KRAKEN: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Oral Once-Daily LY3473329 in Adults With Elevated Lipoprotein(a) at High Risk for Cardiovascular Events
Phase: PHASE2
Conditions: Lipoprotein Disorder
Sponsor: Eli Lilly and Company

Protocol J2O-MC-EKBC (Initial Version)
KRAKEN: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to 
Investigate the Efficacy and Safety of Oral Once-Daily LY3473329 in Adults With 
Elevated Lipoprotein(a) at High Risk for Cardiovascular Events
NCT05563246
Approval Date: 28-Jul-2022

CONFIDENTIAL 
J2O-MC-EKBC 
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Title Page 
Confidential Information 
The information contained in this document is confidential and is intended for the use of clinical investigators. It is the property of 
Eli Lilly and Company or its subsidiaries and should not be copied by or distributed to persons not involved in the clinical 
investigation of LY3473329, unless such persons are bound by a confidentiality agreement with Eli Lilly and Company or its 
subsidiaries.  
Note to Regulatory Authorities: This document may contain protected personal data and/or commercially confidential information 
exempt from public disclosure. Eli Lilly and Company requests consultation regarding release/redaction prior to any public release. 
In the United States, this document is subject to Freedom of Information Act (FOIA) Exemption 4 and may not be reproduced or 
otherwise disseminated without the written approval of Eli Lilly and Company or its subsidiaries. 
Protocol Title:
KRAKEN: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the 
Efficacy and Safety of Oral Once-Daily LY3473329 in Adults with Elevated Lipoprotein(a) at 
High Risk for Cardiovascular Events 
Protocol Number: J2O-MC-EKBC 
Amendment Number: This is the initial protocol. 
Compound: LY3473329 
Brief Title: 
Efficacy and safety of LY3473329 compared with placebo in adults with elevated Lp(a) at high 
risk for cardiovascular events 
Study Phase: 2 
Acronym: KRAKEN 
Sponsor Name: Eli Lilly and Company 
Legal Registered Address: Indianapolis, Indiana, USA 46285 
Regulatory Agency Identifier Number(s): 
IND: 155551 
EU trial number: 2022-501466-21-00 
Document ID: VV-CLIN-070060 
Approval Date: Protocol Electronically Signed and Approved by Lilly on date provided below. 
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Medical Monitor Name and Contact Information will be provided separately. 
 
 
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Table of Contents 
1. 
Protocol Summary ..........................................................................................................6 
1.1. 
Synopsis ............................................................................................................................6 
1.2. 
Schema ..............................................................................................................................9 
1.3. 
Schedule of Activities (SoA) ..........................................................................................10 
2. 
Introduction ...................................................................................................................18 
2.1. 
Study Rationale ...............................................................................................................18 
2.2. 
Background .....................................................................................................................18 
2.2.1. 
Introduction to Lp(a) .......................................................................................................18 
2.2.2. 
Elevated Levels of Lp(a) Are Associated with Increased Risk of 
Cardiovascular Disease ...................................................................................................19 
2.2.3. 
Available Treatments ......................................................................................................20 
2.2.4. 
Introduction to LY3473329 ............................................................................................20 
2.3. 
Benefit/Risk Assessment ................................................................................................20 
2.3.1. 
Risk Assessment .............................................................................................................20 
2.3.2. 
Benefit Assessment .........................................................................................................21 
2.3.3. 
Overall Benefit Risk Conclusion ....................................................................................21 
3. 
Objectives, Endpoints, and Estimands .......................................................................22 
4. 
Study Design ..................................................................................................................24 
4.1. 
Overall Design ................................................................................................................24 
4.2. 
Scientific Rationale for Study Design ............................................................................24 
4.2.1. 
Participant Input into Design ..........................................................................................25 
4.3. 
Justification for Dose ......................................................................................................25 
4.4. 
End of Study Definition ..................................................................................................25 
5. 
Study Population ...........................................................................................................26 
5.1. 
Inclusion Criteria ............................................................................................................26 
5.2. 
Exclusion Criteria ...........................................................................................................27 
5.3. 
Lifestyle Considerations .................................................................................................29 
5.3.1. 
Meals and Dietary Restrictions .......................................................................................29 
5.3.2. 
Blood Donation ...............................................................................................................29 
5.4. 
Screen Failures ................................................................................................................29 
5.5. 
Criteria for Temporarily Delaying 
Enrollment/Randomization/Administration of Study Intervention 
of a Participant ................................................................................................................30 
6. 
Study Intervention(s) and Concomitant Therapy .....................................................31 
6.1. 
Study Intervention(s) Administered................................................................................31 
6.2. 
Preparation, Handling, Storage, and Accountability ......................................................32 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ............................................32 
6.4. 
Study Intervention Compliance ......................................................................................32 
6.5. 
Dose Modification ..........................................................................................................33 
6.6. 
Continued Access to Study Intervention after the End of the 
Study ...............................................................................................................................33 
6.7. 
Treatment of Overdose ...................................................................................................33 
6.8. 
Concomitant Therapy .....................................................................................................33 
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7. 
Discontinuation of Study Intervention and Participant 
Discontinuation/Withdrawal........................................................................................34 
7.1. 
Discontinuation of Study Intervention ............................................................................34 
7.1.1. 
Liver Chemistry Stopping Criteria ..................................................................................35 
7.1.2. 
QTc Stopping Criteria .....................................................................................................35 
7.1.3. 
Temporary Discontinuation ............................................................................................35 
7.1.4. 
Rechallenge .....................................................................................................................35 
7.2. 
Participant Discontinuation/Withdrawal from the Study ................................................36 
7.3. 
Lost to Follow up ............................................................................................................36 
8. 
Study Assessments and Procedures.............................................................................37 
8.1. 
Efficacy Assessments .....................................................................................................37 
8.1.1. 
Primary Efficacy Assessment .........................................................................................37 
8.1.2. 
Secondary Efficacy Assessments ....................................................................................37 
8.2. 
Safety Assessments .........................................................................................................37 
8.2.1. 
Electrocardiograms .........................................................................................................37 
8.2.2. 
Clinical Safety Laboratory Tests ....................................................................................37 
8.2.3. 
Hepatic Safety .................................................................................................................38 
8.2.4. 
Hypersensitivity Reactions .............................................................................................40 
8.2.5. 
Hepatitis B Testing and Monitoring ...............................................................................40 
8.2.6. 
Hepatitis C Testing .........................................................................................................41 
8.3. 
Adverse Events, Serious Adverse Events, and Product 
Complaints ......................................................................................................................41 
8.3.1. 
Timing and Mechanism for Collecting Events ...............................................................42 
8.3.2. 
Pregnancy ........................................................................................................................43 
8.3.3. 
Major Adverse Cardiovascular Events ...........................................................................45 
8.4. 
Pharmacokinetics ............................................................................................................45 
8.5. 
Pharmacodynamics .........................................................................................................46 
8.6. 
Genetics ..........................................................................................................................46 
8.7. 
Biomarkers ......................................................................................................................46 
8.8. 
Immunogenicity Assessments.........................................................................................46 
8.9. 
Health Economics ...........................................................................................................46 
9. 
Statistical Considerations .............................................................................................47 
9.1. 
Statistical Hypotheses .....................................................................................................47 
9.1.1. 
Multiplicity Adjustment ..................................................................................................47 
9.2. 
Analyses Sets ..................................................................................................................47 
9.3. 
Statistical Analyses .........................................................................................................48 
9.3.1. 
General Considerations ...................................................................................................48 
9.3.2. 
Primary Endpoint/Estimand Analysis .............................................................................49 
9.3.3. 
Secondary Endpoint(s)/Estimand(s) Analysis ................................................................50 
9.3.4. 
Exploratory Endpoint(s) Analysis...................................................................................50 
9.3.5. 
Safety Analyses ...............................................................................................................50 
9.3.6. 
Pharmacokinetic and Pharmacodynamic Analyses ........................................................51 
9.3.7. 
Subgroup Analyses .........................................................................................................51 
9.4. 
Interim Analysis ..............................................................................................................51 
9.5. 
Sample Size Determination ............................................................................................52 
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10. 
Supporting Documentation and Operational Considerations ..................................53 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ................................................................................................................53 
10.1.1. Regulatory and Ethical Considerations ...........................................................................53 
10.1.2. Financial Disclosure........................................................................................................54 
10.1.3. Informed Consent Process ..............................................................................................54 
10.1.4. Data Protection................................................................................................................54 
10.1.5. Committees Structure......................................................................................................55 
10.1.6. Dissemination of Clinical Study Data.............................................................................55 
10.1.7. Data Quality Assurance ..................................................................................................55 
10.1.8. Source Documents ..........................................................................................................57 
10.1.9. Study and Site Start and Closure ....................................................................................57 
10.1.10. Publication Policy ...........................................................................................................58 
10.1.11. Investigator Information .................................................................................................58 
10.1.12. Sample Retention ............................................................................................................58 
10.2. 
Appendix 2: Clinical Laboratory Tests ...........................................................................59 
10.2.1. Laboratory Samples to be Obtained at the Time of a Systemic 
Hypersensitivity Event ....................................................................................................62 
10.3. 
Appendix 3: Adverse Events and Serious Adverse Events: 
Definitions and Procedures for Recording, Evaluating, Follow-
up, and Reporting ............................................................................................................64 
10.3.1. Definition of AE .............................................................................................................64 
10.3.2. Definition of SAE ...........................................................................................................65 
10.3.3. Definition of Product Complaints ...................................................................................66 
10.3.4. Recording and Follow-Up of AE and/or SAE and Product 
Complaints ......................................................................................................................66 
10.3.5. Reporting of SAEs ..........................................................................................................68 
10.3.6. Regulatory Reporting Requirements ...............................................................................69 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ..........................................................70 
10.4.1. Definitions.......................................................................................................................70 
10.4.2. Contraception Guidance..................................................................................................70 
10.5. 
Appendix 5: Genetics......................................................................................................73 
10.6. 
Appendix 6: Liver Safety: Suggested Actions and Follow-up 
Assessments ....................................................................................................................74 
10.7. 
Appendix 7: Provisions for Changes in Study Conduct During 
Exceptional Circumstances .............................................................................................76 
10.8. 
Appendix 8: Abbreviations and Definitions ...................................................................80 
11. 
References ......................................................................................................................84 
 
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1. 
Protocol Summary 
1.1. 
Synopsis 
Protocol Title: 
KRAKEN: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the 
Efficacy and Safety of Oral Once-Daily LY3473329 in Adults with Elevated Lipoprotein(a) at 
High Risk for Cardiovascular Events 
Brief Title: 
Efficacy and safety of LY3473329 compared with placebo in adults with elevated Lp(a) at high 
risk for cardiovascular events 
Regulatory Agency Identifier Number(s): 
IND: 155551 
EU trial number: 2022-501466-21-00 
Rationale: 
Elevated lipoprotein(a) (Lp[a]) is recognized as an important risk factor for cardiovascular 
disease; there are currently no approved pharmaceutical interventions for lowering Lp(a). 
LY3473329 is an orally administered disrupter of Lp(a) formation and has been shown to reduce 
Lp(a) in preclinical studies. In Phase 1 Study J2O-MC-EKBA (EKBA) with oral dosing of 
LY3473329 once-daily for 14 days, Lp(a) was significantly decreased and no safety issues were 
identified. This Phase 2 study aims to investigate the impact of a range of LY3473329 doses for 
3 months on Lp(a) level and on safety in a larger population of participants with elevated Lp(a) 
and high risk for cardiovascular events to enable Phase 3 development of this compound. 
Objectives, Endpoints, and Estimands: 
Objectives 
Endpoints 
Primary 
 
 To evaluate if LY3473329 is superior to 
placebo in percent Lp(a) reduction 
 Percent change in Lp(a) from baseline 
to Week 12  
Secondary 
 
 Compare proportion of participants on 
LY3473329 versus placebo achieving 
Lp(a) threshold levels 
 Proportion of participants achieving 
Lp(a) <125 nmol/L at Week 12 
 Compare the effect of LY3473329 to 
placebo on cardiovascular biomarkers 
 Percent change from baseline to Week 
12 for 
o ApoB 
o hsCRP 
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J2O-MC-EKBC 
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Objectives 
Endpoints 
 Characterize the PK of LY3473329 
 Population PK parameters 
Abbreviations: ApoB = apolipoprotein B; hsCRP = high-sensitivity C-reactive protein; Lp(a)_= lipoprotein(a); PK = 
pharmacokinetics. 
Estimands 
The primary clinical question of interest is: What is the intervention difference in percent change 
from baseline in Lp(a) after 12 weeks of study intervention in participants who meet the 
enrollment criteria and would have completed the treatment period? 
A similar estimand for the primary objective will be used for the secondary endpoints. 
Unless specified otherwise, safety assessments will be guided by an estimand comparing safety 
of LY3473329 doses with placebo irrespective of adherence to study intervention, including data 
collected during the treatment period and safety follow-up. 
Overall Design 
Study J2O-MC-EKBC (EKBC) is a parallel, double-blinded, placebo-controlled, dose-finding, 
Phase 2 study of LY3473329 in participants with elevated Lp(a) and at high risk for 
cardiovascular events. 
Approximately 233 participants will be randomized in a 1:2:2:2 ratio to 1 of the following arms 
with daily oral dosing for a 12-week treatment period: 
 Arm A: 10 mg LY3473329 
 Arm B: 60 mg LY3473329 
 Arm C: 240 mg LY3473329 
 Arm D: placebo 
Brief Summary: 
The purpose of this study is to measure difference in percent change in Lp(a) from baseline to 12 
weeks with LY3473329 versus placebo in participants with elevated Lp(a) and high risk for 
cardiovascular events. 
Study details include: 
● The study duration will be up to 22 weeks. 
● The treatment duration will be up to 12 weeks. 
Number of Participants: 
Approximately 233 participants will be randomly assigned to study intervention. 
Intervention Groups and Duration: 
All participants will be required to take 4 tablets by mouth every day for 12 weeks to ensure 
blinding. 
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J2O-MC-EKBC 
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Arm A 
Arm B 
Arm C 
Arm D 
Intervention 
Name 
LY3473329 and 
placebo 
LY3473329 and 
placebo 
LY3473329 
Placebo 
Dose 
Formulation 
Tablet 
Tablet 
Tablet 
Tablet 
Dosage Levels 
 
 
 
 
LY3473329 
10 mg (1 tablet, 
10 mg) 
60 mg (1 tablet, 
60 mg) 
240 mg (4 
tablets, 60 mg) 
0 tablets 
Placebo 
3 tablets 
3 tablets 
0 tablets 
4 tablets 
Frequency 
QD 
QD 
QD 
QD 
Route of 
Administration 
PO 
PO 
PO 
PO 
Authorized as 
defined by EU 
Clinical Trial 
Regulation 
Not authorized 
in EU 
Not authorized 
in EU 
Not authorized 
in EU 
Not authorized 
in EU 
Abbreviations: EU = European Union; PO = by mouth; QD = once daily 
Ethical Considerations of Benefit/Risk: 
Scientists believe that Lp(a) is a harmful kind of cholesterol. The study drug is likely to lower 
Lp(a) while it is being taken, and this effect will go away after the study drug is stopped. Studies 
of the study drug performed so far in animals and in people do not show harmful effects. 
Data Monitoring Committee: No 
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J2O-MC-EKBC 
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1.2. 
Schema 
 
