A 2-Part Study to Evaluate the Relative Bioavailability of 2 New Formulations of UCB0599 and the Effect of Esomeprazole on the PK of UCB0599 in Healthy Participants (Part A, Open-Label) and to Assess the Safety/Tolerability and PK of UCB0599 in Healthy Participants of Japanese and Chinese Origins (Part B, Double-Blind)
Phase: PHASE1
Conditions: Healthy Study Participants
Sponsor: UCB Biopharma SRL

UCB 
26 Oct 2023 
Clinical Study Protocol Amendment 1 
UCB0599 
UP0073 
Confidential 
Page 1 of 101 
A 2-PART STUDY TO EVALUATE THE RELATIVE 
BIOAVAILABILTY OF 2 NEW FORMULATIONS OF UCB0599 
AND THE EFFECT OF ESOMEPRAZOLE ON THE PK OF 
UCB0599 IN HEALTHY PARTICIPANTS (PART A, OPEN-
LABEL) AND TO ASSESS THE SAFETY/TOLERABILITY AND 
PK OF UCB0599 IN HEALTHY PARTICIPANTS OF JAPANESE 
AND CHINESE ORIGINS (PART B, DOUBLE-BLIND) 
PROTOCOL UP0073 AMENDMENT 1 
Phase 1 
SHORT TITLE: 
A randomized, 2-part single-dose crossover Phase 1 study to assess 2 new formulations of 
UCB0599 in healthy participants (Part A, open-label) and to assess UCB0599 in healthy 
participants of Japanese and Chinese origins (Part B, double-blind) 
Sponsor: 
UCB Biopharma SRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
Regulatory agency identifying number(s): 
EudraCT Number: 
Not applicable 
EU Trial Number: 
Not applicable 
EUDAMED Number: 
Not applicable 
IND Number: 
141003 
IDE Number: 
Not applicable 
NCT Number: 
NCT05845645 
Confidential Material 
Confidential 
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB. 
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26 Oct 2023 
Clinical Study Protocol Amendment 1 
UCB0599 
UP0073 
 
 
 
Confidential 
Page 2 of 101 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Document History 
Document 
Date 
Type of amendment 
Amendment 1 
26 Oct 2023 
Not applicable 
Original Protocol 
02 Mar 2023 
Not applicable 
 
Amendment 1 (26 Oct 2023) 
Overall Rationale for the Amendment 
UP0073 Protocol Amendment 1 was completed to include UCB0599 capsules (reference 
formulation in Part A) as a study treatment option for Part B. 
Section # and name 
Description of change 
Brief rationale 
Global 
Throughout, “new” or “newly selected” 
was removed when referring to the 
formulation for Part B. 
To acknowledge the 
addition of the capsule 
formulation as study 
treatment option for Part B. 
Title page  
and  
Section 1.1 Synopsis, 
Short title  
The short title for Part B was changed 
from “…and to assess UCB0599 with the 
new formulation in healthy participants of 
Japanese and Chinese origins (Part B, 
double-blind)” to “…and to assess 
UCB0599 in healthy participants of 
Japanese and Chinese origins (Part B, 
double blind).”  
To align short title with 
study title. 
Title page 
NCT number was added. 
To complete the table with 
regulatory agency 
identifying numbers. 
Section 1.1 Synopsis, 
Rationale 
and  
Section 2.1 Study rationale 
The sentence “This approach will assess 
UCB0599 exposure from film-coated 
tablets with or without encapsulation to 
support the selection of the new 
formulation” was changed to “This 
approach will assess UCB0599 exposure 
from film-coated tablets with or without 
encapsulation to inform formulation 
development.” 
To update wording 
following the addition of 
the Part A reference 
formulation (capsule) as 
study treatment option for 
Part B. 
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26 Oct 2023 
Clinical Study Protocol Amendment 1 
UCB0599 
UP0073 
 
 
 
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Page 3 of 101 
Section 4.2 Scientific 
rationale for study design 
In the last paragraph, the second sentence 
“Thus, this approach will also allow 
comparison of UCB0599 systemic 
exposure from film-coated tablets with or 
without encapsulation to support the 
selection of the new formulation” was 
changed to “Thus, this approach will also 
allow comparison of UCB0599 systemic 
exposure from film-coated tablets with or 
without encapsulation to inform 
formulation development.” 
To update wording 
following the addition of 
the capsule formulation as 
study treatment option for 
Part B. 
Section 4.3 Justification for 
dose 
The first 2 sentences were combined to 
focus on the justification for dose: 
“In Part A, PK data will be collected to 
support the use of a new  formulation. In 
this part of the study, the UCB0599 dose 
level of 180mg single dose is being 
selected based on the PK properties of 
UCB0599.” 
To remove unnecessary 
information. 
Section 6.1 Treatments 
administered 
In Tables 6-1 through 6-3 under 
Packaging and labeling, “carton” was 
changed to “bottle” throughout.  
To correct packaging 
information for study 
medication in both study 
parts. 
Table 6-4 was added. 
To also include UCB0599 
capsules as formulation 
option for Part B. 
Section 9.4.2.2 Part B 
Throughout, “the selected new 
formulation” was changed to “the 
formulation used in Part B.” 
To acknowledge the 
addition of the capsule 
formulation as study 
treatment option for Part B. 
Throughout 
Minor editorial and document formatting 
revisions 
Minor, therefore have not 
been summarized. 
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26 Oct 2023 
Clinical Study Protocol Amendment 1 
UCB0599 
UP0073 
 
 
 
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SERIOUS ADVERSE EVENT REPORTING 
 
Serious adverse event reporting (24h) 
Fax 
US and Canada: +1 800 880 6949 or +1 866 890 3175 
Email 
Global: DS_ICT@ucb.com (for interventional clinical studies) 
 
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Clinical Study Protocol Amendment 1 
UCB0599 
UP0073 
 
 
 
Confidential 
Page 5 of 101 
TABLE OF CONTENTS 
1 
PROTOCOL SUMMARY ............................................................................................... 10 
1.1 
Synopsis ....................................................................................................................... 10 
1.2 
Schema ......................................................................................................................... 16 
1.3 
Schedule of activities ................................................................................................... 19 
2 
INTRODUCTION ........................................................................................................... 25 
2.1 
Study rationale ............................................................................................................. 25 
2.2 
Background .................................................................................................................. 25 
2.3 
Benefit/risk assessment ................................................................................................ 26 
2.3.1 
Coronavirus Disease-2019 benefit/risk assessment ............................................. 27 
2.3.1.1 
COVID-19 risk mitigation measures ......................................................... 27 
2.3.1.2 
COVID-19 benefit/risk conclusion ........................................................... 28 
3 
OBJECTIVES AND ENDPOINTS ................................................................................. 28 
4 
STUDY DESIGN ............................................................................................................. 30 
4.1 
Overall design .............................................................................................................. 30 
4.1.1 
Part A ................................................................................................................... 30 
4.1.2 
Part B ................................................................................................................... 31 
4.2 
Scientific rationale for study design ............................................................................ 33 
4.2.1 
Patient input into design ...................................................................................... 34 
4.3 
Justification for dose .................................................................................................... 34 
4.4 
End of study definition................................................................................................. 35 
5 
STUDY POPULATION .................................................................................................. 35 
5.1 
Inclusion criteria .......................................................................................................... 35 
5.2 
Exclusion criteria ......................................................................................................... 36 
5.3 
Lifestyle restrictions..................................................................................................... 39 
5.3.1 
Meals and dietary restrictions .............................................................................. 39 
5.3.2 
Caffeine, alcohol, and tobacco ............................................................................. 39 
5.3.3 
Activity ................................................................................................................ 40 
5.4 
Screen failures .............................................................................................................. 40 
6 
STUDY TREATMENTS ................................................................................................. 40 
6.1 
Treatments administered .............................................................................................. 40 
6.2 
Preparation, handling, storage, and accountability requirements ................................ 49 
6.2.1 
Drug accountability ............................................................................................. 49 
6.3 
Measures to minimize bias: randomization and blinding ............................................ 49 
6.3.1 
Procedures for maintaining and breaking the treatment blind ............................. 50 
6.3.1.1 
Maintenance of study treatment blind ....................................................... 50 
6.3.1.2 
Breaking the treatment blind in an emergency situation ........................... 50 
6.4 
Treatment compliance .................................................................................................. 51 
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UP0073 
 
 
 
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6.5 
Concomitant medication(s)/treatment(s) ..................................................................... 51 
6.5.1 
Permitted concomitant treatments (medications and therapies) .......................... 51 
6.5.1.1 
Permitted Coronavirus Disease-2019 vaccination..................................... 51 
6.5.2 
Prohibited concomitant treatments (medications and therapies) ......................... 51 
6.5.3 
Rescue medication ............................................................................................... 52 
6.6 
Dose modification ........................................................................................................ 52 
6.7 
Criteria for study hold or dosing stoppage (Part A and Part B) ................................... 52 
6.8 
Treatment after the end of the study ............................................................................ 52 
7 
DISCONTINUATION OF STUDY MEDICATION AND STUDY PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ........................................................................ 52 
7.1 
Discontinuation of study medication ........................................................................... 52 
7.1.1 
Liver chemistry stopping criteria ......................................................................... 52 
7.1.2 
QTc stopping criteria ........................................................................................... 53 
7.1.3 
Renal toxicity stopping criteria ............................................................................ 54 
7.1.4 
Hypersensitivity reaction stopping criteria .......................................................... 54 
7.1.5 
General stopping criteria for the study - Part B only ........................................... 55 
7.1.6 
Rechallenge .......................................................................................................... 55 
7.2 
Participant discontinuation/withdrawal from the study ............................................... 55 
7.3 
Lost to follow up .......................................................................................................... 56 
8 
STUDY ASSESSMENTS AND PROCEDURES ........................................................... 56 
8.1 
Efficacy assessments .................................................................................................... 57 
8.2 
Safety assessments ....................................................................................................... 57 
8.2.1 
Physical examination ........................................................................................... 57 
8.2.2 
Vital signs ............................................................................................................ 58 
8.2.3 
Electrocardiograms .............................................................................................. 58 
8.2.4 
Clinical safety laboratory assessments ................................................................ 58 
8.2.5 
Suicidal risk monitoring ...................................................................................... 59 
8.3 
AEs and SAEs .............................................................................................................. 59 
8.3.1 
Time period and frequency for collecting AE and SAE information .................. 59 
8.3.2 
Method of detecting AEs and SAEs .................................................................... 60 
8.3.3 
Follow up of AEs and SAEs ................................................................................ 60 
8.3.4 
Regulatory reporting requirements for SAEs ...................................................... 60 
8.3.5 
Pregnancy ............................................................................................................ 60 
8.3.6 
AESIs ................................................................................................................... 61 
8.3.6.1 
Hypersensitivity reaction monitoring and management ............................ 61 
8.3.6.2 
Renal function safety monitoring and management .................................. 64 
8.4 
Safety signal detection ................................................................................................. 65 
8.5 
Treatment of overdose ................................................................................................. 65 
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8.6 
Pharmacokinetics ......................................................................................................... 65 
8.6.1 
Part A ................................................................................................................... 66 
8.6.2 
Use of residual plasma samples (Part A only) ..................................................... 66 
8.6.3 
Part B ................................................................................................................... 66 
8.7 
Biomarkers ................................................................................................................... 67 
8.8 
Medical resource utilization and health economics ..................................................... 67 
9 
STATISTICAL CONSIDERATIONS ............................................................................. 67 
9.1 
Definition of analysis sets ............................................................................................ 67 
9.2 
General statistical considerations ................................................................................. 68 
9.3 
Planned efficacy outcome analyses ............................................................................. 68 
9.4 
Planned PK outcome analyses ..................................................................................... 68 
9.4.1 
PK parameters to be measured ............................................................................ 68 
9.4.2 
Analysis of the primary PK endpoint .................................................................. 69 
9.4.2.1 
Part A ......................................................................................................... 69 
9.4.2.2 
Part B ......................................................................................................... 71 
9.4.3 
Other PK endpoint analyses ................................................................................. 72 
9.4.3.1 
Part A ......................................................................................................... 72 
9.4.3.2 
Part B ......................................................................................................... 72 
9.5 
Planned safety and other analyses................................................................................ 72 
9.5.1 
Safety analyses ..................................................................................................... 72 
9.6 
Handling of protocol deviations................................................................................... 73 
9.7 
Handling of dropouts or missing data .......................................................................... 73 
9.8 
Planned interim analysis and data monitoring ............................................................. 73 
9.9 
Determination of sample size ....................................................................................... 73 
9.9.1 
Part A ................................................................................................................... 73 
9.9.2 
Part B ................................................................................................................... 74 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS... 75 
10.1 
Appendix 1: Regulatory, ethical, and study oversight considerations ......................... 75 
10.1.1 
Regulatory and ethical considerations ................................................................. 75 
10.1.2 
Financial disclosure ............................................................................................. 75 
10.1.3 
Informed consent process .................................................................................... 76 
10.1.4 
Recruitment strategy ............................................................................................ 76 
10.1.5 
Data protection ..................................................................................................... 76 
10.1.6 
Committees structure ........................................................................................... 77 
10.1.7 
Dissemination of clinical study data .................................................................... 77 
10.1.8 
Data quality assurance ......................................................................................... 77 
10.1.8.1 
eCRF completion ....................................................................................... 78 
10.1.8.2 
Application ................................................................................................ 78 
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10.1.9 
Source documents ................................................................................................ 78 
10.1.10 
Study and site start and closure ........................................................................... 79 
10.1.11 
Publication policy ................................................................................................ 79 
10.2 
Appendix 2: Clinical laboratory tests .......................................................................... 80 
10.3 
Appendix 3: Adverse events – Definitions and procedures for recording, evaluating, 
follow up, and reporting ............................................................................................... 82 
10.4 
Appendix 4: Contraceptive guidance and collection of pregnancy information ......... 87 
10.5 
Appendix 5: Genetics ................................................................................................... 90 
10.6 
Appendix 6: Liver safety – suggested actions and follow up assessments .................. 91 
10.7 
Appendix 7: Medical device AEs, ADEs, SAEs, and device deficiencies: Definition 
and procedures for recording, evaluating, follow up, and reporting ............................ 94 
10.8 
Appendix 8: Rapid alert procedures ............................................................................ 95 
10.9 
Appendix 9: Country-specific requirements ................................................................ 96 
10.10 Appendix 10: Abbreviations and trademarks .............................................................. 97 
10.11 Appendix 11: Protocol amendment history ................................................................. 99 
11 REFERENCES .............................................................................................................. 100 
SPONSOR DECLARATION ................................................................................................ 101 
 
LIST OF TABLES 
Table 1-1: 
Part A design: Relative bioavailability of UCB0599 under normal or 
elevated gastric pH conditions in healthy participants (3-treatment, 
6-period complete block design) ...................................................................... 17 
Table 1-2: 
Part B design: The PK of UCB0599 in healthy Japanese and Chinese 
participants under normal gastric pH conditions (4-treatment, 6-sequence, 
2-period crossover design) ............................................................................... 18 
Table 1-3: 
Part A Schedule of activities ............................................................................ 19 
Table 1-4: 
Part B Schedule of Activities ........................................................................... 22 
Table 3-1: 
Part A: The relative bioavailability in reference to the current clinical 
formulation in the presence and absence of PPI (esomeprazole) of 2 new 
UCB0599 formulations and the PK of UCB0599 after a single dose in 
healthy participants .......................................................................................... 28 
Table 3-2: 
Part B: The safety, tolerability, and PK of UCB0599 after administration 
of UCB0599 at single dose in healthy participants of Japanese and 
Chinese origins................................................................................................. 29 
Table 6-1: 
Study treatment for Part A ............................................................................... 41 
Table 6-2: 
Study treatment for Part B option: UCB0599 film-coated tablet used as 
new formulation ............................................................................................... 43 
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UP0073 
 
 
 
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Table 6-3: 
Study treatment for Part B option: UCB0599 encapsulated tablet used as 
new formulation ............................................................................................... 45 
Table 6-4: 
Study treatment for Part B option: UCB0599 capsules (Part A reference 
formulation) ..................................................................................................... 47 
Table 9-1: 
Non-compartmental PK parameters for UCB0599 in plasma ......................... 69 
Table 10-1: 
Phase 1 Liver Chemistry Stopping Criteria and Follow up 
AssessmentsTable ............................................................................................ 91 
 
LIST OF FIGURES 
Figure 1-1: 
Overall study schematic ................................................................................... 16 
Figure 7-1: 
Phase I Liver Chemistry Stopping Algorithm ................................................. 53 
 
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U C B  
 
2 6 Oct 2 0 2 3  
Cli nical St u d y Pr ot oc ol A me n d me nt 1  
U C B 0 5 9 9  
U P 0 0 7 3  
 
 
 
C o nfi de ntial  
P a ge 1 0  of 1 0 1  
1  
P R O T O C O L S U M M A R Y  
1. 1  
S y n o p si s  
Pr ot oc ol titl e:  A 2 -p art st u d y t o e val u ate t he relati ve bi oa vaila bilt y of 2 ne w f or m ulati o ns of 
U C B 0 5 9 9 a n d t he effect of es o me praz ole o n t he P K of U C B 0 5 9 9 i n he alt h y partici pa nts ( Part A, 
o pe n -la bel) a n d t o assess t he safet y/t olera bilit y a n d P K of U C B 0 5 9 9 i n healt h y partici pa nts of 
J a pa nese a n d C hi nese ori gi ns ( Part B, d o u ble-bli n d)  
S h ort title: A ra n d o mize d, 2 -part si n gle -d ose cr oss o ver P hase 1 st u d y t o assess 2  ne w 
f or m ulati o ns of U C B 0 5 9 9 i n healt h y p atici pa nts ( Part A, o pe n-la bel) a n d t o assess U C B 0 5 9 9 i n 
healt h y p artici pa nts of J a pa nese a n d C hi nes e ori gi ns ( Part B, d o u ble -bli n d)  
R ati o n ale:  
U C B 0 5 9 9 is a n orall y a v aila ble i n hi bit or of al p ha -s y n uclei n ( A S Y N) misf ol di n g a n d 
d o w nstrea m A S Y N a g gre gati o n. T he c urre nt st u d y, U P 0 0 7 3, is desi g ne d t o e val uate t he relati ve 
bi oa vaila bilit y of 2 ne w f or m ulati o ns ( 1 8 0 m g fil m-c oate d ta bl et c o ntai ni n g 
 wit h or 
wit h o ut e nca ps ulati o n) vers us  t he curre nt cli nical f or m ulati o n (ie, 2 x 9 0 m g  gra n ules i n ca ps ule ), 
i n t he a bse nce a n d prese n ce of es o m e praz ole, o n t he p har mac o ki netics ( P K) of U C B 0 5 9 9 i n 
healt h y p artici pa nts ( Part A, o pe n -la bel); a n d t o assess t he safet y, t olera bilit y, a n d P K of 
U C B 0 5 9 9 i n he alt h y partici pa nts of J a pa nese a n d C hi nese ori gi ns ( Part B, d o u ble -bli n d).  
U C B 0 5 9 9, a w ea k basi c dr u g ( p Ka of 6. 8) f oll o wi n g oral d ose a d mi nistrati o n i n h u ma ns, is 
e x pecte d t o u n der g o p H -de pe n de nt a bs or pti o n o ver differe nt se g me nts of t he gastr oi ntesti nal 
( GI) tract. H o w e ver, it is n ot k n o w n w het her a n el e vate d gastri c p H affects t he s yste mic 
e x p os ure of U C B 0 5 9 9 a n d its meta b olites (
 meta b olite) f or t he c urre nt 
cli nical f or m ulati o n. F or t his reas o n, i n Part A, U P 0 0 7 3 will e val uate 2 f orm ulati o ns  (ie, 
1 8 0 m g  fil m-c o ate d ta blet c o ntai ni n g 
 wit h or wit h o ut e nca ps ul ati o n) t o assess t he 
relati ve bi oa vaila bilit y of 1 8 0 m g U C B 0 5 9 9 c o m p are d wit h t he c urre nt cli nical f or m ulati o n (ie, 
gra n ules i n ca ps ule) i n healt h y partici pa nts. T he h y p ot hesis f or t he i ntr o d ucti o n of 
 
i n t he ta blet is t he a bilit y of t his e x ci pie nt t o re d uce t he micr oe n vir o n m e ntal p H of t he 
disi nte grati n g ta blet a n d p ote ntiall y e n h a nce dr u g diss ol uti o n i n t he st o mac h, i n de pe n de nt of 
gastri c p H. T h us, t he e n ca p s ulati o n is i n vesti gate d si nce it ma y e xte n d t he d urati o n of dr u g 
diss ol uti o n d uri n g l o w micr oe n vir o n me ntal p H.  P art A will als o e val uat e dr u g s yste mic e x p os ure 
u n der b ot h  n or mal a n d  ele vate d gastri c p H c o n diti o ns. T he ele vati o n of t he gastri c p H i n healt h y 
partici pa nts will be ac hie ve d t hr o u g h t he a d mi nistrati o n of t he pr ot o n p u m p i n hi bit or ( P PI) 
es o me praz ole. T his a p pr oac h will assess U C B 0 5 9 9 e x p os ure fr o m fil m -c oate d ta blets wit h or 
wit h o ut e nca ps ulati o n t o i nf or m f or m ulati o n de vel o p me nt . 
Part B of t his st u d y is a n et h n o bri d gi n g st u d y e v al uati n g t he safet y, t olera bilit y, a n d P K of a 
si n gle oral d ose of U C B 0 5 9 9 at 3 d ose le vels ( 9 0 m g, 1 8 0 m g, a n d 3 6 0 m g) u n der n or mal gastri c 
p H c o n diti o ns i n healt h y partici pa nts of J a pa nese a n d C hi nese ori gi ns.  
C CI
C CI
C CI
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

U C B  
 
2 6 Oct 2 0 2 3  
Cli nical St u d y Pr ot oc ol A me n d me nt 1  
U C B 0 5 9 9  
U P 0 0 7 3  
 
 
 
C o nfi de ntial  
P a ge 1 1  of 1 0 1  
O bjecti ves a n d e n d p oi nts  
Part A:  T he relati ve bi o a vaila bilit y i n refere n ce t o t he c urre nt cli nical f or m ulati o n i n t he prese nce 
a n d a bse nce of P PI (es o me praz ole) of 2 ne w U C B 0 5 9 9 f or m ulati o ns a n d t he P K of U C B 0 5 9 9 
after a si n gle d os e i n healt h y partici p a nts  
O bjecti ves  
E n d p oi nts  
Pri m ar y  
•  T o esti mate t he relati ve bi oa vaila bilit y of 
2 ne w U C B 0 5 9 9 f or m ulati o ns vers us 
refere nce ‘ gra n ules i n ca ps ule’ 
f or m ulati o n u n der ele v at e d gastric p H a n d 
u n der n or mal c o n diti o ns i n healt h y 
partici pa nts  
P K e n d p oi nts of U C B 0 5 9 9  
•  C ma x  
•  A U C 0 -t 
•  A U C i nf 
Sec o n d ar y  
•  T o e val uate f or eac h f or m ulati o n t he 
safet y a n d t olera bilit y of si n gle d ose 
U C B 0 5 9 9 al o ne u n d er el e vate d gastri c p H 
a n d u n der n or m al c o n diti o ns i n healt h y 
partici pa nts  
Safet y e n d p oi nts  
•  I n ci de nce of T E A Es 
•  I n ci de nce of treat me nt-e mer ge nt S A Es  
•  I n ci de nce of T E A Es l ea di n g t o 
wit h dra wal fr o m st u d y  
Ot her  
•  T o esti mate t he relati ve bi oa vaila bilit y of 
U C B 0 5 9 9 u n der ele vate d gastri c p H 
vers us n or mal gastric p H f or eac h teste d 
f or m ulati o n 
•  T o f urt her e val uate t he P K of U C B 0 5 9 9 
a n d its 
 
meta b olites after si n gle d ose U C B 0 5 9 9 
al o ne a n d c o -a d mi nistrat e d wit h 
es o me praz ole i n healt h y partici pa nts  
Ot her P K e n d p oi nts  
•  F or U C B 0 5 9 9:  
− C ma x , A U C0 -t, a n d A U Ci nf 
− tma x , t½ , C L/ F, a n d Vz/ F (if p ossi ble 
b ut n ot li mite d)  
•  F or 
 meta b olites:  
− C ma x , tma x , A U C0 -t, a n d A U C i nf 
− meta b olite/ pare nt  C ma x  a n d A U C rati o 
(c orrecte d f or t he m olec ular wei g ht of 
t he e ntities), as a p pr o pr iate 
A U C i nf=area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me zer o t o i nfi nit y; A U C0 -t=area u n der t he plas ma 
c o nce ntrati o n -ti me c ur ve fr o m ti me zer o t o t; C L/ F =a p pare nt t otal b o d y cleara nce; Cma x = ma xi m u m o bser ve d 
plas ma c o nce ntrati o n; P K = p har mac o ki netic(s); S A E =seri o us a d verse e ve nt; t ½ =a p pare nt t er mi nal eli mi nati o n 
half -life; T E A E =treat me nt-e mer ge nt a d ver se e ve nt; t ma x =ti me of occ urre nce of C ma x ; Vz/ F =a p pare nt v ol u me of 
distri b uti o n  
C CI
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

U C B  
 
2 6 Oct 2 0 2 3  
Cli nical St u d y Pr ot oc ol A me n d me nt 1  
U C B 0 5 9 9  
U P 0 0 7 3  
 
 
 
C o nfi de ntial  
P a ge 1 2  of 1 0 1  
Part B:  T he safet y, t olera bilit y, a n d P K of U C B 0 5 9 9 after a d mi nistrati o n of U C B 0 5 9 9 at si n gle 
d ose i n healt h y p artici pa nts of J a pa nese a n d C hi nese ori gi ns  
O bjecti ves  
E n d p oi nts  
Pri m ar y  
•  T o assess t he safet y a n d t olera bilit y of 
U C B 0 5 9 9 aft er a d mi nistrati o n of a si n gl e 
d ose of a n oral f or m ulati o n i n healt h y 
partici pa nts of J a pa nese a n d C hi nese 
ori gi ns  
Safet y e n d p oi nt  
•  I n ci de nce of T E A Es 
•  I n ci de nce of treat me nt-e mer ge nt S A Es  
•  I n ci de nce of T E A Es l ea di n g t o 
wit h dra wal fr o m st u d y  
•  T o e val uate t he pl as ma P K of U C B 0 5 9 9 
after a d mi nistrati o n of a si n gle d ose of a n 
oral f or m ulati o n i n healt h y partici pa nts of 
J a pa nese a n d C hi nese ori gi ns 
C o -pri mar y P K e n d p oi nts f or U C B 0 5 9 9  
•  C ma x  
•  A U C 0 -t 
•  A U C i nf 
Ot her  
•  T o assess a d diti o nal safet y a n d t olera bilit y 
c haracteristics of U C B 0 5 9 9 i n healt h y 
partici pa nts of J a pa nese a n d C hi nese 
ori gi ns  
Ot her safet y e n d p oi nts  
•  C ha n ges fr o m Baseli ne i n vital si g ns 
( p ulse rate, B P, res pir at or y rate, a n d b o d y 
te m perat ur e) 
•  C ha n ges fr o m Baseli ne i n safet y 
la b orat or y dat a ( he mat ol o g y, cli nical 
c he mistr y, uri nal ysis)  
•  C ha n ges fr o m Baseli ne i n 1 2 -lea d E C G 
assess me nt  
•  P h ysical e xa mi nati o n fi n di n gs  
•  T o f urt her e val uate t he P K of U C B 0 5 9 9 
a n d its 
 
met a b olites after a si n gle d ose of a n oral 
f or m ulati o n i n healt h y p artici pa nts of 
J a pa nese a n d C hi nese ori gi ns 
Ot her P K e n d p oi nts  
•  F or U C B 0 5 9 9:  
− tma x , C L/ F, Vz/ F, t1/ 2, Cma x / B W/ D, 
A U C 0 -t/ B W/ D, a n d A U Ci nf/ B W/ D 
•  F or 
 meta b olites: 
− C ma x , tma x , A U C 0 -t, a n d A U Ci nf 
− M eta b olite/ pare nt  C ma x  a n d A U C rati o 
(c orrecte d f or t he m olec ular wei g ht of 
t he e ntities), as a p pr o pr iate 
− M eta b olite/ pare nt  C ma x  a n d A U C rati o 
(c orrecte d f or t he m olec ular wei g ht of 
t he e ntities) per p o p ulati o n, as 
a p pr o priate 
C CI
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

U C B  
 
2 6 Oct 2 0 2 3  
Cli nical St u d y Pr ot oc ol A me n d me nt 1  
U C B 0 5 9 9  
U P 0 0 7 3  
 
 
 
