A Phase IIb, Multicenter, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy, Safety, and Tolerability of AZD0780 in Participants With Dyslipidemia
Phase: PHASE2
Conditions: Dyslipidemia
Sponsor: AstraZeneca

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Clinical Study Protocol
Study Intervention
AZD0780
Study Code
D7960C00006
Version
3.0
Date
15 January 2024
A Phase IIb, Multicenter, Randomized, Parallel-group, Double-
blind, Placebo-controlled, Dose-ranging Study to Evaluate the 
Efficacy, Safety, and Tolerability of AZD0780 in Participants with 
Dyslipidemia
Sponsor Name: AstraZeneca K.K
Legal Registered Address: 3-1 Ofukacho, Kita-ku, Osaka, 530-0011, Japan 
Sponsor Name: AstraZeneca AB
Legal Registered Address: 151 85 Södertälje, Sweden
Regulatory Agency Identifier Number(s): EU CT number: 2023-506197-12-00
This protocol has been subject to a peer review according to AstraZeneca Standard 
procedures. The protocol is publicly registered and the results are disclosed and/or published 
according to the AstraZeneca Global Standard - Bioethics and in compliance with prevailing 
laws and regulations.
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Protocol Number: D7960C00006 
Amendment Number: Not Applicable 
Investigational Product: AZD0780 
Study Phase: Phase IIb
Brief Title: A study to investigate the effect of different doses of AZD0780 on LDL-C levels 
compared with placebo and its safety and tolerability in participants 18 to 75 years of age with 
dyslipidemia
Study Clinical Lead Name and Contact Information will be provided separately

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PROTOCOL AMENDMENT SUMMARY OF CHANGES
DOCUMENT HISTORY
Document
Date
Version 2 (Amendment 1)
01 December 2023
Version 3 (Amendment 2)
15 January 2024
Amendment 1 (01 December 2023)
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the EU. Amendment 1 is 
applicable to European EU CTR countries only.
Overall Rationale for the Amendment
This substantial modification is created in response to the EU CTR Part I RFIs.
Section Number and 
Name 
Description of Changes 
Brief rationale 
Substantial/ 
Non-substantial 
1.2, Table 1, Schedule of 
Activities 
Added HbA1C testing at 
Week 12 
To monitor for variation in 
glycaemic control 
Substantial 
5.2, Exclusion Criteria 
Added exclusion criteria 
in relation to medication 
that causes QT 
prolongation 
Medication that is known 
to cause QT prolongation 
should be restricted during 
the study 
Substantial 
6.4.1, Methods for 
Ensuring Blinding 
a) Clarified that the 
randomization codes are 
generated by a validated 
IT-system, that the 
Sponsor cannot influence 
the randomization to study 
intervention, and that the 
information is access 
controlled. 
b) Clarified that the 
Investigator will not have 
access to the complete 
randomization list. 
c) Removed a paragraph 
referring to methods for 
unblinding, merging the 
information into section 
6.4.2. 
a) In the prior version, it 
was not clear how the 
randomization codes were 
generated and managed. 
b) The previous wording 
regarding access to the 
randomization list could 
be misinterpreted. 
c) The information was 
originally written in the 
wrong section. 
Non-substantial 
6.4.2, Methods of 
Unblinding 
The section is rewritten to 
introduce further detail of 
the process and methods 
for emergency unblinding. 
The previous text was not 
as informative and could 
be misinterpreted. 
Non-substantial 
6.9, Prior and 
Concomitant Therapy 
Added details of 
prohibited medication that 
cause QT prolongation 
Medication that is known 
to cause QT prolongation 
should be restricted during 
the study 
Substantial 

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8.3.9, Reporting of SAEs 
Added wording to indicate 
compliance with safety 
reporting requirements to 
EudraVigilance database. 
Wording required to 
indicate compliance with 
safety reporting 
requirements to 
EudraVigilance database. 
Non-substantial 
8.3.1, Time Period and 
Frequency for Collecting 
AE and SAE Information 
Changed AE collection
time from first dose 
instead of from signature 
of ICF 
Correction of error, 
alignment with Schedule 
of Activities, aligning with 
Sponsor policy 
Non-substantial 
Amendment 2 (15 January 2024)
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the EU.
Overall Rationale for the Amendment
This substantial modification is created in response to FDA feedback, to clarify items throughout 
and the addition of a potential interim analysis.
Section Number and Name
Description of Changes
Brief rationale
Substantial/ 
Non-substantial
List of Abbreviations
Abbreviations added -
Coronary artery bypass graft 
surgery (CABG) &
Percutaneous coronary 
intervention (PCI)
These abbreviations are 
referenced in exclusion 
criteria #5 but not 
originally included in 
list of abbreviations.
Non-substantial
Section 5.2 Exclusion Criteria
Coronary artery bypass graft 
surgery & Percutaneous 
coronary intervention added 
prior to use of abbreviation
Full wording added due 
to first use of the 
abbreviations. 
Non-substantial
Table 1 Schedule of activities, 
8.2.3 Electrocardiograms
Addition of clarification that 
triplicate ECG recordings are 
required throughout the study
Clarification
Non-substantial
2.1 Study Rationale
Clarification of wording of 
standard of care therapy 
regarding statins
Clarification
Non-substantial
Table 1 Schedule of activities, 
Table 6 Laboratory Safety 
Variables
Clarification provided that 
FSH and LH are to be 
obtained only at screening 
visit. Clarification that serum 
beta HCG test is to be 
analysed at central 
laboratory.
Clarification
Non-substantial
Section 3 Objective and 
Endpoints, table 3
Clarify objectives and add 
additional secondary 
objectives, including 
corrections of grammar
Update based on FDA 
recommendation
Substantial

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Section Number and Name
Description of Changes
Brief rationale
Substantial/ 
Non-substantial
Section 3 Objective and 
Endpoints, table 3
Revision to Exploratory 
objective to align with 
Appendix D Optional 
Genomics Initiative
Correction/revision 
Substantial 
Section 3 and Section 9.4.2
Update the wording for 
estimand description, clarify 
intercurrent events of interest 
for both estimands, and 
update the terminology 
corresponding to the 
estimand to align with 
clinical question and interest 
and ICH E9(R1)
Add clarification and 
improve readability
Non-substantial
Section 5.1 Inclusion criteria 6
Removal of upper BMI limit
Update based on FDA 
recommendation
Substantial
Section 5.1 Inclusion criteria 9
Clarification regarding sperm 
donation 
Clarification of wording
Non-Substantial
Section 5.2 Exclusion criteria 10
Change: Uncontrolled 
hypertension defined as 
average sitting DBP > 90 
mmHg changed from DBP > 
100 mmHg, at Visit 1.
To allow sufficient 
window between 
exclusion criteria and 
stopping criteria. 
Substantial
Section 5.2 Exclusion criteria 12
Potassium < LLN added to 
exclusion criteria
Update based on FDA 
recommendation
Substantial
Section 5.2 Exclusion criteria 13
Addition of further detail to
exclusion criteria
Update based on FDA 
recommendation
Substantial
Section 5.2 Exclusion criteria 22
Addition of exclusion of 
fibrate therapy & derivatives
Previously mentioned 
incorrectly as part of 
inclusion criteria 5
Substantial
Section 6.1.1, Table 4, 
Investigational Products
Clarification on tablet shape
Clarification
Non-substantial
Section 6.1.1 Investigational 
Products
Addition of composition of 
the placebo.
Update based on FDA 
recommendation
Non-substantial
Section 6.3 and Section 9.4.1
Clarify randomization for 
Japan and rest of the world
Add clarity on 
randomisation set up
Non-substantial
Section 7.1.1 liver chemistry 
stopping criteria
Addition of criteria
Update based on FDA 
recommendation
Substantial
Section 7.1.2. cardiac stopping 
criteria
Addition of clarification that 
ECGs will be triplicate
Clarification
Non-Substantial
Section 7.1.3 respiratory stopping 
criteria
Clarification of criteria
Update based on FDA 
recommendation
Substantial

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Section Number and Name
Description of Changes
Brief rationale
Substantial/ 
Non-substantial
Section 8 Study Assessments and 
procedures
Added: The approximate 
amount of blood collected 
from each participant over 
the duration of the study is 
around 300ml (approximately 
20 tablespoons)
Add clarity on 
approximate blood 
collection
Non-substantial
Section 8.1, Table 5 and
Section 9.4.2.2: Statistical 
Analysis, Efficacy, Secondary 
Endpoint(s)
Added clarification that the 
VLDL-C will be calculated 
from standard lipid profile. 
Clarification
Non-substantial
Section 8.2.3 Electrocardiograms
Change: The participant 
should be in a resting, seated 
position for at least 10 
minutes
Updated duration of 
resting position to align 
with cardiac stopping 
criteria
Substantial 
Section 8.4 Pharmacokinetics
Clarification regarding 
collection of PK samples
Clarification
Non-Substantial
Table 6
Removal of annotation mark 
corresponding to Leukocyte 
differential count
Correction due to no 
corresponding footnote
Non-substantial
Section 9.2
Update the sample size and 
the rationale for the choice of 
sample size
Update based on FDA 
recommendation
Substantial
Section 9.5 & Appendix A5
Added potential Interim 
Analysis and details on 
Unblinded Review 
Committee
Interim analysis added 
with the purpose of 
informing further 
development of the 
clinical programme
Substantial
Appendix A5
Details of unblinded review 
committee added
Added in line with 
potential Interim 
Analysis
Substantial
Appendix C2
Clarification regarding 
sample handling in instances 
of withdrawal of consent for 
donated biological samples
Clarification
Non-Substantial
Appendix C3
Correction of outdated link
Correction
Non-Substantial

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TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES ....................................................... 3
TABLE OF CONTENTS ............................................................................................................ 7
LIST OF FIGURES................................................................................................................... 10
LIST OF TABLES.................................................................................................................... 10
LIST OF APPENDICES ........................................................................................................... 10
LIST OF ABBREVIATIONS.................................................................................................... 11
1
PROTOCOL SUMMARY ...................................................................................... 13
1.1
Synopsis.................................................................................................................. 13
1.2
Schedule of Activities.............................................................................................. 20
2
INTRODUCTION .................................................................................................. 25
2.1
Study Rationale....................................................................................................... 25
2.2
Background............................................................................................................. 25
2.2.1
Dyslipidemia .......................................................................................................... 25
2.2.2
AZD0780 ............................................................................................................... 26
2.2.3
Supportive Nonclinical Data.................................................................................... 26
2.2.4
Supportive Clinical Data ......................................................................................... 27
2.3
Benefit/Risk Assessment ......................................................................................... 27
2.3.1
Risk Assessment..................................................................................................... 27
2.3.2
Benefit Assessment................................................................................................. 30
2.3.3
Overall Benefit/Risk Conclusion ............................................................................. 31
3
OBJECTIVES, ENDPOINTS, AND ESTIMANDS................................................. 32
4
STUDY DESIGN.................................................................................................... 36
4.1
Overall Design........................................................................................................ 36
4.2
Scientific Rationale for Study Design ...................................................................... 36
4.2.1
Rationale for Selection of Participant Population..................................................... 36
4.2.2
Rationale for Selection of Primary Endpoint............................................................ 37
4.2.3
Rationale for Selection of Comparator..................................................................... 37
4.2.4
Rationale for Selection of Study Duration................................................................ 37
4.3
Justification for Dose............................................................................................... 38
4.4
End-of-study Definition........................................................................................... 38
5
STUDY POPULATION.......................................................................................... 39
5.1
Inclusion Criteria..................................................................................................... 39
5.2
Exclusion Criteria.................................................................................................... 41
5.3
Lifestyle Considerations.......................................................................................... 43
5.3.1
Pregnancy............................................................................................................... 43
5.3.2
Meals and Dietary Restrictions................................................................................ 44

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5.3.3
Caffeine, Alcohol, and Tobacco .............................................................................. 44
5.3.4
Activity .................................................................................................................. 44
5.3.5
Other Restrictions ................................................................................................... 44
5.4
Screen Failures........................................................................................................ 44
5.5
Criteria for Temporarily Delaying Administration of Study Intervention – Not 
Applicable .............................................................................................................. 44
6
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY........................ 45
6.1
Study Intervention(s) Administered ......................................................................... 45
6.1.1
Investigational Products.......................................................................................... 45
6.2
Preparation, Handling, Storage, and Accountability ................................................. 46
6.3
Assignment to Study Intervention............................................................................ 46
6.4
Blinding.................................................................................................................. 47
6.4.1
Methods for Ensuring Blinding................................................................................ 47
6.4.2
Methods for Unblinding .......................................................................................... 48
6.5
Study Intervention Compliance................................................................................ 49
6.6
Dose Modification................................................................................................... 49
6.7
Continued Access to Study Intervention After the End of the Study......................... 49
6.8
Treatment of Overdose............................................................................................ 50
6.9
Prior and Concomitant Therapy............................................................................... 50
6.9.1
Rescue Medicine – Not Applicable.......................................................................... 50
7
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL................................................................ 51
7.1
Discontinuation of Study Intervention...................................................................... 51
7.1.1
Liver Chemistry Stopping Criteria........................................................................... 52
7.1.2
Cardiac Stopping Criteria ........................................................................................ 52
7.1.3
Respiratory stopping criteria ................................................................................... 53
7.2
Participant Discontinuation/Withdrawal from the Study........................................... 53
7.3
Lost to Follow-up.................................................................................................... 54
8
STUDY ASSESSMENTS AND PROCEDURES .................................................... 54
8.1
Efficacy Assessments.............................................................................................. 56
8.2
Safety Assessments ................................................................................................. 57
8.2.1
Physical Examinations............................................................................................ 57
8.2.2
Vital Signs .............................................................................................................. 57
8.2.3
Electrocardiograms................................................................................................. 58
8.2.4
Clinical Safety Laboratory Tests.............................................................................. 58
8.3
AEs, SAEs, and Other Safety Reporting .................................................................. 60
8.3.1
Time Period and Frequency for Collecting AE and SAE Information....................... 60
8.3.2
Follow-up of AEs and SAEs.................................................................................... 60
8.3.3
Causality Collection................................................................................................ 61
8.3.4
AEs Based on Examinations and Tests .................................................................... 61

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8.3.5
AEs Based on Signs and Symptoms......................................................................... 62
8.3.6
Hy’s Law ................................................................................................................ 62
8.3.7
Disease Progression ................................................................................................ 62
8.3.8
Disease Under Study............................................................................................... 63
8.3.9
Reporting of SAEs .................................................................................................. 63
8.3.10
Pregnancy............................................................................................................... 64
8.3.11
Medication Error, Drug Abuse, and Drug Misuse .................................................... 65
8.3.12
Reporting of Overdose ............................................................................................ 65
8.4
Pharmacokinetics .................................................................................................... 66
8.4.1
Collection of Samples for Pharmacokinetics............................................................ 66
8.4.2
Determination of Drug Concentration...................................................................... 66
8.5
Pharmacodynamics.................................................................................................. 66
8.5.1
Collection of Samples for Pharmacodynamics ......................................................... 66
8.6
Optional Genomics Initiative................................................................................... 67
8.7
Biomarkers.............................................................................................................. 67
8.7.1
Mandatory Biomarker Sample Collection................................................................ 67
8.7.2
Other Study-related Biomarker Research................................................................. 67
8.8
Immunogenicity Assessments.................................................................................. 68
8.9
Medical Resource Utilization and Health Economics............................................... 68
8.10
Study Participant Feedback Questionnaire ............................................................... 68
9
STATISTICAL CONSIDERATIONS ..................................................................... 68
9.1
Statistical Hypotheses.............................................................................................. 68
9.2
Sample Size Determination...................................................................................... 68
9.3
Populations for Analyses......................................................................................... 69
9.4
Statistical Analyses ................................................................................................. 70
9.4.1
General Considerations ........................................................................................... 70
9.4.2
Efficacy.................................................................................................................. 70
9.4.3
Safety ..................................................................................................................... 72
9.4.4
Other Analyses ....................................................................................................... 73
9.5
Interim Analyses ..................................................................................................... 73
9.6
Data Monitoring Committee.................................................................................... 73
10
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
............................................................................................................................... 74
10.1.1
E 4.1 Potential Hy’s Law Criteria not met............................................................................ 93
10.1.2
E 4.2 Potential Hy’s Law Criteria met ................................................................................. 93
11
REFERENCES ....................................................................................................... 98

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LIST OF FIGURES
Figure 1
Study Design............................................................................................ 20
LIST OF TABLES
Table 1
Schedule of Activities .............................................................................. 21
Table 2
Risk Assessment of AZD0780.................................................................. 28
Table 3
Objectives and Endpoints......................................................................... 32
Table 4
Investigational Products Administered...................................................... 45
Table 5
Laboratory Efficacy Variables.................................................................. 56
Table 6
Laboratory Safety Variables..................................................................... 59
Table 7
Populations for Analysis .......................................................................... 69
LIST OF APPENDICES
Appendix A
Regulatory, Ethical, and Study Oversight Considerations ......................... 75
Appendix B
AEs: Definitions and Procedures for Recording, Evaluating, Follow-up,
and Reporting........................................................................................... 81
Appendix C
Handling of Human Biological Samples................................................... 86
Appendix D
Optional Genomics Initiative Sample ....................................................... 88
Appendix E
Actions Required in Cases of Increases in Liver Biochemistry and
Evaluation of Hy’s Law ........................................................................... 91
Appendix F
Statin Inclusion Criteria ........................................................................... 97

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LIST OF ABBREVIATIONS
Abbreviation or special 
term
Explanation
AE
Adverse Event
ALP
Alkaline Phosphatase
ALT
Alanine Aminotransferase/Transaminase
ApoA1
Apolipoprotein A-1
ApoB
Apolipoprotein B-100
AST
Aspartate Aminotransferase/Transaminase
BP
Blood Pressure
bpm
Beats Per Minute
CABG
Coronary artery bypass graft surgery
CFR
Code of Federal Regulations
Cmax
Maximum Concentration of Drug Observed after Administration
COVID-19
Coronavirus Disease 2019
CRO
Contract Research Organization
CSP
Clinical Study Protocol
CSR
Clinical Study Report
CTIS
Clinical Trial Information System
CVD
Cardiovascular Disease
DBP
Diastolic Blood Pressure
DILI
Drug Induced Liver Injury
DUS
Disease Under Study
ECG
Electrocardiogram
eCRF
electronic Case Report Form
EDV
EarlyDiscontinuation Visit
EU CT
EU Clinical Trial
EU
European Union
FAS
Full Analysis Set
FDA
Food and Drug Administration
GCP
Good Clinical Practice
HBV
Hepatitis B Virus
HDL-C
High-densitylipoprotein cholesterol
hERG
human Ether-a-go-go-Related Gene
HIV
Human Immunodeficiency Virus
hsCRP
High-sensitivityC-reactive protein
IATA
International Air Transport Association

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Abbreviation or special 
term
Explanation
IB
Investigator’s Brochure
ICE
Intercurrent Event
ICF
Informed Consent Form
ICH
International Council for Harmonisation
IEC
Independent Ethics Committee
IHD
Ischemic Heart Disease
IMP
Investigational Medicinal Product
IRB
Institutional Review Board
IRT
Interactive Response Technology
IS
Ischemic Stroke
LDL-C
Low-Density Lipoprotein Cholesterol
LDLR
LDL Receptor
Lp(a)
Lipoprotein (a)
LS
Least Squares
MAD
Multiple Ascending Dose
MedDRA
Medical Dictionary for Regulatory Activities
MMRM
Mixed Model for Repeated Measures
NOAEL
No-observed-adverse-effect
PCI
Percutaneous coronary intervention
PCSK9
Proprotein Convertase Subtilisin/Kexin Type 9
PD
Pharmacodynamic(s)
PK
Pharmacokinetic(s)
PT
Preferred Term
QTcF
Corrected QT Interval
RTSM
Randomization and Trial Supply Management
SAD
Single Ascending Dose
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SBP
Systolic Blood Pressure
SoA
Schedule of Activities
SoC
Standard of Care
SOC
System Organ Class
TBL
Total Bilirubin
ULN
Upper Limit of Normal
VLDL-C
Very-Low-Density Lipoprotein Cholesterol

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1
PROTOCOL SUMMARY
1.1
Synopsis
Protocol Title: A Phase IIb, Multicenter, Randomized, Parallel-group, Double-blind, 
Placebo-controlled, Dose-ranging Study to Evaluate the Efficacy, Safety, and 
Tolerability of AZD0780 in Participants with Dyslipidemia
Brief Title:
A study to investigate the effect of different doses of AZD0780 on LDL-C levels compared 
with placebo and its safety and tolerability in participants 18 to 75 years of age with 
dyslipidemia.
Regulatory Agency Identifier Number(s):
EU CT number: 2023-506197-12-00
Rationale:
AZD0780 is a small molecule, oral inhibitor of proprotein convertase subtilisin/kexin type 9 
(PCSK9) for the reduction of circulating levels of low-density lipoprotein cholesterol
(LDL-C). This study aims to evaluate the dose-dependent reduction in LDL-C as well as the 
associated adverse effects profile after oral administration of multiple doses of AZD0780 on 
background standard of care therapy including medium to high-intensity statins. The data 
generated will be used to guide choice of doses, dosing regimens, and sample sizes, as well as 
safety and pharmacodynamic (PD) monitoring in the further clinical development program.
Objectives, Endpoints, and Estimands:
This study is designed to explore the efficacy, safety, tolerability, and pharmacokinetics (PK) 
across different dose levels of AZD0780, a small molecule PCSK9 inhibitor, administered 
orally for up to 12 weeks in participants with elevated LDL-C. The study will randomize 
approximately 375 participants.
Objectives
Endpoints
Primary

To evaluate the effect of different doses of 
AZD0780 on LDL-C versus placebo in 
“ideal” scenarios in which intercurrent 
events would not occur (hypothetical 
estimand will be considered)

Percent change from baseline of LDL-C at 
Week 12
Secondary

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
To evaluate the effect of different doses of 
AZD0780 on LDL-C versus placebo in 
“real-world” conditions (treatment policy 
estimand will be considered) 

Percent change from baseline of LDL-C at 
Week 12

To assess the PK of AZD0780

AZD0780 plasma concentrations summarized 
by sampling timepoint

To evaluate the effects of different doses of
AZD0780 on other lipid parameters and 
inflammatory markers versus placebo in 
“ideal” scenarios in which intercurrent events 
would not occur (hypothetical estimand will be 
considered)

Percent change from baseline at Week 12 in:

Total cholesterol

HDL-C

Triglycerides

Non-HDL-C

VLDL-C

ApoA1

ApoB

Lp(a)

Remnant cholesterol

hsCRP

To evaluate the effects of different doses of 
AZD0780 on other lipid parameters and 
inflammatory markers versus placebo in “real-
world” conditions (treatment policy estimand 
will be considered)

Percent change from baseline at Week 12 in: 

Total cholesterol

HDL-C

Triglycerides

Non-HDL-C

VLDL-C

ApoA1

ApoB

Lp(a)

Remnant cholesterol

hsCRP
Safety

To assess the safety and tolerability of 
AZD0780

Safety and tolerability will be assessed in terms 
of AEs, vital signs, ECG, and clinical laboratory 
evaluations
AE = adverse event; ApoA1 = apolipoprotein A-1; ApoB = apolipoprotein B-100; ECG = electrocardiogram; 
HDL-C = high-density lipoprotein cholesterol; hsCRP = high-sensitivity C-reactive protein; LDL-C = low-
density lipoprotein cholesterol; Lp(a) = lipoprotein (a); PK = pharmacokinetic(s); VLDL-C = very-low-density 
lipoprotein cholesterol.
For Exploratory objectives and endpoints, see Section 3 of the protocol.