Abbreviation: QD = once daily. 
NOTE: Optional Pre-Screening for participants to evaluate Lp(a) requirements for inclusion. 
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1.3. 
Schedule of Activities (SoA) 
Period I - Optional Pre-screening: The study includes an optional prescreening visit (Visit 601) as a simple way for sites to determine 
whether participants meet Lp(a) criteria, as assessed by a central laboratory assessment, before the full screening activities are initiated 
at Visit 1. If the participant has not had Lp(a) measured before or is unknown, the prescreening visit should be completed. The 
prescreening visit can be conducted at the study site, or remotely, for example, at a mobile healthcare or alternate laboratory. The 
prescreening determination of Lp(a) will be described in an appropriate informed consent form (ICF). Informed consent for the 
prescreening activities will be obtained, a participant identification number will be assigned, and sample for the Lp(a) prescreening 
laboratory test will be obtained. The optional prescreening visit can be repeated 1 time (no more) per participant if the investigator 
believes the participant would meet criteria at a later time, with a minimum of 4 weeks between visits. Repeated sampling in the 
prescreening visit will not require re-consenting or assignment of a new participant identification number. Note: If the optional 
prescreening is opted for, central laboratory testing for Lp(a) is still required as part of the screening procedures conducted at Visit 1. 
Participants with insufficiently high Lp(a) at Visit 1 will not be eligible for enrollment, despite their values in prescreening. A pre-
screening visit occurring longer or shorter than 3 weeks (21 days) from screening will not be considered a protocol deviation. 
Period II - Screening: Visit 1 procedures may be conducted over more than 1 day as long as all activities are completed prior to Visit 
2. 
Period III - Treatment Period: All procedures (screening and baseline) need to be completed prior to the first dose of study 
intervention. For an early discontinuation (ED) from the study intervention that occurs before the last visit in treatment period, see the 
activities listed for ED in this table. 
Period IV - Post Treatment Follow-Up: After completing Visits 7 and 8, there will be a follow-up Visit 801 approximately 4 weeks 
after discontinuing study intervention. This 4-week duration is greater than 5 times the effective half-life of the drug and thus will 
support adequate drug washout. 
Additionally, laboratory assessments at Visit 801 will provide information about the pharmacodynamic (PD) offset of study 
intervention on Lp(a). 
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Period I - 
Pre-
Screening  
Period II - 
Screening  
Period III - Treatment Period 
Period IV 
- Post-
Treatment 
Follow-Up 
  
Visit number 
601 
1 
2 
3 
4 
5 
6 
7 
8 
ED 
801 
  
Weeks from 
randomization  
≤6 
≤3 
— 
1 
2 
4 
8 
12 
12* 
— 
 4 weeks 
from last 
dose 
*Visit 8 occurs 1-3 days after final dose 
Visit interval tolerance 
(days) 
See Section 
1.3 
 — 
— 
±2 
±3 
±3 
±4 
±4 
— 
— 
 ±5 
 
Fasting Visit 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
If a participant arrives not fasted, schedule the 
laboratory draw for another date. See Section 
5.3.1. 
Pre-Screening informed 
consent 
X 
  
  
  
  
  
  
  
 
  
  
  
Informed consent 
  
X 
  
  
  
  
  
  
 
  
  
The ICF must be signed before any protocol-
specific tests or procedures are performed. 
See Appendix 10.1.3 for additional details. 
Inclusion and exclusion 
criteria, review and 
confirm 
 
X 
X 
  
  
  
  
  
 
  
  
Inclusion and exclusion criteria should be 
confirmed prior to drug assignment and 
administration of first dose of study intervention.  
Demographics 
  
X 
  
  
  
  
  
  
 
  
  
Includes year of birth, sex, ethnicity (where 
permissible), and race. 
Preexisting conditions 
and medical history, 
including relevant 
surgical history 
  
X 
  
  
  
  
  
  
 
  
  
All conditions ongoing and relevant past surgical 
and medical history should be collected.  
Prespecified medical 
history (indication and 
history of interest)  
  
X 
  
  
  
  
  
  
 
  
  
Prespecified medical history includes indication 
and history of cardiovascular events. 
Prior treatments for 
indication 
  
X 
  
  
  
  
  
  
 
  
  
Relevant prior therapies include, but are not 
limited to, lipid lowering medications. 
Substance use (alcohol, 
caffeine, and tobacco use)  
  
X  
 
  
  
  
  
  
 
  
  
  
Concomitant medications 
  
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Additional data will be collected for medications 
of interest. 
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Period I - 
Pre-
Screening  
Period II - 
Screening  
Period III - Treatment Period 
Period IV 
- Post-
Treatment 
Follow-Up 
  
Visit number 
601 
1 
2 
3 
4 
5 
6 
7 
8 
ED 
801 
  
Weeks from 
randomization  
≤6 
≤3 
— 
1 
2 
4 
8 
12 
12* 
— 
 4 weeks 
from last 
dose 
*Visit 8 occurs 1-3 days after final dose 
Visit interval tolerance 
(days) 
See Section 
1.3 
 — 
— 
±2 
±3 
±3 
±4 
±4 
— 
— 
 ±5 
 
Fasting Visit 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
If a participant arrives not fasted, schedule the 
laboratory draw for another date. See Section 
5.3.1. 
AEs 
X  
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Any events that occur after signing the informed 
consent are considered AEs as defined (Section 
10.3). Additional data are collected for certain 
AEs. 
Physical Evaluation 
  
  
  
  
  
  
  
  
 
  
  
  
Height  
  
X 
  
  
  
  
  
  
 
  
  
Participant should remove shoes. 
Weight  
  
X 
X 
  
  
  
  
X 
 
X 
  
Participant should remove shoes. 
Vital signs 
  
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Includes pulse rate and blood pressure measured 
after participant has been sitting at least 5 minutes 
and before ECG tracing and collection of blood 
samples for laboratory testing.  
Physical examination 
  
X 
  
  
  
  
  
  
 
  
  
The physical examination is performed (excludes 
pelvic, rectal, and breast examinations unless 
clinically indicated). 
Symptom-directed 
physical assessment 
  
  
 
X (refer to comment) 
Symptom-directed physical assessment will be 
conducted at the discretion of the PI or qualified 
personnel, per local regulations, as indicated based 
on participant status and standard of care. 
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Period I - 
Pre-
Screening  
Period II - 
Screening  
Period III - Treatment Period 
Period IV 
- Post-
Treatment 
Follow-Up 
  
Visit number 
601 
1 
2 
3 
4 
5 
6 
7 
8 
ED 
801 
  
Weeks from 
randomization  
≤6 
≤3 
— 
1 
2 
4 
8 
12 
12* 
— 
 4 weeks 
from last 
dose 
*Visit 8 occurs 1-3 days after final dose 
Visit interval tolerance 
(days) 
See Section 
1.3 
 — 
— 
±2 
±3 
±3 
±4 
±4 
— 
— 
 ±5 
 
Fasting Visit 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
If a participant arrives not fasted, schedule the 
laboratory draw for another date. See Section 
5.3.1. 
12-Lead ECG (local) 
  
X 
  
  
  
  
  
X 
 
X 
  
Collect single, local ECG prior to collection of 
blood samples for laboratory testing, including PK 
samples. Participants should be supine for 
approximately 5 to 10 minutes before ECG 
collections and remain supine but awake during 
the ECG collection. ECGs may be repeated at the 
PI’s discretion at any visit. See Section 8.2.1. 
Participant Diary (paper) 
  
  
  
  
  
  
  
 
  
  
  
Study drug administration 
log dispensed 
  
  
X 
X 
X 
X 
X 
  
 
  
  
  
Study drug administration 
log return (by participant) 
  
  
  
X 
X 
X 
X 
X 
 
X 
  
  
Study drug administration 
log review 
  
  
  
X 
X 
X 
X 
X 
 
X 
  
  
PROs (Paper) Complete prior to any clinical administered assessments 
SF-36 v2 acute 
  
  
X 
  
  
  
  
X 
 
X 
 
 
Participant Education  
  
  
  
  
  
  
  
  
 
  
  
  
Study drug administration 
log education and 
completion 
 
 
X 
 
 
 
 
 
 
 
 
Additional education can be provided as 
appropriate based on participants needs. 
Participants should be trained to get one pill from 
each bottle and should do this themselves at Visit 
2 under supervision. 
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Period I - 
Pre-
Screening  
Period II - 
Screening  
Period III - Treatment Period 
Period IV 
- Post-
Treatment 
Follow-Up 
  
Visit number 
601 
1 
2 
3 
4 
5 
6 
7 
8 
ED 
801 
  
Weeks from 
randomization  
≤6 
≤3 
— 
1 
2 
4 
8 
12 
12* 
— 
 4 weeks 
from last 
dose 
*Visit 8 occurs 1-3 days after final dose 
Visit interval tolerance 
(days) 
See Section 
1.3 
 — 
— 
±2 
±3 
±3 
±4 
±4 
— 
— 
 ±5 
 
Fasting Visit 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
If a participant arrives not fasted, schedule the 
laboratory draw for another date. See Section 
5.3.1. 
Laboratory Tests and 
Sample Collections 
  
  
  
  
  
  
  
  
 
  
  
  
Hematology  
  
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
  
Clinical chemistry  
  
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
  
Lipid panel 
  
X 
X 
  
  
X 
X 
X 
 
X 
X 
  
Urinalysis  
  
X 
 
  
  
X 
 
X 
 
X 
  
  
UACR 
 
X 
 
 
 
 
 
X 
 
X 
 
 
Serum pregnancy 
  
X 
  
  
  
  
  
X 
 
X 
X  
Only for WOCBP. See Appendix 10.4. 
Urine pregnancy (local) 
  
  
X 
  
  
X 
X 
  
 
  
 
Collect for WOCBP only. Done locally and prior 
to administering study intervention. OR 
Additional pregnancy tests (beyond those required 
per the SoA) should be performed at any time 
during the trial if a menstrual period is missed or 
there is clinical suspicion of pregnancy. See 
Appendix 10.4. 
If required per local regulations and/or institutional 
guidelines, pregnancy testing can occur at other 
times during the study treatment period. 
FSH 
  
X 
  
  
  
  
  
  
 
  
  
Optional; performed as needed to confirm 
postmenopausal status. See Appendix 10.4. 
TSH 
 
X 
 
 
 
 
 
 
 
 
 
 
HbA1c 
 
X 
 
 
 
 
 
 
 
 
 
 
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Period I - 
Pre-
Screening  
Period II - 
Screening  
Period III - Treatment Period 
Period IV 
- Post-
Treatment 
Follow-Up 
  
Visit number 
601 
1 
2 
3 
4 
5 
6 
7 
8 
ED 
801 
  
Weeks from 
randomization  
≤6 
≤3 
— 
1 
2 
4 
8 
12 
12* 
— 
 4 weeks 
from last 
dose 
*Visit 8 occurs 1-3 days after final dose 
Visit interval tolerance 
(days) 
See Section 
1.3 
 — 
— 
±2 
±3 
±3 
±4 
±4 
— 
— 
 ±5 
 
Fasting Visit 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
If a participant arrives not fasted, schedule the 
laboratory draw for another date. See Section 
5.3.1. 
Lp(a) 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
  
ApoB 
  
X 
X 
  
  
X 
X 
X 
 
X 
X 
  
Plasminogen activity 
  
X 
X 
X 
X 
X 
X 
X 
 
X 
X  
  
hsCRP 
  
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
  
HIV screening test 
  
X 
  
  
  
  
  
  
 
  
  
  
HCV screening test 
  
X 
  
  
  
  
  
  
 
  
  
If HCV antibody test is positive, it must be 
followed by a HCV RNA test. See Section 8.2.6.  
HBV screening test 
  
X 
  
  
  
  
  
  
 
  
  
If HBsAg is negative and HBcAb is positive, 
further testing with HBV DNA is required. If the 
screening HBV DNA is negative, the participant is 
not excluded. See Section 8.2.5.  
eGFR 
  
X 
  
  
  
  
  
X 
 
X 
  
Calculated using CKD-EPI method.  
PK sample (predose) 
  
  
X 
X 
X 
 
X 
X 
 
  
  
See Section 6.1 for dosing instructions and Section 
8.4.  
PK sample (postdose) 
 
 
X 
 
 
X 
 
 
X 
 
 
Post-dose PK sample at the following times: 
 
Visit 2: 1 to 2 hours after dose 
 
Visit 5: 4 to 6 hours after dose 
 
Visit 8: 1-3 days after final dose 
Fasting not required for Visit 5 post-dose PK 
sample. 
PK sample (random) 
 
 
 
 
 
 
 
 
 
X 
X 
See Section 8.4. 
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Period I - 
Pre-
Screening  
Period II - 
Screening  
Period III - Treatment Period 
Period IV 
- Post-
Treatment 
Follow-Up 
  
Visit number 
601 
1 
2 
3 
4 
5 
6 
7 
8 
ED 
801 
  
Weeks from 
randomization  
≤6 
≤3 
— 
1 
2 
4 
8 
12 
12* 
— 
 4 weeks 
from last 
dose 
*Visit 8 occurs 1-3 days after final dose 
Visit interval tolerance 
(days) 
See Section 
1.3 
 — 
— 
±2 
±3 
±3 
±4 
±4 
— 
— 
 ±5 
 
Fasting Visit 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
If a participant arrives not fasted, schedule the 
laboratory draw for another date. See Section 
5.3.1. 
Stored Samples 
  
  
  
  
  
  
  
  
 
  
  
  
Optional genetics sample 
  
  
X 
  
  
  
  
  
 
  
  
Sample can be obtained at or after the specified 
visit. See Appendix 10.5. 
Exploratory biomarker 
samples  
  
  
X 
  
  
X 
  
X 
 
X 
X 
  
Randomization and 
Dosing 
  
  
  
  
  
  
  
  
 
  
  
  
Register visit with IWRS 
  
X 
X 
X 
X 
X 
X 
X 
 
X 
X 
Unscheduled visits are not required to be 
registered in IWRS. 
Randomization via IWRS  
  
  
X 
  
  
  
  
  
 
  
  
  
Dispense study 
intervention via IWRS 
  
  
X 
 
 
X 
X 
  
 
  
  
  
Participant take study 
intervention at site 
 
 
X 
 
 
 
 
 
 
 
 
First dose of study intervention must be taken at 
site. For other visits, participants may take study 
invention at site provided they meet PK sample 
timepoints. 
Dispense study 
intervention to participant 
  
  
X 
 
 
X 
X 
  
 
  
  
At Visits 3 and 4, study intervention will be 
assessed for compliance and returned to the 
participant. 
Participant returns study 
intervention  
  
  
  
X 
X 
X 
X 
X 
 
X 
  
   
Assess study intervention 
compliance 
  
  
  
X 
X 
X 
X 
X 
 
X 
  
  
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Abbreviations: AE = adverse event; ApoB = apolipoprotein b; CKD-EPI = Chronic Kidney Disease Epidemiology Collaboration; ECG = electrocardiogram; 
ED = early discontinuation; eGFR = estimated glomerular filtration rate; FSH = follicle-stimulating hormone; HbA1c = hemoglobin A1c; HBcAb = hepatitis 
B core antibody; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; 
hsCRP = high-sensitivity C-reactive protein; ICF = informed consent form; IWRS = Interactive Web-Response System; Lp(a) = Lipoprotein(a); PI = principle 
investigator; PK = pharmacokinetic; PRO = Patient-Reported Outcomes; RNA = ribonucleic acid; SoA = Schedule of Activities; TSH = thyroid stimulating 
hormone; UACR = urine albumin creatinine ratio; WOCBP = women of childbearing potential. 
 