C o nfi de ntial  
P a ge 1 3  of 1 0 1  
A U C i nf=area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me zer o t o i nfi nit y; A U C0 -t=area u n der t he plas ma 
c o nce ntrati o n -ti me c ur ve fr o m ti me zer o t o t; B P = bl o o d press ure; B W = b o d y wei g ht; C L/ F =a p pare nt t otal b o d y 
cleara nce; C ma x = ma xi m u m o bser ve d plas ma c o nce ntrati o n; D = d ose; E C G =electr ocar di o gra m; 
P K = p har mac o ki netic(s); S A E =seri o us a d verse e ve nt; t ½ =a p pare nt ter mi nal eli mi nati o n half -life; 
T E A E =treat me nt -e mer ge nt a d verse e ve nt; t ma x =ti me of occ urre nce of C ma x ; Vz/ F =a p pare nt v ol u me of 
distri b uti o n  
O ver all des i g n 
U P 0 0 7 3 is a ra n d o mize d, 2 -part si n gle -d ose cr oss o ver P hase 1 st u d y. A st u d y o ver vie w of 
U P 0 0 7 3 is pr o vi de d i n Fi g ure  1 -1 . 
T he pri mar y o bje cti ve of Part A is t o esti mate t he relati ve bi oa vaila bilit y of 2 ne w U C B 0 5 9 9 
f or m ulati o ns ( 1 8 0 m g fil m-c oate d ta blet c o ntai ni n g
 wit h or wit h o ut e nca ps ulati o n) 
vers us t he c urre nt cli nical f or m ulati o n ( 2 x 9 0 m g gra n ules i n ca ps ule) u n d er b ot h n or mal a n d 
ele vate d gastric p H c o n diti o ns. T his p orti o n of t he st u d y is a n o pe n -la bel, r a n d o mize d, 2 i n-series 
cr oss o ver s u bst u dies, eac h wit h a fi x e d se q ue nce c o m plete bl oc k desi g n of 3 treat me nt peri o ds i n 
healt h y m ale a n d fe male partici pa nts.  T he sec o n dar y o bjecti ve is t o e val uat e t he safet y a n d 
t olera bilit y of a si n gle d ose U C B 0 5 9 9 al o n e u n der n or mal a n d ele vate d gastric p H. Ot her 
o bjecti ves are t o f urt her e val uate t he P K of U C B 0 5 9 9 a n d its meta b olites (
 
) after a si n gle-d ose U C B 0 5 9 9 al o n e a n d c o -a d mi nistrate d wit h es o me praz ole. See 
Secti o n  3  f or m ore det ails o n t he o bjecti ves a n d e n d p oi nts of t he st u d y. 
Part B of t his  st u d y is a n et h n o bri d gi n g st u d y e v al uati n g t he safet y, t olera bilit y, a n d P K of a 
si n gle oral d ose of U C B 0 5 9 9 at 3 d ose le vels ( 9 0 m g, 1 8 0 m g, a n d 3 6 0 m g) u n der n or mal gastri c 
p H c o n diti o ns i n healt h y partici pa nts of J a pa nese a n d C hi nese ori gi ns. Eac h gr o u p o f et h nic 
ori gi n ( N = 1 5 t otal f or eac h) will be ra n d o mize d t o a 4 -treat me nt, 6-se q ue n ce, 2-peri o d cr oss o v er 
st u d y usi n g U C B 0 5 9 9: pl ace b o i n a 4: 1 rati o, as s h o w n bel o w a n d i n t he St u d y Sc he m a (see 
Secti o n  1. 2 ). Se q ue nces 3 a n d 4 will o nl y c o m me nce aft er Se q ue n ces 1 a n d 2 ha ve bee n 
c o m plete d f or all 5  partici pa nts; Se q ue nces 5 a n d 6 will o nl y c o m me nce aft er Se q ue nces 3 a n d 4 
ha ve bee n c o m plete d f or all 5 p artici pa nts, all o wi n g t he Safet y M o nit ori n g C o m mittee ( S M C) 
re vie w t o be carrie d o ut bef ore t h e start of Se q ue nce 5. 
•  Se q ue nce 1:  
place b o 9 0 m g, f oll o we d b y place b o 1 8 0 m g ( N = 1)  
•  Se q ue nce 2:  
U C B 0 5 9 9 9 0 m g, f oll o we d b y U C B 0 5 9 9 1 8 0 m g ( N = 4)  
•  Se q ue nce 3:  
place b o 1 8 0 m g, f oll o we d b y place b o 3 6 0 m g   ( N = 1) 
•  Se q ue nce 4:  
U C B 0 5 9 9 1 8 0 m g, f oll o w e d b y U C B 0 5 9 9 3 6 0 m g ( N = 4)  
•  Se q ue nce 5:  
place b o 3 6 0 m g, f oll o we d b y place b o 9 0 m g ( N = 1)  
•  Se q ue nce 6:  
U C B 0 5 9 9 3 6 0 m g, f oll o w e d b y U C B 0 5 9 9 9 0 m g ( N = 4)  
T he pri mar y o bje cti ves of Part B are ( 1) t o assess t he safet y a n d t olera bilit y; a n d ( 2) t o e val u ate 
t he plas ma P K of U C B 0 5 9 9 after a d mi nistrati o n of a si n gle d os e of U C B 0 5 9 9 i n healt h y 
partici pa nts of J a pa nese a n d C hi nese ori gi ns. N o partici pa nt will e ver recei ve b ot h U C B 0 5 9 9 a n d 
place b o, a n d t h eref ore n o i ntra -partici pa nt c o m paris o n will be p ossi ble; t he cr oss o ver as pect of 
t he Part B desi g n refers t o t he d ose le vel o ver 2 peri o ds i n or der t o li mit t he n u m ber of 
partici pa nts t o be recr uite d i nt o t his st u d y. T his desi g n will all o w t he c ollecti o n of U C B 0 5 9 9 data 
at eac h d os e le vel f or 8  st u d y partici pa nts of eac h et h nic ori gi n a n d t he c oll ecti o n of d ose-
C CI
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

U C B  
 
2 6 Oct 2 0 2 3  
Cli nical St u d y Pr ot oc ol A me n d me nt 1  
U C B 0 5 9 9  
U P 0 0 7 3  
 
 
 
C o nfi de ntial  
P a ge 1 4  of 1 0 1  
matc hi n g pla ce b o d ata f or 2  st u d y partici pa nts of eac h et h nic ori gi n f or eac h d ose. Partici pa nts 
will be bli n de d t o t he treat me nt (ie, U C B 0 5 9 9 or place b o), b ut n ot t o t he d osa ge wit hi n a 
se q ue nce. T he ot her o bj ecti ves are ( 1) t o assess a d diti o nal safet y a n d t olera bilit y c haracteristics 
of U C B 0 5 9 9; a n d ( 2) t o f urt her e v al uate t he P K of U C B 0 5 9 9 a n d its meta b olites (
 
) after a si n gle d ose of U C B 0 5 9 9 i n healt h y partici pa nts of J a pa nese a n d C hi nese ori gi n. 
See Secti o n  3  f or m ore d etails o n t he o bjecti ves a n d e n d p oi nts of t he st u d y. 
N u m ber of p artici p a nts  
I n Part A, a ma xi m u m of 4 2 healt h y p artici pa nts will be ra n d o ml y assi g n e d t o st u d y me dicati o n 
wit h t he ai m t hat at least 3 6 e val ua ble p artici pa nts c o m plete t he st u d y ( 6 c o m pleters i n eac h 
se q ue nce). 
I n Part B, a ma xi m u m of 3 0 healt h y p artici pa nts acr oss b ot h ori gi ns ( 1 5 of J a pa nese ori gi n a n d 
1 5 of C hi nese ori gi n) will be ra n d o ml y assi g n e d t o t he 4  treat me nts f oll o wi n g a 
U C B 0 5 9 9: place b o 4: 1 r ati o.  
Tre at me nt gr o u ps a n d d ur ati o n  
Part A c o nsists of t he f oll o wi n g (f or a t otal d ur ati o n of u p t o 6 8 da ys): 
•  A 2 8 -da y Scree ni n g Peri o d ( 2 t o 2 8 da ys b ef ore a d mi nistrati o n of st u d y m e dicati o n)  
•  A Bas eli ne healt h stat us o n a d missi o n t o st u d y sit e o n Da y -1.  
•  6 treat me nt peri o ds ( eac h treat me nt peri o d is f oll o we d b y a  4 -d a y Was h o ut Peri o d)  
− T he first 3 peri o ds i ncl u d e t he e val u ati o n of U C B 0 5 9 9 P K f oll o wi n g its si n gle -d os e 
a d mi nistrati o n ( 1 8 0 m g) of eac h f or m ulati o n u n der n or mal gastric p H c o n diti o ns.  
− T he sec o n d 3 p eri o ds i ncl u de t he e val uati o n of U C B 0 5 9 9 P K f oll o wi n g its  si n gle-d os e 
a d mi nistrati o n ( 1 8 0 m g) of eac h f or m ulati o n u n der t he c o n diti o n of ele vate d gastri c p H. 
T he ele vat e d gastric p H will be ac hie ve d b y c o -a d mi nisteri n g es o me praz ole 4 0 m g o nce 
dail y ( Q D) o ver t he d urati o n of t he 3 treat me nt peri o ds ( Da y  1 4 t o Da y  3 3; Ta ble  1 -1 ). 
•  A 7 -da y Safet y F oll o w -U p ( S F U) Peri o d  
I n Treat me nt Peri o d 1 t hr o u g h Peri o d 3 f or Part A, st u d y partici p a nts will fast o ver ni g ht f or at 
least 1 0 h o urs pri or t o st u d y me dicati o n a d mi nistrati o n o n Da y  1, Da y 6, a n d Da y 1 1, acc or di n g 
t o t he ra n d o mizati o n sc he me (see Ta ble  1 -1 ), a n d will c o nti n ue t o fast f or at least 4 h o urs 
p ost -st u d y me dicati o n a d mi nistrati o n; t hereafter partici pa nts will be gi ve n a sta n dar d brea kfast or 
li g ht s nac k. I n Treat me nt Peri o d 4 t hr o u g h Peri o d 6, st u d y partici p a nts will fast o ver ni g ht f or at 
least 9 h o urs pri or t o es o me praz ole a d mi nistrati o n o n Da y 1 9, Da y 2 4, a n d Da y 2 9, a n d will 
c o nti n ue t o fast pri or t o st u d y me dicati o n a d mi nistrati o n ( 1  h o ur f oll o wi n g es o me praz ole 
a d mi nistrati o n) a n d f or at least 4 h o urs p ost -st u d y me dicati o n a d mi nistrati o n (see Ta bl e  1 -1 ); 
t hereafter, partici pa nts will be gi ve n a sta n d ar d m eal (ie, l u nc h). I n bet w ee n eac h Treat me nt 
Peri o d, partici pa nts will u n der g o a 4 -d a y Was h o ut Peri o d. O n ot her da ys d uri n g t he Treat me nt  
Peri o d, st u d y partici pa nts will recei ve sta n d ar d meals a n d s nac ks at a p pr o priate ti mes as 
i n dicate d b y t he cli nic ce nter (see Ta ble  1 -3 ). D uri n g t he w h ol e treat me nt, p artici pa nts will 
re mai n u n der cl ose me di cal s u per visi o n i n t he cli nic. 
O n Da y 3 3, after all t he s c he d ule d pr o ce d ures ha v e bee n p erf or m e d, t he partici pa nt ma y l e a ve 
t he cli nic pr o vi de d t hat, i n t he o pi ni o n of t he I n vesti gat or, t here are n o safet y c o n cer ns. St u d y 
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

U C B  
 
2 6 Oct 2 0 2 3  
Cli nical St u d y Pr ot oc ol A me n d me nt 1  
U C B 0 5 9 9  
U P 0 0 7 3  
 
 
 
C o nfi de ntial  
P a ge 1 5  of 1 0 1  
partici pa nts will ret ur n t o t he cli nic t o c o m plete t he S F U assess me nts. Bl o o d sa m ples f or 
deter mi nati o n of plas ma U C B 0 5 9 9 a n d its 
 meta b olites will be c ollecte d 
o ver 9 6 h o urs p ost d ose (s ee Sc he d ule of Acti vities, Secti o n  1. 3 ). Of n ote, f or s u bst u d y 2 
( Treat me nt Peri o ds 4 t hr o u g h 6), t h e bl o o d sa m pli n g ti me p oi nts will be base d u p o n t he ti mi n g of 
U C B 0 5 9 9 a d mi nistrati o n (t o occ ur 1 h o ur after P PI a d mi nistrati o n).  
Part B  c o nsists of t he f oll o wi n g peri o ds (f or a t otal d urati o n of u p t o 4 5 da ys):  
•  A 2 8 -da y Scree ni n g Peri o d ( 2 t o 2 8 da ys b ef ore a d mi nistrati o n of st u d y m e dicati o n)  
•  2 treat me nt peri o ds (f or a t otal d urati o n of u p t o 1 0 da ys) 
− Eli gi ble st u d y p artici pa nts will c o m me nce t he Treat me nt Peri o d o n Da y  -1. Eac h 
partici pa nt e nr olle d will recei ve a si n gl e oral d ose of U C B 0 5 9 9 (f or m ulati o n  selecte d i n 
Part A) or pla ce b o o n D a y  1 ( 9 0 m g or 1 8 0 m g or 3 6 0 m g of U C B 0 5 9 9 or matc hi n g 
place b o), i n acc or da nce wit h t he ra n d o mizati o n sc he d ule (s ee Ta bl e  1 -2 ). St u d y 
partici pa nts will be a d mi nistere d t he sec o n d si n gl e oral d ose of U C B 0 5 9 9 or place b o o n 
Da y 6. I n bet w ee n eac h Treat me nt Peri o d, partici pa nts will u n der g o a 4-da y W as h o ut 
Peri o d. D uri n g t h e w h ole treat me nt, partici pa nts will re mai n u n der cl os e me dical 
s u per visi o n i n t he cli nic. 
•  A S F U Peri o d ( 7 da ys aft er t he last st u d y m e dicati o n a d mi nistrati o n)  
I n Treat me nt Peri o d 1 t hr o u g h Peri o d 2 f or Part B, st u d y partici p a nts will fast o ver ni g ht f or at 
least 1 0 h o urs pri or t o st u d y me dicati o n a d mi nistratio n o n Da y 1 a n d Da y 6, a n d c o nti n ue t o fast 
f or at least 4 h o urs p ost -st u d y me dicati o n a d mi nistrati o n. T hereafter partici pa nts will be gi ve n a 
sta n dar d brea kfast or li g ht s nac k (see Ta ble  1 -2  a n d Ta ble  1 -4 ). 
O n Da y 1 0, after all t he s c he d ule d pr o ce d ures ha v e bee n p erf or m e d, t he st u d y partici pa nt ma y 
lea ve t he cli nic pr o vi de d t hat, i n t he o pi ni o n of t he I n v esti gat or, t here are n o safet y c o n cer ns. 
St u d y p artici pa nts will ret ur n t o t he cli nic t o c o m plete t he S F U ass ess me nts. Bl o o d sa m ples f or 
deter mi nati o n of plas ma U C B 0 5 9 9 a n d its 
 meta b olites will be c ollecte d 
o ver 9 6 h o urs p ost d ose (s ee Sc he d ule of Acti vities, Secti o n  1. 3 ). U p t o a ma xi m u m of 
6  re place me nts will be tar gete d i n cas e partici p a nts disc o nti n ue Part B (see Secti o n  7 ). 
 
C CI
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

U C B  
 
2 6 Oct 2 0 2 3  
Cli nical St u d y Pr ot oc ol A me n d me nt 1  
U C B 0 5 9 9  
U P 0 0 7 3  
 
 
 
C o nfi de ntial  
P a ge 1 6  of 1 0 1  
1. 2  
S c h e m a  
Fi g ur e  1 -1 : O v er all st u d y s c h e m ati c  
 
C = C hi nese partici pa nts; J =J a pa nese partici pa nts; P K = p har mac o ki netic(s); P PI = pr ot o n p u m p i n hi bit or; Q D = o nce dail y; S M C = Safet y M o nit ori n g C o m mittee  
N ote: A:  1 8 0 m g ( 9 0 m g x 2 gr a n ules i n ca ps ule) c urre nt cli ni cal f or m ulati o n (refere nce f or m ulati o n);  B:  1 8 0 m g n o n -e nc a ps ulate d ta blet c o ntai ni n g 
; 
C:  1 8 0 m g e nca ps ulate d ta blet c o ntai ni n g 
. 
N ote: T he P PI es o me praz ole 4 0 m g Q D will be a d mi nistrate d o n 2 0 -c o nsec uti ve da ys d uri n g s u bst u d y 2.  
C CI
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

U C B  
 
2 6 Oct 2 0 2 3  
Cli nical St u d y Pr ot oc ol A me n d me nt 1  
U C B 0 5 9 9  
U P 0 0 7 3  
 
 
 
C o nfi de ntial  
P a ge 1 7  of 1 0 1  
T a bl e  1 -1 : 
P art A d e si g n: R el ati v e bi o a v ail a bilit y of U C B 0 5 9 9 u n d er n or m al or el e v at e d g a stri c p H c o n diti o n s  
i n h e alt h y p arti ci p a nt s ( 3-tr e at m e nt, 6-p eri o d c o m pl et e bl o c k d e si g n)  
Se q ue nce  
( D urati o n) 
P eri o d 
1  
( D 1) 
W O  
( D 2-5)  
P eri o d 
2  
( D 6) 
W O 
( D 7-1 0)  
P eri o d  
3 ( D 1 1) 
W O
a 
( D 1 2-1 8)  
P eri o d  
4  
( D 1 9) 
W O  
( D 2 0-2 3)  
P eri o d  
5  
( D 2 4) 
W O  
( D 2 5-2 8)  
P eri o d  
6  
( D 2 9) 
W O  
( D 3 0-3 3)  
1 ( A B C) 
A  
 
B  
 
C  
P PI start 
( D 1 4) 
A  
 
B  
 
C  
 
2 ( A C B)  
A  
 
C  
 
B  
P PI start 
( D 1 4) 
A  
 
C  
 
B  
 
3 ( B C A)  
B  
 
C  
 
A  
P PI start 
( D 1 4) 
B  
 
C  
 
A  
 
4 ( B A C)  
B  
 
A  
 
C  
P PI start 
( D 1 4) 
B  
 
A  
 
C  
 
5 ( C A B)  
C  
 
A  
 
B  
P PI start 
( D 1 4) 
C  
 
A  
 
B  
 
6 ( C B A)  
C  
 
B  
 
A  
P PI start 
( D 1 4) 
C  
 
B  
 
A  
 
D = da y;  P PI = pr ot o n p u m p i n hi bit or; Q D = o nce dail y; W O = Was h o ut P eri o d  
N ote: A: 1 8 0 m g ( 9 0 m g x 2 gra n ules i n ca ps ule) c urre nt cli ni cal f or m ulati o n (refere nce f or m ulati o n); B: 1 8 0 m g n o n -e nc a ps ulate d ta blet c o ntai ni n g  
 
; C: 1 8 0 m g e nca ps ulate d t a blet c o ntai ni n g 
 
N ote: T he was h o ut of U C B 0 5 9 9 will ta ke place after eac h p eri o d a n d last f or 4 da ys.  
N ote : All 6 d osi n g da ys will be i n a faste d state. I n Treat me nt P eri o d 1 t hr o u g h P eri o d 3, st u d y partici pa nts will fast o ver ni g ht f or at least 1 0 h o urs pri or t o 
st u d y me dicati o n a d mi nistrati o n o n Da y 1, Da y 6, a n d Da y 1 1, a n d will c o nti n ue t o fast f or at least 4 h o urs p ost -st u d y me dicati o n a d mi nistrati o n. I n 
Treat me nt P eri o d 4 t hr o u g h P eri o d 6, st u d y partici pa nts will fast o ver ni g ht f or at least 9 h o urs pri or t o es o me praz ole a d mi nistrati o n o n Da y 1 9, Da y 2 4, a n d 
Da y 2 9, a n d will c o nti n ue t o fast pri or t o st u d y me dicati o n a d mi nistrati o n, w hic h will be ta ke n 1 h o ur f oll o wi n g es o me pr az ole  a d mi nistrati o n, a n d f or at 
least 4 h o urs p ost-st u d y me dic ati o n a dmi nistrati o n. N o fl ui d i nta ke, a part fr o m t he fl ui d gi ve n at t he ti me of st u d y me dicati o n i nta ke, is all o we d fr o m 2 h o urs 
bef ore u ntil 2  h o urs after d osi n g of st u d y me dicati o n ( Secti o n  5. 3. 1 ). 
a T he P PI es o me praz ole will be a d mi nistrate d at a d ose of 4 0 m g Q D starti n g at t he Was h o ut P eri o d a n d f or 2 0 -c o nsec uti ve da ys ( D 1 4 -D 3 3).  
 
 
C CI
C CI
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

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Clinical Study Protocol Amendment 1 
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Table 1-2: 
Part B design: The PK of UCB0599 in healthy Japanese and Chinese participants under normal 
gastric pH conditions (4-treatment, 6-sequence, 2-period crossover design) 
Sequence 
(Duration) 
Period 1 
(D1) 
WO 
(D2-5) 
Period 2 
(D6) 
WO 
(D7-10) 
1 
Placebo 90mg SD 
 
Placebo 180mg SD 
 
2 
UCB0599 90mg SD 
 
UCB0599 180mg SD 
 
3 
Placebo 180mg SD 
 
Placebo 360mg SD 
 
4 
UCB0599 180mg SD 
 
UCB0599 360mg SD 
 
5 
Placebo 360mg SD 
 
Placebo 90mg SD 
 
6 
UCB0599 360mg SD 
 
UCB0599 90mg SD 
 
D=day; PK=pharmacokinetic(s); SD=single dose; WO=Washout Period 
Note: Of the 30 study participants enrolled in Part B, 15 participants of each ethnic origin will be randomized to the 4 treatments (placebo SD, 
UCB0599 90mg SD, UCB0599 180mg SD, and UCB0599 360mg SD) following a UCB0599:placebo 4:1 ratio. All participants will be dosed under fasting 
conditions. Study participants will fast overnight for at least 10 hours prior to study medication administration and will continue to fast for at least 4 hours 
post-study medication administration. No fluid intake, apart from the fluid given at the time of study medication intake, is allowed from 2 hours before until 
2 hours after dosing of study medication (Section 5.3.1). The Washout Period will take place after each period and last for 4 days. 
 
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1.3 
Schedule of activities 
Table 1-3: 
Part A Schedule of activities 
Procedure 
Screening 
Treatment Period 1—6a 
SFUb / 
ETV 
In-Clinic Period 
D-28 
to 
D-2 
D-1 
D1 
D2 
to 
D5 
D6 
D7 
to 
D10 
D11 
D12 
to 
D18c 
D19 
D20 
to 
D23 
D24 
D25 
to 
D28 
D29 
D30 
to 
D33 
Day 37 
(± 2 days) 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Verification of 
inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography (height, 
weight, BMI) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
 
 
 
 
 
Xd 
(D14) 
 
 
 
 
 
Xd 
(D33) 
X 
General medical/procedure 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy teste (females 
only) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Laboratory assessments 
(hematology, clinical 
chemistry, and urinalysis)f 
X 
X 
 
 
 
 
 
Xg 
(D14) 
 
 
 
 
 
Xg 
(D33) 
X 
SARS-CoV-2 testing 
(PCR)h 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Viral serology (HBsAg, 
HCV-Ab, and HIV) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine cotinine, drug 
screen, and alcohol breath 
test 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECGi 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
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Table 1-3: 
Part A Schedule of activities 
Procedure 
Screening 
Treatment Period 1—6a 
SFUb / 
ETV 
In-Clinic Period 
D-28 
to 
D-2 
D-1 
D1 
D2 
to 
D5 
D6 
D7 
to 
D10 
D11 
D12 
to 
D18c 
D19 
D20 
to 
D23 
D24 
D25 
to 
D28 
D29 
D30 
to 
D33 
Day 37 
(± 2 days) 
Vital signsj 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
Randomization 
 
Xk 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study medication 
administrationk 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Esomeprazole 
administrationc 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
Adverse event review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication 
review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood sampling for PKl 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Genetic blood sampling 
 
 
Xm 
 
 
 
 
 
 
 
 
 
 
 
 
Meals 
 
Xn 
Xo 
Xn 
Xo 
Xn 
Xo 
Xn 
Xo 
Xn 
Xo 
Xn 
Xo 
Xn 
 
Confinement 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xp 
 
AKI=acute kidney injury; BMI=body mass index; BP=blood pressure; COVID-19=Coronavirus Disease 2019; D=Day; ECG=electrocardiogram; 
ETV=Early Termination Visit; HBsAg=hepatitis B surface antigen; HCV=hepatitis C virus; HIV=human immunodeficiency virus; IRT=interactive 
response technology; PCR=polymerase chain reaction; PK=pharmacokinetic(s); QD=once daily; SARS-CoV-2=severe acute respiratory syndrome 
coronavirus 2; SFU=Safety Follow-Up 
a Each study participant will attend 6 treatment periods and will be in the clinical center for every Treatment Period 1, 2, 3, 4, 5 and 6. In Treatment Period 4, 
an oral dose of 40mg esomeprazole will be administered QD for 20-consecutive days from Day 14 to Day 33. On Day 19, Day 24, and Day 29, a single oral 
dose of 180mg UCB0599 will be administered 1 hour after intake of esomeprazole. All 6 dosing days will be in a fasted state (Section 5.3.1). The washout of 
UCB0599 will take place after each period and last for 4 days. 
b Study participants will have SFU procedures performed within 10 days after last dose. Participants who prematurely withdraw from the study will have the 
ETV as soon as possible after the time of withdrawal, and will have all SFU procedures performed. 
c An oral dose of 40mg esomeprazole will be administered QD for 20-consecutive days from Day 14 to Day 33. 
d The physical examination will only be performed on Day 14 and Day 33 during the treatment periods. 
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Table 1-3: 
Part A Schedule of activities 
Procedure 
Screening 
Treatment Period 1—6a 
SFUb / 
ETV 
In-Clinic Period 
D-28 
to 
D-2 
D-1 
D1 
D2 
to 
D5 
D6 
D7 
to 
D10 
D11 
D12 
to 
D18c 
D19 
D20 
to 
D23 
D24 
D25 
to 
D28 
D29 
D30 
to 
D33 
Day 37 
(± 2 days) 
e The blood pregnancy test will be done at the Screening Visit and the urine pregnancy test will be done on all other occasions. 
f Blood hematology and chemistry laboratory tests will be obtained in the fasting state following an overnight fast of at least 10 hours. Urinalysis includes 
standard analysis, microscopy, and renal biomarker analysis. For the AKI biomarkers, analysis should be performed on the fresh urine sample. Spot analysis 
will be performed on either fresh urinalysis sample or 24 hours urine sample, as noted. 
g Only performed on Day 14 and Day 33. 
h A COVID-19 test will take place per site standard to allow flexibility in the event the COVID-19 response plan changes throughout the study (ie, frequency 
of testing). 
i During the Screening Period, at Baseline (only if the ECG was done more than 3 days before screening [between D-28 and D-2, inclusive]), and on Day 1, 
the 12-lead ECG (single recordings) will be performed after a rest of at least 10 minutes predose and 2 hours after dosing. If there are abnormalities that are 
considered clinically significant for a particular study participant, ECG recordings will be performed in triplicate at 2- to 3-minute intervals (3 ECGs within a 
5-minute timeframe) prior to the exclusion of the participant (Section 7.1.2). 
j Systolic and diastolic blood pressure, respiration rate, pulse rate, and tympanic body temperature will be assessed. Vital signs will be performed after a rest 
of at least 5 minutes predose, then 30 min, and 2 hours after study medication dosing on Day 1, Day 6, Day 11, Day 19, Day 24, and Day 29. Vital signs (to 
be taken before blood collection for laboratory tests) will consist of 3 pulse rates and 3 blood pressure (BP) measurements (3 consecutive BP readings will 
be recorded at intervals of at least 1 minute). 
k An IRT will be used for assigning eligible participants to a treatment regimen based on a predetermined production randomization and/or packaging 
schedule provided by UCB (or designee) (Section 6.3). 
l The PK sampling time points will be done at predose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, and 96 hours after UCB0599 administration. 
m Genetic blood sampling will be mandatory for study participation and will be performed on Day 1 (Section 8.7). 
n Study participants will receive standard meals and snacks at appropriate times as indicated by the clinic center, except for when they are required to fast. 
o In Treatment Period 1 through Period 3, study participants will fast overnight for at least 10 hours prior to study medication administration on Day 1, Day 6, 
and Day 11, and will continue to fast for at least 4 hours after study medication administration; thereafter participants will be given a standard meal (ie, 
lunch). In Treatment Period 4 through Period 6, study participants will fast overnight for at least 9 hours prior to esomeprazole administration on Day 19, 
Day 24, and Day 29, and will continue to fast prior to study medication administration (1 hour following esomeprazole administration) and for at least 
4 hours post-study medication administration; thereafter study participants will be given a standard meal (ie, lunch). No fluid intake, apart from the fluid 
given at the time of study medication intake, is allowed from 2 hours before until 2 hours after dosing of study medication. For the rest of the day, study 
participants will receive standard meals and snacks at appropriate times as indicated by the clinic center (Section 5.3.1). 
p Study participants will be discharged from the clinic center after the 96-hour PK sampling time point. 
 
