An Open-Label, Randomized Study to Evaluate the Relative Bioavailability of a New Tablet Formulation of Minzasolmin and the Potential Effect of Food on the Pharmacokinetics of Minzasolmin in Healthy Participants
Phase: PHASE1
Conditions: Healthy Participants
Sponsor: UCB Biopharma SRL

UCB 
 
08 Aug 2024 
Clinical Study Protocol Amendment 2 
Minzasolmin 
UP0152 
 
 
 
Confidential 
Page 1 of 80 
AN OPEN-LABEL, RANDOMIZED STUDY TO EVALUATE THE 
RELATIVE BIOAVAILABILITY OF A NEW TABLET 
FORMULATION OF MINZASOLMIN AND THE POTENTIAL 
EFFECT OF FOOD ON THE PHARMACOKINETICS OF 
MINZASOLMIN IN HEALTHY PARTICIPANTS 
 
PROTOCOL UP0152 AMENDMENT 2 
PHASE 1 
 
SHORT TITLE: 
A randomized, open-label Phase 1 study to assess the relative bioavailability of a new 
formulation of minzasolmin in healthy participants 
Sponsor: 
UCB Biopharma SRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
Regulatory agency identifying number(s): 
EudraCT Number: 
Not applicable 
EU CT Number: 
2024-511301-31 
EUDAMED Number: 
Not applicable 
IND Number: 
Not applicable 
IDE Number: 
Not applicable 
NCT Number: 
Not applicable 
Confidentiality Statement 
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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UP0152 
 
 
 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Document History 
Document 
Date 
Type of amendment 
Amendment 2 
08 Aug 2024 
Not applicable  
Amendment 1 
16 May 2024 
Not applicable  
Original Protocol 
25 Mar 2024 
Not applicable 
 
Amendment 2 (08 Aug 2024) 
Overall Rationale for the Amendment 
UP0152 Protocol Amendment 2 was completed to update the protocol based on Requests for 
Information received during the initial Clinical Trial Application.  
Section # and name 
Description of change 
Brief rationale 
Section 5.1 Inclusion criteria 
Inclusion criterion #5a (previously 
#5) was revised to remove the 
strikethrough text: “Capable of 
giving sSigned informed consent…”  
To clarify the informed 
consent process. 
Section 10.1.3 Informed consent 
process 
In the third paragraph, the possibility 
that the ICF is signed and dated by a 
legal representative was removed. 
To clarify the informed 
consent process. 
Section 10.3.2 Definition of 
SAE 
The first bullet point under “c. 
Requires inpatient hospitalization 
or prolongation of existing 
hospitalization” was revised to 
remove parenthetical text that 
admission usually involves at least 
an overnight stay. 
To clarify that 
hospitalization signifies 
in-patient admission, 
regardless of length of stay. 
 
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UP0152 
 
 
 
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SERIOUS ADVERSE EVENT REPORTING 
Serious adverse event reporting (24h) 
Fax 
Europe and Rest of the World: +32 2 386 24 21 
(Note: a country-specific exit code may need to be added) 
Email 
Global: DS_ICT@ucb.com  
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TABLE OF CONTENTS 
SERIOUS ADVERSE EVENT REPORTING ................................................................................3 
LIST OF ABBREVIATIONS ..........................................................................................................8 
1 
PROTOCOL SUMMARY .....................................................................................................11 
1.1 
Synopsis .............................................................................................................................11 
1.2 
Schema ...............................................................................................................................14 
1.3 
Schedule of Activities ........................................................................................................15 
2 
INTRODUCTION .................................................................................................................18 
2.1 
Study rationale ...................................................................................................................18 
2.2 
Background ........................................................................................................................18 
2.3 
Benefit/risk assessment ......................................................................................................19 
3 
OBJECTIVES AND ENDPOINTS .......................................................................................21 
4 
STUDY DESIGN ...................................................................................................................22 
4.1 
Overall design ....................................................................................................................22 
4.2 
Scientific rationale for study design ..................................................................................22 
4.2.1 
Patient input into design ............................................................................................23 
4.3 
Justification for dose ..........................................................................................................23 
4.4 
End of study definition.......................................................................................................23 
5 
STUDY POPULATION ........................................................................................................24 
5.1 
Inclusion criteria ................................................................................................................24 
5.2 
Exclusion criteria ...............................................................................................................24 
5.3 
Lifestyle restrictions...........................................................................................................27 
5.3.1 
Meals and dietary restrictions ....................................................................................27 
5.3.2 
Caffeine, alcohol, and tobacco ...................................................................................28 
5.3.3 
Activity ......................................................................................................................28 
5.3.4 
Other restrictions .......................................................................................................28 
5.4 
Screen failures ....................................................................................................................28 
6 
STUDY INTERVENTIONS/INVESTIGATIONAL DEVICE AND CONCOMITANT 
THERAPY .............................................................................................................................28 
6.1 
Study interventions administered .......................................................................................28 
6.2 
Preparation, handling, storage, and accountability ............................................................30 
6.2.1 
Drug accountability ...................................................................................................31 
6.3 
Assignment to study intervention ......................................................................................31 
6.4 
Blinding..............................................................................................................................31 
6.5 
Study intervention compliance ..........................................................................................31 
6.6 
Dose modification ..............................................................................................................31 
6.7 
Continued access to study intervention after the end of the study .....................................31 
6.8 
Treatment of overdose .......................................................................................................32 
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6.9 
Concomitant medication(s)/treatment(s) ...........................................................................32 
6.9.1 
Permitted concomitant therapy (medications and therapies) .....................................32 
6.9.2 
Prohibited concomitant therapy (medications and therapies) ....................................32 
6.9.3 
Rescue medication .....................................................................................................32 
7 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..............................................................................32 
7.1 
Discontinuation of study intervention ................................................................................32 
7.1.1 
Liver chemistry stopping criteria ...............................................................................32 
7.1.2 
Corrected QT interval stopping criteria .....................................................................33 
7.1.3 
Temporary discontinuation ........................................................................................33 
7.1.4 
Hypersensitivity reaction stopping criteria ................................................................34 
7.1.5 
Study stopping criteria ...............................................................................................34 
7.2 
Participant discontinuation/withdrawal from the study .....................................................34 
7.3 
Lost to follow up ................................................................................................................35 
8 
STUDY ASSESSMENTS AND PROCEDURES .................................................................35 
8.1 
Administrative and general/baseline procedures ...............................................................36 
8.2 
Efficacy assessments ..........................................................................................................36 
8.3 
Safety assessments .............................................................................................................36 
8.3.1 
Physical examination .................................................................................................36 
8.3.2 
Vital signs ..................................................................................................................37 
8.3.3 
Electrocardiograms ....................................................................................................37 
8.3.4 
Clinical safety laboratory tests ...................................................................................37 
8.3.5 
Pregnancy testing .......................................................................................................38 
8.4 
AEs, SAEs, and other safety reporting ..............................................................................38 
8.4.1 
Time period and frequency for collecting AE and SAE information ........................38 
8.4.2 
Method of detecting AEs and SAEs ..........................................................................38 
8.4.3 
Follow up of AEs and SAEs ......................................................................................38 
8.4.4 
Regulatory reporting requirements for SAEs ............................................................39 
8.4.5 
Pregnancy ..................................................................................................................39 
8.4.6 
Adverse events of special interest ..............................................................................40 
8.4.6.1 
Hypersensitivity reaction monitoring and management ..................................40 
8.5 
Safety signal detection .......................................................................................................44 
8.6 
Pharmacokinetics ...............................................................................................................44 
8.6.1 
Use of residual plasma samples .................................................................................44 
8.7 
Biomarkers .........................................................................................................................45 
8.8 
Immunogenicity assessments .............................................................................................45 
8.9 
Medical resource utilization and health economics ...........................................................45 
9 
STATISTICAL CONSIDERATIONS ...................................................................................45 
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9.1 
Analysis sets.......................................................................................................................45 
9.1.1 
Study Participant Set ..................................................................................................45 
9.1.2 
Randomized Set .........................................................................................................45 
9.1.3 
Safety Set ...................................................................................................................45 
9.1.4 
Pharmacokinetics Set .................................................................................................45 
9.2 
Statistical analyses .............................................................................................................46 
9.2.1 
General consideration ................................................................................................46 
9.2.1.1 
Pharmacokinetic parameter calculation ...........................................................46 
9.2.2 
Primary endpoints analysis ........................................................................................47 
9.2.2.1 
Definition of endpoint(s) .................................................................................47 
9.2.2.2 
Main analytical approach ................................................................................47 
9.2.3 
Other PK endpoint analysis .......................................................................................48 
9.2.4 
Secondary safety endpoints analysis .........................................................................48 
9.2.4.1 
Exploratory safety endpoints analysis .............................................................49 
9.3 
Interim analysis ..................................................................................................................49 
9.4 
Sample size determination .................................................................................................49 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS.........51 
10.1 
Appendix 1: Regulatory, ethical, and study oversight considerations ...............................51 
10.1.1 
Regulatory and ethical considerations .......................................................................51 
10.1.2 
Financial disclosure ...................................................................................................51 
10.1.3 
Informed consent process ..........................................................................................52 
10.1.4 
Recruitment strategy ..................................................................................................52 
10.1.5 
Data protection ...........................................................................................................52 
10.1.6 
Committees structure .................................................................................................53 
10.1.7 
Dissemination of clinical study data ..........................................................................53 
10.1.8 
Data quality assurance ...............................................................................................53 
10.1.8.1 
ClinBase completion .......................................................................................54 
10.1.8.2 
Apps .................................................................................................................54 
10.1.9 
Source documents ......................................................................................................54 
10.1.10 Study and site start and closure .................................................................................55 
10.1.11 Publication policy ......................................................................................................56 
10.2 
Appendix 2: Clinical laboratory tests ................................................................................57 
10.3 
Appendix 3: Adverse events – Definitions and procedures for recording, evaluating, 
follow up, and reporting .....................................................................................................59 
10.3.1 
Definition of AE ........................................................................................................59 
10.3.2 
Definition of SAE ......................................................................................................60 
10.3.3 
Recording and follow up of AE and/or SAE .............................................................61 
10.3.4 
Reporting of SAEs .....................................................................................................62 
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10.4 
Appendix 4: Contraceptive guidance and collection of pregnancy information ...............64 
10.5 
Appendix 5: Genetics .........................................................................................................68 
10.6 
Appendix 6: Liver safety – Suggested actions and follow-up assessments .......................69 
10.7 
Appendix 7: Device adverse events (AEs), adverse device effects (ADEs), serious 
adverse events (SAEs), and device deficiencies: Definition and procedures for 
recording, evaluating, follow-up, and reporting ................................................................72 
10.8 
Appendix 8: Rapid alert procedures ..................................................................................73 
10.9 
Appendix 9: Country-specific requirements ......................................................................74 
10.10 Appendix 10: Protocol amendment history .......................................................................75 
10.10.1 Amendment 1 (16 May 2024) ....................................................................................75 
11 REFERENCES ......................................................................................................................79 
SPONSOR DECLARATION ........................................................................................................80 
 
LIST OF TABLES 
Table 1‒1: 
Objectives and endpoints .......................................................................................12 
Table 3‒1: 
Objectives and endpoints .......................................................................................21 
Table 4‒1: 
Relative bioavailability of minzasolmin under fasting and fed condition 
(3-treatment, 6-sequence, 3-period crossover design) ...........................................22 
Table 6‒1: 
Study interventions administered ...........................................................................29 
Table 9‒1: 
Noncompartmental PK parameters for minzasolmin in plasma ............................46 
Table 10‒1: 
Protocol-required safety laboratory tests ...............................................................57 
Table 10‒2: 
Highly effective contraceptive methodsa ...............................................................65 
Table 10‒3: 
Phase 1 liver chemistry stopping criteria and follow up assessments table ...........69 
 
LIST OF FIGURES 
Figure 1‒1: 
Study schematic .....................................................................................................14 
Figure 7‒1: 
Phase 1 liver chemistry stopping algorithm ...........................................................33 
 
 
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LIST OF ABBREVIATIONS 
AE 
adverse event 
AESI 
adverse event of special interest 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANOVA 
analysis of variance 
AST 
aspartate aminotransferase 
ASYN 
alpha-synuclein 
AUC 
area under the plasma concentration-time curve from time zero to 
infinity 
AUC%Extrap 
area under the plasma concentration-time curve extrapolated from the 
time t to infinity as a percentage of total AUC 
AUC0-t 
area under the plasma concentration-time curve from time 0 to t 
BID 
twice daily 
BMI 
body mass index 
BP 
blood pressure 
CA 
Competent Authority 
CI 
confidence interval 
CL/F 
apparent total body clearance 
Cmax  
maximum observed plasma concentration 
CRF 
case report form 
CRO 
contract research organization 
CV 
coefficient of variation 
DBP 
diastolic blood pressure 
DNA 
deoxyribonucleic acid 
ECG 
electrocardiogram 
ETV 
Early Termination Visit 
EU 
European Union 
EUDAMED 
European Database on Medical Devices 
EudraCT 
European Union Drug Regulating Authorities Clinical Trials 
FSH 
follicle stimulating hormone 
GCP 
Good Clinical Practice 
GMR 
geometric mean ratio 
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HBcAb 
hepatitis B core antibody 
HBsAg 
hepatitis B surface antigen 
HIV 
human immunodeficiency virus 
HRT 
hormonal replacement therapy 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IDE 
Investigational Device Exemption 
IEC 
Independent Ethics Committee 
IgM 
Immunoglobulin M 
IMP 
investigational medicinal product 
IND 
Investigational New Drug 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
IUD 
intrauterine device 
IUS 
intrauterine hormone-releasing system 
LLOQ 
lower limit of quantification 
MedDRA® 
Medical Dictionary for Regulatory Activities 
NCT number 
ClinicalTrials.gov identifier 
NDA 
new drug application 
PD 
Parkinson’s disease 
PDILI 
potential drug-induced liver injury 
PK 
pharmacokinetic(s) 
PKS 
Pharmacokinetics Set 
POC 
proof of concept 
PR 
pulse rate 
QTc 
corrected QT interval 
QTcF 
QT corrected for heart rate using Fridericia’s formula 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SBP 
systolic blood pressure 
SFU 
Safety Follow-Up 
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SoC 
standard of care 
SOP 
standard operating procedure 
SS 
Safety Set 
SUSAR 
suspected unexpected serious adverse reaction 
t½ 
apparent terminal elimination half-life 
TEAE 
treatment-emergent adverse event 
tmax 
time of occurrence of Cmax  
ULN 
upper limit of normal 
Vz/F 
apparent volume of distribution 
WOCBP 
woman of childbearing potential 
 