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2. 
Introduction 
LY3473329 is a small molecule that disrupts the binding of apolipoprotein(a) (apo[a]) to 
apolipoprotein B (ApoB) of low-density lipoprotein (LDL) particles, decreasing the formation 
and plasma steady-state levels of lipoprotein(a) (Lp[a]). 
2.1. 
Study Rationale 
Elevated Lp(a) is recognized as an important risk factor of cardiovascular disease; there are 
currently no approved pharmaceutical interventions for lowering Lp(a). LY3473329 is an orally 
administered disrupter of Lp(a) formation and has been shown to reduce Lp(a) in preclinical 
studies. In Phase 1 Study J2O-MC-EKBA (EKBA) with oral dosing of LY3473329 once-daily 
for 14 days, Lp(a) was significantly decreased and no safety issues were identified. This Phase 2 
study aims to investigate the impact of a range of LY3473329 doses for 3 months on Lp(a) level 
and on safety in a larger population of participants with elevated Lp(a) and high risk for 
cardiovascular events to enable Phase 3 development of this compound. 
2.2. 
Background 
2.2.1. 
Introduction to Lp(a) 
Lp(a) is an atherogenic lipoprotein consisting of an LDL-like particle linked via a disulfide bond 
to apo(a). 
Apo(a) is a protein found in new-world monkeys, great apes, and humans (Utermann 1989). The 
protein, encoded by the LPA gene, includes 10 unique units of kringle IV repeats; the first and 
third through tenth are present in single copies while the second is present in variable copy 
numbers (1 to <50). Additionally, the protein includes a kringle V and a protease-like domain 
that is not biologically active (Dubé et al. 2012; Kronenberg and Utermann 2013; Tsimikas 
2017). 
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Figure 1. 
Representation of Lp(a) particle. 
Abbreviations: Apo(a) = apolipoprotein(a); ApoB = apolipoprotein b; LDL = low-density lipoprotein. 
Lp(a) contains oxidized phospholipids. Plasma levels of Lp(a) are genetically determined. 
Single-nucleotide polymorphisms (SNPs) of the LPA gene are associated with higher or lower 
Lp(a) levels; for example, rs10455872 and rs3798220 are associated with increased Lp(a) 
(Clarke et al. 2009; Li et al. 2011). Additionally, the number of kringle IV2 repeats determines 
protein size, which is inversely proportional to plasma concentration and mass of Lp(a); larger 
apo(a) size is associated with lower concentrations of Lp(a). Despite this genetically induced 
variability in Lp(a) concentrations between individuals, intra-patient variability in Lp(a) is low 
and is not thought to be materially impacted by diet, environmental factors, or exercise (Schmidt 
et al. 2016). However, apo(a) is an acute-phase reactant, and Lp(a) increases, for example, after 
surgery, myocardial infarction, and infection (Maeda et al. 1989; Min et al. 1997; Noma et al. 
1994). 
2.2.2. 
Elevated Levels of Lp(a) Are Associated with Increased Risk of Cardiovascular 
Disease 
Lp(a) particles are thought to exert adverse cardiovascular effects through atherogenic, 
inflammatory, and possibly pro-thrombotic activity (Tsimikas 2017). 
In a meta-analysis of 36 studies, Lp(a) was associated with risk for nonfatal myocardial 
infarction or coronary death (Emerging Risk Factors Collaboration et al. 2009). In studies of 
LPA gene KIV2 repeats or SNPs, genetic variants conferring higher levels of Lp(a) were found 
to be related to risk for myocardial infarction and coronary disease in Mendelian randomization 
and genome-wide association studies (Clarke et al. 2009; Kamstrup et al. 2009). In a study 
including data from the United Kingdom (UK) Biobank, 7 genome-wide association studies, and 
LPA sequencing, Lp(a) was associated with risk of coronary heart disease, stroke, chronic kidney 
disease, aortic valve stenosis, heart failure, and peripheral vascular disease (Emdin et al. 2016). 
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The American Heart Association and American College of Cardiologists Guideline on the 
management of blood cholesterol defined Lp(a) ≥50 mg/dL or ≥125 nmol/L as risk enhancing in 
2018 (Grundy et al. 2019). Elevated Lp(a) >50 mg/dL was present in 24% of samples from a 
reference laboratory and 29.2% of samples from a tertiary care center (Varvel et al. 2016). The 
estimated prevalence of Lp(a) >60 mg/dL is 64 million in the United States, 150 million in 
Europe, and 1.4 billion worldwide (Tsimikas and Stroes 2020). 
2.2.3. 
Available Treatments 
Lipid apheresis is approved and used in some geographies for patients with elevated Lp(a) 
(Jaeger et al. 2009; Nugent et al. 2020). Proprotein convertase subtilisin/kexin type 9 (PCSK9) 
inhibitors, alirocumab, evolocumab, and inclisiran, reduce Lp(a) by approximately 25% 
(Robinson et al. 2015; Sabatine et al. 2015; Stoekenbroek et al. 2019), and prescription-strength 
niacin also produces 15% to 25% reductions in Lp(a) (AIM-HIGH Investigators 2011; HPS2-
THRIVE Collaborative Group et al. 2014), but are not approved treatments for Lp(a) reduction. 
Novel treatments to reduce Lp(a) are under investigation, including an antisense oligonucleotide 
(IONIS-APO(a)-LRx), and 2 siRNA therapies (olpasiran and SLN360), which have been shown 
to lower Lp(a) concentrations in clinical trials (Viney et al. 2016; Ference 2022; Koren et al. 
2022). 
2.2.4. 
Introduction to LY3473329 
LY3473329 binds Apo(a) KIV7/8 domains causing disruption of Lp(a) particle formation in 
vivo. LY3473329 reduces steady-state levels of Lp(a) in both a mouse model transgenic for 
human apo(a) and ApoB, and in cynomolgus monkeys that endogenously express Lp(a). 
LY3473329 was assessed in nonclinical toxicology studies. In summary, up to a daily oral dose 
of 1000 mg/kg, no adverse effects were observed in rats or monkeys. 
In Phase 1 Study EKBA of participants treated with LY3473329 doses up to 800 mg/day for 14 
days, Lp(a) was lowered while there were no clinically relevant changes in plasminogen activity. 
2.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and reasonably 
expected adverse events (AEs) of LY3473329 may be found in the Investigator’s Brochure (IB) 
or Development Safety Update Report. 
2.3.1. 
Risk Assessment 
Study Intervention 
The pharmacodynamic (PD) effect of LY3473329 is anticipated to be lowering of Lp(a). Lp(a) 
serves no known positive functions and is not present in most species. Additionally, people 
homozygous for null mutations of the LPA gene have not been identified to have any related 
health issues. Furthermore, toxicology studies of LY3473329 show no notable adverse drug 
effects. Finally, human phase 1 Study EKBA showed that single and multiple LY3473329 doses 
up to 800 mg/day were safe and generally well tolerated by healthy male and female participants. 
A preclinical finding of LY3473329 showed lowering of plasminogen without any associated 
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toxicological sequelae, but there were no clinically relevant changes in plasminogen activity in 
humans. 
Study Procedures 
The study will include blood draws and safety monitoring, and these procedures are not 
anticipated to be associated with significant participant risk. 
2.3.2. Benefit Assessment 
Lp(a) is a lipoprotein particle with atherogenic, inflammatory, and possibly pro-thrombotic 
activity.  In preclinical studies and a previous Phase 1 study, LY3473329 decreased Lp(a). 
Chronic lowering of Lp(a) is anticipated to have beneficial effects on cardiovascular disease; 
however, the relatively short-term lowering of Lp(a) in this study may be insufficient to confer 
any benefits. Participants may benefit by receiving personal health information from the physical 
examinations and from other routine safety assessments performed in this study. 
2.3.3. Overall Benefit Risk Conclusion 
Treatment with study intervention is anticipated to have an acceptable benefit to risk profile. 
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3. 
Objectives, Endpoints, and Estimands 
Objectives 
Endpoints 
Primary 
 
 To evaluate if LY3473329 is superior to 
placebo in percent Lp(a) reduction 
 Percent change in Lp(a) from baseline 
to Week 12 
Secondary 
 
 Compare proportion of participants on 
LY3473329 versus placebo achieving 
Lp(a) threshold levels 
 Proportion of participants achieving 
Lp(a) <125 nmol/L at Week 12 
 Compare the effect of LY3473329 to 
placebo on cardiovascular biomarkers 
 Percent change from baseline to Week 
12 for 
o ApoB 
o hsCRP  
 Characterize the PK of LY3473329  
 Population PK parameters 
Exploratory 
 
 Compare proportion of participants on 
LY3473329 versus placebo achieving 
absolute lowering of Lp(a) threshold  
 Proportion of participants achieving 
Lp(a) lowering of at least 150 nmol/L at 
Week 12 
 To compare the effect of LY3473329 
versus placebo on plasminogen 
 Change in plasminogen activity 
 Compare the lipid profile in response to 
LY3473329 versus placebo 
 Lipid profile 
o LDL 
o total cholesterol 
o HDL 
o triglycerides 
 Health-related quality of life 
 SF-36v2 acute form domain scores 
Abbreviations: ApoB = apolipoprotein B; HDL = high-density lipoprotein; hsCRP = high-sensitivity C-reactive 
protein; LDL = low-density lipoprotein; Lp(a)_= Lipoprotein (a); PK = pharmacokinetics. 
Primary estimand 
The primary clinical question of interest is: What is the intervention difference in percent change 
from baseline in Lp(a) after 12 weeks of study intervention in participants who meet the 
inclusion criteria and would have completed the treatment period? 
The efficacy estimand is described by the following attributes: 
Population: participants who meet the enrollment criteria. Further details can be found in Section 
5. 
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Endpoint: percent change from baseline to Week 12 in Lp(a). 
Treatment condition: the randomized treatment with allowance for safety. Further details on 
study interventions and concomitant interventions can be found in Section 6. 
The intercurrent event “intervention discontinuation for any reason” is addressed by the 
hypothetical strategy, and the potential outcome of interest is the response in the efficacy 
measurement if participants had adhered to the randomized treatment. There are no remaining 
intercurrent events. 
Population-level summary: mean percent changes in Lp(a). 
Treatment contrast of interest: difference in mean percent changes in Lp(a) between LY3473329 
and placebo. 
Rationale for estimand: This Phase 2 study aims to study the efficacy of LY3473329 under the 
ideal condition that all participants adhere to the randomized treatment. 
 
