 
parameters or other statistical assessment.
Only concentration values within the validated concentration range and actual sampling times 
will be used for the calculation of pharmacokinetic parameters. Concentrations used in the 
pharmacokinetic calculations will be in the same format provided in the bioanalytical report, 
(that is, to the same number of decimal places provided in the bioanalytical report).

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If a predose concentration value is greater than 5% of Cmax, the subject’s pharmacokinetic 
data will be not included in any statistical evaluations, in accordance with international 
guidances. The individual pharmacokinetic parameters of such a subject will be calculated 
and listed separately. If a predose concentration is above below the limit of quantification 
(BLQ), but less than or equal to 5% of the subject’s Cmax value, the subject’s data without any 
adjustments will be included in all pharmacokinetic measurements and calculations.
7.4
HANDLING OF MISSING DATA
7.4.1
Safety
With respect to safety evaluations, it is not planned to impute missing values.
7.4.2
Plasma drug concentration - time profiles
Handling of missing PK data will be performed according to the relevant Corporate 
Procedure of the Sponsor (001-MCS-36-472).
Drug concentration data identified with NOS (no sample available), NOR (no valid result), 
NOA (not analyzed), BLQ, or NOP (no peak detectable) will be displayed as such and not 
replaced by zero at any time point (this rule also applies also to the lag phase, including the 
predose values). 
7.4.3
Pharmacokinetic parameters
Handling of missing PK data will be performed according to the relevant SOP of the Sponsor 
(001-MCS-36-472).
For the non-compartmental analysis, concentration data identified with NOS, NOR or NOA 
will generally not be considered. Concentration values in the lag phase identified as BLQ or 
NOP will be set to zero. All other BLQ/NOP values of the profile will be ignored. The lag 
phase is defined as the period between time zero and the first time point with a concentration 
above the quantification limit.
7.5
RANDOMISATION
Subjects will be randomized to one of the two treatment sequences in a 1:1 ratio. The block 
size will be documented in the CTR.
The sponsor will arrange for the randomization as well as packaging and labelling of trial 
medication. The randomization list will be generated using a validated system, which 
involves a pseudo-random number generator and a supplied seed number so that the resulting 
allocation is both reproducible and non-predictable.
The randomization list will contain additional blocks to allow for subject replacement (refer 
to 3.3.5).

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7.6
DETERMINATION OF SAMPLE SIZE
It is planned to enter a total of 12 subjects in this trial because this sample size is considered 
sufficient to achieve the aims of this exploratory trial.
With this sample size, the following precision in estimating the ratio of geometric means 
(test/reference) can be expected with 95% probability. Precision is defined as the ratio of 
upper CI limit to relative BA estimate. Note that the precision is independent of the actual 
ratio of geometric means. 
 
 
 
 
 
 
 
 
Table 7.6: 1 
Precision that can be expected with 95% tolerance probability and 
illustrative two-sided 90% confidence intervals around the ratios of 
geometric means (T/R) for different gCVs in a 2x2 crossover trial 
(N=12).
gCV [%]
Precision 
upper CL / 
relative BA 
estimate
Ratio [%]*
Lower CL [%]
Upper CL [%]
10
1.105
80
72.40
88.40
10
1.105
100
90.50
110.50
10
1.105
125
113.12
138.13
10
1.105
150
135.74
165.75
10
1.105
200
180.99
221.00
15
1.161
80
68.90
92.89
15
1.161
100
86.13
116.11
15
1.161
125
107.66
145.13
15
1.161
150
129.19
174.16
15
1.161
200
172.26
232.21
20
1.219
80
65.61
97.54
20
1.219
100
82.01
121.93
20
1.219
125
102.52
152.41
20
1.219
150
123.02
182.89
20
1.219
200
164.03
243.86
*Ratio of geometric means (test/reference) for a PK endpoint is defined by exp(T)/exp(R).

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The calculation was performed as described by Julious [R11-5230] using R Version 3.3.2.

