Relative Bioavailability of BI 1810631 as Two Different Oral Formulations Given as Single Doses and Investigation of the Effects of Food and Multiple-dose Rabeprazole on the Pharmacokinetics of Single-dose BI 1810631 Following Oral Administration in Healthy Male Subjects (an Open-label, Randomised, Four-way Crossover Trial)
Phase: PHASE1
Conditions: Healthy
Sponsor: Boehringer Ingelheim



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each treatment
Diagnosis
Not applicable
Main inclusion criteria
Healthy male subjects, age of 18 to 45 years (inclusive), body mass index (BMI) of 
18.5 to 29.9 kg/m2 (inclusive)
Test product 1
BI 1810631 
 (trial formulation 1, TF1), strengths 
dose
mode of admin.
Oral with 240 mL of water 
Test product 2
BI 1810631 
 (new formulation, NF), strength 
dose
mode of admin.
Oral with 240 mL of water 
 
Test product 3
PARIET® (rabeprazole) gastroresistant tablet, strength 20 mg
dose
40 mg (2 tablets à 20 mg)
mode of admin.
Oral with 240 mL of water
Duration of treatment
TF1 fasted (Reference, R): BI 1810631
single dose 
 
 on Day 1, fasted
NF fasted (Test 1, T1): BI 1810631
 single dose 
 on Day 1, 
fasted
NF fed (Test 2, T2): BI 1810631
 single dose 
 on Day 1, 
fed
NF fasted + rabeprazole (Test 3, T3): 
-
BI 1810631 
 single dose on Day 1 
, fasted
-
rabeprazole 40 mg once daily (2 tablets à 20 mg) on Days -4 to 1

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Statistical methods
Comparisons of interest: 
NF fasted (Test 1, T1) vs. TF1 fasted (Reference, R)
NF fed (Test 2, T2) vs. NF fasted (Test 1, T1)
NF fasted + rabeprazole (Test 3, T3) vs. NF fasted (Test 1, T1)
Relative bioavailability will be estimated by the ratios of the geometric means
(T1/R, T2/T1 and T3/T1) 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-test procedure, each at a 5% significance level. 
Since the main focus is on estimation and not testing, a formal hypothesis test and 
associated acceptance range is not specified. The statistical model will be an 
analysis of variance (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.
Descriptive statistics will be calculated for all endpoints.

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FLOW CHART FOR “TF1 FASTED”, “NF FASTED”, AND “NF FED”
Period
Visit
Day
Planned time (relative 
to BI 1810631 adminis-
tration) [h:min]
Approximate clock time 
of actual day [h:min]
Event and comment
Safety laboratory
PK (BI 1810631, blood)
12-lead ECG
Vital signs (BP, PR)
Questioning for AEs 
and concomitant 
therapy 5
SCR
1
-28 to -5
Screening (SCR)1
A
x
x
1/2/3/4 (wash-out of at least 
 between BI 1810631 
administrations in subsequent periods)
2/
3/
4/
5
-5
-122:00
07:00
Ambulatory visit6
B6
x6
-4
-98:00
07:00
Ambulatory visit, treatment allocation6
B7,8
x
-1
-13:00
20:00
Admission to trial site
x
1
-2:00
07:00
x2
x2
x2
x2
-0:30
08:30
0:00
09:00
Admin.: 
 BI 181063110
0:30
09:30
x
1:00
10:00
x
1:30
10:30
x
2:00
11:00
240 mL fluid intake
x
x
x
x
3:00
12:00
x
4:00
13:00
240 mL fluid intake, 
x
x
x
x
6:00
15:00
x
7:00
16:00
8:00
17:00
x
10:00
19:00
x
12:00
21:00
x
x 
2
24:00
09:00
Breakfast (voluntary)3,
discharge from trial site
B
x
x
x
x
34:00
19:00
Ambulatory visit
x
x
3
46:00
07:00
Ambulatory visit
x
x
4
70:00
07:00
Ambulatory visit
x
x
5
94:00
07:00
Ambulatory visit
x
x
6
118:00
07:00
Ambulatory visit
x
x
FU
6
15 to 22
End of study (EoS) examination4
B
x
x
x
1.
Subject must be informed and written informed consent obtained prior to starting any screening procedures. Screening 
procedures include physical examination, check of vital signs, ECG, safety laboratory (including drug screening), 
demographics (including determination of body height and weight, smoking status and alcohol history), relevant 
medical history, concomitant therapy and review of inclusion/exclusion criteria. Pharmacogenetic samples will be 
collected if needed.
2.
The procedure is to be performed and completed within the 3 h prior to BI 1810631 administration.
3.
If several actions are indicated at the same time, the intake of meals will be the last action.
4.
Including physical examination, vital signs, ECG, safety laboratory, recording of AEs and concomitant therapies.
5.
AEs and concomitant therapies will be recorded throughout the trial, but will be specifically asked for at the times
indicated in the Flow Chart above.
6.
Only in period 1. Safety laboratory on Day -5 (including AE&CT questioning on Day -5) can be omitted if the 
screening examination is performed on Day -5. Procedures on Day -5 can be performed anytime on Day -5.
7.
Safety laboratory B only in periods 2, 3, and 4.
8.
Including urine drug screening and alcohol breath test in all four periods
9.
Only in treatment “NF fed”
10. Formulation TF1 in treatment “TF1 fasted” and formulation NF in treatments “NF fasted” and “NF fed”

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FLOW CHART FOR “NF FASTED + RABEPRAZOLE”
Period
Visit
Day
Planned time (relative to 
BI 1810631 
administration) [h:min]
Approximate clock time  
of actual day [h:min]
Event and comment
Safety laboratory
PK (BI 1810631, blood)
PK (rabeprazole, blood)
12-lead ECG
Vital signs (BP, PR)
Questioning for AEs and 
concomitant therapy 5
SCR
1
-28 to -5
Screening (SCR)1
A
x
x
1/2/3/4 (wash-out of at least 
 between BI 1810631 administrations in 
subsequent periods)
2
/
3
/
4
/
5
-5
-122:00
07:00
Ambulatory visit6
B6
x6
-4
-98:00
07:00
Ambulatory visit, treatment allocation6
Admin.: rabeprazole 40 mg
B7,8,9
x9
-3
-74:00
07:00
Ambulatory visit, 
Admin.: rabeprazole 40 mg
x9
-2
-50:00
07:00
Ambulatory visit, 
Admin.: rabeprazole 40 mg
x9
-1
-26:00
07:00
Ambulatory visit, 
Admin.: rabeprazole 40 mg
x9
-13:00
20:00
Admission to trial site
x
1
-2:00
07:00
Admin.: rabeprazole 40 mg
x2
x9
x2
x2
x2
0:00
09:00
Admin.: 
 BI 1810631 NF
x10
0:30
09:30
x
1:00
10:00
x
1:30
10:30
x
x
2:00
11:00
240 mL fluid intake
x
x
x
x
x
3:00
12:00
x
4:00
13:00
240 mL fluid intake, 
x
x
x
x
6:00
15:00
x
7:00
16:00
8:00
17:00
x
10:00
19:00
x
12:00
21:00
x
x 
2
24:00
09:00
Breakfast (voluntary)3,
discharge from trial site
B
x
x
x
x
34:00
19:00
Ambulatory visit
x
x
3
46:00
07:00
Ambulatory visit
x
x
4
70:00
07:00
Ambulatory visit
x
x
5
94:00
07:00
Ambulatory visit
x
x
6
118:00
07:00
Ambulatory visit
x
x
FU
6
15 to 22
End of study (EoS) examination4
B
x
x
x
1.
Subject must be informed and written informed consent obtained prior to starting any screening procedures. Screening 
procedures include physical examination, check of vital signs, ECG, safety laboratory (including drug screening), 
demographics (including determination of body height and weight, smoking status and alcohol history), relevant 
medical history, concomitant therapy and review of inclusion/exclusion criteria. Pharmacogenetic samples will be 
collected if needed.
2.
The procedure is to be performed and completed within the 3 h prior to BI 1810631 administration.
3.
If several actions are indicated at the same time, the intake of meals will be the last action.
4.
Including physical examination, vital signs, ECG, safety laboratory, recording of AEs and concomitant therapies. 
5.
AEs and concomitant therapies will be recorded throughout the trial, but will be specifically asked for at the times
indicated in the Flow Chart above.
6.
Only in period 1. Safety laboratory on Day -5 (including AE&CT questioning on Day -5) can be omitted if the 
screening examination is performed on Day -5. Procedures on Day -5 can be performed anytime on Day -5.
7.
Safety laboratory B only in periods 2, 3, and 4.
8.
Including urine drug screening and alcohol breath test in all four periods
9.
Taken within 2 hours before rabeprazole dosing.
10. Within 10 minutes before the planned intake of BI 1810631. BI 1810631 intake should be on time.