A similar estimand for the primary objective will be used for the secondary objectives. 
Unless specified otherwise, safety assessments will be guided by an estimand comparing safety 
of LY3473329 doses with placebo irrespective of adherence to study intervention, including data 
collected during the treatment period and safety follow-up. 
Secondary estimand 
The primary clinical question of interest is: What is the intervention difference in percent change 
from baseline in Lp(a) after 12 weeks of study intervention in participants who meet the 
inclusion criteria regardless of treatment discontinuation for any reason? 
The treatment-regimen estimand is described by the following attributes: 
Population: participants who meet the enrollment criteria. Further details can be found in Section 
5. 
Endpoint: percent change from baseline to Week 12 in Lp(a). 
Treatment condition: the randomized treatment with allowance for safety. Further details on 
study interventions, and concomitant interventions can be found in Section 6. 
The intercurrent event “intervention discontinuation for any reason” is addressed by the 
treatment-regimen strategy, and the potential outcome of interest is the response in the efficacy 
measurement regardless of whether participants had adhered to the randomized treatment. There 
are no remaining intercurrent events. 
Population-level summary: mean percent changes in Lp(a). 
Treatment contrast of interest: difference in mean percent changes in Lp(a) between LY3473329 
and placebo. 
Rationale for estimand: this estimand aims to study the efficacy of LY3473329 that reflects the 
real-life behavior of the target population. 
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4. 
Study Design 
4.1. 
Overall Design 
Study EKBC is a parallel, double-blinded, placebo-controlled, dose-finding, Phase 2 study of 
LY3473329 in participants with elevated Lp(a) and at high risk for cardiovascular events. 
Approximately 233 participants will be randomized in a 1:2:2:2 ratio to 1 of the following arms 
with daily oral dosing for a 12-week treatment period: 
 Arm A: 10 mg LY3473329 
 Arm B: 60 mg LY3473329 
 Arm C: 240 mg LY3473329 
 Arm D: placebo 
Treatment periods and assessments are described in the Schedule of Activities (SoA) (Section 
1.3) 
The study schema is shown in Section 1.2. 
The study population is described in Section 5. The maximum number of participants entered 
based on familial hypercholesterolemia or type 2 diabetes is approximately 93 (40%). 
The efficacy and safety assessments are described in Sections 8.1 and 8.2, respectively. 
4.2. 
Scientific Rationale for Study Design 
Previously completed Phase 1 Study EKBA showed a decrease in Lp(a) in healthy participants 
with Lp(a) levels ≥75 nmol/L or ≥30 mg/dL given LY3473329 for 14 days. The current study is 
intended to be Phase 3 enabling as it will provide the following information: 
 Efficacy and safety data with daily oral administration of study drug for 12 weeks. This 
duration is anticipated to provide information regarding the maximal lowering of Lp(a) 
with LY3473329 and information regarding an appropriate dose of study drug for Phase 
3. The primary endpoint is at 12 weeks, a time anticipated to achieve nadir levels of Lp(a) 
lowering. 
 Participants for this study will have Lp(a) ≥175 nmol/L at baseline and have high risk for 
cardiovascular events. This study will thus provide relevant efficacy and safety for 
participants appropriate for a Phase 3 cardiovascular outcomes trial. 
The study includes an optional pre-screening Visit 601 where potential participants can be pre-
screened with an assessment of Lp(a). 
Participants qualifying based on the optional pre-screening assessment and those known to have 
a sufficiently elevated Lp(a) can be screened for inclusion in the trial at Visit 1. 
The follow-up visit after the last dose of study drug is to capture any additional safety signals 
and to quantitate the return to baseline for Lp(a). 
Placebo is chosen as the control treatment to assess whether any observed effects are treatment 
related or simply reflect the study conditions. The double-blind design minimizes bias. 
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In this study, collection of demographic information includes race and ethnicity. The scientific 
rationale is to assess variable response in safety and/or efficacy based on these variables. 
4.2.1. Participant Input into Design 
Throughout this protocol, the term "participant" is used to indicate an individual who participates 
in a clinical trial, either as a recipient of an investigational intervention or as a control. This 
usage reflects preferences indicated by patient advocates to more accurately reflect the role of 
people who take part in clinical trials. 
4.3. 
Justification for Dose 
LY3473329 doses of 10 mg, 60 mg, and 240 mg, administered orally QD, were selected based 
on the following: 
 Safety and tolerability of LY3473329 doses up to 800 mg in healthy participants in the 
Phase 1 Study EKBA 
 The selected dose levels and dose range support a robust dose-exposure–response 
analysis of multiple safety and efficacy measures to support selection of dose(s) of 
LY3473329 with optimal benefit/risk ratio for further clinical development 
4.4. 
End of Study Definition 
The end of the study is defined as the date of the last visit of the last participant in the study or 
last scheduled procedure shown in the SoA for the last participant in the trial globally. 
A participant is considered to have completed the study if the participant has completed all 
periods of the study including the last visit or the last scheduled procedure shown in the SoA. 
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5. 
Study Population 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
The maximum number of participants entered based on familial hypercholesterolemia or type 2 
diabetes is approximately 93 (40%). 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
Age 
1. Participants must be at least 40 years old at the time of signing the informed 
consent. 
Type of Participant and Disease Characteristics 
2. Participants with Lp(a) ≥175 nmol/L at Visit 1, measured at the central laboratory. 
3. High risk for cardiovascular events defined as documented coronary artery 
disease (CAD), stroke, or peripheral artery disease or atherosclerotic 
cardiovascular disease (ASCVD) risk equivalents (familial hypercholesterolemia 
or type 2 diabetes). 
 CAD documentation should include at least 1 of the following: 
a. angiographic evidence of ≥50% stenosis of 1 or more major epicardial 
coronary arteries 
b. Coronary Artery Calcification Agatston score on computerized 
tomography (CT) scan of ≥300 
c. history of myocardial infarction documented by positive enzymes, and 
either symptoms of myocardial ischemia, or electrocardiogram (ECG) 
changes (Thygesen et al. 2012) 
d. history of coronary revascularization 
e. evidence of cardiac ischemia on exercise testing or imaging study. 
 Stroke (an acute episode of focal cerebral, spinal, or visual dysfunction caused 
by infarction of central nervous system tissue) documentation should include 
CT scan, magnetic resonance imaging, or other visualization method. 
Transient ischemic attack or embolic stroke (not of atherosclerotic origin) are 
not qualifying events. 
 Peripheral artery disease documentation should include intermittent 
claudication with an ankle-brachial index ≤0.90 and/or limb amputation or 
revascularization due to lower limb ischemia. Thromboangiitis obliterans is 
not a qualifying event. 
4. Participants on the following medications according to local practice must be on a 
stable regimen for at least 4 weeks prior to Visit 1 and expected to remain on a 
stable regimen through the end of the post-treatment follow-up period: 
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a. lipid-lowering drugs (e.g., statins, ezetimibe, PCSK9 inhibitors, 
prescription-dose niacin, fibrates, fish oil, or other products containing 
omega-3 fatty acids, including over-the-counter [OTC] preparations) 
b. testosterone, estrogens, anti-estrogens, progestins, selective estrogen 
receptor modulators, or growth hormone 
Weight 
5. Have a body mass index within the range 18.5 to 40 kg/m2, inclusive. 
Sex and Contraceptive/Barrier Requirements 
6. Male and/or female 
a. Males who agree to use highly effective or effective methods of 
contraception may participate in this trial. Please refer to Appendix 10.4 
for definitions and additional guidance related to contraception. 
b. Women of childbearing potential (WOCBP) who agree to use highly 
effective or effective methods of contraception and women not of 
childbearing potential (WNOCBP) may participate in this trial. See 
Appendix 10.4 for definitions and additional requirements related to 
contraception. 
Contraceptive use by participants should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies. For the contraception 
requirements of this protocol, see Appendix 10.4. 
Informed Consent 
7. Capable of giving signed informed consent as described in Appendix 10.1, which 
includes compliance with the requirements and restrictions listed in the ICF and in 
this protocol. 
Other Inclusions 
8. Are reliable and willing to make themselves available for the duration of the study 
and are willing to follow study procedures, including willing and able to take four 
12-mm round concave tablets of study drug every day for 12 weeks, in the 
opinion of the investigator. 
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
9. Have a history or presence of an underlying disease, or surgical, physical, 
medical, or psychiatric condition that, in the opinion of the investigator, would 
potentially affect participant safety within the study or interfere with participating 
in or completing the study or with the interpretation of data. 
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10. Any of the following, or other events indicating unstable medical condition in the 
opinion of the investigator, within 3 months of Visit 1: 
a. major surgery 
b. coronary, carotid, or peripheral arterial revascularization 
c. stroke or transient ischemic attack 
d. myocardial infarction or unstable angina 
e. acute limb ischemia. 
11. Have, in the 6 months prior to Visit 1, uncontrolled Type 1 or Type 2 diabetes, 
defined as an episode of ketoacidosis or hyperosmolar state requiring 
hospitalization, or have a hemoglobin A1c (HbA1c) ≥8% at Visit 1. 
12. Have uncontrolled hypertension with a resting blood pressure ≥160 mm Hg 
systolic and/or ≥100 mm Hg diastolic at Visit 1; a repeat measure is allowed. 
13. New York Health Association Class III or IV heart failure or last known left 
ventricular ejection fraction <30%. 
14. Active or acute infection requiring systemic antiviral or antimicrobial therapy that 
will not be completed prior to Visit 2. 
15. Malignancy within 5 years, except for basal or squamous cell carcinoma of the 
skin or carcinoma in situ of the cervix that has been successfully treated. 
16. Recent history of, or current drug or alcohol abuse in the opinion of the 
investigator. 
17. Have 2 or more clinically significant or severe drug allergies, or severe post-
treatment hypersensitivity reactions, including, but not limited to 
a. erythema multiforme major 
b. linear immunoglobulin A dermatosis 
c. toxic epidermal necrolysis 
d. exfoliative dermatitis. 
18. Hypersensitivity to the active substance or to any of the excipients. 
19. Have a current infection with hepatitis B virus (HBV), that is, positive for 
hepatitis B surface antigen (HBsAg) and/or PCR positive for HBV 
deoxyribonucleic acid (DNA) (Section 8.2.5). 
20. Have a current infection with hepatitis C virus (HCV), that is, positive for HCV 
ribonucleic acid (RNA) (Section 8.2.6). 
21. Have human immunodeficiency virus (HIV) infection. 
Prior/Concomitant therapy 
22. Lipoprotein apheresis within 3 months of Visit 1, or planned during the study. 
23. Treatment with another investigational drug, biological agent, or device within 1 
month of Visit 1, or 5 half-lives of investigational agent, whichever is longer. 
24. Treatment with any investigational oligonucleotide or siRNA within 9 months of 
Visit 1. 
Prior/Concurrent Clinical Study Experience 
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25. Are currently enrolled in any other clinical study involving an investigational 
product or any other type of medical research judged not to be scientifically or 
medically compatible with this study. 
Diagnostic Assessments 
26. Clinically significant abnormalities in screening laboratory values that would 
render a participant unsuitable for inclusion in the opinion of the investigator. 
27. Any of the following abnormalities: 
a. estimated glomerular filtration rate (eGFR) ˂30 mL/min/1.73 m2 
b. alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 
>3.0x upper limit of normal (ULN) 
c. bilirubin > 1.5x ULN, except for participants diagnosed with Gilbert’s 
syndrome 
Other Exclusions 
28. Are Lilly employees, or are employees of any third party involved in a study that 
requires exclusion of their employees. 
29. Are investigator site personnel directly affiliated with this study and/or their 
immediate families. Immediate family is defined as a spouse, parent, child, or 
sibling, whether biological or legally adopted. 
30. Are pregnant, or intend to become pregnant or to breastfeed during the study. 
31. Are, in the judgment of the investigator, actively suicidal and therefore deemed to 
be at significant risk for suicide. 
5.3. 
Lifestyle Considerations 
5.3.1. 
Meals and Dietary Restrictions 
Participants are required to fast for at least 10 hours before the Visits 1-7. Routine blood 
chemistry and urine samples should be taken after fasting for at least 10 hours. Fasting is not 
required for the Visit 5 post-dose PK sample. During preparation for fasting samples, the 
participant can drink water and they should ensure that they consume sufficient water so they do 
not become dehydrated.  It is not necessary to fast for Visits 601, Visit 8, or for any confirmatory 
test, or test taken for safety reasons; these may be taken without regard to fasting status. 
5.3.2. 
Blood Donation 
Participants must not donate blood for the duration of the study. 
5.4. 
Screen Failures 
A screen failure occurs when a participant who consents to participate in the clinical study is not 
subsequently randomly assigned to study intervention. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes demography, 
screen failure details, eligibility criteria, and any serious adverse event (SAE). 
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Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened once if the investigator believes the participant would meet criteria at a later time. 
Rescreened participants should be assigned a new participant number for every screening or 
rescreening event. 
5.5. 
Criteria for Temporarily Delaying 
Enrollment/Randomization/Administration of Study Intervention 
of a Participant 
Not Applicable. 
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6. 
Study Intervention(s) and Concomitant Therapy 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to/used by a study participant 
according to the study protocol. 
6.1. 
Study Intervention(s) Administered 
All participants will be required to take 4 tablets by mouth every day for 12 weeks to ensure 
blinding. 
 
Arm A 
Arm B 
Arm C 
Arm D 
Intervention 
Name 
LY3473329 and 
placebo 
LY3473329 and 
placebo 
LY3473329 
Placebo 
Dose 
Formulation 
Tablet 
Tablet 
Tablet 
Tablet 
Dosage Levels 
 
 
 
 
LY3473329 
10 mg (1 tablet, 
10 mg) 
60 mg (1 tablet, 
60 mg) 
240 mg (4 
tablets, 60 mg) 
0 tablets 
Placebo 
3 tablets 
3 tablets 
0 tablets 
4 tablets 
Frequency 
QD 
QD 
QD 
QD 
Route of 
Administration 
PO 
PO 
PO 
PO 
Authorized as 
defined by EU 
Clinical Trial 
Regulation 
Not authorized 
in EU 
Not authorized 
in EU 
Not authorized 
in EU 
Not authorized 
in EU 
Abbreviations: EU = European Union; PO = by mouth; QD = once daily. 
LY3473329 and placebo tablets will be taken orally with approximately 240 mL of water at 
approximately the same time, preferably in the morning, each dosing day. On specific visit days, 
participants will be required to not take the drug at home and follow directions provided by the 
site on when to take the drug after they arrive at the clinical site. 
Participants should be trained to get one pill from each bottle and should do this themselves at 
Visit 2 under supervision. 
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6.2. 
Preparation, Handling, Storage, and Accountability 
 The investigator or designee must confirm appropriate storage conditions have 
been maintained during transit for all study intervention received and any 
discrepancies are reported and resolved before use of the study intervention. 
 Only participants enrolled in the study may receive study intervention. Only 
authorized study personnel may supply, prepare, or administer study intervention. 
All study intervention must be stored in a secure, environmentally controlled, and 
monitored (manual or automated) area in accordance with the labeled storage 
conditions with access limited to the investigator and authorized study personnel. 
 The investigator or authorized study personnel are responsible for study 
intervention accountability, reconciliation, and record maintenance (that is, 
receipt, reconciliation, and final disposition records). 
 Further guidance and information for the final disposition of unused study 
interventions are provided in the Study Reference Manual. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
All participants will be centrally assigned to randomized study intervention using an Interactive 
Web-Response System (IWRS). Participants will be stratified by country and baseline Lp(a) 
(<275 nmol/L, ≥275 nmol/L). Before the study is initiated, the log in information and directions 
for the IWRS will be provided to each site. 
Study intervention will be dispensed at the study visits summarized in SoA. 
Returned study intervention should not be re-dispensed to the participants. 
This is a double-blind study in which participants are blinded to study intervention. The IWRS 
will be programmed with blind-breaking instructions. In case of an emergency, the investigator 
has the sole responsibility for determining if unblinding of a participants’ intervention 
assignment is warranted. Participant safety must always be the first consideration in making such 
a determination. If the investigator decides that unblinding is warranted, the investigator should 
make every effort to contact the sponsor prior to unblinding a participant’s intervention 
assignment unless this could delay emergency treatment for the participant. If a participant’s 
intervention assignment is unblinded, the sponsor must be notified immediately within 24 hours 
of this occurrence. The date and reason that the blind was broken must be recorded. 
If an investigator, site personnel performing assessments, or participant is unblinded, the 
participant may be continued in the study. 
6.4. 
Study Intervention Compliance 
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 and documented in the source documents and case report form (CRF). 
A record of the number of study intervention tablets dispensed to and taken by each participant 
must be maintained and reconciled with study intervention and compliance records. Intervention 
start and stop dates, including dates for intervention delays, will also be recorded in the CRF. 
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6.5. 
Dose Modification 
This protocol does not allow dose adjustments. 
6.6. 
Continued Access to Study Intervention after the End of the Study 
LY3473329 will not be made available to participants after completion of the study. 
6.7. 
Treatment of Overdose 
For this study, any dose of LY3473329 greater than the planned dose will be considered an 
overdose. 
The sponsor does not recommend specific treatment for an overdose. 
In the event of an overdose, the investigator/treating physician should: 
● contact the medical monitor immediately 
● evaluate the participant to determine, in consultation with the medical monitor, 
whether study intervention should be interrupted or whether the dose should be 
reduced, and 
● closely monitor the participant for any AE/SAE and laboratory abnormalities until 
study intervention no longer has a clinical effect or can no longer be detected 
systemically (at least 14 days). 
6.8. 
Concomitant Therapy 
Any medication or vaccine, including OTC or prescription medicines, vitamins, and/or herbal 
supplements, that the participant is receiving at the time of enrollment or receives during the 
study must be recorded along with 
● reason for use 
● dates of administration including start and end dates, and 
● dosage information including dose and frequency for concomitant therapy of 
special interest. 
The medical monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
Participants on the following medications according to local practice must be on a stable regimen 
for at least 4 weeks prior to screening and expected to remain on a stable regimen through the 
end of the post-treatment follow-up period, unless changes need to be made because of AEs: 
 lipid-lowering drugs (e.g., statins, ezetimibe, PCSK9 inhibitors, prescription-dose niacin, 
fibrates, fish oil, or other products containing omega-3 fatty acids, including OTC 
preparations), and 
 testosterone, estrogens, progesterone, growth hormone, or progestins. 
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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 10.1. 
7.1. 
Discontinuation of Study Intervention 
When necessary, a participant may be permanently discontinued from study intervention. If so, 
the participant will remain in the study to complete procedures for an ED visit and post-treatment 
follow-up, if applicable, as shown in the SoA. 
A participant should be permanently discontinued from study intervention if 
 the participant becomes pregnant during the study 
 in the opinion of the investigator, the participant should permanently discontinue the 
study intervention for safety reasons 
 if the investigator determines that a systemic hypersensitivity reaction has occurred 
related to study intervention administration, the participant may be permanently 
discontinued from the study intervention, and the sponsor’s designated medical monitor 
should be notified. If the investigator is uncertain about whether a systemic 
hypersensitivity reaction has occurred and whether discontinuation of study intervention 
is warranted, the investigator may consult the sponsor 
 the participant has an AE or an SAE or a clinically significant change in a laboratory 
value that, in the opinion of the investigator, merits discontinuation of study intervention 
and appropriate measures being taken 
 if the participant experiences a hepatic event or liver test abnormality as specified in the 
liver chemistry stopping criteria (see Section 7.1.1), and 
 HBV or HCV: The participant tests positive for HBV DNA (see Section 8.2.5) or tests 
positive for HCV RNA (Section 8.2.6). 
Note: The HBV DNA result is to be confirmed if initial positive test result is positive 
but below the level of quantification. Prior to discontinuation of any 
immunomodulatory and/or immunosuppressive therapy, including study intervention, 
the participant is to be referred to, evaluated, and managed by a specialist physician 
with expertise in evaluation and management of viral hepatitis. The timing of 
discontinuation from study intervention relative to the initiation of any antiviral 
treatment for hepatitis is to be based on the recommendation of the consulting 
specialist physician, in conjunction with the investigator, and aligned with medical 
guidelines and standard of care. 
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7.1.1. 
Liver Chemistry Stopping Criteria 
The study drug should be interrupted or discontinued if 1 or more of these conditions occur: 
Elevation 
Exception 
ALT or AST >8x ULN 
 
ALT or AST >5x ULN for more than 2 weeks 
 
ALT or AST >3x ULN and either TBL >2x ULN or INR >1.5  
In participants with Gilbert’s syndrome, 
doubling of direct bilirubin should be used 
for drug interruption/ discontinuation 
decisions rather than TBL >2x ULN 
ALT or AST >3x ULN with the appearance of fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, fever, rash, 
and/or eosinophilia (>5%) 
 
ALP >3x ULN, when the source of increased ALP is the liver 
 
ALP >2.5x ULN and TBL > 2x ULN  
In participants with Gilbert’s syndrome, 
doubling of direct bilirubin should be used 
for drug interruption/ discontinuation 
decisions rather than TBL>2x ULN 
ALP >2.5x ULN with the appearance of fatigue, nausea, vomiting, 
right upper quadrant pain or tenderness, fever, rash, and/or 
eosinophilia (>5%) 
 