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Clinical Study Protocol Amendment 1 
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Table 1-4: 
Part B Schedule of Activities 
Procedure 
Screening 
Treatment Period 1 
Treatment Period 2 
SFUa/ETV 
In-Clinic Period 
In-Clinic Period 
D-28 to  
D-2 
D-1 
D1 
D2-4 
D5 
D6 
D7-9 
D10 
D13 
(±2 days) 
Informed consent 
X 
 
 
 
 
 
 
 
 
Verification of inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
Demography (height, weight, BMI) 
X 
 
 
 
 
 
 
 
 
Physical examination 
X 
X 
 
 
X 
 
 
X 
X 
General medical/procedure history 
X 
X 
 
 
 
 
 
 
 
Pregnancy testb (females only) 
X 
X 
 
 
 
 
 
 
X 
Laboratory assessments (hematology, 
clinical chemistry, and urinalysis)c 
X 
X 
 
 
X 
 
 
X 
X 
SARS-CoV-2 testing (PCR)d 
 
X 
 
 
 
 
 
 
 
Viral serology (HBsAg, HCV-Ab, and 
HIV) 
X 
 
 
 
 
 
 
 
 
Urine cotinine, drug screen, and alcohol 
breath test 
X 
X 
 
 
 
 
 
 
 
12-lead ECGe 
X 
X 
X 
X 
 
X 
X 
 
X 
Vital signsf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomizationg 
 
X 
 
 
 
 
 
 
 
Study medication administrationg 
 
 
X 
 
 
X 
 
 
 
Adverse event review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medication review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood sampling for PKh 
 
 
X 
X 
X 
X 
X 
X 
 
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Clinical Study Protocol Amendment 1 
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Table 1-4: 
Part B Schedule of Activities 
Procedure 
Screening 
Treatment Period 1 
Treatment Period 2 
SFUa/ETV 
In-Clinic Period 
In-Clinic Period 
D-28 to  
D-2 
D-1 
D1 
D2-4 
D5 
D6 
D7-9 
D10 
D13 
(±2 days) 
Genetic blood sampling 
 
 
Xi 
 
 
 
 
 
 
Mealsj 
 
X 
Xk 
X 
X 
Xk 
X 
X 
 
Confinement 
 
X 
X 
X 
X 
X 
X 
Xl 
 
AE=adverse event; AKI=acute kidney injury; BMI=body weight index; COVID-19=Coronavirus Disease 2019; D=Day; ECG=electrocardiogram; ETV=Early 
Termination Visit; HBsAg=hepatitis B surface antigen; HCV=hepatitis C virus; HIV=human immunodeficiency virus; PCR= polymerase chain reaction; 
PK=pharmacokinetic(s); QD=once daily; SFU=Safety Follow Up 
a An SFU Visit is planned after 7 days of the last study medication administration. Participants who prematurely withdraw from the study will have the ETV 
as soon as possible after the time of withdrawal, and will have all SFU procedures performed. 
b The blood pregnancy test will be done at the Screening Visit and the urine pregnancy test will be done on all other occasions. 
c Blood hematology and chemistry laboratory tests will be obtained in the fasting state following an overnight fast of at least 10 hours. Urinalysis includes 
standard analysis, microscopy, and renal biomarker analysis. For the AKI biomarkers, analysis should be performed on the fresh urine sample. Spot analysis 
will be performed on either fresh urinalysis sample or 24 hours urine sample, as noted. 
d A COVID-19 test will take place per site standard to allow flexibility in the event the COVID-19 response plan changes throughout the study (ie, frequency 
of testing). 
e 12-lead ECGs (single recordings) will be performed during the Screening Period, at Baseline (only if the ECG was done more than 3 days before screening 
[between D-28 and D-2, inclusive]), Day 1 (after a rest of at least 10 minutes predose and 2 hours after dosing), Day 2 (24 hours postdose), Day 6 (after a 
rest of at least 10 minutes predose and 2 hours after dosing), Day 7 (24 hours postdose), and the SFU Visit. If there are abnormalities that are considered 
clinically significant for a particular study participant, ECG recordings will be performed in triplicate at 2- to 3-minute intervals (3 ECGs within a 5-minute 
timeframe) prior to the exclusion of the participant (Section 7.1.2). 
f Systolic and diastolic blood pressure, respiration rate, pulse rate, and tympanic body temperature will be assessed. Vital signs will be performed after a rest 
of at least 5 minutes. On Day 1 and Day 6, vital signs will be measured predose, then 30 minutes, 2 hours, and 24 hours after study medication 
administration. 
g An IRT will be used for assigning eligible participants to a treatment regimen based on a predetermined production randomization and/or packaging 
schedule provided by UCB (or designee) (see Section 6.3). Study participants will receive 3 dose levels (90mg, 180mg, and 360mg) of UCB0599 or placebo 
under normal gastric pH conditions. The Washout Period will take place after each period and last for 4 days. See Section 4.1 for details on the overall study 
design of Part B. 
h The PK sampling time points will be done at predose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, and 96 hours after UCB0599 administration. 
i Genetic blood sampling will be mandatory for study participation and will be performed on Day 1 (Section 8.7). 
j Study participants will receive standard meals and snacks at appropriate times as indicated by the clinic center, except for when they are required to fast. 
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Table 1-4: 
Part B Schedule of Activities 
Procedure 
Screening 
Treatment Period 1 
Treatment Period 2 
SFUa/ETV 
In-Clinic Period 
In-Clinic Period 
D-28 to  
D-2 
D-1 
D1 
D2-4 
D5 
D6 
D7-9 
D10 
D13 
(±2 days) 
k In Treatment Period 1 and Period 2, study participants will fast overnight for at least 10 hours prior to study medication administration on Day 1 and Day 6, 
and will continue to fast for at least 4 hours after study medication administration; thereafter study participants will be given a standard meal (ie, lunch). No 
fluid intake, apart from the fluid given at the time of study medication intake, is allowed from 2 hours before until 2 hours after dosing of study medication 
(Section 5.3.1). 
l Study participants will be discharged from the clinic center after the 96-hour PK sampling time point. 
 
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U C B  
 
2 6 Oct 2 0 2 3  
Cli nical St u d y Pr ot oc ol A me n d me nt 1  
U C B 0 5 9 9  
U P 0 0 7 3  
 
 
 
C o nfi de ntial  
P a ge 2 5  of 1 0 1  
2  
I N T R O D U C TI O N 
2. 1  
St u d y r ati o n al e  
U C B 0 5 9 9 is a n orall y a v aila ble i n hi bit or of A S Y N misf ol di n g a n d d o w nstrea m A S Y N 
a g gre gati o n. A g gre gat e d f or ms of A S Y N are t he hall mar k fi brillar pr otei n d e p osit s i n 
Par ki ns o n’s disease ( P D) a n d ot her s y n uclei n o p at hies, a n d e vi de nce s u g gests t hat t he misf ol de d 
f or ms of A S Y N pr o p a gat e t hr o u g h t he ce ntral ner v o us s yste m ( C N S) d uri n g diseas e pr o gressi o n. 
T he acc u m ulati o n of A S Y N f or ms ne ur o nal i ncl usi o ns referre d t o as Le w y b o dies a n d Le w y 
ne urites.  
T he c urre nt st u d y, U P 0 0 7 3, is desi g ne d t o e val uat e t he relati ve bi o a vaila bilt y of 2 ne w 
f or m ulati o ns c o m pare d wit h t he c urre nt cli nical f or m ulati o n a n d t he effect of es o me praz ole o n 
t he P K of U C B 0 5 9 9 i n h ealt h y p artici pa nts ( Part A, o pe n-la bel); a n d t o assess t he safet y, 
t olera bilit y, a n d P K of U C B 0 5 9 9 i n healt h y partici pa nts of J a pa nese a n d C hi nese ori gi ns ( Part B, 
d o u ble -bli n d).  
U C B 0 5 9 9, a w ea k basi c dr u g ( p Ka  of 6. 8) f oll o wi n g oral d ose a d mi nistrati o n i n h u ma ns, is 
e x pecte d t o u n der g o p H -de pe n de nt a bs or pti o n o ver differe nt se g me nts of t he GI tract. H o we v er, 
it is n ot k n o w n w het her a n ele vate d gastric p H affects t he s yste mic e x p os ure of U C B 0 5 9 9 a n d its 
meta b oli tes (
 meta b olite) f or t he c urre nt cli nical f or m ulati o n. F or t his 
reas o n, i n Part A, U P 0 0 7 3 will e val uate 2 f or m ulati o ns (ie, 1 8 0 m g fil m -c o ate d ta blet c o ntai ni n g 
 wit h or wit h o ut e nca ps ulati o n) t o ass ess t he relati ve bi oa v aila bilit y of 
1 8 0 m g  U C B 0 5 9 9 c o m pare d wit h t he c urre nt cli ni cal f or m ulati o n (ie, gra n ules i n ca ps ule) i n 
healt h y p artici pa nts.  T he h y p ot hesis f or t h e i ntr o d ucti o n of 
 i n t he ta blet is t he a bilit y 
of t his e x ci pie nt t o re d uce t he micr oe n vir o n m e ntal p H of t he disi nte grati n g ta blet a n d p ote ntiall y 
e n ha nce dr u g diss ol uti o n i n t he st o mac h, i n de pe n de nt of gastric p H. T h us, t he e nca ps ulati o n is 
i n vesti gate d si nce it ma y e xte n d t he d urati o n of dr u g diss ol uti o n d uri n g l o w micr oe n vir o n me ntal 
p H.  Part  A will als o e val uate dr u g s yste mic e x p os ure u n der b ot h  n or mal a n d  ele vate d gastric p H 
c o n diti o ns. T he ele vati o n of t he gastric p H i n healt h y partici pa nts will be ac hie ve d t hr o u g h t he 
a d mi nistrati o n of es o me praz ole. T his a p pr oac h will assess U C B 0 5 9 9 e x p os ure fr o m f il m-c o ate d 
ta blets wit h or wit h o ut e nca ps ulati o n t o i nf or m f or m ulati o n de vel o p me nt. 
Part B of t his st u d y is a n et h n o bri d gi n g st u d y e v al uati n g t he safet y, t olera bilit y, a n d P K of a 
si n gle oral d ose of U C B 0 5 9 9 at 3 d ose le vels ( 9 0 m g, 1 8 0 m g, a n d 3 6 0 m g) u n der n or mal gastri c 
p H c o n diti o ns i n healt h y partici pa nts of J a pa nese a n d C hi nese ori gi ns.  
2. 2  
B a c k gr o u n d  
Par ki ns o n’s disease is a pr o gressi ve ne ur o de ge nerati ve dis or der t hat pr ese nts wit h a s pectr u m of 
m ot or a n d n o n m ot or si g ns a n d s y m pt o ms. T he mea n a ge at o nset i s 6 0 years. T he i nci de nce of 
P D is a p pr o xi matel y 2 0/ 1 0 0, 0 0 0 pers o ns per year; h o we ver, it is m uc h hi g her i n t he p o p ulati o n 
a ge d 6 5 years or ol der ( > 1 0 0/ 1 0 0, 0 0 0 pers o ns per year) ( T wel v es et al, 2 0 0 3). T he cli nical 
dia g n osis of P D relies o n t he prese n ce of t he car di nal m ot or si g ns: bra d y ki nesia, ri gi dit y, tre m or, 
a n d p ost ural i nsta bilit y. H o we ver, n o n m ot or s y m pt o ms s uc h as l oss of s mell, de pressi o n, 
c o nsti pati o n, d ysa ut o n o mia, a n d ra pi d e ye m o ve me nt slee p be ha vi or dis or der ca n occ ur se v eral 
years bef ore t h e o nset of m ot or s y m pt o ms.  
Earl y -sta ge P D is c h aract erize d b y mil d, ma na gea ble m ot or s y m pt o ms t hat ma y n ot r e q uire 
s y m pt o matic treat me nt or t hat s h o w a g o o d res p o nse t o l o w-d ose le v o d o pa, w hic h re prese nts t he 
C CI
C CI
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

UCB 
 
26 Oct 2023 
Clinical Study Protocol Amendment 1 
UCB0599 
UP0073 
 
 
 
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standard of care (SoC) first-line symptomatic treatment. Other commonly used SoC symptomatic 
medications include dopamine agonists, monoamine oxidase-B inhibitors, and 
catechol-O-methyltransferase inhibitors. 
Parkinson’s disease is pathologically characterized by the loss of dopaminergic neurons in the 
substantia nigra, associated with ASYN pathology (neuronal cytosolic inclusions called Lewy 
bodies, which consist of misfolded, pathological aggregates of ASYN). Treatments that prevent 
misfolding and aggregation of ASYN may slow the neurodegeneration in PD, resulting in slower 
progression of motor symptoms, thus providing a therapeutic benefit to patients with PD. 
UCB0599 is an orally available inhibitor of ASYN misfolding and downstream ASYN 
aggregation. In vivo and nonclinical pharmacology data suggest UCB0599 may slow 
neurodegeneration in PD, resulting in slower disease progression, thus providing a therapeutic 
benefit to patients with PD. 
UCB0599 has not been approved by any health authorities worldwide as of the date of this 
document. UCB has conducted 5 Phase 1 clinical studies to support the development of 
UCB0599 that have demonstrated good PK properties and an acceptable safety and tolerability 
profile (UP0023, UP0030, TM0017, and UP0077) as well as a minimal food effect on the PK 
profile for UCB0599 (UP0078). Minzalsolmin is currently being tested in a running Phase 2a 
trial (PD0053) and its extension study (PD0055). Further information regarding UP0023, 
UP0030, TM0017, UP0077, and UP0078 is provided in the Investigator’s Brochure (IB). 
2.3 
Benefit/risk assessment 
This study will not provide any benefit to the study population, ie, healthy study participants, 
instead it will provide relevant pharmacological and clinical safety information to support 
UCB0599 new formulation development as well as to support the further development of 
UCB0599 in Japanese and Chinese populations. In Phase 1 development of UCB0599, 5 studies 
(UP0030, TM0017, UP0023, UP0077, and UP0078) demonstrated that UCB0599 has acceptable 
safety, PK, and tolerability profiles for further clinical development. 
Drug hypersensitivity is an important identified risk for UCB0599. Cardiac effects are an 
important potential risk based on nonclinical data. Overall, the majority of treatment-emergent 
adverse events (TEAEs) seen in the Phase 1 and Phase 2 studies were mild or moderate in 
intensity and resolved. In UP0030, 2 events of hypersensitivity were reported. An additional 
2 events of hypersensitivity occurred in study participants who received UCB0599 in UP0077. A 
causal relationship between the reported events of drug hypersensitivity and UCB0599 is 
considered plausible. There have been no reports of anaphylaxis in the UCB0599 clinical 
program. 
Based on the results of UP0030, drug hypersensitivity and symptoms commonly associated with 
anaphylaxis and angioedema have been considered adverse events of special interest (AESI) and 
an important identified risk, based on reasonable clinical judgment. To minimize the risks for 
study participants, the study team at UCB and the contract research organization (CRO) will 
continue to systematically review safety data and UCB0599 exposure data. The site will be 
informed and trained appropriately about the risk of a hypersensitivity reaction (such as rash, 
angioedema, or anaphylaxis) and the actions that need to be taken in case of a hypersensitivity 
reaction. The participant will be informed by the Investigator during the consent procedure about 
the risk of a hypersensitivity reaction and other important potential risks for UCB0599. Risk 
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UCB 
 
26 Oct 2023 
Clinical Study Protocol Amendment 1 
UCB0599 
UP0073 
 
 
 
Confidential 
Page 27 of 101 
mitigation measures include using a standard approach of: (1) obtaining a detailed history of the 
hypersensitivity reaction and its evolution; (2) response with appropriate treatment, if needed; 
(3) a detailed physical examination and regular monitoring of vital signs; and, (4) the addition of 
guidance for the evaluation of suspected hypersensitivity reactions (refer to Section 8.3.6.1) and 
reporting of the suspected hypersensitivity reaction as an AESI. 
Considering the potential benefits, risks, and mitigation measures in place, the overall 
benefit-risk ratio for study participants who will be receiving single doses of UCB0599 is 
considered to be acceptable in the current study. 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events (AEs) of UCB0599 may be found in the IB. 
2.3.1 
Coronavirus Disease-2019 benefit/risk assessment 
UCB0599 is not known to exert an effect on the immune or respiratory systems, and its 
mechanism of action is not linked to immune or respiratory system agonism or inhibition. 
To date, no increased risk of infection or respiratory problems has been identified in association 
with clinical UCB0599 administration. No such risks have been identified through regular 
review of published literature. 
Although there is some evidence that severe acute respiratory syndrome coronavirus 2 
(SARS-CoV-2) might affect the CNS, there is no reason to assume on the basis of the 
mechanism of action that UCB0599 will have any substantial effect to worsen a Coronavirus 
Disease-2019 (COVID-19) infection or increase the risk of CNS and other complications in case 
a study participant acquires SARS-CoV-2. 
Therefore, UCB0599 is not expected to pose an additional risk of complications or poor 
prognosis of COVID-19. 
Considering the mechanism of action, the inclusion and exclusion criteria, and the measures to 
mitigate risks described in this protocol, the risk to study participants in UP0073, both in terms 
of exposure to SARS-CoV-2 and morbidity from COVID-19, is not expected to be significantly 
different from the general population. The benefit-risk profile of UCB0599 in UP0073 in the 
context of COVID-19 vaccination remains positive. 
2.3.1.1 
COVID-19 risk mitigation measures 
• Current national laws and local recommendations for the prevention and control of the 
pandemic will be strictly adhered to. 
• Participants are asked to follow the visit schedule to the extent possible. If they are unable to 
come to the study site, the Investigator may contact the participant directly via telephone 
and/or video conference calls. 
• Participants will be closely monitored for and encouraged to report any signs and symptoms 
of COVID-19. The Investigator will consider the individual benefit/risk of the study 
participant upon identification of any signs and symptoms of COVID-19 infection (eg, 
continuation of dosing, site visits). 
• COVID-19 testing by optional laboratory assessment will be conducted based on availability 
and other practical considerations (eg, test capacity and turnaround time) of approved tests 
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UCB 
 
26 Oct 2023 
Clinical Study Protocol Amendment 1 
UCB0599 
UP0073 
 
 
 
Confidential 
Page 28 of 101 
and at the Investigator’s discretion. The Investigator will consider the individual benefit/risk 
of the study participant in case of a positive COVID-19 test. 
• The possibility of virus transmission will be controlled as much as possible by: 
− Advising participants to adhere to local requirements for reduction of exposure to the 
public while ambulatory. 
− Advising participants to adhere to clinical site requirements for reduction of exposure 
while at the site or interacting with site staff. This advice will be included in the Informed 
Consent form (ICF). 
• COVID-19 testing for clinical staff will be conducted if required by local guidelines. 
2.3.1.2 
COVID-19 benefit/risk conclusion 
Considering the mechanism of action of UCB0599, the inclusion and exclusion criteria, and the 
measures to mitigate risks described in this protocol, the risk to study participants in UP0073, 
both in terms of exposure to SARS CoV-2 and morbidity from COVID-19, is not expected to be 
significantly different from the general population. 
3 
OBJECTIVES AND ENDPOINTS 
Table 3-1: 
Part A: The relative bioavailability in reference to the current 
clinical formulation in the presence and absence of PPI 
(esomeprazole) of 2 new UCB0599 formulations and the PK of 
UCB0599 after a single dose in healthy participants 
Objectives 
Endpoints 
Primary 
• To estimate the relative bioavailability of 
2 new UCB0599 formulations versus 
reference ‘granules in capsule’ 
formulation under elevated gastric pH and 
under normal conditions in healthy 
participants 
PK endpoints of UCB0599 
• Cmax 
• AUC0-t 
• AUCinf 
Secondary 
• To evaluate for each formulation the 
safety and tolerability of single dose 
UCB0599 alone under elevated gastric pH 
and under normal conditions in healthy 
participants 
Safety endpoints 
• Incidence of TEAEs 
• Incidence of treatment-emergent SAEs 
• Incidence of TEAEs leading to 
withdrawal from study 
Other 
• To estimate the relative bioavailability of 
UCB0599 under elevated gastric pH 
Other PK endpoints 
• For UCB0599: 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

U C B  
 
2 6 Oct 2 0 2 3  
Cli nical St u d y Pr ot oc ol A me n d me nt 1  
U C B 0 5 9 9  
U P 0 0 7 3  
 
 
 
C o nfi de ntial  
P a ge 2 9  of 1 0 1  
T a bl e  3 -1 : 
P art A:  T h e r el ati v e bi o a v ail a bilit y i n r ef er e n c e t o t h e c urr e nt 
cli ni c al f or m ul ati o n i n t h e pr e s e n c e a n d a b s e n c e of P PI 
( e s o m e pr a z ol e) of 2 n e w U C B 0 5 9 9 f or m ul ati o n s a n d t h e P K of 
U C B 0 5 9 9 aft er a si n gl e d o s e i n h e alt h y p arti ci p a nt s  
O bjecti ves  
E n d p oi nts  
vers us n or mal gastric p H f or eac h teste d 
f or m ulati o n 
•  T o f urt her e val uate t he P K of U C B 0 5 9 9 
a n d its 
 meta b olites 
after si n gle d ose U C B 0 5 9 9 al o ne a n d c o -
a d mi nistrate d wit h es o me praz ole i n 
healt h y p artici pa nts  
− C ma x , A U C0 -t, a n d A U Ci nf 
− tma x , t½ , C L/ F, a n d Vz/ F (if p ossi ble 
b ut n ot li mite d)  
•  
 meta b olites: 
− C ma x , tma x , A U C0 -t, a n d A U C i nf 
− meta b olite/ pare nt  C ma x  a n d A U C rati o 
(c orrecte d f or t he m olec ular wei g ht of 
t he e ntities), as a p pr o pr iate 
A U C i nf=area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me zer o t o i nfi nit y; A U C0 -t=area u n der t he plas ma 
c o nce ntrati o n -ti me c ur ve fr o m ti me zer o t o t; C L/ F =a p pare nt t otal b o d y cleara nce; Cma x = ma xi m u m o bser ve d 
plas ma c o nce ntrati o n; P K = p har mac o ki netic(s); S A E =seri o us a d verse e ve nt; t ½ =a p pare nt t er mi nal eli mi nati o n 
half -life; T E A E =treat me nt e mer ge nt a d verse e ve nt; tma x =ti me of occ urre nce of C ma x ; Vz/ F =a p pare nt v ol u me of 
distri b uti o n  
 
T a bl e  3 -2 : 
P art B:  T h e s af et y, t ol er a bilit y, a n d P K of U C B 0 5 9 9 aft er 
a d mi ni str ati o n of U C B 0 5 9 9 a t si n gl e d o s e i n h e alt h y p arti ci p a nt s of 
J a p a n e s e a n d C hi n e s e ori gi n s  
O bjecti ves  
E n d p oi nts  
Pri m ar y  
•  T o assess t he safet y a n d t olera bilit y of 
U C B 0 5 9 9 aft er a d mi nistrati o n of a si n gl e 
d ose of a n oral f or m ulati o n i n healt h y 
partici pa nts of J a pa nese a n d C hi nese 
ori gi ns  
Safet y e n d p oi nt  
•  I n ci de nce of T E A Es 
•  I n ci de nce of treat me nt-e mer ge nt S A Es  
•  I n ci de nce of T E A Es l ea di n g t o 
wit h dra wal fr o m st u d y  
•  T o e val uate t he pl as ma P K of U C B 0 5 9 9 
after a d mi nistrati o n of a si n gle d ose of a n 
oral f or m ulati o n i n healt h y partic i pa nts of 
J a pa nese a n d C hi nese ori gi ns 
C o -pri mar y P K e n d p oi nts f or U C B 0 5 9 9  
•  C ma x  
•  A U C 0 -t 
•  A U C i nf 
Ot her  
•  T o assess a d diti o nal safet y a n d t olera bilit y 
c haracteristics of U C B 0 5 9 9 i n healt h y 
partici pa nts of J a pa nese a n d C hi nese 
ori gi ns  
Ot her safet y e n d p oi nts  
•  C ha n ges fr o m Baseli ne i n vital si g ns 
( p ulse rate, bl o o d press ur e [ B P], 
res pirat or y rate, a n d b o d y te m perat ur e) 
C CI
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

U C B  
 
2 6 Oct 2 0 2 3  
Cli nical St u d y Pr ot oc ol A me n d me nt 1  
U C B 0 5 9 9  
U P 0 0 7 3  
 
 
 
C o nfi de ntial  
P a ge 3 0  of 1 0 1  
T a bl e  3 -2 : 
P art B:  T h e s af et y, t ol er a bilit y, a n d P K of U C B 0 5 9 9 aft er 
a d mi ni str ati o n of U C B 0 5 9 9 a t si n gl e d o s e i n h e alt h y p arti ci p a nt s of 
J a p a n e s e a n d C hi n e s e ori gi n s  
O bjecti ves  
E n d p oi nts  
•  C ha n ges fr o m Baseli ne i n safet y 
la b orat or y dat a ( he mat ol o g y, cli nical 
c he mistr y, uri nal ysis)  
•  C ha n ges fr o m Baseli ne i n 1 2 -lea d E C G 
assess me nt  
•  P h ys ical e xa mi nati o n fi n di n gs 
•  T o f urt her e val uate t he P K of U C B 0 5 9 9 
a n d its 
 meta b olites 
after a si n gle d os e of a n oral f or m ulati o n 
i n healt h y p artici pa nts of J a pa nese a n d 
C hi nese ori gi ns  
Ot her P K e n d p oi nts  
•  F or U C B 0 5 9 9:  
− tma x , C L/ F, Vz/ F, t1/ 2, Cma x / B W/ D, 
A U C 0 -t/ B W/ D, a n d A U Ci nf/ B W/ D 
•  F or 
 meta b olites: 
− C ma x , tma x , A U C0 -t, a n d A U Ci nf 
− M eta b olite/ pare nt  C ma x  a n d A U C rati o 
(c orrecte d f or t he m olec ular wei g ht of 
t he e ntities), as a p pr o pr iate 
− M eta b olite/ pare nt  C ma x  a n d A U C rati o 
(c orrecte d f or t he m olec ular wei g ht of 
t he e ntities) per p o p ulati o n, as 
a p pr o priate 
A U C i nf=area u n der t he plas ma c o nce ntrati o n -ti me c ur ve fr o m ti me zer o t o i nfi nit y; A U C0 -t=area u n der t he plas ma 
c o nce ntrati o n -ti me c ur ve fr o m ti me zer o t o t; B W = b o d y wei g ht; C L/ F =a p pare nt t otal b o d y cleara nce; 
C ma x = ma xi m u m o bser ve d plas ma c o nce ntrati o n; D = d ose; E C G = electr ocar di o gra m; P K = p har mac o ki netic(s); 
S A E =seri o us a d verse e ve nt; t ½ =a p pare nt ter mi nal eli mi nati o n half -life; T E A E =treat me nt e mer ge nt a d verse 
eve nt; t ma x =ti me of occ urre nce of C ma x ; Vz/ F =a p pare nt v ol u me of distri b uti o n 
4  
S T U D Y D E SI G N  
4. 1  
O v er all d e si g n  
U P 0 0 7 3 is a ra n d o mize d, 2 -part si n gle -d ose cr oss o ver P hase 1 st u d y. T he st u d y will e nr oll 
a p pr o xi matel y 4 2 healt h y partici pa nts i nt o o pe n -la bel Part A a n d 3 0 healt h y partici pa nts ( 1 5 of 
J a pa nese ori gi n a n d 1 5 of C hi nese ori gi n) i nt o d o u ble-bli n d Part B at a si n gle st u d y site. A st u d y 
o ver vie w of U P 0 0 7 3 is pr o vi de d i n Fi g ure  1 -1 . 
4. 1. 1  
P art A  
Part A  is a n o pe n-la b el, r a n d o mize d, 2 i n-series cr oss o ver s u bst u dies, eac h wit h a fi x e d se q ue nce 
c o m plete bl oc k desi g n of 3 treat me nt peri o ds i n healt h y male a n d fe m ale partici pa nts.  Eac h 
s u bst u d y e val u ates t he U C B 0 5 9 9 relati ve bi oa v aila bilit y of t he ne w f or m ul ati o ns ( 1 8 0 m g  fil m-
c oate d ta blet c o nt ai ni n g 
 wit h or wit h o ut e nca ps ulati o n) vers us t he c urre nt cli nical 
C CI
C CI
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

U C B  
 
2 6 Oct 2 0 2 3  
Cli nical St u d y Pr ot oc ol A me n d me nt 1  
U C B 0 5 9 9  
U P 0 0 7 3  
 
 
 