Cli nical St u d y Pr ot oc ol - 3. 0 
A Z D 0 7 8 0 - D 7 9 6 0 C 0 0 0 0 6
Astra Ze neca
C O N FI D E N TI A L A N D P R O P RI E T A R Y
1 5 of 9 9
D oc I D: T M P -0 0 1 0 2 2 5
Te m pl ate Versi o n N u m ber 8. 0
O ver all Desi g n S y n o psis:
T his is a ra n d o mize d, m ult ice nter, parallel-gr o u p, d o u bl e- bli n d, place b o -c o ntr olle d, d ose-
ra n gi n g, P hase II b st u d y in a p pr o xi matel y 3 7 5 partici pa nts wit h d ysli pi de mia. T he pri mar y 
o bj ect i ve of t he st u d y is t o i n vesti gate t he effect of A Z D 0 7 8 0 o n L D L-C le vels acr oss 
differe nt d ose levels. A n o ver vie w of t he st u d y desi g n is pr o vi de d i n Fi g ure 1. T he st u d y will 
be c o n d ucte d at u p t o 6 5 sites i n u p t o 8 c o u ntries.
T he st u d y  p o p ulat i on will c o nsist of male a n d fe male partici pa nts of n o n- c hil d beari n g 
p ote nti al, 1 8 t o 7 5 years of a ge wit h a fasti n g L D L - C of ≥7 0 ( 1. 8 m m o l/ L) a n d < 1 9 0 m g/ d L 
( 4. 9 m m ol/L) at scree ni n g .
T he scree ni n g peri o d will be u p t o 3 wee ks pri or t o ra n d o mizat i on. O nce partici pa nts ha ve 
f ulfille d t he eli gi bility criteria, t he y ca n be ra n d o mize d at a n y t i me bet wee n Da y -2 1 a n d
D a y - 1. Parti cip a nts wit h a fasti n g L D L -C of ≥7 0 m g/ d L a n d < 1 9 0 m g/ d L, a n d
trigl yceri des < 4 0 0 m g/ d L at scree ni n g will be eli gi ble. 
P arti cipa nts will als o be recei vi n g m o derate or hi g h -i nte nsit y stati n t hera p y for at least 2 
m o nt hs pri or t o scree ni n g ( please refer t o  A p pe n di x F) . Eli gi ble part ici pa nts will atte n d 6
visit s d uri n g t he treat me nt peri o d a n d o ne a d ditio n al  visit in t he f o ll ow- u p peri o d. 
Eli gi ble partici pa nts will be ra n d o mize d acr oss 5 differe nt treat me nt ar ms i n a 1: 1: 1: 1: 1 
r atio f or a 1 2 -wee k treat me nt peri o d. T he pla n ne d trea t me nts ar ms are A Z D 0 7 8 0
m g,
A Z D 0 7 8 0
m g, A Z D 0 7 8 0
 mg, A Z D 0 7 8 0
 m g, a n d place b o.
Bl o o d sa m ples will be c ollecte d f or a nal ysis of L D L -C ( Fri e de wal d calc ulati o n + refle x 
testi n g f or tri gl yceri des > 4 0 0 m g/ d L a n d/ or L D L-C < 4 0 m g/ d L) t o assess t he effects of 
A Z D 0 7 8 0 o n t hese para m eters. Bl o o d sa m ples f or a nal ysis of li pi d pr ofile (t otal c h o lester ol, 
hi g h -de nsit y li p o pr otei n c h olester ol [ H D L-C], tri gl yceri des, a p oli p o pr otei n B -1 0 0 [ A p o B], 
li p o pr otei n (a) [ L p(a)], a p oli p o pr otei n A- 1 [ A p o A 1]) will be o bt ai ne d t o assess t he effects of  
A Z D 0 7 8 0 o n t hese para meters. Sa m ples will be c ollecte d, la bele d, st ore d a n d s hi p pe d as 
detaile d i n t he La b orat or y  Ma n ual.
T he st u d y  is d o u ble-bli n d a n d A Z D 0 7 8 0 a n d place b o will be matc he d f or a p peara nce. 
P arti cip a nts will be gi n tr e at me nt ( place b o or A Z D 0 7 8 0) o n Da y 1 a n d c o nt i n ue f or 1 2 wee ks. 
After t he treat me nt peri o d, partici pa nts will ha ve o ne f o ll ow- u p visi t 2 wee ks p ost last d ose. 
F or detaile d i nf or mat i on, pl ease refer t o t he Sc he d ule of Act i vities ( S o A; Ta ble 1 ).
Brief S u m m ar y:
T he p ur p ose of t his st u d y is t o meas ure t he effect of differe nt dail y d oses of A Z D 0 7 8 0 o n 
L D L -C le vels c o m pare d wit h place b o i n partici pa nts wit h d ysli pi de mia.
C CI
C CI
C CI
C CI

Cli nical St u d y Pr ot oc ol - 3. 0 
A Z D 0 7 8 0 - D 7 9 6 0 C 0 0 0 0 6
Astra Ze neca
C O N FI D E N TI A L A N D P R O P RI E T A R Y
1 6 of 9 9
D oc I D: T M P -0 0 1 0 2 2 5
Te m pl ate Versi o n N u m ber 8. 0
T he st u d y will c o m pr ise 3 peri o ds t otali n g u p t o 1 7 wee ks:

A scree ni n g peri o d of u p t o 3 wee ks

A tr e at me nt peri o d of 1 2 wee ks

Di s pe nsi n g visit s will be at Wee k
1, Wee k
4, a n d Wee k
8

T he visit fre q ue nc y will be at Wee k
1, Wee k
2, a n d Wee k
4; t he n o nce m o nt hl y u p t o 
Wee k 1 2

A fi nal f oll ow- u p visit at Wee k
1 4
Discl os ure St ate me nt :
T his is a ra n d o mize d, m ult ice nter, parallel-gr o u p, d o u bl e- bli n d, place b o -c o ntr olle d, d ose-
ra n gi n g P hase II b st u d y wi t h 5 treat me nt ar ms t hat will e val uate t he safety, t olera bilit y, P K, 
a n d efficac y of m ult i ple d oses of A Z D 0 7 8 0 a d mi nistere d orall y f or u p t o 1 2 wee ks i n 
parti ci pa nts wit h ele vate d L D L-C.
N u m ber of P artici p a nts:
A p pr o xi matel y 6 5 0 parti ci pa nts will be scree ne d/e nr olle d t o ac hie ve a p pr o xi matel y 
3 7 5 partici pa nts ra n d o ml y assi g ne d t o A Z D 0 7 8 0 o r place b o.
N ote : “ E nr olle d” mea ns a parti ci pa nt's, or t heir le gall y acce pta ble re prese ntati ve’s, a gree me nt 
t o partici pate i n a cli nical st u d y fol l owi n g c o m plet i o n of t he i nf or me d c o nse nt pr ocess.
P ote nti al part ici pa nts w h o are scree ne d f or t he p ur p ose of deter mi ni n g eli gi bilit y f or t he
st u d y, b ut are n ot ra n d o ml y assi g ne d/assi g ne d i n t he st u d y, are c o nsidere d “scree n fail ures”, 
u nless ot her wise s pecifie d b y t he pr ot oc ol.
St u d y Ar ms a n d D ur ati o n:
P arti cip a nts will be ra n d omize d t o o nce dail y d osi n g of pl ac e b o or o ne of t he A Z D 0 7 8 0 d oses. 
D osi n g s h o ul d be s u per vise d a n d d oc u me nte d b y  st u d y staff w he n st u d y int er ve nt i on is 
a d mi nistere d i n t he cli nic. Eli gi ble part ici pa nts will be ra n d omize d acr oss 5 differe nt treat me nt 
ar ms i n a 1: 1: 1: 1: 1 rati o f or a 1 2-wee k treat me nt perio d. T he pl a n ne d treat me nts ar ms are 
A Z D 0 7 8 0 
m g, A Z D 0 7 8 0 
m g, A Z D 0 7 8 0 
 m g, A Z D 0 7 8 0 
 m g, a n d place b o.
T he st u d y will c o m pr ise 3 peri o ds t otali n g u p t o 1 7 wee ks:

A scree ni n g peri o d of u p t o 3 wee ks

A t otal treat me nt peri o d of 1 2 wee ks

A safety f oll ow- u p p eri o d of 2 wee ks
C CI
C CI
C CI
C CI

Cli nical St u d y Pr ot oc ol - 3. 0 
A Z D 0 7 8 0 - D 7 9 6 0 C 0 0 0 0 6
Astra Ze neca
C O N FI D E N TI A L A N D P R O P RI E T A R Y
1 7 of 9 9
D oc I D: T M P -0 0 1 0 2 2 5
Te m pl ate Versi o n N u m ber 8. 0
St atistic al Met h o ds 
S a m ple Size Esti m ati o n
T he st u d y  will ra n d o mize a p pr o xi matel y 3 7 5 participa nts i n or der t o ha ve a p pr o xi matel y 3 2 0 
e val ua ble part ici pa nts w h o c o mplete t he 1 2- wee k treat me nt peri o d t o s u p p ort t he e val uat i on
of  t he pri mar y e nd p oi nt (t he di sc o nti n uatio n rate is ass u me d t o be a p pr o xi matel y  1 5 %). 
P arti cipa nts will be ra n d o mize d i n a 1: 1: 1: 1: 1 ma n ner t o recei ve A Z D 0 7 8 0 
m g, 
m g, 
m g, 
 m g, or c orres p o n di n g place b o.
T he sa m ple size is dri ve n b y  t he o bject i ve t o assess t he safety a n d t olera bilit y of A Z D 0 7 8 0. 
T he c h ose n sa m ple size is belie ve d t o be s ufficie nt f or t he creati o n of a r o b ust safety 
data base.
T he sa m ple size of a p pr o xi matel y 6 4 e val ua ble partici pa nts w h o c o m plete t he 1 2 -wee k 
treat me nt perio d i n eac h ar m will pr o vi de m ore t ha n 9 0 % p o wer f or t he test of eac h d ose of 
A Z D 0 7 8 0 vers us pl ace b o t o detect a differe nce of
i n perce nt c ha n ge fr om baseli ne i n 
L D L - C t o Wee k
1 2. T he calc ulat i ons ass u me S D =  
 a n d a 2 -si de d al p ha le vel of 0. 0 5 a n d
are base d o n a t -test wit h n or mal a p pr o xi mati on f or perce nt c ha n ge fr om baseli ne .
Pri m ar y E n d p oi nt A n al ysis
T he pri mar y o bjecti ve is t o de m o nstrate s u peri orit y of A Z D 0 7 8 0 c o mpare d t o place b o o n 
L D L -C. T o s u p p ort t he pri mar y  o bjecti ve, t he pri mar y e n d p o i nt is perce nt c ha n ge fr om 
baseli ne of L D L -C at Wee k 1 2.
T he h y p ot heti cal est i ma n d will be use d f or t he pri mar y a nal ysis.
T he s u m mar y meas ure f or t he pri mar y e n d p o i nt will be least s q uares mea n of perce nt c ha n ge 
fr om baseli ne. T he pri mar y e n d p oi nt will be a nal yze d usi n g a mi xe d m o del f or re peate d 
meas ures ( M M R M) base d o n t he f ull a nal ysis set ( F A S) p o p ulat i on. T he m o del will i ncl u de 
t he fi xe d effects of baseli ne, treat me nt, visit, a n d treat me nt - b y-visit i nteracti o n, a n d t he 
ra n d om effect (ra n d o m i nterce pt) o f parti ci pa nt. T he Restricte d Ma xi m u m Li keli h o o d 
esti mat i on a p pr oac h will be use d wit h a c o m p o u n d s y m metr y c o varia nce str uct ure f or
re peate d meas ures. T he treat me nt effects will be s u m marize d b y t he differe nce i n least s q uares 
mea ns, 9 5 % c o nfi de nce i nter val, a n d p-val ue.
T o str o n gl y c o ntr ol t he famil y wise err or rate at t he 0. 0 5 level, t he alp ha e x pe n dit ure of 0. 0 5 
( 2‑side d) will be all ocate d t o t he f o ll owi n g h y p ot heses ( H) f or t he pri mar y  e n d p oi nt:

H 1: 𝜇A Z D 0 7 8 0
m g = 𝜇pl ac e b o

H 2: 𝜇A Z D 0 7 8 0
m g = 𝜇pl ac e b o

H 3: 𝜇A Z D 0 7 8 0
m g = 𝜇pl ac e b o
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI

Cli nical St u d y Pr ot oc ol - 3. 0 
A Z D 0 7 8 0 - D 7 9 6 0 C 0 0 0 0 6
Astra Ze neca
C O N FI D E N TI A L A N D P R O P RI E T A R Y
1 8 of 9 9
D oc I D: T M P -0 0 1 0 2 2 5
Te m pl ate Versi o n N u m ber 8. 0

H 4: 𝜇A Z D 0 7 8 0
m g = 𝜇pl ac e b o
W here
µ de n otes t he perce nt c ha n ge fr om baseli ne of L D L - C at Wee k
1 2.
A hierarc hical testi n g strate g y ( close d testi n g pr oce d ure) will be e m pl o ye d. H 1 will be teste d 
first usi n g t he f ull test ma ss al p ha. If H 1 is r ejecte d, t he n t he f ull test ma ss will be rec ycle d t o 
test H 2. If H 2 is r ejecte d, t he n H 3 will be teste d wit h f ull al p ha, a n d if H 3 is rejecte d, H 4 will 
be f urt her teste d wit h f ull al p ha. F urt her details of m ulti plicity testi n g are pr o vide d i n t he 
statistical a nal ysis pla n ( S A P).
Sec o n d ar y E n d p oi nt A n al yses
As a sec o n dar y e n d p o i nt t he perce nt c ha n ge fr om baseli ne of L D L -C at Wee k 1 2 will be 
esti mate d u n der “real -w orl d” c o n di tio ns. T he treat me nt p olic y est i ma n d will be us e d f or t his
a nal ysis. Wit h t he treat me nt p olic y esti ma n d t he a nal ysis will i ncl u de all meas ure me nts ta ke n 
re gar dless of t he occ urre nce of i nterc urre nt e ve nts ( I C Es). Parti ci pa nts will be a nal yze d 
acc or di n g t o t heir ra n d o mize d i n vest i gati onal me dici nal pr o d uct (I M P) assi g n me nt
irres pecti ve of t he treat me nt t he y recei ve d.
T he s u m mar y meas ure will be least s q uares mea n of perce nt c ha n ge fr o m baseli ne. T he 
a nal ysis will be t he sa me as f or t he pri mar y e n d p o i nt.
Ot her sec o n dar y e n d p o i nts i ncl u de:

Perce nt c ha n ge fr om baseli ne t o Wee k
1 2 i n:

N o n- H D L - C

V er y -l ow- de nsit y li p o pr otei n c h o lester ol( V L D L-C) (calc ulate d fr o m sta n dar d li pi d 
pr ofile) 

A p o A 1

A p o B

T ot al c h olester ol

L D L - C

H D L - C

Tri gl yceri des

L p(a)

Re m na nt c h olester ol (calc ulate d fr o m sta n dar d li pi d pr ofile)

Hi g h -se nsitivit y C-reacti ve pr otei n ( hs C R P)
T he perce nt c ha n ge fr o m baseli ne of t hese para meters at Wee k 1 2 will be esti mate d u n der b ot h 
“i deal” sce nari os i n w hic h i nterc urre nt e ve nts w o ul d n ot occ ur (i.e., h yp ot heti cal strate g y) a n d 
“real-w orl d ” c o n ditio ns (i.e., treat me nt p olic y strate g y).
T he F A S will be use d i n t he a nal ysis of t he sec o n dar y efficac y e n d p o i nts. T he statistical 
a nal yses will i n ge neral c o nsist of t he f o ll owi n g 4 pai r wise treat me nt c o mparis o ns:
C CI

Cli nical St u d y Pr ot oc ol - 3. 0 
A Z D 0 7 8 0 - D 7 9 6 0 C 0 0 0 0 6
Astra Ze neca
C O N FI D E N TI A L A N D P R O P RI E T A R Y
1 9 of 9 9
D oc I D: T M P -0 0 1 0 2 2 5
Te m pl ate Versi o n N u m ber 8. 0

C o m paris o n of A Z D 0 7 8 0
m g vers us pl ace b o

C o m paris o n of A Z D 0 7 8 0
m g vers us pl ace b o

C o m paris o n of A Z D 0 7 8 0
m g vers us place b o

C o m paris o n of A Z D 0 7 8 0
m g vers us place b o
I n ge neral, m ulti ple testi n g a dj ust me nt will n ot be a p plie d t o t he sec o n dar y e n d p oi nts e xce pt 
f or t he " perce nt c ha n ge fr o m baseli ne of L D L - C at
Wee k 1 2 " e n d p o i nt ( u n der “real-w orl d” 
c o n ditio ns) , i n w hic h case t he m ulti plicity a dj ust me nt met h o d will be t he sa me as t hat f or t he 
pri mar y e n d p o i nt for c o m paris o n p ur p oses.
S afet y A n al ysis
S af et y data will be s u m marize d descri pti vel y a n d will n ot be f or mall y teste d. All safety data 
will be prese nte d i n data list i n gs.
A d verse e ve nts ( A Es) will be s u m marize d b y preferre d t er m ( P T) a n d s yste m or ga n class ( S O C) 
usi n g Me dical Dict i onar y  for Re g ulat or y Acti vit ies ( Me d D R A) v oca b ular y . F urt her mor e, listi n gs
of serio us a d verse e ve nts ( S A Es) a n d A Es t hat le d t o wit h dra wal will be ma de a n d t he n u m ber of
parti ci pa nts w h o ha d a n y A E, S A Es, A Es t hat le d t o wit h dra wal, a n d A Es wit h se vere i nte nsit y 
will be s u m marize d.
Ta b ulat i ons a n d list i n gs of data f or vital sig ns, cli nical la b orat or y tests will be prese nte d. 
Res ults fr o m safety electr ocar di o gra ms ( E C Gs) will be liste d. A n y ne w or a g gra vate d 
cli nicall y rele va nt a b n or mal me dical p h ysical e xa mi nat i on fi n di n g c o mpare d t o t he baseli n e 
assess me nt will be re p orte d as a n A E.
O ut -of -ra n ge val ues f or safety lab orat or y will be fla g ge d i n i n di vi d ual listi n gs as well as 
s u m marize d descri pti vel y.
C CI
C CI
C CI
C CI

Cli nical St u d y Pr ot oc ol - 3. 0 
A Z D 0 7 8 0 - D 7 9 6 0 C 0 0 0 0 6
Astra Ze neca
C O N FI D E N TI A L A N D P R O P RI E T A R Y
2 0 of 9 9
D oc I D: T M P -0 0 1 0 2 2 5
Te m pl ate Versi o n N u m ber 8. 0
Sc he m a
Fi g ure 1
St u d y Desi g n
St u d y Desi g n
1 2 -w e e k Tr e at m e nt
St u d y Sc he d ule
C V = car di o vasc ular; e G F R = esti mate d gl o mer ular filtrati o n rate; L D L - C = l o w de nsit y li p o pr otei n c h olester ol; 
M A D = m ulti ple asce n di n g d ose.
1. 2
Sc he d ule of Acti vities
T he Sc he d ule of Act i vities ( S o A) is pr o vi de d i n Ta ble 1.
P arti ci p a nt s wit h d y sli pi d e mi a, L D L - C
≥7 0 m g/ d L a n d < 1 9 0 m g/ d L
a n d
R e c ei vi n g m o d er at e
or hi g h -i nt e n sit y
st ati n t h er a p y f or at l e a st 2 m o nt h s
pri or t o s cr e e ni n g
e G F R > 4 5
N o a c ut e i s c h e mi c C V e v e nt < 1 2 m o
A Z D 0 7 8 0
m g, d ail y, n = 7 5
A Z D 0 7 8 0
m g, d ail y, n = 7 5
A Z D 0 7 8 0
m g, d ail y, n = 7 5
A Z D 0 7 8 0
m g, d ail y, n = 7 5
Pl a c e b o, d ail y, n = 7 5
C CI
C CI
C CI
C CI

Clinical Study Protocol - 3.0 
AZD0780 - D7960C00006
AstraZeneca
CONFIDENTIAL AND PROPRIETARY
21 of 99
Doc ID: TMP-0010225
Template Version Number 8.0
Table 1
Schedule of Activities
Screening
Treatment period
Final 
follow-
up/EDV
Visit number
1
2
3
4
5
6
7
8
Study day
D -21 to
D -1
D1
D8
D15
D29
D57
D85
D99
Visit window
± 3 days
± 3 days
± 3 days
± 3 days
± 3 days
± 3 days
Informed consent
X
Inclusion/exclusion criteria
X
X
Demographic data
X
Medical history
X
Height, weight, and BMI (height at
screening only)
X
X
X
X
X
X
X
X
Drugs of abuse screeninga
X
Urine pregnancytest (local)b
X
X
FSH
X
LH
X
HbA1c
X
X
Serology
X
COVID-19 testc
X
X
Concomitant medication review
X
X
X
X
X
X
X
X
Dispensing of AZD0780/Placebo 
(35 tablets per bottle)
X
X
X
Studyintervention administration 
(AZD0780/Placebo)
X (Once daily oral dosing; Day 1 through Day 84)

Clinical Study Protocol - 3.0 
AZD0780 - D7960C00006
AstraZeneca
CONFIDENTIAL AND PROPRIETARY
22 of 99
Doc ID: TMP-0010225
Template Version Number 8.0
Table 1
Schedule of Activities
Screening
Treatment period
Final 
follow-
up/EDV
Visit number
1
2
3
4
5
6
7
8
Study day
D -21 to
D -1
D1
D8
D15
D29
D57
D85
D99
Visit window
± 3 days
± 3 days
± 3 days
± 3 days
± 3 days
± 3 days
Safety and Tolerability
Adverse event review
X
(SAEs
only)
X
(AEs as of 
dosing)
X
X
X
X
X
X
Physical examination (full)
X
X
X
Physical examination (brief)
X
X
X
X
X
Vital signs (BP, pulse and temperature, 
respiratory rate, pulse oximetry)d
X
X
X
X
X
X
X
X
12-lead safety ECGe
X
X
X
X
X
X
X
X
Clinical safety laboratory evaluations 
(chemistry, hematology, coagulation, 
urinalysis)
X
X
X
X
X
X
X
X
Urine renal safety biomarkers: albumin, 
creatinine, total protein
X
X
X
X
X
X
X
X
Efficacy/Pharmacokinetics/Pharmacodynamics 
(fasted)f
Lipid profile (TC, HDL-C, non-HDL-C, 
triglycerides)
X
X
X
X
X
X
X
X
LDL-C
X
X
X
X
X
X
X
X
ApoB
X
X
X
X
X
X
X

Clinical Study Protocol - 3.0 
AZD0780 - D7960C00006
AstraZeneca
CONFIDENTIAL AND PROPRIETARY
23 of 99
Doc ID: TMP-0010225
Template Version Number 8.0
Table 1
Schedule of Activities
Screening
Treatment period
Final 
follow-
up/EDV
Visit number
1
2
3
4
5
6
7
8
Study day
D -21 to
D -1
D1
D8
D15
D29
D57
D85
D99
Visit window
± 3 days
± 3 days
± 3 days
± 3 days
± 3 days
± 3 days
ApoA1
X
X
X
X
X
Lp(a)
X
X
X
X
X
hsCRP
X
X
X
X
X
PK plasma samplesf
X
X
X
X
X
Exploratory
Blood sample for total PCSK9
X
Blood (serum) sample for biomarker 
analyses
X
X
X
X
X
Blood (plasma) sample for biomarker 
analyses
X
X
X
X
X
Urine sample for biomarker analyses
X
X
X
X
X
Sample for Genomic Initiative (optional) g
X
a
Screening for drugs of abuse may be performed as per guidelines at local site.
b
Eligibility is confirmed by negative urine pregnancy test. Confirmatory serum test analyzed at the central laboratory is indicated if urine test is positive at Visit 1. 
c
COVID-19 tests will be performed as per investigator's discretion and according to the study centers’ local procedures.
d
Three consecutive BP and pulse readings should be recorded at intervals of at least 2 minutes.
e
12-lead ECGs should be obtained in triplicate.
f
Blood samples must be obtained pre-dose of IMP for each applicable visit.
g
Consent and sample collection for genetic testing will only be conducted in countries where genetic testing is allowed in this study. If sample is not 
collected at Visit 2, it can be collected at any subsequent visit until the last study visit; to be collected per local guidelines.
Participants are required to fast for at least 8 hours overnight prior to all study visits (including screening). Participants are permitted to drink water during this 
period of fasting until 1 hour before blood sampling.

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AE = adverse event; ApoA1 = apolipoprotein A-1; ApoB = apolipoprotein B-100; BMI = body mass index; BP = blood pressure; COVID-19 = Coronavirus 
disease 2019; ECG = electrocardiogram; EDV = early discontinuation visit; FSH = follicle stimulating hormone; HbA1c = hemoglobin A1c; HDL-C = high-
density lipoprotein cholesterol; hsCRP = high-sensitivity C-reactive protein; IMP = investigational medicinal product; LDL-C = low-density lipoprotein 
cholesterol; LH = luteinizing hormone; Lp(a) = lipoprotein (a); PCSK9 = proprotein convertase subtilisin/kexin type 9; PK = pharmacokinetic(s);
SAE = serious adverse event; TC = total cholesterol.