Source: FDA Guidance for Industry: Drug-Induced Liver Injury: Premarketing Clinical Evaluation, July 2009 and 
other consensus guidelines, with minor modifications 
Abbreviations: ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
INR = international normalized ratio; TBL = total bilirubin; ULN= upper limit of normal. 
Resumption of the study drug can be considered only in consultation with the Lilly-designated 
medical monitor and only if the liver test results return to baseline and if a self-limited, non-drug 
etiology is identified. 
7.1.2. 
QTc Stopping Criteria 
If a clinically significant finding is identified, including, but not limited to changes from baseline 
in QT interval corrected using Fridericia’s formula (QTcF) after enrollment, the investigator or 
qualified designee will determine if the participant can continue in the study and if any change in 
participant management is needed. This review of the ECG printed at the time of collection must 
be documented. Any new clinically relevant finding should be reported as an AE. 
7.1.3. 
Temporary Discontinuation 
If for some reason, study intervention is temporarily stopped for reasons other than safety, 
participant should resume intervention as soon as possible. 
7.1.4. 
Rechallenge 
If study intervention is temporarily stopped for safety, participants may be rechallenged with 
study intervention once if appropriate in the opinion of the investigator. 
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7.2. 
Participant Discontinuation/Withdrawal from the Study 
Discontinuation is expected to be uncommon. 
A participant may withdraw from the study: 
● at any time at the participant’s own request 
● at the request of the participant’s designee, for example, parents or legal guardian 
● at the discretion of the investigator for safety, behavioral, compliance, or 
administrative reasons 
● if enrolled in any other clinical study involving an investigational product, or 
enrolled in any other type of medical research judged not to be scientifically or 
medically compatible with this study 
At the time of discontinuing from the study, if possible, the participant will complete procedures 
for an ED visit and post-treatment follow-up, if applicable, as shown in the SoA. If the 
participant has not already discontinued the study intervention, the participant will be 
permanently discontinued from the study intervention at the time of the decision to discontinue 
the study. 
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. If a participant 
withdraws from the study, the participant may request destruction of any samples taken and not 
tested, and the investigator must document this in the site study records. 
7.3. 
Lost to Follow up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. Site personnel or designee are 
expected to make diligent attempts to contact participants who fail to return for a scheduled visit 
or were otherwise unable to be followed up by the site. 
Site personnel, or an independent third party, will attempt to collect the vital status of the 
participant within legal and ethical boundaries for all participants randomized, including those 
who did not get investigational product. Public sources may be searched for vital status 
information. If vital status is determined to be deceased, this will be documented and the 
participant will not be considered lost to follow-up. Sponsor personnel will not be involved in 
any attempts to collect vital status information. 
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8. 
Study Assessments and Procedures 
● Study procedures and their timing are summarized in the SoA. 
● 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. 
● 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. 
8.1. 
Efficacy Assessments 
8.1.1. 
Primary Efficacy Assessment 
Elevated Lp(a) is recognized as an important risk factor for cardiovascular disease. Lp(a) will be 
collected for each participant at the times shown in the SoA (Section 1.3). 
8.1.2. 
Secondary Efficacy Assessments 
The 2018 AHA/ACC Guideline on the management of blood cholesterol identified Lp(a) 
≥50 mg/dL (≥125 nmol/L) as risk enhancing. As a responder analysis, the proportions of 
participants achieving Lp(a) <125 nmol/L at Week 12 will be assessed. 
At times specified in the SoA, blood samples will be collected to measure changes in levels of 
these markers 
 ApoB 
 hsCRP 
See Section 9.3 for definitions of the efficacy endpoints. 
8.2. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA. 
8.2.1. 
Electrocardiograms 
Single 12-lead ECG will be obtained as outlined in the SoA (see Section 1.3) using an ECG 
machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc 
intervals. Refer to Section 7.1.2 for QTc withdrawal criteria and any additional QTc readings 
that may be necessary. 
8.2.2. 
Clinical Safety Laboratory Tests 
● See Appendix 10.2 for the list of clinical laboratory tests to be performed and the 
SoA for the timing and frequency. 
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● The investigator must review the laboratory results, document this review, and 
report any clinically relevant changes occurring during the study as an AE. The 
laboratory results must be retained with source documents unless a Source 
Document Agreement or comparable document cites an electronic location that 
accommodates the expected retention duration. Clinically significant abnormal 
laboratory findings are those which are not associated with the underlying disease, 
unless judged by the investigator to be more severe than expected for the 
participant’s condition. 
● All laboratory tests with values considered clinically significantly abnormal 
during participation in the study or within 4 weeks after the last dose of study 
intervention should be repeated until the values return to normal or baseline or are 
no longer considered clinically significant by the investigator or medical monitor. 
○ If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified and the 
sponsor notified. 
○ All protocol-required laboratory assessments, as defined in Appendix 10.2, 
must be conducted in accordance with the SoA, standard collection 
requirements, and laboratory manual. 
● If laboratory values from non-protocol-specified laboratory assessments 
performed at an investigator-designated local laboratory require a change in 
participant management or are considered clinically significant by the 
investigator, for example, SAE or AE or dose modification, then report the 
information as an AE. 
8.2.3. 
Hepatic Safety 
Close hepatic monitoring 
Laboratory tests (Appendix 10.6), including ALT, AST, ALP, TBL, direct bilirubin (D. Bil), 
gamma-glutamyltransferase (GGT), and creatine kinase (CK), should be repeated within 48 to 
72 hours to confirm the abnormality and to determine if it is increasing or decreasing, if 1 or 
more of these conditions occur: 
If a participant with baseline results 
of...  
develops the following elevations: 
ALT or AST <1.5x ULN 
ALT or AST ≥3x ULN 
ALP <1.5x ULN 
ALP ≥2x ULN 
TBL <1.5x ULN 
TBL ≥2x ULN, except for participants with Gilbert’s 
syndrome 
ALT or AST ≥1.5x ULN 
ALT or AST ≥2x baseline 
ALP ≥1.5x ULN 
ALP ≥2x baseline 
TBL ≥1.5x ULN 
TBL ≥1.5x baseline, except for participants with 
Gilbert’s syndrome 
 
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If the abnormality persists or worsens, clinical and laboratory monitoring, and evaluation for 
possible causes of abnormal liver tests should be initiated by the investigator in consultation with 
the Lilly-designated medical monitor. At a minimum, this evaluation should include physical 
examination and a thorough medical history, including symptoms, recent illnesses (for example, 
heart failure, systemic infection, hypotension, or seizures), recent travel, history of concomitant 
medications (including over the counter), herbal and dietary supplements, history of alcohol 
drinking and other substance abuse. 
Initially, monitoring of symptoms and hepatic biochemical tests should be done at a frequency of 
1 to 3 times weekly, based on the participant’s clinical condition and hepatic biochemical tests. 
Subsequently, the frequency of monitoring may be lowered to once every 1 to 2 weeks, if the 
participant’s clinical condition and laboratory results stabilize. Monitoring of ALT, AST, ALP, 
and TBL should continue until levels normalize or return to approximate baseline levels. 
Comprehensive hepatic evaluation 
A comprehensive evaluation should be performed to search for possible causes of liver injury if 1 
or more of these conditions occur: 
If a participant with baseline 
results of...  
develops the following elevations: 
ALT or AST <1.5x ULN 
ALT or AST ≥3x ULN with hepatic signs/symptomsa, or 
ALT or AST ≥5x ULN 
ALP <1.5x ULN 
ALP ≥3x ULN 
TBL <1.5x ULN 
TBL ≥2x ULN (except for participants with Gilbert’s 
syndrome) 
ALT or AST ≥1.5x ULN 
ALT or AST ≥2x baseline with hepatic signs/symptomsa, or 
ALT or AST ≥3x baseline 
ALP ≥1.5x ULN 
ALP ≥2x baseline 
TBL ≥1.5x ULN 
TBL ≥2x baseline (except for participants with Gilbert’s 
syndrome)  
a Hepatic signs or symptoms are severe fatigue, nausea, vomiting, right upper quadrant abdominal pain, fever, rash, 
and/or eosinophilia >5%. 
At a minimum, this evaluation should include physical examination and a thorough medical 
history, as outlined above, as well as tests for prothrombin time (PT)-INR; tests for viral hepatitis 
A, B, C, or E; tests for autoimmune hepatitis; and an abdominal imaging study, for example, 
ultrasound or CT scan. 
Based on the participant’s history and initial results, further testing should be considered in 
consultation with the Lilly-designated medical monitor, including tests for hepatitis D virus 
(HDV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), acetaminophen levels, 
acetaminophen protein adducts, urine toxicology screen, Wilson’s disease, blood alcohol levels, 
urinary ethyl glucuronide, and blood phosphatidylethanol. Based on the circumstances and the 
investigator’s assessment of the participant’s clinical condition, the investigator should consider 
referring the participant for a hepatologist or gastroenterologist consultation, magnetic resonance 
cholangiopancreatography, endoscopic retrograde cholangiopancreatography, cardiac 
echocardiogram, or a liver biopsy. 
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Additional hepatic data collection (hepatic safety CRF) in study participants who have 
abnormal liver tests during the study 
Additional hepatic safety data collection in hepatic safety CRF should be performed in study 
participants who meet 1 or more of the following 5 conditions: 
1. Elevation of serum ALT to ≥5x ULN on 2 or more consecutive blood tests, if baseline 
ALT <1.5x ULN 
➢ In participants with baseline ALT ≥1.5x ULN, the threshold is ALT ≥3x baseline 
on 2 or more consecutive tests 
2. Elevated TBL to ≥ 2x ULN, if baseline TBL <1.5x ULN, except for cases of known 
Gilbert’s syndrome 
➢ In participants with baseline TBL ≥1.5x ULN, the threshold should be TBL ≥2x 
baseline 
3. Elevation of serum ALP to ≥2x ULN on 2 or more consecutive blood tests, if baseline 
ALP <1.5x ULN 
➢ In participants with baseline ALP ≥1.5x ULN, the threshold is ALP ≥2x baseline 
on 2 or more consecutive blood tests 
4. Hepatic event considered to be an SAE 
5. Discontinuation of study drug due to a hepatic event 
Note: the interval between the 2 consecutive blood tests should be at least 2 days. 
8.2.4. 
Hypersensitivity Reactions 
Many drugs, including oral agents and biologic agents, carry the risk of systemic hypersensitivity 
reactions. If such a reaction occurs, additional data should be provided to the sponsor in the 
designated CRFs. 
Sites should have appropriately trained medical staff and appropriate medical equipment 
available when study participants are receiving study intervention. It is recommended that 
participants who experience a systemic hypersensitivity reaction be treated per national and 
international guidelines. 
In the case of a suspected systemic hypersensitivity event, additional blood samples should be 
collected as described in Appendix 10.2.1. Laboratory results are provided to the sponsor via the 
central laboratory. 
8.2.5. 
Hepatitis B Testing and Monitoring 
As specified in the SoA (Section 1.3), initial testing for HBV infection includes HBsAg and 
hepatitis B core antibody (HBcAb). 
● If HBsAg is positive, the participant is excluded. 
● If HBsAg is negative and HBcAb is negative, the participant is not excluded. 
● If HBsAg is negative and HBcAb is positive, further testing for HBV DNA is 
required. 
○ If the screening HBV DNA is positive, the participant is excluded. 
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○ If the screening HBV DNA is negative, the participant is not excluded. Repeat 
testing for HBV DNA is required at least every 3 months during the study. 
Management of enrolled participants with detectable HBV DNA during the study 
If HBV DNA is detected, study intervention will be temporarily withheld or permanently 
discontinued, as described in Section 7.1, and the participant should receive appropriate follow-
up medical care. 
8.2.6. 
Hepatitis C Testing 
As specified in the SoA (Section 1.3), initial testing for HCV infection includes testing for 
anti-HCV. 
● If anti-HCV is positive, a test for circulating HCV RNA is required. 
● If HCV RNA test is negative, the participant is not excluded. 
● If HCV RNA test is positive, the participant is excluded. 
Participants who have had HCV infection and have been successfully treated, defined as a 
sustained virologic response (HCV RNA by PCR negative for at least 24 weeks following 
treatment completion), are not excluded on the basis of HCV as long as HCV RNA test is 
negative at screening. 
If HCV RNA is detected during the study, the study intervention will be discontinued 
(Section 7.1), and the participant should receive appropriate follow-up medical care. 
8.3. 
Adverse Events, Serious Adverse Events, and Product Complaints 
The definitions of the following events can be found in Appendix 10.3: 
 AEs 
 SAEs, and 
 Product complaints (PCs). 
These events will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant’s legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet these definitions and remain responsible for following up events that 
are serious, considered related to the study intervention or study procedures, or that caused the 
participant to discontinue the study intervention or study (see Section 7). 
Care will be taken not to introduce bias when detecting events. Open-ended and non-leading 
verbal questioning of the participant is the preferred method to inquire about event occurrences. 
After the initial report, the investigator is required to proactively follow each participant at 
subsequent visits or contacts. All SAEs will be followed until resolution, stabilization, the event 
is otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). For PCs, 
the investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality. Further information on 
follow-up procedures is provided in Appendix 10.3. 
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8.3.1. 
Timing and Mechanism for Collecting Events 
This table describes the timing, deadlines, and mechanism for collecting events. 
Event 
Collection 
Start 
Collection 
Stop 
Timing for Reporting 
to Sponsor or 
Designee 
Mechanism for 
Reporting 
Back-up 
Method of 
Reporting 
Adverse Event 
AE 
Signing of 
the ICF 
Participation 
in study has 
ended 
As soon as possible 
upon site awareness 
AE CRF 
N/A 
AE – related to 
prescreening 
study procedure 
Signing of 
the 
prescreening 
ICF 
Signing of 
the ICF 
As soon as possible 
upon site awareness 
AE CRF 
N/A 
Serious Adverse Event 
SAE and SAE 
updates – prior 
to start of study 
intervention and 
deemed 
reasonably 
possibly related 
to study 
procedures 
Signing of 
the ICF 
Start of 
intervention 
Within 24 hours of 
awareness 
SAE CRF 
SAE paper 
form 
SAE and SAE 
updates – after 
start of study 
intervention 
Start of 
intervention 
Participation 
in study has 
ended 
Within 24 hours of 
awareness 
SAE CRF 
SAE paper 
form 
SAEa – after 
participant’s 
study 
participation has 
ended and the 
investigator 
becomes aware 
After 
participant’s 
study 
participation 
has ended 
N/A 
Promptly 
SAE paper form 
N/A 
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Event 
Collection 
Start 
Collection 
Stop 
Timing for Reporting 
to Sponsor or 
Designee 
Mechanism for 
Reporting 
Back-up 
Method of 
Reporting 
Pregnancy 
Pregnancy in 
female 
participants and 
female partners 
of male 
participants 
After the 
start of study 
intervention 
At least 65 
days after the 
last dose of 
study 
intervention 
Within 24 hours (see 
Section 8.3.2) 
Pregnancy paper 
form 
Pregnancy 
paper form 
Product Complaints 
PC associated 
with an SAE or 
might have led 
to an SAE 
Start of study 
intervention 
End of study 
intervention 
Within 24 hours of 
awareness 
PC form 
N/A 
PC not 
associated with 
an SAE 
Start of study 
intervention 
End of study 
intervention 
Within 1 business day 
of awareness 
PC form 
N/A 
Updated PC 
information 
— 
— 
As soon as possible 
upon site awareness 
Originally 
completed PC form 
with all changes 
signed and dated by 
the investigator 
N/A 
PC, if 
investigator 
becomes aware 
Participation 
in study has 
ended 
N/A 
Promptly 
PC form 
 