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8.
INFORMED CONSENT, DATA PROTECTION, TRIAL
RECORDS
The trial will be carried out in compliance with the protocol, the principles laid down in the 
Declaration of Helsinki, in accordance with the ICH Harmonized Tripartite Guideline for 
Good Clinical Practice (GCP) and relevant BI SOPs.
The investigator should inform the sponsor immediately of any urgent safety measures taken 
to protect the study subjects against any immediate hazard, and also of any serious breaches 
of the protocol or of ICH GCP.
As a general rule, no trial results should be published prior to finalization of the CTR.
Insurance Coverage: The terms and conditions of the insurance coverage must be given to 
each subject and are made available to the investigator via documentation in the ISF.
8.1
STUDY APPROVAL, SUBJECT INFORMATION, AND 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 are to be retained by the investigator as part of the trial records. A copy of 
the signed and dated written informed consent and any additional subject information must be 
given to each subject or the subject’s legally accepted representative.
The subject must be informed that his/her personal trial-related data will be used by 
Boehringer Ingelheim in accordance with the local data protection law. The level of 
disclosure must also be explained to the subject.
The subject must be informed that his or her medical records may be examined by authorized
monitors (Clinical Monitor Local/Clinical Research Associate) or Clinical Quality Assurance 
auditors appointed by Boehringer Ingelheim, by appropriate IRB/IEC members, and by 
inspectors from regulatory authorities.
8.2
DATA QUALITY ASSURANCE
A quality assurance audit/inspection of this trial may be conducted by the sponsor or 
sponsor’s designees, by IRBs/IECs, 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.
The data management procedures to ensure the quality of the data are described in detail in 
the trial data management and analysis plan (TDMAP) available in the TMF.

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8.3
RECORDS
CRFs for individual subjects will be provided by the sponsor. For drug accountability, refer 
to Section 4.1.8.
ClinBaseTM
In the Human Pharmacology Centre (HPC) – Boehringer Ingelheim's Phase I unit – the 
validated ClinBaseTM system is operated for processing information and controlling data 
collected in clinical studies. In addition to its function as a procedure control system, 
ClinBaseTM serves as data base. Instead of being entered into CRFs, selected data are directly 
entered into the system.
8.3.1
Source documents
Source documents provide evidence for the existence of the subject and substantiate the 
integrity of the data collected. Source documents are filed at the investigator’s site.
All data reported in the CRFs must be consistent with the source data or the discrepancies 
must be explained.
Data directly entered into ClinBaseTM (that is, without prior written or electronic record) are 
considered to be source data. The place where data is entered first will be defined in a trial 
specific Source Data Agreement. The data in ClinBaseTM are available for inspection at any 
time.
The investigator may need to request previous medical records or transfer records, depending 
on the trial.
8.3.2
Direct access to source data and documents
The investigator/institution will permit trial-related monitoring, audits, IRB/IEC review and 
regulatory inspection, providing direct access to all related source data/documents. CRFs and 
all source documents, including progress notes (if applicable) and copies of laboratory and 
medical test results must be available at all times for review by the sponsor’s clinical trial 
monitor, auditor and inspection by health authorities (e.g. FDA). The Clinical Research 
Associate/on site monitor and auditor may review all CRFs, and written informed consents. 
The accuracy of the data will be verified by reviewing the documents described in Section 
8.3.1.
8.3.3
Storage period of records
Trial site:
The trial site must retain the source and essential documents (including ISF) according to the 
national or local requirements (whatever is longer) valid at the time of the end of the trial.
Sponsor:
The sponsor must retain the essential documents according to the sponsor’s SOPs.

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8.4
EXPEDITED REPORTING OF ADVERSE EVENTS
BI is responsible to fulfil their legal and regulatory reporting obligation in accordance with 
regulatory requirements.
8.5
STATEMENT OF CONFIDENTIALITY
Individual subject medical information obtained as a result of this trial is considered
confidential and disclosure to third parties is prohibited with the exceptions noted below. 
Subject confidentiality will be ensured by using subject identification code numbers.
Data protection and data security measures are implemented for the collection, storage and
processing of patient data in accordance with the principles 6 and 12 of the WHO GCP
handbook. 
Treatment data may be provided to the subject’s personal physician or to other appropriate 
medical personnel responsible for the subject’s welfare. Data generated 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, i.e. the CA.
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 from clinical trial participants and the corresponding data, in
particular:

A Quality Management System has been implemented to ensure the adherence with
the Principles of Good Clinical Practice as outlined in 'Note For Guidance On Good
Clinical Practice' (CPMP/ICH/13 5/95)

The BI-internal facilities storing and analyzing biological samples and data from
clinical trial participants as well as the laboratories' activities for clinical trials
sponsored by Boehringer Ingelheim are regularly audited. The analytical groups and
the banking facility are therefore assessed to be qualified for the storage and use of
biological samples and data collected in clinical trials.