C o nfi de ntial  
P a ge 3 1  of 1 0 1  
f or m ulati o n ( 2 x 9 0 m g gra n ules i n ca ps ule) u n der b ot h n or mal a nd ele vat e d gastri c p H c o n diti o ns, 
res pecti vel y. See Secti o n 3  f or m ore det ails o n t he o bjecti ves a n d e n d p oi nts of t he st u d y. 
Part A c o nsists of t he f oll o wi n g (f or a t otal d ur ati o n of u p t o 6 8 da ys):  
•  A 2 8 -da y Scree ni n g Peri o d ( 2 t o 2 8 da ys b ef ore a d mi nistrati o n of st u d y m e dicati o n)  
•  A Bas eli ne healt h stat us o n a d missi o n t o st u d y sit e o n Da y -1.  
•  6 treat me nt peri o ds ( eac h treat me nt peri o d is f oll o we d b y a 4 -d a y Was h o ut Peri o d)  
− T he first 3 peri o ds i ncl u d e t he e val u ati o n of U C B 0 5 9 9 P K f oll o wi n g its si n gle -d os e 
a d mi nistrati o n ( 1 8 0 m g) of eac h f or m ulati o n u n der n or mal gastric p H c o n diti o ns.  
− T he sec o n d 3 p eri o ds i ncl u de t he e val uati o n of U C B 0 5 9 9 P K f oll o wi n g its si n gle -d os e 
a d mi nistrati o n ( 1 8 0 m g) of eac h f or m ulati o n u n der t he c o n diti o n of ele vate d gastri c p H. 
T he ele vat e d gastric p H will be ac hie ve d b y c o -a d mi nisteri n g es o me praz ole 4 0 m g Q D 
o ver t he d urat i o n of t he 3 treat me nt peri o ds ( Da y 1 4 t o Da y 3 3; s ee Ta bl e  1 -1 ). 
•  A 7 -da y Safet y F oll o w -U p ( S F U) Peri o d  
I n Treat me nt Peri o d 1 t hr o u g h Peri o d 3 f or Part A, st u d y partici p a nts will fast o ver ni g ht f or at 
least 1 0 h o urs pri or t o st u d y me dicati o n a d mi nistrati o n o n Da y 1, Da y 6, a n d Da y 1 1, acc or di n g 
t o t he ra n d o mizati o n sc he me (see Ta ble  1 -1 ), a n d will c o nti n ue t o fast f or at least 4 h o urs 
p ost -st u d y me dicati o n a d mi nistrati o n; t hereafter partici pa nts will be gi ve n a sta n dar d brea kfast or 
li g ht s nac k. I n Treat me nt Peri o d 4 t hr o u g h Peri o d 6, st u d y partici p a nts will fast o ver ni g ht f or at 
least 9 h o urs pri or t o es o me praz ole a d mi nistrati o n o n Da y 1 9, Da y 2 4, a n d Da y 2 9, a n d will 
c o nti n ue t o fast pri or t o st u d y me dicati o n a d mi nistrati o n ( 1  h o ur f oll o wi n g es o me praz ole 
a d mi nistrati o n) a n d f or at least 4 h o urs p ost -st u d y me dicati o n a d mi nistrati o n (see Ta bl e  1 -1 ); 
t hereafter partici pa nts will be gi ve n a sta n dar d m eal (ie, l u nc h). I n b et wee n eac h Treat me nt 
Peri o d, partici pa nts will u n der g o a 4 -d a y Was h o ut Peri o d. O n ot her da ys d uri n g t he Treat me nt  
Peri o d, st u d y partici pa nts will recei ve sta n d ar d meals a n d s nac ks at a p pr o priate ti mes as 
i n dicate d b y t he cli nic ce nter (see Ta ble  1 -3 ). D uri n g t he w h ol e treat me nt, p artici pa nts will 
re mai n u n der cl ose me di cal s u per visi o n i n t he cli nic. 
O n Da y 3 3, after all t he s c he d ule d pr o ce d ures ha v e bee n p erf or m e d, t he partic i pa nt ma y l ea ve 
t he cli nic pr o vi de d t hat, i n t he o pi ni o n of t he I n vesti gat or, t here are n o safet y c o n cer ns. St u d y 
partici pa nts will ret ur n t o t he cli nic t o c o m plete t he S F U assess me nts. Bl o o d sa m ples f or 
deter mi nati o n of plas ma U C B 0 5 9 9 a n d its 
 meta b olites will be c ollecte d 
o ver 9 6 h o urs p ost d ose (s ee Sc he d ule of Acti vities, Secti o n  1. 3 ). Of n ote, f or s u bst u d y 2 
( Treat me nt Peri o ds 4 t hr o u g h 6), t h e bl o o d sa m pli n g ti me p oi nts will be base d u p o n t he ti mi n g of 
U C B 0 5 9 9 a d mi nistrati o n (t o occ ur 1 h o ur after P PI a d mi nistrati o n).  
4. 1. 2  
P art B  
Part B of t his st u d y is a n et h n o bri d gi n g st u d y e v al uati n g t he safet y, t olera bilit y, a n d P K of a 
si n gle oral d ose of U C B 0 5 9 9 at 3 d ose le vels ( 9 0 m g, 1 8 0 m g, a n d 3 6 0 m g) u n der n or mal gastri c 
p H c o n diti o ns i n healt h y partici pa nts of J a pa nese a n d C hi nese ori gi ns. Eac h gr o u p of et h nic 
ori gi n ( N = 1 5 t otal f or eac h) will be ra n d o mize d t o a 4 -treat me nt, 6-se q ue n ce, 2-p eri o d cr oss o v er 
st u d y usi n g U C B 0 5 9 9: pl ace b o i n a 4: 1 rati o, as s h o w n bel o w a n d i n t he St u d y Sc he m a ( Fi g ure  1 -
1 ). Se q ue nce 6 will o nl y c o m me nce after Se q u e nce 5 has bee n c o m plete d f or all 4 partici pa nts. 
Se q ue nces 3 a n d 4 ( C o h ort 3) will o nl y c o m me n ce after Se q u e nces 1 a n d 2 ( C o h ort 2) ha ve b ee n 
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

U C B  
 
2 6 Oct 2 0 2 3  
Cli nical St u d y Pr ot oc ol A me n d me nt 1  
U C B 0 5 9 9  
U P 0 0 7 3  
 
 
 
C o nfi de ntial  
P a ge 3 2  of 1 0 1  
c o m plete d f or all 5  partici pa nts; Se q ue nces 5 a n d 6 ( C o h ort 4) will o nl y c o m me nce aft er 
Se q ue nces 3 a n d 4 ha ve b ee n c o m plete d f or all 5 partici pa nts all o wi n g t he S M C  re vie w t o be 
carri e d o ut bef ore t he start of Se q ue nce 5.  
•  Se q ue nce 1:  
place b o 9 0 m g, f oll o we d b y place b o 1 8 0 m g ( N = 1)  
•  Se q ue nce 2:  
U C B 0 5 9 9 9 0 m g f oll o we d b y U C B 0 5 9 9 1 8 0 m g ( N = 4)  
•  Se q ue nce 3:  
place b o 1 8 0 m g, f oll o we d b y place b o 3 6 0 m g  ( N = 1) 
•  Se q ue nce 4:  
U C B 0 5 9 9 1 8 0 m g, f oll o w e d b y U C B 0 5 9 9 3 6 0 m g ( N = 4)  
•  Se q ue nce 5:  
place b o 3 6 0 m g, f oll o we d b y place b o 9 0 m g ( N = 1)  
•  Se q ue nce 6:  
U C B 0 5 9 9 3 6 0 m g, f oll o w e d b y U C B 0 5 9 9 9 0 m g ( N = 4)  
See Secti o n  3  f or m ore d etails o n t he o bjecti ves a n d e n d p oi nts of t he st u d y. 
N o partici pa nt will e ver recei ve b ot h U C B 0 5 9 9 a n d place b o, a n d t h eref ore n o i ntra -partici pa nt 
c o m paris o n will be p ossi bl e; t he cr oss o ver as pect of t he Part B d esi g n refers t o t he d ose le vel 
o ver 2 peri o ds i n or d er t o li mit t he n u m ber of partici pa nts t o be recr uite d i nt o t his st u d y. T his 
desi g n will all o w t he c oll ecti o n of U C B 0 5 9 9 d ata at eac h d os e le vel f or 8  st u d y partici pa nts of 
eac h et h nic ori gi n a n d t h e c ollecti o n of d ose -matc hi n g place b o data f or 2  st u d y partici pa nts of 
eac h et h nic ori gi n f or eac h d ose. Partici pa nts will be bli n de d t o t he treat me nt (ie, U C B 0 5 9 9 or 
place b o), b ut n ot t o t he d osa ge wit hi n a se q ue n ce.  
Part B c o nsists of t he f oll o wi n g peri o ds (f or a t otal d urati o n of u p t o 4 5 da ys):  
•  A 2 8 -da y Scree ni n g Peri o d ( 2 t o 2 8 da ys b ef ore a d mi nistrati o n of st u d y m e dicati o n)  
•  2 treat me nt peri o ds (f or a t otal d urati o n of u p t o 1 0 da ys)  
− Eli gi ble st u d y p artici pa nts will c o m me nce t he Treat me nt Peri o d o n Da y  -1. Eac h 
partici pa nt e nr olle d will recei ve a si n gl e oral d ose of U C B 0 5 9 9 (f or m ulati o n selecte d i n 
Part A) or pla ce b o o n D a y  1 ( 9 0 m g or 1 8 0 m g or 3 6 0 m g of U C B 0 5 9 9 or matc hi n g 
place b o), i n acc or da nce wit h t he ra n d o mizati o n sc he d ule (s ee Ta bl e  1 -2 ). St u d y 
partici pa nts will be a d mi nistere d t he sec o n d si n gl e oral d ose of U C B 0 5 9 9 or place b o o n 
Da y 6. I n bet w ee n eac h Treat me nt P eri o d, partici pa nts will u n der g o a 4 -da y W as h o ut 
Peri o d. D uri n g t h e w h ole treat me nt, partici pa nts will re mai n u n der cl ose me dical 
s u per visi o n i n t he cli nic. 
•  A S F U Peri o d ( 7 da ys aft er t he last st u d y m e dicati o n a d mi nistrati o n)  
I n Treat me nt Peri o d 1 t hr o u g h Peri o d 2 f or Part B, st u d y partici p a nts will fast o ver ni g ht f or at 
least 1 0 h o urs pri or t o st u d y me dicati o n a d mi nistrati o n o n Da y 1 a n d Da y 6, a n d c o nti n ue t o fast 
f or at least 4 h o urs p ost -st u d y me dicati o n a d mi nistrati o n. T hereafter partici pa nts will be gi ve n a 
sta n dar d brea kfast or li g ht s nac k (see Ta ble  1 -2  a n d Ta ble  1 -4 ). 
O n Da y 1 0, after all t he s c he d ule d pr o ce d ures ha v e bee n p erf or m e d, t he st u d y partici pa nt ma y 
lea ve t he cli nic pr o vi de d t hat, i n t he o pi ni o n of t he I n v esti gat or, t here are n o safet y c o n cer ns. 
St u d y p artici pa nts will ret ur n t o t he cli nic t o c o m plete t he S F U ass ess me nts. Bl o o d sa m ples f or 
deter mi nati o n of plas ma U C B 0 5 9 9 a n d its 
 meta b olites will be c ollecte d 
o ver 9 6 h o urs p ost d ose (s ee Sc he d ule of Acti vities, Secti o n  1. 3 ). U p t o a ma xi m u m of 
6  re place me nts will be tar gete d i n cas e partici p a nts disc o nti n ue Part B (see Secti o n 7 ). 
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

U C B  
 
2 6 Oct 2 0 2 3  
Cli nical St u d y Pr ot oc ol A me n d me nt 1  
U C B 0 5 9 9  
U P 0 0 7 3  
 
 
 
C o nfi de ntial  
P a ge 3 3  of 1 0 1  
T here is 1 pla n ne d i nteri m a nal ysis f or Part B i n w hic h safet y d ata fr o m P art B will be a nal yz e d 
( Secti o n 9. 8 ). T hr o u g h o ut t he st u d y, data will be re vie we d o n a n o n g oi n g b asis b y a n S M C. 
4. 2  
S ci e ntifi c r ati o n al e f or st u d y d e si g n  
U P 0 0 7 3 has a 2 -part desi g n a n d is i nte n de d t o e val uate t he relati ve bi o a vail a bilt y of 2 ne w 
U C B 0 5 9 9 f or m ulati o ns ( 1 8 0 m g fil m -c o ate d ta blet c o ntai ni n g 
 wit h or wit h o ut 
e nca ps ulati o n ) v ers us  t he c urre nt cli nical f or m ulati o n (ie, 2 x 9 0 m g  gra n ules i n ca ps ule ); t o 
e val uate t he effect of es o me praz ole o n t he P K of U C B 0 5 9 9 i n healt h y partici pa nts ( Part A, o pe n-
la bel); a n d t o assess t he s afet y, t olerabilit y, a n d P K of U C B 0 5 9 9 i n healt h y partici pa nts of 
J a pa nese a n d C hi nese ori gi ns ( Part B, d o u ble -bli n d).  
Pre vi o usl y p u blis he d st u dies a n d n o ncli nical r esearc h de m o nstr ate t hat si g nifica nt et h nic 
differe n ces ca n e xist i n t he meta b olis m of s o me dr u gs, w hi c h  are ca use d b y c yt o c hr o me P 4 5 0 
( C Y P) p ol y m or p his m. C yt oc hr o m e 2 D 6, 2 C 1 9, a n d 2 C 9 p ol y m or p his ms acc o u nt f or t he m ost 
fre q ue nt v ariati o ns i n t he P hase 1 meta b olis m of dr u gs. F or e x a m ple, a p pr o xi matel y 5 t o 1 4 % of 
Ca ucasia ns a n d 0 t o 1 % of Asia ns lac k C Y P 2 D 6 acti vit y a n d are k n o w n as p o or meta b olizers. 
H o we ver, t here is i ns uffi cie nt e vi de nce t o s h o w t hat t here are s o me et h nic differe n ces f or 
C Y P 3 A 4 p ol y m or p his m. Base d o n precli nical dr u g meta b olis m st u dies, n o differe n ces i n 
e x p os ure are e x pecte d i n healt h y p a rtici pa nts of J a pa nese a n d C hi nes e ori gi ns c o m pare d wit h 
Ca ucasia n partici pa nts.  
Part B of t his st u d y will be c o n d ucte d t o ge nerate c o nti n ue d cli nical de vel o p me nt of U C B 0 5 9 9 
d oses u p t o 3 6 0 m g/ da y. T he rati o nale f or testi n g t he pr o p ose d d ose l e vels of U C B 0 5 9 9 ( 9 0 m g, 
1 8 0 m g, a n d 3 6 0 m g/ da y si n gle d ose) i n t his healt h y p o p ulati o n is base d o n data fr o m pre vi o usl y 
c o n d ucte d st u dies ( U P 0 0 3 0, U P 0 0 7 7, a n d U P 0 0 7 8) as well as P K i nf or m ati o n f or m ulti ple d ose 
e x p os ures of 1 8 0 m g/ da y f or u p t o 2 1 da ys i n el derl y healt h y v ol u nteers ( defi ne d as ≥5 5 a n d 
≤7 5  years of a ge) (see Secti o n  4. 3  f or m ore det ails). T he P K a nal ysis of U C B 0 5 9 9 re v eale d t h at 
e x p os ure i ncreas e d cl ose t o pr o p orti o nall y wit h i n creas e d d oses bet w ee n 4 5 m g a n d 4 5 0 m g 
(si n gle d os es teste d). F urt her m ore, m ulti ple d ose e x p os ures ( A U Cta u) were pre dicta ble fr o m 
si n gle d ose e x p os ures, i n dicati n g li near P K be ha vi or. T heref ore, t h e e val u ati o n of U C B 0 5 9 9 
1 8 0 m g si n gle d ose t o ass ess relati ve bi oa v aila bilit y s h o ul d pr o vi de a de q uat e g ui d a nce f or t he 
de vel o p me nt of a n e w f or m ulati o n f or f urt her cli nical de vel o p me nt i n P has e 2 a n d 3 st u dies.  
A p pr o xi matel y 2 5 % of P D patie nts recei ve aci d re d uci n g a ge nts as c o n c o mita nt  me dicati o ns t o 
ma na ge aci d refl u x t hr o u g h t he ele vati o n of t he gastric p H ( Lai et al, 2 0 2 0). U C B 0 5 9 9 is a wea k 
basic dr u g ( p Ka of 6. 8) f oll o wi n g oral d ose a d mi nistrati o n i n h u ma ns, a n d is e x pecte d t o u n der g o 
p H -de pe n d e nt a bs or pti o n o ver differe nt se g me nts  of t he GI tract, wit h m ore a bs or pti o n i n t he 
i ntesti ne ( p H ra n ge 6 t o 8) c o m pare d wit h t he u p per se g me nts of t he GI tract ( p H ra n ge is 2 t o 6). 
H o we ver, it is n ot k n o w n w het her a n ele vat e d gastric p H affects t he s yste mi c e x p os ure of 
U C B 0 5 9 9 a n d its meta b o lites (
 meta b olite) f or t he c urre nt cli nical 
f or m ulati o n. F or t his reas o n, i n Part A, U P 0 0 7 3 will e val uate 2 f or m ulati o ns (ie, fil m-c oate d 
ta blet c o ntai ni n g 
 wit h or wit h o ut e nca ps ulati o n) t o assess t he relati ve bi oa vaila bi lit y 
of 1 8 0 m g U C B 0 5 9 9 c o m pare d wit h t he c urre nt cli nical f or m ulati o n (ie, gra n ules i n ca ps ule) i n 
healt h y p artici pa nts. T he a d diti o n of 
 e x ci pie nt t o t he ne w ta blet is e x pecte d t o creat e 
a “ micr oe n vir o n me nt” i n t he ta blet w hic h s h o ul d all o w U C B 0 5 9 9 t o diss ol ve u nif or ml y i n t he 
st o mac h i n de pe n de nt of gastri c p H ( Ba d a w y a n d H ussai n, 2 0 0 7).  
C CI
C CI
C CI
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

U C B  
 
2 6 Oct 2 0 2 3  
Cli nical St u d y Pr ot oc ol A me n d me nt 1  
U C B 0 5 9 9  
U P 0 0 7 3  
 
 
 
C o nfi de ntial  
P a ge 3 4  of 1 0 1  
T he use a n d i ncl usi o n of 
 is s u p p orte d b y res ults fr o m bi orele va nt diss ol uti o n testi n g 
(Ta ni g uc hi et al, 2 0 1 4) . Data i n dicate t hat t he e nca ps ulati o n of t he ta blet ma y res ult i n a n 
i m pr o ve d r o b ust ness i n vitr o i n s o me bi o pre dicti ve i n-vitr o e x peri me nts. T his i n vitr o 
o bser vati o n ma y be e x plai ne d b y t he fact t hat t he prese nce of t he ca ps ule res ults i n a n i nti mate 
c o ntact bet w ee n t he acti ve p har mace utica l i n gre die nt ( A PI) a n d aci difier 
, t here b y 
res ulti n g i n hi g her c o nce ntrati o ns of 
 cl ose t o t he s urface of t h e A PI ( Ba da w y a n d 
H ussai n, 2 0 0 7).  
As t he c urre nt st u d y will e val uate h ealt h y p artici p a nts, ele vati o n of t he gastric p H wil l be 
ac hie ve d t hr o u g h t h e a d mi nistrati o n of a P PI (es o me praz ole), i n w hic h dr u g s yste mic e x p os ure 
will be c o m pare d i n t he a bse nce or prese n ce of P PI. T h us, t his a p pr oac h will als o all o w 
c o m paris o n of U C B 0 5 9 9 s yste mic e x p os ure fr o m fil m-c oate d ta blets wit h or wit h o ut 
e nca ps ulati o n  t o i nf or m f or m ulati o n de vel o p me nt. T he c urre nt c o m plete bl oc k st u d y d esi g n i n 
Part A will e val uate eac h st u d y partici p a nt u n der b ot h ele vate d a n d n or mal gastri c p H c o n diti o ns.  
4. 2. 1  
P ati e nt i n p ut i nt o d e si g n  
N ot a p plica ble.  
4. 3  
J u stifi c ati o n  f or d o s e 
I n Part A, t he U C B 0 5 9 9 d ose le vel of 1 8 0 m g si n gle d ose is bei n g s electe d base d o n t he P K 
pr o perties of U C B 0 5 9 9. U p o n oral i nta ke of d os es 9 0 m g t o 4 5 0 m g, b ot h C ma x  a n d A U C i ncrease 
a p pr o xi matel y li nearl y wit h d ose, i n dicati n g d ose pr o p orti o nalit y.  I n a d diti o n, cli nical data s h o w 
t hat A U C at stea d y state o ver t he d ose i nter val is si milar t o A U Ci nf after si n gle d ose, s u g gesti n g 
li near be ha vi or of U C B 0 5 9 9 i n t he cli nicall y teste d d ose ra n ge of 1 8 0 m g/ da y t o 3 6 0 m g/ da y; 
he nce U C B 0 5 9 9 1 8 0 m g si n gle d ose a d mi nistrati o n is pr ojecte d t o pr o vi de e x p os ure i nf or mati o n 
t hat ca n be use d t o bri d ge bet wee n t he c urre nt cli nical f or m ulati o n a n d a n e w f or m ulati o n. 
I n Part B, U P 0 0 7 3 will b e c o n d ucte d t o ge nerate s u p p orti ve safet y, t olera bilit y, a n d P K data i n 
healt h y p ar tici pa nts of J a pa nese a n d C hi nes e ori gi ns f or t he c o nti n ue d cli ni cal de vel o p me nt of 
U C B 0 5 9 9 d oses u p t o 3 6 0 m g/ da y. T he rati o nale f or testi n g t he pr o p os e d d ose le vels of 
U C B 0 5 9 9 ( 9 0 m g, 1 8 0 m g, a n d 3 6 0 m g/ da y si n gle d ose) i n t his healt h y p o p ul ati o n is base d o n  data 
fr o m pre vi o usl y c o n d uct e d st u dies ( U P 0 0 3 0, U P 0 0 7 7, a n d U P 0 0 7 8). U P 0 0 3 0 teste d 9 0 m g t wice 
per da y f or 2 1 da ys i n el d erl y h ealt h y partici pa nts t o assess t he safet y, t olera bilit y, a n d P K 
i nf or mati o n f or m ulti ple d ose e x p os ures. T his st u d y s h o w e d t hat U CB 0 5 9 9 e x p os ures i ncreas e d 
li nearl y ( b ot h Cma x  a n d A U C) acr oss t he t este d d os e ra n ge ( 9 0 m g t o 4 5 0 m g, si n gle d ose). 
U P 0 0 7 7 pr o vi de d t he safet y, t olera bilit y, a n d P K of U C B 0 5 9 9 f or m ulti ple d oses of 1 8 0 m g/ d a y 
a n d 3 6 0 m g/ da y i n P D patie nts. T he c ollecti ve dat a fr o m U P 0 0 3 0 a n d U P 0 0 7 7 f urt her s h o we d 
t hat e x p os ure after m ulti ple d osi n g is pre dict a ble fr o m si n gle-d ose data a n d t hat d ose -e x p os ure 
relati o ns hi p is si milar bet wee n (el derl y) healt h y partici pa nts a n d P D patie nts. T hese 2 d ose le vels 
( 1 8 0 m g/ da y a n d 3 6 0 m g/ da y, ac hie v e d b y t wice d ail y d osi n g) were s electe d f or t he 
pr o of -of -c o nce pt st u d y P D 0 0 5 3 t o o btai n i nitial e vi de nce of U C B 0 5 9 9 effi cac y i n sl o wi n g P D 
disease pr o gressi o n. T he t hera pe utic d os e of U C B 0 5 9 9 is li kel y t o b e ≤3 6 0 m g/ da y. He nce, 
3 6 0 m g was c h ose n as  t h e ma xi m u m si n gle d ose i n Part B of t his st u d y; 2 d ose le vels bel o w 
3 6 0 m g ha v e bee n s electe d ( 9 0 m g a n d 1 8 0 m g) a n d are set i n a c o m m o n rati o of 2 t o a de q uatel y 
e val uate t he P K c haracteristics a n d d ose pr o p orti o nalit y of U C B 0 5 9 9. T heref ore, t h ese 3 d ose 
levels ( 9 0 m g, 1 8 0 m g, a n d 3 6 0 m g) are b elie ve d t o be a p pr o pri ate d oses f or t his p orti o n of t he 
st u d y, a n d stea d y state P K will be pr ojecte d base d o n si n gle d ose d ata.  
C CI
C CI
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

UCB 
 
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UCB0599 
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Further information regarding UP0030, UP0077, and UP0078 is provided in the most recent IB. 
4.4 
End of study definition 
A participant is considered to have completed the study if he/she has completed all periods of the 
study including the SFU Visit (within 10 days after the last dose for Part A or 7 days after the 
last dose for Part B). 
The end of the study is defined as the date of the last scheduled procedure for the last study 
participant in the study (see Section 1.3 for details on Schedule of Activities). 
5 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age 
1. Participant must be 18 to 55 years of age inclusive at the time of signing the ICF. 
Type of participant and disease characteristics 
2. Participants who are overtly healthy as determined by medical evaluation including medical 
history, physical examination, laboratory tests, and cardiac monitoring. 
Note: study participants must have clinical laboratory test results within the local reference 
ranges or values that are considered as not clinically relevant by the Investigator and 
approved by the Medical Monitor. Laboratory parameters outside the reference ranges may 
be retested once and if the retest is within the reference range or considered as clinically not 
relevant, the study participants will be allowed in the study (Section 5.4). 
3. Part A only: all healthy study participants except for those participants who are eligible for 
Part B of the study. 
4. For participants of Japanese origin (Part B): study participant is of Japanese descent as 
evidenced by appearance and verbal confirmation of familial heritage (a participant has all 
4 Japanese grandparents born in Japan). 
For participants of Chinese origin (Part B): study participant is of Chinese descent as 
evidenced by appearance and verbal confirmation of familial heritage (a participant has all 
4 Chinese grandparents born in China). 
Weight 
5. Body weight within 45 to 100kg (female) and 50 to 100kg (male) and body mass index 
(BMI) within the range 18 to 30 kg/m2 (inclusive at screening). 
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Sex 
6. Healthy male and female study participants 
• A male participant must agree to use contraception as detailed in Appendix 4 of this protocol 
during the treatment period and for at least 1 week after the last dose of study medication, 
and refrain from donating sperm during this period (Section 10.4) 
• A female participant is eligible to participate if she is not pregnant (see Appendix 4, 
Section 10.4), not breastfeeding, and at least one of the following conditions applies: 
− Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 
OR 
A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 during the 
treatment period and for at least 1 week after the last dose of study medication. 
Informed consent 
7. Capable of giving signed informed consent as described in Appendix 1 (Section 10.1) which 
includes compliance with the requirements and restrictions listed in the ICF and in this 
protocol. 
5.2 
Exclusion criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical conditions 
1. Participant has any medical or psychiatric condition that, in the opinion of the Investigator, 
could jeopardize or would compromise the study participant’s ability to participate in this 
study. 
2. Participant has a history or presence of/significant history of cardiovascular, respiratory, 
hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders 
capable of significantly altering the absorption, metabolism, or elimination of drugs; 
constituting a risk when taking the study intervention; or interfering with the interpretation of 
data. 
3. Participant has had lymphoma, leukemia, or any malignancy within the past 5 years, except 
for basal cell carcinomas that have been resected, squamous epithelial carcinomas of the skin 
that have been resected with no evidence of metastatic disease for 3 years. 
4. Participant has had breast cancer within the past 10 years. 
5. Participant has a history of alcohol or drug abuse within the last 1 year from Screening, as 
defined according to the Diagnostic and Statistical Manual of Mental Disorders. 
6. Participant has a known hypersensitivity to any components of the study medication or 
comparative drugs as stated in this protocol. 
7. Participant has a consumption of more than 600mg of caffeine/day at screening and 
throughout the study (1 cup of coffee contains approximately 100mg of caffeine, 1 cup of tea 
approximately 30mg, and 1 glass of cola approximately 20mg). 
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UP0073 
 
 
 