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2
INTRODUCTION
2.1
Study Rationale
AZD0780 is a small molecule inhibitor of PCSK9 for the reduction of circulating levels of 
LDL-C. This study aims to evaluate the dose-dependent reduction in LDL-C as well as the 
associated adverse effects profile after oral administration of multiple doses of AZD0780 on 
background standard of care therapy including medium to high-intensity statins. The data 
generated will be used to guide choice of doses, dosing regimens, and sample sizes, as well as 
safety and PD monitoring in the further clinical development program.
2.2
Background
2.2.1
Dyslipidemia
Dyslipidemias are alterations to the plasma lipid profile that are often associated with clinical 
conditions. Hypercholesterolemia due to elevated LDL-cholesterol levels is a common form
of dyslipidemia and is a major causal factor for IHD and IS in both the developed and the 
developing world. Elevated LDL-C can be genetically determined (primary or familial 
dyslipidemias) or secondary to other conditions (such as diabetes mellitus, obesity or an 
unhealthy lifestyle), the latter being more common. The global burden of dyslipidemia has 
increased over the past 30 years (Pirillo et al 2021). Cardiovascular disease (CVD), principally 
IHD and IS, is the leading cause of global mortality and a major contributor to disability.
Prevalent cases of CVD nearly doubled from 271 million in 1990 to 523 million in 2019, and 
the number of CVD deaths steadily increased from 12.1 million in 1990, reaching 18.6 million 
in 2019 (Pirillo et al 2021). The global trends for disability-adjusted life years and years of
lost life also increased significantly due to IHD and IS. Cardiovascular disease burden 
continues its decades-long rise for almost all countries (Roth et al 2020). Elevated LDL-C 
remains the main interventional and pharmacologic target for prevention of CVD (Pirillo et al
2021, Ference et al 2018, Roth et al 2020).
Statins are the first-line therapy for lowering of LDL-C recommended by the latest 
dyslipidemia guidelines (Mach et al 2020; Reiter-Brennan et al 2020). Reduction of LDL-C 
levels by statins leads to significant reduction in cardiovascular events including coronary 
artery disease and other cardiovascular related deaths (Collins et al 2016). However, despite 
the substantial benefits of statin therapy, many patients do not reach LDL-C target levels.
Current guidelines call for LDL-C to be lowered ≥50% with maximally tolerated statins in 
patients with existing atherosclerotic CVD (Atar et al 2021). Additional evidence 
demonstrates that aggressively lowering LDL-C levels to < 40 mg/dL lowers CVD risk in a
wider range of patients (Marston et al 2021). This underscores the medical need for 
developing new cost-effective LDL-C lowering medicines to achieve the most recent 
dyslipidemia guidelines for primary and secondary prevention of CVD.

Cli nical St u d y Pr ot oc ol - 3. 0 
A Z D 0 7 8 0 - D 7 9 6 0 C 0 0 0 0 6
C O N FI D E N TI A L A N D P R O P RI E T A R Y
2 6 of 9 9
D oc I D: T M P -0 0 1 0 2 2 5
Te m pl ate Versi o n N u m ber 8. 0
2. 2. 2
A Z D 0 7 8 0
A n i m p orta nt disc o ver y i n t he re g ulati on of L D L -C l e vels has bee n t he i de ntificat i on of 
P C S K 9. L oss -of -f unct i on m ut atio ns i n P C S K 9 ha ve bee n ass ociate d wit h l o w L D L -C l e vels 
a n d pr otecti o n fr o m C V D (C o he n et al 2 0 0 5) . P C S K 9 is pr o d uce d i n t he li ver a n d pr o m otes 
de gra dati o n of t he L D L R. T heref ore, re d ucti o n or i n hi biti on of P C S K 9 i ncreases L D L R levels 
a n d c o nse q ue ntl y l o weri n g plas ma circ ulat i n g L D L-C l e vels. As s uc h, P C S K 9 has bee n t he 
s u bject of i nte nse researc h as a p har mac o l ogi c tar get. T w o P C S K 9 ne utralizi n g m o n ocl o nal 
a nt i b o dies, alir oc u ma b a n d e v ol oc u ma b, ha ve bee n a p pr o ve d as L D L-C l o weri n g t hera pi es.
T hese a nt i b o dies l o wer L D L-C b y  as muc h as 6 0 % a n d l o wers car di o vasc ul ar e ve nt rates 
( Sa bat i ne et al 2 0 1 7). M ore rece nt l y, a s mall i nterferi n g R N A (siR N A) m ol ec ule tar geti n g 
P C S K 9, i nclisira n, has bee n s h o w n t o re d uce L D L- C b y  ap pr o xi matel y 5 0 % (Ra y et al 2 0 2 0) .
T he U S F D A rece ntl y a p pr o ve d i nclisira n i njecti on ( Le q vi o ® ) t o be use d wit h diet a n d stati n 
t hera p y in a d ults wit h heter oz y g o us f a milial h y perc h olester ole mia or cli nical at her oscler otic 
C V D w h o re q uir e a d ditio n al l oweri n g of L D L - C has als o bee n a p pr o ve d (F D A a p pr o ve d a d d-
o n t hera p y  t o lo wer c h ol ester ol a mo n g certai n hi g h -ris k a d ults).
Des pite t he i nterest i n P C S K 9 as a tar get t o l o wer L D L -C, n o orall y a vaila ble t hera p y  has 
bee n s uccessf ull y de vel o pe d. Astra Ze neca is de vel o pi n g a s mall m o lec ule, A Z D 0 7 8 0, t o 
i n hi bit P C S K 9 a n d l ower L D L -C l e vels. A Z D 0 7 8 0 ma y pr o vi de a n o vel, or al , c ost -effecti ve 
me dicat i on as a n alter nat i ve t o t he c urre nt a p pr o ve d i njecta ble P C S K 9 i n hi bit ors.
2. 2. 3
S u p p orti ve N o ncli nic al D at a
Bri efl y, AZ D 0 7 8 0 bi n ds h u ma n a n d c y n o m o l g us m on ke y P C S K 9 s pecificall y  wit h hi g h 
affi nit y i n hi biti n g its acti vit y o n t he L D L -rece pt ors. I n vit r o st u dies a n d i n vi v o t o xic o l og y  
st u dies d e mo nstrate d acce pta bl e safet y pr ofiles. T he N O A E Ls were esta blis he d at
m g/ k g/ da y i n rat a n d
m g/ k g/ da y i n c y n o m o l g us m o n ke y  after 2 8 d a y s of o nce dail y 
or al  d osi n g.
A Z D 0 7 8 0 has bee n e val uate d f or ge n ot o xicit y p ote nt ial i n b ot h i n vitr o a n d i n vi v o st u dies. 
P ote nti al muta ge nic act i vity has bee n assesse d i n bacteria cells i n vitr o b y t he Bacterial 
Re verse M utati o n ( A mes) t est. T he ge n ot o xi c p ote nt ial of A Z D 0 7 8 0 has bee n assesse d i n i n 
vit r o a n d i n vi v o micr o n ucle us tests i n t he L 5 1 7 8 Y m o use l y m p h oma cell li ne a n d i n rat, 
res pecti vel y. Base d o n t he w ei g ht of e vi de nce fr om all ge net ic t o xic o l og y st u dies c o n d ucte d 
wi t h A Z D 0 7 80, i t was c o nclu de d t hat A Z D 0 7 8 0 is n ot m uta ge nic or clast o ge nic.
A Z D 0 7 8 0 was n ot p h ot ot o xic i n t he N R U 3 T 3 P h ot ot o xi cit y Assa y.
A detaile d descri pt i on of t he n o ncli nical p h ar m ac ol o g y, P K, dr u g meta b o lis m, a n d t o xic olo g y  
ca n be f o u n d i n Sect i on 4 of t he I B.
C CI
C CI

Cli nical St u d y Pr ot oc ol - 3. 0 
A Z D 0 7 8 0 - D 7 9 6 0 C 0 0 0 0 6
C O N FI D E N TI A L A N D P R O P RI E T A R Y
2 7 of 9 9
D oc I D: T M P -0 0 1 0 2 2 5
Te m pl ate Versi o n N u m ber 8. 0
2. 2. 4
S u p p orti ve Cli nic al D at a
A n o n g oi n g P hase I stu d y ( St u d y D 7 9 6 0 C 0 0 0 0 1) is a first i n h u ma n ( FI H) st u d y t o assess t he 
safety,  t olera bilit y, P K a n d P D of si n gle a n d M A Ds of A Z D 0 7 8 0, a d mi nistere d orall y as 
ta blets, i n healt h y partici pa nts wit h or wit h o ut ele vate d L D L-C.
F o ll owi n g si n gle ( 
 m g d ose) a n d m ult i ple asce n di n g (
 m g d ose) a d mi nistrati o n of 
A Z D 0 7 8 0 t o healt h y parti ci pa nts wi t h or wi t ho ut ele vate d L D L - C le vels, i nteri m data fr om 
St u d y  D 7 9 6 0 C 0 0 0 0 1 ha ve de m onstrate d a n acce pta ble safet y pr ofile.
2. 3
Be nefit/ Ris k Assess me nt
I n or der t o e val uate t he cli nical be nefit/ris k bala nce f or A Z D 0 7 8 0, n o ncli nical a n d cli nical 
data were ta ke n i nto c o nsi derat i on, as well as re vie w of t he a vaila ble i nf or mati on f or P C S K 9 
i n hi bit ors t hat are a p pr o ve d a n d markete d, or i n de vel o p me nt, f or t he treat me nt of 
d ysli pi de mia.
M ore
detaile d i nf or mati on a b o ut t he k n o w n a n d e x pecte d be nefit s a n d p ote nti al ris ks of  
A Z D 0 7 8 0 ca n be f o u n d i n t he I B.
2. 3. 1
Ris k Assess me nt
T his st u d y has bee n desi g ne d wi t h a p pr o priat e meas ures i n pl ace t o m o nit or a n d mi ni mize a n y 
p ote nti al h e alt h ris ks t o partici pa nts.
Details of t he ris k assess me nt i n t his st u d y ar e prese nte d i n Ta ble 2. Refer t o t he I B f or detaile d i nf or mati o n 
o n t he ris ks of A Z D 0 7 8 0 . 
C CI
C CI

Cli nical St u d y Pr ot oc ol - 3. 0 
A Z D 0 7 8 0 - D 7 9 6 0 C 0 0 0 0 6
C O N FI D E N TI A L A N D P R O P RI E T A R Y
2 8 of 9 9
D oc I D: T M P -0 0 1 0 2 2 5
Te m pl ate Versi o n N u m ber 8. 0
T a ble 2
Ris k Assess me nt of A Z D 0 7 8 0
P ote nti al ris k of 
cli nic al si g nific a nce
S u m m ar y of d at a/r ati o n ale f or ris k
Miti g ati o n
str ate g y
Q T -pr ol o n gati o n
I n a n i n vitr o assa y, A Z D 0 7 8 0 was s ho w n t o be
a n i n hi bit or of t h e h E R G c ha n nel ( h u ma n et h er-
a- g o- g o- relate d ge ne). h E R G c ha n nel i n hi biti o n
ca n ca use Q T -pr ol o n gati o n a n d p ote ntiall y
car diac arr h yt h mia, i ncl u di n g T orsa de de
P oi ntes. Base d o n t he i n vitr o data, m o deli n g
pre dicte d a hi g h li keli h o o d of Q T -pr ol o n gati o n
at free plas ma le vels of A Z D 0 7 8 0 at d oses t o be
i n vesti gate d i n A Z D 0 7 8 0 cli nical st u dies.
I n t he car di o vasc ular safet y st u dies a n d t he
1 m o nt h t o xic ol o g y st u d y of A Z D 0 7 8 0 i n
c yn o m ol g us m o n ke y s, alt h o u g h
Q T -pr ol o n gati o n was o bser ve d, t he pr e-cli nical
data were c o nsiste nt wit h a re versi ble m o de of
h E R G c ha n nel i n hi biti o n a n d Q T -pr ol o n gati o n.
T here were n o o bser vati o ns of A Z D 0 7 8 0
relate d arr yt h mias i n t he i n vi v o st u dies at t he
d ose le vels teste d.
N o E C G fi n di n gs of safet y c o ncer n ha ve bee n
i de ntifie d i n t he o n g oi n g p hase 1 cli nical st u d y
( St u d y D 7 9 6 0 C 0 0 0 0 1) at si n gle d oses of u p t o
m g or re peate d d oses u p t o  
m g o nce
dail y.

E xcl usi o n of partici pa nts 
wit h cli nicall y i m p orta nt 
a b n or malities i n r h yt h m, 
c o n d ucti o n or m or p h ol o g y of 
t he resti n g E C G a n d a n y 
cli nicall y i m p orta nt 
a b n or malities i n t he 1 2 lea d 
E C G; Q Tc F > 4 5 0 ms; A V -
bl oc k gra de II-III; si n us n o de 
d y sf u ncti o n wit h si g nifica nt 
si n us pa use u ntreate d wit h 
pace ma ke r; a n d car diac 
tac h yarr h yt h mias (e xcl usi o n 
criteria 1 3-1 4).

Re g ular E C G rec or di n gs a n d 
assess me nt.

I n di vi d ual st o p pi n g criteria 
ha ve bee n defi ne d t o c o nsi der 
Q Tc a n d Q Tc F val ues
o utsi de pre -s pecifie d ra n ges.
Bl o o d press ure 
ele vati o n
I n t he car di o vasc ular safet y st u dies of A Z D 0 7 8 0 
i n c yn o m ol g us m o n ke ys, a tra nsie nt i ncrease i n 
arterial B P was o bser ve d bet wee n 0. 5 h – 8 h p ost
d ose at t he hi g hest teste d d ose of 
 m g/ k g (free 
C ma x of  
 μ m ol/ L).

O nl y partici pa nts wit hi n a 
defi ne d ra n ge of B P will be 
i ncl u de d i n t he st u d y 
(e xcl usi o n criteri o n 1 0).

It is rec o m me n de d t hat 
a nti h yperte nsi ve 
treat me nt is 
c o nsi dere d/i nitiate d at t he 
PI’s discreti o n a n d i n 
acc or da nce wit h 
a p plica ble cli nical 
g ui deli nes i n or der t o 
o pti mize bl o o d press ure 
f or partici pa nts wit h 
h y perte nsi o n d uri n g t he 
cli nical st u d y. B P will be
m o nit ore d t hr o u g h o ut t he
st u d y.
C CI
C CI
C CI
C CI

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Potential risk of 
clinical significance
Summary of data/rationale for risk
Mitigation strategy
Dyspnea
In in vitro studies, AZD0780 is an adenosine 
transport inhibitor (IC50 ~15 µM). Inhibition of 
adenosine transporters can result in dyspnea
and bronchospasm in patients with respiratory 
disease. In addition, inhibition of α1A 
adrenoceptors (Ki=18 μM and functional IC50
~47 μM) identified in AZD0780 in vitro 
studies, can result in dyspnea, observed in 
clinical trials with α-adrenoceptor antagonists.
The respiratory safety pharmacology study with 
AZD0780 in rats did not show any effect on 
respiratory parameters as assessed by 
plethysmography.

Exclusion of participants 
with any uncontrolled or 
serious disease, or any 
medical (eg, known major 
active infection or major 
hematological, renal, 
metabolic, gastrointestinal, 
respiratory, or endocrine 
dysfunction) or surgical 
condition that, in the opinion 
of the investigator, may 
either interfere with 
participation in the clinical 
study and/or put the 
participant at significant risk 
(exclusion criterion 3).

Adverse events, physical 
examinations and vital signs, 
including respiratoryrate and 
pulse oximetry, will be 
monitored throughout the 
study.

Individual stopping 
criteria have been 
defined to consider 
exacerbation of 
respiratory disease.
Effects on
Reproduction
AZD0780 was shown to be an antagonist of the
serotonin receptor 5-hydroxytryptamine
receptor 2B (5-HT2B). Possible adverse effects
of 5-HT2B receptor antagonism include 
developmental toxicity (based on complete
knockout).
AZD0780 inhibits α1A adrenoceptor. In clinical
studies α1A adrenoceptor antagonism has 
resulted in a reduction of uterine and vas
deferens contractility and AE reports of
abnormal ejaculation.
Nonclinical developmental toxicity studies for
AZD0780 have not yet been performed.

Women of childbearing 
potential will be excluded 
from the study (inclusion 
criteria 1 and 8).

Reproductive restrictions will 
be in place throughout the 
study.

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Potential risk of 
clinical significance
Summary of data/rationale for risk
Mitigation strategy
Vomiting
In in vitro studies, AZD0780 was shown to be 
an antagonist of the serotonin receptor 5-HT2B
(Ki = 9.4 µM, functional IC50 >100 µM). This 
receptor is expressed in the gastrointestinal tract 
and mediates smooth muscle contraction.
Inhibition mayreduce gastric motility and 
result in symptoms such as nausea and 
vomiting.
In the 1-month toxicology study with AZD0780 
in cynomolgus monkeys, vomiting was 
observed and was a dose-limiting factor.
Nausea/emesis may translate to humans but since
the mechanism for the vomiting observed with 
AZD0780 treatment is unknown, there is no
understanding of the PK/PD relationship for 
predicting translatability to human.

Potential gastrointestinal 
effects will be monitored 
throughout the study by the 
reporting of AEs.

Physical examinations 
and vital signs will be
monitored throughout the 
study.
AE = adverse event; BP = blood pressure; ECG = electrocardiogram; hERG = human ether-a-go-go-related gene; 
PD = pharmacodynamic(s); PK = pharmacokinetic(s); QTcF = corrected QT interval.
AZD0780 is an inhibitor of PCSK9. Several drugs (siRNA and antibody based) aimed at 
lowering PCSK9 levels are either on the market or in clinical development. So far no safety 
concerns related to inhibition of PCSK9 has been reported in the literature (Ray et al 2020,
Karatasakis et al 2017, Geng et al 2021).
In human PCSK9 polymorphisms with low or no PCSK9 expression, no adverse phenotypes 
are described (Schmidt et al 2019).
Potential risks of the study procedures are the following:

Blood draws

Routine blood draws have a well-established risk profile. Risks will be mitigated by 
following institutional/study site guidelines.

Electrocardiogram

Routine ECGs are noninvasive, safe, and painless procedures. Participants will be 
informed that they may develop a mild rash or skin irritation where the electrodes 
were attached.
2.3.2
Benefit Assessment
The purpose of this Phase IIb study is to evaluate the safety, tolerability, PK, and efficacy of
AZD0780 in participants with dyslipidemia.
Participants will be required to continue on stable doses of their dyslipidemia maintenance 

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therapy (SoC) throughout the study to minimize the risk of disease worsening during the 
study.
For participants randomized to AZD0780, there is a potential benefit in terms of reduction of 
circulating levels of LDL-C. Plasma samples for analysis of lipid profile (total cholesterol, 
HDL-C, triglycerides, ApoB, Lp(a), ApoA1) will also be obtained to assess the effects of 
AZD0780 on these parameters.
Two PCSK9 neutralizing monoclonal antibodies, alirocumab and evolocumab, have been 
approved as LDL-C lowering therapies. These antibodies lower LDL-C by as much as 60% 
and lowers cardiovascular event rates (Sabatine et al 2017). More recently, an siRNA 
molecule targeting PCSK9, inclisiran, has been shown to reduce LDL-C by approximately 
50% (Ray et al 2020). While the clinical effect of AZD0780 in participants with dyslipidemia 
is yet to be determined, it is conceivable that treatment with AZD0780 will lead to similar 
improvement. However, it is possible that participants will not receive any individual benefit 
from participating in this study. All participants in this clinical study, irrespective of whether 
treated with AZD0780 or placebo, will be receiving SoC and closer medical attention 
compared to ordinary medical practice.
2.3.3
Overall Benefit/Risk Conclusion
The overall goal of the study is to examine if PCSK9 inhibition by AZD0780 is safe and 
clinically efficacious in dose-dependent reduction in LDL-C levels after oral administration of 
multiple doses of AZD0780 in participants with dyslipidemia.
Based on the available information regarding the potential risks of AZD0780, the safety data 
available to date, the inclusion/exclusion criteria, and additional precautions implemented in 
the clinical study, the prospect of individual benefit based on the IMP’s mechanism of action, 
and the clinical efficacy observed with administration of LDL-C lowering therapies targeting 
PCSK9 inhibition, the benefit-risk profile for study participants is considered acceptable.

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OBJECTIVES, ENDPOINTS, AND ESTIMANDS
The objectives and endpoints for the study are detailed in Table 3.
Table 3
Objectives and Endpoints
Objectives
Endpoints
Primary

To evaluate the effect of different doses of 
AZD0780 on LDL-C versus placebo in 
“ideal” scenarios in which intercurrent 
events would not occur

Percent change from baseline of LDL-C at 
Week 12
Secondary

To evaluate the effect of different doses of 
AZD0780 on LDL-C versus placebo in 
“real-world” conditions

Percent change from baseline of LDL-C at Week 
12

To assess the PK of AZD0780

AZD0780 plasma concentrations summarized by 
sampling timepoint

To evaluate the effects of different doses of
AZD0780 on other lipid parameters and 
inflammatory markers versus placebo in 
“ideal” scenarios in which intercurrent events 
would not occur

Percent change from baseline at Week 12 in:

Total cholesterol

HDL-C

Triglycerides

Non-HDL-C

VLDL-C

ApoA1

ApoB

Lp(a)

Remnant cholesterol

hsCRP

To evaluate the effects of different doses of 
AZD0780 on other lipid parameters and 
inflammatory markers versus placebo in “real-
world” conditions

Percent change from baseline at Week 12 in: 

Total cholesterol

HDL-C

Triglycerides

Non-HDL-C

VLDL-C

ApoA1

ApoB

Lp(a)

Remnant cholesterol

hsCRP
Safety

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
To assess the safety and tolerability of 
AZD0780

Safety and tolerability will be assessed in terms 
of AEs, vital signs, ECG, and clinical laboratory 
evaluations
Exploratory

To assess baseline PCSK9 levels

Results of baseline PCSK9 levels may be 
reported outside of the CSR

To collect and store plasma, serum, and urine 
samples for potential future exploratory 
biomarkers involved in PK, PD, safety and 
tolerability related to AZD0780 treatment 
and/or cardiometabolic diseases

Results of potential future exploratory 
biomarkers may be reported outside of the CSR

To explore how genetic variations may affect 
clinical parameters, risk and prognosis of 
diseases and the response to medications as 
detailed in Appendix D Optional Genomics 
Initiative. 
Note: The sample is taken from consented 
participants for DNA isolation and storage. 
Results will not be reported in the CSR. 

Exploratory endpoints are related to the data 
generated from the genetic analysis of part or 
all of the participant’s genetic information 
AE = adverse event; ApoA1 = apolipoprotein A-1; ApoB = apolipoprotein B-100; CSR = clinical study report; 
ECG = electrocardiogram; HDL-C = high-density lipoprotein cholesterol; hsCRP = high-sensitivity C-reactive 
protein; LDL-C = low-density lipoprotein cholesterol; Lp(a) = lipoprotein (a); PCSK9 = proprotein convertase 
subtilisin/kexin type 9; PD = pharmacodynamic(s); PK = pharmacokinetic(s); VLDL-C = very-low-density 
lipoprotein cholesterol.
Estimand for efficacy endpoints
Intercurrent events (ICE) are events occurring after treatment initiation that affect either the 
interpretation or the existence of the measurements associated with the clinical question of 
interest. In this study, ICEs of interest for efficacy evaluation include treatment discontinuation, 
change in background therapy, and intake of prohibited medication.
Estimand for the primary objective
The primary clinical question of interest is:
What is the difference in means of percent change in LDL-C from baseline to Week 12 in 
eligible participants with dyslipidemia treated with AZD0780 vs placebo in “ideal” scenarios 
in which intercurrent events would not occur?
The estimand is described by the following attributes:

Treatment: AZD0780 or placebo.

Population: Male and female participants of non-childbearing potential, 18 to 75 years of 
age with dyslipidemia.

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
Endpoint: Percent change in LDL-C from baseline to Week 12.

Population-level summary measure: Difference in means of percent change in LDL-C 
from baseline to Week 12 between AZD0780 and placebo.

Handling of intercurrent event: The hypothetical strategy will be used for the 
primary analysis. With this strategy, efficacy assessments obtained after ICEswill 
not be used for treatment effect estimation.
Estimand for secondary objectives
For the objective "To evaluate the effect of different doses of AZD0780 on LDL-C 
versus placebo in “real-world” conditions "
The clinical question of interest is:
What is the difference in means of percent change in LDL-C from baseline to Week 12in 
eligible participants with dyslipidemia treated with AZD0780 vs placebo, regardless of the 
occurrence of ICEs?
The estimand is described by the following attributes:

Treatment: AZD0780 or placebo.

Population: Male and female participants of non-childbearing potential, 18 to 75 years of 
age with dyslipidemia.

Endpoint: Percent change in LDL-C from baseline to Week 12.

Population-level summary measure: Difference in means of percent change in LDL-C 
from baseline to Week 12 between AZD0780 and placebo.

Handling of intercurrent event: The treatment policy strategy will be used for this 
analysis. With this strategy, efficacy assessments are used for treatment effect estimation 
regardless of the occurrence of ICEs.
For the objective "To evaluate the effects of different doses of AZD0780 on other lipid
parameters and inflammatory markers versus placebo in “ideal” scenarios in which 
intercurrent events would not occur"
The clinical question of interest is:
What is the difference in means of percent change in other lipid parameters and inflammatory 
markers from baseline to Week 12 in eligible participants with dyslipidemia treated with 
AZD0780 vs placeboin “ideal” scenarios in which intercurrent events would not occur ?