 
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1 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol title: An open-label, randomized study to evaluate the relative bioavailability of a new 
tablet formulation of minzasolmin and the potential effect of food on the pharmacokinetics of 
minzasolmin in healthy participants 
Short title: A randomized, open-label Phase 1 study to assess the relative bioavailability of a 
new formulation of minzasolmin in healthy participants 
 
Regulatory agency identifying numbers: 
EudraCT Number: 
Not applicable 
EU CT Number: 
2024-511301-31 
EUDAMED Number: 
Not applicable 
IND Number: 
Not applicable 
IDE Number: 
Not applicable 
NCT Number: 
Not applicable 
 
Rationale: 
A new tablet formulation has been developed for minzasolmin. The current study UP0152 is 
designed to evaluate the relative bioavailability of a new tablet formulation compared with the 
current clinical formulation (ie, granules in capsule) under fasting conditions. UP0152 will 
provide safety, tolerability, and pharmacokinetic (PK) information of minzasolmin in fed and 
fasting conditions after single oral doses of minzasolmin 
 administered once per period in 
healthy study participants. In addition, the study is also designed to evaluate the potential effect 
of a high-fat meal on the PK of minzasolmin when administered as tablet formulation. 
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Objectives, endpoints, and estimands: 
Table 1‒1: 
Objectives and endpoints 
Objectives 
Endpoints 
Primary 
• 
To estimate the relative 
bioavailability of a new 
minzasolmin tablet 
formulation versus reference 
‘granules in capsule’ 
formulation in healthy 
participants and to evaluate 
the effect of food with the 
new tablet formulation on 
the PK of minzasolmin. 
Primary PK Endpoint(s) 
 
• 
AUC0-t, AUC, and Cmax in fasting (for both granules in 
capsule and tablet formulations) and fed (tablet formulation 
only) conditions for minzasolmin 
 
Secondary 
• 
To evaluate the safety and 
tolerability of single-dose 
administration of 
minzasolmin in healthy 
participants using different 
formulations in fed 
condition (tablet 
formulation) and fasting 
condition (tablet and 
‘granules in capsule’ 
formulations). 
Secondary Safety Endpoint(s) 
• 
Occurrence of TEAEs 
• 
Occurrence of treatment-emergent SAEs 
• 
Occurrence of TEAEs leading to withdrawal from study 
Other 
• 
To further evaluate the PK 
of minzasolmin and its 
 
metabolites after single-dose 
administration with 
reference ‘granules in 
capsule’ formulation or the 
new tablet formulation in 
fasting (tablet and ‘granules 
in capsule’ formulations) or 
fed condition (tablet 
formulation). 
Other PK Endpoints 
• 
For minzasolmin: 
− 
tmax, t½, CL/F, and Vz/F (if possible but not limited) 
• 
For 
 metabolites: 
− 
AUC0-t, AUC, Cmax, and tmax, in fasting and fed conditions 
− metabolite/parent Cmax and AUC ratio, as appropriate 
AUC=area under the plasma concentration-time curve from time zero to infinity; AUC0-t=area under the plasma 
concentration-time curve from time zero to t ; CL/F=apparent total body clearance; Cmax=maximum observed 
plasma concentration; PK=pharmacokinetic(s); SAE=serious adverse event; t½=apparent terminal elimination 
half-life; TEAE=treatment-emergent adverse event; tmax=time of occurrence of Cmax; Vz/F=apparent volume of 
distribution 
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Overall design: 
This is a Phase 1, 3-treatment, 6-sequence, 3-period crossover, open-label study in healthy male 
and female participants designed to evaluate the relative bioavailability under fasting condition 
of a new tablet formulation when compared with the current granules in capsule formulation 
used in clinical studies (Treatment B and A, respectively). The study is also designed to evaluate 
effect of high fat meal on the PK of minzasolmin following administration of a single dose of the 
new tablet formulation in fed condition (Treatment C). The safety and tolerability of single-dose 
administration of minzasolmin will also be investigated. 
Within each sequence, study participants will receive a single dose of minzasolmin (
 
capsules or tablets as shown in the 3 treatment conditions below) on 3 separate occasions (Day 1, 
Day 6, and Day 11 [Period 1, Period 2, and Period 3]): 
• Treatment A: under fasting conditions 
 (
 granules in capsules (in Period 1, 
Period 2, or Period 3) followed by a 4-day Washout Period  
• Treatment B: under fasting conditions 
 tablet (in Period 1, Period 2, or Period 3) 
followed by a 4-day Washout Period  
• Treatment C: under fed condition 
 tablet (in Period 1, Period 2, or Period 3) followed 
by a 4-day Washout Period  
The order of the 3 treatment conditions received will differ between each sequence. 
Number of participants: 
A maximum of 18 healthy participants will be randomized in this study. 
Study duration: 
The maximum study duration will be 48 days, including the Treatment Period and the Safety 
Follow-Up (SFU) Period. There are 3 study periods in this study: 
• Screening Period: Eligibility will be assessed during the Screening Period (up to 28 days). 
Treatment must be started as soon as possible for participants who have fulfilled the 
eligibility criteria. 
• Treatment Period: Participants who have been confirmed eligible will be randomized to 
receive open-label single doses of minzasolmin 
 on Days 1, 6, and 11 with a 4-day 
Washout Period between doses. 
• Safety Follow-Up Period: Study participants will have SFU procedures performed within 5 to 
9 days after final dose. Participants who prematurely withdraw from the study will return to 
the clinic center for the Early Termination Visit (ETV) as soon as possible after the time of 
withdrawal and will have all SFU procedures performed.  
Data monitoring/Other committee: No 
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1.2 
Schema 
Figure 1‒1: Study schematic 
 
ETV=Early Termination Visit; SFU=Safety Follow-Up 
Note: Participants who have been confirmed eligible will be randomized to receive single doses of minzasolmin 
 with a 4-day Washout Period between 
doses.  
Note: Study participants will have SFU procedures performed within 5 to 9 days after their final dose. Participants who prematurely withdraw from the study will 
return to the study clinic center for the ETV as soon as possible after the time of withdrawal and will have all SFU procedures performed. 
Sequence 1: Minzasolmin
A
B
C
Sequence 2: Minzasolmin
B
C
A
Sequence 3: Minzasolmin
C
A
B
Screening
(up to 28 days)
N=18 
participants
Sequence 4: Minzasolmin
A
C
B
Sequence 5: Minzasolmin
B
A
C
Sequence 6: Minzasolmin
C
B
A
A: Granules in capsules (fasted)
B: Tablet formulation (fasted)
C: Tablet formulation (with food)
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1.3 
Schedule of Activities 
Procedure 
Screening 
Treatment Period A, B and Ca  
 
In-Clinic Period 
SFUb/ETV 
D -28 
to -2 
D -1 
D1c 
D2-5 
D6c 
D7-10 
D11c 
D12-14 
D15 
D18 (±2 
days)  
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Verification of 
inclusion/exclusion 
criteria 
X 
X 
 
 
 
 
 
 
 
 
Verification of 
withdrawal criteria 
 
 
X 
X 
X 
X 
X 
X 
X 
 
Demography 
(height, weight, 
BMI) 
X 
 
 
 
 
 
 
 
 
 
Physical 
examination 
X 
X 
Xd 
Xd 
Xd 
Xd 
Xd 
Xd 
Xd 
X 
General 
medical/procedure 
history 
X 
 
 
 
 
 
 
 
 
 
Blood pregnancy 
test (WOCBP only) 
X 
X 
 
 
 
 
 
 
 
X 
Laboratory 
assessments 
(hematology, 
clinical chemistry, 
urinalysis, and FSH 
and estradiol)e 
X 
X 
 
X 
(D5) 
 
X 
(D10) 
 
 
X 
X 
SARS-CoV-2 
testing (PCR) 
  
X 
 
 
 
 
 
 
 
 
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Procedure 
Screening 
Treatment Period A, B and Ca  
 
In-Clinic Period 
SFUb/ETV 
D -28 
to -2 
D -1 
D1c 
D2-5 
D6c 
D7-10 
D11c 
D12-14 
D15 
D18 (±2 
days)  
Viral serology 
(HBsAg, HCV-Ab, 
HIV, and HBcAb) 
X 
 
 
 
 
 
 
 
 
 
Urine cotinine, drug 
screen and urine 
alcohol test 
X 
X 
 
 
 
 
 
 
 
 
12-lead ECGf 
X 
X 
  
 
X 
 
X 
 
X 
X 
Vital signsg 
X 
X 
X 
 
X 
 
X 
 
X 
X 
Randomization  
 
X 
 
 
 
 
 
 
 
 
Minzasolmin 
administration 
 
 
X 
 
X 
 
X 
 
 
 
Adverse event 
review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Prior- and 
concomitant 
medication review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood sampling for 
PKh 
 
 
X 
X 
X 
X 
X 
X 
X  
 
Blood sampling for 
exploratory genetic 
biomarkers (DNA) 
 
X 
 
 
 
 
 
 
 
 
Mealsi  
 
X 
X 
X 
X 
X 
X 
X 
 
 
Confinement 
 
X 
X 
X 
X 
X 
X 
X 
 
 
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Procedure 
Screening 
Treatment Period A, B and Ca  
 
In-Clinic Period 
SFUb/ETV 
D -28 
to -2 
D -1 
D1c 
D2-5 
D6c 
D7-10 
D11c 
D12-14 
D15 
D18 (±2 
days)  
Discharge 
 
 
 
 
 
 
 
 
X 
 
BMI=body mass index; D=day; DBP=diastolic blood pressure; DNA=deoxyribonucleic acid; ECG=electrocardiogram; ETV=Early Termination Visit; 
FSH=follicle stimulating hormone; HBcAb=hepatitis B core antibody; HBsAg=hepatitis B surface antigen; HCV-Ab=hepatitis C virus antibody; HIV=human 
immunodeficiency virus; PCR=polymerase chain reaction; PK=pharmacokinetic(s); PR=pulse rate; SARS-CoV-2=severe acute respiratory syndrome 
coronavirus 2; SBP=systolic blood pressure; SFU=Safety Follow-Up; WOCBP=women of childbearing potential 
a Each participant will attend 3 Treatment Periods. Participants will be in the clinical center for the whole Treatment Period A, B and C. 
b Study participants will have SFU procedures performed within 5 to 9 days after final dose. Participants who prematurely withdraw from the study will return to 
the clinic center for the ETV as soon as possible after the time of withdrawal and will have all SFU procedures performed. 
c Clinical assessments performed on Days 1, 6, and 11 need to be performed predose. 
d Complete physical examinations will be performed during Screening, at Day -1, and at SFU/ETV. Symptom-directed physical examinations will be performed 
during Treatment Periods. 
e Blood hematology and chemistry laboratory tests will be obtained in the fasting state following an overnight fast of at least 10 hours. Hepatic function tests only 
will also be performed 24 hours before each dosing (ie, Day 5 and Day 10). Note that FSH and estradiol will only be determined for females at the Screening 
Visit. 
f 12-lead ECG will be performed in single after a rest in supine position for at least 10 minutes before recordings, but can be repeated in triplicate if clinically 
indicated.  
g SBP, DBP, respiration rate, PR, and body temperature. Vital signs will be performed after a rest of at least 5 minutes. 
h The PK sampling timepoints will be: predose and at 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 48, 72, and 96h after minzasolmin administration on Day 1, Day 6, and 
Day 11. 
i Study participants will receive standard meals and snacks at appropriate times indicated by the clinic center, except when they are required to fast. All 
participants fast overnight for at least 10 hours before minzasolmin administration. Participants in Treatment A and B continue fasting for at least 4 hours after 
minzasolmin administration. Thereafter they receive a standard lunch. Fed study participants (Treatment C) should start the recommended high-fat high-calorie 
meal 30 minutes before administration of minzasolmin. Study participants should eat this meal in 30 minutes or less; however, minzasolmin should be 
administered 30 minutes after start of the meal. No food should be allowed for at least 4 hours postdose. During the rest of the day, study participants receive 
standard meals and snacks at appropriate times indicated by the clinic center.
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2 
INTRODUCTION 
2.1 
Study rationale 
A new tablet formulation is developed for minzasolmin, which is planned to be used in future 
studies and for commercialization purpose. The current study UP0152 is designed to evaluate the 
relative bioavailability of a new tablet formulation compared with the current clinical 
formulation (ie, granules in capsule) under fasting condition. In addition, the study is also 
designed to evaluate the potential effect of a high-fat meal on the pharmacokinetics (PK) of 
minzasolmin when administered as tablet formulation. 
2.2 
Background 
Parkinson’s disease (PD) is a progressive neurodegenerative disorder that presents with a 
spectrum of motor and nonmotor signs and symptoms. The mean age at onset is 60 years. The 
incidence of PD is approximately 20/100,000 persons per year; however, it is much higher in the 
population aged 65 years or older (>100/100,000 persons per year) (Twelves et al, 2003). The 
clinical diagnosis of PD relies on the presence of the cardinal motor signs: bradykinesia, rigidity, 
tremor, and postural instability. However, nonmotor symptoms such as loss of smell, depression, 
constipation, dysautonomia, and rapid eye movement sleep behavior disorder can occur several 
years before the onset of motor symptoms. 
Early-stage PD is characterized by mild, manageable motor symptoms that may not require 
symptomatic treatment or that show a good response to low-dose levodopa, which represents the 
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 alpha-synuclein (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. 
Minzasolmin is an orally available inhibitor of ASYN misfolding and downstream ASYN 
aggregation. Aggregated forms of ASYN are the hallmark fibrillar protein deposits in PD and 
other synucleinopathies, and evidence suggests that the misfolded forms of ASYN propagate 
through the central nervous system during disease progression. The accumulation of ASYN 
forms neuronal inclusions referred to as Lewy bodies and Lewy neurites. In vivo and nonclinical 
pharmacology data suggest minzasolmin may slow neurodegeneration in PD, resulting in slower 
disease progression, thus providing a therapeutic benefit to patients with PD. 
Minzasolmin 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 
minzasolmin. The pharmacokinetics (PK) of minzasolmin has been well characterized following 
administration of single and multiple doses in healthy volunteers and patients with PD (UP0030, 
UP0023, TM0017, UP0077, UP0078). Minzasolmin is rapidly absorbed following administration 
of single (
 or multiple doses (
) with maximum plasma 
concentration were attained within 1.5 to 2 hours and had moderate to extensive tissue 
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distribution. The apparent terminal elimination half-life (t½) of minzasolmin at single doses of 
 
 has been found to be approximately 11 to 13 hours. In general, the maximum observed 
plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero 
to infinity (AUC) increased in an approximately dose-proportional manner after a single dose (
 