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8. Participant has consumed any grapefruit, grapefruit juice, grapefruit-containing products, or 
star fruit within 14 days prior to administration of study medication or is not willing to 
refrain from consuming these products for the duration of the study. 
9. Participant is excluded if any of the following COVID-19 criteria apply: 
• Participant has a positive test result for SARS-CoV-2 using reverse transcription-polymerase 
chain reaction (RT-PCR) on admission. 
• Participant has clinical signs and symptoms consistent with COVID-19 (eg, fever, dry cough, 
dyspnea, sore throat, fatigue) or confirmed infection by appropriate laboratory test within the 
previous 14 days prior to screening or on admission or a history of in-patient hospitalization 
secondary to COVID-19. 
• Participant is currently in quarantine (has been in contact with a SARS-CoV-2 positive 
patient in the last 14 days). 
• Participant has had a severe course of COVID-19 (eg, requiring extracorporeal membrane 
oxygenation, mechanical ventilation or hospitalization). 
10. Participant has, in the opinion of the Investigator, a known relevant allergy (not including 
mild seasonal hay fever and/or conjunctivitis or low-grade food intolerances), a preexisting 
history of a relevant allergic condition, or a predisposition for an allergic reaction (eg, total 
immunoglobulin E [IgE] value above normal range at screening). 
Prior/concomitant therapy 
11. Participant has received or intends to use any prescription or nonprescription medicines, 
including enzyme inhibitors or inducers, any gastric pH modifying agents, over the counter 
remedies, herbal and dietary supplements (including St. John’s Wort) up to 2 weeks (4 weeks 
for enzyme inducers) or 5 half-lives of the respective drug (whichever is longer) before the 
first administration of study medication and during the clinical part of the study, unless 
required to treat an AE. Drugs with known CYP3A4 interaction (strong inducers and 
inhibitors) are prohibited. This does not include oral contraceptives exceeding 30μg ethinyl 
estradiol or postmenopausal hormone replacement therapy or implants, patches, or 
intrauterine devices (IUDs)/intrauterine hormone-releasing system (IUSs) delivering 
progesterone (for female study participants). 
Prior/concurrent clinical study experience 
12. Participant has previously participated in this study or participant has previously been 
assigned to treatment in a study of the medication under investigation in this study. 
13. Participant has participated in another study of a study medication (and/or an investigational 
device) within the previous 30 days or 5 half-lives, whichever is greatest, or is currently 
participating in another study of an study medication (and/or an investigational device). 
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Diagnostic assessments 
14. Participant has a medical history or current diagnosis of renal impairment and/or screening 
laboratory results show: 
• An estimated glomerular filtration rate (eGFR) <80mL/min/1.73m2 (using the Chronic 
Kidney Disease Epidemiology Collaboration formula) 
• An albumin/creatinine ratio ≥30mg/mmol 
• Participant has a urinary tract infection but could be rescreened once the infection has been 
resolved 
• Clinically significant electrolyte abnormalities 
15. Participant has any clinically relevant abnormal findings in physical examination, laboratory 
tests, or vital signs, which, in the opinion of the Investigator, may place the participant at risk 
because of participation in the study. 
16. Presence of hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to 
dosing. 
17. Positive hepatitis C antibody test (HCVAb) result at screening or within 3 months prior to 
starting study intervention. NOTE: Participants with positive HCVAb due to prior resolved 
disease can be enrolled if a confirmatory negative hepatitis C ribonucleic acid (RNA) test is 
obtained. 
18. Positive hepatitis C RNA test result at screening or within 3 months prior to first dose of 
study medication. NOTE: Test is optional and participants with negative HCVAb test are not 
required to also undergo hepatitis C RNA testing. 
19. Positive immunodeficiency virus antibody test (HIV1Ab and HIV2Ab) at screening. 
20. Participant has alanine transaminase (ALT), aspartate transaminase (AST) or alkaline 
phosphatase (ALP) are greater than the upper limit of normal (ULN) at Screening. 
For randomized participants with a baseline result >ULN for ALT, AST, ALP, or total 
bilirubin, a baseline diagnosis and/or the cause of any clinically meaningful elevation must 
be understood and recorded in the electronic case report form (eCRF). 
If study participant has >ULN ALT, AST, or ALP that does not meet the exclusion limit at 
screening, repeat the tests, if possible, prior to dosing to ensure there is no further ongoing 
clinically relevant increase. In case of a clinically relevant increase, inclusion of the 
participant must be discussed with the Medical Monitor. 
Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated 
once for confirmation. This includes rescreening. 
21. Participant has bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if 
fractionated and direct bilirubin <35%). 
22. Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the 
exception of Gilbert's syndrome or asymptomatic gallstones). 
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26 Oct 2023 
Clinical Study Protocol Amendment 1 
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UP0073 
 
 
 
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23. Participant has any clinically relevant electrocardiogram (ECG) finding at the Screening 
Visit or at Baseline, or a family history of sudden death due to long QT syndrome which, in 
the opinion of the Investigator, would put the participant at increased risk of QT prolongation 
during the study (See Section 7.1.2 for QTcF withdrawal criteria). In addition, any study 
participant with any of the following findings will be excluded at Screening: QT interval 
correlated for heart rate using Fridericia’s formula >450 msec for males and 470msec for 
females; other conduction abnormalities (defined as PR>=220 ms), irregular rhythm other 
than sinus arrhythmia or occasional, rare supraventricular, and rare ventricular ectopic beats. 
Other exclusions 
24. For women of childbearing potential, study participant is pregnant, planning on becoming 
pregnant during the study, or is breastfeeding. 
25. Participants who may have a history of confirmed gastric ulceration. 
5.3 
Lifestyle restrictions 
5.3.1 
Meals and dietary restrictions 
Study participants receive standard meals and snacks at appropriate times indicated by the clinic 
center, except when they are required to fast. 
• Fasting and water restrictions: Participants will fast (ie, no food or fluids except water) for at 
least 10 hours prior to study medication dosing and will continue to fast for at least 4 hours 
after study medication dosing. No fluid intake, apart from the fluid given at the time of study 
medication intake, is allowed from 2 hours before until 2 hours after dosing of study 
medication. There is no water restriction for esomeprazole dosed 1 hour prior to UCB0599 
administration in Periods 4 through 6 (Part A). At all other times, participants may drink 
water ad libitum. UCB0599 will be administered with approximately 240mL of water and 
esomeprazole with approximately 250ml of water. 
• No grapefruit, grapefruit juice, grapefruit-containing products, or star fruit is to be consumed 
within 14 days before the start of study treatment until after the final dose. Participants who 
are not willing to refrain from consuming these products for the duration of the study will be 
excluded (Section 5.2). These fruits are not allowed during the Treatment Period and 
throughout the study due to an ingredient that is an inhibitor sensitive substrate of CYP3A. If 
a deviation occurs, it must be noted in the database. 
• No cruciferous vegetables (eg, brussel sprouts, broccoli, cabbage, cauliflower) may be 
ingested for 7 days prior to first dosing until after study completion. If a deviation occurs, it 
must be noted in the database. 
5.3.2 
Caffeine, alcohol, and tobacco 
• Participants will abstain from ingesting more than 600mg of caffeine/day at screening and 
throughout the study (1 cup of coffee contains approximately 100mg of caffeine, 1 cup of tea 
approximately 30mg, and 1 glass of cola approximately 20mg) (see Section 5.2 and 
Section 5.3.1). 
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UCB 
 
26 Oct 2023 
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UP0073 
 
 
 
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• Participants will abstain from alcohol for 48 hours before the first dosing until after the SFU 
Visit or Early Termination Visit (ETV) evaluation. 
• Use of tobacco products will not be allowed from screening until after study completion. 
• Use of cannabis will not be permitted for 4 weeks before screening until after study 
completion. 
5.3.3 
Activity 
Strenuous activity (eg, weight training, aerobics, football) is to be restricted from screening until 
the SFU Visit or ETV evaluation. Participants may participate in light recreational activities 
during the study. 
5.4 
Screen failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomly assigned to study medication. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details, eligibility criteria, and any serious adverse event (SAE). 
Study participants who do not meet the criteria for participation in this study (screen failures) 
may be rescreened once at the discretion of the Investigator. 
Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated 
once for confirmation. This includes rescreening. 
6 
STUDY TREATMENTS 
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo, or 
medical device(s) intended to be administered to a study participant according to the study 
protocol. 
6.1 
Treatments administered 
The treatments for Part A are described in Table 6-1 and the possible treatment options for 
Part B are described in Table 6-2 (UCB0599 film-coated tablet), Table 6-3 (UCB0599 
encapsulated tablet), and Table 6-4 (UCB0599 capsule). For Part B only, the preferred 
formulation will depend on the formulation that will be selected at the end of Part A. 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

U C B  
 
2 6 Oct 2 0 2 3  
Cli nical St u d y Pr ot oc ol A me n d me nt 1  
U C B 0 5 9 9  
U P 0 0 7 3  
 
 
 
C o nfi de ntial  
P a ge 4 1  of 1 0 1  
T a bl e  6 -1 : 
St u d y tr e at m e nt f or P art A  
Tre at me nt n a me  
U C B 0 5 9 9  
1 8 0 m g/ da y ca ps ules  
U C B 0 5 9 9  
1 8 0 m g/ da y ta blets  
U C B 0 5 9 9 1 8 0 m g/ da y 
e nca ps ulate d ta blets  
C o -a d mi nistrati o n of P PI  
I nter ve nti o n 
n a me  
U C B 0 5 9 9  
U C B 0 5 9 9  
U C B 0 5 9 9  
Es o me praz ole  
T y pe  
Dr u g  
Dr u g  
Dr u g  
Dr u g  
D ose 
f or m ul ati o n 
Gra n ules i n oral ca ps ules 
(refere nce f or m ulati o n) 
Oral fil m -c oate d ta blets wit h 
 
Oral e nca ps ulate d ta blets 
wit h 
 
Oral ca ps ules  
U nit d ose 
stre n gt h(s) 
9 0 m g  
1 8 0 m g  
1 8 0 m g  
4 0 m g ca ps ules ( Ne xi u m ® 
dela ye d -release ca ps ule) 
D os a ge le vel(s)  
1 8 0 m g/ da y S D  
( 2 x 9 0 m g ca ps ules) 
1 8 0 m g/ da y S D  
( 1 ta blet) 
1 8 0 m g/ da y S D 
( 1 e nca ps ulate d ta blet)  
4 0 m g Q D  
( 1 ca ps ule) 
R o ute of 
a d mi nistr ati o n  
Oral  
Oral  
Oral  
Oral  
Use  
E x peri me ntal  
E x peri me ntal  
E x peri me ntal  
E x peri me ntal  
I M P a n d 
NI M P/ A x M P  
I M P 
I M P 
I M P 
NI M P  
S o urci n g  
Pr o vi de d ce ntrall y b y t he 
S p o ns or  
Pr o vi de d ce ntrall y b y t he 
S p o ns or  
Pr o vi de d ce ntrall y b y t he 
S p o ns or  
S o urce d l ocall y b y t he 
cli nical site 
P ac k a gi n g a n d 
l a beli n g 
T he st u d y me dicati o n is 
ma n ufact ure d, pac ka ge d , a n d 
la bele d acc or di n g t o G M P 
g ui deli nes a n d i n acc or da nce 
wit h all a p plica ble la ws or 
re g ulati o ns. Eac h st u d y 
me dicati o n b ottle will be 
la bele d acc or di n g t o 
i n di vi d ual c o u ntr y 
re q uire me nts. Details of t he 
pac ka gi n g a n d la beli n g will 
T he st u d y me dicati o n is 
ma n ufact ure d, pac ka ge d, 
a n d la bele d acc or di n g t o 
G M P g ui deli nes a n d i n 
acc or da nce wit h all 
a p plica ble la ws or 
re g ulati o ns. Eac h st u d y 
me dicati o n b ottle will be 
la bele d acc or di n g t o 
i n di vi d ual c o u ntr y 
re q uire me nts. Details of t he 
T he st u d y me dicati o n is 
ma n ufact ure d, pac ka ge d, 
a n d la bele d acc or di n g t o 
G M P g ui deli nes a n d i n 
acc or da nce wit h all 
a p plica ble la ws or 
re g ulati o ns. Eac h st u d y 
me dicati o n b ottle will be 
la bele d acc or di n g t o 
i n di vi d ual c o u ntr y 
re q uire me nts. Details of t he 
N A  
C CI
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

UCB 
 
26 Oct 2023 
Clinical Study Protocol Amendment 1 
UCB0599 
UP0073 
 
 
 
Confidential 
Page 42 of 101 
Table 6-1: 
Study treatment for Part A 
be provided in the study 
medication Handling Manual. 
packaging and labeling will 
be provided in the study 
medication Handling 
Manual. 
packaging and labeling will 
be provided in the study 
medication Handling 
Manual. 
Current/ former 
name 
UCB0599 
UCB0599 
UCB0599 
NA 
AxMP=auxiliary medicinal product; GMP=Good Manufacturing Practices; IMP=investigational medicinal product; NA=not applicable; 
NIMP=non-investigational medicinal product; PPI=proton pump inhibitor; QD=once daily; SD=single dose 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

U C B  
 
2 6 Oct 2 0 2 3  
Cli nical St u d y Pr ot oc ol A me n d me nt 1  
U C B 0 5 9 9  
U P 0 0 7 3  
 
 
 
C o nfi de ntial  
P a ge 4 3  of 1 0 1  
T a bl e  6 -2 : 
St u d y tr e at m e nt f or P art B o pti o n: U C B 0 5 9 9 fil m-c o at e d t a bl et u s e d a s n e w f or m ul ati o n 
Tre at me nt n a me  
U C B 0 5 9 9  
9 0 m g ta blets  
U C B 0 5 9 9 
matc hi n g place b o 
9 0 m g ta blets  
U C B 0 5 9 9  
1 8 0 m g ta blets  
U C B 0 5 9 9 
matc hi n g place b o 
1 8 0 m g ta blets  
U C B 0 5 9 9  
3 6 0 m g ta blets  
U C B 0 5 9 9 
matc hi n g place b o 
3 6 0 m g ta blets  
I nter ve nti o n 
n a me  
U C B 0 5 9 9  
Place b o  
U C B 0 5 9 9  
Place b o  
U C B 0 5 9 9  
Place b o  
T y pe  
Dr u g  
Place b o  
Dr u g  
Place b o  
Dr u g  
Place b o  
D ose f or m ul ati o n Oral fil m -c oate d 
ta blets wit h 
 
Matc hi n g place b o 
ta blets 
Oral fil m -c oate d 
ta blets wit h 
 
Matc hi n g place b o 
ta blets 
Oral fil m -c oate d 
ta blets wit h 
 
Matc hi n g place b o 
ta blets 
U nit d ose 
stre n gt h(s) 
9 0 m g  
0 m g  
1 8 0 m g  
0 m g  
1 8 0 m g  
0 m g  
D os a ge le vel(s)  
9 0 m g/ da y S D  
( 1 ta blet) 
0 m g/ da y S D  
( 1 matc hi n g 
place b o ta blet)  
1 8 0 m g/ da y S D  
( 1 ta blet) 
0 m g/ da y S D  
( 1 matc hi n g 
place b o ta blet)  
3 6 0 m g/ da y S D  
( 2 x 1 8 0 m g ta blets) 
0 m g/ da y S D  
( 2 matc hi n g 
place b o ta blets)  
R o ute of 
a d mi nistr ati o n  
Oral  
Oral  
Oral  
Oral  
Oral  
Oral  
Use  
E x peri me ntal  
E x peri me ntal  
E x peri me ntal  
E x peri me ntal  
E x peri me ntal  
E x peri me ntal  
I M P a n d 
NI M P/ A x M P  
I M P 
I M P 
I M P 
I M P 
I M P 
I M P 
S o urci n g  
Pr o vi de d ce ntrall y 
b y t he S p o ns or  
Pr o vi de d ce ntrall y 
b y t he S p o ns or  
Pr o vi de d ce ntrall y 
b y t he S p o ns or  
Pr o vi de d ce ntrall y 
b y t he S p o ns or  
Pr o vi de d ce ntrall y 
b y t he S p o ns or  
Pr o vi de d ce ntrall y 
b y t he S p o ns or  
C CI
C CI
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

UCB 
 
26 Oct 2023 
Clinical Study Protocol Amendment 1 
UCB0599 
UP0073 
 
 
 
Confidential 
Page 44 of 101 
Table 6-2: 
Study treatment for Part B option: UCB0599 film-coated tablet used as new formulation 
Packaging and 
labeling 
The study 
medication is 
manufactured, 
packaged, and 
labeled according 
to GMP 
guidelines and in 
accordance with 
all applicable 
laws or 
regulations. Each 
study medication 
bottle will be 
labeled according 
to individual 
country 
requirements. 
Details of the 
packaging and 
labeling will be 
provided in the 
study medication 
Handling Manual. 
The study 
medication is 
manufactured, 
packaged, and 
labeled according 
to GMP 
guidelines and in 
accordance with 
all applicable 
laws or 
regulations. Each 
study medication 
bottle will be 
labeled according 
to individual 
country 
requirements. 
Details of the 
packaging and 
labeling will be 
provided in the 
study medication 
Handling Manual. 
The study 
medication is 
manufactured, 
packaged, and 
labeled according 
to GMP 
guidelines and in 
accordance with 
all applicable 
laws or 
regulations. Each 
study medication 
bottle will be 
labeled according 
to individual 
country 
requirements. 
Details of the 
packaging and 
labeling will be 
provided in the 
study medication 
Handling Manual. 
The study 
medication is 
manufactured, 
packaged, and 
labeled according 
to GMP 
guidelines and in 
accordance with 
all applicable 
laws or 
regulations. Each 
study medication 
bottle will be 
labeled according 
to individual 
country 
requirements. 
Details of the 
packaging and 
labeling will be 
provided in the 
study medication 
Handling Manual. 
The study 
medication is 
manufactured, 
packaged, and 
labeled according 
to GMP 
guidelines and in 
accordance with 
all applicable 
laws or 
regulations. Each 
study medication 
bottle will be 
labeled according 
to individual 
country 
requirements. 
Details of the 
packaging and 
labeling will be 
provided in the 
study medication 
Handling Manual. 
The study 
medication is 
manufactured, 
packaged, and 
labeled according 
to GMP 
guidelines and in 
accordance with 
all applicable laws 
or regulations. 
Each study 
medication bottle 
will be labeled 
according to 
individual country 
requirements. 
Details of the 
packaging and 
labeling will be 
provided in the 
study medication 
Handling Manual. 
Current/ former 
name 
UCB0599 
NA 
UCB0599 
NA 
UCB0599 
NA 
AxMP=auxiliary medicinal product; GMP=Good Manufacturing Practices; IMP=investigational medicinal product; NA=not applicable; 
NIMP=non-investigational medicinal product; SD=single dose 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

U C B  
 
2 6 Oct 2 0 2 3  
Cli nical St u d y Pr ot oc ol A me n d me nt 1  
U C B 0 5 9 9  
U P 0 0 7 3  
 
 
 
C o nfi de ntial  
P a ge 4 5  of 1 0 1  
T a bl e  6 -3 : 
St u d y tr e at m e nt f or P art B o pti o n: U C B 0 5 9 9 e n c a p s ul at e d t a bl et u s e d a s n e w f or m ul ati o n  
Tre at me nt n a me  
U C B 0 5 9 9  
9 0 m g 
e nca ps ulate d 
ta blets 
U C B 0 5 9 9 
matc hi n g place b o 
9 0 m g 
e nca ps ulate d 
ta blets 
U C B 0 5 9 9  
1 8 0 m g 
e nca ps ulate d 
ta blets 
U C B 0 5 9 9 
matc hi n g place b o 
1 8 0 m g 
e nca ps ulate d 
ta blets 
U C B 0 5 9 9  
3 6 0 m g 
e nca ps ulate d 
ta blets 
U C B 0 5 9 9 
matc hi n g place b o 
3 6 0 m g 
e nca ps ulate d 
ta blets 
I nter ve nti o n 
n a me  
U C B 0 5 9 9  
Place b o  
U C B 0 5 9 9  
Place b o  
U C B 0 5 9 9  
Place b o  
T y pe  
Dr u g  
Place b o  
Dr u g  
Place b o  
Dr u g  
Place b o  
D ose f or m ul ati o n  Oral e nca ps ulate d 
ta blets wit h 
 
Matc hi n g place b o 
e nca ps ulate d 
ta blets 
Oral e nca ps ulate d 
ta blets wit h 
 
Matc hi n g place b o 
e nca ps ulate d 
ta blets 
Oral e nca ps ulate d 
ta blets wit h 
 
Matc hi n g place b o 
e nca ps ulate d 
ta blets 
U nit d ose  
stre n gt h(s) 
9 0 m g  
0 m g  
1 8 0 m g  
0 m g  
1 8 0 m g  
0 m g  
D os a ge le vel(s)  
9 0 m g/ da y S D  
( 1 e nca ps ulate d 
ta blet) 
0 m g/ da y S D  
( 1 matc hi n g 
place b o 
e nca ps ulate d 
ta blet) 
1 8 0 m g/ da y S D  
( 1 e nca ps ulate d 
ta blet) 
0 m g/ da y S D  
( 1 matc hi n g 
place b o 
e nca ps ulate d 
ta blet) 
3 6 0 m g/ da y S D  
( 2 x 1 8 0 m g 
e nca ps ulate d 
ta blets) 
0 m g/ da y S D  
( 2 matc hi n g 
place b o 
e nca ps ulate d 
ta blets) 
R o ute of 
a d mi nistr ati o n  
Oral  
Oral  
Oral  
Oral  
Oral  
Oral  
Use  
E x peri me ntal  
E x peri me ntal  
E x peri me ntal  
E x peri me ntal  
E x peri me ntal  
E x peri me ntal  
I M P a n d 
NI M P/ A x M P  
I M P 
I M P 
I M P 
I M P 
I M P 
I M P 
S o urci n g  
Pr o vi de d ce ntrall y 
b y t he S p o ns or  
Pr o vi de d ce ntrall y 
b y t he S p o ns or  
Pr o vi de d ce ntrall y 
b y t he S p o ns or  
Pr o vi de d ce ntrall y 
b y t he S p o ns or  
Pr o vi de d ce ntrall y 
b y t he S p o ns or  
Pr o vi de d ce ntrall y 
b y t he S p o ns or  
C CI
C CI
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

UCB 
 
26 Oct 2023 
Clinical Study Protocol Amendment 1 
UCB0599 
UP0073 
 
 
 
Confidential 
Page 46 of 101 
Table 6-3: 
Study treatment for Part B option: UCB0599 encapsulated tablet used as new formulation 
Packaging and 
labeling 
The study 
medication is 
manufactured, 
packaged, and 
labeled according 
to GMP 
guidelines and in 
accordance with 
all applicable 
laws or 
regulations. Each 
study medication 
bottle will be 
labeled according 
to individual 
country 
requirements. 
Details of the 
packaging and 
labeling will be 
provided in the 
study medication 
Handling Manual. 
The study 
medication is 
manufactured, 
packaged, and 
labeled according 
to GMP 
guidelines and in 
accordance with 
all applicable 
laws or 
regulations. Each 
study medication 
bottle will be 
labeled according 
to individual 
country 
requirements. 
Details of the 
packaging and 
labeling will be 
provided in the 
study medication 
Handling Manual. 
The study 
medication is 
manufactured, 
packaged, and 
labeled according 
to GMP 
guidelines and in 
accordance with 
all applicable 
laws or 
regulations. Each 
study medication 
bottle will be 
labeled according 
to individual 
country 
requirements. 
Details of the 
packaging and 
labeling will be 
provided in the 
study medication 
Handling Manual. 
The study 
medication is 
manufactured, 
packaged, and 
labeled according 
to GMP 
guidelines and in 
accordance with 
all applicable 
laws or 
regulations. Each 
study medication 
bottle will be 
labeled according 
to individual 
country 
requirements. 
Details of the 
packaging and 
labeling will be 
provided in the 
study medication 
Handling Manual. 
The study 
medication is 
manufactured, 
packaged, and 
labeled according 
to GMP 
guidelines and in 
accordance with 
all applicable 
laws or 
regulations. Each 
study medication 
bottle will be 
labeled according 
to individual 
country 
requirements. 
Details of the 
packaging and 
labeling will be 
provided in the 
study medication 
Handling Manual. 
The study 
medication is 
manufactured, 
packaged, and 
labeled according 
to GMP 
guidelines and in 
accordance with 
all applicable laws 
or regulations. 
Each study 
medication bottle 
will be labeled 
according to 
individual country 
requirements. 
Details of the 
packaging and 
labeling will be 
provided in the 
study medication 
Handling Manual. 
Current/ Former 
name 
UCB0599 
NA 
UCB0599 
NA 
UCB0599 
NA 
AxMP=auxiliary medicinal product; GMP=Good Manufacturing Practices; IMP=investigational medicinal product; NA=not applicable; 
NIMP=non-investigational medicinal product; SD=single dose 
 
 
PUBLIC COPY 
This document cannot be used to support any marketing authorization 
application and any extensions or variations thereof.

UCB 
 
26 Oct 2023 
Clinical Study Protocol Amendment 1 
UCB0599 
UP0073 
 
 
 
Confidential 
Page 47 of 101 
Table 6-4: 
Study treatment for Part B option: UCB0599 capsules (Part A reference formulation)  
Treatment name 
UCB0599  
90mg capsules 
UCB0599 
matching placebo 
90mg capsules 
UCB0599  
180mg capsules 
UCB0599 
matching placebo 
180mg capsules 
UCB0599  
360mg capsules 
UCB0599 
matching placebo 
360mg capsules 
Intervention 
name 
UCB0599 
Placebo 
UCB0599 
Placebo 
UCB0599 
Placebo 
Type 
Drug 
Placebo 
Drug 
Placebo 
Drug 
Placebo 
Dose formulation Granules in oral 
capsules 
Matching placebo 
capsules 
Granules in oral 
capsules 
Matching placebo 
capsules 
Granules in oral 
capsules 
Matching placebo 
capsules 
Unit dose 
strength(s) 
90mg 
0mg 
90mg 
0mg 
90mg 
0mg 
Dosage level(s) 
90mg/day SD 
(1 capsule) 
0mg/day SD 
(1 matching 
placebo capsules) 
180mg/day SD 
(2 capsules) 
 
0mg/day SD 
(2 matching 
placebo capsules) 
360mg/day SD 
(4 capsules) 
 