Abbreviations: AE = adverse event; CRF = case report form; ICF = informed consent form; N/A = not applicable; 
PC = product complaint; SAE = serious adverse event. 
a SAEs should not be reported unless the investigator deems them to be possibly related to study treatment or study 
participation. 
8.3.2. 
Pregnancy 
Collection of pregnancy information 
Male participants with partners who become pregnant 
● The investigator will attempt to collect pregnancy information on any male 
participant’s female partner who becomes pregnant while the male participant is 
in this study. This applies only to male participants who receive study 
intervention. 
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● After learning of a pregnancy in the female partner of a study participant, the 
investigator will 
o obtain a consent to release information from the pregnant female partner 
directly, and 
o within 24 hours after obtaining this consent will record pregnancy information 
on the appropriate form and submit it to the sponsor. 
The female partner will also be followed to determine the outcome of the 
pregnancy. Information on the status of the mother and child will be forwarded to 
the sponsor. Generally, the follow-up will be no longer than 6 to 8 weeks 
following the estimated delivery date. Any termination of the pregnancy will be 
reported regardless of gestational age, fetal status (presence or absence of 
anomalies), or indication for the procedure. 
Female participants who become pregnant 
● The investigator will collect pregnancy information on any female participant 
who becomes pregnant while participating in this study. The initial information 
will be recorded on the appropriate form and submitted to the sponsor within 24 
hours of learning of a participant's pregnancy. 
● The participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on the participant and the neonate 
and the information will be forwarded to the sponsor. Generally, follow-up will 
not be required for longer than 6 to 8 weeks beyond the estimated delivery date. 
Any termination of pregnancy will be reported, regardless of gestational age, fetal 
status (presence or absence of anomalies), or indication for the procedure. 
● While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE. 
● A spontaneous abortion (occurring at <20 weeks gestational age) or still birth 
(occurring at ≥20 weeks gestational age) is always considered to be an SAE and 
will be reported as such. 
● Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in 
protocol Section 8.3.1. While the investigator is not obligated to actively seek this 
information in former study participants, he or she may learn of an SAE through 
spontaneous reporting. 
● Any female participant who becomes pregnant while participating in the study 
will discontinue study intervention or be withdrawn from the study. If the 
participant is discontinued from the study, follow the standard discontinuation 
process and continue directly to the follow-up phase. The follow-up on the 
pregnancy outcome should continue independent of intervention or study 
discontinuation. 
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8.3.3. 
Major Adverse Cardiovascular Events 
Nonfatal cardiovascular AEs will be adjudicated by a committee of physicians external to Lilly 
with cardiology expertise. This committee will be blinded to treatment assignment. 
The nonfatal cardiovascular AEs to be adjudicated include 
 myocardial infarction, 
 hospitalization for unstable angina, 
 hospitalization for heart failure, 
 coronary interventions, such as coronary artery bypass graft or percutaneous coronary 
intervention, 
 cerebrovascular events, including cerebrovascular accident (stroke) and transient 
ischemic attack, 
 cardiogenic shock, 
 resuscitated sudden death, 
 peripheral revascularization procedure, and 
 peripheral arterial event. 
8.4. 
Pharmacokinetics 
 At the visits and times specified in the SoA (Section 1.3), blood samples will be collected 
to determine the LY3473329 plasma concentrations. 
 Instructions for the collection and handling of blood samples will be provided by the 
sponsor. Sampling times for PK evaluation are provided as a guidance and should be 
adhered to as closely as possible. The actual date and time (24-hour clock time) of each 
sample collection will be recorded. 
 The pre-dose sample at Visit 2 can be taken between waking up and dosing. On 
subsequent dosing days, pre-dose samples should be obtained no more than 1 hour prior 
to dosing. 
 A maximum of 3 additional PK samples may be drawn at other time points during the 
study, if warranted and agreed upon by both the investigator and the sponsor. A PK 
sample should be obtained at the ED visit, if applicable and the follow-up visit. 
 Drug concentration information that would unblind the study will not be reported to 
investigative sites or blinded personnel until the study has been unblinded. 
● A validated assay will be used to determine plasma LY3473329 concentrations 
from the blood samples collected. The blood samples will be analyzed at a 
laboratory approved by the sponsor. The samples will be retained for a maximum 
of 1 year following last study visit for the study. During this time, any samples 
remaining after the bioanalysis is complete may be used for exploratory analyses, 
such as metabolism, protein binding, or bioanalytical method development or 
validation work. 
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8.5. 
Pharmacodynamics 
Samples to evaluate the Pharmacodynamic properties of LY3473329 are included in the efficacy 
measures and not applicable here. 
8.6. 
Genetics 
An optional blood sample for DNA isolation will be collected from participants. 
See Appendix 10.5 for information regarding genetic research and Appendix 10.1.12 for details 
about sample retention and custody. 
8.7. 
Biomarkers 
Serum and plasma samples will be collected and used for exploratory biomarker research, where 
local regulations allow. See Clinical Laboratory Tests and the SoA for sample collection 
information. 
Samples will be used for research on the drug target, disease process, variable response to 
LY3473329, pathways associated with lipid metabolism, mechanism of action of LY3473329, 
and/or research method, or for validating diagnostic tools or assay(s) related to lipid metabolism 
or other relevant disease states. 
Samples may be used for research to develop methods, assays, prognostics, and/or companion 
diagnostics related to the intervention target, disease state, pathways associated with disease, 
and/or the mechanism of action of the study intervention. 
Sample retention is described in Section 10.1.12. 
8.8. 
Immunogenicity Assessments 
Immunogenicity is not evaluated in this study. 
8.9. 
Health Economics 
Health economics or medical resource utilization and health economics parameters are not 
evaluated in this study. 
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9. 
Statistical Considerations 
The statistical analysis plan (SAP) will be finalized prior to first participant first visit, and it will 
include a more technical and detailed description of the statistical analyses described in this 
section. This section is a summary of the planned statistical analyses of the most important 
endpoints, including primary and secondary endpoints. 
9.1. 
Statistical Hypotheses 
The study hypothesis for the primary objective is that oral QD administration of LY3473329 
10 mg, 60 mg, or 240 mg is superior to placebo in percent change from baseline for Lp(a) at 
Week 12 in participants with elevated Lp(a) and at high risk for cardiovascular events at 
baseline. 
9.1.1. 
Multiplicity Adjustment 
Treatment comparisons will be performed for the primary objective at the full significance level 
of 0.05. No multiplicity adjustments will be made for the analysis of secondary and exploratory 
objectives. 
9.2. 
Analyses Sets 
This table defines the analysis population and datasets for the purposes of analysis. 
Population 
Description 
Screened 
All participants who sign the ICF. 
Randomized 
All participants who are randomly assigned to a treatment arm. 
Efficacy Analysis Set 
(EAS) 
Data obtained during treatment period from all randomly 
assigned participants who are exposed to at least 1 dose of 
double-blind study treatment. Excludes data after discontinuation 
of study drug and for participants inadvertently enrolled. 
Participants will be included in the treatment group to which they 
were randomly assigned. 
Full Analysis Set (FAS) 
Data obtained during the treatment period from all randomly 
assigned participants who are exposed to at least 1 dose of 
intervention, regardless of adherence to intervention. Excludes 
data for participants inadvertently enrolled. Participants will be 
included in the treatment group to which they were randomly 
assigned.  
Safety Analysis Set (SS) 
Data obtained during the treatment period plus safety follow-up 
from all randomly assigned participants who are exposed to at 
least 1 dose of intervention, regardless of adherence to 
intervention. Participants will be included in the treatment group 
to which they were randomly assigned. 
 