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The estimand is described by the following attributes:

Treatment: AZD0780 or placebo.

Population: Male and female participants of non-childbearing potential, 18 to 75 years of 
age with dyslipidemia.

Endpoint: Percent change in other lipid parameters and inflammatory markers from 
baseline to Week 12.

Population-level summary measure: Difference in means of percent change in other lipid 
parameters and inflammatory markers from baseline to Week 12 between AZD0780 and 
placebo.

Handling of intercurrent event: The hypothetical strategy will be used for these analyses.
With this strategy, efficacy assessments obtained after ICEs will not be used for treatment 
effect estimation.
For the objective "To evaluate the effects of different doses of AZD0780 on other lipid 
parameters and inflammatory markers versus placebo in “real-world” conditions"
The clinical question of interest is:
What is the difference in means of percent change in other lipid parameters and inflammatory 
markers from baseline to Week 12 in eligible participants with dyslipidemia treated with 
AZD0780 vs placebo, regardless of the occurrence of ICEs?
The estimand is described by the following attributes:

Treatment: AZD0780 or placebo.

Population: Male and female participants of non-childbearing potential, 18 to 75 years of 
age with dyslipidemia.

Endpoint: Percent change in other lipid parameters and inflammatory markers from
baseline to Week 12.

Population-level summary measure: Difference in means of percent change in other
lipid parameters and inflammatory markers from baseline to Week 12 between 
AZD0780 and placebo.

Handling of intercurrent event: The treatment policy strategy will be used for this 
analysis. With this strategy, efficacy assessments are used for treatment effect estimation 
regardless of the occurrence of ICEs.

Cli nical St u d y Pr ot oc ol - 3. 0 
A Z D 0 7 8 0 - D 7 9 6 0 C 0 0 0 0 6
C O N FI D E N TI A L A N D P R O P RI E T A R Y
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4
S T U D Y D E SI G N
4. 1
O ver all Desi g n
T his is a ra n d o mize d, m ult ice nter, parallel-gr o u p, d o u bl e- bli n d, place b o -c o ntr olle d, d ose-
ra n gi n g, P hase II b st u d y in a p pr o xi matel y 3 7 5 partici pa nts wit h d ysli pi de mia. T he pri mar y 
o bj ect i ve of t he st u d y is t o i n vesti gate t he effect of A Z D 0 7 8 0 o n L D L-C le vels acr oss 
differe nt d ose levels. A n o ver vie w of t he st u d y desi g n is pr o vi de d i n Fi g ure 1. T he st u d y will 
be c o n d ucte d at u p t o 6 5 sites i n u p t o 8 c o u ntries.
T he st u d y  p o p ulat i on will c o nsist of male a n d fe male partici pa nts of n o n- c hil d beari n g 
p ote nti al, 1 8 t o 7 5 years of a ge wit h a fasti n g L D L - C of ≥7 0 ( 1. 8 m m o l/ L) a n d < 1 9 0 m g/ d L 
( 4. 9 m m ol/L) at scree ni n g.
T he scree ni n g peri o d will be u p t o 3 wee ks pri or t o ra n d o mizat i on, i e, partici pa nts will be 
ra n d omize d at a n y t i me bet wee n Da y -2 1 a n d Da y -1 pr o vi di n g all eli gi bilit y crit eria ha ve 
bee n met. Partici pa nts wit h a fasti n g L D L -C of  ≥ 7 0 m g/ d L a n d < 1 9 0 m g/ d L, a n d 
trigl yceri des < 4 0 0 m g/ d L at scree ni n g will be eli gi ble. Partici pa nts will als o be recei vi n g 
m o derate or hi g h- i nte nsit y stati n t hera p y for at l east 2 mo nt hs pri or t o scree ni n g ( please refer 
t o A p pe n di x F ). Eli gi ble partici pa nts will atte n d 6 visits d uri n g t he treat me nt peri o d a n d o ne 
a d ditio nal  visit in t he f o ll ow- u p peri o d. Eli gi ble partici pa nts will be ra n d o mize d acr oss 5 
differe nt treat me nt ar ms i n a 1: 1: 1: 1: 1 rati o f or a 1 2 -wee k treat me nt peri o d. T he pla n ne d 
treat me nts ar ms are A Z D 0 7 8 0
m g, A Z D 0 7 8 0
m g, A Z D 0 7 8 0
 mg, A Z D 0 7 8 0
 mg, a n d 
place b o.
Bl o o d sa m ples will be c ollecte d f or a nal ysis of L D L -C ( Fri e de wal d calc ulati o n + refle x 
testi n g f or tri gl yceri des > 4 0 0 m g/ d L a n d/ or L D L-C < 4 0 m g/ d L) will be o b tai ne d t o assess 
t he effects of A Z D 0 7 8 0 o n t hese para meters. Bl o o d sa mples f or a nal ysis of li pi d pr ofile (t ot al 
c h o lester ol, H D L -C, tri gl yceri des, A p o B, L p(a), A p o A 1) will be o btai ne d t o assess t he effects 
of A Z D 0 7 8 0 o n t hese para meters. Sa m ples will be c ollecte d, la bele d, st ore d a n d s hi p pe d as 
detaile d i n t he La b orat or y  Ma n ual.
T he st u d y  is d o u ble-bli n d a n d A Z D 0 7 8 0 a n d place b o will be matc he d f or a p peara nce. 
P arti cip a nts will be gi n tr e at me nt ( place b o or A Z D 0 7 8 0) o n Da y 1 a n d c o nt i n ue f or 1 2 wee ks. 
After t he treat me nt peri o d, partici pa nts will ha ve o ne f o ll ow- u p visi t 2 wee ks p ost last d ose. 
F or detaile d i nf or mat i on, pl ease refer t o t he S o A (Ta ble 1 ).
4. 2
Scie ntific R ati o n ale f or St u d y Desi g n
4. 2. 1
R ati o n ale f or Selecti o n of P artici p a nt P o p ul ati o n
A Z D 0 7 8 0 is a p ote ntial first-i n-class oral s mall m o lec ule P C S K 9 i n hi bit or, a n d t his st u d y is 
part of a pr o gra m t o c o nfir m if A Z D 0 7 8 0 will l ower car di o vasc ular ris k i n b ot h pri mar y a n d 
sec o n dar y pre ve nti on, w he n ta ke n o nce dail y al o n g wit h S o C.
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The population included in this study comprises male or female participants of non-
childbearing potential, 18 to 75 years of age with a fasting LDL-C of ≥70 (1.8 mmol/L) and
< 190 mg/dL (4.9 mmol/L) at screening. Each participant should meet all the inclusion criteria 
and none of the exclusion criteria to be assigned/randomized to a study intervention. Under no 
circumstances can there be exceptions to this rule. Participants who do not meet the entry 
requirements are screen failures (Section 5.4).
4.2.2
Rationale for Selection of Primary Endpoint
Statins are the first-line therapy for lowering of LDL-C recommended by the latest 
dyslipidemia guidelines (Mach et al 2020; Reiter-Brennan et al 2020). Reduction of LDL-C 
levels by statins leads to significant reduction in cardiovascular events including coronary 
artery disease and other cardiovascular related deaths (Collins et al 2016). However, despite 
the substantial benefits of statin therapy, many patients do not reach LDL-C target levels.
Current guidelines call for LDL-C to be lowered ≥50% with maximally tolerated statins in 
patients with existing atherosclerotic CVD (Atar et al 2021). Additional evidence 
demonstrates that aggressively lowering LDL-C levels to < 40 mg/dL lowers CVD risk in a
wider range of patients (Marston et al 2021). This underscores the medical need for 
developing new cost-effective LDL-C lowering medicines to achieve the most recent 
dyslipidemia guidelines for the prevention of CVD.
4.2.3
Rationale for Selection of Comparator
The comparator in this study is placebo. Both AZD0780 and placebo will be administered on 
top of moderate or high-intensity statin therapy; therefore, the treatment of the placebo group 
will correspond to current SoC for participants with dyslipidemia.
The use of placebo will allow for a double-blinded treatment period and to provide a control 
arm, so as to enable a continued comparison of efficacy, in particular the comparison of dose-
dependent change in LDL-C after oral administration of multiple doses of AZD0780, and to 
act as a comparator to contextualize safety observations.
4.2.4
Rationale for Selection of Study Duration
The treatment length in the study is 12 weeks. Based on data from a MAD study
(Study D7960C00001), steady state in plasma exposure of AZD0780 was reached after one 
week of once daily dosing with AZD0780, while steady state in the LDL-C lowering effect
was reached within approximately 2 weeks of treatment. With a treatment length of 12 weeks 
participants are predicted to be at least 10 weeks on stable LDL-C lowering effect, allowing 
for a robust assessment of the lipid effects of AZD0780. Twelve weeks of dosing is also 
predicted to allow for a robust assessment of safety, tolerability and the PK of AZD0780 to 
guide dose selection for further clinical development of AZD0780.

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4. 3
J u stific ati o n f or D o se
Si n gle d oses of A Z D 0 7 8 0 u p t o  
 m g a n d m ult i ple d oses of A Z D 0 7 8 0 u p t o 
 m g o nce 
dail y  for u p t o 4 wee ks of d osi n g ha ve bee n e val uate d a n d s h o w n t o be well t olerate d i n 
parti ci pa nts wit h ele vate d L D L-C ( o n g oi n g St u d y D 7 9 6 0 C 0 0 0 0 1). T he d oses f or t he c urre nt 
st u d y were selecte d base d o n t he o bser ve d safety,  t olera bilit y, a n d L D L - C re d uci n g data fr o m 
t he M A D c o h orts.
T he mi d a n d hi g h d ose, pla n ne d t o be 
 m g a n d 
 m g A Z D 0 7 8 0, were selecte d t o reac h 
close t o ma xi m u m ac hie va ble re d ucti on i n L D L -C. T he a i m wi t h t he hi g hest d ose (
m g) is 
t o s h o w t hat a n i ncrease a b o ve t he 
 m g d ose will n ot res ult i n a n y f urt her cli nicall y 
sig nifica nt re d ucti o n i n L D L -C c o m pare d t o 
 m g A Z D 0 7 8 0. D ue t o t he u ncertai nt y i n 
d ose/e x p os ure res p o nse at d oses bel o w 
 m g, t w o l ower d oses were als o selecte d f or t his 
st u d y, 
mg a n d
m g. T he ai m is t o ha ve at least o ne d ose t hat s h o ws a cli nicall y si g nifica nt 
l ower L D L -C re d ucti o n as c o m pare d t o t he 
 m g a n d 
 m g d oses. T he 2 mi d d oses, 
m g 
a n d 
 mg, were t h us sel ecte d f or t he p ote ntial t o be i n t he t hera pe utic d ose ra n ge.
Pri or t o t he start of d osi n g i n t he c urre nt st u d y , safet y a n d t olera bilit y d at a f r o m mul tiple 
d osi n g of
 mg A Z D 0 7 8 0 o nce dail y f or 4 wee ks will ha ve bee n e val uate d i n t he o n g oi n g 
St u d y  D 7 9 6 0 C 0 0 0 0 1 i n pa rtici pa nts wi t h ele vate d L D L-C.
4. 4
E n d -of -st u d y Defi niti o n
F or t he p ur p ose of Cli nical Tri al Tra ns pare nc y t he defi nitio n of t he e n d of t he st u d y differs 
u n der F D A a n d E U re g ulat or y  r e q uire me nts:
E ur o pea n U ni o n re q uire me nts defi ne st u d y c o mpl eti o n as t he last visit of t he last s u bject f or 
a n y pr ot oc ol relate d acti vit y.
F o o d a n d Dr u g A d mi nistrati o n re q uire me nts defi nes 2 c o mplet i on dates:
Pri mar y C o m p leti on Date – t he date t hat t he fi nal partici pa nt is e xa mi ne d or recei ves a n 
i nter ve nt i on f or t he p ur p oses of  fi nal c ollecti on of data f or t he pri mar y  o ut c o me meas ure, 
w het her t he cli nical st u d y  c o ncl u de d acc or di n g t o t he pre-s pecifie d pr ot oc ol or was 
ter mi nate d. I n t he case of cli nical st u dies wi t h m o re t ha n o ne pri mar y o ut c o m e me as ure wi t h 
differe nt c o mplet i on dates, t his ter m refers t o t he date o n w hic h data c ollect i on is c o m plete d 
f or all of t he pri mar y o ut c o mes.
St u d y C o m plet i on Date – t he date t he fi nal part ici pa nt is e xa mi ne d or recei ves a n i nter ve nt i on 
f or p ur p oses of fi nal c ollecti o n of data f or t he pri mar y a n d sec o n dar y o ut c o me meas ures a n d 
A Es (f or e xa m ple, last partici pa nt’s last visit), w het her t he cli nical st u d y c o nclu des acc or di n g 
t o t he pre-s pecifie d pr ot oc ol or is ter mi nate d.
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A participant is considered to have completed the study if they have completed all phases of 
the study including the last visit.
5
STUDY POPULATION
Participants will be males and females of non-childbearing potential (ie, postmenopausal or 
surgically sterile), aged 18 to 75 years (inclusive), with a fasting LDL-C ≥ 70 mg/dL
(1.8 mmol/L) and< 190 mg/dL (4.9 mmol/L), fasting triglycerides < 400 mg/dL 
(< 4.52 mmol/L), and have a BMI at or above 19.0 kg/m2.
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known 
as protocol waivers or exemptions, is not permitted.
Each participant should meet all the inclusion criteria and none of the exclusion criteria for 
this study. Under no circumstances can there be exceptions to this rule.
5.1
Inclusion Criteria
Participants are eligible to be included in the study only if all of the following criteria apply:
Age
1
Males, and females of non-childbearing potential, 18 to 75 years of age, inclusive, at
the time of signing the informed consent.
Type of Participant and Disease Characteristics
2
Participants with a fasting LDL-C ≥70 mg/dL (1.8 mmol/L) and < 190 mg/dL 
(4.9 mmol/L) at screening.
3
Participants with fasting triglycerides < 400 mg/dL (< 4.52 mmol/L) at screening.
4
Should be receiving moderate or high-intensity statin therapy for ≥ 2 months prior to 
screening, according to ACC/AHA guidelines on blood cholesterol management, or to 
local guidelines, eg, Japanese Atherosclerosis Society guidelines.
5
There should be no planned medication or dose change during study participation. 
Weight
6
Body mass index at or above 19.0 kg/m2.
Sex
7
Male participants:
(a) Males must be surgically sterile or using, in conjunction with their female partner, a 
highly effective method of contraception for the duration of the study (from the 
time they sign consent) and for 3 months after the final follow up visit to prevent 
pregnancy in a partner. Acceptable methods of contraception include birth control 
pills, injections, implants, or patches, IUDs, tubal ligation/occlusion, and 
vasectomy. A barrier method is not necessary if the female partner is sterilized. 
Male study participants must not donate or bank sperm during this same time 

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period.
8
Female participants:
(a) Female participants must not be pregnant and must have a negative pregnancy test 
at screening and randomization, must not be lactating, and must not be of 
childbearing potential. Women not of childbearing potential are defined as women 
who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or 
bilateral salpingectomy), or who are postmenopausal. Women will be considered 
postmenopausal if they have been amenorrhoeic for 12 months prior to the planned 
date of randomization without an alternative medical cause. The following age-
specific requirements apply:
(i)
Women < 50 years of age would be considered postmenopausal if they have 
been amenorrhoeic for 12 months or more following cessation of exogenous 
hormonal treatment and FSH levels in the postmenopausal range.
(ii) Women ≥ 50 years of age would be considered postmenopausal if they have 
been amenorrhoeic for 12 months or more following cessation of all exogenous 
hormonal treatment.
9
Restrictions for male participants
(a) All male participants should avoid fathering a child by either true abstinence or by 
using (together with their female partner/spouse) a highly effective contraception 
form of birth control in combination with a barrier method, starting from the time of 
study intervention administration until 3 months after the Final Follow-Up visit. 
Acceptable methods of preventing pregnancy include birth control pills, injections, 
implants, or patches, IUDs, tubal ligation/occlusion, and vasectomy.
(b) Male participants who have been sterilized are required to use 1 barrier method of 
contraception (condom) from the time of study intervention administration until 
after the Final Follow-Up Visit. A barrier method is not necessary if the female 
partner is sterilized.
(c) Male participants should not donate sperm for the duration of the study and for at 
least 3 months post last follow-up visit.
Informed Consent
10 Capable of giving signed informed consent as described in Appendix A 3, which 
includes compliance with the requirements and restrictions listed in the ICF and in this 
protocol.
11 Provision of signed and dated, written ICF prior to any mandatory study specific 
procedures, sampling, and analyses. Participants who consent only to the main study 
may participate in other components of the main study without participating in the 
optional component of the study. However, to participate in the optional component of 
the study, the participant must sign and date both the consent forms for the main study 
and optional component of the study. If a participant declines to participate in the 

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optional component of the study, there will be no penalty or loss of benefit to the 
participant. The participant will not be excluded from other aspects of the study 
described in this protocol.
Other Inclusion Criteria
Participants should refrain from blood donation throughout the study, including the follow-up 
period.
5.2
Exclusion Criteria
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1
Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m2 using the Chronic 
Kidney Disease-Epidemiology Collaboration (CKD-Epi 2021(Age, Sex)) equation 
at Visit 1.
2
History or presence of gastrointestinal, hepatic or renal disease or any other conditions 
known to interfere with absorption, distribution, metabolism, or excretion of drugs.
3
Any uncontrolled or serious disease, or any medical (eg, known major active infection 
or major hematological, renal, metabolic, gastrointestinal, respiratory, or endocrine 
dysfunction) or surgical condition that, in the opinion of the investigator, may either 
interfere with participation in the clinical study and/or put the participant at significant 
risk.
4
Poorly controlled type 2 diabetes mellitus, defined as HbA1c > 10% at Visit 1.
5
Acute ischemic cardiovascular event in the last 12 months prior to randomization however
patients can be included if it is > 6 months from coronary artery bypass graft surgery
(CABG) surgery and > 3 months after percutaneous coronary intervention (PCI).
6
Heart failure with New York Heart Association (NYHA) Class III-IV.
7
Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast 
ductal carcinoma in-situ, or Stage 1 prostate carcinoma) within the last 10 years.
8
Recipient of any major organ transplant, eg, lung, liver, heart, bone marrow, renal.
9
LDL or plasma apheresis within 12 months prior to randomization.
10 Uncontrolled hypertension defined as average sitting SBP > 160 mmHg or 
DBP > 90 mmHg at Visit 1. It is recommended that antihypertensive 
treatment should be considered/initiated at the PI’s discretion and in 
accordance with applicable clinical guidelines in order to optimize blood 
pressure for participants with hypertension during the clinical study.
11 Heart rate after 10 minutes supine rest < 50 bpm or > 100 bpm at Visit 1.
12 Any laboratory values with the following deviations at Screening Visit 1; test may be 
repeated at the discretion of the investigator if abnormal:
(a) Any positive result on screening for hepatitis B, hepatitis C or HIV.

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(b) ALT > 1.5 × ULN
(c) AST > 1.5 × ULN
(d) TBL > ULN
(e) Hemoglobin < 12 g/dL in men or < 11 g/dL in women
(f)
Potassium < LLN
13 Any clinically important abnormalities in rhythm, conduction or morphology of the 
resting ECG and any clinically important abnormalities in the 12 lead ECG as judged by 
the investigator including shortened QTcF< 340ms; family history of long QT 
syndrome; PR interval shortening < 120 ms; PR interval prolongation >220 ms,
intermittent second or third degree AV block or AV dissociation; persistent or
intermittent complete bundle branch block, incomplete bundle branch, or
interventricular conduction delay with QRS > 110 ms.
14 QTcF > 450 ms; high degree atrioventricular-block grade II-III and sinus node 
dysfunction with significant sinus pause untreated with pacemaker; and cardiac 
tachyarrhythmias.
15 Known or suspected history of drug abuse as judged by the investigator.
16 History of alcohol abuse or excessive intake of alcohol as judged by the investigator.
17 History of severe allergy/hypersensitivity or ongoing clinically important 
allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to 
drugs with a similar chemical structure.
18 Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of 
the first administration of study intervention. History or evidence of any other clinically 
significant disorder (eg, cognitive impairment), condition, or disease other than those 
outlined above that, in the opinion of the investigator or Sponsor physician, if consulted, 
may compromise the ability of the participant to give written informed consent, would 
pose a risk to participant safety, or interfere with the study evaluation, procedures, or 
completion.
Prior/Concomitant Therapy
19 Current/previous administration of inclisiran.
20 Lomitapide within 12 months prior to randomization.
21 Previous administration of PCSK9 inhibition treatment within 12 months prior to 
randomization (approved or investigational).
22 Fibrate therapy and derivatives are prohibited.
23 Receiving or has received within 14 days of screening, medication that contains a black box 
warning for significant QT prolongation. 
Prior/Concurrent Clinical Study Experience
24 Participation in another clinical study with a study intervention administered in the last 3 
months prior to randomization or 5 half-lives from last dose to first administration of 
study intervention, whichever is the longest.

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25 Received another new chemical entity (defined as a compound which has not been 
approved for marketing) within 30 days of last follow-up to first administration of the 
study intervention of this study or 5 half-lives from last dose to first administration of 
study intervention, whichever is the longest.
26 Use of other investigational products or investigational devices during the course of the 
study.
Other Exclusions
27 Involvement in the planning and/or conduct of the study (applies to both Sponsor staff 
and/or staff at the study site or their close relatives).
28 Judgement by the investigator that the participant should not participate in the study if 
the participant is unlikely to comply with study procedures, restrictions and 
requirements.
29 As judged by the investigator, any evidence of disease conditions that, in the 
investigator’s opinion, makes it undesirable for the participant to participate in the trial.
30 Previous screening in the present study.

Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened. At the investigator’s discretion, participants may be rescreened 
once during the recruitment period.
31 Participants who cannot communicate reliably with the investigator.
32 Vulnerable participants, eg, kept in detention, protected adults under guardianship, 
trusteeship, or committed to an institution by governmental or juridical order.
33 Plasma donation within 1 month of the screening visit at the clinic or any blood 
donation/blood loss > 500 mL (> 400 mL in Japan only) during the 3 months prior to
screening visit.
Optional Genetic Sampling
34 Exclusion from this genetic research may be for any of the exclusion criteria specified 
for the main study or any of the following:
(a) Previous allogeneic bone marrow transplant.
(b) Non-leukocyte depleted whole blood transfusion within 120 days of genetic sample 
collection.
5.3
Lifestyle Considerations
5.3.1
Pregnancy
Participants will be instructed that if they or their partner becomes pregnant during the study 
this should be reported to the investigator. The investigator should also be notified of 
pregnancy occurring during the study but confirmed after completion of the study. In the event 
that a participant’s partner is subsequently found to be pregnant after the participant is 
included in the study, then consent will be sought from the partner (via the participant’s 
request that their partner contact the study site) and, if granted, any pregnancy will be 

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followed, and the status of mother and/or child will be reported to the Sponsor after delivery.
5.3.2
Meals and Dietary Restrictions
For all study visits (including screening), participants must be fasted for 8 hours prior to blood 
sampling for LDL-C and other lipid profile. No fluids will be allowed apart from water, which 
can be given until 1 hour before blood sampling for LDL-C and other lipid profile.
5.3.3
Caffeine, Alcohol, and Tobacco
Participants who use alcohol may participate in the study unless their consumption is deemed 
excessive by the investigator.
5.3.4
Activity
Participants should not start any new physical training activities or increase the intensity of 
their usual physical training from 5 days prior to randomization until the end of the study.
5.3.5
Other Restrictions
Participants should refrain from blood donation throughout the study, including the follow-up 
period.
5.4
Screen Failures
A screen failure occurs when a participant who has consented to participate in the clinical 
study is not subsequently randomly assigned to study intervention/entered in the study. A 
minimal set of screen failure information is required to ensure transparent reporting of screen 
failure participants to meet the Consolidated Standards of Reporting Trials (CONSORT) 
publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, eligibility criteria, and any SAE.
Participants may be rescreened once if the reason for screen failure was transient (including 
but not limited to study-supplied equipment failure or unforeseen personal events that
mandate missed screening visits). Rescreened participants should be assigned the same 
participant number as for the initial screening. Individuals who do not meet a specific criterion 
may have this parameter retested if the investigator determines there is a reason to believe that 
this was caused by a temporary/transient reason.
5.5
Criteria for Temporarily Delaying Administration of Study 
Intervention – Not Applicable

Cli nical St u d y Pr ot oc ol - 3. 0 
A Z D 0 7 8 0 - D 7 9 6 0 C 0 0 0 0 6
C O N FI D E N TI A L A N D P R O P RI E T A R Y
4 5 of 9 9
D oc I D: T M P -0 0 1 0 2 2 5
Te m pl ate Versi o n N u m ber 8. 0
6
S T U D Y I N T E R V E N TI O N( S) A N D C O N C O MI T A N T T H E R A P Y
St u d y i nter ve nt i on is defi ne d as a n y i n vesti gati onal i nter ve nt i on(s), mar kete d pr o d uct(s) or
pl ace b o i nte n de d t o be a d mi nistere d t o or me d ical de vice(s) utilize d b y a st u d y s u bject 
acc or di n g t o t he st u d y pr ot oc ol.
6. 1
St u d y I nter ve nti o n(s) A d mi nistere d
6. 1. 1
I n vesti g ati o n al Pr o d ucts
I n vesti gati onal me dici nal pr o d uct will be all o cate d via a n I R T s yste m a n d st u d y-sit e staff will  
di s pe nse pr o per b ottles t o t he partici pa nts. A d dit i onal i nf or mati on re gar di n g t he
a d mi nistrati o n of I M P is pr o vi de d i n t he P h ar mac y Ma n ual.
Ta ble 4 i ncl u des a descri pt i on of t he I M Ps use d i n t his st u d y, t heir d ose f or mulat i on, u nit d ose 
stre n gt h, d osa ge le vel, r o ute of a d mi nistrati o n, use, s o urci n g, a n d pac ka gi n g a n d la beli n g.
T a ble 4
I n vesti g ati o n al Pr o d ucts A d mi nistere d
Ar m n a me
A Z D 0 7 8 0
Place b o
I nter ve nti o n n a me
A Z D 0 7 8 0
Place b o
T y pe
Dr u g
Place b o
D ose f or m ul ati o n
R o u n d t a blet
R o u n d t a blet
U nit d ose stre n gt h(s)
m g
Place b o t o matc h
D os a ge le vel(s)
m g
Place b o t o matc h
R o ute of a d mi nistr ati o n
Oral
Oral
Re gi me n
Q D
Q D
Use
E x peri me ntal
Place b o
I M P
I M P
I M P
S o urci n g
Pr o vi de d ce ntrall y b y t he S p o ns or
Pr o vi de d ce ntrall y b y t he S p o ns or
P ac k a gi n g a n d l a beli n g
St u d y treat me nt will be pr o vi de d i n 
plastic b ottles. La bels f or st u d y
i nter ve nti o n s u p plie d b y
Astra Ze neca will be pre pare d i n
acc or da nce wit h 
G M P
a n d l ocal 
re g ulat or y g ui deli nes 
St u d y treat me nt will be pr o vi de d i n 
plastic b ottles. La bels f or st u d y
i nter ve nti o n s u p plie d b y
Astra Ze neca will be pre pare d i n
acc or da nce wit h 
G M P
a n d l ocal 
re g ulat or y g ui deli nes 
G M P = G o o d Ma n ufact uri n g
Practice; I M P = i n vesti gati o nal me dici nal pr o d uct; Q D = o n ce dail y.
T he pl ace b o t o matc h c o ntai ns cell ul o se micr ocr ystalli ne/ micr ocr ystalli ne cell ulos e a n d 
s o diu m stear yl  fu marate. T he fil m -c oat c o ntai ns p ol y(vi n yl alc o h o l)/p ol y vi n yl alc o h o l, 
tita ni u m dio xi de, macr o g ol / p ol yet hyle ne gl yc o l, talc, ir o n o xide yell o w/f erric o xid e, i r o n 
o xi de re d/ferric o xi de, a n d ir o n o xi de blac k/ferr os oferric o xi de. 
Details of t he batc h n u m bers will be i ncl u de d i n t h e trial master file a n d fi nal C S R.
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6.2
Preparation, Handling, Storage, and Accountability
The IMP will be supplied by AstraZeneca as labeled bottles (QP released by AstraZeneca)
with a study specific label. The labels will fulfill Good Manufacturing Practice Annex 13 
requirements and medical device directive for labeling.
No special procedures for the safe handling of AZD0780/placebo are required.
The investigator or designee must confirm appropriate conditions (eg, temperature) have been 
maintained during transit for all study intervention received at the site and throughout the 
entire study until authorization is provided for on-site destruction or removal of the IMP, 
reflecting completion of the study. In the event of a temperature excursion detected at any 
time during the study, sites will follow the reporting procedures for notifying the Sponsor (or 
designated party); release of IMP for clinical use can only occur once the event has been 
reviewed and approval is provided by the Sponsor (or designated party).
Only participants randomized in the study may receive study intervention, and only authorized 
site staff may dispense proper IMP to participants. Prior to dispensing to study participants, all 
IMP 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 
authorized site staff. Participants will be given instructions around storage of IMP and self-
administering IMP at home.
The investigator, or delegated, authorized site staff, is responsible for the IMP accountability, 
reconciliation, and record maintenance (i.e., receipt, reconciliation, and final disposition 
records). The Sponsor will be permitted upon request to audit the supplies, storage,
dispensing procedures and records, provided that the blind of the study is not compromised.
Further guidance and information for the final disposal of unused study interventions are 
provided in the Pharmacy Manual.
6.3
Assignment to Study Intervention
All participants will be centrally assigned to randomized study intervention using an 
IRT/RTSM. The participant numbers will be obtained during screening for all participants, 
after the signature of the ICF, while the randomization codes will be assigned only to the 
participants proceeding to the treatment phase of the study. Before the study is initiated, the 
telephone number and call-in directions for the IRT and/or the log in information and 
directions for the RTSM will be provided to each site in the IRT/RTSM user manual.
In case of rescreening, the rescreened participants should be assigned the same participant 
number as for the initial screening.
Participants will be randomized to once daily dosing of placebo or different dose levels of 
AZD0780. Dosing should be supervised and documented by study staff when study 
intervention is administered in the clinic. Eligible participants will be randomized across 5
different treatment arms (approximately 75 participants in each arm) in a 1:1:1:1:1 ratio for a 

Cli nical St u d y Pr ot oc ol - 3. 0 
A Z D 0 7 8 0 - D 7 9 6 0 C 0 0 0 0 6
C O N FI D E N TI A L A N D P R O P RI E T A R Y
4 7 of 9 9
D oc I D: T M P -0 0 1 0 2 2 5
Te m pl ate Versi o n N u m ber 8. 0
1 2- wee k treat me nt peri o d. T he pla n ne d treat me nts ar ms are A Z D 0 7 8 0 
m g, A Z D 0 7 8 0
m g,
A Z D 0 7 8 0
m g, A Z D 0 7 8 0
 mg, a n d place b o. A mi ni m u m of 5 partici pa nts a n d a 
ma xi m u m o f 1 0 parti ci pa nts i n eac h ar m (a mi ni m u m of 2 5 i n t otal a n d a ma xi m u m o f 5 0 i n 
t otal) will be allocate d t o si tes i n Ja pa n. Se parate ra n d o mizat i on lists will be ge nerate d f or 
Ja pa n a n d f or t he rest of t he w orl d.
I n vesti gati onal me dici nal pr o d uct will be a vaila ble as fil m-c oate d oral ta blets i n labele d 
b ottl es c o ntai ni n g eit her A Z D 0 7 8 0 ta blets or place b o ta blets ( 3 5 ta blets i n a b ottle).
Ret ur ne d st u d y i nter ve nt i on s h o uld n ot be re-dis pe nse d t o partici pa nts.
6. 4
Bli n di n g
6. 4. 1
Met h o ds
f or E n s uri n g Bli n di n g
T his is a d o u bl e- bli n d st u d y i n w hic h t he i n vesti gati o nal sit e staff a n d parti ci pa nts r e mai n 
bli n de d d uri n g t he cli nical st u d y .
All pac ka gi n g a n d la beli n g of I M P will be d o ne i n s uc h a wa y  as t o e ns ure bli n di n g f or all 
parti ci pa nts, S p o ns or, a n d i n vest i gati onal site staff. I n vesti gat ors, bli n de d S p o ns or, a n d 
i n vesti gati onal sit e staff a n d partici p a nts will re mai n bli n de d t o eac h pa rtici pa nt’s assi g ne d 
I M P t hr o u g h o ut t he c o urse of t he st u d y.
I n t he e ve nt of a Q ualit y Ass ura nce a u dit, t he a u dit or(s) will be allo we d access t o u n bli n de d 
I M P rec or ds at t he site(s) t o verif y t hat ra n d o mizati on/ dis pe nsi n g has bee n perf or me d 
acc uratel y.
A S p o ns or si t e mo ni t or will perf or m I M P acc o u nta bility.  I n t he e ve nt t hat t he treat me nt 
all ocat i on f or a partici pa nt bec o mes k n o w n t o t he i n vesti gat or or ot her stu d y staff i n v ol ve d i n 
t he ma na ge me nt of st u d y parti ci pa nts, or nee ds t o be k n o w n t o treat a n i n d i vi d ual partici pa nt 
f or a n A E, t he S p o ns or m ust be n otifie d i m me diatel y b y t he i n vesti gat or a n d, if p ossi ble, 
bef ore u n bli n di n g.
T he f oll owi n g pers o n nel will ha ve access t o t he ra n d omizat i on list d uri n g t he st u d y, pri or t o 
data base l oc k:

T h ose carr yi n g o ut t he pac ka gi n g a n d la beli n g of I M P.

T h ose ge nerat i n g t he ra n d o mizati o n list.

T he S p o ns or s u p pl y c hai n d e p art m e nt.

T he I n vesti gat or i n case of a me dical e mer ge nc y w here t he treat me nt nee ds t o be re veale d 
d ue t o safet y  reas o ns, a n d t he n o nl y for t he at o ne c o ncer ne d partici pa nt(s). 

La bc or p Bi o a nal yt ical Ser vices L L C (res p o nsi ble f or a nal yzi n g t he sa m ples).

I n t he e ve nt of  a n i nteri m a nal ysis, desi g nate d s p o ns or pers o n nel will be u n bli n de d as part of 
t he U n bli n de d Re vie w C o m mit tee as descri be d i n A p pe n di x A 5.
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The information in the randomization list will be kept from other personnel involved in the 
conduct of the study in a secure location until the end of the study. No other member of the 
extended study team at the Sponsor, or any CRO handling data, will have access to the
randomization scheme during the conduct of the study. Randomization codes will not be 
broken for the planned analyses of data until all decisions on the evaluability of the data from 
each individual participant have been made and documented.
The randomization codes are generated by a validated IT-system and are provided by a third 
party vendor, who provides and manages the RTSM system.
Sponsor safety staff may unblind the intervention assignment for any participant with an
SAE. If the SAE requires that an expedited regulatory report be sent to one or more 
regulatory agencies, a copy of the report, identifying the participant’s intervention 
assignment, may be sent to investigators in accordance with local regulations and/or sponsor 
policy.
6.4.2
Methods for Unblinding
The Investigator has sole responsibility for the medical care of the individual study 
participants throughout the clinical trial duration. It is the Investigator’s independent decision 
to break the randomization code in the event of an emergency that requires a rapid response. 
This action does not require the Sponsor’s representative approval. To maintain the blinding 
of the assigned study intervention of other participants the emergency unblinding is 
performed via a specifically programmed transaction within the RTSM system that only 
reveals the assigned study intervention of the concerned participant(s). The specific process 
will be described in the RTSM user manual that will be provided to each site. 
Access to the transaction is restricted and emergency unblinding can only be performed by 
appropriate users. The Sponsor applies two options for emergency unblinding: primary line 
and secondary line. 
The primary line for emergency unblinding grants access only for medically qualified site 
personnel: 

Principal Investigator (PI) 

Sub-Investigator (SI) 
Note: Study Coordinators (SC) and any other non-medically qualified site personnel are not 
allowed to perform emergency unblinding. 
In the unlikely event that the Investigator is unable to access the RTSM system for e.g. 
technical issues or loss of log-in details, there is an IRT Helpdesk service available to assist, 
which is available 24 hours per day, 7 days per week. 
The secondary line for emergency unblinding is a local back-up solution which only allows 
an appointed user (Local Safety Unblinder) to reveal the study participant’s assigned study 

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intervention when the primary line point of contact is not available. The local back-up 
solution is available 24 hours per day, 7 days per week. 
If a participant’s assigned study intervention is unblinded, the sponsor must be notified within 
24 hours after breaking the blind. The unblinding action is reported to the Sponsor without 
revealing the assigned study intervention to the Sponsor staff. 
In conjunction with the investigator, the Sponsor can request unblinding of the assigned study 
intervention for participant(s) with SAEs that are unexpected and are suspected to be causally 
related to IMP. If the SAE requires that an expedited regulatory report be sent to one or more 
regulatory agencies, a copy of the report, identifying the participant’s intervention 
assignment, may be sent to investigators in accordance with local regulations and/or sponsor 
policy. 
6.5
Study Intervention Compliance
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 if applicable, of dose 
administered in the clinic will be recorded in the source documents and recorded in the eCRF.
When participants self-administer study intervention(s) at home, compliance with study 
intervention will be assessed at each visit. Compliance will be assessed by direct questioning 
and counting returned tablets during the site visits and documented in the source documents 
and eCRF. Deviation(s) from the prescribed dosage regimen should be recorded in the eCRF.
A record of the quantity of AZD0780 dispensed to and administered by each participant must 
be maintained and reconciled with study intervention and compliance records. Intervention 
start and stop dates, including dates for intervention delays and/or dose reductions will also
be recorded in the eCRF.
6.6
Dose Modification
No dose modifications are allowed during the study.
6.7
Continued Access to Study Intervention After the End of the 
Study
There is no planned intervention following the end of the study.

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6.8
Treatment of Overdose
For this study, any dose of AZD0780 greater than planned will be considered an overdose. 
The Sponsor does not recommend specific treatment for an overdose.
In the event of an overdose, the treating physician should:

Evaluate the participant to determine, in consultation with the Study Clinical Lead, if 
possible, whether study intervention should be interrupted or whether the dose should be 
reduced.

Closely monitor the participant for any AE/SAE and laboratory abnormalities as 
medically appropriate and at least until the next scheduled follow-up. Refer to 
Section 8.3.12 for details of AE/SAE reporting related to overdose.

Document the quantity of the excess dose as well as the duration of the overdose.
6.9
Prior and Concomitant Therapy
Any medication or vaccine (including over the counter or prescription medicines, recreational 
drugs, vitamins, and/or herbal supplements) that the participant (except for screen failures) is 
receiving at the time of enrollment or receives during the study, or other specific categories of 
interest such as cholesterol lowering therapy within the last 12 months must be recorded
along with:

Reason for use

Dates of administration including start and end dates

Dosage information including dose, frequency and route.
Participants will be required to continue on stable doses of their dyslipidemia maintenance 
therapy (SoC) throughout the study to minimize the risk of disease worsening during the 
study.
The Study Clinical Lead should be contacted if there are any questions regarding concomitant 
or prior therapy.
Concomitant medications that contain a black box warning for significant QT prolongation 
are prohibited within this study.
Fibrate therapy and derivatives are prohibited.
Paracetamol at doses of £ 2 grams/day, is permitted for use any time during the study. Other 
concomitant medication may be considered on a case-by-case basis by the investigator in 
consultation with the Study Clinical Lead if required.
6.9.1
Rescue Medicine – Not Applicable

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7
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL
Discontinuation of specific sites or of the study as a whole are handled as part of Appendix A.
It may be necessary for a participant to permanently discontinue study intervention. Note that 
discontinuation from study intervention is not the same thing as a discontinuation or 
withdrawal from the study (see Section 7.2).
7.1
Discontinuation of Study Intervention
An individual participant will not receive further IMP if any of the following occur in the 
participant in question:

Hy’s Law (HL) defined as ‘an increase in AST of ALT ≥3 x ULN and TBL ≥2 x ULN’ 
where no other reason, other than IMP, can be found to explain the combination of 
increases.

A severe hypersensitivity reaction.

Participant decision. The participant is at any time free to discontinue treatment, without 
prejudice to further treatment.

An SAE that is assessed as possibly related to the study intervention by the Investigator.

An AE or other safety reasons as judged by the investigator and/or sponsor where 
continued treatment may put the participant at undue risk.

Severe noncompliance with the CSP.

Pregnancy; if a participant becomes pregnant during the study the study intervention 
should be discontinued immediately and a Sponsor representative notified.

Signs or symptoms of severe hepatic impairment, as described in Section 7.1.1.

Cardiovascular findings, as described in Section 7.1.2.

Respiratory symptoms, as described in Section 7.1.3
If a participant discontinues IMP, he or she will be encouraged to return to the study site for 
the Early Discontinuation Visit (EDV; see Table 1). Where possible, the EDV should be at
the next visit according to the original visit schedule, unless consent is withdrawn from 
further study participation, or the participant is lost to follow-up. Participants attending an 
EDV should also be asked to return for a follow-up visit (Visit 8, as if they have completed 
all doses) unless they are unable or unwilling to return.
If study intervention is permanently discontinued, the participant should, if at all possible, 
remain in the study. See the SoA (Section 1.2) for data to be collected at the time of 
discontinuation of study intervention and follow-up and for any further evaluations that need 
to be completed.

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7.1.1
Liver Chemistry Stopping Criteria
Discontinuation of study intervention for abnormal liver tests is required by the investigator 
when a participant meets one of the conditions outlined below or in the presence of abnormal 
liver chemistries not meeting protocol-specified stopping rules, if the investigator believes that 
it is in best interest of the participant.

ALT and/or AST are > 3 × ULN and TBL > 2 × ULN

ALT and/or AST are > = 5 × ULN for ≥14 consecutive days, at any time after initial 
confirmatory results

ALT and/or AST are > 8 × ULN

ALT or AST > 3 x ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%)

ALT or AST > 3 x ULN and INR > 1.5 (applicable for participants with a baseline INR ≤ 1.1)
Please refer to Appendix E for further instruction on cases of increases in liver biochemistry 
and evaluation of Hy’s Law
7.1.2
Cardiac Stopping Criteria
Discontinuation of study intervention for abnormal cardiac tests is required by the
investigator when a participant meets one of the conditions outlined below:

Average absolute (regardless of baseline value) cardiac QTc interval corrected for heart 
rate by QTcF > 500 msec, or an increase of QTcF > 60 msec above the baseline value, 
confirmed (persistent for ≥ 5 minutes) on repeat triplicate 12-lead ECGs.
Any one of the following:

Tachycardia, defined as resting supine pulse rate > 125 beats per minute persisting for at 
least 10 minutes.

Symptomatic bradycardia, defined as resting supine pulse rate < 40 beats per minute 
while awake, persisting for at least 10 minutes.

Asymptomatic bradycardia, defined as resting supine pulse rate < 30 beats per minute 
while awake persisting for at least 10 minutes.

Hypertension, defined as an increase from baseline in resting supine systolic > 40 mmHg 
or above 180 mmHg and persisting for at least 10 minutes and/or increase from baseline 
in resting supine diastolic BP > 20 mmHg or above 100 mmHg and persisting for at least 
10 minutes.

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7.1.3
Respiratory stopping criteria
Discontinuation of study intervention is required by the investigator when a participant with 
respiratory disease meets the condition below:

Exacerbation of known respiratory disease that requires hospital admission.

Note: If any respiratory problems arise such as ongoing infection (for example, 
bronchitis, bronchiolitis or mild pneumonia, or acute dyspnea due to new onset 
arrhythmia), or change in respiratory medications is needed, to include, starting, or 
an increase in frequency of use of inhaler therapy, it is up to the Investigator to 
determine whether the participant may remain in the study whilst adjusting the 
other therapies or to permanently discontinue the participant from the study 
intervention.
7.2
Participant Discontinuation/Withdrawal from the Study
Discontinuation of the participant from the study by the investigator:

A participant may be discontinued from the study 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 the participant has not been discontinued 
from the study intervention, see Section 7.1.
Voluntary withdrawal from the study by the participant:

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 who wishes to withdraw from the study must be informed by the 
investigator about modified follow-up options (eg, telephone contact, a contact with a 
relative or treating physician, or information from medical records).

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 the participant withdraws from the study, the Sponsor may retain and continue to use 
any samples collected before such a withdrawal of consent for the purposes the 
participant originally consented unless the participant withdraws consent for use of 
samples already collected. If the participant specifically withdraws consent for any use of 
samples, it must be documented in the site study records by the investigator and the 
investigator must inform the Local and Global Study Team. Destruction of any samples 
taken and not yet tested should be carried out in line with documented sample withdrawal 
wishes in conjunction with what was stated in the informed consent and local regulation.

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7.3
Lost to Follow-up
A participant will be considered lost to follow-up if the participant 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 study site for a 
required study visit:

The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible. The participant should be counseled on the importance of maintaining the 
assigned visit schedule. At this time ascertain whether the participant should or wishes to 
or 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 (where possible, 3 telephone calls, texts, 
emails, and if necessary, a certified letter to the participant’s last known mailing address 
or local equivalent methods). These contact attempts should be documented in the 
participant’s medical record.

Should the participant continue to be unreachable, the participant will be considered to 
have been lost to follow-up.
8
STUDY ASSESSMENTS AND PROCEDURES

Study procedures and their timing are summarized in the SoA (Section 1.2). Protocol 
waivers or exemptions are not allowed.

Urgent safety concerns should be discussed with the investigator upon occurrence or 
awareness to determine if the participant should continue or discontinue study 
intervention.

Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct.

All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable.

Procedures conducted as part of the participant’s routine clinical management (eg, blood 
count) and obtained before signing of the ICF may be utilized for screening or baseline 
purposes provided the procedures met the protocol-specified criteria and were performed 
within the time frame defined in the SoA.

Instructions for the collection and handling of HBS will be provided in the study-specific 
laboratory manual. Samples should be stored in a secure storage space with adequate 
measures to protect confidentiality. For further details on handling of HBS see
Appendix C.

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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.
Laboratory and analyte results that could unblind the study will not be reported to 
investigative sites or other blinded personnel until the study has been unblinded.
The approximate amount of blood collected from each participant over the duration of the 
study is around 300ml (approximately 20 tablespoons), and 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 500 mL (approximately 33 tablespoons). 
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with 
the samples.

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8.1
Efficacy Assessments
Planned timepoints for all efficacy assessments are provided in the SoA (Section 1.2).
Laboratory efficacy variables are shown in Table 5.
Table 5
Laboratory Efficacy Variables
Primary endpoint
Secondary endpoints
•
Percent change from baseline of LDL-C at 
Week 12 (in “ideal” scenarios where 
intercurrent events would not occur)
•
Percent change from baseline of LDL-C at 
Week 12 (in “real-world” conditions)
•
Percent change from baseline at Week 12 (in 
“ideal” scenarios) in:

Total cholesterol

HDL-C

Triglycerides

Non-HDL-C

VLDL-C*

ApoA1

ApoB

Lp(a)

Remnant cholesterol*

hsCRP
•
Percent change from baseline at Week 12 (in 
“real-world” conditions) in: 

Total cholesterol

HDL-C

Triglycerides

Non-HDL-C

VLDL-C*

ApoA1

ApoB

Lp(a)

Remnant cholesterol*

hsCRP
* Calculated from standard lipid profile. 
ApoA1 = apolipoprotein A-1; ApoB = apolipoprotein B-100; HDL-C = high-density lipoprotein cholesterol; 
hsCRP = high-sensitivity C-reactive protein; LDL-C = low-density lipoprotein cholesterol;
Lp(a) = lipoprotein (a); VLDL-C = very-low-densitylipoprotein cholesterol.