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TABLE OF CONTENTS
TITLE PAGE ......................................................................................................1
CLINICAL TRIAL PROTOCOL SYNOPSIS ................................................2
FLOW CHART FOR “TF1 FASTED”, “NF FASTED”, AND “NF 
FED”.............................................................................................................5
FLOW CHART FOR “NF FASTED + RABEPRAZOLE” ...........................6
TABLE OF CONTENTS ...................................................................................7
ABBREVIATIONS.......................................................................................... 11
1.
INTRODUCTION.................................................................................... 14
1.1
MEDICAL BACKGROUND............................................................................14
1.2
DRUG PROFILE...............................................................................................14
1.2.1
BI 1810631 .............................................................................................14
1.2.2
Rabeprazole...........................................................................................17
1.2.3
Residual Effect Period..........................................................................19
1.3
RATIONALE FOR PERFORMING THE TRIAL........................................19
1.4
BENEFIT - RISK ASSESSMENT ...................................................................19
1.4.1
Expected benefit for the target population.........................................19
1.4.2
Procedure-related risks ........................................................................20
1.4.3
Drug-related risks and safety measures - BI 1810631.......................20
1.4.4
Drug-related risks and safety measures – rabeprazole .....................23
1.4.5
Risks related to the drug-drug interaction between BI 1810631 
and rabeprazole.....................................................................................23
1.4.6
Risk assessment in the context of SARS-CoV-2 pandemic ...............24
1.4.7
Overall benefit-risk assessment ...........................................................24
2.
TRIAL OBJECTIVES AND ENDPOINTS........................................... 25
2.1
MAIN OBJECTIVES, PRIMARY AND SECONDARY ENDPOINTS ......25
2.1.1
Main objectives......................................................................................25
2.1.2
Primary endpoints ................................................................................25
2.1.3
Secondary endpoint ..............................................................................25
2.2.2.2
Safety and tolerability..............................................................26
3.
DESCRIPTION OF DESIGN AND TRIAL POPULATION.............. 27
3.1
OVERALL TRIAL DESIGN AND PLAN ......................................................27
3.2
DISCUSSION OF TRIAL DESIGN, INCLUDING THE CHOICE OF 
CONTROL GROUPS........................................................................................27
3.3
SELECTION OF TRIAL POPULATION ......................................................28

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3.3.1
Main diagnosis for trial entry..............................................................28
3.3.2
Inclusion criteria...................................................................................28
3.3.3
Exclusion criteria ..................................................................................28
3.3.4
Withdrawal of subjects from treatment or assessments ...................30
3.3.4.1
Withdrawal from trial treatment ..............................................30
3.3.4.2
Withdrawal of consent to trial participation ............................31
3.3.4.3
Discontinuation of the trial by the sponsor..............................31
3.3.5
Replacement of subjects .......................................................................31
4.
TREATMENTS........................................................................................ 32
4.1
INVESTIGATIONAL TREATMENTS ..........................................................32
4.1.1
Identity of the Investigational Medicinal Products ...........................32
4.1.2
Selection of doses in the trial................................................................33
4.1.3
Method of assigning subjects to treatment groups ............................33
4.1.4
Drug assignment and administration of doses for each subject .......34
4.1.5
Blinding and procedures for unblinding ............................................35
4.1.6
Packaging, labelling, and re-supply ....................................................36
4.1.7
Storage conditions.................................................................................36
4.1.8
Drug accountability ..............................................................................36
4.2
OTHER TREATMENTS, EMERGENCY  PROCEDURES,
RESTRICTIONS ...............................................................................................37
4.2.1
Other treatments and emergency procedures....................................37
4.2.2
Restrictions............................................................................................38
4.2.2.1
Restrictions regarding concomitant treatment .........................38
4.2.2.2
Restrictions on diet and life style.............................................38
4.2.2.3
Contraception requirements.....................................................39
4.3
TREATMENT COMPLIANCE.......................................................................39
5.
ASSESSMENTS....................................................................................... 40
5.1
ASSESSMENT OF EFFICACY.......................................................................40
5.2
ASSESSMENT OF SAFETY............................................................................40
5.2.1
Physical examination ............................................................................40
5.2.2
Vital signs...............................................................................................40
5.2.3
Safety laboratory parameters..............................................................40
5.2.4
Electrocardiogram................................................................................42
5.2.5
Other safety parameters.......................................................................43
5.2.6
Assessment of adverse events...............................................................43
5.2.6.1
Definitions of adverse events...................................................43

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5.2.6.1.1 Adverse event ............................................................43
5.2.6.1.2 Serious adverse event ................................................43
5.2.6.1.3 AEs considered ‘Always Serious’.............................44
5.2.6.1.4 Adverse events of special interest .............................44
5.2.6.1.5 Intensity (severity) of AEs.........................................45
5.2.6.1.6 Causal relationship of AEs ........................................45
5.2.6.2
Adverse event collection and reporting ...................................46
5.2.6.2.1 AE collection.............................................................46
5.2.6.2.2 AE reporting to the sponsor and timelines ................47
5.2.6.2.3 Information required..................................................47
5.2.6.2.4 Pregnancy ..................................................................47
5.3
DRUG CONCENTRATION MEASUREMENTS AND 
PHARMACOKINETICS..................................................................................48
5.3.1
Assessment of pharmacokinetics .........................................................48
5.3.2
Methods of sample collection...............................................................48
5.3.2.1
Blood sampling for pharmacokinetic analysis.........................48
5.4
ASSESSMENT OF BIOMARKERS................................................................49
5.5
BIOBANKING ...................................................................................................49
5.6
OTHER ASSESSMENTS .................................................................................49
5.6.1
Pharmacogenomic evaluation..............................................................49
5.7
APPROPRIATENESS OF MEASUREMENTS.............................................49
6.
INVESTIGATIONAL PLAN.................................................................. 50
6.1
VISIT SCHEDULE............................................................................................50
6.2
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS ................51
6.2.1
Screening period....................................................................................51
6.2.2
Treatment periods.................................................................................51
6.2.3
Follow-up period and trial completion ...............................................51
7.
STATISTICAL METHODS AND DETERMINATION OF
SAMPLE SIZE......................................................................................... 52
7.1
STATISTICAL DESIGN – MODEL ...............................................................52
7.2
NULL AND ALTERNATIVE HYPOTHESES ..............................................52
7.3
PLANNED ANALYSES....................................................................................52
7.3.1
Primary endpoint analyses...................................................................53
7.3.2
Secondary endpoint analyses ...............................................................55
7.3.4
Safety analyses.......................................................................................55
7.4
INTERIM ANALYSES .....................................................................................56
7.5
HANDLING OF MISSING DATA ..................................................................56
7.5.1
Safety......................................................................................................56

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7.5.2
Pharmacokinetics..................................................................................56
7.6
RANDOMISATION ..........................................................................................56
7.7
DETERMINATION OF SAMPLE SIZE ........................................................57
8.
INFORMED CONSENT, TRIAL RECORDS, DATA 
PROTECTION, PUBLICATION POLICY, AND 
ADMINISTRATIVE STRUCTURE...................................................... 59
8.1
TRIAL APPROVAL, SUBJECT INFORMATION, INFORMED 
CONSENT ..........................................................................................................59
8.2
DATA QUALITY ASSURANCE .....................................................................60
8.3
RECORDS..........................................................................................................60
8.3.1
Source documents .................................................................................60
8.3.2
Direct access to source data and documents.......................................61
8.3.3
Storage period of records.....................................................................62
8.4
EXPEDITED REPORTING OF ADVERSE EVENTS .................................62
8.5
STATEMENT OF CONFIDENTIALITY AND SUBJECT PRIVACY.......62
8.5.1
Collection, storage and future use of biological samples and 
corresponding data ...............................................................................62
8.6
TRIAL MILESTONES .....................................................................................63
8.7
ADMINISTRATIVE STRUCTURE OF THE TRIAL ..................................63
9.
REFERENCES......................................................................................... 65
9.1
PUBLISHED REFERENCES...........................................................................65
9.2
UNPUBLISHED REFERENCES........................................................................67
10. APPENDICES .......................................................................................... 68
11. DESCRIPTION OF GLOBAL AMENDMENT(S).............................. 69
11.1
GLOBAL AMENDMENT 1 .............................................................................69
11.2
GLOBAL AMENDMENT 2 .............................................................................70

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ABBREVIATIONS
ADME
Absorption, distribution, metabolism, and excretion
AE
Adverse event
AESI
Adverse events of special interest
ANOVA
Analysis of variance
AR
Accumulation ratio
AUC0-12
Area under the concentration time curve of the analyte in plasma over the 
time interval from 0 to 12 hours
AUC0-∞
Area under the concentration-time curve of the analyte in plasma over the 
time interval from 0 extrapolated to infinity
%AUCtz-∞
Percentage of AUC0-∞obtained by extrapolation
AUCt1-t2
Area under the concentration-time curve of the analyte in plasma over the 
time interval t1 to t2
AUCτ,ss
Area under the concentration-time curve of the analyte in plasma at 
steady state over a uniform dosing interval τ
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
BI
Boehringer Ingelheim
b.i.d.
Twice daily
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
Cmax,ss
Maximum measured concentration of the analyte in plasma at steady state
CRF
Case Report Form, paper or electronic (sometimes referred to as ‘eCRF’)
CTCAE
Common Terminology Criteria for Adverse Events
CTP
Clinical trial protocol
CTR
Clinical trial report
DBL
Data base lock
DDI
Drug-drug interaction
DILI
Drug induced liver injury
DLT
Dose-limiting toxicity
ECG
Electrocardiogram