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9.3. 
Statistical Analyses 
9.3.1. General Considerations 
Statistical analysis of this study will be the responsibility of Lilly or its designee. 
Any change to the data analysis methods described in the protocol will require an amendment 
only if it changes a principal feature of the protocol. Any other change to the data analysis 
methods described in the protocol, and the justification for making the change, will be described 
in the SAP or the clinical study report (CSR). Additional exploratory analyses of the data will be 
conducted as deemed appropriate. 
Unless otherwise noted, all tests of treatment effects will be conducted at a 2-sided alpha level of 
0.05, and confidence intervals will be calculated at 95%, 2-sided. All tests of interactions 
between treatment groups and other factors will be conducted at a 2-sided alpha level of 0.10. 
Baseline is defined as the last non-missing measurement recorded on or before the randomization 
visit, prior to first dose of intervention, unless otherwise specified. 
Primary estimand of interest and efficacy assessment 
The primary estimand is a precise definition of the treatment effect to be estimated. The primary 
estimand of interest is comparing efficacy of LY3473329 doses to placebo and is named the 
“efficacy estimand” (Section 3). The efficacy estimand represents the efficacy prior to 
discontinuation of intervention. The primary efficacy assessment guided by the efficacy estimand 
will be conducted using the EAS (Section 9.2). 
Secondary estimand of interest 
The secondary estimand of interest is comparing efficacy of LY3473329 doses to placebo and is 
named the “treatment-regimen estimand” (Section 3). The treatment-regimen estimand 
represents the efficacy regardless of discontinuation of intervention. The secondary efficacy 
assessment guided by the treatment-regimen estimand will be conducted using the FAS (Section 
9.2). 
Safety assessments 
Unless specified otherwise, safety assessments will be guided by an estimand comparing safety 
of LY3473329 doses with placebo irrespective of adherence to intervention. Thus, safety 
analyses will be conducted using the SS (Section 9.2). 
Exploratory analyses 
Additional exploratory analyses may be performed as deemed appropriate. Details will be 
provided in the SAP. 
Continuous data 
Continuous data will be summarized using the sample size, mean, SD, median, minimum, and 
maximum. The analysis model to make comparisons among treatment groups relative to 
continuous measurements assessed over time, in addition to the baseline and end-of-treatment 
measurements, will be a mixed model for repeated measures (MMRM). 
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The model terms are 
 treatment 
 visit 
 treatment-by-visit interaction 
 baseline-by-visit interaction 
 baseline measurement 
 baseline Lp(a) stratum (<275 nmol/L, ≥275 nmol/L), and 
 country or region. 
Analysis of covariance (ANCOVA) may be used to make comparisons among treatment groups 
for continuous measurements with only 1 post-baseline assessment. In this case, ANCOVA will 
be conducted with available data and missing values will not be imputed in the analysis. 
Categorical data 
Categorical data will be summarized by sample size, frequency, and percentage. Fisher’s exact 
test will be used to examine the treatment difference in categorical outcomes. Logistic regression 
may be used to examine the treatment difference in binary efficacy outcomes. The negative 
binomial regression model may be used for the treatment comparison of discrete count measures 
if deemed appropriate. Participant-specific random effects may be added to the logistic and the 
negative binomial regression models if longitudinal measurements are available. Model terms in 
the longitudinal logistic or negative binomial regression models are the same as in the MMRM. 
Other statistical methods may be used, as appropriate, and details will be documented in the 
SAP. 
Handling of missing, unused, and spurious data are addressed prospectively in the overall 
statistical methods described in the protocol and in the SAP, where appropriate. Adjustments to 
the planned analyses are described in the final CSR. 
9.3.2. 
Primary Endpoint/Estimand Analysis 
The primary efficacy assessment, guided by the efficacy estimand, will be conducted using the 
EAS for the primary endpoint. 
For the efficacy estimand, the hypothetical strategy is used to handle the intercurrent events of 
permanent discontinuation of intervention. The “treatment-regimen” estimand, which represents 
the efficacy regardless of treatment discontinuation, may also be used to compare the primary 
efficacy of LY3473329 doses with placebo. The analysis guided by the “treatment-regimen” 
estimand will use the FAS. 
The primary efficacy comparison will be based on the contrast between each treatment group of 
LY3473329 and placebo for the mean percent change of Lp(a) from randomization at Visit 2 to 
Week 12 at Visit 7. 
The primary analyses model will be MMRM as described in Section 9.3.1. The Lp(a) will be log 
transformed before statistical analyses, and then back-transformed to present percentage change 
from baseline. Treatment comparisons will be performed at the full significance level of 0.05. 
Additional covariates may be added, and this analysis will be detailed in the SAP. 
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9.3.3. 
Secondary Endpoint(s)/Estimand(s) Analysis 
Secondary endpoints are listed in Section 3. 
The efficacy analyses for the secondary endpoints will use the EAS described in Section 9.3.1. 
The continuous clinical measures, including change in ApoB and hsCRP, may be log 
transformed before statistical analyses, if deemed necessary. Analyses will be conducted in a 
manner similar to the primary efficacy analyses discussed in Section 9.3.2. 
Analyses for percentages of participants reaching Lp(a) <125 nmol/L at Week 12 will be 
conducted using a longitudinal logistic regression model described in Section 9.3.1. Missing 
Lp(a) data at Week 12 may be imputed first before conducting the analyses. 
In these models, additional covariates may be added, if deemed necessary. The details will be 
provided in the SAP. 
9.3.4. 
Exploratory Endpoint(s) Analysis 
Exploratory endpoints are listed in Section 3. 
The continuous clinical measures, including change in lipid profile and change in plasminogen 
activity, will be analyzed using an MMRM. Baseline measures will be used for adjustment. The 
change in SF-36v2 acute form domain scores will be analyzed using an ANCOVA model. 
Baseline domain scores will be used for adjustment. Analyses for proportion of participants 
achieving Lp(a) lowering of at least 150 nmol/L at Week 12 will be conducted using a 
longitudinal logistic regression model described in Section 9.3.1. 
Details of other analyses used for the exploratory objectives will be provided in the SAP. 
9.3.5. 
Safety Analyses 
Safety assessments will be guided by an estimand comparing safety of LY3473329 doses with 
placebo irrespective of adherence to intervention. Thus, safety analyses will be conducted using 
the SS. 
AEs will be coded from the actual term using the Medical Dictionary for Regulatory Activities 
(MedDRA) and reported with preferred terms and system organ class. Selected notable AEs of 
interest may be reported using high-level terms or Standardized MedDRA Queries. 
Summary statistics will be provided for incidence of 
 TEAEs 
 SAEs 
 study discontinuation due to AEs 
 intervention discontinuation due to AEs 
 deaths, and 
 other cardiovascular endpoints. 
Counts and proportions of participants experiencing AEs will be reported for each treatment 
group, and Fisher’s exact test will be used to compare the treatment groups. 
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9.3.5.1. 
Laboratory Measures, Vital Signs, and Electrocardiograms 
Laboratory measures and vital signs will be summarized for each scheduled visit by 
 actual measures at baseline and postbaseline 
 change from baseline to postbaseline, or 
 percent change from baseline to postbaseline. 
The laboratory measures may be log transformed before statistical analyses, if deemed necessary. 
Continuous variables, as well as the change from baseline for these variables or other appropriate 
transformed variables, will be analyzed by MMRM models as described in Section 9.3.1. 
The percentages of participants with treatment-emergent abnormal, high, or low measures, 
including laboratory and vital parameters, will be summarized and compared between treatment 
groups using Fisher’s exact test. 
The analysis details will be provided in the SAP. 
9.3.6. 
Pharmacokinetic and Pharmacodynamic Analyses 
LY3473329 concentration data will be analyzed using a population PK approach via nonlinear 
mixed-effects modeling with the NONMEM software. The relationships between LY3473329 
dose and/or concentration and efficacy, tolerability, and safety endpoints may be characterized. 
Additionally, the impact of intrinsic and extrinsic participant factors, such as age, weight, gender, 
and renal function on PK and/or PD parameters, may be examined as needed. 
9.3.7. 
Subgroup Analyses 
Subgroup analyses of important factors, such as baseline SF-36v2 acute form domain scores , 
baseline Lp(a) level, and other factors to be specified in the SAP, are planned for the key 
outcomes. The models used for these analyses will vary depending on the subgroups and the 
outcome. Other exploratory subgroup analyses may be performed as deemed appropriate. Details 
of the modeling will be provided in the SAP. 
9.4. 
Interim Analysis 
A planned interim analysis may be conducted when at least 50% of the participants complete 
Week 12 at Visit 7 or discontinue the study. The interim will be for the purpose of internal 
planning and decision-making and may assess safety, PK, and/or efficacy measures. Additional 
details related to statistical methods will be described in the SAP. If this happens, an assessment 
committee (AC) will be formed to review the interim analyses in an unblinded manner. The 
details regarding the number of participants and type of analysis will be provided in the AC 
charter and in the unblinding plan. Study team members who have potential contact with the sites 
will remain blinded throughout the study. Information that may unblind the study during the 
analyses will not be reported to study sites or blinded study team members before the study has 
been unblinded. Study sites will receive information about interim results only if deemed 
necessary for the safety of the participants. The study will not be stopped based on the efficacy 
of LY3473329 versus placebo. Therefore, there will be no inflation of the type 1 error rate, and 
no need to employ an alpha spending function or multiplicity adjustment. 
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The database lock and primary data analysis for Study EKBC may occur when all participants 
have completed the study. Unblinded data and results will not be shared with the study sites to 
maintain blinding at the sites while the study is still ongoing. Details will be specified in the 
blinding or unblinding plan and in the AC charter. 
The addition of an interim analysis can be determined at any time during the study and will not 
result in a protocol amendment. 
9.5. 
Sample Size Determination 
The sample size calculation is based on the primary efficacy estimand and its endpoint, percent 
change from baseline at Week 12 in Lp(a). 
Approximately 233 participants will be randomly assigned in a 1:2:2:2 ratio to LY3473329 
10 mg:60 mg:240 mg:placebo. Assuming a 10% dropout rate, this results in approximately 30 
completers for the 10 mg group and 60 completers per arm for the rest of the groups. 
Assuming a standard deviation of 20%, and a 2-sided alpha level of 0.05, the completers for each 
treatment arm will provide >99% power to detect a treatment difference of 60% reduction for the 
primary endpoint of LY3473329 verses placebo. The sample size was determined appropriate to 
provide a sufficient amount of safety data. 
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10. 
Supporting Documentation and Operational Considerations 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
● 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 and Council for International Organizations of 
Medical Sciences (CIOMS) International Ethical Guidelines 
○ Applicable ICH Good Clinical Practice (GCP) Guidelines 
○ Applicable laws and regulations 
● The protocol, protocol amendments, ICF, IB, and other relevant documents, for 
example, advertisements, must be submitted to an Institutional Review Board 
(IRB)/Independent Ethics Committees (IEC) by the investigator and reviewed and 
approved by the IRB/IEC before the study is initiated. 
● Any amendments to the protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants. 
● Protocols and any substantial amendments to the protocol will require health 
authority approval prior to initiation except for changes necessary to eliminate an 
immediate hazard to study participants. 
● The investigator will be responsible for the following: 
○ Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB/IEC 
○ Notifying the IRB/IEC of SAEs or other significant safety findings as required 
by IRB/IEC procedures 
○ Providing oversight of study conduct for participants under their responsibility 
and adherence to requirements of 21 Code of Federal Regulations (CFR), ICH 
guidelines, the IRB/IEC, European regulation 536/2014 for clinical studies (if 
applicable), and all other applicable local regulations 
○ Reporting to the sponsor or designee significant issues related to participant 
safety, participant rights, or data integrity 
● Investigator sites are compensated for participation in the study as detailed in the 
clinical trial agreement (CTA). 
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10.1.2. 
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 course of the study and for 
1 year after completion of the study. 
10.1.3. 
Informed Consent Process 
● The investigator or the investigator’s representative will explain the nature of the 
study, including the risks and benefits, to the participant and answer all questions 
regarding the study. 
● Participants must be informed that their participation is voluntary. 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 entered in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF. 
● Participants must be reconsented 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 and is kept on file. 
Participants who are rescreened are required to sign a new ICF. 
10.1.4. 
Data Protection 
● Participants will be assigned a unique identifier by the sponsor. Any participant 
records, datasets, or tissue samples 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 the participant’s personal study-related data 
will be used by the sponsor in accordance with local data protection law. The 
level of disclosure must also be explained to the participant who will be required 
to give consent for their data to be used as described 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. 
● The sponsor has processes in place to ensure data protection, information security, 
and data integrity. These processes include appropriate contingency plan(s) for 
appropriate and timely response in the event of a data security breach. 
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10.1.5. 
Committees Structure 
10.1.5.1. External Clinical Endpoints Committee 
An independent clinical endpoint committee, external to Lilly, will be formed to adjudicate 
MACE and deaths. This committee will be blinded to treatment assignment. 
10.1.6. 
Dissemination of Clinical Study Data 
Reports 
The sponsor will disclose a summary of study information, including tabular study results, on 
publicly available websites where required by local law or regulation. 
The summary of results will be posted within the time frame specified by local law or regulation. 
If the study remains ongoing in some countries and a statistical analysis of an incomplete dataset 
would result in analyses lacking scientific rigor (for example, underpowered) or compromise the 
integrity of the overall analyses (for example, trial not yet unblinded), the summary of results 
will be submitted within 1 year after the end of the study globally or as soon as available, 
whichever is earlier. 
Data 
The sponsor provides access to all individual participant data collected during the trial, after 
anonymization, with the exception of PK or genetic data. Data are available to request 6 months 
after the indication studied has been approved in the US and EU and after primary publication 
acceptance, whichever is later. No expiration date of data requests is currently set once data are 
made available. 
Access is provided after a proposal has been approved by an independent review committee 
identified for this purpose and after receipt of a signed data-sharing agreement. Data and 
documents, including the study protocol, SAP, CSR, and blank or annotated case report forms, 
will be provided in a secure data-sharing environment for up to 2 years per proposal. 
For details on submitting a request, see the instructions provided at www.vivli.org. 
10.1.7. 
Data Quality Assurance 
● All participant data relating to the study will be recorded on printed or electronic 
CRFs unless transmitted to the sponsor or designee electronically, for example, 
laboratory data. The investigator is responsible for verifying that data entries are 
accurate and correct by physically or electronically signing the CRF. 
● The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF. 
● The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents. 
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● Quality tolerance limits (QTLs) will be pre-defined to identify systematic issues 
that can impact participant safety and/or reliability of study results. These pre-
defined parameters will be monitored during the study, and important excursions 
from the QTLs and remedial actions taken will be summarized in the CSR. 
● Monitoring details describing strategy (for example, 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, are 
provided in the Monitoring Plan. 
● The sponsor or designee is responsible for the data management of this study 
including quality checking of the data. 
● The sponsor assumes accountability for actions delegated to other individuals, for 
example, contract research organizations. 
● Study monitors will perform ongoing source data verification to confirm that data 
transcribed into the CRF 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 the time period outlined in the CTA 
unless local regulations or institutional policies require a longer retention period. 
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. 
● In addition, sponsor or its representatives will periodically check a sample of the 
participant data recorded against source documents at the study site. The study 
may be audited by sponsor or its representatives, and/or regulatory agencies at 
any time. Investigators will be given notice before an audit occurs. 
Data Capture System 
The investigator is responsible for ensuring the accuracy, completeness, legibility, and timeliness 
of the data reported to the sponsor. 
An electronic data capture system (EDC) will be used in this study for the collection of CRF 
data. The investigator maintains a separate source for the data entered by the investigator or 
designee into the sponsor-provided EDC system. The investigator is responsible for the 
identification of any data to be considered source and for the confirmation that data reported are 
accurate and complete by signing the CRF. 
Additionally, clinical outcome assessment data (participant-focused outcome instrument) and 
other data and study drug administration log will be collected by the participant via a paper 
source document, and the information required from this document for completing the CRF will 
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be transcribed by the authorized study personnel into the EDC system and will serve as the 
source documentation. 
Data collected via the sponsor-provided data capture system(s) will be stored at third parties. The 
investigator will have continuous access to the data during the study and until decommissioning 
of the data capture systems. Prior to decommissioning, the investigator will receive or access an 
archival copy of pertinent data for retention. 
Data managed by a central vendor, such as laboratory test data, will be stored electronically in 
the central vendor’s database system, and reports will be provided to the investigator for review 
and retention. Data will subsequently be transferred from the central vendor to the sponsor data 
warehouse. 
Data from complaint forms submitted to the sponsor will be encoded and stored in the global 
product complaint management system. 
10.1.8. 
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 reported on or entered in the CRF and 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 can be found in Section 10.1.7. 
10.1.9. 
Study and Site Start and Closure 
First Act of Recruitment 
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 participant to enter screening. 
Study or Site Termination 
The sponsor or sponsor’s designee reserves the right to close the study site or terminate the study 
at any time for any reason at the sole discretion of the sponsor. Study sites will be closed upon 
study completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to 
For study termination: 
● 
Discontinuation of further study intervention development 
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For site termination: 
● Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor’s procedures, or GCP guidelines 
● Inadequate recruitment (evaluated after a reasonable amount of time) of 
participants by the investigator 
● Total number of participants included earlier than expected. 
If the study is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any contract research organization(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. 
10.1.10. 
Publication Policy 
In accordance with the sponsor’s publication policy, the results of this study will be submitted 
for publication by a peer-reviewed journal. 
10.1.11. 
Investigator Information 
Researchers with appropriate education, training, and experience, as determined by the sponsor, 
will participate as investigators in this clinical trial. 
10.1.12. 
Sample Retention 
Sample retention enables use of new technologies, response to regulatory questions, and 
investigation of variable response that may not be observed until later in the development of 
LY3473329 or after LY3473329 become(s) commercially available. 
 
Sample Type 
Custodian 
Retention Period After Last 
Participant Visita 
Exploratory Biomarker Samples 
Sponsor or Designee 
7 years 
PK 
Sponsor or Designee 
1 years  
Genetics 
Sponsor or Designee 
7 years 
Abbreviation: PK = pharmacokinetic. 
a Retention periods may differ locally. 
 
 
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10.2. 
Appendix 2: Clinical Laboratory Tests 
● The tests detailed in the table below will be performed as noted in the table below. 
● Local laboratory results are only required in the event that the central laboratory 
results are not available in time for either study intervention administration and/or 
response evaluation. If a local sample is required, it is important that the sample 
for central analysis is obtained at the same time. Additionally, if the local 
laboratory results are used to make either a study intervention decision or 
response evaluation, the results must be recorded. 
● In circumstances where the sponsor approves local laboratory testing in lieu of 
central laboratory testing (in the table below), the local laboratory must be 
qualified in accordance with applicable local regulations. 
● Protocol-specific requirements for inclusion or exclusion of participants are 
detailed in Section 5 of the protocol. 
● Additional tests may be performed at any time during the study as determined 
necessary by the investigator or required by local regulations. 
● Investigators must document their review of the laboratory safety results. 
Laboratory results that could unblind the study will not be reported to investigative sites or other 
blinded personnel. 
Clinical Laboratory Tests  
Comments  
Hematology 
Assayed by Lilly-designated laboratory. 
Hemoglobin 
  
Hematocrit 
  
Erythrocyte count (RBCs) 
  
Mean cell volume  
  
Mean cell hemoglobin 
  
Mean cell hemoglobin concentration  
  
Absolute neutrophil count (calculation)  
  
Leukocytes (WBCs)  
  
Differential 
  
Percent and/or absolutes count of: 
  
   Neutrophils, segmented 
  
   Bands  
  
   Lymphocytes 
  
   Monocytes 
  
   Eosinophils 
  
   Basophils 
  
Platelets 
  
Cell morphology (RBCs and WBCs) 
  
  
  
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Clinical Laboratory Tests  
Comments  
Clinical Chemistry 
Assayed by Lilly-designated laboratory. 
Sodium 
  
Potassium 
  
Chloride 
  
Bicarbonate 
  
Total bilirubin 
  
Direct bilirubin 
  
ALP 
  
ALT 
  
AST 
  
GGT 
  
BUN 
  
Creatinine  
  
CK 
  
Uric acid 
  
Total protein 
  
Albumin 
  
Calcium 
  
Phosphorus 
  
Glucose 
  
  
  
Lipid Panel 
Assayed by Lilly-designated laboratory. 
HDL 
 
LDL-C 
Generated by Lilly-designated laboratory. 
If triglycerides are >400; LDL will be measured. 
VLDL-C 
Generated by Lilly-designated laboratory. 
Cholesterol 
 
Triglycerides 
 
  
  
Urinalysis 
Assayed by Lilly-designated laboratory. 
Specific gravity 
  
pH 
  
Protein 
  
Glucose 
  
Ketones 
  
Bilirubin 
  
Urobilinogen 
  
Blood 
  
Nitrite 
  
Urine leukocyte esterase 
  
Microscopic examination of sediment 
  
  
  
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Clinical Laboratory Tests  
Comments  
Hormones (female) 
  
Serum pregnancy  
Assayed by Lilly-designated laboratory.  
Urine pregnancy 
Assayed and evaluated locally. 
FSH  
Assayed by Lilly-designated laboratory.  
  
  
Calculations 
Generated by Lilly-designated laboratory. 
eGFR (CKD-EPI)  
  
UACR 
 
  
  
TB, HIV, and Hepatitis Serology 
Assayed by Lilly-designated laboratory. 
HIV testing  
 
HCV testing: 
 
   HCV antibody  
 
   HCV RNA 
 
HBV testing:  
 
   HBV DNA  
Performed only for participants who test positive 
for HBcAb.  
   HBcAb  
  
   HBsAg  
  
   HBsAb 
  
  
  
Pharmacokinetic Samples  
Assayed by Lilly-designated laboratory. 
 
LY3473329 concentration 
Results will not be provided to the investigative 
sites. 
 
 
Additional Testing  
Assayed by Lilly-designated laboratory. 
Lp(a) 
Results will be provided to the investigative sites 
during prescreening or screening. Results will 
not be provided to the investigative sites after 
randomization. 
ApoB 
Results will not be provided to the investigative 
sites. 
Plasminogen activity 
Results will be provided to the investigative 
sites. 
hsCRP 
Results will be provided to the investigative 
sites. 
TSH 
HbA1c  
  
  
  
  
Genetics Sample 
Assayed by Lilly-designated laboratory.  
Results will not be provided to the investigative 
sites. 
Whole blood (EDTA) 
  
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Clinical Laboratory Tests  
Comments  
Exploratory Biomarker Storage Samples 
Assayed by Lilly-designated laboratory.  
Results will not be provided to the investigative 
sites. 
  Serum 
  
  Plasma (EDTA) 
  
Abbreviations: ALP = alkaline phosphatase; ALT = alanine aminotransferase; ApoB = apolipoprotein b; AST = 
aspartate aminotransferase; BUN = blood urea nitrogen; CK = creatine kinase; CKD-EPI = chronic kidney 
disease epidemiology collaboration; EDTA = ethylenediamine tetraacetic acid; eGFR = estimated glomerular 
filtration rate; FSH = follicle-stimulating hormone; GGT = gamma-glutamyl transferase; HbA1c = hemoglobin 
A1c; HBcAb = hepatitis B core antibody; HBsAb = hepatitis B surface antibody; HBsAg = hepatitis B surface 
antigen; HBV = hepatitis B virus; HCV = hepatitis C virus; HDL = high-density lipoprotein; HIV = human 
immunodeficiency virus; hsCRP = high-sensitivity C-reactive protein; LDL-C = low-density lipoprotein; Lp(a) = 
Lipoprotein(a); RBC = red blood cell; TSH = thyroid stimulating hormone; UACR = urine albumin creatinine 
ratio; VLDL-C = very low-density lipoprotein; WBC = white blood cell. 
10.2.1. 
Laboratory Samples to be Obtained at the Time of a Systemic Hypersensitivity 
Event 
Purpose of collecting samples after a systemic hypersensitivity event 
The samples listed in this appendix are not collected for acute study participant management. 
The sponsor will use the laboratory test results from these samples to characterize 
hypersensitivity events across the clinical development program. 
When to collect samples after a systemic hypersensitivity event occurs 
Collect the samples listed below if a systemic hypersensitivity event is suspected. The timing 
should be as designated in the table, assuming the participant has been stabilized. 
Obtain follow-up pre-dose samples at the next regularly scheduled laboratory sample collection, 
ideally prior to the next dose after the event, to assess post-event return-to-baseline values. 
Timing 
Sample Type 
Laboratory Testa 
Collect from 30 minutes to 4 hours 
after the start of the event. 
● 
Note: The optimal collection 
time is from 1 to 2 hours after 
the start of event. 
Serum 
Total tryptase 
Serum 
Complements (C3) 
Plasma 
Complements (C3a and C5a) 
Serum 
Cytokine panel (IL-6, IL‐1β, IL‐10, or any cytokine 
panel that includes these 3 cytokines)  
a All samples for hypersensitivity testing will be assayed by Lilly-designated laboratory. Results will not be 
provided to the study site. If samples are not collected or are collected outside the specified time period, this will 
not be considered a protocol deviation. 
Abbreviations: ADA = anti-drug antibodies; IL = interleukin. 
What information to record 
Record the date and time when the samples are collected. 
Allowed additional testing for participant management 
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The investigator may perform additional tests locally, if clinically indicated, for acute study 
participant management. 
 