0mg/day SD 
(4 matching 
placebo capsules) 
Route of 
administration 
Oral 
Oral 
Oral 
Oral 
Oral 
Oral 
Use 
Experimental 
Experimental 
Experimental 
Experimental 
Experimental 
Experimental 
IMP and 
NIMP/AxMP 
IMP 
IMP 
IMP 
IMP 
IMP 
IMP 
Sourcing 
Provided centrally 
by the Sponsor 
Provided centrally 
by the Sponsor 
Provided centrally 
by the Sponsor 
Provided centrally 
by the Sponsor 
Provided centrally 
by the Sponsor 
Provided centrally 
by the Sponsor 
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Table 6-4: 
Study treatment for Part B option: UCB0599 capsules (Part A reference formulation)  
Packaging and 
labeling 
The study 
medication is 
manufactured, 
packaged, and 
labeled according 
to GMP 
guidelines and in 
accordance with 
all applicable 
laws or 
regulations. Each 
study medication 
bottle will be 
labeled according 
to individual 
country 
requirements. 
Details of the 
packaging and 
labeling will be 
provided in the 
study medication 
Handling Manual. 
The study 
medication is 
manufactured, 
packaged, and 
labeled according 
to GMP 
guidelines and in 
accordance with 
all applicable 
laws or 
regulations. Each 
study medication 
bottle will be 
labeled according 
to individual 
country 
requirements. 
Details of the 
packaging and 
labeling will be 
provided in the 
study medication 
Handling Manual. 
The study 
medication is 
manufactured, 
packaged, and 
labeled according 
to GMP 
guidelines and in 
accordance with 
all applicable 
laws or 
regulations. Each 
study medication 
bottle will be 
labeled according 
to individual 
country 
requirements. 
Details of the 
packaging and 
labeling will be 
provided in the 
study medication 
Handling Manual. 
The study 
medication is 
manufactured, 
packaged, and 
labeled according 
to GMP 
guidelines and in 
accordance with 
all applicable 
laws or 
regulations. Each 
study medication 
bottle will be 
labeled according 
to individual 
country 
requirements. 
Details of the 
packaging and 
labeling will be 
provided in the 
study medication 
Handling Manual. 
The study 
medication is 
manufactured, 
packaged, and 
labeled according 
to GMP 
guidelines and in 
accordance with 
all applicable 
laws or 
regulations. Each 
study medication 
bottle will be 
labeled according 
to individual 
country 
requirements. 
Details of the 
packaging and 
labeling will be 
provided in the 
study medication 
Handling Manual. 
The study 
medication is 
manufactured, 
packaged, and 
labeled according 
to GMP 
guidelines and in 
accordance with 
all applicable laws 
or regulations. 
Each study 
medication bottle 
will be labeled 
according to 
individual country 
requirements. 
Details of the 
packaging and 
labeling will be 
provided in the 
study medication 
Handling Manual. 
Current/ Former 
name 
UCB0599 
NA 
UCB0599 
NA 
UCB0599 
NA 
AxMP=auxiliary medicinal product; GMP=Good Manufacturing Practices; IMP=investigational medicinal product; NA=not applicable; 
NIMP=non-investigational medicinal product; SD=single dose 
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6.2 
Preparation, handling, storage, and accountability requirements 
The Investigator or designee must confirm that appropriate temperature conditions have been 
maintained during transit for all study medication received, and any discrepancies are reported 
and resolved before use of the study treatment. 
Only participants enrolled in the study may receive the study medication and only authorized site 
staff may supply or administer the study medication. All study medication must be stored in a 
secure, environmentally controlled, and monitored (manual or automated) area in accordance 
with the labeled storage conditions, with access limited to the investigator and authorized site 
staff. 
The Investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study medication accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records). 
In case an out-of-range temperature is noted, it must be immediately reported as per instructions 
contained in the study medication Handling Manual. 
The Investigator (or designee) will instruct the participant to store the study medication 
following the instructions on the label. 
Further guidance and information for the final disposition of unused study medication are 
provided in the study medication Handling Manual. 
6.2.1 
Drug accountability 
A Drug Accountability form will be used to record study medication dispensing and return 
information on a by-participant basis and will serve as source documentation during the course 
of the study. Details of any study medication lost, damaged (due to breakage or wastage), not 
used, partially used, disposed of at the study site, or returned to the Sponsor or designee must 
also be recorded on the appropriate forms. All supplies and pharmacy documentation must be 
made available throughout the study for UCB (or designee) to review. 
The Investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of study medication until returned or destroyed. 
The Investigator may assign some of the Investigator’s duties for drug accountability at the study 
site to an appropriate pharmacist/designee. 
The Investigator must ensure that the study medication is used only in accordance with the 
protocol. 
Periodically, and/or after completion of the clinical phase of the study, all used (including empty 
containers/partially used), unused, damaged, and/or expired study medication must be reconciled 
and either destroyed at the site according to local laws, regulations, and UCB standard operating 
procedures (SOPs) or returned to UCB (or designee). Investigational medicinal product intended 
for the study cannot be used for any other purpose than that described in this protocol. 
6.3 
Measures to minimize bias: randomization and blinding 
Part A is an open-label, randomized, 2 in-series crossover substudies, each with a fixed sequence 
complete block design of 3 treatment periods in healthy male and female participants. This 
portion of the study is planned to enroll up to 42 study participants, in which 7 participants will 
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be randomized (approximately 6 completers) to each sequence. Randomization numbers will be 
assigned at the site in an unblinded fashion and will be entered into the eCRF. 
In Part B, 15 study participants of each ethnic origin will be randomized to the 4 treatments 
following a UCB0599:placebo 4:1 ratio (see Section 4.1 for study design details). Participants 
will be blinded to the treatment (ie, UCB0599 or placebo), but not to the dosage within a 
sequence. As study participants are being screened for Part B, participants will be randomized to 
blocks of 2 sequences at a time: Sequences 1 and 2 (Cohort 2), followed by 
Sequences 3 and 4 (Cohort 3), and finally Sequences 5 and 6 (Cohort 4) after the SMC review. 
An interactive response technology (IRT) will be used for assigning eligible participants (in 
Part A and Part B) to a treatment regimen (as applicable) based on a predetermined production 
randomization and/or packaging schedule provided by UCB (or designee). The randomization 
schedule will be produced by the IRT vendor. The IRT will generate individual assignments for 
kits of the study medication, as appropriate, according to the visit schedule. 
To enroll a study participant (Visit 1), the Investigator or designee will contact the IRT and 
provide brief details about the participant to be enrolled. Each participant will receive a 5-digit 
number assigned at screening that serves as the participant identifier throughout the study. The 
participant number will be required in all communication between the Investigator or designee 
and the IRT regarding a particular participant. Participant numbers and kit numbers will be 
tracked via the IRT. 
To randomize a participant, the Investigator or designee will contact the IRT and provide brief 
details about the participant to be randomized. The IRT will automatically inform the 
investigator or designee of the participant’s randomization number. The IRT will allocate kit 
numbers to the participant based on the participant number during the course of the study. The 
randomization number must be incorporated into the eCRF. 
All participant treatment details will be allocated and maintained by the IRT. The following 
individuals will have received the randomization code at the start of the UP0073 study: 
• Designated CRO bioanalytical staff analyzing samples 
• Sponsor clinical study supply staff 
• IRT provider 
The following individuals may have access to the randomization code as indicated: 
• Sponsor patient safety staff as needed for reporting SAEs to regulatory authorities 
6.3.1 
Procedures for maintaining and breaking the treatment blind 
6.3.1.1 
Maintenance of study treatment blind 
All participant treatment details will be allocated and maintained by IRT system. 
6.3.1.2 
Breaking the treatment blind in an emergency situation 
In the event of an emergency, it will be possible to determine to which treatment arm and dose 
the participant has been allocated by contacting the IRT. The site will be provided with details of 
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how to contact the system for code breaking at the start of the study. The Medical Monitor or 
equivalent should be consulted prior to unblinding, whenever possible. 
The Clinical Project Manager will be informed immediately via the IRT when a code is broken, 
but will remain blinded to specific treatment information. Any unblinding of the study 
medication performed by the investigator must be recorded in the source documents and on the 
Study Termination eCRF page. 
6.4 
Treatment compliance 
For all study participants, study medication will be administered at the study unit. 
Drug accountability must be recorded on the Drug Accountability form. 
6.5 
Concomitant medication(s)/treatment(s) 
6.5.1 
Permitted concomitant treatments (medications and therapies) 
The following concomitant medications are permitted during the study: 
• Paracetamol/acetaminophen for the treatment of mild symptoms (eg, headache or other pain), 
given at most every 6 hours to 8 hours, not exceeding 2g per day, and with a total of no more 
than 5g over 7 days. 
• Ibuprofen, not exceeding 1.2g per day. 
• Nasal corticosteroids for seasonal rhinitis and topical corticosteroids for controlled 
dermatological conditions. 
• Oral contraceptives not exceeding 30μg ethinyl estradiol or postmenopausal hormonal 
replacement therapy (HRT) or implants, patches, or IUDs/IUSs delivering progesterone (for 
female study participants). 
For all study participants: if a concomitant medication is required during the Washout Period and 
if there is no impact on the study participant’s safety and the impact on quality of further study 
data is deemed to be minimal, the study participant can remain in the study after Sponsor 
approval. If the concomitant medication use does not violate these criteria and no drug allergy 
has been reported, the study participant will be permitted to continue in the study. 
6.5.1.1 
Permitted Coronavirus Disease-2019 vaccination 
During the study, COVID-19 vaccinations are allowed as long as they are not administered in the 
10 days prior to or in the 7 days after administration of the final dose of the study medication. 
6.5.2 
Prohibited concomitant treatments (medications and therapies) 
The following concomitant medications are prohibited during the study: 
• Medicines known to strongly interact with CYP3A4 (both inducers [including St. John's 
Wort] and inhibitors). 
• Medicines known to strongly affect gastric pH (excluding esomeprazole as used per protocol 
in Part A). 
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6.5.3 
Rescue medication 
No rescue medication will be provided as part of this study. 
6.6 
Dose modification 
There is no dose modification allowed in UP0073. 
6.7 
Criteria for study hold or dosing stoppage (Part A and Part B) 
Study medication will be stopped if the study participant develops a medical condition (or 
laboratory abnormality or ECG change) that, in the opinion of the Investigator, compromises the 
study participant’s ability to participate or compromises the study participant’s safety. 
In all cases, the study participant should be followed until the condition has resolved as agreed 
by the Investigator and the UCB Study Physician. 
See the Schedule of Activities (Section 1.3) for data to be collected at the time of treatment 
discontinuation and follow up and for any further evaluations that need to be completed. 
Detailed procedures for reporting SAEs and other safety events which may meet study hold 
criteria are provided in Appendix 8 (Section 10.8). 
6.8 
Treatment after the end of the study 
There are no plans for study participant continued care after the end of the study, since study 
participants are healthy volunteers. 
7 
DISCONTINUATION OF STUDY MEDICATION AND STUDY 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of study medication 
7.1.1 
Liver chemistry stopping criteria 
Discontinuation of study medication for abnormal liver function should be considered by the 
Investigator when a participant meets one of the conditions outlined in Figure 7-1 or if the 
Investigator believes that it is in best interest of the participant. Study medication will be 
discontinued immediately and permanently for a healthy participant if liver chemistry stopping 
criteria are met. 
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Figure 7-1: Phase I Liver Chemistry Stopping Algorithm 
 
ALT=alanine transaminase; ULN=upper limit of normal 
Specific assessments and follow up actions for potential drug-induced liver injury (PDILI) are 
provided in Appendix 6 (Section 10.6). 
7.1.2 
QTc stopping criteria 
A study participant who meets either bulleted criterion based on a single 12-lead ECG reading 
will be withdrawn from study treatment. If there are abnormalities that are considered clinically 
significant for a particular study participant, ECG recordings will be performed in triplicate at 
2- to 3-minute intervals (3 ECGs within a 5-minute timeframe) prior to the exclusion of the 
participant. 
• QT corrected for heart rate using Fridericia's formula (QTcF) >500ms OR Uncorrected 
QT >600ms 
• Change from Baseline of QTcF >60ms 
For study participants with underlying bundle branch block, follow the discontinuation criteria 
listed below: 
Baseline QTc with bundle branch block 
Discontinuation QTc threshold with bundle 
branch block 
<450ms 
>500ms 
450 to 480ms 
≥530ms 
If a clinically significant finding is identified (including, but not limited to, changes from 
Baseline in QTcF after enrollment), the Investigator or qualified designee will determine if the 
study participant can continue the study medication and if any change in study participant 
management is needed. This review of the ECG printed at the time of collection must be 
documented. Any new clinically relevant finding should be reported as an AE. 
See the Schedule of Activities (Section 1.3) for data to be collected at the time of treatment 
discontinuation and follow up and for any further evaluations that need to be completed. 
Continue Study Treatment 
Discontinue Study Treatment 
ALT ≥3xULN 
No
Yes
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7.1.3 
Renal toxicity stopping criteria 
Participants must be discontinued from the study medication if renal toxicity considered possibly 
related to the study treatment occurs. 
Laboratory tests suggestive of renal toxicity which should trigger further assessment may 
include: 
• Increase in serum creatinine ≥0.3mg/dL from Baseline OR 
• Increase in serum creatinine to ≥1.5 times from Baseline OR 
• New persistent albuminuria or clinically significant increase in preexisting albuminuria. 
Any clinically significant findings in laboratory results for renal function will be monitored until 
resolution or stabilization. 
7.1.4 
Hypersensitivity reaction stopping criteria 
Study participants will be informed that if they develop any symptoms suggestive of an 
hypersensitivity reaction (eg, rash, angioedema, or anaphylaxis), they should contact the 
Investigator immediately. The Investigator should assess the presenting symptoms to determine 
if this is possibly a hypersensitivity reaction. 
If the event is not considered to be a hypersensitivity reaction, the Investigator should document 
this and the participant may continue dosing. If the event is possibly a hypersensitivity reaction, 
the Investigator will withhold dosing and arrange additional investigations. Study participants 
may be referred to a dermatologist for additional investigation. The event should be reported to 
UCB as an AESI. 
• Two or more study participants have an hypersensitivity reaction that, based on reasonable 
medical judgement, could lead to significant toxicities that would be unacceptable for this 
study population OR 
• Two or more study participants have a study medication-related severe hypersensitivity 
reaction (Grade 3 according to the Common Terminology Criteria for Adverse Events 
[CTCAE] classification) OR 
• One or more study participants have a study medication-related hypersensitivity reaction of 
Grade 4 or 5 according to the CTCAE classification. 
If any of the above events occur during the study, the following should take place: 
− Further administration of the study medication will be suspended for all study 
participants. 
− The SMC will meet as soon as possible and will provide recommendations regarding 
individual study participants, individual groups, the study overall, the suspension or 
continuation of dosing, the stopping or continuation of the study or the modification of 
the protocol. 
Detailed procedures for reporting SAEs and other safety events which may meet study hold 
criteria are provided in Appendix 8 (Section 10.7). 
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7.1.5 
General stopping criteria for the study - Part B only 
UCB will halt further dosing if any of the following criteria are met during the course of the 
study and following case review to confirm causality and seriousness and/or severity of reported 
events. 
During the study, planned dosing and procedures must be discontinued or suspended for all 
remaining study participants who are yet to be dosed in the study and appropriate follow-up 
procedures established for (but not limited to) any of the following reasons:One study participant 
has an SAE considered related to the study medication as judged by the Investigator.Two or 
more study participants in a single cohort have a severe AE, similar clinically significant 
abnormal laboratory results or other clinically significant safety findings that would be 
unacceptable for this study population.If one of the stopping criteria for dosing and single dose 
escalation has been met, the SMC will meet as soon as possible to make a recommendation on 
discontinuation, pausing, or suspension of study medication dosing or on the stopping or 
continuation of the study. Consideration will be given to severity and relatedness of events. 
Further details on the role and process of ensuring close safety monitoring through the SMC are 
provided in the respective charters.See the Schedule of Activities (Section 1.3) for data to be 
collected at the time of treatment discontinuation and follow up.Temporary discontinuation  
The Investigator or SMC may consider temporary discontinuation of dosing of study participants 
on a case-by-case basis (for Part B only). 
7.1.6 
Rechallenge 
The Investigator after agreement with the SMC may consider rechallenge of study participants 
on a case-by-case basis (for Part B only). 
7.2 
Participant discontinuation/withdrawal from the study 
Participants are free to withdraw from the study at any time, without prejudice to their continued 
care. 
A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the Investigator for safety, behavioral, compliance, or 
administrative reasons. 
If the participant withdraws consent for disclosure of future information, the Sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. 
If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the Investigator must document this in the site study records. 
See the Schedule of Activities (Section 1.3)for data to be collected at the time of study 
discontinuation and follow up and for any further evaluations that need to be completed. 
Participants should be withdrawn from the study if any of the following events occur: 
1. Participant develops a clinically relevant medical condition (physical or psychiatric) that, in 
the opinion of the Investigator, jeopardizes or compromises the study participant’s ability to 
participate in the study or makes it unsafe to continue. 
2. Participant is noncompliant with the study procedures or medications in the opinion of the 
Investigator. 
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3. Participant’s laboratory tests suggest evidence of renal toxicity. 
4. Participant takes prohibited concomitant medications as defined in this protocol. 
5. Participant withdraws his/her consent. 
6. There is confirmation of a pregnancy during the study, as evidenced by a positive serum 
pregnancy test. 
7. Participant has an anaphylactic reaction after their first administration. 
8. The Sponsor or a regulatory agency requests withdrawal of the participant. 
Investigators should attempt to obtain information on study participants in the case of 
withdrawal. 
Investigators should contact the UCB Medical Monitor, whenever possible, to discuss the 
withdrawal of a study participant in advance. See Appendix 1 (Section 10.1 for details on study 
discontinuation). 
Participants who withdraw in Part A will not be replaced, and participants who withdraw in 
Part B will be replaced up to a maximum of 6 study participants. 
7.3 
Lost to follow up 
A participant will be considered lost to follow up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant wishes to and/or should continue in the 
study. 
• Before a participant is deemed lost to follow up, the Investigator or designee must make 
every effort to regain contact with the participant (at least 1 phone call and 1 written message 
to the participant), and document his/her effort (date and summary of the phone call and copy 
of the written message in the source documents), to complete the final evaluation. All results 
of these evaluations and observations, together with a narrative description of the reason(s) 
for removing the participant, must be recorded in the source documents. The eCRF must 
document the primary reason for withdrawal. 
Should the participant continue to be unreachable, he/she will be considered to have withdrawn 
from the study with a primary reason of lost to follow up documented in the eCRF. 
8 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the Schedule of Activities (Section 1.3 for 
Part A [Table 1-3] and Part B [Table 1-4]). 
Protocol waivers or exemptions are not allowed. 
Immediate safety concerns should be discussed with the sponsor immediately upon occurrence or 
awareness to determine if the participant should continue or discontinue study medication. 
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Adherence to the study design requirements, including those specified in the Schedule of 
Activities (Section 1.3), is essential and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria. The Investigator will maintain a screening log to record details of all 
participants screened and to confirm eligibility or record reasons for screening failure, as 
applicable. 
Procedures conducted as part of the participant’s routine clinical management (eg, blood count) 
and obtained before signing of the ICF may be utilized for screening or baseline purposes 
provided the procedures met the protocol-specified criteria and were performed within the time 
frame defined in the Schedule of Activities (Section 1.3). 
The maximum amount of blood collected from each participant over the duration of the study, 
including any extra assessments that may be required, will not exceed 500mL. Repeat or 
unscheduled samples may be taken for safety reasons or for technical issues with the samples. 
8.1 
Efficacy assessments 
Not applicable. 
8.2 
Safety assessments 
Planned time points for all safety assessments are provided in the Schedule of Activities 
(Section 1.3 for Part A [Table 1-3] and Part B [Table 1-4]). 
8.2.1 
Physical examination 
Physical examinations will be performed at the scheduled time points presented in Section 1.3 
for Part A (Table 1-3) and Part B (Table 1-4). 
A complete physical examination will include, at a minimum, general appearance; ear, nose, and 
throat; eyes, hair, and skin; and assessments of the cardiovascular, respiratory, gastrointestinal, 
neurological (including sensation, muscle strength, reflexes, balance and mental state), 
musculoskeletal, and hepatic systems. 
Height and weight will be measured and recorded at the Screening Visit, and the study 
participant’s BMI will be calculated. Height will be measured with the study participant not 
wearing shoes, and the outcome will be rounded to the nearest 1cm. Body weight will be 
measured with the study participant wearing light clothing and without wearing shoes; the 
outcome will be rounded to the nearest 0.1kg. The BMI will be calculated 
(weight [kg]/[height (m2)]) and will be reported to 1 decimal place. 
A symptom-directed physical examination will include, at a minimum, assessments of the skin, 
lungs, cardiovascular system, and abdomen (liver and spleen). A physical examination of the 
skin will include, at a minimum, a visual check of the skin, and may be conducted by a nurse or 
physician. 
Investigators and site staff should pay special attention to clinical signs related to previous 
serious illnesses. 
Clinically relevant findings or worsening of previous findings will be recorded as AEs. 
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8.2.2 
Vital signs 
Vital signs, including pulse rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), 
respiratory rate, and tympanic body temperature will be measured with a completely automated 
device after 5 minutes of rest in a supine position (in a quiet setting without distractions such as a 
television or cell phones). Pulse rate, SBP, and DBP will be measured with a completely 
automated device. Manual techniques will be used only if an automated device is not available. 
Any clinically significant abnormality in the view of the Investigator will be recorded as an AE. 
Vital signs (to be taken before blood collection for laboratory tests) will be measured in 
triplicate. The mean values will be calculated and recorded on the eCRF. The vital signs will 
consist of 3 pulse rates and 3 blood pressure (BP) measurements (3 consecutive BP readings will 
be recorded at intervals of at least 1 minute). 
Vital signs will be performed at the scheduled time points presented in Section 1.3 for Part A 
(Table 1-3) and Part B (Table 1-4). 
8.2.3 
Electrocardiograms 
Single 12-lead ECG recordings will be obtained as outlined in the Schedule of Activities in 
Section 1.3 for Part A (Table 1-3) and Part B (Table 1-4) using an ECG machine that 
automatically calculates the pulse rate and measures PR, QRS, QT, and QTcF intervals. Refer to 
Section 7.1.2 for QTcF withdrawal criteria and any additional QTc readings that may be 
necessary. 
The study participant should be resting in the supine position for at least 10 minutes before the 
start of the recordings. 
The Investigator should review all ECG recordings and, if there are abnormalities that are 
considered clinically significant for a particular study participant, then the Investigator should 
initiate a review by a specialist of all ECG data pertaining to that study participant. The 
following ECG parameters will be recorded in the eCRF: heart rate, PR-interval, QRS-duration, 
QT-interval, QTcF, and Investigator’s conclusion on ECG profile. 
8.2.4 
Clinical safety laboratory assessments 
See Appendix 2 (Section 10.2) for the list of clinical laboratory tests to be performed and to the 
Schedule of Activities (Section 1.3 for Part A [Table 1-3] and Part B [Table 1-4]) for the timing 
and frequency. 
The Investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the eCRF. The 
laboratory reports must be filed with the source documents. Clinically significant abnormal 
laboratory findings are those which are not associated with the underlying disease, unless judged 
by the Investigator to be more severe than expected for the study participant's condition. 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or within 14 days after the final dose of study medication should be repeated until 
the values return to normal or Baseline or are no longer considered clinically significant by the 
Investigator or UCB Study Physician. 
If such values do not return to normal/Baseline within a period of time judged reasonable by the 
Investigator, the etiology should be identified and the UCB Study Physician notified. 
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All protocol-required laboratory assessments, as defined in Appendix 2 (Section 10.2), must be 
conducted in accordance with the laboratory manual and the Schedule of Activities (Section 1.3). 
If laboratory values from nonprotocol-specified laboratory assessments performed at the 
institution’s local laboratory require a change in study participant management or are considered 
clinically significant by the Investigator (eg, SAE or AE or dose modification), then the results 
must be recorded in the eCRF. 
8.2.5 
Suicidal risk monitoring 
Suicidal risk moditoring is not applicable for this single-dose study. 
8.3 
AEs and SAEs 
The definitions of an AE or SAE can be found in Appendix 3 (Section 10.3). 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver or 
surrogate). 
The Investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE or SAE and remain responsible for following up AEs 
that are serious, considered related to the study medication or study procedures, or that caused 
the participant to discontinue UCB0599 (see Section 7). 
Note that in this case the national recommendation for reporting AEs related to COVID-19 
vaccines should be followed. 
For results disclosure on public registries (eg, ClinicalTrials.gov), TEAEs and treatment 
emergent SAEs will be published. 
8.3.1 
Time period and frequency for collecting AE and SAE information 
All AEs and SAEs will be collected from the signing of the ICF until the SFU Visit at the time 
points specified in the Schedule of Activities (Section 1.3 for Part A [Table 1-3] and Part B 
[Table 1-4]). 
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the ICF), including any pretreatment and posttreatment periods required by the 
protocol, must be reported in the eCRF even if no study medication was taken but specific study 
procedures were conducted. This includes all AEs not present prior to the initial visit and all AEs 
that recurred or worsened after the initial visit. 
All SAEs will be recorded and reported to the sponsor or designee within 24 hours, as indicated 
in Appendix 3 (Section 10.3). The Investigator will submit any updated SAE data to the Sponsor 
within 24 hours of it being available. 
The Investigator is specifically requested to collect and report to UCB (or its representative) any 
SAEs (even if the Investigator is certain that they are in no way associated with the study 
medication), up to 30 days from the end of the study for each participant, and to also inform 
participants of the need to inform the Investigator of any SAE within this period. Serious AEs 
that the Investigator thinks may be associated with the study medication must be reported to 
UCB regardless of the time between the event and the end of the study. 
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The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 3 (Section 10.3). 
8.3.2 
Method of detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.  
8.3.3 
Follow up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs and nonserious AESIs (as defined in 
Section 8.3.6), will be followed until resolution, stabilization, the Investigator determines that it 
is no longer clinically significant, the event is otherwise explained, or the participant is lost to 
follow up (as defined in Section 7.3). Further information on follow up procedures is given in 
Appendix 3 (Section 10.3). 
8.3.4 
Regulatory reporting requirements for SAEs 
Prompt notification by the Investigator to the UCB Study Physician of a SAE is essential so that 
legal obligations and ethical responsibilities towards the safety of study participants and the 
safety of an study medication under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study medication under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, Independent Ethics Committee (IEC), and Investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSAR) according to local regulatory requirements and Sponsor policy and forwarded to 
Investigators as necessary. 
An Investigator who receives an Investigator safety report describing a SAE or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will review and then file it 
along with the UCB0599 IB and will notify the Institutional Review Board (IRB)/IEC, if 
appropriate according to local requirements. 
8.3.5 
Pregnancy 
Details of all pregnancies in female participants and, if consented, female partners of male 
participants will be collected after the start of study medication and until at least 12 months after 
the delivery date. 
If a pregnancy is reported, the Investigator must immediately inform the Sponsor within 24 hours 
of learning of the pregnancy and should follow the procedures outlined in 
Appendix 4 (Section 10.4). 
The participant should be withdrawn from the study as soon as pregnancy is known (by positive 
pregnancy test [ie, a positive urine test confirmed with a blood test]), and the following should be 
completed: 
• The participant should return for an ETV. 
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• The participant should immediately stop the intake of the study medication as instructed at 
the ETV. 
• An SFU Visit should be scheduled approximately 10 days after the participant has 
discontinued her study medication. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs. 
8.3.6 
AESIs 
An AESI is any AE that a regulatory authority has mandated be reported on an expedited basis, 
regardless of the seriousness, expectedness, or relatedness of the AE to the administration of a 
UCB product/compound. 
For UCB0599, the following events require immediate reporting (within 24 hours regardless of 
seriousness) to UCB: 
• Hy’s Law 
− Potential Hy’s Law, defined as ≥3xULN, ALT or AST with coexisting ≥2xULN total 
bilirubin in the absence of ≥2xULN ALP, with no alternative explanation for the 
biochemical abnormality (ie, without waiting for any additional etiologic investigations 
to have been concluded). Follow up information should be reported if an alternative 
etiology is identified during investigation and monitoring of the participant. 
• Hypersensitivity reactions (such as rash, angioedema, or anaphylaxis) 
8.3.6.1 
Hypersensitivity reaction monitoring and management 
If a study participant experiences a hypersensitivity reaction (such as rash, angioedema, or 
anaphylaxis), he or she will contact the clinical site immediately (24 hours a day) or seek urgent 
medical advice in accordance with instructions from the Investigator. 
The advice will be based on the clinical presentation and may be to present to the clinical site or 
seek medical attention in the community. 
The study participant should be rapidly and thoroughly assessed in line with the actions below. 
Hypersensitivity reactions will be AESIs and require expedited reporting to UCB, regardless of 
seriousness, expectedness, or relatedness in line with Section 8.3.6. This will allow for rapid 
evaluation. 
In case of a suspected hypersensitivity reaction or any clinical indication of an unexpected 
immune response, the points described in Sections 8.3.6.1.1 through Section 8.3.6.1.6 should be 
observed. 
Consideration for restarting study medication is provided in Section 7.1.4. 
Procedures for the management of UCB0599 are provided in Appendix 3 (Section 10.3). 
8.3.6.1.1 
Medical history 
Detailed history of the hypersensitivity reaction (eg, rash, angioedema, or anaphylaxis) with 
onset time of symptoms and signs, location of symptoms and signs, first appearance, its 
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evolution (eg, where the rash appeared and to where it spread), any other symptoms (eg, pruritus, 
swelling, breathlessness), especially if showing a systemic involvement (anaphylaxis), will be 
recorded. The criteria for anaphylaxis are described in Section 8.3.6.1.1.1. 
The clinical progression of the hypersensitivity reactions symptoms should be recorded and any 
change in symptoms or severity should also be recorded together with the timing. 
All AEs reported concurrently should be included within the review. 
It will also be important to investigate any recent intake of new medications, herbs, supplements, 
or the recent use of any topical substances. 
8.3.6.1.1.1 
Anaphylaxis 
Sampson et al. listed criteria for the diagnosis of anaphylaxis. This was developed at the Second 
National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network 
symposium (Sampson et al, 2006). 
Acute onset=minutes to a few hours. 
Criteria for diagnosis-1 or more of the following: 
• Acute onset of an illness with symptom complex 1 (see below) 
• Acute onset of symptom complex 2 (see below) after exposure to a likely allergen 
• Acute onset of a reduced SBP after exposure to a known allergen for the participant 
Symptom complex 1: both of the following: 
• At least 1 of the following: 
− Skin involvement (generalized hives, pruritis, flushing) 
− Mucous membrane involvement (swollen lips, swollen tongue, swollen uvula) 
• At least 1 of the following: 
− Respiratory compromise (dyspnea, wheezing, bronchospasm, stridor, reduced peak 
expiratory flow, hypoxemia) 
− Reduced SBP, collapse, syncope, incontinence or other symptom of end-organ 
dysfunction 
Symptom complex 2: Two or more of the following: 
• Skin or mucous membranes (as above) 
• Respiratory compromise (as above) 
• Reduced BP (as above) 
• Persistent GI tract symptoms (cramping, abdominal pain, vomiting) 
Reduced SBP is indicated by 1 of the following: 
• BP <70% of Baseline SBP 
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Limitations: 
Treudler et al. found that the criteria may not perform as well as others for the recognition of 
severe, immediate reactions (Treudler et al, 2008). 
8.3.6.1.2 
Complete physical examination 
Evaluation of a possible hypersensitivity reaction includes a complete physical examination of 
the entire body as soon as feasible after reporting by the study participant. The complete physical 
examination includes a detailed description of the signs such as rash or angioedema, the location 
of the signs, and an examination for other possible signs, such as: 
• Blanched or flushed skin 
• Mucous membrane erosions or ulceration 
• Maculae 
• Papulae 
• Blisters 
• Confluent erythema 
• Angioedema: face, lips, and/or tongue swelling, also back of hands or feet 
• Wheeze, stridor, dyspnea 
• Palpable purpura 
• Lymphadenopathy 
An examination of the entire skin surface, not just local to the site of reaction, is required. 
Furthermore, a complete physical examination will also include: 
• Vital signs (high fever, dyspnea, or hypotension) 
− Vital signs (pulse rate, SBP, diastolic BP, respiratory rate, body temperature, and oxygen 
saturation) will be taken when the AE of hypersensitivity is reported and at regular 
intervals (approximately 20 to 30 minutes) for a minimum of 2 hours. The frequency 
thereafter will be based on clinical judgement. If there is worsening of clinical status, the 
Investigator will apply the appropriate treatment and safety procedures (eg, call 
emergency) and contact the UCB study physician. 
• Photography of rash and other symptoms at the first opportunity and with reasonable time 
sequence to document resolution. If timely site visit is not possible the participant may be 
requested to take photos to ensure photos of active symptoms. If participant is requested to 
provide photos the Investigator should advise the participant in data protection requirements 
(eg, avoidance of identifying features such as characteristic tattoos, parts of the face). The 
Investigator will ensure that identifiable characteristics are removed/hidden before sharing 
the pictures with the Sponsor. 
• Re-examination should the symptoms significantly worsen 
• Occurrence of other recent or current symptoms, even if they appear not related 
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8.3.6.1.3 
Additional investigations 
Investigators should arrange for the following investigations; further investigations may be 
requested after consultation with the Medical Monitor: 
• Additional blood sampling for extended etiological characterization of the hypersensitivity 
reaction including: 
− Basophil Activation Test 
− Lymphocyte Transformation Test assays 
− Tryptase 
− Immunoglobulin E 
• Rapid referral to experts (ie, dermatologist, allergist, or immunologist) 
Additionally, a skin biopsy may be considered following review by expert. 
8.3.6.1.4 
Treatment 
Investigators will administer the appropriate treatment as deemed necessary in cases of 
hypersensitivity. This includes the use of antihistamines for urticaria and the appropriate 
management in case of potentially life-threatening events such as anaphylaxis, Stevens-Johnson 
Syndrome, and toxic epidermal necrolysis. 
8.3.6.1.5 
Blood sampling 
Blood samples should be taken as soon as possible for safety and/or for further identification of 
the underlying mechanism of the reaction (hematology: eosinophilia; chemistry: check renal 
function including electrolytes, liver function tests, immunology, and IgE). Specific laboratory 
parameters (eg, cytokines, tryptase, complement, high-sensitivity C-reactive protein) will be 
collected at Day -1, and will be stored and used only in case of a hypersensitivity event (see 
Section 1.3). 
The timing of the blood collection and other details for each test will be specified in the 
laboratory manual, and the full set of clinical laboratory tests are provided in 
Appendix 2 (Section 10.2). 
8.3.6.1.6 
Rapid referral to experts 
Expert consulting (eg, dermatologist/allergist/immunologist) is required for expert opinion 
(diagnosis), diagnostic testing (eg, prick test for other potential allergens), further treatment, and 
follow up. Same day referral is required, especially if there is presentation of systemic symptoms 
and/or signs. 
8.3.6.2 
Renal function safety monitoring and management 
If a participant develops clinically significant renal dysfunction, repeat laboratory testing should 
be undertaken as soon as possible and other appropriate investigations may be arranged. An 
increase in serum creatinine of >25% from the previous value will trigger repeat testing within 
48 hours. The Medical Monitor should be notified, and consideration should be given to more 
frequent monitoring. 
Clinically significant renal dysfunction will trigger an SMC review. 
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Participants must be discontinued from study medication (but not necessarily from the study) if 
laboratory tests suggest evidence of renal toxicity (see Section 7.1.3 for renal toxicity stopping 
criteria and Section 7.2 for participant discontinuation/withdrawal from the study). Any 
clinically significant findings in laboratory results for renal function will be monitored until 
resolution or stabilization. 
The SMC charter will include further details regarding the assessment of renal function. 
8.4 
Safety signal detection 
Selected data from this study will be reviewed periodically to detect as early as possible any 
safety concern(s) related to the study medication so that Investigators, clinical study participants, 
regulatory authorities, and IRBs/IECs will be informed appropriately and as early as possible. 
The study physician or medically qualified designee/equivalent will conduct an ongoing review 
of SAEs and perform ongoing SAE reconciliations in collaboration with the Patient Safety 
representative. 
As appropriate for the stage of development and accumulated experience with the study 
medication, medically qualified personnel at UCB may identify additional safety measures (eg, 
AEs, vital signs, laboratory or ECG results) for which data will be periodically reviewed during 
the course of the study. 
8.5 
Treatment of overdose 
For this study, any administration of UCB0599 totaling greater than 360mg within 
approximately a 24-hour time period will be considered an overdose. 
Overdose events are only considered AEs or SAEs if there are associated clinical signs and 
symptoms or if the act of taking the excess study medication itself is an AE or SAE (eg, suicide 
attempt). 
UCB does not recommend specific treatment for an overdose. 
In the event of an overdose, the Investigator or treating physician should: 
• Stop dosing and contact the Medical Monitor immediately. 
• Closely monitor the participant for any AE/SAE and laboratory abnormalities until UCB0599 
can no longer be detected systemically (approximately 5 days). 
• Document the quantity of the excess dose as well as the duration of the overdose in the 
eCRF. 
Decisions regarding dose interruptions or modifications will be made by the Investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the participant. 
8.6 
Pharmacokinetics 
Pharmacokinetic sampling will be mandatory for study participation in Part A and Part B. 
Samples will be collected predose and at several time points after study medication 
administration. These samples are a required component of the protocol as specified in the 
Schedule of Activities (Section 1.3 for Part A [Table 1-3] and Part B [Table 1-4]). 
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U C B  
 