) and multiple doses (
). In the dose range evaluated, minzasolmin follows 
linear kinetics (no change in apparent total body clearance [CL/F] and apparent volume of 
distribution [Vz/F] was observed), and steady state was achieved by Day 7 following multiple 
dose administration. The PK of minzasolmin were also comparable between healthy volunteers 
and patients with PD (UP0030 and UP0077). Minzasolmin had an acceptable safety and 
tolerability profile (UP0023, UP0030, TM0017, and UP0077). 
The effect of food has been evaluated with granules in capsule in the previous study UP0078. 
Food intake delays gastric emptying as expected thereby increasing tmax (1.5 hour to 3 hour). The 
rate and extent of minzasolmin absorption (Cmax and AUC, respectively) were not impacted by 
food. The point estimates for the geometric least squares mean ratio of fed/fasting calculated for 
minzasolmin Cmax and AUC were 104.5% and 109.4%, respectively. The elimination rates were 
similar between the fed and fasting groups for minzasolmin and its metabolites. 
Minzasolmin is currently being tested in an ongoing Phase 2a study (PD0053), its extension 
study (PD0055), and an ongoing Phase 1 study (UP0073). 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 a benefit to the study population, ie, healthy study participants. This 
study will provide relevant PK and clinical safety information to support minzasolmin new tablet 
formulation development. 
A summary of possible risks and adverse reactions is provided in the IB based on a review of 
adverse event (AE) data from 98 study participants exposed to minzasolmin in completed 
clinical studies UP0030 (51 participants), TM0017 (4 participants), UP0077 (21 participants), 
and UP0078 (22 participants), and based on the review of safety data in the ongoing clinical 
studies UP0073 (42 participants), and PD0053 and its extension study PD0055 conducted in 
approximately 490 participants (from PD0053). 
Overall, the majority of treatment-emergent adverse events (TEAEs) observed in clinical studies 
with minzasolmin to date 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 minzasolmin in UP0077. A causal relationship between the reported 
events of hypersensitivity and minzasolmin is considered plausible. Hypersensitivity reactions 
are considered an important identified risk for minzasolmin and are further described in the IB. 
There have been no reports of anaphylaxis in the minzasolmin clinical program.  
Of all the adverse drug reactions reported in completed minzasolmin clinical studies, based on 
the frequency of occurrence, all are considered common (≥1% and <10%).  
In the ongoing Phase 2 study (where participants are receiving daily doses of Study Drug for 
18 months), of the 496 participants, 8 reports of aspartate aminotransferase (AST) and/or alanine 
transaminase (ALT) elevations >3x upper limit of normal (ULN) (of which 2 were >10xULN) 
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have been received. In the majority of reports, the transaminase elevations were noted 2 to 
3 months after the first dose of study medication. None of the reports had an increase in bilirubin 
or international normalized ratio (INR) and none met Hy’s law criteria. Transaminase values 
decreased spontaneously without study drug discontinuation in 3 participants or after 
discontinuation of the drug in 5 participants.  
As a consequence, monthly routine liver function tests should now be conducted during the first 
6 months of treatment for study participants who receive multiple doses of Study Drug. The 
protocol contains relevant safety monitoring activities for hepatic effects as well as instructions 
for the management of patients with hepatic enzyme elevations.  
To minimize the risks for study participants, the study team at UCB and the contracted contract 
research organization (CRO) will continue to closely monitor study participants, systematically 
review safety data and minzasolmin exposure data. 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of minzasolmin may be found in the IB. 
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3 
OBJECTIVES AND ENDPOINTS 
Table 3‒1: 
Objectives and endpoints 
Objectives 
Endpoints 
Primary 
• 
To estimate the relative 
bioavailability of a new 
minzasolmin tablet 
formulation versus reference 
‘granules in capsule’ 
formulation in healthy 
participants and to evaluate 
the effect of food with the 
new tablet formulation on 
the PK of minzasolmin. 
Primary PK Endpoint(s) 
 
• 
AUC0-t, AUC, and Cmax in fasting (for both granules in 
capsule and tablet formulation) and fed (tablet formulation 
only) conditions for minzasolmin 
 
Secondary 
• 
To evaluate the safety and 
tolerability of single-dose 
administration of 
minzasolmin in healthy 
participants using different 
formulations in fed 
condition (tablet 
formulation) and fasting 
condition (tablet and 
‘granules in capsule’ 
formulation). 
Secondary Safety Endpoint(s) 
• 
Occurrence of TEAEs 
• 
Occurrence of treatment-emergent SAEs 
• 
Occurrence of TEAEs leading to withdrawal from study 
Other 
• 
To further evaluate the PK 
of minzasolmin and its 
 
metabolites after single-dose 
administration with 
reference ‘granules in 
capsule’ formulation or the 
new tablet formulation in 
fasting (tablet and ‘granules 
in capsule’formulation) or 
fed condition (tablet 
formulation). 
Other PK Endpoints 
• 
For minzasolmin: 
− 
tmax, t½, CL/F, and Vz/F (if possible but not limited) 
• 
For 
 metabolites: 
− 
AUC0-t, AUC, Cmax and tmax, in fasting and fed conditions 
− metabolite/parent Cmax and AUC ratio, as appropriate 
AUC=area under the plasma concentration-time curve from zero to infinity; AUC0-t=area under the plasma 
concentration-time curve from time zero to t; CL/F=apparent total body clearance; Cmax=maximum observed 
plasma concentration; PK=pharmacokinetic(s); t½=apparent terminal elimination half-life; SAE=serious adverse 
event; TEAE=treatment-emergent adverse event; tmax=time of occurrence of Cmax; Vz/F=apparent volume of 
distribution 
 
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4 
STUDY DESIGN 
4.1 
Overall design 
UP0152 is an open-label, randomized, 3-treatment, 6-sequence, 3-period crossover study in 
healthy male and female participants designed to evaluate relative bioavailability under fasting 
condition of a new tablet formulation when compared with the current granules in capsule 
formulation used in clinical studies (Treatment B and A, respectively). The study is also 
designed to evaluate effect of high fat meal on the PK of minzasolmin following administration 
of a single dose of the new tablet formulation in fed condition (Treatment C). Eighteen 
participants will be randomized in the study to ensure a minimum of 2 completers in each of the 
6 sequences. The study consists of a Screening Period of up to 28 days, a baseline health status 
assessment (on Day -1) and 3 Treatment Periods with washout periods between the treatments. 
After all the scheduled procedures have been performed, the participant may leave the clinic 
provided that, in the opinion of the investigator, there are no safety concerns. Participants will 
return to the clinic to complete the SFU Visit assessments 7 days (±2 days) after the final dose 
(Table 4‒1). 
Table 4‒1: 
Relative bioavailability of minzasolmin under fasting and fed 
condition (3-treatment, 6-sequence, 3-period crossover design) 
Sequence 
Period 
1 
Washout 
Period 
2 
Washout 
Period 
3 
Washout Discharge 
SFU 
Day 
D1 
D2-5 
D6 
D7-10 
D11 
D12-15 
D15 
D18 (±2 
days) 
1 (ABC) 
A 
 
B 
 
C 
 
 
 
2 (BCA) 
B 
 
C 
 
A 
 
 
 
3 (CAB) 
C 
 
A 
 
B 
 
 
 
4 (ACB) 
A 
 
C 
 
B 
 
 
 
5 (BAC) 
B 
 
A 
 
C 
 
 
 
6 (CBA) 
C 
 
B 
 
A 
 
 
 
D=day; SFU=Safety Follow-Up 
Note: A: Granules in capsule (fasting); B: Tablet formulation (fasting); C: Tablet formulation (fed). 
4.2 
Scientific rationale for study design 
A new tablet formulation is developed for minzasolmin, which is planned to be used in future 
studies and for commercialization purpose. The current study UP0152 is designed to evaluate the 
relative bioavailability of a new tablet formulation compared with the current clinical 
formulation (ie, granules in capsule) under fasting condition. In addition, the study is also 
designed to evaluate the potential effect of a high-fat meal on the PK of minzasolmin when 
administered as tablet formulation. A crossover study design was selected as it provides more 
robust comparison between different formulations and fed conditions as each participant will 
receive all study treatments. Six sequences were implemented in order to balance the allocation 
of treatments across study periods.  
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The half-life of minzasolmin and its 2 metabolites (
) are 11, 10 and 
16 hours, respectively (see the IB for further details). Considering 5 half-lives for elimination of 
the drug, the 4 days washout is considered adequate for the study. In study UP0073, a similar 
design and washout period was used, and carryover (<5% of Cmax) was observed in only few 
participants. The tmax for minzasolmin and the 
 metabolites were 1.5, 2.0, 
and 2.0 hours, respectively (see the IB for further details).  
UP0152 will provide safety, tolerability, and PK information of minzasolmin formulations in fed 
condition (tablet formulation) and fasting condition (tablet and ‘granules in capsule’ formulation) 
after single oral doses of minzasolmin 
 administered once per period in healthy study 
participants. 
4.2.1 
Patient input into design 
Not applicable.  
4.3 
Justification for dose 
The rationale for testing the proposed dose level of minzasolmin 
 in healthy participants is 
based on the data from previously conducted studies (UP0030, UP0077, and UP0078) and doses 
currently being explored in the Phase 2 proof of concept (POC) study PD0053 and the Phase 1 
study UP0073. UP0030 showed that minzasolmin exposures increase linearly (both AUC and 
Cmax) across the tested dose range (
, single dose). UP0030 also evaluated 
 