Samples and data are used only if an appropriate informed consent is available.
8.6
COMPLETION OF TRIAL
The EC /competent authority in each participating EU member state needs to be notified
about the end of the trial (last subject / subject out, unless specified differently in Section
6.2.3 of the CTP) or early termination of the trial.

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9.
REFERENCES 
9.1
PUBLISHED REFERENCES
R03-2269
Guidance for industry: food-effect bioavailability and fed bioequivalence 
studies. In: U.S. Department of Health and Human Services, Food and Drug 
Administration, Center for Drug Evaluation and Research (CDER) 2002:1-
9.
P11-07084
 
 
R11-2587
 
 
P15-07539
 
 
 
 
 
R17-0915
 
 
 
 
 
R17-0919
 
 
 
 
R10-1559
R17-0158
 
R17-0916
 

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R17-1539
 
R17-1540
 
 
R17-1542
 
 
R14-1795
 
R10-1555
 
 
 
R94-1529
Chow SC, Liu JP. Design and Analysis of Bioavailability and 
Bioequivalence Studies. New York: Marcel Dekker Inc 1992
R11-5230
Julious SA. Sample sizes for clinical trials. Boca Raton: Taylor & Francis 
Group 2010
R12-5527
 
 
R17-2431
 
 
R17-2432
 
 
9.2
UNPUBLISHED REFERENCES
c02094779-02
 
 
c01843325
Safety, tolerability and 
pharmacokinetics of single rising oral doses of BI 1015550 in healthy male 
volunteers (a partially randomised, single-blinded, placebo-controlled Phase 
I study). 1305.1. 21 Jun 2013
c02191718-02
Safety, 
tolerability and pharmacokinetics of multiple rising oral doses of BI 
1015550 powder for oral solution in healthy male volunteers q.d. or b.i.d. 
for 14 days (a randomised, double-blind, placebo-controlled within dose 
groups Phase I trial). 1305.2. 15 Apr 2014

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c15772185-02
 Safety, tolerability, and pharmacokinetics 
of single (Part 1) and multiple rising oral doses (Part 2) of BI 1015550 in 
healthy male subjects. 1305.11. 18 May 2017
001-MCS-36-472 Standards and processes for analyses performed within Clinical 
Pharmacokinetics/Pharmacodynamics. Current version

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10.
APPENDICES
Not applicable. 

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11.
DESCRIPTION OF GLOBAL AMENDMENT(S)
This is the original protocol.
Number of global amendment
Date of CTP revision
EudraCT number
BI Trial number
BI Investigational Product(s)
Title of protocol
To be implemented only after 
approval of the IRB / IEC /
Competent Authorities
To be implemented 
immediately in order to 
eliminate hazard –
IRB / IEC / Competent 
Authority to be notified of 
change with request for 
approval
Can be implemented without 
IRB / IEC / Competent 
Authority approval as changes 
involve logistical or 
administrative aspects only
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 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
c17549115
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clinical-trial-protocol
Relative bioavailability of BI 1015550 following oral administration under fed and
fasted conditions in healthy male subjects
Author-Trial Clinical
Pharmacokineticist
12 Jul 2017 09:44 CEST
Approval-Therapeutic Area 
12 Jul 2017 10:12 CEST
Approval-Trial Clinical Monitor
12 Jul 2017 12:06 CEST
Approval-Team Member Medicine
12 Jul 2017 14:06 CEST
Verification-Paper Signature
Completion
13 Jul 2017 10:53 CEST
Approval-Project Statistician
17 Jul 2017 17:13 CEST

Boehringer Ingelheim 
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Document Number: 
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(Continued) Signatures (obtained electronically) 
 
Meaning of Signature  
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Date Signed 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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