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eCRF
Electronic case report form
eDC
Electronic data capture
EGFR
Epidermal growth factor receptor
EoS
End of study
EudraCT
European Clinical Trials Database
FDA
U.S. Food & Drug Administration
FU
Follow-up
GCP
Good Clinical Practice
gCV
Geometric coefficient of variation
gMean
Geometric mean
HER2
Human epidermal growth factor receptor 2
IB
Investigator’s brochure
IEC
Independent Ethics Committee
IRB
Institutional Review Board
ISF
Investigator site file
LC-MS/MS
Liquid chromatography with tandem mass spectrometry
MDA
Methylenedioxyamphetamine
MDMA
Methylenedioxymethamphetamine
MedDRA
Medical Dictionary for Regulatory Activities
MRT,ex
Mean residence time of the analyte in the body, extravascular
NF
New formulation
NSCLC
Non-small-cell lung cancer
PK
Pharmacokinetic(s)
PKS
Pharmacokinetic set
PPI
Proton pump inhibitor
PR
Pulse rate
q.d.
Once daily
QT
Time between start of the Q-wave and the end of the T-wave in an 
electrocardiogram
QTc
QT interval corrected for heart rate using the method of Fridericia (QTcF) 
or Bazett (QTcB)
R
Reference treatment
REP
Residual effect period
SAE
Serious adverse event
SCR
Screening
SmPC
Summary of Product Characteristics

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SOP
Standard operating procedure
ss
(at) steady state
T
Test product or treatment
TF1
Trial formulation 1
t1/2
Terminal half-life of the analyte in plasma
tmax
Time from (last) dosing to the maximum measured concentration of the 
analyte in plasma
TS
Treated set
tz
Time of last measurable concentration of the analyte in plasma
TSAP
Trial statistical analysis plan
ULN
Upper limit of normal
Vz/F
Apparent volume of distribution during the terminal phase after 
extravascular administration
XTC
Ecstasy 

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1.2.2
Rabeprazole
Rabeprazole is a proton pump inhibitor (PPI) indicated for treatment of diseases that profit of 
an increased gastric pH such as ulcus ventriculi, ulcus duodeni, reflux esophagitis or 

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Risk mitigation:
!
Subjects 
 and will be asked at pre-defined time 
points for AEs (see Flow Chart) and will be instructed to report AEs spontaneously
!
Subjects will be asked at pre-defined time points for AEs (see Flow Chart) and will be 
instructed to report AEs spontaneously

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2.
TRIAL OBJECTIVES AND ENDPOINTS
2.1
MAIN OBJECTIVES, PRIMARY AND SECONDARY ENDPOINTS
2.1.1
Main objectives
The main objectives of this trial are to investigate
!
the relative bioavailability of two different BI 1810631 
 formulations (trial 
formulation 1, TF1, Reference, R; and new formulation, NF, Test 1, T1) under fasting
conditions
!
the relative bioavailability of BI 1810631 NF under fasting (T1) and fed (T2) 
conditions
!
the relative bioavailability of BI 1810631 NF given alone (T1) and together with the 
proton pump inhibitor rabeprazole (T3) under fasting conditions
2.1.2
Primary endpoints
The following pharmacokinetic parameters will be determined for BI 1810631:
!
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)
2.1.3
Secondary endpoint
The following pharmacokinetic parameter will be determined for BI 1810631:
!
AUC0-∞(area under the concentration-time curve of the analyte in plasma over the 
time interval from 0 extrapolated to infinity)

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2.2.2.2
Safety and tolerability
Safety and tolerability of BI 1810631 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)

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3.3
SELECTION OF TRIAL POPULATION
It is planned that 
healthy male subjects will enter the study. They will be recruited from 
the volunteers' pool of the trial site.
Only male subjects are included in the study 
 
.
A log of all subjects enrolled into the trial (i.e. who have signed informed consent) will be 
maintained in the ISF, irrespective of whether they have been treated with investigational 
drug or not.
3.3.1
Main diagnosis for trial entry
The study will be performed in healthy subjects.
Please refer to Section 8.3.1 (Source Documents) for the documentation requirements 
pertaining to the in- and exclusion criteria.
3.3.2
Inclusion criteria
Subjects will only be included in the trial if they meet the following criteria:
1. Healthy male subjects according to the assessment of the investigator, as based on a 
complete medical history including a physical examination, vital signs (BP, PR), 12-lead 
ECG, and clinical laboratory tests 
2. Age of 18 to 45 years (inclusive) 
3. BMI of 18.5 to 29.9 kg/m2 (inclusive) 
4. Signed and dated written informed consent in accordance with ICH-GCP and local 
legislation prior to admission to the trial
3.3.3
Exclusion criteria
Subjects will not be allowed to participate, if any of the following general criteria apply:
1. Any finding in the medical examination (including BP, PR or ECG) deviating from 
normal and assessed as clinically relevant by the investigator
2. Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, 
diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the 
range of 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 assessed as clinically relevant by the investigator
5. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or 
hormonal disorders
6. Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the 
pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)

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7. Diseases of the central nervous system (including but not limited to any kind of seizures 
or stroke), and other relevant neurological or psychiatric disorders 
8. History of relevant orthostatic hypotension, fainting spells, or blackouts
9. Relevant chronic or acute infections
10. Any documented active or suspected malignancy or history of malignancy
11. History of relevant allergy or hypersensitivity (including allergy to the trial medication or 
its excipients) 
12. Use of drugs within 30 days of planned administration of trial medication that might 
reasonably influence the results of the trial (including drugs that cause QT/QTc interval
prolongation)
13. Intake of an investigational drug in another clinical trial within 60 days of planned  
administration of investigational drug in the current trial, or concurrent participation in 
another clinical trial in which investigational drug is administered
14. Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
15. Inability to refrain from smoking on specified trial days
16. Alcohol abuse (consumption of more than 24 g per day)
17. Drug abuse or positive drug screening
18. Blood donation of more than 100 mL within 30 days of planned administration of trial 
medication or intended blood donation during the trial
19. Intention to perform excessive physical activities within one week prior to the 
administration of trial medication or during the trial
20. Inability to comply with the dietary regimen of the trial site
21. A marked prolongation of QT/QTc interval (such as QTc intervals that are repeatedly 
greater than 450 ms) or any other relevant ECG finding at screening
22. A history of additional risk factors for Torsade de Pointes (such as heart failure, 
hypokalaemia, or family history of Long QT Syndrome)
23. Subject is assessed as unsuitable for inclusion by the investigator, for instance, because 
the subject is not considered able to understand and comply with study requirements, or 
has a condition that would not allow safe participation in the study 
24. During COVID-19 pandemic: Laboratory test indicative of an ongoing SARS-CoV-2 
infection
25. Male subjects with WOCBP partner who are unwilling to use highly effective 
contraception from time point of first administration of BI 1810631 until 30 days after the 
last administration of BI 1810631. Highly effective methods of contraception are:
- Subject is sexually abstinent
- Subject is vasectomized (with appropriate post-vasectomy documentation of the absence 
of sperm in the ejaculate) and uses condom
- Use of intrauterine device or intrauterine hormone-releasing system by female partner 
plus use of condom
- Use of progestogen-only hormonal contraception by female partner that inhibits 
ovulation (injectables or implants) plus use of condom
- Use of combined (estrogen and progestogen containing) hormonal contraception by 

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female partner that prevents ovulation (oral, intravaginal or transdermal) plus use of 
condom
- Bilateral tubal occlusion in the female partner plus use of condom
Sperm donation is not allowed from the time point of first administration of BI 1810631
until 30 days after the last administration of BI 1810631
For study restrictions, refer to Section 4.2.2.
3.3.4
Withdrawal of subjects from treatment or assessments
Subjects may withdraw or may be removed from trial treatment or may withdraw consent to 
trial participation as a whole (‘withdrawal of consent’) with very different implications; 
please see sections 3.3.4.1 and 3.3.4.2 below.
If a subject is removed from or withdraws from the trial prior to the first administration of 
trial medication, the data of this subject will not be entered in the case report form (CRF) and 
will not be reported in the clinical trial report (CTR). 
If a subject is removed from or withdraws from the trial after the first administration of trial 
medication, this will be documented and the reason for discontinuation must be recorded in 
the CRF; in addition, trial data will be included in the CRF and will be reported in the CTR. 
Following removal or withdrawal, a complete end-of-trial examination should be performed. 
If the discontinuation or withdrawal occurs before the end of the REP (see Section 1.2.3), the
discontinued subject should, if possible, be questioned for AEs and concomitant therapies at 
or after the end of the REP in order to ensure collection of AEs and concomitant therapies 
throughout the REP, if not contrary to any consent withdrawal of the subject.
3.3.4.1
Withdrawal from trial treatment
An individual subject will discontinue trial treatment if:
1. The subject wants to withdraw from trial treatment. The subject will be asked to explain 
the reasons but has the right to refuse to answer
2. The subject has repeatedly shown to be non-compliant with important trial procedures 
and, in the opinion of both, the investigator and sponsor representative, the safety of the 
subject cannot be guaranteed as he is not willing or able to adhere to the trial 
requirements in the future.
3. The subject needs to take concomitant medication that interferes with the investigational 
medicinal product or other trial treatment
4. The subject can no longer receive trial treatment for medical reasons (such as surgery, 
adverse events [AEs], or diseases)
5. The subject has an elevation of AST and/or ALT ≥3-fold ULN and an elevation of total 
bilirubin ≥2-fold ULN (measured in the same blood sample) and/or needs to be followed 
up according to the DILI checklist provided in the ISF
In addition to these criteria, the investigator may discontinue subjects at any time based on 
his or her clinical judgment.