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8.2
Safety Assessments
Planned time points for all safety assessments are provided in the SoA (Section 1.2).
Immediate safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention.
8.2.1
Physical Examinations
A complete physical examination will be performed and include assessments of the following; 
general appearance, respiratory, cardiovascular, abdomen, skin, head and neck (including ears, 
eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal (including spine and 
extremities), and neurological systems.
A brief physical examination will include, at a minimum, assessments of the skin, lungs, 
cardiovascular system, and abdomen (liver and spleen).
New or worsening abnormalities may qualify as AEs; see Section 8.3 for details
Height will be assessed using locally available tools without the participant wearing shoes. 
Weight will be assessed using the same scale (properly maintained and calibrated), and with 
the participant wearing a similar amount of clothes (eg, underwear only or light indoor 
clothing only) at each time.
Physical examination will be performed at timepoints as specified in the SoA (Section 1.2).
8.2.2
Vital Signs
Vital signs will be performed at timelines as specified in the SoA (Section 1.2). Vital signs will 
be assessed before any interventional study procedures (blood sampling, ECG, IMP 
administration). The participant should be in a resting, seated position for at least 5 minutes 
prior to the collection of vital sign, as follow:

Body temperature (measured in Celsius). Oral measurement is preferred, but other 
methods are acceptable as per local standards of care

Heart (pulse) rate

Respiratory rate

Oxygen saturation (SpO2) measured by pulse oximetry

Blood pressure (systolic and diastolic)
Blood pressure and pulse measurements should be taken by an adequately trained health care 
professional and assessed with a completely automated device (a calibrated 
sphygmomanometer is preferred). If not available, another device calibrated carefully in 

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proportion to a mercury sphygmomanometer should be used. The use of aneroid manometers
should be avoided. An appropriate cuff size must be used to ensure accurate measurement. The 
disappearance of sound (Korotkov Phase V) should be used for the diastolic reading. 
Blood pressure and pulse measurements should be assessed with the participant rested in a
seated position, their back supported and feet on the ground. Three consecutive blood pressure 
and pulse readings should be recorded at intervals of at least 2 minutes. The average of the  
SBP, DBP and pulse readings should be recorded in the eCRF.
8.2.3
Electrocardiograms
12-lead ECG will be performed at timepoints as specified in the SoA (Section 1.2).
All 12-lead ECGs will be obtained in triplicate with no more than a 5-minute interval between 
each reading using a properly maintained and calibrated machine. The mean value from the 
three ECG readings will be recorded in the eCRF. The recordings should be done after the 
participant has been lying down to rest for at least 10 minutes. For participants with 
pacemakers, ECG variables should be read manually. ECGs may also be performed according
to clinical judgment or as indicated based on any symptoms or clinical events (eg, cardiac 
arrhythmia).
The following ECG parameters should be collected: PR interval, RR interval, QRS duration, 
QT and QTcF intervals, and heart rate. An overall evaluation of the ECG results should also be 
performed.
8.2.4
Clinical Safety Laboratory Tests
Blood and urine samples for determination of clinical chemistry, haematology, coagulation, 
and urinalysis will be taken at the visits indicated in the SoA (Section 1.2).
The clinical chemistry, hematology, coagulation, and urinalysis will be performed at a central 
laboratory. Sample tubes and sample sizes will be described in the Laboratory Manual.
Additional safety samples may be collected if clinically indicated at the discretion of the 
investigator.
Drugs of abuse screening will be performed at a central laboratory, unless the investigator 
performs these locally per each study site’s guidelines.
The following laboratory variables will be measured (Table 6).

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Table 6
Laboratory Safety Variables
ALP = alkaline phosphatase; ALT = alanine aminotransferase/transaminase; AST = aspartate 
aminotransferase/transaminase; CRP = C-reactive protein; eGFR = estimated glomerular filtration rate;
FSH = follicle stimulating hormone; GGT = gamma glutamyl transpeptidase; Hb = hemoglobin; HIV = human 
immunodeficiency virus; HBsAg = hepatitis B surface antigen; LH = luteinizing hormone; MCH = mean 
corpuscular hemoglobin; MCHC = mean corpuscular hemoglobin concentration; MCV = mean corpuscular 
volume; RBC = red blood cell.
a Confirmatory serum test analyzed at the central laboratory is indicated if local urine pregnancy test is positive at 
visit 1.
In case a participant shows an AST or ALT ≥3 × ULN together with TBL ≥2 × ULN please 
refer to Appendix E, for further instructions.
Clinical Chemistry

Plasma/Serum
o
Albumin
o
ALP
o
ALT
o
AST
o
Bilirubin, total
o
Bicarbonate
o
Blood urea nitrogen
o
Creatinine
o
GGT
o
High sensitivity CRP
o
Potassium
o
Sodium
o
Total Protein
Endocrinology

Serum
o
FSH (women only, at screening)
o
LH (women only, at screening)
Pregnancy Dipstick Test

Pregnancy test (urine human chorionic 
gonadotropin)a
Viral Serology (screening only)

HIV I

HIV II

HBsAg

Hepatitis C virus antibody
Hematology/Hemostasis/Glycaemic control

Blood
o
Hematocrit
o
Hb
o
Leukocyte count
o
Leukocyte differential count (absolute count)
o
MCV
o
MCH
o
MCHC
o
Platelet count
o
RBC
o
Reticulocyte absolute count
o
Coagulation
o
HbA1C
Urinalysis

Microscopy including white blood cell/RBC and 
casts

Urine
o
Appearance and color
o
Urobilinogen
o
Blood
o
Glucose
o
Ketones
o
Leukocytes
o
Nitrites
o
pH
o
Protein
o
Specific gravity

Urine renal safety biomarkers
o
Albumin
o
Creatinine
o
eGFR
o
Total protein

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8.3
AEs, SAEs, and Other Safety Reporting
The Principal Investigator is responsible for ensuring that all staff involved in the study are 
familiar with the content of this section.
The definitions of an AE or SAE can be found in Appendix B.
Participants (or, when appropriate, a caregiver, surrogate, or the participant’s legally 
authorized representative) will notify the investigator or designees of symptoms. These must 
then be assessed by the investigator and if considered an AE it will be reported by the 
investigator.
The investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE.
8.3.1
Time Period and Frequency for Collecting AE and SAE Information
Adverse Events will be collected from time of first dose, throughout the treatment period, and 
including the follow-up period.
Serious Adverse Events will be recorded from the time of signing of the ICF.
If the investigator becomes aware of an SAE with a suspected causal relationship to the IMP 
that occurs after the end of the clinical study in a treated participant, the investigator shall, 
without undue delay, report the SAE to the Sponsor.
8.3.2
Follow-up of AEs and SAEs
Any AEs that are unresolved at the participant’s last AE assessment in the study are followed 
up by the investigator for as long as medically indicated, but without further recording in the 
eCRF. The Sponsor retains the right to request additional information for any participant with 
ongoing AE(s)/SAE(s) at the end of the study, if judged necessary.
AE variables
The following variables will be collected for each AE:

Adverse Event (verbatim). Note: for COVID-19 related events, the investigator should 
add ‘COVID’ as part of the verbatim term

The date and time when the AE started and stopped

Maximum intensity

Intensity grading: mild, moderate, or severe

Whether the AE is serious or not

Investigator causality rating against the IMP(s) (yes or no)

Action taken with regard to IMP(s)

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
AE caused participant’s withdrawal from the study (yes or no)

Outcome
In addition, the following variables will be collected for SAEs:

Date AE met criteria for SAE

Date investigator became aware of SAE

AE description

AE is serious due to

Date of hospitalization

Date of discharge

Probable cause of death

Date of death

Autopsy performed

Causality assessment in relation to study procedure(s)

Causality assessment to other medication
8.3.3
Causality Collection
The investigator should assess causal relationship between IMP and each AE, and answer 
‘yes’ or ‘no’ to the question ‘Do you consider that there is a reasonable possibility that the 
event may have been caused by the IMP?’
For SAEs causal relationship should also be assessed for other medication and study 
procedures. Note that for SAEs that could be associated with any study procedure the causal 
relationship is implied as ‘yes’.
A guide to the interpretation of the causality question is found in Appendix B.
8.3.4
AEs Based on Examinations and Tests
Deterioration as compared to baseline in protocol-mandated laboratory values and vital signs, 
should only be reported as AEs if they meet any of the following:

Fulfil any of the SAE criteria

Are the reason for discontinuation of the IMP

Are clinically relevant as judged by the investigator (which may include but is not limited 
to consideration as to whether intervention or non-planned visits were required or other 
action was taken with the IMP, eg, dose adjustment or drug interruption).
If deterioration in a laboratory value/vital sign is associated with clinical signs and symptoms, 
the sign or symptom will be reported as an AE and the associated laboratory result/vital sign 

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will be considered as additional information. Wherever possible the reporting investigator 
uses the clinical, rather than the laboratory term (eg, anemia vs low hemoglobin value). In the 
absence of clinical signs or symptoms, clinically relevant deteriorations in non-mandated 
parameters should be reported as AE(s).
Deterioration of a laboratory value, which is unequivocally due to disease progression, should 
not be reported as an AE/SAE.
Any new or aggravated clinically relevant abnormal medical finding at a physical examination 
as compared with the baseline assessment will be reported as an AE unless unequivocally 
related to the DUS.
The results from the protocol mandated laboratory tests and vital signs will be summarized in 
the CSR.
8.3.5
AEs Based on Signs and Symptoms
All signs or symptoms spontaneously reported by the participant or reported in response to the 
open question from the study site staff: ‘Have you had any health problems since the previous 
visit/you were last asked?’, or revealed by observation will be collected and recorded in the 
eCRF.
When collecting AEs, the recording of diagnoses is preferred (when possible) to recording a 
list of signs and symptoms. However, if a diagnosis is known and there are other signs or 
symptoms that are not generally part of the diagnosis, the diagnosis and each sign or symptom 
will be recorded separately.
8.3.6
Hy’s Law
Cases where a participant shows elevations in liver biochemistry may require further 
evaluation, and occurrences of AST or ALT ≥3 × ULN together with TBL ≥2 × ULN may 
need to be reported as SAEs. Please refer to Appendix E for further instruction on cases of 
increases in liver biochemistry and evaluation of Hy’s Law.
8.3.7
Disease Progression
Disease progression can be considered as a worsening of a participant’s condition attributable 
to the disease for which the IMP is being studied. It may be an increase in the severity of the 
DUS and/or increases in the symptoms of the disease. The development of symptoms of DUS 
are those which might be expected to occur as a result of dyslipidemia (eg, increase in blood 
lipid levels) should be considered as disease progression and not an AE. Events, which are 
unequivocally due to disease progression, should not be reported as AEs during the study.

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8.3.8
Disease Under Study
Symptoms of DUS are those which might be expected to occur as a direct result of 
dyslipidemia. Events which are unequivocally due to DUS should not be reported as AEs 
during the study unless they meet SAE criteria or lead to discontinuation of the IMP.
8.3.9
Reporting of SAEs
All SAEs must be reported whether or not considered causally related to the IMP. All SAEs 
will be recorded in the eCRF.
If any SAE occurs during the study, investigators or other site personnel will inform the 
appropriate Sponsor representatives within one day, ie, immediately but no later than 
24 hours of when he or she becomes aware of it.
The designated Sponsor representative will work with the investigator to ensure that all the 
necessary information is provided to the AstraZeneca Patient Safety data entry site within
one calendar day of initial receipt for fatal and life-threatening events and within 5 calendar 
days of initial receipt for all other SAEs.
For fatal or life-threatening AEs where important or relevant information is missing, active 
follow-up will be undertaken immediately. Investigators or other site personnel will inform the 
Sponsor representative of any follow-up information on a previously reported SAE within one 
calendar day, ie, immediately but no later than 24 hours of when he or she becomes aware of 
it.
Once the investigators or other site personnel indicate an AE is serious in the Electronic Data 
Capture (EDC) system, an automated email alert is sent to the designated Sponsor 
representative.
If the EDC system is not available, then the investigator or other study site staff reports the 
SAE via secure method to the appropriate Sponsor representative.
When the EDC is temporarily not accessible, the Sponsor Study Representative should 
confirm that the investigator/site staff enters the SAE in the AstraZeneca EDC when access 
resumes.
For further guidance on the definition of an SAE, see Appendix B.
The reference document for definition of expectedness/listedness is the IB for the AstraZeneca 
IMP.
In the European Union, the Sponsor will comply with safety reporting requirements and 
procedures as described in the European Clinical Trials Regulation (EU) No 536/2014. All 
suspected unexpected serious adverse reactions (SUSARs) to investigational medicinal 
product will be reported to the EudraVigilance database within the required regulatory 
timelines.

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8.3.10
Pregnancy
Participants will be instructed that if they or their partner becomes pregnant during the study 
this should be reported to the investigator. The investigator should also be notified of 
pregnancy occurring during the study but confirmed after completion of the study. In the event 
that a participant’s partner is subsequently found to be pregnant after the participant is 
included in the study, then consent will be sought from the partner (via the participant’s 
request that their partner contact the study site) and, if granted, any pregnancy will be 
followed, and the status of mother and/or child will be reported to the Sponsor after delivery.
8.3.10.1
Maternal Exposure
Females of childbearing potential are not allowed to be included in this study. Should a 
pregnancy still occur, the study intervention should be discontinued immediately, and the 
pregnancy reported to the Sponsor.
Pregnancy itself is not regarded as an AE unless there is a suspicion that the study intervention 
may have interfered with the effectiveness of a contraceptive medication. Congenital 
anomalies/birth defects and spontaneous miscarriages should be reported and handled as 
SAEs. Elective abortions without complications should not be handled as AEs. The outcome 
of all pregnancies (spontaneous miscarriage, elective termination, ectopic pregnancy, normal 
birth or congenital anomaly/birth defect) should be followed up and documented even if the 
participant was discontinued from the study.
If any pregnancy occurs during the study, then the investigator or other site personnel informs 
the appropriate Sponsor representative immediately but no later than 24 hours after he or she 
becomes aware of it.
The designated Sponsor representative works with the investigator to ensure that all relevant 
information is provided to the AstraZeneca Patient Safety data entry site within one or
5 calendar days for pregnancies associated with SAEs (Section 8.3.9) and within 30 days for 
all other pregnancies.
The same timelines apply when outcome information is available.
8.3.10.2
Paternal Exposure
Male participants should refrain from fathering a child or donating sperm during the study and 
for 3 months following the last follow-up visit.
Pregnancy of the participant’s partners is not considered to be an AE. However, the outcome 
of all pregnancies (spontaneous miscarriage, elective termination, ectopic pregnancy, normal
birth or congenital anomaly), occurring from the date of the first dose until 10 months after
the last dose should, if possible, be followed up and documented in the Pregnancy Report 
Form.

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Consent from the pregnant partner must be obtained before the Pregnancy Report Form is 
completed.
8.3.11
Medication Error, Drug Abuse, and Drug Misuse
8.3.11.1
Timelines
If an event of medication error, drug abuse, or drug misuse occurs during the study, then the 
investigator or other site personnel informs the appropriate Sponsor representative within one 
calendar day, ie, immediately but no later than 24 hours of when they become aware of it.
The designated Sponsor representative works with the investigator to ensure that all relevant 
information is completed within one (initial fatal/life-threatening or follow-up fatal/life-
threatening) or 5 (other serious initial and follow-up) calendar days if there is an SAE 
associated with the event of medication error, drug abuse, or misuse (Section 8.3.9) and 
within 30 days for all other events.
8.3.11.2
Medication Error
For the purposes of this clinical study a medication error is an unintended failure or mistake 
in the treatment process for an IMP that either causes harm to the participant or has the 
potential to cause harm to the participant.
The full definition and examples of medication error can be found in Appendix B 4.
8.3.11.3
Drug Abuse
Drug abuse is the persistent or sporadic intentional, non-therapeutic excessive use of IMP for 
a perceived reward or desired non-therapeutic effect.
The full definition and examples of drug abuse can be found in Appendix B 4.
8.3.11.4
Drug Misuse
Drug misuse is the intentional and inappropriate use (by a study participant) of IMP for 
medicinal purposes outside of the authorized product information, or for unauthorized IMPs, 
outside the intended use as specified in the protocol and includes deliberate administration of 
the product by the wrong route.
The full definition and examples of drug misuse can be found in Appendix B 4.
8.3.12
Reporting of Overdose
For this study, any dose of AZD0780 greater than the planned dose within the planned study 
period will be considered an overdose.

An overdose with associated AEs is recorded as the AE diagnoses/symptoms on the 
relevant AE modules in the eCRF and on the Overdose eCRF module.

An overdose without associated symptoms is only reported on the Overdose eCRF 
module.

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If an overdose on an IMP occurs in the course of the study, the investigator or other site 
personnel inform the appropriate Sponsor representative immediately, but no later than 24 
hours of when he or she becomes aware of it.
The designated Sponsor representative works with the investigator to ensure that all relevant 
information is provided to the AstraZeneca Patient Safety data entry site within one or
5 calendar days for overdoses associated with an SAE (Section 8.3.9) and within 30 days for 
all other overdoses.
Refer to Section 6.8 for definition and treatment of overdose.
8.4
Pharmacokinetics
8.4.1
Collection of Samples for Pharmacokinetics
Blood samples will be collected for measurement of plasma concentrations of AZD0780 as 
specified in the SoA (Section 1.2).  On days where PK samples are to be collected the patient 
should refrain from taking the study medication prior to coming to the clinic. The PK samples 
are to be collected prior to administering the study medication at the clinic.
Plasma concentrations will be summarized by treatment (dose level of AZD0780) for each 
sampling time point, using descriptive statistics based on the PK analysis set and included in 
the CSR.
Samples will be collected, labeled, stored, and shipped as detailed in the Laboratory Manual.
PK data from this study, possibly together with data from other studies, may be used for 
population PK/PD analysis. The results of any such modeling activity will be provided in a 
separate report (as an appendix to the CSR or as a stand-alone report).
8.4.2
Determination of Drug Concentration
Samples for determination of drug concentration in plasma will be assayed by Labcorp 
Bioanalytical Services LLC on behalf of the Sponsor, using an appropriately validated 
bioanalytical method. Full details of the analytical method used will be described in a separate 
Bioanalytical Report.
Only samples from participants on active treatment will be analyzed, unless there is a need to 
confirm the correct treatment has been given to study participants.
Incurred sample reproducibility analysis or additional assay development work, if any, will be
performed alongside the bioanalysis of the test samples. The results from the evaluation, if 
performed, will be reported in a separate Bioanalytical Report.
8.5
Pharmacodynamics
8.5.1
Collection of Samples for Pharmacodynamics

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Samples will be collected, labeled, stored, and shipped as detailed in the Laboratory Manual.
Blood samples will be collected for measurement of LDL-C, lipid profile, ApoA1, ApoB, 
Lp(a), hsCRP, and PK profile at the time points specified in the SoA (Table 1).
For storage, re-use, and destruction of samples for PD see Appendix C.
8.6
Optional Genomics Initiative
Collection of optional samples for Genomics Initiative research is also part of this study as 
specified in the SoA and is subject to participant agreement in the optional genetic research 
information ICF.
The blood sample for genetic research will be obtained at Visit 2, subject to participant 
agreement in the optional genetic research information ICF.
Blood samples for DNA isolation will be collected from participants who have consented to 
participate in the genomic analysis component of the study. Participation is optional.
Participants who do not wish to participate in genomic research may still participate in the 
study.
See Appendix D for information regarding the Genomics Initiative genetic samples. Details on 
processes for collection and shipment and destruction of these samples can be found either in 
Appendix D of this protocol or in the Laboratory Manual.
8.7
Biomarkers
8.7.1
Mandatory Biomarker Sample Collection
By consenting to participate in the study the participant consents to the mandatory research 
components of the study.

Samples for biomarker research are required and will be collected from all participants in 
this study as specified in the SoA (Section 1.2).

Samples will be tested for safety, PK/PD, and for exploratory research to evaluate their 
association with the observed clinical responses to AZD0780.
8.7.2
Other Study-related Biomarker Research
Already collected samples may be analyzed on different biomarkers thought to play a role in
dyslipidemia, lipid metabolism, metabolic disorders, and/or ASCVD including, but not limited to, 
blood (plasma and serum) and urine sample analysis to evaluate their association with observed 
clinical responses to study intervention. Targeted and unbiased metabolomic, lipidomic, and/or 
proteomic approaches may be used for PD biomarkers and biomarker research relevant to safety,
tolerability, PK profile, and efficacy related to AZD0780 treatment.
For storage, re-use, and destruction of biomarker samples see Appendix C.

Cli nical St u d y Pr ot oc ol - 3. 0 
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8. 8
I m m u n o ge nicit y Assess me nts
I mm u n o ge nicit y sa m ples are n ot c o llecte d i n t his st u d y.
8. 9
Me dic al
Res o urce Utiliz ati o n a n d He alt h Ec o n o mics
Me dical res o urce utilizati o n a n d heal t h ec o n o mics para m eters are n ot e val uate d i n t his stu d y.
8. 1 0
St u d y P artici p a nt Fee d b ac k Q u esti o n n aire
A st u d y parti ci pa nt fee d bac k q uest i on naire is n ot i ncl u de d i n t his st u d y.
9
S T A TI S TI C A L C O N SI D E R A TI O N S
T he S A P will be fi nalize d pri or t o data base l oc k a n d it will i ncl u de a m o re tec h nical a n d 
detaile d descri pt i on of t he pla n ne d statistical a nal yses. T his sect i on is a s u m mar y of t he 
pl a n ne d statistical a nal yses of t he m ost i m p orta nt e n d p o i nts i ncl u di n g pri mar y a n d ke y 
sec o n dar y e n d p oi nts.
9. 1
St atistic al H y p ot heses
T he pri mar y o bject i ve is t o de m o nstrate s u peri orit y of A Z D 0 7 8 0 c o m pare d t o place b o o n 
L D L -C. T o s u p p ort t he pri mar y  o bjecti ve, t he pri mar y e n d p o i nt is perce nt c ha n ge fr om 
baseli ne of L D L - C at Wee k 1 2. T o str o n gl y c o ntr ol t he famil y wi s e err or rate at t he 0. 0 5 lev el  
( 2-side d), t he al p ha e x pe n dit ure will be allocate d t o test t he f oll owi n g n ull h y p ot heses ( H) f or 
t he pri mar y e nd p oi nt:

H 1: 𝜇A Z D 0 7 8 0
m g = 𝜇pl ac e b o

H 2: 𝜇A Z D 0 7 8 0
m g = 𝜇pl ac e b o

H 3: 𝜇A Z D 0 7 8 0
m g = 𝜇pl ac e b o

H 4: 𝜇A Z D 0 7 8 0
m g = 𝜇pl ac e b o
W here
µ de n otes t he perce nt c ha n ge fr om baseli ne of L D L - C at Wee k
1 2.
A hierarc hical test i n g strate g y ( close d testi n g pr oce d ure) will be e m pl o ye d. H 1 will be teste d 
first usi n g t he f ull test ma ss al p ha. If H 1 is rejecte d, t he n t he f ull test mass will be rec ycle d t o
test H 2. If H 2 is r ejecte d, t he n H 3 will be teste d wit h f ull al p ha, a n d if H 3 is r ejecte d, H 4 will 
be f urt her teste d wit h f ull al p ha. F urt her details of m ulti plicity testi n g are pr o vi de d i n t he 
statistical a nal ysis pla n ( S A P).
9. 2
S a m ple Size Deter mi n ati o n
T he st u d y  will ra n d o mize a p pr o xi matel y 3 7 5 partici pa nts i n or der t o ha ve a p pr o xi matel y 3 2 0
e val ua ble part ici pa nts w h o c o mplete t he 1 2- wee k treat me nt peri o d t o s u p p ort t he e val uat i on of  
t he pri mar y e nd p oi nt (t he disc o nti n uati on rate i s ass u me d t o be a p pr o xi matel y 1 5 %). 
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A Z D 0 7 8 0 - D 7 9 6 0 C 0 0 0 0 6
C O N FI D E N TI A L A N D P R O P RI E T A R Y
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Te m pl ate Versi o n N u m ber 8. 0
P arti cipa nts will be ra n d o mize d i n a 1: 1: 1: 1: 1 ma n ner t o recei ve A Z D 0 7 8 0 
m g, 
m g, 
m g, 
 m g, or c orres p o n di n g place b o.
T he sa m ple size is dri ve n b y  t he o bjecti ve t o assess t he safety a nd t ol era bilit y of A Z D 0 7 8 0. 
T he c h ose n sa m ple size is belie ve d t o be s ufficie nt f or t he creati o n of a r o b ust safety data base.
T he sa m ple size of a p pr o xi matel y 6 4 e val ua ble partici pa nts w h o c o m plete t he 1 2 -wee k 
treat me nt perio d i n eac h ar m will pr o vi de m ore t ha n 9 0 % p o wer f or t he test of eac h d ose of  
A Z D 0 7 8 0 vers us place b o t o detect a differe nce of
i n perce nt c ha n ge fr om baseli ne i n 
L D L - C t o Wee k
1 2. T he calc ulat i ons ass u me S D =  
 a n d a 2-si de d al p ha le vel of 0. 0 5 , a n d 
are base d o n a t -test wit h n or mal a p pr o xi mat i on f or perce nt c ha n ge fr om baseli ne
9. 3
P o p ul ati o ns f or A n al yses
T he f oll owi n g p o p ul at i ons are defi ne d:
T a ble 7
P o p ul ati o ns f or A n al ysis
P o p ul ati o n/ a n al ysis set
Descri pti o n
E nr olle d
All partici pa nts w h o si g n t he I C F.
Ra n d o ml y Assi g ne d t oSt u d y 
Treat me nt Set
All partici pa nts w h o were ra n d o mize d. Par tici pa nts will be a nal yze d 
acc or di n g t o t he treat me nt t o w hic h t he y were ra n d o mize d.
F ull A nal ysis Set
All ra n d o mize d partici pa nts w h o recei ve d at least o ne d ose of st u d y 
i nter ve nti on. Partici pa nts will be i ncl u de d i n t he a nal ysis acc or di n g t o t he 
treat me nt t o w hic h t he y were ra n d o mize d.
Safet y A n al y sis Set
All ra n d o mize d partici pa nts w h o recei ve d at least o ne d ose of st u d y 
i nter ve nti on. Partici pa nts will be i ncl u de d i n t he a nal ysis acc or di n g t o t he
treat me nt t he y act uall y recei ve d.
P K A n al ysis Set
All partici pa nts w h o recei ve d at least o ne d ose of A Z D 0 7 8 0 a n d w h o ha d 
e val ua ble P K data. Par tici pa nts will be i ncl u de d i n t he a nal ysis acc or di n g t o 
t he treat me nt t he y act uall y recei ve d.
I C F = i nf or me d co nse nt f orm; P K = p har mac o ki netic(s).
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9.4
Statistical Analyses
9.4.1
General Considerations
Separate randomization lists will be generated for Japan and for the rest of the world. No 
stratification factor will be used for statistical analysis. 
Statistical tests will be performed using 2-sided tests at the 5% significance level, if not 
explicitly specified otherwise.
The baseline value is defined as the last non-missing value prior to the administration of the 
first dose of study intervention unless otherwise stated.
Participant disposition will be summarized and will include the following information (also 
including the percentage for each category): number of participants randomized, number of 
participants who received treatment, number of participants who did not receive any 
treatment, number of participants who completed treatment, number of participants 
completing the study and the number of participants who were withdrawn (including reasons 
for withdrawal). Participants and/or data excluded from the analysis set will be listed 
including the reason for exclusion.
Demographic variables (age, gender, race, ethnicity, height, weight and BMI) will be listed by 
participant. Demographic characteristics (age, gender, race and ethnicity) and participant 
characteristics (height, weight, and BMI) will be summarized by treatment (dose level of 
AZD0780 and placebo) for all randomized participants.
A more comprehensive description of statistical procedures and assessments will be available 
in the SAP.
9.4.2
Efficacy
Unless otherwise specified, participants will be analyzed according to their randomized IMP 
assignment, irrespective of the treatment they actually received. Participants who were 
randomized and received at least 1 dose of study intervention will be included in the FAS
population. The FAS will be considered the primary analysis set for the primary and 
secondary endpoints unless otherwise specified.
Efficacy data will be listed for each participant and summarized descriptively (including, but 
not limited to, mean, SD, minimum, median, maximum; geometric mean and geometric 
coefficient of variation will be presented where appropriate) by treatment and time point/visit. 
Figures of the mean response (absolute change from baseline and/or percent change from 
baseline where appropriate) may be used to visualize the average PD response over time.
Further details for analyses of efficacy endpoints will be found in the SAP.