twice daily (BID) for 21 days in elderly healthy study participants to assess the 
safety/tolerability, and PK following multiple doses. UP0077 provided the safety, tolerability, 
and PK information of minzasolmin for multiple-dose administration of 
 and 
 in study participants with PD for 28 days. The collective data from UP0030 and 
UP0077 further showed that exposure after multiple dosing is predictable from single-dose data 
and that the dose-exposure relationship is similar between healthy study participants and study 
participants with PD.  
In addition, doses of 
 BID and 
 BID are being evaluated in the POC study PD0053 
in participants with PD. In the study, 
 BID is the highest expected therapeutic dose being 
evaluated. Considering linear kinetics and dose proportionality between 
 doses of 
minzasolmin, the highest dose evaluated in the Phase 2 study is proposed for the current study. 
This dose also provides the opportunity to compare exposure of minzasolmin across previously 
conducted Phase 1 studies (UP0030, UP0077, UP0078, and UP0073).  
The selection of minzasolmin 
 to evaluate the food effect is in line with the Guidance for 
Industry “Assessing the Effects of Food on Drugs in INDs and NDAs — Clinical Pharmacology 
Considerations” (Food and Drug Administration, Guidance for Industry, 2022) where it is 
recommended using the highest dose to be marketed for this assessment. 
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 5 to 9 days after final dose). 
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). 
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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 informed 
consent form (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. 
Weight 
3. Body weight within 45 to 100kg (female) and 50 to 100kg (male) and body mass index 
(BMI) within the range 18 to 30kg/m2 (inclusive). 
Sex and contraceptive/barrier requirements 
4. Male and female. 
• 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 final dose of study 
intervention, and refrain from donating sperm during this period. 
• A female participant is eligible to participate if she is not pregnant (see Appendix 4 
[Section 10.4]), not breastfeeding (including pumping breastmilk to feed a child), and at 
least 1 of the following conditions applies: 
◦ 
Not a woman of childbearing potential (WOCBP) as defined in Appendix 4 
(Section 10.4). 
OR 
◦ 
A WOCBP who agrees to follow the contraceptive guidance in Appendix 4 
(Section 10.4) during the Treatment Period and for at least 1 week after the final dose 
of study intervention. 
Informed consent 
5a. Signed informed consent as described in Appendix 1 (Section 10.1.3) 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: 
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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 any history of cancer in the past 10 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 a history of chronic alcohol abuse (more than 24g [males] or 12g [females] 
per day; 12g pure alcohol are contained in approximately 300mL of beer (5%), 1 small glass 
[125 mL] of wine [12%], or 1 measure [40mL] of spirits [37.5%]) or drug abuse within the 
last 1 year from Screening, as defined according to the Diagnostic and Statistical Manual of 
Mental Disorders. 
5. Participant has a history of smoking within 3 months before Screening.  
6. Participant has a known hypersensitivity to any components of the study intervention or 
comparative drugs as stated in this protocol. 
7. 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 value above normal range at screening).  
8. Study participant has a consumption of more than 600mg of caffeine/day at study entry 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). 
9. Study participant has consumed cruciferous vegetables (eg, Brussel sprouts, broccoli, 
cabbage, cauliflower) within 7 days before administration of minzasolmin or is not willing to 
refrain from consuming these products for the duration of the study.  
10. Study participant has consumed any grapefruit, grapefruit juice, grapefruit-containing 
products, or star fruit within 14 days before administration of minzasolmin or is not willing 
to refrain from consuming these products for the duration of the study. 
11. Participant has a positive test result for severe acute respiratory syndrome coronavirus 2using 
reverse transcription polymerase chain reaction. 
Prior/Concomitant therapy 
12. Study 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 
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longer) before the first administration of minzasolmin. This does not include 
paracetamol/acetaminophen, ibuprofen, or oral contraceptives not exceeding 30μg ethinyl 
estradiol or postmenopausal hormonal replacement therapy (HRT) or implants, patches, or 
intrauterine devices/intrauterine hormone-releasing systems (IUDs/IUSs) delivering 
progesterone (for female study participants) (see Section 6.9.1). 
Prior/Concurrent clinical study experience 
13. Participant has previously participated in this study or participant has previously been 
assigned to intervention in a study of the medication under investigation in this study. 
14. Participant has participated in another study of an investigational medicinal product (IMP) 
(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 IMP (and/or an investigational 
device). 
Diagnostic assessments 
15a.Participant has any clinically relevant abnormal findings in physical examination or 
laboratory tests or a value outside the normal range for vital signs (systolic blood pressure 
90-139mmHg, diastolic blood pressure 50-89mmHg, or pulse rate 50-90bpm), which, in the 
opinion of the investigator, may place the participant at risk because of participation in the 
study. 
16a. Participant has ALT, AST, or alkaline phosphatase (ALP) >1.0x ULN. 
Tests that result in ALT, AST, or ALP up to 25% above the exclusion limit may be repeated 
once for confirmation. This includes rescreening. 
17. Participant has total bilirubin >1.0xULN. Bilirubin >ULN and ≤1.5xULN is acceptable if 
fractioned and direct bilirubin <35%, and if a baseline diagnosis of Gilbert’s syndrome is 
understood and recorded in ClinBase.  
18. Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the 
exception of Gilbert’s syndrome or asymptomatic gallstones). 
19. 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 Protocol Section 7.1.2).  
In addition, any study participant with any of the following findings will be excluded at 
Screening:  
• QT interval corrected for heart rate using Fridericia’s formula >450 msec for males 
and >470msec for females 
• other conduction abnormalities (defined as PR interval ≥220ms) 
• irregular rhythm other than sinus arrhythmia or occasional, rare supraventricular, and 
rare ventricular ectopic beats 
20. Study participant has a medical history or current diagnosis of renal impairment and/or 
Screening laboratory results show: 
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• An estimated glomerular filtration rate <90 mL/min/1.73m2 (using the Chronic 
Kidney Disease Epidemiology Collaboration formula) 
• An albumin/creatinine ratio ≥30mg/mmol 
• Urinary tract infection; in this case a study participant can be rescreened once the 
infection has been resolved 
• Clinically significant electrolyte abnormalities 
21. Presence of hepatitis B surface antigen (HBsAg) [or hepatitis B core antibody (HBcAb) 
immunoglobulin M], indicative of active hepatitis B, at Screening or within 3 months before 
first dose of study intervention. 
22. Positive hepatitis C antibody test result at Screening or within 3 months before starting study 
intervention. NOTE: Participants with positive hepatitis C antibody test results due to prior 
resolved disease can be enrolled only if a confirmatory negative hepatitis C ribonucleic acid 
test is obtained. 
23. Positive human immunodeficiency virus (HIV) antibody test. 
Other exclusion criteria 
24. Participants who have a history of confirmed gastric ulceration. 
25. Vulnerable study participants (eg, participants kept in detention, protected adults under 
guardianship or trusteeship, and soldiers or participants committed to an institution by 
governmental or juridical order), employees of the sponsor or the CRO with direct 
involvement in the proposed study or other studies under the direction of the investigator or 
the CRO, as well as family members of the employees or the investigator. 
26. Participant has donated blood or experienced blood loss >350mL within the last 1 month 
before the first IMP administration. 
5.3 
Lifestyle restrictions 
5.3.1 
Meals and dietary restrictions 
• Study participants receive standard meals and snacks at appropriate times indicated by 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 before Screening and dosing. Participants in Treatment Period A and B 
continue fasting for at least 4 hours after dosing. Thereafter they receive a standard lunch. 
Fed study participants (Treatment C) should start the recommended high-fat high-calorie 
meal within 30 minutes before dosing. Study participants should eat this meal in 30 minutes 
or less; however, minzasolmin should be administered 30 minutes after start of the meal. No 
food should be allowed for at least 4 hours postdose. During the rest of the day, study 
participants receive standard meals and snacks at appropriate times indicated by the clinic 
center. Please refer to the dosing instructions in Table 6‒1.  
• Intake of xanthine (eg, caffeine) containing food or beverages must be discontinued 48 hours 
before first dosing. Consumption of such foods and beverages (ie, coffee, tea, soda, 
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chocolate) is not permitted at any time while the participants are confined. 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 before first dosing until study completion. If a deviation occurs, it must 
be noted in the database. 
• No grapefruit-containing products and star fruit are to be consumed for 14 days before first 
dosing until 7 days following the final dose. If a deviation occurs, it must be noted in the 
database. 
5.3.2 
Caffeine, alcohol, and tobacco 
The following restrictions related to caffeine, alcohol, tobacco are applicable for this study: 
• No alcohol for 48 hours before first dosing until after end of study evaluation 
• No cannabis use for 4 weeks before screening until after study completion 
• No cigarettes/use of nicotine products from screening until after study completion 
5.3.3 
Activity 
The following restriction related to activity is applicable for this study: 
• No strenuous physical exercise (eg, weight training, aerobics, football) within 48 hours 
before admission until study completion 
5.3.4 
Other restrictions 
Not applicable. 
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 intervention. 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 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). 
Individuals who do not meet the criteria for participation in this study (screen failure) 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 INTERVENTIONS/INVESTIGATIONAL DEVICE AND 
CONCOMITANT THERAPY 
Study interventions are all prespecified, investigational and noninvestigational medicinal 
products, medical devices, and other interventions (eg, surgical and behavioral) intended to be 
administered to the study participants during the study conduct. 
6.1 
Study interventions administered 
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Table 6‒1: 
Study interventions administered 
Arm name 
Minzasolmin 
 
capsules under fasting 
conditions 
Minzasolmin 
 
tablet under fasting 
conditions 
Minzasolmin 
 
tablet under fed 
conditions 
Intervention 
name 
A 
B 
C 
Type 
Drug 
Drug 
Drug 
Dose 
formulation 
Granules in oral capsules 
Oral film-coated tablets 
Oral film-coated tablets 
Unit dose 
strength(s) 
Dosage level(s) 
 SD: 
2 capsules of 
 
 SD: 
1 tablet of 
 
 SD: 
1 tablet of 
 
Dosing 
instructions 
During Treatment A, a 
single 
 dose of 
minzasolmin will be 
administered under 
fasting conditions, 
according to the 
randomization scheme. 
Participants will have an 
overnight fast of at least 
10h before dosing. 
Minzasolmin should be 
administered with 240mL 
(8 fluid ounces) of water. 
No food should be 
allowed for at least 4h 
postdose. Water can be 
allowed as desired except 
for 1h before and 1h after 
drug administration. 
Study participants should 
receive standardized 
meals scheduled at the 
same time in each period 
of the study. 
During Treatment B, a 
single 
 dose of 
minzasolmin will be 
administered under 
fasting conditions, 
according to the 
randomization scheme. 
Participants will have an 
overnight fast of at least 
10h before dosing. 
Minzasolmin should be 
administered with 240mL 
(8 fluid ounces) of water. 
No food should be 
allowed for at least 4h 
postdose. Water can be 
allowed as desired except 
for 1h before and 1h after 
drug administration. 
Study participants should 
receive standardized 
meals scheduled at the 
same time in each period 
of the study. 
During Treatment C, a 
single 
 dose of 
minzasolmin will be 
administered under fed 
(standard high-fat, high-
calorie meal) conditions, 
according to the 
randomization scheme. 
Participants will have an 
overnight fast of at least 
10h before dosing. 
Participants should start 
the recommended meal 
within 30 minutes before 
administration of 
minzasolmin. Study 
participants should eat 
this meal in 30 minutes 
or less; however, 
minzasolmin should be 
administered 30 minutes 
after start of the meal. 
Minzasolmin should be 
administered with 
240mL (8 fluid ounces) 
of water. No food should 
be allowed for at least 4h 
postdose. Water can be 
allowed as desired except 
for 1h before and 1h after 
drug administration. 
Study participants should 
receive standardized 
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Table 6‒1: 
Study interventions administered 
meals scheduled at the 
same time in each period 
of the study. 
Route of 
administration 
Oral 
Oral 
Oral 
Use 
Experimental 
Experimental 
Experimental 
IMP and 
NIMP/AxMP 
IMP 
IMP 
IMP 
Sourcing 
Provided centrally by the 
sponsor 
Provided centrally by the 
sponsor 
Provided centrally by the 
sponsor 
Packaging and 
labeling 
Minzasolmin capsules are 
manufactured, packaged, 
and labeled according to 
GMP guidelines and 
applicable laws or 
regulations. 
Minzasolmin tablets are 
manufactured, packaged, 
and labeled according to 
GMP guidelines and 
applicable laws or 
regulations. 
Minzasolmin tablets are 
manufactured, packaged, 
and labeled according to 
GMP guidelines and 
applicable laws or 
regulations. 
Comment 
 
Tablet formulation 
without fumaric acid 
Tablet formulation 
without fumaric acid 
Current/Former 
name 
UCB0599 
UCB0599 
UCB0599 
AxMP=auxiliary medicinal product; GMP=Good Manufacturing Practice; IMP=investigational medicinal 
product; NIMP=non-investigational medicinal product; SD=single dose 
6.2 
Preparation, handling, storage, and accountability 
The investigator or designee must confirm that appropriate temperature conditions have been 
maintained during transit for all study interventions received, and any discrepancies are reported 
and resolved before use of the study intervention. 
Only participants enrolled in the study may receive study intervention, and only authorized site 
staff may supply, prepare, or administer study intervention. All study interventions 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), or 
authorized site staff is responsible for study intervention 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 IMP Handling Manual. 
The investigator (or designee) will instruct the participant to store the study intervention 
following the instructions on the label. 
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Further guidance and information for the final disposition of unused study intervention are 
provided in the IMP Handling Manual.  
6.2.1 
Drug accountability  
Dispensing of study intervention will be documented in ClinBase to record study intervention 
dispensing on a by-participant basis and will serve as source documentation during the course of 
the study. Details of any study intervention lost, damaged (due to breakage or wastage), not used, 
partially used, or disposed of at the study site 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 intervention until destroyed. 
The investigator may assign some of the investigator’s duties for study intervention 
accountability at the study site to an appropriate pharmacist/designee. 
The investigator must ensure that the study intervention 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 intervention must be 
reconciled and destroyed at the site according to local laws, regulations, and UCB standard 
operating procedures (SOPs). Study intervention intended for the study cannot be used for any 
other purpose than that described in this protocol. 
6.3 
Assignment to study intervention 
Randomization numbers will be assigned at the site in an unblinded fashion and will be entered 
into ClinBase. 
6.4 
Blinding 
This is an open-label study. Blinding will not be performed. 
6.5 
Study intervention compliance 
For all study participants, minzasolmin will be administered at the study site. 
When participants are dosed at the site, they will receive study intervention directly from the 
investigator or designee, under medical supervision. The date and time of each dose administered 
in the clinic will be recorded in the source documents. The dose of study intervention and study 
participant identification will be confirmed at the time of dosing by a member of the study site 
staff other than the person administering the study intervention. 
6.6 
Dose modification 
There is no dose modification allowed in UP0152.  
6.7 
Continued access to study intervention after the end of the 
study 
There will be no access to study intervention after the end of the study. 
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6.8 
Treatment of overdose 
For all study participants, minzasolmin will be administered at the study site. No treatment for 
overdose is recommended by UCB and treatment for overdose should be at the discretion of the 
principal investigator. 
6.9 
Concomitant medication(s)/treatment(s) 
6.9.1 
Permitted concomitant therapy (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 
• Oral contraceptives not exceeding 30μg ethinyl estradiol or postmenopausal HRT or 
implants, patches, or IUDs/IUSs delivering progesterone (for female study participants) 
6.9.2 
Prohibited concomitant therapy (medications and therapies) 
Concomitant medications are not allowed with the exceptions listed in Section 6.9.1. 
6.9.3 
Rescue medication 
No rescue medication will be provided as part of this study. 
7 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of study intervention 
7.1.1 
Liver chemistry stopping criteria 
Study intervention will be discontinued immediately and permanently for a participant if liver 
chemistry stopping criteria are met. 
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Figure 7‒1: Phase 1 liver chemistry stopping algorithm 
 