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U C B 0 5 9 9  
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C o nfi de ntial  
P a ge 6 6  of 1 0 1  
A n y c ha n ges i n t he ti mi n g or a d diti o n of ti me p oi nts f or a n y pla n ne d st u d y assess me nts m ust be 
d oc u me nte d a n d a p pr o ve d b y t he rele va nt st u d y tea m me m ber a n d t he n arc hi ve d i n t he S p o ns or 
a nd site st u d y files, b ut will n ot c o nstit ute a pr ot oc ol a me n d me nt. T he I E C will be i nf or me d of 
a n y s afet y iss ues t hat r e q uire alterati o n of t he safet y m o nit ori n g s c he me or a me n d me nt of t he 
I C F. 
A d diti o nal sa m ples ma y be c ollecte d at a d diti o nal ti me p oi nts d uri n g t he st u d y if warra nte d a n d 
a gree d u p o n b et wee n t he I n v esti gat or a n d t he S p o ns or. I nstr ucti o ns f or t he c ollecti o n a n d 
ha n dli n g of bi ol o gical s a m ples will be pr o vi de d b y t he S p o ns or. T h e act ual date a n d ti me 
( 2 4 h o ur cl oc k ti me) of eac h sa m ple will be rec or de d. 
See Secti o n  5. 3  f or g ui deli nes o n lifest yle restricti o ns i ncl u di n g details o n meals a n d dietar y 
restricti o ns. 
8. 6. 1  
P art A  
Plas ma sa m ples (a p pr o x i matel y 2 m L w h ole bl o o d c ollecti o n) will be use d t o e val uate t he 
pri mar y P K para meters ( Ta ble  3 -1 ), i n w hic h t h e relati ve bi oa vaila bilit y of 2 ne w U C B 05 9 9 
f or m ulati o ns will be assesse d c o m pare d wit h a refere nce ‘ gra n ules i n ca ps ule’ f or m ulati o n i n t he 
prese nce a n d a bse nce of es o me praz ole i n healt h y partici pa nts. Esti mate d P K para met ers ma y be 
use d f or t he e x p os ure -res p o nse assess me nt of safet y a n d t olerabilit y o bser vati o ns of eac h 
f or m ulati o n a n d acr oss f or m ulati o ns i n t he a bse nce/ pres e nce of es o me praz ole (Ta ble  3 -1 ). 
C ollecti o n of sa m ples f or ot her P K para m eters will be d o ne as part of t he st u d y o bjecti ves a n d 
will e val uate t he P K of U C B 0 5 9 9 f or eac h teste d f or m ulati o n  i n t he prese nce a n d a bse n ce of 
es o me praz ole ; a n d t he P K of U C B 0 5 9 9 a n d its meta b olites 
 after a 
si n gle d ose of U C B 0 5 9 9 al o ne a n d c o-a d mi nistrat e d wit h es o me praz ole ( T a ble  3 -1 ). I nstr ucti o ns 
pertai ni n g t o s a m ple c ollecti o n, pr ocess i n g, st ora ge, la beli n g, a n d s hi p pi n g are pr o vi d e d i n t he 
la b orat or y ma n u al f or t his st u d y. All c ollecte d s a m ples ma y be us e d f or researc h p ur p oses 
f oc usi n g o n m et h o d de vel o p me nt a n d assa y de v el o p me nt. C ollecti o n of t hese sa m ples will 
e na ble e v al uati o n of rel e va nt p har mac ol o gical i nf or mati o n t o s u p p ort U C B 0 5 9 9 ne w f or m ulati o n 
de vel o p me nt.  
8. 6. 2  
U s e of r e si d u al pl a s m a s a m pl e s ( P art A o nl y)  
A n y resi d ual a n d/ or s ur pl us P K plas ma sa m ples re mai ni n g aft er t he pr ot o c ol -defi ne d i nteri m 
a nal ysis h as bee n p erf or me d ma y b e use d f or a d diti o nal e x pl orat or y a nal ysis relate d t o t he 
p ur p ose of t his st u d y. T his ma y i ncl u de, b ut is n ot li mite d t o, bi o mar ker assa y 
de vel o p me nt/ o pti mizati o n, pr otei n bi n di n g, e x pl orat or y m eta b olite pr ofili n g/ q ua ntificati o n, or 
ot her bi oa nal ytical p ur p oses (e g, cr oss c hec k bet w ee n differe nt sites a n d/ or sta bilit y assess me nt). 
Gi ve n t he e x pl orat or y nat ure of t he w or k, t he a nal ytica l met h o d use d f or t h ose assess me nts will 
n ot be vali date d. As s uc h, t he res ults fr o m t his e x pl orat or y a nal ysis will n ot be i ncl u de d i n t he 
Cli nical St u d y Re p ort.  
Resi d ual a n d/ or s ur pl us P K plas ma sa m ples will n ot be use d f or a n y ge netic bi o mar ker researc h.  
8. 6. 3  
P art B  
Plas ma sa m ples (a p pr o xi matel y 2 m L w h ole bl o o d c ollecti o n) will be c ollecte d t o e val uate  t he 
plas ma c o nce ntrati o ns of U C B 0 5 9 9, as w ell as t o f urt her ass ess ot her P K e n d p oi nts of U C B 0 5 9 9 
a n d its meta b olites 
, as s p ecifie d i n t he Sc he d ul e of Acti vities 
( Secti o n 1. 3 ), after a d mi nistrati o n of a si n gle oral d ose of t he f or m ulati o n selecte d fr o m Part A i n 
C CI
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

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healthy participants of Japanese and Chinese origins. See Section 3 (Table 3-2) for details on 
primary and other PK endpoints. 
Estimated PK parameters may be used for the exposure-response assessment of safety and 
tolerability observations. 
Drug concentration information that would unblind the study will not be reported to investigative 
sites or blinded personnel until the study has been unblinded. 
8.7 
Biomarkers 
Genetic blood sampling will be mandatory for study participation. Collection of 
deoxyribonucleic acid (DNA) blood samples will occur as specified in the Schedule of Activities 
(Section 1.3) and may be used for exploratory research to further the understanding of how 
genetic variation may influence the metabolism, distribution, and elimination of UCB0599. No 
other analysis will be performed on the participant’s DNA. Instructions pertaining to sample 
collection, processing, storage, labeling, and shipping are provided in the laboratory manual for 
this study. 
Additional information is presented in Appendix 5 (Section 10.5). 
8.8 
Medical resource utilization and health economics 
Not applicable. 
9 
STATISTICAL CONSIDERATIONS 
A description of statistical methods follows and will be described in more detail in the Statistical 
Analysis Plan (SAP). 
9.1 
Definition of analysis sets 
The following analysis sets will be used: 
• All Study Participants (ASP): All study participants who signed the ICF for Part A or Part B, 
separately. 
• The Randomized Sets A (RS A) and B (RS B): All study participants who are randomized to 
Part A or to Part B, respectively. Of note, this set will only be produced if it differs from the 
Safety Set (SS). 
• The Safety Sets (SS; referred to as SS A and SS B for Part A and Part B, respectively): All 
study participants who are randomized and receive full or partial study medication according 
to the treatment that the participants actually received. The SS will be used for summaries of 
demographics, medical history, prior and concomitant medications, study medication 
exposure, and general safety outcomes such as AEs, laboratory parameters, vital signs, and 
ECGs. 
• The Pharmacokinetic Set (PKS; referred to as PKS A and PKS B for Part A and Part B, 
respectively): This is a subset of the SS and consists of those study participants who received 
at least 1 total dose of study medication and have at least 1 observable PK measurement 
without important protocol deviations that would affect the PK. 
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9.2 
General statistical considerations 
All analyses will be performed using SAS® version 9.4 or later (SAS Institute, Cary, NC, US). 
The appropriate noncompartmental PK parameters will be calculated from the UCB0599 plasma 
concentration-time data using Phoenix® WinNonlin® Version 8.0 or higher. Actual sample times 
will be used in the calculations of the PK parameters. 
For calculation of the plasma PK parameters of UCB0599 and metabolites, the actual sampling 
time points will be used in order to evaluate the PK parameters. 
9.3 
Planned efficacy outcome analyses 
There will be no efficacy endpoint in this study. 
9.4 
Planned PK outcome analyses 
9.4.1 
PK parameters to be measured 
The following PK parameters will be determined using the actual recorded sampling times and 
non-compartmental method(s) with Phoenix WinNonlin® (Version 8.3.4), as applicable: Cmax, 
tmax, AUClast, AUCinf, AUC%Extrap, t1/2, Lambda_z (z), CL/F (UCB0599 only), 
Vz/F (UCB0599), MRCmax, and MRAUCinf from the plasma concentration-time data. 
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Table 9-1: 
Non-compartmental PK parameters for UCB0599 in plasma 
PK Parameter 
Definition 
AUCinf 
The AUC from time zero to infinity (mass * time * volume-1). 
AUClast 
The AUC from time zero to the last measurable drug concentration sampling time 
(tlast) (mass * time * volume-1). 
Cmax 
The maximum (peak) observed drug concentration following a single dose 
administration (mass * volume-1). 
tmax 
The time to reach maximum (peak) drug concentration following a single dose 
administration (time). 
t1/2 
The elimination half-life associated with the terminal slope (λz) of a 
semilogarithmic concentration-time curve (time). 
CL/Fa 
The total apparent body clearance of drug (volume/time). 
Vz/Fa 
The apparent volume of distribution during terminal phase (associated with λz) 
(volume). 
Lambda_z (λz) 
Terminal elimination rate constant (1/time). 
AUC%Extrapb 
Area under the <matrix> concentration-time curve extrapolated from the time t to 
infinity as a percentage of total AUC. 
Rsq_adjc 
 
Square of the correlation coefficient (adjusted for the number of data points 
included) associated with λz. 
MRCmaxd 
Cmax metabolite to parent ratio. 
MRAUCinfd 
AUC0-inf metabolite to parent ratio. 
a For UCB0599 only 
b AUC%Extrap is listed if AUCinf is presented 
c Rsq_adj is listed only 
d Metabolites only 
The linear trapezoidal rule will be used for AUC calculation. Regression analysis of the terminal 
plasma elimination phase for the determination of t1/2 will include at least 3 data points after 
Cmax. If the Rsq_adj value of the regression analysis of the terminal phase is less than 0.75, no 
value is to be reported for AUCinf, t1/2, CL/F, and Vz/F. 
9.4.2 
Analysis of the primary PK endpoint 
9.4.2.1 
Part A 
The plasma concentration-time profiles and PK parameters of UCB0599 will be summarized by 
dose level and group using descriptive statistics (number of available observations, arithmetic 
mean, standard deviation, geometric mean, coefficient of variation of geometric mean, median, 
minimum, and maximum). Values below the lower limit of quantification (LLOQ) will be 
reported with a clear sign indicating that they were below the LLOQ. Descriptive statistics of 
concentrations will be calculated if at least two-thirds of the individual data points are 
quantifiable (≥LLOQ). 
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U C B  
 
2 6 Oct 2 0 2 3  
Cli nical St u d y Pr ot oc ol A me n d me nt 1  
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C o nfi de ntial  
P a ge 7 0  of 1 0 1  
T he pri mar y o bje cti ve of Part A is t o esti mate t he relati ve bi o vaila bilit y  of 2 ne w U C B 0 5 9 9 
f or m ulati o ns (fil m-c oate d ta blet c o ntai ni n g 
 wit h or wit h o ut e nca ps ulati o n) vers us 
t he c urre nt refere n ce f or m ulati o n ( gra n ules i n ca ps ule) u n der n or m al or ele vate d p H gastric 
c o n diti o ns i n healt h y partici pa nts. T he Part A pri m ar y P K e n d p oi nts are C ma x , A U C0 -t, a n d 
A U C i nf f or U C B 0 5 9 9 a d mi nistere d wit h o ut a n d wit h es o me praz ole. Descri pti ve statistics will be 
e x ec ute d f or all P K para meters esti mate d.  
I n di vi d ual c o n ce ntr ati o n-ti me pr ofiles will be dis pla ye d gra p hicall y o n a li near-li near scale a n d 
se mil o garit h mic scale. O verall ge o metric m ea n pl as ma c o nce ntrati o ns-ti me c ur ves a n d 
c orres p o n di n g 9 5 % CIs will be dis pla ye d b y f or m ulati o n a n d c o n diti o n (ele vate d a n d n or mal 
gastic p H).  
T he P K para m eters ( C ma x , A U C0 -t, a n d A U Ci nf) will be use d t o esti mate t he f oll o wi n g:  
•  Pri mar y o bje cti ve: t he rel ati ve bi oa vaila bilit y of 2 ne w U C B 0 5 9 9 f or m ulati o ns vers us 
refere nce ‘ gra n ules i n ca ps ule’ f or m ulati o n u n der ele vate d gastric p H a n d u n der n or mal 
c o n diti o ns  
T he pri mar y c o m p aris o ns of i nterest are:  
•  n o n -e nca ps ul ate d ta blets vs gra n ules i n ca ps ule u n der n or mal p H c o n diti o n  
•  e nca ps ulate d t a blets vs gra n ules i n ca ps ule u n d er n or mal p H c o n diti o n  
•  n o n -e nca ps ul ate d ta blets vs gra n ules i n ca ps ule u n der ele vate d p H c o n diti o n  
•  e nca ps ulate d t a blets vs gra n ules i n ca ps ule u n d er ele vate d p H c o n diti o n  
I n or der t o esti mate t h ese c o m paris o ns, t he pri mar y a n al ysis m o del will be a p plie d t o t he 2 sets 
of data se p aratel y; na m el y, t he d ata u n der n or mal gastri c p H c o n diti o n (first 3 -peri o d cr oss o v er 
desi g n s u bst u d y) a n d t h e d ata u n der ele vate d gastric p H c o n diti o n (sec o n d 3 -peri o d cr oss o v er 
desi g n s u bst u d y).  
F oll o wi n g l o g -tr a nsf or m ati o n, t he pri mar y P K para meters ( Cma x , A U C0 -t, a n d A U Ci nf) will eac h 
be e val uat e d acc or di n g t o a li near mi x e d effect m o del wit h a ra n d o m i nterce pt ter m f or 
partici pa nt a n d fi x e d effect cate g ori cal ter ms f or treat me nt, se q ue n ce, a n d p eri o d t o acc o u nt f or 
t he cr oss o ver nat ure of t he desi g n f or Part A. 
T he P K a nal yses will be perf or me d o n t h e P K dat a fr o m Part A.  
F or eac h set of data, t he esti mate of t h e rati o of ge o metric mea n f or t he U C B 0 5 9 9 fil m -c oate d 
ta blet vers us ca ps ul e (refere nce f or m ulati o n) a n d f or t he U C B 0 5 9 9 e nca ps ulate d ta blet vers us 
ca ps ule (refere n ce f or m ulati o n) treat me nts will be calc ulate d al o n g wit h its c orres p o n di n g 
9 0 %  c o nfi de n ce i nt er val ( CI) i n or der t o assess t he U C B 0 5 9 9 relati ve bi oa vaila bilit y.  
Se nsiti vit y a n al ys es t o t he m o del a b o ve ma y b e perf or me d o n t he P K p ara m eters, s uc h as li near 
mi x e d effect m o dels a p plie d se paratel y t o t he data f or eac h ne w f or m ulati o n vers us refere nce 
for m ulati o n.  
A n ot her o bjecti ve of t he st u d y is t o esti mate t he relati ve bi oa vaila bilit y of U C B 0 5 9 9 u n der 
ele vate d gastric p H vers us n or mal gastric p H f or eac h teste d f or m ulati o n. T o t hat effect, a 
s u p ple me ntar y a n al ysis will be perf or me d usi n g t he P K para met ers ( Cma x , A U C0 -t, a n d A U Ci nf) 
w here d ata fr o m all 6 peri o ds ( n or mal a n d ele vate d gastri c p H data) will be c o m bi ne d i nt o a 
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

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single linear mixed effect model with a random intercept for participant and fixed effect 
categorical terms for treatment, gastric status, treatment by gastric status interaction, sequence, 
and period within substudy (ie, 3-level categorical variable). As before, ratios and corresponding 
90% CIs will be obtained for the UCB0599 capsule, non-encapsulated tablet, or encapsulated 
tablet under elevated gastric pH condition versus the respective formulation under normal gastric 
pH condition. 
9.4.2.2 
Part B 
The primary objective of Part B is to evaluate the plasma PK of UCB0599 after administration of 
a single dose of an oral formulation in healthy participants of Japanese and Chinese origins. 
The PK parameters (Cmax, AUC0-t, and AUCinf) will be used to estimate the following: 
• PK parameters for the 3 groups (Part A healthy participants, Japanese participants, and 
Chinese participants) 
• Dose proportionality for each group, including graphical presentation 
Individual concentration-time profiles will be displayed graphically on a linear-linear scale and 
semilogarithmic scale. 
Overall geometric mean plasma concentration-time curves and corresponding 95% CIs will be 
displayed by group. 
No formal comparison will be made. 
The PK analyses will be performed on the PK data from Part B. 
The plasma concentration-time profiles and PK parameters of UCB0599 will be summarized by 
dose level and group using descriptive statistics (number of available observations, arithmetic 
mean, standard deviation, geometric mean, coefficient of variation of geometric mean, median, 
minimum, and maximum). Values below the LLOQ will be reported with a clear sign indicating 
that they were below the LLOQ. Descriptive statistics of concentrations will be calculated if at 
least two-thirds of the individual data points are quantifiable (≥LLOQ). 
Descriptive statistics will be executed for all PK parameters estimated by ethnicity and dose. For 
tmax, only the median, minimum, and maximum will be reported. 
The PK descriptive statistics from Part A healthy participants who receive 180mg dose of the 
formulation used in Part B will be presented alongside. 
Dose proportionality for Cmax, AUC0-t, and AUCinf will be examined for each ethnic group and 
for Part A healthy participants who receive a 180mg dose of the formulation used in Part B and 
graphically reported. Dose proportionality could be achieved by dose normalization and 
log-transforming Cmax and AUC data, in which a linear regression Cmax versus dose and AUC 
versus dose will be used to assess if the slope of the regression line deviates statistically 
significantly from zero. If the slope is not different from zero, then it can be concluded that the 
PK is proportional to dose. 
The co-primary PK endpoint data obtained for the UCB0599 formulation used in Part B at the 
180mg dose under normal gastric pH condition for the three ethnicities (ie, N=36 participants 
from Part A, N=8 participants of Japanese origin, and N=8 participants of Chinese origin) will be 
log-transformed. As an exploratory analysis, transformed data will be combined into an Analysis 
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U C B  
 
2 6 Oct 2 0 2 3  
Cli nical St u d y Pr ot oc ol A me n d me nt 1  
U C B 0 5 9 9  
U P 0 0 7 3  
 
 
 
C o nfi de ntial  
P a ge 7 2  of 1 0 1  
of Varia n ce ( A N O V A) m o del wit h fi x e d effect t er ms f or c o h ort, ass u mi n g t he data f or eac h 
et h nicit y c o m e fr o m a si n gle p arallel ar m de si g n. P oi nt esti mates f or t he ge o metric mea n rati os 
a n d c orres p o n di n g 9 0 % CIs will be o btai ne d a n d c o m pare d b et wee n t h e J a pa nese partici pa nts 
vers us t he Part A partici pa nts, a n d bet wee n t he C hi nese partici pa nts vers us t he Part  A 
partici pa nts usi n g le ast s q uares me a ns a n d r o ot m ea n s q uares of err or fr o m t he m o del wit h 
s u bse q ue nt e x p o ne ntial tra nsf or mati o n. 
9. 4. 3  
Ot h er P K e n d p oi nt a n al y s e s  
9. 4. 3. 1  
P art A  
T he ot her P K para meters of U C B 0 5 9 9 a n d m eta b olites will be s u m marize d b y f or m ulati o n a n d 
c o n diti o n of gastri c p H (ele vat e d a n d n or mal) usi n g des cri pti ve statistics as descri be d i n 
Secti o n  9. 4. 2. 1 . 
•  F or U C B 0 5 9 9: t ma x , t½ , C L/ F, a n d Vz/ F (if p ossi bl e b ut n ot li mite d). F or tma x , o nl y t he 
me dia n, mi ni m u m, a n d ma xi m u m will be re p orte d.  
•  F or 
 meta b olites: Cma x , tma x , A U C0 -t, A U Ci nf, a n d eac h 
meta b olite/ pare nt C ma x  a n d A U C rati o (c orrecte d f or t he m olec ular wei g ht of t he e ntities), as 
a p pr o priate.  
9. 4. 3. 2  
P art B  
T he  ot her P K para meters of U C B 0 5 9 9 a n d m eta b olites will be s u m marize d b y et h nicit y a n d d os e 
usi n g descri pti ve statistics as descri be d i n Secti o n  9. 4. 2. 2 . 
•  Ot her P K para meters of U C B 0 5 9 9: t ma x , C L/ F, Vz/ F, t1/ 2, Cma x / B W/ D, A U C0 -t/ B W/ D, a n d 
A U C i nf/ B W/ D. F or tma x , o nl y t he me dia n, mi ni m u m, a n d ma xi m u m will be re p orte d. 
•  Ot her P K para meters of 
 meta b olites: C ma x , tma x , A U C 0 -t, a n d A U Ci nf, 
a n d eac h meta b olite/ pare nt A U C rati o, as a p pr o priate.  
9. 5  
Pl a n n e d s af et y a n d ot h er a n al y s e s  
9. 5. 1  
S af et y a n al y s e s  
U nless state d ot her wise, all safet y a n al ys es will be perf or me d o n t he S S.  
All A Es will be c o de d usi n g t he m ost rece nt Me di cal Dicti o nar y f or Re g ulat or y Acti vities 
( Me d D R A® ) a n d c haract erize d as pretr eat me nt a n d treat me nt e mer ge nt acc or di n g t o t he i nta ke of 
t he st u d y me dicati o n. 
T he occ urre n ce a n d i n ci de nce of T E A Es will be s u m marize d b y Me d D R A s yste m or ga n class 
( S O C), H L T, a n d preferre d ter m ( P T), a n d b y tr eat me nt a n d et h nic gr o u p (f or Part B o nl y). T h e 
occ urre nce a n d i nci de n ce of T E A Es will als o be s u m marize d b y ma xi m u m e ve nt i nte nsit y a n d 
b y relati o ns hi p t o t he st u d y me dicati o n. A d verse e ve nts will be cate g orize d b y se v erit y 
( mil d/ m o derate/se vere). All A Es will be liste d a n d will i ncl u de acti o ns ta ke n f or eac h A E, t h e 
ti me of o nset of t he A E after d osi n g, a n d t he d urati o n of eac h A E. A d verse e ve nts lea di n g t o 
disc o nti n uati o n a n d S A Es will als o be s u m marize d b y treat me nt gr o u p a n d et h nic gr o u p. 
La b orat or y  v aria bles a n d c ha n ges fr o m Baseli ne will be s u m marize d b y ti me p oi nt a n d will be 
prese nte d b y tr eat me nt a n d et h nic gr o u p. F or cat e g orize d val ues acc or di n g t o t he refere nce 
ra n ge, s hift ta bles fr o m Baseli ne ( Da y -1, or Da y 1 pri or t o first treat me nt) t o ea c h p ost -Bas eli ne 
C CI
C CI
P U B LI C C O P Y 
T hi s d o c u m e nt c a n n ot b e u s e d t o s u p p ort a n y m ar k eti n g a ut h ori z ati o n 
a p pli c ati o n a n d a n y e xt e n si o n s or v ari ati o n s t h er e of.