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9. 4. 2. 1
Pri m ar y E n d p oi nt(s)
T he pri mar y e n d p o i nt is perce nt c ha n ge fr om baseli ne of L D L -C at Wee k 1 2. T his will be 
assesse d f or eac h d ose of A Z D 0 7 8 0 vers us place b o. T he h y p ot hetical est i ma n d will be use d 
f or t his e n d p o i nt. Wit h t he h y p ot hetical est i ma n d, L D L -C meas ure me nts ta ke n after t he 
occ urre nce of i nterc urre nt e ve nts w o ul d n ot be use d f or effect esti mat i on. M ore details o n 
esti ma n d are pr o vi de d i n Sect i on 3.
T he s u m mar y meas ure f or t he pri mar y e n d p o i nt will be least s q uares mea n of perce nt c ha n ge 
fr om baseli ne o f L D L -C at Wee k 1 2. T he pri mar y  e n d p oi nt will be a nal yze d usi n g a M M R M 
base d o n t he F A S p o p ulati o n. T he m o del will i ncl u de t he fi xe d effects of baseli ne, treat me nt, 
visit, a n d treat me nt - b y-visit i nteracti o n, a n d t he ra n d o m effect (ra n d o m i nterce pt) of 
parti ci pa nt. T he Restricte d Ma xi m u m Li keli h o o d esti mat i on a p pr oac h will be use d wit h a 
c o mp o u n d s y m metr y c o varia nce str uct ure f or re peate d meas ures. T he treat me nt effects will
be s u m marize d b y t he differe nce i n least s q uares mea ns, 9 5 % c o nfi de nce i nter val, a n d p -
val ue.
T he hierarc hical testi n g strate g y will be e m pl o ye d t o str o n gl y c o ntr ol t he famil y wise err or rate 
at t he 0. 0 5 le vel ( 2 -side d), as descri be d i n Sect i on 9. 1.
9. 4. 2. 2
Sec o n d ar y E n d p oi nt(s)
F or sec o n dar y efficac y e n d p o i nts, t he statistical a nal yses will i n ge neral c o nsist of t he 
f oll owi n g 4 pair wise treat me nt c o mparis o ns:

C o m paris o n of A Z D 0 7 8 0
m g vers us pl ace b o

C o m paris o n of A Z D 0 7 8 0
m g vers us place b o

C o m paris o n of A Z D 0 7 8 0
m g vers us place b o

C o m paris o n of A Z D 0 7 8 0
m g vers us place b o
T he treat me nt p olic y esti ma n d will be use d f or t he sec o n dar y e n d p o i nt t he perce nt c ha n ge 
fr om baseli ne o f L D L -C at Wee k 1 2 (i n “real-w orl d ” c o n ditio n s). Wit h t he treat me nt p olic y 
esti ma n d, L D L -C assess me nts are use d f or treat me nt effect esti mat i on re gar dless of t he 
occ urre nce of i nterc urre nt e ve nts . Details o n t he h a n dli n g of missi n g data a n d will be 
descri be d i n S A P. P arti ci pa nts will be a nal yze d acc or di n g t o t heir ra n d o mize d I M P 
assi g n me nt, irres pect i ve of t he treat me nt t he y act uall y recei ve d. T he s u m mar y meas ure f or 
t his sec o n dar y e n d p oi nt will be least s q uares mea n of perce nt c ha n ge fr o m baseli ne of L D L - C
at Wee k
1 2. T he a nal ysis will be t he sa me as f or t he pri mar y e n d p oi nt. T he sa me m ult i plicity 
a djust m e nt met h o d as f or t he pri mar y e n d p o i nt will be a p plie d t o t his sec o n dar y e n d p oi nt for 
c o mparis o n p ur p oses.
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Other secondary endpoints include:

Percent change from baseline to Week 12 in:

Non-HDL-C

VLDL-C (Calculated from standard lipid profile)

ApoA1

ApoB

Total cholesterol

HDL-C

Triglycerides

Lp(a)

Remnant cholesterol (Calculated from standard lipid profile)

hsCRP
The percent change from baseline of these parameters at Week 12 will be estimated under 
both “ideal” scenarios in which intercurrent events would not occur (i.e., hypothetical 
strategy) and “real-world” conditions (i.e., treatment policy strategy). Details on the handling 
of missing data will be described in SAP.
These endpoints will be analyzed using MMRM based on the FAS. The model will include
the fixed effects of baseline, treatment, visit, and treatment-by-visit interaction, and the 
random effect (random intercept) of participant. Restricted Maximum Likelihood will be used 
with a compound symmetry covariance structure for repeated measures. Treatment effects 
will be summarized by the difference in lsmeans, 95% confidence interval, and p-value. 
Multiplicity adjustment will not be applied to these endpoints.
9.4.2.3
Exploratory Endpoints
The analysis of the exploratory objectives, where required, may be presented in the SAP or a 
separate exploratory analysis plan.
9.4.3
Safety
Safety data will be summarized descriptively and will not be formally tested.
Safety data will be presented in the data listings.
Adverse events will be summarized by PT and SOC using MedDRA vocabulary.
Furthermore, listings of SAEs and AEs that led to withdrawal will be made and the number of 
participants who had any AE, SAEs, AEs that led to withdrawal, and AEs with severe
intensity will be summarized.
Tabulations and listings of data for vital signs, clinical laboratory tests be presented. Results 
from safety ECGs will only be listed. Any new or aggravated clinically relevant abnormal 

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medical physical examination finding compared to the baseline assessment will be reported
as an AE.
Out-of-range values for safety laboratory will be flagged in individual listings as well as
summarized descriptively.
Safety analyses will be performed using the safety analysis set unless otherwise specified. 
Details of safety analyses will be provided in the SAP.
9.4.4
Other Analyses
Pharmacokinetics
One secondary objective is to assess the PK of AZD0780.
PK analyses will be based on the PK analysis set unless otherwise specified.
Plasma concentration data of AZD0780 will be summarized by treatment (dose level of AZD0780) 
for each sampling timepoint using descriptive statistics.
If data permits a population PK model may be developed, possibly with the support of PK data 
from other studies, using nonlinear mixed effects regression analysis in NONMEM.
All PK modeling will be described in a separate data analysis plan. Moreover, the results of any
such modeling will be provided in a separate population PK report (as an appendix to the CSR or 
as a stand-alone report).
9.5
Interim Analyses
The Sponsor will potentially conduct an interim analysis with the purpose of informing further 
development of the clinical programme, including but not limited to dose selection for Phase 3. The
interim analysis will be performed when at least 175 randomized participants have completed 12 
weeks of treatment. An Unblinded Review Committee (URC) will review the interim analysis. The 
outcome of the interim analysis will have no impact on study conduct. 
The unblinded interim analysis will be conducted by an independent team who are not involved in 
the conduct of the study. The members who will review the results from the interim analysis will 
be described in relevant charter and/or the study integrity plan. . All necessary steps will be taken 
to ensure the integrity of the trial by keeping the study team blinded throughout the study. 
Details on the planned interim analysis will be prospectively described in relevant charter and/or 
SAP. 
9.6
Data Monitoring Committee
If an interim analysis is performed, an Unblinded Review Committee will be used in this study.
For details on the Unblinded Review Committee, refer to Appendix A5.

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10
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS

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Appendix A
Regulatory, Ethical, and Study Oversight Considerations
A 1
Regulatory and Ethical Considerations

This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki as amended at 64th WMA General Assembly, Fortaleza, 
Brazil, October 2013 and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines

Applicable ICH GCP Guidelines

Applicable laws and regulations

The protocol, revised protocol, ICF, IB, and other relevant documents (eg, 
advertisements) must be submitted to an IRB/IEC by the investigator and reviewed and 
approved by the IRB/IEC before the study is initiated.

Any revised protocol will require IRB/IEC and applicable Regulatory Authority approval 
before implementation of changes made to the study design, except for changes necessary 
to eliminate an immediate hazard to study participants.

The Sponsor will be responsible for obtaining the required authorizations to conduct the 
study from the concerned Regulatory Authority. This responsibility may be delegated to a 
CRO, but the accountability remains with the Sponsor.

The investigator will be responsible for providing oversight of the conduct of the study at 
the site and adherence to requirements of 21 CFR 312.120, ICH guidelines, the IRB/IEC, 
European Regulation 536/2014 for clinical studies (if applicable), European Medical 
Device Regulation 2017/745 for clinical device research (if applicable), and all other 
applicable local regulations.
Regulatory Reporting Requirements for SAEs

Prompt notification by the investigator to the Sponsor of an SAE 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.

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, IRB/IEC, and investigators.

For all studies except those utilizing medical devices, investigator safety reports must be 
prepared for suspected unexpected serious adverse reactions according to local regulatory 
requirements and sponsor policy and forwarded to investigators as necessary.

Adherence to European Medical Device Regulation 2017/745 for clinical device research 
(if applicable), and all other applicable local regulations

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
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.
Regulatory Reporting Requirements for Serious Breaches

Prompt notification by the investigator to the Sponsor of any (potential) serious breach of 
the protocol or regulations is essential so that legal and ethical obligations are met.

A ‘serious breach’ means a breach likely to affect to a significant degree the safety 
and rights of a participant or the reliability and robustness of the data generated in the 
clinical study.

If any (potential) serious breach occurs in the course of the study, investigators or other 
site personnel will inform the appropriate Sponsor representative immediately after he or 
she becomes aware of it.

In certain regions/countries, the Sponsor has a legal responsibility to notify both the local 
regulatory authority and other regulatory agencies about such breaches.

The Sponsor will comply with country-specific regulatory requirements relating to 
serious breach reporting to the regulatory authority, IRB/IEC, and investigators. If 
EU CT Regulation 536/2014 applies, the Sponsor is required to enter details of 
serious breaches into the European Medicines Agency (EMA) Clinical Trial 
Information System (CTIS). It is important to note that redacted versions of serious 
breach reports will be available to the public via CTIS.

The investigator should have a process in place to ensure that:
o
The site staff or service providers delegated by the investigator/institution are 
able to identify the occurrence of a (potential) serious breach

A (potential) serious breach is promptly reported to the Sponsor or delegated party, 
through the contacts (email address or telephone number) provided by the Sponsor.
A 2
Financial Disclosure
Investigators and sub-investigators will provide the Sponsor with sufficient, accurate financial 
information as requested to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the study and for one 
year after completion of the study.

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A 3
Informed Consent Process

The investigator or their representative will explain the nature of the study to the 
participant or their legally authorized representative and answer all questions regarding 
the study.

Participants must be informed that their participation is voluntary, and they are free to 
refuse to participate and may withdraw their consent at any time and for any reason
during the study. Participants will be required to sign a statement of informed consent that 
meets the requirements of 21 CFR 50, local regulations, ICH guidelines, privacy and data 
protection requirements, where applicable, and the IRB/IEC or study center.

The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICF.

If new information requires changes to the ICF, consider if participants must be
re-consented and if so, this must be to the most current version of the ICF(s) during their 
participation in the study.

A copy of the ICF(s) must be provided to the participant or the participant’s legally 
authorized representative.
Participants who are rescreened are required to sign another ICF.
The ICF will contain a separate section that addresses and documents the collection and use of 
any mandatory and/or optional HBS. The investigator or authorized designee will explain to 
each participant the objectives of the analysis to be done on the samples and any potential 
future use. Participants will be told that they are free to refuse to participate in any optional 
samples or the future use, and may withdraw their consent at any time and for any reason 
during the retention period.
A 4
Data Protection

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 participant must be informed that their personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure and use of 
their data must also be explained to the participant in the informed consent.

The participant must be informed that their 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.

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
The participant must be informed that data will be collected only for the business needs. 
We will only collect and use the minimum amount of personal data to support our 
business activities and will not make personal data available to anyone (including internal 
staff) who is not authorized or does not have a business need to know the information.

The participant must be informed that in some cases their data may be pseudonymized. 
The General Data Protection Regulation defines pseudonymization as the processing of 
personal data in such a way that the personal data can no longer be attributed to a specific 
individual without the use of additional information, provided that such additional 
information is kept separately and protected by technical and organizational measures to 
ensure that the personal data are not attributed to an identified or identifiable natural 
person.
A 5
Committees Structure
If an interim analysis is performed, an Unblinded data Review Committee (URC) will be used in 
this study.
Unblinded Review Committee:  A URC consisting of a limited number of sponsor personnel will 
be formed to review data for an interim analysis should it be performed, with the purpose of 
informing further development of the clinical programme, including but not limited to dose 
selection phase 3. The URC will review the risk/benefit profile and make recommendations on the 
dose for phase 3.
A 6
Dissemination of Clinical Study Data
Any results, both technical and lay summaries for this trial, will be submitted to EU CTIS 
within a year from global End of Trial Date in all participating countries, due to scientific 
reasons, as otherwise statistical analysis is not relevant.
A description of this clinical study will be available on 
http://astrazenecagrouptrials.pharmacm.com and http://www.clinicaltrials.gov as will the 
summary of the study results when they are available. The clinical study and/or summary of 
study results may also be available on other websites according to the regulations of the 
countries in which the study is conducted.
A 7
Data Quality Assurance

All participant data relating to the study will be recorded on eCRF unless transmitted to 
the Sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by electronically 
signing the eCRF.

The investigator must maintain accurate documentation (source data) that supports the 

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information entered in the eCRF.

The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.

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 included in the 
Monitoring Plan.

The Sponsor or designee is responsible for medical oversight throughout the conduct of 
the study which includes clinical reviews of study data in accordance with the currently 
approved protocol. Monitoring details describing clinical reviews of study data from a 
medical perspective are included in more detail in the Monitoring Plan.

The Sponsor or designee is responsible for the data management of this study including 
quality checking of the data.

The Sponsor assumes accountability for actions delegated to other individuals (eg, 
CROs).

Study monitors will perform ongoing source data verification as per the 
Monitoring Plan(s) to confirm that data entered into the eCRF by authorized site
personnel are accurate, complete, and verifiable 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.

Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the investigator for 25 years after study archiving or as required by 
local regulations, according to the AstraZeneca Global retention and Disposal (GRAD) 
Schedule. No records may be destroyed during the retention period without the written 
approval of the Sponsor. No records may be transferred to another location or party 
without written notification to the Sponsor.
A 8
Source Documents

Source documents provide evidence for the existence of the participant and substantiate 
the integrity of the data collected. Source documents are filed at the investigator’s site.

Data entered in the eCRF that are transcribed from source documents must be consistent 
with the source documents or the discrepancies must be explained. The investigator may 
need to request previous medical records or transfer records, depending on the study. 
Also, current medical records must be available.

Definition of what constitutes source data and its origin can be found in the Monitoring 
Plan.

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A 9
Study and Site Start and Closure
The study start date is the date on which the clinical study will be open for recruitment of 
participants.
The first act of recruitment is the first site open and will be the study start date.
The Sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the Sponsor or the investigator may include but 
are not limited to:

Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the Sponsor’s procedures, or GCP guidelines

Inadequate recruitment of participants by the investigator

Discontinuation of further study intervention development
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
investigators, the IRBs/IECs, 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.
A 10
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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Appendix B
AEs: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting
B 1
Definition of AEs
An AE is the development of any untoward medical occurrence in a patient or clinical study 
participant administered a medicinal product, and which does not necessarily have a causal 
relationship with this treatment. An AE can therefore be any unfavorable and unintended sign 
(eg, an abnormal laboratory finding), symptom (for example nausea, chest pain), or disease 
temporally associated with the use of a medicinal product, whether it’s considered related to 
the medicinal product.
The term AE is used to include both serious and non-serious AEs and a deterioration of a pre-
existing medical occurrence. An AE may occur at any time, including run-in or washout 
periods, even if no study intervention has been administered.
B 2
Definition of SAEs
An SAE is an AE occurring during any study phase (ie, run-in, treatment, washout, 
follow-up), that fulfils one or more of the following criteria:

Results in death.

Is immediately life-threatening.

Requires in-patient hospitalization or prolongation of existing hospitalization.

Results in persistent or significant disability or incapacity.

Is a congenital anomaly or birth defect.

Is an important medical event that may jeopardize the participant or may require medical 
treatment to prevent one of the outcomes listed above.
Adverse Events for malignant tumors reported during a study should generally be assessed 
as SAEs. If no other seriousness criteria apply, the ‘Important Medical Event’ criterion should 
be used. In certain situations, however, medical judgment on an individual event basis should 
be applied to clarify that the malignant tumor event should be assessed and reported as a
non-SAE. For example, if the tumor is included as medical history and progression occurs 
during the study, but the progression does not change treatment and/or prognosis of the 
malignant tumor, the AE may not fulfil the attributes for being assessed as serious, although 
reporting of the progression of the malignant tumor as an AE is valid and should occur. Also, 
some types of malignant tumors, which do not spread remotely after a routine treatment that 
does not require hospitalization, may be assessed as non-serious; examples in adults include 
Stage 1 basal cell carcinoma and Stage 1A1 cervical cancer removed via cone biopsy.

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Life-threatening
‘Life-threatening’ means that the participant was at immediate risk of death from the AE as it 
occurred, or it is suspected that use or continued use of the medicinal product would result in 
the participant’s death. ‘Life-threatening’ does not mean that had an AE occurred in a more 
severe form it might have caused death (eg, hepatitis that resolved without hepatic failure).
Hospitalization
Outpatient treatment in an emergency room is not in itself a SAE, although the reasons for it 
may be (eg, bronchospasm, laryngeal oedema). Hospital admissions and/or surgical operations 
planned before or during a study are not considered AEs if the illness or disease existed before 
the participant was enrolled in the study, provided that it did not deteriorate in an unexpected 
way during the study.
Important Medical Event or Medical Treatment
Medical and scientific judgment should be exercised in deciding whether a case is serious in 
situations where important medical events may not be immediately life threatening or result in 
death, hospitalization, disability, or incapacity but may jeopardize the participant or may 
require medical treatment to prevent one or more outcomes listed in the definition of serious. 
These should usually be considered as serious.
Simply stopping the suspect drug does not mean that it is an important medical event; medical 
judgment must be used. The following are examples of an Important Medical Event:

Angioedema not severe enough to require intubation but requiring IV hydrocortisone 
treatment.

Hepatotoxicity caused by paracetamol (acetaminophen) overdose requiring treatment with 
N-acetylcysteine

Intensive treatment in an ER or at home for allergic bronchospasm

Blood dyscrasias (eg, neutropenia or anemia requiring blood transfusion, etc.) or 
convulsions that do not result in hospitalization

Development of drug dependency or drug abuse
Intensity Rating Scale

Mild (awareness of sign or symptom, but easily tolerated)

Moderate (discomfort sufficient to cause interference with normal activities)

Severe (incapacitating, with inability to perform normal activities)
It is important to distinguish between serious and severe AEs. Severity is a measure of 
intensity whereas seriousness is defined by the criteria in Appendix B 2. An AE of severe
intensity need not necessarily be considered serious. For example, nausea that persists for 

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several hours may be considered severe nausea, but not an SAE unless it meets the criteria 
shown in Appendix B 2. On the other hand, a stroke that results in only a limited degree of 
disability may be considered a mild stroke but would be an SAE when it satisfies the criteria 
shown in Appendix B 2.
B 3
A Guide to Interpreting the Causality Question
When assessing causality consider the following factors when deciding if there is a 
‘reasonable possibility’ that an AE may have been caused by the medicinal product.

Time Course. Exposure to suspect drug. Has the participant received the suspect drug? 
Did the AE occur in a reasonable temporal relationship to the administration of the 
suspect drug?

Consistency with known drug profile. Was the AE consistent with the previous 
knowledge of the suspect drug (pharmacology and toxicology) or drugs of the same 
pharmacological class? Or could the AE be anticipated from its pharmacological 
properties?

De-challenge experience. Did the AE resolve or improve on stopping or reducing the dose 
of the suspect drug?

No alternative cause. The AE cannot be reasonably explained by another etiology such as 
the underlying disease, other drugs, other host, or environmental factors.

Re-challenge experience. Did the AE reoccur if the suspected drug was reintroduced after 
having been stopped? The Sponsor would not normally recommend or support a
re-challenge.

Laboratory tests. A specific laboratory investigation (if performed) has confirmed the 
relationship.
In difficult cases, other factors could be considered such as:

Is this a recognized feature of overdose of the drug?

Is there a known mechanism?
Causality of ‘related’ is made if following a review of the relevant data, there is evidence for a 
‘reasonable possibility’ of a causal relationship for the individual case. The expression 
‘reasonable possibility’ of a causal relationship is meant to convey, in general, that there are 
facts (evidence) or arguments to suggest a causal relationship.
The causality assessment is performed based on the available data including enough information
to make an informed judgment. With no available facts or arguments to suggest a causal
relationship, the event(s) will be assessed as ‘not related’.
Causal relationship in cases where the DUS has deteriorated due to lack of effect should be 

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classified as ‘no reasonable possibility’.
B 4
Medication Error, Drug Abuse, and Drug Misuse
Medication Error
For the purposes of this clinical study a medication error is an unintended failure or mistake 
in the treatment process for an IMP or Sponsor NIMP that either causes harm to the 
participant or has the potential to cause harm to the participant.
A medication error is not lack of efficacy of the drug, but rather a human or process related 
failure while the drug is in control of the study site staff or participant.
Medication error includes situations where an error:

Occurred

Was identified and participant received the drug

Did not occur, but circumstances were recognized that could have led to an error
Examples of events to be reported in clinical studies as medication errors:

Drug name confusion

Dispensing error, eg, medication prepared incorrectly, even if it was not actually given to 
the participant

Drug not administered as indicated, eg, wrong route or wrong site of administration

Drug not taken as indicated, eg, tablet dissolved in water when it should be taken as a 
solid tablet

Drug not stored as instructed, eg, kept in the refrigerator when it should be at room 
temperature

Wrong participant received the medication (excluding IRT/RTSM errors)

Wrong drug administered to participant (excluding IRT/RTSM errors)
Examples of events that do not require reporting as medication errors in clinical studies:

Errors related to or resulting from IRT/RTSM - including those which led to one of the 
above listed events that would otherwise have been a medication error

Participant accidentally missed drug dose(s), eg, forgot to take medication

Accidental overdose (will be captured as an overdose)

Participant failed to return unused medication or empty packaging
Medication errors are not regarded as AEs but AEs may occur as a consequence of the 
medication error.