ALT=alanine aminotransferase; AST=aspartate aminotransferase; INR=international normalized ratio; 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 
Corrected QT interval stopping criteria 
A participant who meets either bulleted criterion based on single 12-lead ECG readings will be 
withdrawn from the study. 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) before the exclusion of the participant.  
• QTcF >500ms OR Uncorrected QT >600ms 
• Change from Baseline (Day -1, before first treatment, Day 6, and Day 11) of QTcF >60ms 
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 
participant can continue on the study intervention and if any change in participant management is 
needed. This review of the ECG printed at the time of collection must be documented. Any new 
clinically significant finding should be reported as an AE. 
See the Schedule of Activities (Section 1.3) for data to be collected at the time of intervention, 
discontinuation and follow up and for any further evaluations that need to be completed. 
7.1.3 
Temporary discontinuation  
Study participants may be temporarily discontinued from study intervention (but not necessarily 
from the study) if there is a positive pregnancy test. Refer to Section 8.4.5 for additional 
procedures related to pregnancy in a study participant. 
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7.1.4 
Hypersensitivity reaction stopping criteria 
Study participants will be informed that if they develop any symptoms suggestive of a 
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 via the SAE reporting form. 
7.1.5 
Study stopping criteria 
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: 
• A pattern of AEs, considered as related to the study drug, occurs that in the opinion of the 
investigator and/or UCB Study Physician contraindicates the further dosing of additional 
study participants. 
• If the sponsor or its designee judges it necessary for medical, safety, regulatory, or any other 
reasons consistent with applicable laws, regulations, and Good Clinical Practice (GCP). 
Where it is possible to do so without threatening the safety of study participants, such 
discontinuation/suspension should be discussed with the UCB Study Physician before its 
implementation. 
7.2 
Participant discontinuation/withdrawal from the study 
A participant may withdraw from the study at any time at the participant’s own request for any 
reason (or without providing any reason). 
A participant may withdraw at any time at the discretion of the investigator for safety, 
behavioral, compliance, or administrative reasons. 
At the time of discontinuing from the study, if possible, an ETV should be conducted, as shown 
in the Schedule of Activities (Section 1.3). See Schedule of Activities for data to be collected at 
the time of study discontinuation and follow up and for any further evaluations that need to be 
completed. 
The participant will permanently discontinue from the study intervention and the study at that 
time. 
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, the participant 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. 
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Participants must 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 withdraws his/her consent.  
3. The sponsor or a regulatory agency requests withdrawal of the participant. 
4. Participant has a confirmed positive serum pregnancy test. 
Participants should be withdrawn from the study if any of the following events occur: 
1. Participant is noncompliant with the study procedures or medications in the opinion of the 
investigator. 
2. Participant takes prohibited concomitant medications as defined in this protocol. 
Investigators should attempt to obtain information on study participants in the case of 
withdrawal. 
Investigators should contact the study physician, whenever possible, to discuss the withdrawal of 
a study participant in advance. 
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, 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 ClinBase 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 
ClinBase.  
8 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the Schedule of Activities (Section 1.3).  
Protocol waivers or exemptions are not allowed. 
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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.  
In the event of a significant study-continuity issue (eg, caused by a pandemic), alternate 
strategies for participant visits, assessments, medication distribution, and monitoring may be 
implemented by the sponsor or the investigator, as per local health authority/ethics requirements. 
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 
Administrative and general/baseline procedures 
Participant’s informed consent (see Section 10.1.3) and general medical/procedure history will 
be obtained at the Screening Visit. Baseline procedures including urine cotinine test, drug screen, 
urine alcohol test, and verification of inclusion/exclusion criteria will be performed at the 
Screening Visit and on Day -1. Prior and concomitant medication will be reviewed at all visits 
throughout the study.  
8.2 
Efficacy assessments 
Not applicable. 
8.3 
Safety assessments 
Planned time points for all safety assessments are provided in the Schedule of Activities 
(Section 1.3). 
8.3.1 
Physical examination 
Physical examinations will be performed at the scheduled time points presented in Section 1.3. 
A complete physical examination will include, at a minimum, general appearance; ears, 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 be performed in case of emerging symptoms. 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 should pay special attention to clinical signs related to previous serious illnesses. 
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Clinically significant findings or worsening of previous findings will be recorded as AEs.  
8.3.2 
Vital signs 
Vital signs, including heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), 
respiratory rate, and aural temperature will be measured after 5 minutes of rest in a supine 
position (in a quiet setting without distractions such as a television or cell phones). Heart 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 consist of 3 heart rate 
and 3 blood pressure (BP) measurements (3 consecutive BP readings will be recorded at intervals 
of at least 1 minute). The average of the 3 BP readings will be recorded in ClinBase. 
8.3.3 
Electrocardiograms 
A single 12-lead ECG will be obtained as outlined in the Schedule of Activities (Section 1.3) -
but can be repeated in triplicate if clinically indicated - using an ECG machine that automatically 
calculates the heart 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 ClinBase: heart rate, PR-interval, 
QRS-duration, QT-interval, QTcF, and investigator’s conclusion on ECG profile. 
8.3.4 
Clinical safety laboratory tests 
See Appendix 2 (Section 10.2) for the list of clinical laboratory tests to be performed and refer to 
the Schedule of Activities (Section 1.3) for the timing and frequency.  
The investigator must review the laboratory report, document this review, and record any 
clinically significant changes occurring during the study as an AE. The laboratory results must 
be filed with the source documents.  
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or within 7 days after SFU/ETV should be repeated until the values return to normal 
or Baseline (Day -1, or Day 1 before first treatment) or are no longer considered clinically 
significant by the investigator or UCB Study Physician. 
If clinically significant values do not return to normal/Baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified, and the sponsor notified. 
All protocol-required laboratory tests, as defined in Appendix 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 tests performed at the institution’s 
local laboratory require a change in participant management or are considered clinically 
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significant by the investigator (eg, SAE or AE or dose modification), then the results must be 
recorded. 
8.3.5 
Pregnancy testing 
Refer to Appendix 4 (Section 10.4) for pregnancy testing guidelines. 
8.4 
AEs, SAEs, and other safety reporting 
The definitions of AEs and SAEs can be found in Appendix 3 (Section 10.3). 
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 intervention, or that caused the study participant 
to discontinue minzasolmin (see Section 10.3). This includes events reported by the participant.  
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3 
(Section 10.3). 
8.4.1 
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 or ETV (if 
applicable) at the time points specified in the Schedule of Activities (Section 1.3) and must be 
reported in the ClinBase even if no study intervention was taken but specific study procedures 
were conducted. This includes all AEs not present before the initial visit and all AEs that 
recurred or worsened after the initial visit. 
All SAEs will be recorded and reported to the UCB Study Physician or designee immediately 
and under no circumstance should this exceed 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. 
Investigators are not obligated to actively seek information on AEs or SAEs after conclusion of 
the study participation. However, if the investigator learns of any SAE, including a death, at any 
time after a participant has been discharged from the study, and the investigator considers the 
event to be reasonably related to the study intervention or study participation, the investigator 
must promptly notify the sponsor. 
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). 
8.4.2 
Method of detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences.  
8.4.3 
Follow up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each study 
participant at subsequent visits/contacts. All AEs, and SAEs, will be followed until resolution, 
stabilization, the investigator determines that it is no longer clinically significant, the event is 
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otherwise explained, or the study 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). 
8.4.4 
Regulatory reporting requirements for SAEs 
Prompt notification of an SAE by the investigator to the sponsor is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
intervention under clinical investigation are met.  
Further to the reporting of an SAE from the investigator to the sponsor, an expectedness 
assessment will be made per the IB, as reference safety information for this study, and relevant 
sponsor’s SOPs, and appropriate reporting of suspected unexpected serious adverse reactions 
(SUSARs) will be carried out to health authorities as per International Council for 
Harmonisation (ICH) and local regulatory requirements. Investigator safety reports must be 
prepared for SUSARs according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. The 
sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, Institutional Review Boards (IRB)/Independent Ethics Committees 
(IEC), and investigators. 
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAEs) from the sponsor will review and then file it 
along with the IB and will notify the IRB/IEC, if appropriate according to local requirements. 
8.4.5 
Pregnancy 
Details of all pregnancies in female study participants and, if consented, in female partners of 
male study participants will be collected after the start of study intervention and, until at least 
12 months after the delivery date. 
If a pregnancy is reported, the investigator will record pregnancy information on the appropriate 
form and submit it to the sponsor within 24 hours of learning of the pregnancy, and should 
follow the procedures outlined in Appendix 4 (Section 10.4). 
While pregnancy itself is not considered to be an AE, any pregnancy will need to be reported. In 
some circumstances, a pregnancy report is considered as an SAE: miscarriage, elective abortion 
when medically indicated (eg, when pregnancy is endangering life or health of woman or when 
fetus will be born with severe abnormalities), unintended pregnancy after hormonal 
contraceptive failure (if the hormonal contraceptive was correctly used), ectopic pregnancy, fetal 
demise, or any congenital anomaly/birth defect of the baby. 
The participant/pregnant female partner will be followed to determine the outcome of the 
pregnancy. The investigator will collect follow-up information on the participant/pregnant 
female partner and the neonate, and the information will be forwarded to the sponsor. 
Any poststudy pregnancy-related SAE in either the mother or the neonate considered reasonably 
related to the study intervention by the investigator will be reported to the sponsor as described 
in Section 8.4.4. While the investigator is not obligated to actively seek this information in 
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former study participants/pregnant female partner, he or she may learn of an SAE through 
spontaneous reporting. 
Any female participant who becomes pregnant while participating in the study will discontinue 
study intervention and return for an ETV as described in the Schedule of Activities (Section 1.3). 
If the study participant decides to completely withdraw from the study, an SFU visit should be 
scheduled 5 to 9 days after the final dose of study intervention.  
The investigator must inform the participant of any known potential risks the study intervention 
may have to the mother and/or the developing fetus/infant as well as any available treatment 
alternatives.  
The investigator should discuss with the participant the possibility of continuing study 
participation by attending the scheduled visits for assessments as their condition allows but 
without the participant continuing study intervention. Protocol-specified blood sample collection 
will be adapted as indicated in the Schedule of Activities (Section 1.3) considering the study 
participant’s condition during the study. The tests or assessments that are considered 
contraindicated during the pregnancy should not be performed. Caution is required with respect 
to concomitant medication if not contraindicated in pregnancy. As indicated, investigators are 
advised to discuss the case with the sponsor study physician to gain feedback on 
protocol-defined actions. 
8.4.6 
Adverse events of special interest 
An adverse event of special interest (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 or associated medical device.For 
minzasolmin, the following events require immediate reporting (within 24 hours regardless of 
seriousness) to UCB: 
• Possible Hy’s Law (as per Section 7.1.1) 
− 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) 
8.4.6.1 
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. 
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Hypersensitivity reactions will be AESIs and require expedited reporting to UCB, regardless of 
seriousness, expectedness, or relatedness in line with Section 8.4.6. This will allow for rapid 
evaluation.  
Procedures for the management of minzasolmin are provided in Appendix 3 (Section 10.3). 
8.4.6.1.1 
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 
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 8.4.6.1.1.1. 
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. 
8.4.6.1.1.1 
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 include 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 is indicated by 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 is indicated by 2 or more of the following: 
• Skin or mucous membranes (as above) 
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• 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 
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). 
8.4.6.1.2 
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, DBP, 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 
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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. 
8.4.6.1.3 
Additional investigations 
Investigators should arrange for the following investigations; further investigations may be 
requested after consultation with the study physician: 
• 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. 
8.4.6.1.4 
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. 
8.4.6.1.5 
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 immunoglobulin E).  
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). 
8.4.6.1.6 
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 
or signs, or both. 
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8.5 
Safety signal detection 
Selected data from this study will be reviewed periodically to detect as early as possible any 
safety concern(s) related to minzasolmin so that investigators, clinical study participants, 
regulatory authorities, and IRBs/IECs will be informed appropriately and as early as possible. 
As appropriate for the stage of development and accumulated experience with the study 
intervention, 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. 
8.6 
Pharmacokinetics 
Pharmacokinetic sampling will be mandatory for study participation.  
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). 
Any changes in the timing or addition of time points for any planned study assessments must be 
documented and approved by the relevant study team member and then archived in the sponsor 
and site study files, but will not constitute a protocol amendment. The IEC will be informed of 
any safety issues that require alteration of the safety monitoring scheme or amendment of the 
ICF. 
Additional samples may be collected at additional time points during the study if warranted and 
agreed upon between the investigator and the sponsor. Instructions for the collection and 
handling of biological samples will be provided by the sponsor. The actual date and time (24-
hour clock time) of each sample will be recorded. 
See Section 5.3 for guidelines on lifestyle restrictions including details on meals and dietary 
restrictions. 
Plasma samples (approximately 2mL whole blood collection) will be used to measure 
minzasolmin and its metabolite plasma concentration and derive the primary PK parameters 
(Table 3‒1). The derived PK parameters will be used to evaluate the relative bioavailability of 
the new minzasolmin tablet formulation versus reference granules in capsule formulation in 
healthy participants and to evaluate the effect of food with the new tablet formulation on the PK 
of minzasolmin.   
Instructions pertaining to sample collection, processing, storage, labeling, and shipping are 
provided in the laboratory manual for this study. Collection of these samples will enable 
evaluation of relevant pharmacological information to support minzasolmin formulation 
development and food affects.  
8.6.1 
Use of residual plasma samples  
Any residual and/or surplus PK plasma samples remaining after the protocol-defined analysis has 
been performed may be used for additional exploratory analysis related to the purpose of this 
study. This may include, but is not limited to, biomarker assay development/optimization, 
protein binding, exploratory metabolite profiling/quantification, or other bioanalytical purposes 
(eg, cross check between different sites and/or stability assessment). Given the exploratory 
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nature of the work, the analytical method used for those assessments will not be validated. As 
such, the results from this exploratory analysis will not be included in the Clinical Study Report. 
8.7 
Biomarkers 
Blood sampling for exploratory genetic biomarkers 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 
Immunogenicity assessments 
Immunogenicity assessments including the assessment of antibodies to minzasolmin are not 
applicable in this study. 
8.9 
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). The SAP will include a more technical and detailed description of the 
statistical analyses described in this section. This section is a summary of the planned statistical 
analyses of the most important endpoints including primary and key secondary endpoints. 
9.1 
Analysis sets 
9.1.1 
Study Participant Set 
All study participants who signed the ICF. 
9.1.2 
Randomized Set 
The Randomized Set consists of all study participants who are randomized, regardless of whether 
the participant received investigational intervention. Of note, this set will only be produced if it 
differs from the Safety Set (SS). 
9.1.3 
Safety Set 
The SS consists of all study participants who randomized and received full or partial study 
medication according to the treatment that the participants actually received. Participants who 
have data documenting they did not administer investigational intervention, even if received, are 
excluded from the SS. 
9.1.4 
Pharmacokinetics Set 
The Pharmacokinetics Set (PKS) consists of all study participants in the SS who have at least 1 
observable PK concentration data point and who have no important protocol deviations affecting 
the PK during the study.  
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9.2 
Statistical analyses 
9.2.1 
General consideration 
All analyses will be performed using SAS® version 9.4 or later (SAS Institute, Cary, North 
Carolina, United States). 
9.2.1.1 
Pharmacokinetic parameter calculation 
For calculation of the plasma PK parameters of minzasolmin and metabolites, the actual 
sampling time points will be used to evaluate the PK parameters (Table 9‒1).  
The following PK parameters will be determined using the actual recorded sampling times and 
noncompartmental method(s) with Phoenix WinNonlin® (Version 8.3.4), as applicable: area 
under the plasma concentration-time curve from time 0 to t (AUC0-t), AUC, Cmax, tmax, t½, CL/F 
(minzasolmin), Vz/F (minzasolmin), Cmax metabolite to parent ratio, and AUC metabolite to 
parent ratio from the plasma concentration-time data. 
Additional parameters (eg, AUC%Extrap, Lambda_z (λz)) will be calculated as appropriate. 
Table 9‒1: 
Noncompartmental PK parameters for minzasolmin in plasma 
PK Parameter 
Definition 
AUC 
The area under the plasma concentration-time 
curve from time zero to infinity (mass * time * 
volume-1). 
AUC0-t 
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). 
t½  
The elimination half-life associated with the 
terminal slope (λz) of a semi logarithmic 
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 plasma concentration-time curve 
extrapolated from the time t to infinity as a 
percentage of total AUC. 
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Table 9‒1: 
Noncompartmental PK parameters for minzasolmin in plasma 
PK Parameter 
Definition 
Rsq_adjc 
 