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If new efficacy or safety information becomes available, Boehringer Ingelheim will review 
the benefit-risk-assessment and, if needed, pause or discontinue the trial treatment for all 
subjects or take any other appropriate action to guarantee the safety of the trial subjects.
3.3.4.2
Withdrawal of consent to trial participation
Subjects may withdraw their consent to trial participation at any time without the need to 
justify the decision. If a subject wants to withdraw consent, the investigator should be 
involved in the discussion with the subject and explain the difference between trial treatment 
discontinuation and withdrawal of consent to trial participation, as well as explain the options 
for continued follow up after trial treatment discontinuation, please see section 3.3.4.1 above
3.3.4.3
Discontinuation of the trial by the sponsor
Boehringer Ingelheim reserves the right to discontinue the trial at any time for any of the 
following reasons (if reasons 4 and/or 5 are met, the trial should be discontinued 
immediately):
1. Failure to meet expected enrolment goals overall or at a particular trial site.
2. The sponsor decides to discontinue the further development of the investigational 
products
3. Deviation from GCP, or the CTP, impairing the appropriate conduct of the trial
4. New toxicological findings, serious adverse events, or any safety information invalidating
the earlier positive benefit-risk-assessment (see Section 3.3.4.1).
5. More than 50% of the subjects show drug-related and clinically relevant adverse events of 
CTCAE grade 2 or grade 3 severity (except for grade 2 headache), or if at least 1 drug-
related serious adverse event is reported.
Headaches occur frequently in Phase I studies in healthy volunteers, even after placebo 
treatment [R22-0652]. Relationship of headache to study treatment may be difficult to assess 
and, if in doubt, may be attributed to study drug. The current study includes four treatment 
periods 
, thus the 
cumulative number of incidental headaches may be high. Moreover, headaches are frequently 
observed during rabeprazole treatment [R21-4490], and the dose of rabeprazole is high (see 
Section 4.1.2). Therefore, grade 2 headaches are excepted from the count for trial 
discontinuation criterion 5 to avoid unnecessary discontinuation. 
3.3.5
Replacement of subjects
In case more than 4 subjects do not complete the trial (including subjects non-evaluable for 
PK), subjects may be replaced if considered necessary to reach the objectives of the trial. 
Subjects who withdraw or are withdrawn from treatment or assessments because of a drug-
related adverse event will not be replaced. The Clinical Trial Leader together with the Trial 
Pharmacokineticist and the Trial Statistician are to decide, if and how many subjects will be 
replaced. The total number of replacements may not exceed 1/3 of the total number of 
evaluable subjects anticipated to complete the trial. A replacement subject will be assigned a 

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4.1.6
Packaging, labelling, and re-supply
The investigational medicinal products will be provided by BI. They will be packaged and 
labelled in accordance with the principles of Good Manufacturing Practice (GMP). 
For details of packing and the description of the label, refer to the ISF.
The name, address and telephone number of the trial site are provided in the subject 
information form. The EudraCT number is indicated on the title page of this protocol as well 
as on the subject information and informed consent forms.
Packaging and labelling of BI 1810631 will be performed in such a way that the required 
reserve samples as per FDA requirements 21CFR320 are available for storage by the 
investigational site and that the trial drugs can be chosen in a random way by the Investigator.
Rabeprazole will be obtained by the trial site from a public pharmacy. The drug will be 
dispensed out of the original, unmodified packages.
No re-supply is planned.
4.1.7
Storage conditions
Drug supplies will be kept in their original packaging and in a secure limited access storage 
area in accordance with the recommended (labelled) storage conditions. If necessary, a 
temperature log must be maintained to make certain that the drug supplies are stored at the 
correct temperature. If the storage conditions are found to be outside the specified range, the 
Clinical Research Associate (as provided in the list of contacts) is to be contacted
immediately.
4.1.8
Drug accountability
The investigator or designee will receive the investigational drugs that are delivered from the 
sponsor (BI 1810631) when the following requirements are fulfilled:
!
Approval of the clinical trial protocol by the IRB / ethics committee
!
Approval/notification of the regulatory authority, e.g. competent authority
!
Availability of the curriculum vitae of the Principal Investigator
!
Availability of a signed and dated clinical trial protocol  
Pariet® (rabeprazole) may be purchased at any time by the investigational site.
Only authorised personnel documented in the form 'Trial Staff List' may dispense 
investigational drugs to trial subjects. Investigational drugs are not allowed to be used outside 
of this protocol.
The investigator or designee must maintain records of the product’s delivery to the trial site, 
the inventory at the site, the use by each subject, and the disposal of unused products.These 
records will include dates, quantities, batch / serial numbers, expiry ('use-by') dates, and the 
unique code numbers assigned to the investigational medicinal product and trial subjects. The 

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investigator or designee will maintain records that document adequately that the subjects 
were provided the doses specified by the CTP and reconcile all investigational medicinal 
products received from the sponsor. At the time of disposal of remaining trial medication, the 
investigator or designee must verify that no remaining supplies are in the investigator’s 
possession.
All unused medication will be disposed of locally by the trial site upon written authorisation 
of the Clinical Trial Leader. Receipt, usage and disposal of trial medication must be 
documented on the appropriate forms. Account must be given for any discrepancies.
4.2
OTHER TREATMENTS, EMERGENCY  PROCEDURES,
RESTRICTIONS
4.2.1
Other treatments and emergency procedures
There are no special emergency procedures to be followed. No additional treatment is 
planned. However, if adverse events require treatment, the investigator can authorise 
symptomatic therapy. In those cases, subjects will be treated as necessary and, if required, 
kept under supervision at the trial site or transferred to a hospital until all results of medical 
evaluations are acceptable.

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5.
ASSESSMENTS
5.1
ASSESSMENT OF EFFICACY
Not applicable.
5.2
ASSESSMENT OF SAFETY
5.2.1
Physical examination
At screening, the medical examination will include demographics, height and body weight,
smoking and alcohol history (alcohol history not mandatory to be entered into CRF or to be 
reported), relevant medical history and concomitant therapy, review of inclusion and 
exclusion criteria, review of vital signs (BP, PR), 12-lead ECG, laboratory tests, and a 
physical examination. At the end of trial examination, it will include review of vital signs, 12-
lead ECG, laboratory tests, and a physical examination.
5.2.2
Vital signs
Systolic and diastolic blood pressures (BP) as well as pulse rate (PR) or heart rate (heart rate 
is considered to be equal to pulse rate) will be measured by a blood pressure monitor 
(Dinamap Pro 100,
at the times indicated in the 
Flow Chart, after subjects have rested for at least 5 min in a supine position. All recordings 
should be made using the same type of blood pressure recording instrument on the same arm, 
if possible.
5.2.3
Safety laboratory parameters
For the assessment of laboratory parameters, blood and urine samples will be collected by the 
trial site at the times indicated in the Flow Chart after the subjects have fasted for at least 
10 h. For retests, at the discretion of the investigator or designee, overnight fasting is not 
required.
The parameters to be assessed are listed in Tables 5.2.3: 1 and 5.2.3: 2. Reference ranges will 
be provided in the ISF. 
Manual differential white blood cell count or urine sediment examinations will only be 
performed if there is an abnormality in the automatic blood cell count or in the urinalysis, 
respectively.
Deviations of laboratory results from normal range will be assessed for clinical relevance by 
a physician, and clinically relevant deviations will be reported as baseline conditions / as 
parts of baseline conditions or as adverse events / as parts of adverse events, as applicable.