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Drug Abuse
For the purpose of this study, drug abuse is defined as the persistent or sporadic intentional, 
non-therapeutic excessive use of IMP or Sponsor NIMP for a perceived reward or desired 
non-therapeutic effect.
Any events of drug abuse, with or without associated AEs, are to be captured and forwarded to 
the Data Entry Site (DES) using the Drug Abuse Report Form. This form should be used both 
if the drug abuse happened in a study participant or if the drug abuse involves a person not 
enrolled in the study (such as a relative of the study participant).
Examples of drug abuse include but are not limited to:

The drug is used with the intent of getting a perceived reward (by the study participant 
or a person not enrolled in the study)

The drug in the form of a tablet is crushed and injected or snorted with the intent of 
getting high
Drug Misuse
Drug misuse is the intentional and inappropriate use (by a study participant) of IMP or 
Sponsor NIMP for medicinal purposes outside of the authorized product information, or for 
unauthorized IMPs or Sponsor NIMPs, outside the intended use as specified in the protocol 
and includes deliberate administration of the product by the wrong route.
Events of drug misuse, with or without associated AEs, are to be captured and forwarded to 
the DES using the Drug Misuse Report Form. This form should be used both if the drug 
misuse happened in a study participant or if the drug misuse regards a person not enrolled in 
the study (such as a relative of the study participant).
Examples of drug misuse include but are not limited to:

The drug is used with the intention to cause an effect in another person

The drug is sold to other people for recreational purposes

The drug is used to facilitate assault in another person

The drug is deliberately administered by the wrong route

The drug is split in half because it is easier to swallow, when it is stated in the protocol 
that it must be swallowed whole

Only half the dose is taken because the study participant feels that he/she is feeling 
better when not taking the whole dose

Someone who is not enrolled in the study intentionally takes the drug.

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Appendix C
Handling of Human Biological Samples
C 1
Chain of Custody
A full chain of custody is maintained for all samples throughout their lifecycle.
The investigator at each center keeps full traceability of collected biological samples from the 
participants while in storage at the center until shipment or disposal (where appropriate) and 
records relevant processing information related to the samples whilst at the site.
The sample receiver keeps full traceability of the samples while in storage and during use until 
used or disposed of or until further shipment, and keeps record of receipt of arrival and
onward shipment or disposal.
The Sponsor or delegated representatives will keep oversight of the entire life cycle through 
internal procedures, monitoring of study sites, auditing or process checks, and contractual 
requirements of external laboratory providers.
Samples retained for further use will be stored in the Sponsor-assigned biobanks or other 
sample archive facilities and will be tracked by the appropriate Sponsor team for the 
remainder of the sample life cycle.
If required, the Sponsor will ensure that remaining biological samples are returned to the site 
according to local regulations or at the end of the retention period, whichever is the sooner.
C 2
Withdrawal of Informed Consent for Donated Biological Samples
AstraZeneca ensures that biological samples are returned to the source or destroyed at the end
of a specified period as described in the informed consent.
If a participant withdraws consent to the use of donated biological samples, the samples will 
be disposed of/destroyed/repatriated, and the action documented. If samples are already 
analyzed, the Sponsor is not obliged to destroy the results of this research.
Following withdrawal of consent for biological samples, further study participation should be 
considered in relation to the withdrawal processes outlined in the informed consent.
The Investigator:

Ensures the participant’s withdrawal of informed consent to the use of donated samples is 
highlighted immediately to the Sponsor or delegate.

Ensures that relevant human biological samples from that participant, if stored at the 
study site, are immediately identified, disposed of as appropriate, and the action 
documented.

Ensures that the participant and the Sponsor are informed about the sample disposal.
The Sponsor ensures the organization(s) holding the samples is/are informed about the withdrawn

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consent immediately and that samples are disposed of or repatriated as appropriate, and the action 
is documented, and the study site is notified.
C 3
International Air Transport Association Guidance Document 62nd
edition
LABELING AND SHIPMENT OF BIOHAZARD SAMPLES
The International Air Transport Association (IATA) 
(https://www.iata.org/whatwedo/cargo/dgr/Pages/download.aspx) classifies infectious 
substances into 3 categories: Category A, Category B, or Exempt
Category A Infectious Substances are infectious substances in a form that, when exposure to 
it occurs, is capable of causing permanent disability, life-threatening or fatal disease in 
otherwise healthy humans or animals.
Category A Pathogens are, eg, Ebola, Lassa fever virus. Infectious substances meeting these 
criteria which cause disease in humans or both in humans and animals must be assigned to 
UN 2814. Infectious substances which cause disease only in animals must be assigned to
UN 2900.
Category B Infectious Substances are infectious substances that do not meet the criteria for 
inclusion in Category A. Category B pathogens are, eg, Hepatitis A, C, D, and E viruses. They 
are assigned the following UN number and proper shipping name:

UN 3373 – Biological Substance, Category B

Are to be packed in accordance with UN 3373 and IATA 650
Exempt Substances are substances which do not contain infectious substances, or substances 
which are unlikely to cause disease in humans or animals, are not subject to these regulations 
unless they meet the criteria for inclusion in another class.

Clinical study samples will fall into Category B or exempt under IATA regulations.

Clinical study samples will routinely be packed and transported at ambient temperature in 
IATA 650 compliant packaging (https://www.iata.org/whatwedo/cargo/dgr/Documents/DGR-
60-EN-PI650.pdf)

Biological samples transported in dry ice require additional dangerous goods specification 
for the dry ice content.

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Appendix D
Optional Genomics Initiative Sample
D 1
Use/Analysis of DNA

AstraZeneca intends to collect and store DNA for genetic research to explore how genetic 
variations may affect clinical parameters, risk and prognosis of diseases, and the response to 
medications. 

This genetic research may lead to better understanding of diseases, better diagnosis of diseases 
or other improvements in health care and to the discovery of new diagnostics, treatments or 
medications. Therefore, where local regulations and IRB/IEC allow, a blood sample will be 
collected for DNA analysis from consenting participants.

This optional genetic research may consist of the analysis of the structure of the participant´s 
DNA, ie, the entire genome. 

The results of genetic analyses may be reported in a separate study summary.

AstraZeneca will store the DNA samples in a secure storage space with adequate measures to 
protect confidentiality.
D 2
Genetic Research Plan and Procedures
Selection of Genetic Research Population
All eligible adult participants will be asked to participate in this genetic research. Participation 
is voluntary and if a participant declines to participate there will be no penalty or loss of 
benefit. The participant will not be excluded from any aspect of the main study.
Inclusion Criteria
For inclusion in this genetic research, participants must fulfil all of the inclusion criteria 
described in the main body of the protocol and: Provide informed consent for the Genomics 
Initiative sampling and analyses.
Exclusion Criteria

Exclusion from this genomic research may be for any of the exclusion criteria specified in
the main study or any of the following:
-
Previous allogeneic bone marrow transplant
-
Non-leukocyte depleted whole blood transfusion in 120 days of genetic sample collection
Healthy Volunteers and paediatric patient samples will not be collected for the Genomics 
Initiative.

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Withdrawal of Consent for Genetic Research

Participants may withdraw from this genomic research at any time, independent of any 
decision concerning participation in other aspects of the main study. Voluntary 
withdrawal will not prejudice further treatment. Procedures for withdrawal are outlined in 
Section 7.2 of the main protocol and Appendix C2.
Collection of Samples for Genetic Research

The optional blood sample for this genetic research will be obtained from the 
participants at Visit 2 after randomization. Although DNA is stable, early sample
collection is preferred to avoid introducing bias through excluding participants who may 
withdraw due to an AE. If for any reason the sample is not drawn at Visit 2, it may be 
taken at any visit until the last study visit. Only one sample should be collected per 
participant for genetics research during the study, subject to consent.
Coding and Storage of DNA Samples
The processes adopted for the coding and storage of samples for genetic analysis are 
important to maintain participant confidentiality. Samples will be stored for a maximum of 
15 years from the date of last participant last visit, after which they will be destroyed. DNA
is a finite resource that will be used up during analyses. Samples will be stored and used until
no further analyses are possible or the maximum storage time has been reached.

An additional second code will be assigned to the samples either before or at the time of 
sample processing (DNA extraction), replacing the information on the sample tube. 
Thereafter, the sample will be identifiable only by the second, unique number. This 
number is used to identify the sample and corresponding data at the Sponsor genetics 
laboratories, or at the designated organization. No personal details identifying the
individual will be available to any person (AstraZeneca employee or designated 
organizations working with the DNA).

The link between the participant enrollment/randomization code and the second number 
will be maintained and stored in a secure environment, with restricted access at the 
AstraZeneca or designated organizations. The link will be used to identify the relevant 
samples for analysis, facilitate correlation of genotypic results with clinical data, allow 
regulatory audit, and permit tracing of samples for destruction in the case of withdrawal 
of consent.
Ethical and Regulatory Requirements

The principles for ethical and regulatory requirements for the study, including this 
genomics research component, are outlined in Appendix A.

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Informed Consent

The genetic component of this study is optional and the participant may participate in 
other components of the main study without participating in this genetic component. To 
participate in the genetic component of the study the participant must sign and date both 
the consent form for the main study and the addendum for the Genomics Initiative 
component of the study. Copies of both signed and dated consent forms must be given to 
the participant and the originals filed at the study center. The Principal Investigator(s) is
responsible for ensuring that consent is given freely, and that the participant understands 
that they may freely withdraw from the genetic aspect of the study at any time.
Participant Data Protection

AstraZeneca will not provide individual genotype results to participants, any insurance 
company, any employer, their family members, general physician unless required to do so by 
law.

Extra precautions are taken to preserve confidentiality and prevent genetic data being linked 
to the identity of the participant. In exceptional circumstances, however, certain individuals 
might see both the genetic data and the personal identifiers of a participant. For example, in 
the case of a medical emergency, an AstraZeneca Physician or an investigator might know a 
participant’s identity and also have access to his or her genetic data. Regulatory authorities 
may require access to the relevant files, though the participant’s medical information and the 
genetic files would remain physically separate.
Data management

Any genetic data generated in this study will be stored at a secure system at the Sponsor 
and/or designated organizations to analyze the samples.

AstraZeneca and its designated organizations may share summary results (such as genetic 
differences from groups of individuals with a disease) from this genetic research with 
other researchers, such as hospitals, academic organizations, or health insurance
companies. This can be done by placing the results in scientific databases, where they can 
be combined with the results of similar studies to learn even more about health and 
disease. The researchers can only use this information for health-related research 
purposes. Researchers may see summary results, but they will not be able to see 
individual participant data or any personal identifiers.

Some or all of the clinical datasets from the main study may be merged with the genetic 
data in a suitable secure environment separate from the clinical database.

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Appendix E
Actions Required in Cases of Increases in Liver Biochemistry 
and Evaluation of Hy’s Law
E 1
Introduction
This appendix describes the process to be followed in order to identify and appropriately 
report potential Hy’s Law cases and Hy’s Law cases. It is not intended to be a comprehensive 
guide to the management of elevated liver biochemistries. Specific guidance on managing 
liver anomalies can be found in Section 8.3.6 of the CSP.
During the study the investigator will remain vigilant for increases in liver biochemistry. The 
investigator is responsible for determining whether a participant meets potential Hy’s Law 
criteria at any point during the study.
All sources of laboratory data are appropriate for the determination of potential Hy’s Law and 
Hy’s Law events; this includes samples taken at scheduled study visits and other visits 
including central and all local laboratory evaluations even if collected outside of the study 
visits; for example, potential Hy’s Law criteria could be met by an elevated ALT from a 
central laboratory and/or elevated TBL from a local laboratory.
The investigator will also review AE data (for example, for AEs that may indicate elevations 
in liver biochemistry) for possible potential Hy’s Law events.
The investigator participates, together with the Sponsor clinical project representatives, in 
review and assessment of cases meeting potential Hy’s Law criteria to agree whether Hy’s 
Law criteria are met. Hy’s Law criteria are met if there is no alternative explanation for the 
elevations in liver biochemistry other than DILI caused by the IMP.
The investigator is responsible for recording data pertaining to potential Hy’s Law/Hy’s Law 
cases and for reporting SAEs and AEs according to the outcome of the review and assessment 
in line with standard safety reporting processes.
E 2
Definitions
Potential Hy’s Law
Aspartate aminotransferase or ALT ≥3 × ULN together with TBL ≥2 × ULN at any point 
during the study following the start of study medication irrespective of an increase in ALP.
Hy’s Law
Aspartate aminotransferase or ALT ≥3 × ULN together with TBL ≥2 × ULN, where no other 
reason, other than the IMP, can be found to explain the combination of increases, eg, elevated 
ALP indicating cholestasis, viral hepatitis, another drug.

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For potential Hy’s Law and Hy’s Law the elevation in transaminases must precede or be 
coincident with (ie, on the same day) the elevation in TBL, but there is no specified timeframe 
within which the elevations in transaminases and TBL must occur.
E 3
Identification of Potential Hy’s Law Cases
In order to identify cases of potential Hy’s Law it is important to perform a comprehensive 
review of laboratory data for any participant who meets any of the following identification 
criteria in isolation or in combination:

ALT ≥ 3 × ULN

AST ≥ 3 × ULN

TBL ≥ 2 × ULN
Central Laboratories Being Used:
When a participant meets any of the potential Hy’s Law identification criteria, in isolation or 
in combination, the central laboratory will immediately send an alert to the investigator (also 
sent to the Sponsor representative).
The investigator will also remain vigilant for any local laboratory reports where the potential 
Hy’s Law identification criteria are met, where this is the case, the investigator will:

Notify the Sponsor representative.

Request a repeat of the test (new blood draw) by the central laboratory without delay

Complete the appropriate unscheduled laboratory eCRF module(s) with the original local 
laboratory test result
When the identification criteria are met from central or local laboratory results the investigator 
will without delay:

Determine whether the participant meets potential Hy’s Law criteria (see Appendix E 2
for definition) by reviewing laboratory reports from all previous visits (including both 
central and local laboratory results).
Local Laboratories Being Used:
The investigator will without delay review each new laboratory report and, if the identification 
criteria are met, will:

Notify the Sponsor representative.

Determine whether the participant meets potential Hy’s Law criteria (see Appendix E 2
for definition) by reviewing laboratory reports from all previous visits.

Promptly enter the laboratory data into the laboratory eCRF.

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E 4
Follow-up
10.1.1
E 4.1
Potential Hy’s Law Criteria not met
If the participant does not meet potential Hy’s Law criteria the investigator will:

Inform the Sponsor representative that the participant has not met potential Hy’s Law 
criteria.

Perform follow-up on subsequent laboratory results according to the guidance provided in 
the protocol.
10.1.2
E 4.2
Potential Hy’s Law Criteria met
If the participant does meet potential Hy’s Law criteria the investigator will:

Notify the Sponsor representative who will then inform the central Study Team.

Within one day of potential Hy’s Law criteria being met, the investigator will report the 
case as an SAE of Potential Hy’s Law; serious criteria ‘Important medical event’ and 
causality assessment ‘yes/related’ according to the protocol process for SAE reporting.

For participants who met potential Hy’s Law criteria prior to starting IMP, the 
investigator is not required to submit a potential Hy’s Law SAE unless there is a 
significant change# in the participant’s condition.

The Study Clinical Lead will contact the investigator, to provide guidance, discuss, and 
agree an approach for the study participant’s follow-up (including any further laboratory 
testing) and the continuous review of data

Subsequent to this contact the investigator will:

Monitor the participant until liver biochemistry parameters and appropriate clinical 
symptoms and signs return to normal or baseline levels, or as long as medically 
indicated. Complete follow-up SAE Form as required.

Investigate the etiology of the event and perform diagnostic investigations as 
discussed with the Study Clinical Lead. This includes deciding which tests available 
in the Hy’s Law laboratory kit should be used.

Complete the 3 Liver eCRF Modules as information becomes available.
#
A ‘significant’ change in the participant’s condition refers to a clinically relevant change 
in any of the individual liver biochemistry parameters (ALT, AST, or TBL) in isolation or in 
combination, or a clinically relevant change in associated symptoms. The determination of 
whether there has been a significant change will be at the discretion of the investigator, this may 
be in consultation with the Study Clinical Lead if there is any uncertainty.

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E 5
Review and Assessment of Potential Hy’s Law Cases
The instructions in this appendix should be followed for all cases where potential Hy’s Law 
criteria are met.
As soon as possible after the biochemistry abnormality is initially detected, the Study Clinical 
Lead will contact the investigator in order to review available data and agree on whether there 
is an alternative explanation for meeting potential Hy’s Law criteria other than DILI caused 
by the IMP, to ensure timely analysis and reporting to health authorities within 15 calendar 
days from date potential Hy’s Law criteria was met. The Sponsor Global Clinical Lead or 
equivalent and Global Safety Physician will also be involved in this review together with 
other subject matter experts as appropriate.
According to the outcome of the review and assessment, the investigator will follow the 
instructions below.
Where there is an agreed alternative explanation for the ALT or AST and TBL elevations, a 
determination of whether the alternative explanation is an AE will be made and subsequently 
whether the AE meets the criteria for an SAE:

If the alternative explanation is not an AE, record the alternative explanation on the 
appropriate eCRF.

If the alternative explanation is an AE/SAE: Update the previously submitted Potential 
Hy’s Law SAE and AE eCRFs accordingly with the new information (reassessing event 
term, causality and seriousness criteria) following the Sponsor standard processes.
If it is agreed that there is no explanation that would explain the ALT or AST and TBL 
elevations other than the IMP:

Send updated SAE (report term ‘Hy’s Law’) according to Sponsor standard processes.

The ‘Medically Important’ serious criterion should be used if no other serious 
criteria apply.

As there is no alternative explanation for the Hy’s Law case, a causality 
assessment of ‘related’ should be assigned.

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If, there is an unavoidable delay, of over 15 calendar days in obtaining the information
necessary to assess whether the case meets the criteria for Hy’s Law, then it is assumed that 
there is no alternative explanation until such time as an informed decision can be made:

Provide any further update to the previously submitted SAE of Potential Hy’s Law, 
(report term now ‘Hy’s Law case’) ensuring causality assessment is related to IMP and 
seriousness criteria is medically important, according to protocol process for SAE 
reporting.

Continue follow-up and review according to agreed plan. Once the necessary 
supplementary information is obtained, repeat the review and assessment to determine 
whether Hy’s Law criteria are still met. Update the previously submitted potential Hy’s 
Law SAE report following protocol process for SAE reporting, according to the outcome 
of the review and amending the reported term if an alternative explanation for the liver 
biochemistry elevations is determined.

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E 6
Laboratory Tests
Hy’s Law Laboratory Kit for Central Laboratories
Additional standard chemistry and coagulation 
tests
GGT 
LDH
Prothrombin time
INR
Viral hepatitis
IgM anti-HAV 
HBsAg
IgM and IgG anti-HBc 
HBV DNA a
IgG anti-HCV 
HCV RNA b
IgM anti-HEV
HEV RNA
Other viral infections
IgM & IgG anti-CMV 
IgM & IgG anti-HSV
IgM & IgG anti-EBV
Alcoholic hepatitis
Carbohydrate deficient transferrin (CD-
transferrin) c
Autoimmune hepatitis
Antinuclear antibody (ANA)
Anti-Liver/Kidney Microsomal Ab (Anti-LKM) 
Anti-Smooth Muscle Ab (ASMA)
Metabolic diseases
alpha-1-antitrypsin 
Ceruloplasmin
Iron
Ferritin
Transferrin c
Transferrin saturation
a
HBV DNA is only recommended when IgG anti-HBc is positive.
b
HCV RNA is only recommended when IgG anti-HCV is positive or inconclusive.
c
CD-transferrin and Transferrin are not available in China. Study teams should amend this list accordingly.
E 7 References specific for Appendix E
Aithal et al, 2011
Aithal et al 2011, Clinical Pharmacology and Therapeutics 89(6):806-815.
FDA Guidance for Industry, July 2009
FDA Guidance for Industry (issued July 2009) ‘Drug-induced liver injury: Premarketing
clinical evaluation’. Available from; https://www.fda.gov/regulatory-information/search-fdaguidance-
documents/drug-induced-liver-injury-premarketing-clinical-evaluation.

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Appendix F
Statin Inclusion Criteria
F 1
Statin Inclusion Criteria (excluding participants from Japan)
High and Moderate-intensity Statin Therapy
High-dose Statin Therapies
Moderate-dose Statin Therapies
•
atorvastatin 40 to 80 mg once daily
•
atorvastatin 10 to 20 mg once daily
•
rosuvastatin 20 to 40 mg once daily
•
lovastatin 40 mg once daily
•
pravastatin 40 mg once daily
•
rosuvastatin 5 to 10 mg once daily
•
simvastatin 40 mg once daily
Based on the American College of Cardiology / American Heart Association 2018 Guideline on the Management 
of Blood Cholesterol.
Grundy et al. J Am Coll Cardiol. Nov 2018: DOI: 10.1016/j.jacc.2018.11.003
F 2
Statin Inclusion Criteria (participants from Japan only)
Statin Therapy
These statin therapies are selected by refering to moderate- or high-intensity statin therapies in the American College
of Cardiology/American Heart Association 2018 Guideline on the Management of Blood Cholesterol, and expected to 
lower LDL-C levels by ≥ 30% in Japanese patients.
•
atorvastatin 10 to 40 mg daily
•
rosuvastatin 2.5 to 20 mg daily
•
simvastatin 10 to 20 mg once daily
•
pitavastatin 1 to 4 mg once daily
•
Fluvastatin 60 mg once daily

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11
REFERENCES
Atar et al 2021
Atar D, Jukema JW, Molemans B, Taub PR, Goto S, Mach F, et al. New cardiovascular 
prevention guidelines: how to optimally manage dyslipidaemia and cardiovascular risk in 
2021 in patients needing secondary prevention. Atherosclerosis. 2021;319:51-61.
Cohen et al 2005
Cohen J, Pertsemlidis A, Kotowski IK, Graham R, Garcia CK, Hobbs HH. Low LDL 
cholesterol in individuals of African descent resulting from frequent nonsense mutations in 
PCSK9. Nat Genet. 2005;37(2):161-5.
Collins et al 2016
Collins R, Reith C, Emberson J, Armitage J, Baigent C, Blackwell L, et al. Interpretation of 
the evidence for the efficacy and safety of statin therapy. Lancet. 2016;388(10059):2532-561.
Ference et al 2018
Ference BA, Graham I, Tokgozoglu L, Catapano AL. Impact of lipids on cardiovascular 
health: JACC Health Promotion Series.. J Am Coll Cardiol. 2018;72(10):1141-56.
Geng et al 2021
Geng Q, Li X, Sun Q, Wang Z. Efficacy and safety of PCSK9 inhibition in cardiovascular 
disease: a meta-analysis of 45 randomized controlled trials. J Cardiol. 2022;29(4):574-81.
Karatasakis et al 2017
Karatasakis A, Danek BA, Karacsonyi J, Rangan BV, Roesle MK, Knickelbine T, et al. Effect 
of PCSK9 inhibitors on clinical outcomes in patients with hypercholesterolemia: a
meta- analysis of 35 randomized controlled trials. J Am Heart Assoc 2017, Dec 
9;6(12):e006910.
Mach et al 2020
Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS 
guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular 
risk. Eur Heart J. 2020;41(1):111-88.
Marston et al 2021
Marston NA, Giugliano RP, Park JG, Ruzza A, Sever PS, Keech AC, et al. Cardiovascular 
benefit of lowering low-density lipoprotein cholesterol below 40 mg/dL. Circulation.
2021;144(21):1732-1734.
Pirillo et al 2021
Pirillo A, Casula M, Olmastroni E, Norata GD, Catapano AL. Global epidemiology of 
dyslipidemias. Nat Rev Cardiol. 2021;18(10):689-700.

Clinical Study Protocol - 3.0 
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Doc ID: TMP-0010225
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Ray et al 2020
Ray KK, Wright RS, Kallend D, Koenig W, Leiter LA, Raal FJ, et al. Two phase 3 trials of 
inclisiran in patients with elevated LDL cholesterol. N Engl J Med. 2020;16;382(16):1507-
1519.
Reiter-Brennan et al 2020
Reiter-Brennan C, Osei AD, Iftekhar Uddin SM, Orimoloye OA, Obisesan OH, Mirbolouk M, 
et al. ACC/AHA lipid guidelines: personalized care to prevent cardiovascular disease. Cleve 
Clin J Med. 2020;87(4):231-239.
Roth et al 2020
Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Global 
burden of cardiovascular diseases and risk factors 1990-2019. update from the GBD 2019 
study. J Am Coll Cardiol. 2020;76(25):2982-3021.
Sabatine et al 2017
Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA et al. 
Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 
2017;376(18):1713-22.
Schmidt et al 2019
Schmidt AF, Holmes MV, Preiss D, Swerdlow DI, Denaxas S, Fatemifar G, et al. Phenome-
wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9. BMC 
Cardiovasc Disord. 2019;19:240.

SI G N A T U R E P A G E
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