Square of the correlation coefficient (adjusted for 
the number of data points included) associated 
with λz. 
MRCmaxd 
Cmax metabolite to parent ratio. 
MRAUCd 
AUC metabolite to parent ratio. 
a For minzasolmin only. 
b AUC%Extrap was listed if AUC was presented. 
c Rsq_adj was listed only. 
d Metabolites only. Pharmcokinetic parameters will be derived after noncompartmental analysis.  
The linear trapezoidal rule will be used for estimation of area under the curve (AUC and 
AUC0-t). Regression analysis of the terminal plasma elimination phase for the determination of t½ 
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 0.8 or the AUC%Extrap value is greater than 20%, no value is to be 
reported for AUC, t½, CL/F, and Vz/F. 
9.2.2 
Primary endpoints analysis 
PK analyses will be performed on the PKS.  
The plasma concentration-time profiles and PK parameters of minzasolmin will be summarized 
by formulation and feeding condition (fed vs fasting) using descriptive statistics (number of 
available observations, arithmetic mean, standard deviation, geometric mean, coefficient of 
variation (CV) of geometric mean, median, interquartile range, 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). 
Individual concentration-time profiles will be displayed graphically on a linear-linear scale and 
on a semilogarithmic scale. Overall geometric mean plasma concentrations-time curves and 
corresponding 95% confidence intervals (CIs) will be displayed by formulation and feeding 
condition (fed vs fasting). 
9.2.2.1 
Definition of endpoint(s) 
The primary PK parameters are AUC0-t, AUC, and Cmax for minzasolmin. 
The primary comparisons of interest are: 
• Tablet versus granules in capsule under fasting condition 
• Tablet under fed condition versus tablet under fasting condition 
9.2.2.2 
Main analytical approach 
9.2.2.2.1 
Estimation of geometric mean ratios 
Following log-transformation, the primary PK parameters (AUC0-t, AUC, and Cmax) will each be 
evaluated using a linear mixed effect model with a random intercept term for study participant 
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and fixed effect categorical terms for Treatment (3 formulation x feeding conditions), Sequence, 
and Period to account for the crossover nature of the study design. 
Two separate analysis of variance (ANOVA) models, (1) one including data for the new 
formulation versus the reference formulation under the fasting condition and (2) the other one 
including data for the new tablet formulation under fed condition versus the tablet formulation 
under fasting condition will be used to align with the assumptions made for conditional power 
estimations (see Section 9.4 below). 
The estimate of the geometric mean ratio (GMR) and associated 90% CI for the tablet (test) 
versus the capsule (reference) formulations given under fasting condition will be derived using 
the first ANOVA model in order to assess the minzasolmin relative bioavailability between the 2 
formulations. 
The estimate of the GMR and associated 90% CI for the tablet under fed condition (test) versus 
the tablet under fasting condition (reference) treatment will be derived using the second ANOVA 
model in order to assess the food effect. 
Other sensitivity analyses may also be performed on the PK parameters, such as a common 
ANOVA model including all data. 
9.2.3 
Other PK endpoint analysis  
The other PK parameters of minzasolmin and metabolites will be summarized by formulation 
and feeding condition (fed vs fasting) using descriptive statistics as below: 
• For minzasolmin: tmax, t½, CL/F, and Vz/F (if possible but not limited). For tmax, only the 
median, minimum, and maximum will be reported. 
• For 
 metabolites: Cmax, tmax, AUC0-t, AUC, and each metabolite/parent 
Cmax and AUC ratio (corrected for the molecular weight of the entities), as appropriate. 
• Additional analyses of PK parameters might be conducted as appropriate. 
9.2.4 
Secondary safety endpoints analysis 
Secondary safety endpoints in this study are the occurrence of TEAEs, treatment-emergent 
SAEs, and the occurrence of TEAEs leading to withdrawal from the study. 
Unless stated otherwise, all safety analyses will be performed on the SS. 
All AEs will be coded using the most recent Medical Dictionary for Regulatory Activities 
(MedDRA®) and characterized as pre-treatment and treatment-emergent according to the intake 
of the IMP. 
The occurrence and incidence of TEAEs will be summarized by MedDRA system organ class 
and preferred term and by treatment group. The occurrence and incidence of TEAEs will also be 
summarized by maximum event intensity and by relationship to the study medication. Adverse 
events will be categorized by severity (mild/moderate/severe). Adverse events leading to 
discontinuation and SAEs will also be summarized by treatment group. All AEs will be listed 
and will include actions taken for each AE, the time of onset of the AE after dosing, and the 
duration of each AE.  
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9.2.4.1 
Exploratory safety endpoints analysis 
Laboratory variables and changes from Baseline (Day -1, or Day 1 before first treatment) will be 
summarized by time point and will be presented by treatment group. For categorized values 
according to the reference range, shift tables from Baseline to each post-Baseline 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, DBP, PR, respiration rate, and body temperature) and changes from 
Baseline (Day -1, or Day 1 before first treatment) will be summarized by time point and will be 
presented by treatment group. 
The single 12-lead ECG will be recorded as timepoints defined in schedule of activities. 
Descriptive statistics will be presented for ECG values and changes from Baseline (Day -1, 
before first treatment, Day 6, and Day 11) through treatment periods. 
9.3 
Interim analysis 
No interim analysis or data monitoring is planned for this study. 
9.4 
Sample size determination 
The plan is to randomize 18 participants into the study; dropouts are assumed to be minimal and 
will not be replaced. 
Conditional power was estimated for the key comparisons of interest based on the Primary PK 
Objective. 
Primary comparison: 
• To assess noninferiority of the AUC0-t of a new tablet formulation versus the reference 
‘granules in capsule’ formulation in fasting state (relative bioavailability) 
Secondary comparison: 
• To assess noninferiority of the AUC0-t of a new tablet formulation in fed state versus the 
same formulation in fasting state (food effect) 
Other comparisons: 
• To assess nonsuperiority of the Cmax of a new tablet formulation versus the reference 
‘granules in capsule’ formulation in fasting state (relative bioavailability) 
• To assess nonsuperiority of the Cmax of a new tablet formulation in fed state versus the same 
formulation in fasting state (food effect) 
The assessments were based on a one-sided noninferiority t-test, calculated exact via noncentral 
t-distribution for a 2-treatment 2-period crossover design for continuous response data on the log 
scale with significance level of 0.05 (5%), assuming: 
• A ratio of geometric means (ρ) between the new tablet formulation and the reference 
formulation under the alternative hypothesis (H1) of 1.0 for AUC0-t or 0.95 for Cmax 
• A lower margin of 0.8 for noninferiority and 1.25 for nonsuperiority 
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• A geometric intra-participant CV based on estimates of the residual variance obtained from 
linear mixed effect models (ANOVA) applied to the log-transformed AUC0-t and Cmax data 
from UP0073, a minzasolmin Phase 1 study with similar participant demographics (males 
and females aged 18 to 55 years) which used a crossover design 
Relative bioavailability comparisons: 
For the assessment of noninferiority of the AUC0-t or the assessment of nonsuperiority of the 
Cmax, for the new tablet formulation versus the reference ‘granules in capsule’ formulation, the 
estimates of variability were based on the UP0073 2-by-2 ANOVA models comparing the 
(nonencapsulated) fumaric acid tablet to the ‘granules in capsule’ formulation under condition of 
normal gastric pH (ie, relevant treatment periods from UP0073 Part A). 
This assumes homogenous variance for the 2 different formulations under fasting condition. 
Food effect comparisons: 
For the assessment of noninferiority of the AUC0-t or the assessment of nonsuperiority of the 
Cmax, for the new tablet formulation under fed state versus the fasting state, the estimates of 
variability were based on the UP0073 2-by-2 ANOVA models comparing the encapsulated 
fumaric acid tablet to the (nonencapsulated) fumaric acid tablet formulations under condition of 
normal gastric pH (ie, relevant treatment periods from UP0073 Part A). 
This assumes homogenous variance for the encapsulated and the nonencapsulated forms of the 
fumaric acid tablet, homogenous variance for the nonencapsulated tablet with or without fumaric 
acid, and homogenous variance for the fed and fasting states of the new tablet. 
Analyses were performed using the function power.noninf from the R package PowerTOST 
(https://CRAN.R-project.org/package=PowerTOST). 
For the primary treatment comparison of interest, 12 completers would provide over 96% power 
to assess noninferiority of the AUC0-t conditional on the GMR being 1.0. For a GMR of 0.95 
(equivalent to the GMR observed in UP0073 for the fumaric acid tablet versus the ‘granules in 
capsule’ formulation), power would be 85% for 12 completers, 92% power for 15 completers 
and 96% for 18 completers. 
For the secondary treatment comparison of interest, 12 completers would provide over 99% 
power to assess noninferiority of the AUC0-t conditional on the GMR being 0.95, equivalent to 
the GMR observed in UP0073 for the encapsulated fumaric acid tablet versus (nonencapsulated) 
fumaric acid tablet.  
Details of the conditional power estimations can be found in the “UP0152 sample size 
documentation form” located in the sample size folder of the electronic trial master file. 
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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 a Competent Authority (CA) and/or IRB/IEC, 
as defined in local regulations, ICH-GCP, and in accordance with the ethical principles that have 
their origin in the Declaration of Helsinki. 
UCB/the investigator will ensure that a CA and 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. Before 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/CA for their review 
and approval. 
Before initiating a study, the investigator will have written and dated full approval from the 
responsible IRB/IEC/CA 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. UCB will submit relevant information to the CA in 
accordance with regulatory requirements. 
The investigator/UCB will not make any changes in the study or study conduct without 
IRB/IEC/CA 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/UCB to obtain an expedited review 
by the IRB/IEC/CA, as allowed. 
As part of the IRB/IEC/CA requirements for continuing review of approved studies, the 
investigator will be responsible for submitting periodic progress reports to the IRB/IEC 
according to local requirements and UCB will be responsible for submitting periodic progress 
reports to the CA, 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 and UCB should provide a final report to the CA following study completion. 
UCB (or its representative) will communicate safety information to the appropriate regulatory 
authorities/CA 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. 
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Finance and insurance are addressed in the investigator and/or CRO agreements, as applicable. 
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. 
Before 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. 
Before participation in the study, the ICF should be signed and personally dated by the 
participant and by the person who conducted the informed consent discussion (investigator or 
designee). The participant 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. 
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. A ClinBase 
entry 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 clinic center, as well as by 
advertisement. 
10.1.5 
Data protection 
UCB staff (or designee) will affirm and uphold the participant’s confidentiality. Participants will 
be assigned a unique identifier by the sponsor. Any participant records or datasets that are 
transferred to the sponsor will contain the identifier only; participant names or any information 
which would make the participant identifiable will not be transferred.  
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 will be informed how his/her personal data collected in the study will be used by 
the sponsor and that it will be used in accordance with local data protection laws. The level of 
disclosure will also be explained to the participant.  
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The participant will 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. 
The personal data of the investigator and any site staff involved in the study will be processed by 
UCB in accordance with the UCB Data Protection Notice for Healthcare Professionals available 
at https://www.ucb.com/Privacy-policy-for-Healthcare-Professionals. 
The contract between UCB or its designee and study sites specifies responsibilities of the parties 
and the timelines related to data protection, including handling of data security breaches and 
respective communication and cooperation of the parties in order to mitigate any possible 
deleterious consequences for the participants. 
Information technology systems used to collect, process, and store study-related data are secured 
by technical and organizational security measures designed to protect such data against 
accidental or unlawful loss, alteration, or unauthorized disclosure or access. 
10.1.6 
Committees structure 
No Safety Monitoring Committee will be included in this study. 
10.1.7 
Dissemination of clinical study data 
This study will be registered and results posted on public registries as required and in line with 
UCB policies. A plain language summary of results may also be written. Investigators may 
request access to anonymized individual participant-level data and redacted study documents 
after product approval in the United States and Europe. However, once the study completes, if 
the risk of re-identifying study participants is determined to be too high, then individual 
participant-level data will not be made available. 
For results disclosure on public registries (eg, ClinicalTrials.gov), TEAEs and 
treatment-emergent SAEs will be published. 
A summary of the results is planned to be posted to the EU database within 1 year of study 
completion, in accordance with international standards and irrespective of the outcome of the 
clinical study. 
10.1.8 
Data quality assurance 
All participant data relating to the study will be recorded on printed case report form (CRF) or in 
ClinBase 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 
signing the CRF or electronically signing in ClinBase.  
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 participant that supports 
the information entered in the ClinBase. 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.  
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Monitoring details describing strategy, including definition of study critical data items and 
processes (eg, risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques (central, 
remote, or on-site monitoring) are provided in the monitoring plan. 
The sponsor or designee is responsible for the data management of this study including quality 
checking of the data.  
UCB assumes accountability for actions delegated to other individuals (eg, CROs). 
Study monitors will perform ongoing source data verification to confirm that data entered into 
ClinBase by authorized site personnel are accurate, legible, contemporaneous, original, 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 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 before 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 
ClinBase completion 
The investigator is responsible for prompt reporting of accurate, complete, and legible data in 
ClinBase and in all required reports. 
Any change or correction to ClinBase after saving must be accompanied by a reason for the 
change.  
10.1.8.2 
Apps 
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). Photocopies and/or printouts of CRFs are not considered 
acceptable source documents.  
The investigator must maintain accurate documentation (source data) that supports the 
information entered in ClinBase.  
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, 
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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. 
Electronic data records, such as Holter monitor records or electroencephalogram records, must 
be saved and stored as instructed by UCB (or designee). 
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 or 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: 
For study termination: 
• Discontinuation of further study intervention development. 
For site termination: 
• 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 or no recruitment (evaluated after a reasonable amount of time) of participants by 
the investigator. 
• Individual recruitment goal for site reached earlier than expected. 
• 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. 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any CRO(s) used in the study of the 
reason for termination or suspension, as specified by the applicable regulatory requirements. The 
investigator shall promptly inform the participant and should assure appropriate participant 
therapy and/or follow up. 
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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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10.2 
Appendix 2: Clinical laboratory tests 
• All clinical laboratory tests will be processed at the local laboratory, with only the PK 
samples analyzed by a central laboratory. The tests detailed below in Table 10‒1 will be 
performed. 
• Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5.1 and Section 5.2 of the protocol. 
• Additional tests may be performed at any time during the study as determined necessary by 
the investigator or required by local regulations. 
Table 10‒1: Protocol-required safety laboratory tests 
Laboratory tests 
Parameters 
Hematologya 
Platelet count  
RBC indices: 
Mean 
corpuscular 
volume Mean 
corpuscular 
hemoglobin  
%Reticulocytes 
WBC count with 
differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC count 
Hemoglobin 
Hematocrit 
Clinical chemistrya,b 
Blood urea 
nitrogen  
Potassium 
AST/serum 
glutamic-
oxaloacetic 
transaminasec  
Total and direct 
bilirubinc 
 