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Table 5.2.3: 1
Routine laboratory tests
Functional lab group
BI test name [comment/abbreviation]
A
B
Haematology
Haematocrit
Haemoglobin
Red Blood Cell Count/Erythrocytes 
White Blood Cells/Leukocytes
Platelet Count/Thrombocytes (quant)
X
X
X
X
X
X
X
X
X
X
Automatic WBC 
differential, relative
Neutrophils/Leukocytes; Eosinophils/Leukocytes; Basophils/ 
Leukocytes; Monocytes/Leukocytes; Lymphocytes/Leukocytes 
X
X
Automatic WBC 
differential, absolute 
Neutrophil, absol.; Eosinophils, absol.; Basophils, absol.; Monocytes, 
absol.; Lymphocytes, absol.
X
X
Manual differential 
WBC (if automatic
differential WBC is 
abnormal)
Neut. Poly (segs); Neut. Poly (segs), absol.; Neutrophils Bands;  
Neutrophils Bands, absol.; Eosinophils/Leukocytes; Eosinophils, 
absol.; Basophils/ Leukocytes; Basophils, absol.; Monocytes/ 
Leukocytes; Monocytes, absol.; Lymphocytes/Leukocytes; 
Lymphocytes, absol.
Coagulation
Activated Partial Thromboplastin Time 
Prothrombin time
Prothrombin time – INR (International Normalization Ratio)
X
X
X
X
X
X
Enzymes
AST [Aspartate transaminase] /GOT, SGOT 
ALT [Alanine transaminase] /GPT, SGPT
Alkaline Phosphatase
Gamma-Glutamyl Transferase 
Creatine Kinase [CK]
Creatine Kinase Isoenzyme MB [only if CK is elevated] 
Lactic Dehydrogenase
Lipase
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Hormones
Thyroid Stimulating Hormone 
X
--
Substrates
Glucose (Plasma)
Creatinine 
Bilirubin, Total 
Bilirubin, Direct
Protein, Total
C-Reactive Protein (Quant)  
Cholesterol, total 
X
X
X
X
X
X
X
X
X
X
X
--
X
X
Electrolytes
Sodium
Potassium
Calcium
Phosphate (as Phosphorus, Inorganic)
X
X
X
X
X
X
X
X
Urinalysis1 (Stix)
Urine Nitrite (qual)
Urine Protein (qual)
Urine Glucose (qual)
Urine Ketone (qual)
Urobilinogen (qual)
Urine Bilirubin (qual)
Urine RBC/Erythrocytes (qual)
Urine WBC/Leukocytes (qual)
Urine pH
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine sediment1
Only positive findings will be reported2
1 microscopic examination if erythrocytes, leukocytes, nitrite or protein are abnormal in urine
2 e.g., the presence of sediment bacteria, casts in sediment, squamous epithelial cells, erythrocytes, leukocytes
A: Safety laboratory at screening. B: Safety laboratory during the study and at end-of-trial visit

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The tests listed in Table 5.2.3: 2 are exclusionary laboratory tests that may be repeated as 
required. The results will not be entered in the CRF/database and will not be reported in the 
CTR. Except for drug screening, it is planned to perform these tests during screening only. 
Drug screening will be performed at screening and 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
 
) 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.
The laboratory tests listed in Tables 5.2.3: 1 and 5.2.3: 2 will be performed at 
 
, with the exception of 
drug screening tests. These tests will be performed at the trial site using 
urine 
drug test, or comparable test systems. In case of drug screening confirmation test, testing may 
be done at 
(address see above).
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 
computerised electrocardiograph 
 
, 
) at the times provided in the Flow Chart. 
To achieve a stable heart rate at rest and to assure high quality recordings, the site personnel 
will be instructed to assure a relaxed and quiet environment, so that all subjects are at 
complete rest.
All ECGs will be recorded for a 10 sec duration after subjects have rested for at least 5 min in 
a supine position. ECG assessment will always precede all other study procedures scheduled 
for the same time to avoid compromising ECG quality. 

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All ECGs will be stored electronically on the 
 (
 
). 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. Abnormal 
findings will be reported as AEs (during the trial) or baseline conditions (if identified at the
screening visit) if assessed to be clinically relevant by the investigator. Any ECG 
abnormalities will be carefully monitored and, if necessary, the subject will be removed from 
the trial and will receive the appropriate medical treatment. 
ECGs may be repeated for quality reasons (for instance, due to alternating current artefacts, 
muscle movements, or electrode dislocation) and the repeated ECG will be used for analysis. 
Additional (unscheduled) ECGs may be collected by the investigator for safety reasons. 
5.2.5
Other safety parameters
Not applicable.
5.2.6
Assessment of adverse events
5.2.6.1
Definitions of adverse events
5.2.6.1.1
Adverse event
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered a medicinal product and which does not necessarily have 
to have a causal relationship with this treatment.
An AE can therefore be any unfavourable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
product, whether considered related or not.
The following should also be recorded as an AE in the CRF and BI SAE form (if applicable):
!
Worsening of the underlying disease or of other pre-existing conditions 
!
Changes in vital signs, ECG, physical examination, and laboratory test results, if they 
are judged clinically relevant by the investigator
If such abnormalities already pre-exist prior to trial inclusion, they will be considered as 
baseline conditions and should be collected in the eCRF only.
5.2.6.1.2
Serious adverse event
A serious adverse event (SAE) is defined as any AE which fulfils at least one of the 
following criteria:
!
Results in death 
!
Is life-threatening, which refers to an event in which the patient was at risk of death 
at the time of the event; it does not refer to an event that hypothetically might have 
caused death if more severe 

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!
Requires inpatient hospitalisation or prolongation of existing hospitalisation  
!
Results in persistent or significant disability or incapacity 
!
Is a congenital anomaly/birth defect 
!
Is deemed serious for any other reason if it is an important medical event when based 
upon appropriate medical judgment which may jeopardise the patient and may 
require medical or surgical intervention to prevent one of the other outcomes listed in 
the above definitions. Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalisation or development of dependency or 
abuse
5.2.6.1.3
AEs considered ‘Always Serious’
In accordance with the European Medicines Agency initiative on Important Medical Events, 
Boehringer Ingelheim has set up a list of 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 
defined above.
The latest list of ‘Always Serious AEs’ can be found in the eDC system, an electronic data 
capture system which allows the entry of trial data at the trial site. A copy of the latest list of 
‘Always Serious AEs’ will be provided upon request. These events should always be reported 
as SAEs as described in Section 5.2.6.2.
Cancers of new histology must be classified as a serious event regardless of the time since 
discontinuation of the trial medication and must be reported as described in 5.2.6.2, 
subsections ‘AE Collection’ and ‘AE reporting to sponsor and timelines’.
5.2.6.1.4
Adverse events of special interest
The term adverse events of special interest (AESI) relates to any specific AE that has been 
identified at the project level as being of particular concern for prospective safety monitoring 
and safety assessment within this trial, e.g. the potential for AEs based on knowledge from 
other compounds in the same class. AESIs need to be reported to the sponsor’s 
Pharmacovigilance Department within the same timeframe that applies to SAEs, please see 
section 5.2.6.2.2.
The following are considered as AESIs:
!
Potential severe DILI
A potential severe Drug Induced Liver Injury (DILI) that requires follow-up is 
defined by the following alterations of hepatic laboratory parameters: 
o
An elevation of AST (aspartate transaminase) and/or ALT (alanine 
transaminase) ≥3-fold ULN combined with an elevation of total bilirubin 
≥2-fold ULN measured in the same blood sample, or in samples drawn within 
30 days of each other, or
o
Aminotransferase (ALT, and/or AST) elevations ≥10 fold ULN
These lab findings constitute a hepatic injury alert and the subjects showing these lab 
abnormalities need to be followed up according to the ‘DILI checklist’ provided in the 

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ISF or via eDC as applicable. In case of clinical symptoms of hepatic injury (icterus, 
unexplained encephalopathy, unexplained coagulopathy, right upper quadrant 
abdominal pain, etc.) without lab results (ALT, AST, total bilirubin) available, the 
Investigator should make sure that these parameters are analysed, if necessary in an 
unscheduled blood test. Should the results meet the criteria of hepatic injury alert, the 
procedures described in the DILI checklist should be followed.
5.2.6.1.5
Intensity (severity) of AEs
The intensity (severity) of AEs should be classified and recorded in the CRF according to the 
Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 [R18-1357].
5.2.6.1.6
Causal relationship of AEs
Medical judgment should be used to determine whether there is a reasonable possibility of a 
causal relationship between the AE and the given trial treatment, considering all relevant 
factors, including pattern of reaction, temporal relationship, de-challenge or re-challenge, 
confounding factors such as concomitant medication, concomitant diseases and relevant 
history.
Arguments that may suggest that there is a reasonable possibility of a causal relationship 
could be:

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!
The event is consistent with the known pharmacology of the drug 
!
The event is known to be caused by or attributed to the drug class
!
A plausible time to onset of the event relative to the time of drug exposure
!
Evidence that the event is reproducible when the drug is re-introduced
!
No medically sound alternative aetiologies that could explain the event (e.g. pre-
existing or concomitant diseases, or co-medications)
!
The event is typically drug-related and infrequent in the general population not 
exposed to drugs (e.g. Stevens-Johnson syndrome)
!
An indication of dose-response (i.e. greater effect size if the dose is increased, smaller 
effect size if dose is reduced)
Arguments that may suggest that there is no reasonable possibility of a causal relationship 
could be:
!
No plausible time to onset of the event relative to the time of drug exposure is evident 
(e.g. pre-treatment cases, diagnosis of cancer or chronic disease within days / weeks 
of drug administration; an allergic reaction weeks after discontinuation of the drug 
concerned)
!
Continuation of the event despite the withdrawal of the medication, taking into 
account the pharmacological properties of the compound (e.g. after 5 half-lives). Of 
note, this criterion may not be applicable to events whose time course is prolonged 
despite removing the original trigger
!
There is an alternative explanation (e.g. situations where other drugs or underlying 
diseases appear to provide a more likely explanation for the observed event than the 
drug concerned)
!
Disappearance of the event even though the trial drug treatment continues or remains 
unchanged
5.2.6.2
Adverse event collection and reporting
5.2.6.2.1
AE collection
Upon enrolment into a trial, the subject’s baseline condition is assessed (for instance, by 
documentation of medical history/concomitant diagnoses), and relevant changes from 
baseline are noted subsequently. 
Subjects will be required to report spontaneously any AEs. In addition, each subject will be 
regularly assessed by the medical staff throughout the clinical trial and whenever the 
investigator deems necessary. As a minimum, subjects will be questioned for AEs (and 
concomitant therapies) at the time points indicated in the Flow Chart. Assessment will be 
made using non-specific questions such as ‘How do you feel?’. Specific questions will be 
asked wherever necessary in order to more precisely describe an AE.
A carefully written record of all AEs shall be kept by the investigator in charge of the trial. 
Records of AEs shall include data on the time of onset, end time, intensity of the event, and 
any treatment or action required for the event and its outcome.