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time point will be presented for selected variables to be defined in the SAP. Values outside the 
reference range will be flagged in the listings. 
Vital sign variables (SBP and DBP, pulse rate, respiration rate, and body temperature) and 
changes from Baseline (Day -1, or Day 1 prior to first treatment) will be summarized by time 
point and will be presented by treatment and ethnic group. 
Single 12-lead ECGs will be recorded at each time point as noted in the study Schedule of 
Activities (Section 1.3). Descriptive statistics will be presented for ECG values and changes 
from Baseline (Day -1, or Day 1 prior to first treatment) over time. 
See Section 9.8 for details on planned interim analyses and data monitoring. 
9.6 
Handling of protocol deviations 
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on study conduct, or on the PK and key safety for an individual study 
participant. The criteria for identifying important protocol deviations will be defined within the 
appropriate protocol-specific document. Important protocol deviations will be reviewed as part 
of the ongoing data cleaning process and all important deviations will be identified and 
documented to confirm exclusion from analysis sets. All important deviations will be identified 
and documented to confirm exclusion from the analysis sets. 
9.7 
Handling of dropouts or missing data 
In general, there will be no imputation of missing data. Handling of missing or partial dates 
and/or times for safety assessments will be described in the SAP. 
9.8 
Planned interim analysis and data monitoring 
There is 1 planned interim analysis. After completion of Part A, an interim analysis will be 
performed on key PK endpoints for all data, to support the decision on selection of the Part B 
formulation. 
An SMC will be established before the start of the study (as described in Section 10.1.6). During 
Part B, data will be examined after Cohort 3, in order to proceed to the next dose level in the 
Japanese and Chinese participants. Throughout the study, safety and tolerability data will be 
reviewed on an ongoing basis by the SMC as described in Section 4.1. A detailed description of 
the composition and conduct of the SMC will be provided in a separate SMC Charter. 
9.9 
Determination of sample size 
9.9.1 
Part A 
To assess the relative bioavailability of 2 new formulations (film-coated tablet or encapsulated 
tablet) to the reference formulation (capsule) under conditions of normal or elevated gastric pH 
with the desired power of 90%, the study was estimated to require approximately 36 completers 
with a maximum of 42 randomized participants. No replacements are planned. 
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The assessment was based on two 1-sided ratio of means tests (TOST) for a 3-treatment, 
6-sequence, 3-period complete Williams’ square crossover design for continuous response data 
with significance level of 0.05 (5%), assuming: 
• a ratio of means between any of the 2 new formulations and the reference formulation under 
the alternative hypothesis (H1) of 1.0 
• lower and upper limits of 0.8 and 1.25, respectively 
• a geometric intra-participant coefficient of variation (CV) of 28.5% based on the mean 
estimate of the residual variance obtained from the linear mixed effect model of the 
log-transformed Cmax data from the UP0078 study (𝜎2=0.0782), a trial with similar 
participants demographics (males and female aged 18 to 55), and which used a crossover 
design. 
For more details, please refer to the UCB0599 UP0073 sample size calculation documentation 
form (eTMF: “UCB0599_UP0073_Sample_size_calculation_documentation_form.doc”). 
9.9.2 
Part B 
A formal sample size calculation has not been performed; the group sizes are based upon 
historical precedent and regulatory requirements. 
In order to estimate PK and safety profiles in 2 ethnic groups (Japanese and Chinese origins), it 
is considered that a group size of at least 10 participants in each ethnicity (8 participants on 
active drug at each dose and 2 participants on placebo) is appropriate. Chinese Center for Drug 
Evaluation (CDE) guidance suggests 8 to 12 participants per dose, whereas Japanese 
Pharmaceuticals and Medical Devices Agency (PMDA) guidance suggests 6 participants per 
dose for PK studies; both suggest 2 participants on placebo. 
The Asian Pacific cohort participants will be recruited from the same clinical center as the 
participants from Part A (based on prior recommendation, see PMDA report on Opicapone, 
2020 https://www.pmda.go.jp/files/000243472.pdf); and therefore, the Part A cohort of healthy 
participants can be used for assessment alongside the Japanese and Chinese cohorts, using the 
Part A PK data for a formulation of choice. 
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10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 
Appendix 1: Regulatory, ethical, and study oversight 
considerations 
10.1.1 
Regulatory and ethical considerations 
The study will be conducted under the auspices of an IRB/IEC, as defined in local regulations, 
International Council for Harmonisation (ICH)-GCP (ICH E6[R2]), and in accordance with the 
ethical principles that have their origin in the Declaration of Helsinki (1996). 
The Investigator/UCB will ensure that an appropriately constituted IRB/IEC that complies with 
the requirements of the current ICH-GCP version or applicable country-specific regulations will 
be responsible for the initial and continuing review and approval of the clinical study. Prior to 
initiation of the study, the Investigator/UCB will forward copies of the protocol, ICF, IB, 
Investigator’s curriculum vitae (if applicable), advertisement (if applicable), and all other 
participant related documents to be used for the study to the IRB/IEC for its review and 
approval. 
Before initiating a study, the Investigator will have written and dated full approval from the 
responsible IRB/IEC for the protocol. 
The Investigator will also promptly report to the IRB/IEC all changes in the study, all 
unanticipated problems involving risks to participants or others, and any protocol deviations, to 
eliminate immediate hazards to participants. 
The Investigator will not make any changes in the study or study conduct without IRB/IEC 
approval, except where necessary to eliminate apparent immediate hazards to the participants. 
For minor changes to a previously approved protocol during the period covered by the original 
approval, it may be possible for the Investigator to obtain an expedited review by the IRB/IEC as 
allowed. 
As part of the IRB/IEC requirements for continuing review of approved studies, the Investigator 
will be responsible for submitting periodic progress reports to the IRB/IEC (based on IRB/IEC 
requirements), at intervals appropriate to the degree of participant risk involved, but no less than 
once per year. The Investigator should provide a final report to the IRB/IEC following study 
completion. 
UCB (or its representative) will communicate safety information to the appropriate regulatory 
authorities and all active investigators in accordance with applicable regulatory requirements. 
The appropriate IRB/IEC will also be informed by the Investigator or the Sponsor, as specified 
by the applicable regulatory requirements in each concerned country. Where applicable, 
Investigators are to provide the Sponsor (or its representative) with evidence of such IRB/IEC 
notification. 
10.1.2 
Financial disclosure 
Insurance coverage will be handled according to local requirements. 
Finance and insurance are addressed in the Investigator and/or CRO agreements, as applicable. 
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10.1.3 
Informed consent process 
Participant’s informed consent must be obtained and documented in accordance with local 
regulations, ICH-GCP requirements, and the ethical principles that have their origin in the 
principles of the Declaration of Helsinki. 
Prior to obtaining informed consent, information should be given in a language and at a level of 
complexity understandable to the participant in both oral and written form by the Investigator (or 
designee). Each participant will have the opportunity to discuss the study and its alternatives 
with the Investigator. 
Prior to participation in the study, an IRB/IEC approved, written ICF should be signed and 
personally dated by the participant, or his/her legal representative, and by the person who 
conducted the informed consent discussion (Investigator or designee). The participant or his/her 
legal representative must receive a copy of the signed and dated ICF. As part of the consent 
process, each participant must consent to direct access to his/her medical records for 
study-related monitoring, auditing, IRB/IEC review, and regulatory inspection. 
If the ICF is amended during the study, the Investigator (or the Sponsor, if applicable) must 
follow all applicable regulatory requirements pertaining to the approval of the amended ICF by 
the IRB/IEC and use of the amended form. 
All studies conducted at centers in the United States must include the use of a Health Insurance 
Portability and Accountability Act authorization form. 
The participant may withdraw his/her consent to participate in the study at any time. A 
participant is considered as enrolled in the study when he/she has signed the ICF. An eCRF must 
not be started, nor may any study specific procedure be performed for a given participant, 
without having obtained his/her written consent to participate in the study. 
10.1.4 
Recruitment strategy 
The participants will be recruited from the volunteer database of the study center, as well as by 
advertisement. 
10.1.5 
Data protection 
UCB staff (or designee) will affirm and uphold the participant’s confidentiality. Throughout this 
study, all data forwarded to UCB (or designee) will be identified only by the participant number 
assigned at screening. 
The Investigator agrees that representatives of UCB, its designee, representatives of the relevant 
IRB/IEC, or representatives of regulatory authorities will be allowed to review that portion of the 
participant’s primary medical records that directly concerns this study (including, but not limited 
to, laboratory test result reports, ECG reports, admission/discharge summaries for hospital 
admissions occurring during a participant’s study participation, and autopsy reports for deaths 
occurring during the study). 
The participant must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant. 
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The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
10.1.6 
Committees structure 
An SMC will review the safety/tolerability data in this study as described in Section 4.1. 
Ad hoc SMC meetings can be held for other reasons if determined appropriate by the Sponsor. 
At a minimum, the SMC must include the following study participants: Investigator(s), Sponsor 
Study Physician, Sponsor Patient Safety representative, Quantitative Clinical Pharmacologist, 
and Sponsor Biostatistician. 
10.1.7 
Dissemination of clinical study data 
All Phase 1-4 clinical studies in participants will be registered on ClinicalTrials.gov with results 
posted after completion of the study. 
A plain language summary of the results of all Phase 1-4 clinical studies will be developed and 
shared on UCB’s website. 
UCB is committed to submitting all Phase 2-4 clinical study results, irrespective of outcome, for 
publication in a credible, peer-reviewed journal. While there are some exceptions owing to 
intellectual property considerations in early clinical development, our policy is also to submit 
Phase 1 study results for publication in a peer-reviewed journal wherever possible. 
Due to the small sample size in this study, individual patient-level data cannot be adequately 
anonymized as there is a reasonable likelihood that individual participants could be re-identified. 
For this reason, data from this study cannot be shared. 
10.1.8 
Data quality assurance 
All participant data relating to the study will be recorded on printed or eCRF unless transmitted 
to the Sponsor or designee electronically (eg, laboratory data). The Investigator is responsible for 
verifying that data entries are accurate and correct by physically or electronically signing the 
CRF. 
The Investigator must prepare and maintain adequate and accurate documentation (source data) 
of all observations and other data pertinent to the clinical study for each participants that 
supports the information entered in the eCRF. Frequent communication between the clinical unit 
and the Sponsor is essential to ensure that the safety of the study is monitored adequately. The 
Investigators will make all appropriate safety assessments on an ongoing basis. 
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
The Sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, legible, contemporaneous, original, 
complete, verifiable, and attributable from source documents; that the safety and rights of 
participants are being protected; and that the study is being conducted in accordance with the 
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currently approved protocol and any other study agreements, ICH-GCP, and all applicable 
regulatory requirements. 
All essential documents must be retained by the Investigator for the minimum retention period 
mandatory under the applicable local laws and regulations. The Investigator will contact UCB 
for authorization prior to the destruction of any study records or in the event of accidental loss or 
destruction of any study records. The Investigator will also notify UCB should he/she relocate or 
move the study-related files to a location other than that specified in the Sponsor’s trial master 
file. 
Quality tolerance limits will be established for the study using parameters related to patient 
safety reporting and reliability of study results. The parameters will be monitored throughout the 
study to identify systematic issues. Parameters used, parameter values, important deviations from 
the quality tolerance limits, and actions taken will be summarized in the clinical study report. 
10.1.8.1 
eCRF completion 
The Investigator is responsible for prompt reporting of accurate, complete, and legible data in the 
eCRFs and in all required reports. 
Any change or correction to the eCRF after saving must be accompanied by a reason for the 
change. 
Corrections made after the Investigator’s review and approval (by means of a 
password/electronic signature) will be reapproved by the Investigator. 
The Investigator should maintain a list of personnel authorized to enter data into the eCRF. 
Detailed instructions will be provided in the eCRF Completion Guidelines. 
10.1.8.2 
Application 
Not applicable. 
10.1.9 
Source documents 
All source documents must be accurate, clear, unambiguous, permanent, and capable of being 
audited. They should be made using some permanent form of recording (ink, typing, printing, 
optical disc). They should not be obscured by correction fluid or have temporary attachments 
(such as removable self-stick notes). 
Source documents are original records in which raw data are first recorded. These may include 
hospital/clinic/general practitioner records, charts, diaries, x rays, laboratory results, printouts, 
pharmacy records, care records, ECG, or other printouts, completed scales, Quality-of-Life 
questionnaires, or video, for example. Source documents should be kept in a secure, limited 
access area. 
Source documents that are computer generated and stored electronically must be printed for 
review by the monitor (eg, ECG reports). Once printed, these copies should be signed and dated 
by the Investigator and become a permanent part of the participant’s source documents. The 
Investigator will facilitate the process for enabling the monitor to compare the content of the 
printout and the data stored in the computer to ensure all data are consistent. 
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10.1.10 
Study and site start and closure 
The start of recruitment 
The start of recruitment is the first participant’s first visit and is also the start date of the clinical 
study. 
Study/site termination 
The Sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The Investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include but are 
not limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the Sponsor's procedures, or GCP guidelines 
• Inadequate recruitment of participants by the Investigator 
• Discontinuation of further study medication development 
• Required adaptation of the maximum insurance sum is not possible (ie, the risk/benefit 
estimation changes, leading to insufficient insurance coverage while the maximum insurance 
sum is not adapted) 
• The positive evaluation or approval is withdrawn by the IEC or local health authority 
The criteria for study holds due to AEs are provided in Section 8.3 and Appendix 3 
(Section 10.3). 
10.1.11 
Publication policy 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the Investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. 
This allows the Sponsor to protect proprietary information and to provide comments. 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating Investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 
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10.4 
Appendix 4: Contraceptive guidance and collection of 
pregnancy information 
Definitions 
Woman of childbearing potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below). 
Women in the following categories are not considered WOCBP: 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
− Documented hysterectomy 
− Documented bilateral salpingectomy 
− Documented bilateral oophorectomy 
Note: Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview. 
3. Postmenopausal female 
− A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high FSH level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or HRT. However, in 
the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. 
− Females on HRT and whose menopausal status is in doubt will be required to use one of 
the non-estrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
Contraception guidance 
Male participants 
Male participants with female partners of childbearing potential are eligible to participate if they 
agree to ONE of the following: 
• Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent 
on a long-term and persistent basis) and agree to remain abstinent. 
• Agree to use a male condom plus partner use of a contraceptive method with a failure rate of 
<1% per year as described in the table below when having penile-vaginal intercourse with a 
woman of childbearing potential who is not currently pregnant. 
In addition, male participants must refrain from donating sperm for the duration of the study and 
for 3 months after the last dose of study medication. 
Male participants with a pregnant or breastfeeding partner must agree to remain abstinent from 
penile vaginal intercourse or use a male condom during each episode of penile penetration during 
the protocol-defined time frame and for 1 week after the last dose of study medication. 
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Female participants 
Female participants of childbearing potential are eligible to participate if they agree to use a 
highly effective method of contraception consistently and correctly as described in the table 
below. 
Highly effective contraceptive methodsa 
Highly effective contraceptive methods that are user dependentb 
Failure rate of <1% per year when used consistently and correctly.  
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of 
ovulationc 
• 
Oral 
• 
Intravaginal 
• 
Transdermal 
Progestogen only hormonal contraception associated with inhibition of ovulation 
• 
Oral 
• 
Injectable 
Highly effective methods that are user independentc 
Implantable progestogen only hormonal contraception associated with inhibition of ovulation 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS) 
• 
Bilateral tubal occlusion 
Vasectomized partner 
A vasectomized partner is a highly effective contraception method provided that the partner is the sole 
male sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional 
highly effective method of contraception should be used. 
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the 
preferred and usual lifestyle of the participant. 
NOTES: 
a) In case of newly started contraception pills/IUDs, PI should consider the correct timing of 
starting/applying such methods in relation to the menstrual cycle and the manufacturing instruction as to 
when these newly started methods would become effective. 
b) Typical use failure rates may differ from those when used consistently and correctly. Use should be 
consistent with local regulations regarding the use of contraceptive methods for participants participating 
in clinical studies. 
c) Hormonal contraception may be susceptible to interaction with the IMP, which may reduce the 
efficacy of the contraceptive method. In this case, two highly effective methods of contraception should 
be utilized during the treatment period and for at least 1 week after the last dose of study treatment. 
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Pregnancy testing 
• A WOCBP should only be included after a confirmed menstrual period and a negative highly 
sensitive serum pregnancy test at the Screening Visit. 
• Additional urine pregnancy testing should be performed on Day -1 and at the SFU Visit after 
the last dose of study medication (and as required on all other occations). 
• Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected. 
• A positive urine test should be confirmed by a blood test with a sensitivity of 25 mIU/mL. 
Male participants with partners who become pregnant 
• The Investigator will attempt to collect pregnancy information on any male participant’s 
female partner who becomes pregnant while the male participant is in this study. This applies 
only to male participants who receive study treatment. If the participant is later found to be 
on placebo, then pregnancy data collection can stop. 
• After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the Investigator will record pregnancy information on the appropriate form and 
submit it to the Sponsor within 1 working day of learning of the partner’s pregnancy. The 
female partner will also be followed to determine the outcome of the pregnancy. Information 
on the status of the mother and child will be forwarded to the Sponsor. Generally, the follow 
up will be at least 12 months after the delivery date. Any termination of the pregnancy will 
be reported regardless of fetal status (presence or absence of anomalies) or indication for the 
procedure. 
Female participants who become pregnant 
• Any female participant who becomes pregnant while participating in the study will 
discontinue study medication or be withdrawn from the study. 
• The Investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate 
form and submitted to the Sponsor within 1 working day of learning of a participant's 
pregnancy. The participant will be followed to determine the outcome of the pregnancy. The 
Investigator will collect follow up information on the participant and the neonate and the 
information will be forwarded to the Sponsor. Generally, the follow up will be at least 
12 months after the delivery date. Any termination of pregnancy will be reported, regardless 
of fetal status (presence or absence of anomalies) or indication for the procedure. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE. A spontaneous 
abortion is always considered to be a SAE and will be reported as such. Any poststudy 
pregnancy-related SAE considered reasonably related to the study medication by the 
Investigator will be reported to the Sponsor as described in Section 8.3.5. While the 
Investigator is not obligated to actively seek this information in former participants, he or she 
may learn of a SAE through spontaneous reporting. 
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10.5 
Appendix 5: Genetics 
Use and analysis of DNA 
• Normal inter-individual and inter-ethnic genetic variation may impact a participant’s 
response to study medication due to how it may affect the way the body handles the drug (ie, 
drug absorption, distribution, metabolism, and excretion). In addition, genetic differences 
may also play a role in determining response to the drug, where response is defined broadly 
to include safety and tolerability. 
• DNA samples will only be used for research related to exposure and response to UCB0599. 
They may also be used to develop tests/assays including diagnostic tests related to UCB0599. 
Genetic research may consist of the analysis of one or more candidate genes or the analysis 
of genetic markers throughout the genome. 
• The samples may be analyzed as part of a multi-study assessment of genetic factors involved 
in the response to UCB0599 or study medications of this class to understand study disease or 
related conditions. 
• The results of genetic analyses may be reported in the Clinical Study Report or in a separate 
study summary. 
• The Sponsor will store the DNA samples in a secure storage space with adequate measures to 
protect confidentiality. 
• The samples will be retained while research on UCB0599 continues but no longer than 
20 years or other period as per local requirements. 
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10.6 
Appendix 6: Liver safety – suggested actions and follow up 
assessments 
Participants with PDILI must be assessed to determine if study medication must be discontinued. 
In addition, all concomitant medications and herbal supplements that are not medically necessary 
should also be discontinued. 
Investigators should attempt to obtain information on participants in the case of study medication 
discontinuation to complete the final evaluation. 
Participants with PDILI should not be withdrawn from the study until investigation and 
monitoring are complete. All results of these evaluations and observations, as well as the 
reason(s) for study medication discontinuation and/or participant withdrawal (if applicable), 
must be recorded in the source documents. The eCRF must document the primary reason for 
discontinuation of study medication. 
A specific monitoring plan must be agreed between the UCB study physician and the 
Investigator for participants who have ALT >5 ULN. The monitoring plan should include any 
necessary follow up assessments (until resolution of the abnormal laboratory values). 
Phase 1 liver chemistry stopping criteria are designed to assure participant safety and to evaluate 
liver event etiology (see Section 7.1.1 and Table 10-1). 
Table 10-1: Phase 1 Liver Chemistry Stopping Criteria and Follow up 
Assessments Table 
Liver Chemistry Stopping Criteria 
ALT-absolute 
ALT ≥3xULN 
If ALT ≥3xULN AND bilirubin 2xULN (>35% direct bilirubin) or INR >1.5, 
report as a SAEa b 
See additional actions and follow up assessments below 
Required Actions and Follow up Assessments 
Actions 
Follow up Assessments 
• Immediately discontinue study 
intervention 
• Report the event to the Sponsor within 
24 hours 
• Complete the liver event eCRF, and 
complete an SAE data collection tool if the 
event also met the criteria for an SAEb 
• Perform liver function follow up 
assessments 
• Monitor the participant until liver function 
test abnormalities resolve, stabilize, or 
return to baseline (see MONITORING) 
• Viral hepatitis serologyc 
• Obtain INR and recheck with each liver 
chemistry assessment until the 
transaminases values show downward 
trend 
• Obtain blood sample for PK analysis at 
predose and at 0.25, 0.5, 1, 1.5, 2, 4, 8, 
12, 24, 36, 48, 72, and 96 hours after the 
most recent dose of UCB0599d 
• CPK and LDH 
• Fractionate bilirubin, if total bilirubin 
 2xULN 
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Table 10-1: Phase 1 Liver Chemistry Stopping Criteria and Follow up 
Assessments Table 
• Consider the need for a toxicology 
screening. 
MONITORING: 
If ALT ≥3xULN AND bilirubin 2xULN or 
INR >1.5 
• Repeat liver function tests (include ALT, 
AST, alkaline phosphatase, bilirubin) and 
perform liver function follow up 
assessments within 24 hours. 
• Monitor participant twice weekly until 
liver function test abnormalities resolve, 
stabilize, or return to baseline. 
• A specialist or hepatology consultation is 
recommended. 
If ALT ≥3xULN AND bilirubin <2xULN 
and INR ≤1.5: 
• Repeat liver function tests (include ALT, 
AST, alkaline phosphatase, bilirubin) and 
perform liver function follow up 
assessments within 24 to 72 hours 
• Monitor participants weekly until liver 
function abnormalities resolve, stabilize, or 
return to baseline 
• Complete blood count with differential to 
assess eosinophilia 
• Record the appearance or worsening of 
clinical symptoms of liver injury, or 
hypersensitivity, on the AE CRF 
• Record use of concomitant medications 
(including acetaminophen, herbal 
remedies, and other over-the-counter 
medications) on the concomitant 
medications CRF 
• Record alcohol use on the liver event 
alcohol intake CRF 
If ALT ≥3xULN AND bilirubin 2xULN 
or INR >1.5: 
• Anti-nuclear antibody, anti-smooth 
muscle antibody, Type 1 anti-liver 
kidney microsomal antibodies, and 
quantitative total IgG or gamma 
globulins 
• Serum acetaminophen adduct HPLC 
assay (quantifies potential acetaminophen 
contribution to liver injury in participants 
with definite or likely acetaminophen use 
in the preceding week [James, 2009]) 
NOTE: Not required in China. 
• Liver imaging (ultrasound, magnetic 
resonance, or computerized tomography) 
and/or liver biopsy to evaluate liver 
disease; complete liver imaging and/or 
liver biopsy CRFs 
AE=adverse event; ALT= alanine aminotransferase; AST=aspartate transaminase; CPK=serum creatine 
phosphokinase; CRF=case report form; HPLC=high performance liquid chromatography; 
IgG= immunoglobulin G; INR=international normalized ratio; LHD=lactate dehydrogenase; 
PK=pharmacokinetic(s); SAE=serious adverse event; ULN=upper limit of normal 
a Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study intervention if ALT 3xULN and bilirubin 2xULN. Additionally, if 
serum bilirubin fractionation testing is unavailable, record the absence/presence of detectable urinary 
bilirubin on dipstick which is indicative of direct bilirubin elevations suggesting liver injury. 
b All events of ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin) or ALT 3xULN and INR >1.5 
may indicate severe liver injury (possible ‘Hy’s Law’) and must be reported as an SAE (excluding studies 
of hepatic impairment or cirrhosis). The INR measurement is not required and the stated threshold value will 
not apply to participants receiving anticoagulants. 
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Table 10-1: Phase 1 Liver Chemistry Stopping Criteria and Follow up 
Assessments Table 
c Includes: Hepatitis A immunoglobulin M (IgM) antibody; HBsAg and HBcAb; hepatitis C RNA; 
cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, heterophile 
antibody or monospot testing); and hepatitis E IgM antibody. 
d PK sample may not be required for participants known to be receiving placebo or non-comparator interventions. 
Record the date/time of the PK blood sample draw and the date/time of the last dose of study intervention prior 
to the PK blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the participant’s 
best approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot be 
collected in the time period indicated above, do not obtain a PK sample. Instructions for sample handling and 
shipping are in the Study Reference Manual. 
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10.7 
Appendix 7: Medical device AEs, ADEs, SAEs, and device 
deficiencies: Definition and procedures for recording, 
evaluating, follow up, and reporting 
Not applicable. 
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10.8 
Appendix 8: Rapid alert procedures 
Not applicable. 
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10.9 
Appendix 9: Country-specific requirements 
Not applicable. 
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10.10 
Appendix 10: Abbreviations and trademarks 
AE 
adverse event 
AESI 
adverse events of special interest 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANOVA 
Analysis of Variance 
API 
active pharmaceutical ingredient 
AST 
aspartate aminotransferase 
ASYN 
alpha synuclein 
BMI 
body mass index 
BP 
blood pressure 
CI 
confidence interval 
CNS 
central nervous system 
COVID-19 
Coronavirus Disease 2019 
CRO 
contract research organization 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
DBP 
diastolic blood pressure 
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
ETV 
Early Termination Visit 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
HBsAg 
hepatitis B surface antigen 
HCVAb 
hepatitis C antibody 
HIV 
immunodeficiency virus 
HRT 
hormonal replacement therapy 
IB 
Investigator’s Brochure 
ICF 
Informed Consent form 
ICH 
International Council for Harmonisation 
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IEC 
Independent Ethics Committee 
IgE 
immunoglobulin E 
IRB 
Institutional Review Board 
IRT 
interactive response technology 
IUD 
intrauterine devices 
IUS 
intrauterine hormone-releasing system 
LLOQ 
lower limit of quantification 
MedDRA® 
Medical Dictionary for Regulatory Activities 
PD 
Parkinson’s Disease 
PDILI 
potential drug-induced liver injury 
PK 
pharmacokinetic(s) 
PKS 
Pharmacokinetic Set 
PKS A 
Pharmacokinetic Set A 
PKS B 
Pharmacokinetic Set B 
PPI 
proton pump inhibitor 
QD 
once daily 
QTcF 
QT corrected for heart rate using Fridericia's formula 
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SBP 
systolic blood pressure 
SFU 
Safety Follow-Up 
SMC 
Safety Monitoring Committee 
SoC 
standard of care 
SOP 
standard operating procedure 
SS 
Safety Set 
TEAE 
treatment-emergent adverse events 
TOST 
two 1-sided ratio of means tests 
ULN 
upper limit of normal 
WOCBP 
woman of childbearing potential 
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10.11 
Appendix 11: Protocol amendment history 
Not applicable. 
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11 
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J Pharm Sci. 2007;96(5):948-59. 
James LP, Letzig L, Simpson PM, et al. Pharmacokinetics of Acetaminophen-Adduct in Adults 
with Acetaminophen Overdose and Acute Liver Failure. Drug Metab Dispos. 
2009;37(8):1779-84. 
Lai SW, Liao KF, Lin CL, et al. Association between Parkinson's disease and proton pump 
inhibitors therapy in older people. Biomedicine (Taipei). 2020;10(3):1-4. 
Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the definition and 
management of anaphylaxis: summary report--Second National Institute of Allergy and 
Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy Clin Immunol. 
2006;117(2):391-7. 
Taniguchi C, Kawabata Y, Wada K, et al. Microenvironmental pH-modification to improve 
dissolution behavior and oral absorption for drugs with pH-dependent solubility. Expert Opin 
Drug Deliv. 2014;11(4):505-16. 
Treudler R, Kozovska Y, Simon JC. Severe immediate type hypersensitivity reactions in 105 
German adults: when to diagnose anaphylaxis. J Investig Allergol Clin Immunol. 
2008;18(1):52-8. 
Twelves D, Perkins KS, Counsell C. Systematic review of incidence studies in Parkinson’s 
disease. Mov Disord. 2003;18(1):19-31. 
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SPONSOR DECLARATION 
I confirm that I have carefully read and understand this protocol and agree to conduct this 
clinical study as outlined in this protocol, according to Clinical Trial Regulation EU 536/2014, 
and according to current Good Clinical Practice. 
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