Creatinine 
Sodium 
ALT/serum 
glutamic-pyruvic 
transaminasec  
Total protein 
 
Glucose 
(fasting)  
Calcium 
ALPc, d 
Creatine 
phosphokinase,  
Lactate  
dehydrogenase,  
serum aldolase,  
Cystatin C  
 
Coagulation 
(INR, PT, 
and aPTT) 
Estimated 
glomerular 
filtration 
ratee 
 
 
Routine urinalysis 
• 
Specific gravity 
• 
Albumin/creatinine ratio 
• 
pH, glucose, protein, blood, ketones, bilirubin, 
urobilinogen, nitrite, leukocyte esterase by dipstick 
• 
Upon a positive urine test from leucocytes, blood, nitrite, or 
protein, the investigator may require further urine analysis, 
such as flow cytometry. Results of additional urine analyses 
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Table 10‒1: Protocol-required safety laboratory tests 
Laboratory tests 
Parameters 
will be included in the database. If the flow cytometry 
examination shows a different result than the urine sticks, 
the urine will be investigated by fully automated digital 
imaging where leucocytes, erythrocytes, casts in urine will 
be analyzed. 
Pregnancy testing 
• 
Highly sensitive serum human chorionic gonadotropin 
pregnancy test (as needed for women of childbearing 
potential)  
Other screening tests 
• 
Total immunoglobulin E test 
• 
Urine alcohol and cotinine test  
• 
Follicle stimulating hormone and estradiol (females only) 
• 
Urine drug screen (to include at minimum: amphetamines, 
barbiturates, cocaine, opiates, cannabinoids, and 
benzodiazepines, creatinine [to exclude dilution of urine 
samples])  
• 
Serology (HIV antibody, HBsAg, HCV-Ab, and HBcAb 
[IgG and IgM])  
The results of each test must be entered into ClinBase.  
ALP=alkaline phosphatase; ALT=alanine aminotransferase; aPTT=activated partial prothrombin time; 
AST=aspartate aminotransferase; HBcAb=hepatitis B core antibody; HBsAg=hepatitis B surface antigen; 
HCV-Ab=hepatitis C virus antibody; HIV=human immunodeficiency virus; IgG=immunoglobulin G; 
IgM=immunoglobulin M; INR=international normalized ratio; PT=prothrombin time; RBC=red blood cell; 
ULN=upper limit of normal; WBC=white blood cell 
a Blood hematology and chemistry laboratory tests will be obtained in the fasting state following an overnight fast 
of at least 10 hours. 
b Details of liver chemistry stopping criteria and required actions and follow up are given in Section 7.1.1 and 
Section 10.6. All events of ALT [or AST] 3 × ULN and bilirubin 2 × ULN (>35% direct bilirubin) or ALT 
[or AST] 3 × ULN and INR >1.5, (if INR measured) which may indicate severe liver injury (possible Hy’s 
Law), must be reported to UCB in an expedited manner (excluding studies of hepatic impairment or cirrhosis). 
c The following parameters are part of hepatic function testing: ALP, ALT, AST, and bilirubin. 
d If ALP is elevated, consider fractionating. 
e Estimated glomerular filtration rate, based on the Chronic Kidney Disease Epidemiology Collaboration 2021 
equation, only at screening.  
Investigators must document their review of each laboratory safety report. 
 
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10.3 
Appendix 3: Adverse events – Definitions and procedures for 
recording, evaluating, follow up, and reporting 
10.3.1 
Definition of AE 
AE definition 
• An AE is any untoward medical occurrence in a clinical study participant, temporally 
associated with the use of study intervention, whether or not considered related to the study 
intervention. 
• NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of study intervention. 
Events meeting the AE definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other 
safety assessments (eg, ECG, radiological scans, vital signs measurements), including those 
that worsen from baseline, considered clinically significant in the medical and scientific 
judgment of the investigator (ie, not related to progression of underlying disease, or more 
severe than expected for the participant’s condition). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an increase 
in frequency and/or intensity of the condition. 
• New condition detected or diagnosed after study intervention administration even though it 
may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study intervention 
or a concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is 
an intentional overdose taken with possible suicidal/self-harming intent. Such overdoses 
should be reported regardless of sequelae. 
Events not meeting the AE definition 
• Any abnormal laboratory findings or other abnormal safety assessments that are associated 
with the underlying disease, unless judged by the investigator to be more severe than 
expected for the participant’s condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition. 
• Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to the 
procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
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10.3.2 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
An SAE is defined as any untoward medical occurrence that, at any dose, meets 1 or more of the 
criteria listed: 
a. Results in death 
b. Is life-threatening 
The term life-threatening in the definition of serious refers to an event in which the participant 
was at risk of death at the time of the event. It does not refer to an event, which hypothetically 
might have caused death, if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
− In general, hospitalization signifies that the participant has been admitted at the hospital 
or emergency ward for observation and/or treatment that would not have been appropriate 
in the physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other 
serious criteria, the event is serious. When in doubt as to whether hospitalization occurred 
or was necessary, the AE should be considered serious. 
− Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. 
d. Results in persistent or significant disability/incapacity 
− The term disability means a substantial disruption of a person’s ability to conduct normal 
life functions. 
− This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (eg, sprained ankle) that may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Other situations: 
− Medical or scientific judgment should be exercised by the investigator in deciding 
whether SAE reporting is appropriate in other situations such as important medical events 
that that may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to prevent 
one of the other outcomes listed in the above definition. These events should usually be 
considered serious. 
◦ 
Examples of such events include, but are not limited to, invasive or malignant 
cancers, intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias, convulsions not resulting in hospitalization, or 
development of intervention dependency or intervention abuse. 
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10.3.3 
Recording and follow up of AE and/or SAE 
AE and SAE recording 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostics reports) 
related to the event. 
• The investigator will then record all relevant AE/SAE information. 
• It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to UCB in lieu of completion of the ClinBase. 
• There may be instances when copies of medical records for certain cases are requested by 
UCB. In this case, all participant identifiers, with the exception of the participant number, 
will be redacted on the copies of the medical records before submission to UCB. 
• The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
Assessment of intensity 
The investigator will make an assessment of intensity for each AE and SAE reported during the 
study and assign it to 1 of the following categories:  
• Mild: 
A type of AE that is usually transient and may require only minimal treatment or therapeutic 
intervention. The event does not generally interfere with usual activities of daily living. 
• Moderate:  
A type of AE that is usually alleviated with additional specific therapeutic intervention. The 
event interferes with usual activities of daily living, causing discomfort but poses no 
significant or permanent risk of harm to the research participant. 
• Severe:  
A type of AE that interrupts usual activities of daily living, or significantly affects clinical 
status, or may require intensive therapeutic intervention. An AE that is assessed as severe 
should not be confused with a SAE. Severe is a category utilized for rating the intensity of an 
event; and both AEs and SAEs can be assessed as severe. 
• An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of a SAE, NOT when it is rated as severe (eg, a severe AE may be 
either serious or not serious, depending on whether these criteria are also met). 
The National Cancer Institute Common Terminology Criteria for Adverse Events should be used 
as a supportive standardization instrument to evaluate AEs and SAEs but the final intensity 
grading by the investigator must be mild, moderate, or severe. 
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Assessment of causality 
• The investigator is obligated to assess the relationship between study intervention and each 
occurrence of each AE/SAE. The investigator will use clinical judgment to determine the 
relationship. 
• A reasonable possibility of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, 
as well as the temporal relationship of the event to study intervention administration, will be 
considered and investigated. 
• For causality assessment, the investigator will also consult the IB and/or product information, 
for marketed products. 
• The investigator must review and provide an assessment of causality for each AE/SAE and 
document this in the medical notes. There may be situations in which an SAE has occurred 
and the investigator has minimal information to include in the initial report to UCB. 
However, it is very important that the investigator always make an assessment of causality 
for every event before the initial transmission of the SAE data to UCB. 
• The investigator may change their opinion of causality in light of follow-up information and 
send an SAE follow-up report with the updated causality assessment. 
• The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
Follow up of AEs and SAEs 
• The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by UCB to elucidate 
the nature and/or causality of the AE or SAE as fully as possible. This may include additional 
laboratory tests or investigations, histopathological examinations, or consultation with other 
health care professionals. 
• An AE should be followed until it has resolved, has a stable sequelae, the investigator 
determines that it is no longer clinically significant, or the participant is lost to follow up. 
This follow-up requirement applies to AEs, SAEs, and AEs of special interest. 
• If a participant dies during participation in the study or during a recognized follow-up period, 
the investigator will provide UCB with a copy of any postmortem findings including 
histopathology. 
• New or updated information will be recorded in the originally completed ClinBase. 
• The investigator will submit any updated SAE data to UCB immediately and under no 
circumstance should this exceed 24 hours of receipt of the information. 
10.3.4 
Reporting of SAEs 
SAE reporting to UCB via paper data collection tool 
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• Initial notification via telephone does not replace the need for the investigator to complete 
and sign the SAE data collection tool within the designated reporting timeframes. 
• Contacts for SAE reporting can be found in SERIOUS ADVERSE EVENT REPORTING. 
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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 follicle stimulating hormone (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 nonestrogen 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 during the protocol-defined time frame in Section 5.1: 
• 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 
WOCBP 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 final dose of study intervention. 
Male participants with a pregnant or breastfeeding (including pumping breastmilk to feed a 
child) partner must agree to remain abstinent from penile-vaginal intercourse or use a male 
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condom during each episode of penile penetration during the protocol-defined time frame and for 
1 week after the final dose of study medication. 
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 10‒
2 below. 
Table 10‒2: Highly effective contraceptive methodsa 
Highly effective contraceptive methods that are user dependentb,c,d 
Failure rate of <1% per year when used consistently and correctly.  
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of 
ovulationc,d  
• 
Oral  
• 
Intravaginal  
• 
Transdermal  
Progestogen only hormonal contraception associated with inhibition of ovulation 
• 
Oral  
• 
Injectable  
Highly effective methods that are user independentc,d 
• 
Implantable progestogen only hormonal contraception associated with inhibition of ovulation 
• 
IUD 
• 
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 intervention. 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.  
IUD=intrauterine device; IUS=intrauterine hormone-releasing system; WOCBP=woman of childbearing potential 
a In case of newly started contraception pills/IUDs, the principal investigator 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 If locally required, in accordance with Clinical Trial Facilitation Group guidelines, acceptable contraceptive 
methods are limited to those which inhibit ovulation as the primary mode of action. 
d Hormonal contraception may be susceptible to interaction with the study intervention, which may reduce the 
efficacy of the contraceptive method. In this case, male condoms must be used in addition to hormonal 
contraception during the Treatment Period and for at least 1 week after the final dose of study intervention. 
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Pregnancy testing 
• WOCBP should only be included after a confirmed menstrual period and a negative highly 
sensitive serum pregnancy test at the Screening Visit. 
• Additional pregnancy testing should be performed on Day -1 and at the SFU Visit after the 
final dose of study intervention and as required locally. 
• Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected.  
• Pregnancy testing, with a sensitivity of 25 mIU/mL will be performed.  
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 intervention. If the study 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 intervention.  
• The investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. Upon notification of a pregnancy, the investigator 
must immediately (within 24 hours) notify UCB’s Patient Safety department by entering all 
pregnancy information on the appropriate pregnancy paper forms provided by UCB. 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 via an update to ClinBase. 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, any pregnancy will need to be reported 
to UCB Patient Safety. In some circumstances a pregnancy-related AE or outcome should be 
considered as an SAE: miscarriage, elective abortion when medically indicated (eg, when 
pregnancy is endangering life or health of mother or when fetus will be born with severe 
abnormalities), unintended pregnancy after hormonal contraceptive failure (if the hormonal 
contraceptive was correctly used), ectopic pregnancy, fetal demise, or any congenital 
anomaly/birth defect of the baby. Any post-study pregnancy-related SAE in either the mother 
or the neonate considered reasonably related to the study intervention by the investigator will 
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be reported to the sponsor as described in Section 8.4.5. While the investigator is not 
obligated to actively seek this information in former study participants, he or she may learn 
of an SAE through spontaneous reporting.  
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10.5 
Appendix 5: Genetics 
Use and analysis of deoxyribonucleic acid (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. 
• Deoxyribonucleic acid samples will only be used for research related to exposure and 
response to minzasolmin. They may also be used to develop tests/assays including diagnostic 
tests related to minzasolmin. Genetic research may consist of the analysis of 1 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 minzasolmin 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 minzasolmin 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 intervention 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 study participants in the case of study 
intervention discontinuation to complete the final evaluation.  
Study 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 intervention discontinuation and/or participant withdrawal (if applicable), 
must be recorded in the source documents. ClinBase must document the primary reason for 
discontinuation of study intervention.  
A specific monitoring plan must be agreed between the study physician and the investigator for 
study 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 10‒3). 
Table 10‒3: 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 ClinBase, 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) 
• 
Consider the need for a toxicology screening. 
• 
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 0.5, 1, 1.5, 2, 4, 8, 12, 24, 36, 
48, 72, and 96 hours after minzasolmin 
administrationd 
• 
CPK and LDH 
• 
Fractionate bilirubin, if total bilirubin 
 2xULN 
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Table 10‒3: Phase 1 liver chemistry stopping criteria and follow up 
assessments table 
MONITORING: 
If ALT ≥3xULN AND bilirubin ≥2xULN or 
INR >1.5 
• 
Repeat liver function tests (include ALT, 
AST, ALP, 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, ALP, 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 
• 
Record use of concomitant medications 
(including acetaminophen, herbal remedies, 
and other over-the-counter medications) 
• 
Record alcohol use  
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 assay, when 
available, to assess potential acetaminophen 
contribution to liver injury in participants with 
definite or likely acetaminophen use in the 
preceding week. NOTE: Not required in 
China. 
• 
Liver imaging (ultrasound, magnetic 
resonance, or computerized tomography) 
and/or liver biopsy to evaluate liver disease 
AE=adverse event; ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; 
CPK=serum creatine phosphokinase; HBsAg=hepatitis B surface antigen; HBcAb=hepatitis B core antibody; 
HPLC=high performance liquid chromatography; IgG=immunoglobulin G; IgM=immunoglobulin M; 
INR=international normalized ratio; LDH=lactate dehydrogenase; PK=pharmacokinetic(s); RNA=ribonucleic 
acid; 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. 
c Includes: Hepatitis A 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 noncomparator interventions. 
Record the date/time of the PK blood sample draw and the date/time of the final dose of study intervention 
before the PK blood sample draw. If the date or time of the final dose is unclear, provide the participant’s best 
approximation. If the date/time of the final cannot be approximated OR a PK sample cannot be collected in the 
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Table 10‒3: Phase 1 liver chemistry stopping criteria and follow up 
assessments table 
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: Device adverse events (AEs), adverse device 
effects (ADEs), serious adverse events (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: Protocol amendment history 
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents.  
10.10.1 
Amendment 1 (16 May 2024) 
Overall Rationale for the Amendment 
UP0152 Protocol Amendment 1 was completed to clarify protocol procedures.  
Section # and name 
Description of change 
Brief rationale 
Title page – Regulatory agency 
identifying number(s) table 
and  
Section 1.1 Regulatory agency 
identifying numbers table 
The EU CT Number was updated to 
remove trailing zeros. 
Administrative change. 
Section 1.3 Schedule of 
Activities 
Physical examination: Footnote ‘d’ 
was moved from the assessment 
name to each X in the Treatment 
Period (D1, D2-5, D6, D7-10, D11, 
D12-14; D15).  
To clarify protocol 
procedures. 
 