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The following must be collected and documented on the appropriate CRF(s) by the 
investigator:
!
From signing the informed consent onwards until an individual subject’s end of trial
(the End of Study (EoS) visit): 
o
All AEs (serious and non-serious) and all AESIs 
o
The only exception to this rule are AEs (serious and non-serious) and AESIs 
in Phase I trials in healthy volunteers, when subjects discontinue from the trial 
due to screening failures prior to administration of any trial medication. In 
these cases, the subjects’ data must be collected at trial site but will not be 
entered in the CRF 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 any occurrence of cancer and trial treatment related SAEs
and trial treatment related AESIs of which the investigator may become aware 
of by any means of communication, e.g. phone call. Those AEs should be 
reported on the BI SAE form (see Section 5.2.6.2.2), but not on the CRF.
5.2.6.2.2
AE reporting to the sponsor and timelines
The Investigator must report SAEs, AESIs, and non-serious AEs which are relevant for the 
reported SAE or AESI, on the BI SAE form immediately after becoming aware of the event 
(without undue delay) to the sponsor’s unique entry point (the country specific reporting 
process will be provided in the ISF). The same timeline applies if follow-up information 
becomes available. On specific occasions, the Investigator could inform the sponsor upfront 
via telephone. This does not replace the requirement to complete and send the BI SAE form. 
With receipt of any further information to these events, a follow-up SAE form has to be 
provided. For follow-up information, the same rules and timeline apply as for initial 
information. All (S)AEs, including those persisting after the individual subject’s end of trial, 
must be followed up until they have resolved, have been sufficiently characterized (e.g. as 
‘chronic’ or ‘stable’), or no further information can be obtained.
5.2.6.2.3
Information required
All (S)AEs, including those persisting after the individual subject’s end of trial, must be 
followed up until they have resolved, have been sufficiently assessed as ‘chronic’ or ‘stable’, 
or no further information can be obtained.

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completion of the additional investigations but not later than 5 years after the CTR is 
archived.
5.4
ASSESSMENT OF BIOMARKERS
Not applicable.
5.5
BIOBANKING
Not applicable.
5.6
OTHER ASSESSMENTS
5.6.1
Pharmacogenomic evaluation
Pharmacogenomic investigations explore the role of genetic variation in determining an 
individual’s response to drugs. For this purpose, a sample of at most 10 mL of blood will be 
obtained at the screening examination from each subject whose genotype has not been 
previously determined. Separate informed consent for genotyping will be obtained from each 
volunteer prior to sampling.
DNA will be extracted from the blood sample in order to sequence genes coding for proteins 
that are involved in the absorption, distribution, metabolism, and excretion (ADME) of drugs. 
The gene sequences to be determined include known and likely functional variations of key 
ADME genes and incorporate more than 90% of ADME-related genetic markers identified by 
the PharmaADME group (weblink.pharmaadme.org). It is not intended to include the 
pharmacogenomic data in the CTR. However, the data may be part of the CTR, if necessary.
5.7
APPROPRIATENESS OF MEASUREMENTS
All measurements performed during this trial are standard measurements and will be 
performed in order to monitor subjects’ safety and to determine pharmacokinetic parameters 
in an appropriate way. The scheduled measurements will allow monitoring of changes in vital 
signs, standard laboratory values, and ECG parameters that might occur as a result of 
administration of trial medication. The safety assessments are standard, are accepted for 
evaluation of safety and tolerability of an orally administered drug, and are widely used in 

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clinical trials. The pharmacokinetic parameters and measurements outlined in Section 5.3 are 
generally used assessments of drug exposure. 
6.
INVESTIGATIONAL PLAN
6.1
VISIT SCHEDULE
Exact times of measurements outside the permitted time windows will be documented. The 
acceptable time windows for screening and the end of trial examination are provided in the 
Flow Chart.
In period “NF fasted + rabeprazole”, a time window of +/- 120 min around planned time 
applies to rabeprazole dosings in the mornings of Days -4 to -2. In that period, in the morning 
of Day -1, a time window of +/- 60 min around planned time applies to rabeprazole dosing.
In periods “TF1 fasted”, “NF fasted”, and “NF fed”, a time window of +/- 180 min around 
planned time applies to procedures in the morning of Day -4.
On the evening of Day -1, a time window of +/- 180 min applies to the planned procedures;
in any case admission is to be completed no later than 10 hours prior to BI 1810631
administration on Day 1. 
For time windows before drug administration in the mornings of Days -4 to 1 refer to the 
Flow Chart.
The acceptable deviation from the scheduled time for vital signs, ECG, and laboratory tests 
will be ± 30 min on Day 1 and ± 60 min on Day 2 if not specified otherwise in the Flow 
Chart.
For PK samples and other procedures starting from planned time of 46 hours (inclusive) after 
administration, a time window of +/- 120 minutes applies. 
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 venepuncture are scheduled for the same time, venepuncture should be the last of 
the measurements due to its inconvenience to the subject and possible influence on 
physiological parameters.
For planned blood sampling times, refer to the Flow Chart. While these nominal times should 
be adhered to as closely as possible, the actual sampling times will be recorded and used for 
the determination of pharmacokinetic parameters.
If a subject misses an appointment, it will be rescheduled if possible. The relevance of 
measurements outside the permitted time windows will be assessed no later than at the Report 
Planning Meeting.

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6.2
DETAILS OF TRIAL PROCEDURES AT SELECTED VISITS
6.2.1
Screening period
After having been informed about the trial, all subjects will provide written informed consent 
in accordance with GCP and local legislation prior to enrolment in the study.
For information regarding laboratory tests (including drug and virus screening), ECG, vital 
signs, and physical examination, refer to Sections 5.2.1 to 5.2.4.
Genotyping will be performed in those volunteers whose genotypes have not been previously 
determined (for details, see Section 5.6).
6.2.2
Treatment periods
Each subject is expected to participate in 4 treatment periods (period 1: Day -5 until Day 6; 
periods 2-4: Day -4 until Day 6). 
will separate administrations of 
BI 1810631 in subsequent treatment periods.
Order of treatments is randomized; allocation to treatment sequence is in the morning of Day 
-4 of the first period.
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 BI 1810631
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, subjects will be treated 
in an ambulatory fashion.
For details on time points and procedures for collection of plasma samples for PK analysis, 
refer to Flow Chart and Section 5.3.2.
The safety measurements performed during the treatment period are specified in Section 5.2
of this protocol and in the Flow Chart. For details on times of all other trial procedures, refer 
to the Flow Chart. AEs and concomitant therapy will be assessed continuously from 
obtaining subject’s written informed consent until the end of trial examination.
6.2.3
Follow-up period and trial completion
For AE assessment, laboratory tests, recording of ECG and vital signs, and physical 
examination during the follow-up period, see Section 5.2.
Subjects who discontinue treatment before the end of the planned treatment period should 
undergo the EoS Visit.
If needed in the opinion of the investigator, additional visits may be scheduled after the EoS 
visit for continued safety monitoring.
All abnormal values (including laboratory parameters) that are assessed as clinically relevant 
by the investigator will be monitored using the appropriate tests until a return to a medically 
acceptable level is achieved. (S)AEs persisting after a subject’s EoS Visit must be followed 
until they have resolved, have been sufficiently characterised, or no further information can 
be obtained. 

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contributes only one PK parameter value for one period to the statistical assessment.
Descriptive and model based analyses of PK parameters will be based on the PKS.
Adherence to the protocol will be assessed by the trial team. Important protocol deviation
(IPD) categories will be suggested in the IPD specification file. IPDs will be identified no
later than in the Report Planning Meeting, and the IPD categories will be updated as needed.
Pharmacokinetics
The pharmacokinetic parameters listed in Section 2.1 and 2.2.2 for drug BI 1810631 will be 
calculated according to the relevant BI internal procedures.
Plasma concentration data and parameters of a subject will be included in the statistical 
pharmacokinetic (PK) analyses if they are not flagged for exclusion due to a protocol 
deviation relevant to the evaluation of PK (to be decided no later than in the Report Planning 
Meeting) or due to PK non-evaluability (as revealed during data analysis, based on the 
criteria specified below). Exclusion of a subject’s data will be documented in the CTR.
Relevant protocol deviations may be
!
Incorrect trial medication taken, i.e. the subject received at least one dose of trial
medication the subject was not assigned to
!
Incorrect dose of trial medication taken
!
Use of restricted medications
Plasma concentrations and/or parameters of a subject will be considered as non-evaluable, if 
for example
!
The subject experienced emesis that occurred at or before two times median tmax of 
the respective treatment (Median tmax is to be determined excluding the subjects 
experiencing emesis), 
!
A predose concentration is >5% Cmax value of that subject
!
Missing samples/concentration data at important phases of PK disposition curve
Plasma concentration data and parameters of a subject which is flagged for exclusion will be 
reported with its individual values but will not be included in the statistical analyses. 
Descriptive and statistical models of PK parameters will be based on the PKS.
Only concentration values within the validated concentration range and actual sampling times
will be used for the calculation of pharmacokinetic parameters. Concentrations used in the 
pharmacokinetic calculations will be in the same format provided in the bioanalytical report, 
(that is, to the same number of decimal places provided in the bioanalytical report). 
7.3.1
Primary endpoint analyses
Primary analyses
The statistical model used for the analysis of the primary endpoints will be an analysis of 
variance (ANOVA) model on the logarithmic scale. That is, the PK endpoints will be log-

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transformed (natural logarithm) prior to fitting the ANOVA model. This model will include 
effects accounting for the following sources of variation: sequence, subjects within 
sequences, period and 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 measured on subject m in sequence i receiving treatment  
k in period j,
# = the overall mean,
∃i = the ith sequence effect, i = 1, …,4,
sim = the effect associated with the mth subject in the ith sequence,
m = 1, 2, ..., ni
%j = the jth period effect, j = 1, …,4,
&k = the kth treatment effect, k = 1, …,4,
eijkm = the random error associated with the mth subject in sequence i who received
treatment k in period j.
where s ~ N(0, σ
) i.i.d., e ~ N(0, σ
 ) i.i.d. and sim, eijkm are independent random 
variables.
Point estimates for the ratios of the geometric means (T1/R, T2/T1 and T3/T1) for the 
primary endpoints (see Section 2.1) and their two-sided 90% confidence intervals (CIs) will 
be provided.
For each endpoint, the difference between the expected means for log(T1)-log(R), log(T2)-
log(T1) and log(T3)-log(T1) will be estimated by the difference in the corresponding adjusted 
means (Least Squares Means). Additionally, their two-sided 90% confidence intervals will be 
calculated based on the residual error from the ANOVA and quantiles from the t-distribution. 
These quantities will then be back-transformed to the original scale to provide the point 
estimate and 90% CIs for each endpoint.

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7.3.2
Secondary endpoint analyses
The secondary endpoint (refer to Section 2.1.3) will be calculated according to the BI internal 
procedures and will be assessed statistically using the same methods as described for the 
primary endpoints.
7.3.4
Safety analyses
Safety will be analysed based on the assessments described in Section 2.2.2.2. All treated 
subjects (TS, refer to Section 7.2) will be included in the safety analysis. Safety analyses will 
be descriptive in nature and based on BI standards. No hypothesis testing is planned.
For all analyses, the treatment actually administered (= treatment at onset) to the subject will 
be used (any deviations from the randomised treatment will be discussed in the minutes of the 
Report Planning Meeting).
Treatments will be compared in a descriptive way. Tabulations of frequencies/proportions 
will be used to evaluate categorical (qualitative) data, and tabulations of descriptive statistics 
will be used to analyse continuous (quantitative) data.
Measurements (such as ECG, vital signs, or laboratory parameters) or AEs will be assigned to 
treatments (see Section 4.1) based on the actual treatment at the time of the measurement or 
on the recorded time of AE onset (concept of treatment emergent AEs). Therefore, 
measurements performed or AEs recorded prior to first intake of trial medication will be 
assigned to the screening period, those between first trial medication intake (BI 1810631 or 
rabeprazole) in each period and end of REP (see Section 1.2.3) or start of a new trial 
medication intake will be assigned to the respective treatment period. Events occurring after 
the REP but prior to next intake or end of trial termination date will be assigned to ’follow-
up’. In case of two or more treatments, the follow-up will be summarized according to the 
previous treatment. These assignments including the corresponding time intervals will be 
defined in detail in the TSAP. Note that AEs occurring after the last per protocol contact but 
entered before final database lock will be reported to Pharmacovigilance only and will not be 
captured in the trial database.
Additionally, further treatment intervals (analysing treatments) may be defined in the TSAP 
in order to provide summary statistics for time intervals, such as combined treatments, on-
treatment totals, or periods without treatment effects (such as screening and follow-up 
intervals.
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). Frequency, severity, and causal relationship of AEs will be tabulated by 
treatment, system organ class, and preferred term. SAEs, AESIs (see Section 5.2.6.1), and 
other significant AEs (according to ICH E3) will be listed separately.

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Previous and concomitant therapies will be presented per treatment group without 
consideration of time intervals and treatment periods.
Laboratory data will be compared to their reference ranges. Values outside the reference 
range will be highlighted in the listings. Additionally, differences from baseline will be 
evaluated.
Vital signs or other safety-relevant data will be assessed with regard to possible on-treatment 
changes from baseline.
Relevant ECG findings will be reported as AEs.
7.4
INTERIM ANALYSES
No formal interim analysis is planned.
A preliminary, exploratory PK analysis of BI 1810631 and rabeprazole may be performed 
based on evaluable data at any time prior to data base lock. This may be necessary, e.g. in 
case the information is needed to inform other activities during the development of 
BI 1810631. In contrast to the final PK calculations, the preliminary, exploratory analysis 
will be based on planned sampling times rather than on actual times, regardless of whether 
actual times were within the time windows or not. Therefore, minor deviations of preliminary 
and final results may occur. No formal preliminary PK report will be written.
7.5
HANDLING OF MISSING DATA
7.5.1
Safety
It is not planned to impute missing values for safety parameters. For partial or missing AE 
onset and/or end dates, BI internal rules will be followed.
7.5.2
Pharmacokinetics
Handling of missing PK data will be performed according to the relevant BI internal 
procedures. 
PK parameters that cannot be reasonably calculated based on the available drug 
concentration-time data will not be imputed.
7.6
RANDOMISATION
Subjects will be randomised to one of the 4 treatment sequences in a 1:1:1:1 ratio. The block 
size will be documented in the CTR.
The sponsor will arrange for the randomisation as well as packaging and labelling of trial 
medication. The randomisation list will be generated using a validated system that uses a 
pseudo-random number generator and a supplied seed number so that the resulting allocation 
is both reproducible and non-predictable.

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The randomisation list will contain additional blocks to allow for subject replacement (refer 
to Section 3.3.5).
7.7
DETERMINATION OF SAMPLE SIZE
It is planned to enter a total of 
subjects in the trial with the aim of ≥ 
 evaluable subjects, 
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 the relative BA estimate. Note that the precision is independent of the actual 
ratio of geometric means.
The observed intra-individual coefficient of variation (gCV) for BI 1810631 in the previous 
trial 1479-0001 (results given in 1.2.1) was roughly 
 for Cmax and 
 for AUC.
For various assumptions of the gCV between 
Table 7.7: 1 provides an 
overview of the achievable precision for estimating the ratio of geometric means 
(test/reference). For illustrative purposes, the expected 90% confidence intervals are 
displayed for different values of the ratios T/R of geometric means.
Table 7.7: 1
Precision that can be expected with 95% probability and illustrative 
two-sided 90% confidence intervals around the ratios of geometric 
means (T/R) for different gCVs in a 4x4 crossover trial (N=12)
gCV [%]
Precision upper 
CL / relative BA 
estimate
Ratio [%]*
Lower CL [%]
Upper CL [%]
*Ratio of geometric means (test/reference) for a PK endpoint is defined by exp(#T)/exp(#R).
The expected 90% confidence interval limits in the table were derived by
CI limit,  = exp(ln(θ) ± ω),
with θ being the ratio (T/R) on original scale and ω the distance from the estimate θ to either 
confidence interval limit on the log-scale, which was obtained from the achievable precision 
on the original scale.

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The calculation was performed as described by Julious [R11-5230] using R Version 4.0.1.