Blood pregnancy test (females only) 
was changed to Blood pregnancy test 
(WOCBP only). 
To align with Appendix 2 
Table 10-1. 
 
Laboratory assessments: The 
parenthetical addition to the 
assessment name was updated to 
include estradiol to align with 
Table 10-1. 
To clarify protocol 
procedures. 
 
Laboratory assessments: Xs were 
added for D5 and D10; refer to the 
related update of footnote ‘e’ below. 
To clarify protocol 
procedures. 
 
SARS-CoV-2 testing (PCR): Testing 
was removed from Screening (D -28 
to -2) and will only be done at D -1. 
To clarify protocol 
procedures. 
 
Footnote ‘d’: Day -1 was added to 
complete the list of time points for 
the complete physical examination. 
Minor correction to align 
with the Schedule of 
Activities. 
Section 1.3 Schedule of 
Activities 
The second sentence in footnote ‘e’ 
was updated to clarify when hepatic 
function tests will be done. 
To clarify protocol 
procedures. 
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Section # and name 
Description of change 
Brief rationale 
 
A third sentence was added to 
footnote ‘e’ to provide the following 
clarification: 
Note that FSH and estradiol will only 
be determined for females at the 
Screening Visit. 
To clarify protocol 
procedures. 
Section 5.2 Exclusion criteria 
Exclusion criterion #15a (previously 
#15) was updated to include normal 
ranges for vital signs. 
To clarify eligibility 
criteria. 
 
Exclusion criterion #16a (previously 
#16) was updated to remove text on 
hepatic enzyme baseline results 
>ULN that do not apply. 
To clarify eligibility 
criteria. 
Section 5.4 Screen failures 
The second paragraph was updated 
to note that participants who are 
screen failures may be rescreened 
once at the discretion of the 
investigator. 
To clarify protocol 
procedures. 
Section 7.1.1 Liver chemistry 
stopping criteria 
Introductory text to Figure 7-1 was 
updated to clarify that study 
intervention will be discontinued 
immediately and permanently for a 
participant if liver chemistry 
stopping criteria are met. 
To clarify liver chemistry 
stopping criteria and align 
with current UCB protocol 
template. 
Section 7.1.2 Corrected QT 
interval stopping criteria 
Discontinuation criteria for 
participants with underlying bundle 
branch block were removed. 
To remove discontinuation 
criteria that do not apply in 
a healthy volunteer study. 
Section 7.2 Participant 
discontinuation/withdrawal from 
the study 
The criteria for participant 
withdrawal from the study were 
separated into those for which 
participants must be withdrawn and 
those for which participants should 
be withdrawn. 
To clarify protocol 
procedures. 
Section 8 STUDY 
ASSESSMENTS AND 
PROCEDURES 
A paragraph referring to the 
participant’s routine clinical 
management was removed. 
To remove text that does 
not apply in a healthy 
volunteer study. 
Section 8.1 Administrative and 
general/baseline procedures 
In the second sentence, ‘viral 
serology (HBsAg, hepatitis C virus 
antibody, HIV, and HBcAb)’ was 
removed from the list of Baseline 
procedures done at Screening and 
Day -1 (only done at Screening). 
To align with the schedule 
of activities. 
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Section # and name 
Description of change 
Brief rationale 
Section 8.3.1 Physical 
examination 
In the fourth paragraph, the 
assessment of skin, lungs, 
cardiovascular system, and abdomen 
(liver and spleen) was removed as a 
minimum requirement for symptom-
directed physical examination in case 
of emerging symptoms.  
To clarify protocol 
procedures. 
Section 8.3.2 Vital signs 
The first sentence was updated to 
remove the reference to ‘a 
completely automated device.’ This 
only applies to heart rate and blood 
pressure, as noted in the second 
sentence, and not to all vital signs 
measurements. 
Minor correction. 
Section 8.4.5 Pregnancy 
The seventh paragraph was updated 
to remove text on continuing in the 
study off treatment.  
To remove a protocol 
procedure that does not 
apply to the study. 
Section 8.4.6.1.5 Blood 
sampling 
The second sentence in the first 
paragraph on specific laboratory 
parameters to be collected at baseline 
(Day -1) was removed. 
To remove a protocol 
procedure that does not 
apply to the study. 
Section 8.7 Biomarkers 
Text on biomarkers was 
inadvertently deleted during protocol 
development and was added back to 
the protocol.  
Correction. 
Section 10.1.8.1 ClinBase 
completion 
The section was updated to remove 
procedures that do not apply for 
reporting in ClinBase.  
To remove procedures that 
do not apply to the study. 
Section 10.1.9 Source 
documents 
The fourth paragraph about printed 
source documents was removed. 
To remove procedures that 
do not apply to the study. 
Section 10.2 Appendix 2: 
Clinical laboratory tests 
Table 10-1: Protocol-required 
safety laboratory tests 
Clinical chemistry: A new footnote 
‘c’ was added to ALP, ALT, AST, 
and bilirubin to identify the 
parameters included in hepatic 
function tests. Subsequent footnotes 
were renumbered. 
To clarify protocol 
procedures. 
Section 10.2 Appendix 2: 
Clinical laboratory tests  
Table 10-1 Protocol-required 
safety laboratory tests 
Clinical chemistry: The parenthetical 
addition for glucose was updated to 
clarify this will be assessed in the 
fasting state throughout.  
The enzyme name of 
‘phosphokinase’ was corrected to 
‘Creatine phosphokinase.’ 
Minor corrections. 
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Section # and name 
Description of change 
Brief rationale 
 
Other screening tests: The 
parenthetical addition for ‘Follicle 
stimulating hormone and estradiol’ 
was changed to ‘females only’ to 
align with the Schedule of Activities. 
Creatinine was removed as separate 
bullet and integrated into the urine 
drug screen (to exclude dilution of 
urine samples). 
Minor clarifications. 
 
In footnote ‘e’ (previously ‘d’) the 
year 2021 was added in the reference 
to the equation for the estimated 
glomerular filtration rate. 
Minor clarification.  
 
Footnote ‘f’ (previously ‘e’) was 
removed because the information is 
already included in the table. 
To remove an unnecessary 
footnote. 
Section 10.3.4 Reporting of 
SAEs 
Text on reporting of SAEs via 
facsimile was removed. 
To remove protocol 
procedures that do not 
apply to the study. 
Section 10.4 Appendix 4: 
Contraceptive guidance and 
collection of pregnancy 
information 
 
Text on Female participants who 
become pregnant was updated to 
clarify that pregnancy information is 
entered on the appropriate forms 
provided by UCB, not in ClinBase. 
To clarify protocol 
procedures. 
Section 10.6 Appendix 6: Liver 
safety – Suggested actions and 
follow-up assessments  
Table 10-3 Phase 1 liver 
chemistry stopping criteria and 
follow up assessments table 
Text on the serum acetaminophen 
adduct assay was updated. 
The cited literature reference of 
James et al, 2009 was removed from 
the REFERENCES section (not 
listed separately). 
To allow for flexibility in 
the assay used. 
Throughout 
Minor editorial and document 
formatting revisions 
Minor, therefore have not 
been summarized. 
 
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11 
REFERENCES 
Food and Drug Administration. U.S. Department of Health and Human Services. Assessing the 
effects of food on drugs in INDs and NDAs — clinical pharmacology considerations. Guidance 
for Industry. June 2022, Clinical Pharmacology. Available from 
www.fda.gov/media/121313/download (accessed 07 Mar 2024). 
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. 
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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Approval Signatures
Name:
up0152-protocol-amend-2-08aug2024
Version:
1. 0
Document Number:
CLIN-000261760
Title:
UP0152 Protocol Amendment 2
Approved Date:
08 Aug 2024
Document Approvals
Approval
Verdict: Approved
Name: 
Capacity: Medical
Date of Signature: 08-Aug-2024 12:56:33 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Management Approval
Date of Signature: 08-Aug-2024 14:42:20 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 08-Aug-2024 14:44:43 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Subject Matter Expert
Date of Signature: 08-Aug-2024 14:53:36 GMT+0000
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