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8.
INFORMED CONSENT, TRIAL RECORDS, DATA 
PROTECTION, PUBLICATION POLICY, AND 
ADMINISTRATIVE STRUCTURE
The trial will be carried out in compliance with the protocol, the ethical principles laid down 
in the Declaration of Helsinki, in accordance with the ICH Harmonized Guideline for Good 
Clinical Practice (GCP), relevant BI Standard Operating Procedures (SOPs), the EU directive 
2001/20/EC, and other relevant regulations. Investigators and site staff must adhere to these 
principles. Deviation from the protocol, the principles of ICH GCP or applicable regulations 
will be treated as ‘protocol deviation’.
Standard medical care (prophylactic, diagnostic, and therapeutic procedures) remains the 
responsibility of the subject’s treating physician.
The investigator will inform the sponsor immediately of any urgent safety measures taken to 
protect the trial subjects against any immediate hazard, as well as of any serious breaches of 
the protocol or of ICH GCP.
The Boehringer Ingelheim transparency and publication policy can be found on the following 
web page: trials.boehringer-ingelheim.com. As a general rule, no trial results should be 
published prior to archiving of the CTR.
The terms and conditions of the insurance coverage are made available to the investigator and 
the  subjects, and are stored in the ISF.
8.1
TRIAL APPROVAL, SUBJECT INFORMATION, INFORMED CONSENT
This trial will be initiated only after all required legal documentation has been reviewed and 
approved by the respective Institutional Review Board (IRB / Independent Ethics Committee 
(IEC and competent authority (CA) according to national and international regulations. The 
same applies for the implementation of changes introduced by amendments.
Prior to a subject’s participation in the trial, written informed consent must be obtained from 
each subject according to ICH-GCP and to the regulatory and legal requirements of the 
participating country. Each signature must be personally dated by each signatory and the 
informed consent and any additional subject-information form retained by the investigator as 
part of the trial records. A signed copy of the informed consent and any additional subject 
information must be given to each subject.
The subject must be given sufficient time to consider participation in the trial. The 
investigator or delegate obtains written consent of the subject’s own free will with the 
informed consent form after confirming that the subject understands the contents. The 
investigator or 
 delegate must sign (or place a seal on) and date the informed consent form. 
If a trial collaborator has given a supplementary explanation, the trial collaborator also signs 
(or places a seal on) and dates the informed consent.
Re-consenting may become necessary when new relevant information becomes available and 
should be conducted according to the sponsor’s instructions.
The consent and re-consenting process should be properly documented in the source 
documentation.

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Before providing any copy of subjects’ source documents to the sponsor, the investigator 
must ensure that all subject identifiers (e.g., subject’s name, initials, address, phone number, 
and social security number) have properly been removed or redacted to ensure subject 
confidentiality.
If the subject is not compliant with the protocol, any corrective action (e.g. re-training) must 
be documented in the subject file.
For the CRF, data must be derived from source documents, for example:
!
Subject identification: sex, year of birth (in accordance with local laws and 
regulations)
!
Subject participation in the trial (substance, trial number, subject number, date subject 
was informed)
!
Dates of subject’s visits, including dispensing of trial medication
!
Medical history (including trial indication and concomitant diseases, if applicable)
!
Medication history
!
AEs and outcome events (onset date [mandatory], and end date [if available])
!
SAEs (onset date [mandatory], and end date [if available])
!
Concomitant therapy (start date, changes)
!
Originals or copies of laboratory results and other imaging or testing results, with 
proper documented medical evaluation (in validated electronic format, if available)
!
ECG results (original or copies of printouts)
!
Completion of subject’s participation in the trial (end date; in case of premature 
discontinuation, document the reason for it, if known)
!
Prior to allocation of a subject to a treatment into a clinical trial, there must be 
documented evidence in the source data (e.g. medical records) that the trial participant 
meets all inclusion criteria and does not meet any exclusion criteria. The absence of 
records (either medical records, verbal documented feedback of the subject or testing 
conducted specific for a protocol) to support inclusion/exclusion criteria does not 
make the subject eligible for the clinical trial.
Data directly entered into 
(that is, without prior written or electronic record) are 
considered to be source data. The place where data are entered first will be defined in a trial 
specific Source Data Agreement. The data in 
are available for inspection at any 
time.
8.3.2
Direct access to source data and documents
The investigator /institution will allow site trial-related monitoring, audits, IRB / IEC review 
and regulatory inspections. Direct access must be provided to the CRF and all source 
documents/data, including progress notes, copies of laboratory and medical test results, which 
must be available at all times for review by the Clinical Research Associate, auditor and 
regulatory inspector (e.g. FDA). They may review all CRFs and informed consents. The 
accuracy of the data will be verified by direct comparison with the source documents 

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described in section 8.3.1. The sponsor will also monitor compliance with the protocol and 
GCP.
8.3.3
Storage period of records
Trial site:
The trial site(s) must retain the source and essential documents (including ISF) according to 
the local requirements valid at the time of the end of the trial.
Sponsor:
The sponsor must retain the essential documents according to the sponsor’s SOPs.
8.4
EXPEDITED REPORTING OF ADVERSE EVENTS
BI is responsible to fulfil their legal and regulatory reporting obligation in accordance with 
regulatory requirements.
8.5
STATEMENT OF CONFIDENTIALITY AND SUBJECT PRIVACY
Data protection and data security measures are implemented for the collection, storage and 
processing of subject data in accordance with the principles 7 and 12 of the WHO GCP 
handbook.
Individual subject data obtained as a result of this trial is considered confidential and 
disclosure to third parties is prohibited with the following exceptions:
Personalised treatment data may be given to the subject’s personal physician or to other 
appropriate medical personnel responsible for the subject’s welfare. Data generated at the site 
as a result of the trial need to be available for inspection on request by the participating 
physicians, the sponsor’s representatives, by the IRB / IEC and the regulatory authorities.
8.5.1
Collection, storage and future use of biological samples and corresponding 
data
Measures are in place to comply with the applicable rules for the collection, storage and 
future use of biological samples and clinical data, in particular
!
Sample and data usage has to be in accordance with the informed consent
!
The BI-internal facilities storing biological samples from clinical trial participants as 
well as the external storage facility are qualified for the storage of biological samples 
collected in clinical trials.
!
An appropriate sample and data management system, incl. audit trail for clinical data 
and samples to identify and destroy such samples according to ICF is in place
!
A fit for the purpose documentation (e.g. biomarker proposal, analysis plan and 
report) ensures compliant usage
!
A fit for purpose approach will be used for assay/equipment validation depending on 
the intended use of the biomarker data
!
Samples and/or data may be transferred to third parties and other countries as 
specified in the ICF

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8.6
TRIAL MILESTONES
The start of the trial is defined as the date when the first subject in the whole trial signs 
informed consent.
The end of the trial is defined as the date of the last visit of the last subject in the whole trial 
(‘Last Subject Completed’).
Early termination of the trial is defined as the premature termination of the trial due to any 
reason before the end of the trial as specified in this protocol.
Temporary halt of the trial is defined as any unplanned interruption of the trial by the sponsor 
with the intention to resume it.
Suspension of the trial is defined as an interruption of the trial based on a Health Authority 
request.
The IEC/competent authority in each participating EU member state will be notified about 
the trial milestones according to the laws of each member state. 
A final report of the clinical trial data will be written only after all subjects have completed 
the trial in all countries (EU or non-EU), so that all data can be incorporated and considered 
in the report.
The sponsor will submit to the EU database a summary of the final trial results within one 
year from the end of a clinical trial as a whole, regardless of the country of the last subject
(EU or non-EU).
8.7
ADMINISTRATIVE STRUCTURE OF THE TRIAL
The trial is sponsored by Boehringer Ingelheim (BI).
The trial will be conducted at the 
 under the supervision of the Principal Investigator. Relevant 
documentation on the participating (Principal) Investigators (e.g. their curricula vitae) will be 
filed in the ISF. The investigators will have access to the BI web portal Clinergize to access 
documents provided by the sponsor.
BI has appointed a Clinical Trial Leader (CT Leader), responsible for coordinating all 
required trial activities, in order to 
!
Manage the trial in accordance with applicable regulations and internal SOPs
!
Direct the clinical trial team in the preparation, conduct, and reporting of the trial
!
Ensure appropriate training and information of local Clinical Trial Managers (CT 
Managers), Clinical Research Associates (CRAs), and investigators of participating 
trial sites
The trial medication (BI 1810631) will be provided by the 
. Rabeprazole (Pariet®) will be purchased by 
the clinical site at a public pharmacy.
Safety laboratory tests will be performed by the local laboratory of the trial site (
 
).

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Analyses of BI 1810631 and rabeprazole concentrations in plasma will be performed at 
.
On-site monitoring will be performed by BI or a contract research organisation appointed by 
BI.
Data management and statistical evaluation will be done by BI or by a contract research 
organization appointed by BI.
Tasks and functions assigned in order to organise, manage, and evaluate the trial are defined 
according to BI SOPs. A list of responsible persons and relevant local information can be 
found in the ISF.

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10.
APPENDICES
Not applicable

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11.
DESCRIPTION OF GLOBAL AMENDMENT(S)
11.1
GLOBAL AMENDMENT 1
Date of amendment
25 Apr 2022
EudraCT number
2022-000268-23
BI Trial number
1479-0003
BI Investigational Medicinal 
Product
BI 1810631
Title of protocol
Relative bioavailability of BI 1810631 as two 
different 
 formulations given as single doses 
and investigation of the effects of food and 
multiple-dose rabeprazole on the pharmacokinetics 
of single-dose BI 1810631 following oral 
administration in healthy male subjects (an open-
label, randomised, four-way crossover trial)
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
1) Synopsis, Section 3.3.2: Inclusion criterion 2
2) Section 3.3.3: Exclusion criterion 10
3) Section 8.1
Description of change
1) Upper age limit reduced from 50 to 45
2) Any current malignancy or history of 
malignancy is now an exclusion criterion
3) Deletion of “the subject’s legally acceptable 
representative”
Rationale for change
1) To address deficiency issued by competent 
authority (BfArM)
2) To address deficiency issued by competent 
authority (BfArM)
3) To address deficiency issued by competent 
authority (BfArM)

 
 
 
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