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10.3. 
Appendix 3: Adverse Events and Serious Adverse Events: Definitions 
and Procedures for Recording, Evaluating, Follow-up, and 
Reporting 
10.3.1. 
Definition of AE 
AE Definition 
 An AE is any untoward medical occurrence in a participant administered a 
pharmaceutical product and which does not necessarily have a causal relationship with 
the study intervention. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a medicinal (investigational) product, whether or 
not related to the medicinal (investigational) product. 
 
Events Meeting the AE Definition 
 Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (for example, ECG, radiological scans, and vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator, that is, not related 
to progression of underlying disease. 
 Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
 New condition detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study. 
 Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
 Medication error, misuse, or abuse of investigational medicinal product, including 
signs, symptoms, or clinical sequelae. 
 Lack of efficacy or failure of expected pharmacological action per se will not be 
reported as an AE or SAE. Such instances will be captured in the efficacy assessments. 
However, the signs, symptoms, and/or clinical sequelae resulting from lack of efficacy 
will be reported as AE or SAE if they fulfill the definition of an AE or SAE.  
 
Events NOT Meeting the AE Definition 
 Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
 The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition. 
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 Medical or surgical procedure (for example, endoscopy, appendectomy): the condition 
that leads to the procedure is the AE. 
 Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
 Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.  
10.3.2. 
Definition of SAE 
An SAE is defined as any untoward medical occurrence that, at any dose, meets 1 or 
more of the criteria listed: 
a. Results in death 
b. Is life-threatening 
The term life-threatening in the definition of serious refers to an event in which the participant 
was at risk of death at the time of the event. It does not refer to an event, which hypothetically 
might have caused death, if it were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
 In general, hospitalization signifies that the participant has been admitted to hospital or 
emergency ward (usually involving at least an overnight stay) for observation and/or 
treatment that would not have been appropriate in the physician’s office or outpatient 
setting. Complications that occur during hospitalization are AEs. If a complication 
prolongs hospitalization or fulfills any other serious criteria, the event is serious. When 
in doubt as to whether hospitalization occurred or was necessary, the AE should be 
considered serious. 
 Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE. 
d. Results in persistent disability/incapacity 
 The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
 This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, 
and accidental trauma (for example, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect 
 Abnormal pregnancy outcomes (for example, spontaneous abortion, fetal death, 
stillbirth, congenital anomalies, ectopic pregnancy) are considered SAEs. 
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f. 
Other situations: 
 Medical or scientific judgment should be exercised by the investigator in deciding 
whether SAE reporting is appropriate in other situations such as important medical 
events that may not be immediately life-threatening or result in death or hospitalization 
but may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events should 
usually be considered serious. 
 
Examples of such events include invasive or malignant cancers, intensive treatment in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency or 
drug abuse.  
 
10.3.3. 
Definition of Product Complaints 
Product Complaint 
 A product complaint is any written, electronic, or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, effectiveness 
or performance of a study intervention. When the ability to use the study intervention 
safely is impacted, the following are also PCs: 
o Deficiencies in labeling information, and 
o Use errors for device or drug-device combination products due to ergonomic 
design elements of the product. 
 Product complaints related to study interventions used in clinical trials are collected in 
order to ensure the safety of participants, monitor quality, and to facilitate process and 
product improvements. 
 Investigators will instruct participants to contact the site as soon as possible if he or she 
has a product complaint or problem with the study intervention so that the situation can 
be assessed. 
 An event may meet the definition of both a product complaint and an AE/SAE. In such 
cases, it should be reported as both a PC and as an AE/SAE. 
 
10.3.4. 
Recording and Follow-Up of AE and/or SAE and Product Complaints 
AE, SAE, and Product Complaint Recording 
 When an AE/SAE/product complaint occurs, it is the responsibility of the investigator 
to review all documentation (for example, hospital progress notes, laboratory reports, 
and diagnostics reports) related to the event. 
 The investigator will then record all relevant AE/SAE/product complaint information 
in the participant’s medical records, in accordance with the investigator’s normal 
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clinical practice. AE/SAE information is reported on the appropriate CRF page and 
product complaint information is reported on the Product Complaint Form. 
Note: An event may meet the definition of both a product complaint and an AE/SAE. 
In such cases, it should be reported as both a product complaint and as an AE/SAE. 
 It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to Sponsor or designee in lieu of completion of the CRF page for AE/SAE and 
the Product Complaint Form for PCs. 
 There may be instances when copies of medical records for certain cases are requested 
by Sponsor or designee. In this case, all participant identifiers, with the exception of 
the participant number, will be redacted on the copies of the medical records before 
submission to Sponsor or designee. 
 The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE.  
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported during 
the study and assign it to one of the following categories:  
 Mild: A type of AE that is usually transient and may require only minimal treatment or 
therapeutic intervention. The event does not generally interfere with usual activities of 
daily living. 
 Moderate: A type of AE that is usually alleviated with additional specific therapeutic 
intervention. The event interferes with usual activities of daily living, causing 
discomfort but poses no significant or permanent risk of harm to the research 
participant. 
 Severe: A type of AE that interrupts usual activities of daily living, or significantly 
affects clinical status, or may require intensive therapeutic intervention. An AE that is 
assessed as severe should not be confused with a SAE. Severe is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as severe. 
An event is defined as ‘serious’ when it meets at least one of the predefined outcomes 
as described in the definition of an SAE, NOT when it is rated as severe.  
 
Assessment of Causality 
 The investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. The investigator will use clinical judgment to 
determine the relationship/ 
 A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out. 
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 Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
 The investigator will also consult the IB and/or Product Information, for marketed 
products, in their assessment. 
 For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
 There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to Sponsor or designee. However, it 
is very important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to Sponsor or designee. 
 The investigator may change their opinion of causality in light of follow-up 
information and send a SAE follow-up report with the updated causality assessment. 
 The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of AEs and SAEs 
 The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by Sponsor or 
designee to elucidate the nature and/or causality of the AE or SAE as fully as possible. 
This may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals. 
10.3.5. 
Reporting of SAEs 
SAE Reporting via an Electronic Data Collection Tool 
 The primary mechanism for reporting an SAE will be the electronic data collection 
tool. 
 If the electronic system is unavailable, then the site will use the SAE paper form (see 
next section) in order to report the event within 24 hours.  
 The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
 After the study is completed at a given site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data. 
 If a site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a SAE paper form (see next 
section) or to the medical monitor/SAE coordinator by telephone. 
 Contacts for SAE reporting can be found in the SAE paper form.  
 
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SAE Reporting via Paper Form 
 Facsimile transmission of the SAE paper form is the preferred method to transmit this 
information to the medical monitor or the SAE coordinator. 
 Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time frames. 
 Contacts for SAE reporting can be found in the SAE paper form.  
10.3.6. 
Regulatory Reporting Requirements 
SAE Regulatory Reporting 
● Prompt notification by the investigator to the sponsor of a 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. 
● An investigator who receives an investigator safety report describing a SAE or 
other specific safety information (for example, summary or listing of SAEs) 
from the sponsor will review and then file it along with the IB or state other 
documents and will notify the IRB/IEC, if appropriate according to local 
requirements.  
 
 
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10.4. 
Appendix 4: Contraceptive and Barrier Guidance 
10.4.1. 
Definitions 
Word/Phrase 
Definition 
Women of 
childbearing 
potential 
(WOCBP) 
Adult females are considered WOCBP unless they are WNOCBP. 
 
Women not of 
childbearing 
potential 
(WNOCBP) 
Females are considered WNOCBP if they 
 have a congenital anomaly such as Müllerian agenesis 
 are infertile due to surgical sterilization, or 
 are postmenopausal. 
Examples of surgical sterilization include total hysterectomy, bilateral 
salpingo-oophorectomy, bilateral salpingectomy, or bilateral oophorectomy. 
Postmenopausal 
state 
The postmenopausal state is defined as a woman: 
 at any age at least 6 weeks post-surgical bilateral oophorectomy 
with or without hysterectomy, confirmed by operative or medical 
note; or 
 aged at least 40 years and up to 55 years with an intact uterus, not 
on hormone therapya, who has had cessation of menses for at least 
12 consecutive months without an alternative medical cause, AND 
with a follicle-stimulating hormone >40 mIU/mL; or 
 55 years or older not on hormone therapy, who has had at least 12 
months of spontaneous amenorrhea, or 
 aged at least 55 years with a diagnosis of menopause prior to 
starting hormone replacement therapy. 
 
a Women should not be taking medications during amenorrhea such as oral 
contraceptives, hormones, gonadotropin-releasing hormone, anti-estrogens, 
SERMs, or chemotherapy that could induce transient amenorrhea. 
 
10.4.2. 
Contraception Guidance 
Contraception methods should be aligned with local regulations for both male and female 
participants. 
WOCBP who are completely abstinent as their preferred and usual lifestyle, or in a same-sex 
relationship as their preferred and usual lifestyle: 
Must… 
Must not… 
agree to either 
remain abstinent or 
stay in a same-sex 
relationship without 
sexual relationships 
with males 
 use periodic abstinence methods 
o calendar 
o ovulation 
o symptothermal, or 
o post-ovulation 
 declare abstinence just for the duration of a trial, or 
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 use the withdrawal method 
 
WOCBP who are NOT completely abstinent as their preferred and usual lifestyle, or NOT in a 
same-sex relationship as their preferred and usual lifestyle, must do the following: 
Topic 
Condition 
Pregnancy testing 
Have a negative serum test result at screening followed by a negative 
urine result within 24 hours prior to treatment exposure. See the protocol 
SoA for subsequent pregnancy testing requirements. 
Contraception 
Agree to use 2 forms of effective contraception, where at least 1 form 
must be highly effective. 
 
These forms of contraception must be used during the study and after the 
study for at least 95 days after the last dose of the study intervention. 
 
Examples of different forms of contraception: 
Methods 
Examples 
Highly effective 
contraception (less 
than 1% failure rate) 
 female sterilization 
 combination oral contraceptive pill 
 progestin-only contraceptive pill (mini-pill) 
 implanted contraceptives 
 injectable contraceptives 
 contraceptive patch (only women <198 pounds or 90 kg) 
 total abstinence 
 vasectomy (if only sexual partner) 
 fallopian tube implants (if confirmed by 
hysterosalpingogram) 
 combined contraceptive vaginal ring, or 
 intrauterine devices 
Effective contraception 
 male or female condoms with spermicide 
 diaphragms with spermicide or cervical sponges 
 barrier method with use of a spermicide 
o condom with spermicide 
o diaphragm with spermicide, or 
o female condom with spermicide 
 
Note: The barrier method must include use of a spermicide (that is, 
condom with spermicide, diaphragm with spermicide, or female 
condom with spermicide) to be considered effective. 
Ineffective forms of 
contraception whether 
used alone or in any 
combination 
 spermicide alone 
 periodic abstinence 
 fertility awareness (calendar method, temperature method, 
cervical mucus, or symptothermal) 
 withdrawal 
 postcoital douche, or 
 lactational amenorrhea 
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The tables below describes contraception guidance for men. 
Topic 
Guidance 
For all men 
Should refrain from sperm donation for the 
duration of the study and for the predicted time 
until estimated plasma levels of partner would be 
below the level of toxicologic concern, plus 90 
days 
Contraception for men with partners of 
childbearing potential  
 
either remain abstinent (if this is their 
preferred and usual lifestyle), or 
 
 
must use condoms during intercourse for 
the duration of the study, and 
 
for the predicted time until estimated 
plasma levels of partner would be below 
the level of toxicologic concern, plus 90 
days 
Contraception for men in exclusively same-sex 
relationships, as their preferred and usual lifestyle 
Are not required to use contraception 
 
 
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10.5. 
Appendix 5: Genetics 
Use/Analysis of DNA 
● Genetic variation may impact a participant’s response to study intervention, 
susceptibility to, and severity and progression of disease. Variable response to 
study intervention may be due to genetic determinants that impact drug 
absorption, distribution, metabolism, and excretion; mechanism of action of the 
drug; disease etiology; and/or molecular subtype of the disease being treated. 
Therefore, where local regulations and IRB/IEC allow, an optional blood sample 
will be collected for DNA analysis from consenting participants. 
● DNA samples will be used for research related to study intervention or 
cardiovascular disease and related diseases. They may also be used to develop 
tests or assays including diagnostic tests related to study intervention and 
cardiovascular disease. Genetic research may consist of the analysis of 1 or more 
candidate genes or the analysis of genetic markers throughout the genome or 
analysis of the entire genome (as appropriate). 
● The samples may be analyzed as part of a multi-study assessment of genetic 
factors involved in the response to study intervention or study interventions of this 
class to understand study disease or related conditions. 
● The results of genetic analyses may be reported in the CSR or in a separate study 
summary. 
● The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality. 
● The samples will be retained while research on study intervention continues but 
no longer than 7 years or other period as per local requirements. 
 
 
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10.6. 
Appendix 6: Liver Safety: Suggested Actions and Follow-up 
Assessments 
Hepatic Evaluation Testing 
See Section 8.2.3 for guidance on appropriate test selection. 
The Lilly-designated central laboratory should complete the analysis of all selected testing 
except for testing listed in the investigator-designated local laboratory table. The central 
laboratory will report results if a validated test or calculation is available. 
Local testing may be performed in addition to central testing when necessary for immediate 
participant management. 
The local laboratory must be qualified in accordance with applicable local regulations. 
Tests assayed by Lilly-designated central laboratory 
Hepatic Hematology Panel 
Hepatitis A virus (HAV) testing: 
   Hemoglobin 
    HAV total antibody 
   Hematocrit 
    HAV IgM antibody 
   Erythrocytes (RBCs - red blood cells) 
Hepatis B virus (HBV) testing: 
   Leukocytes (WBCs - white blood cells) 
    Hepatitis B surface antigen (HBsAg) 
   Differential: 
    Hepatitis B surface antibody (anti-HBs) 
       Neutrophils, segmented 
    Hepatitis B core total antibody (anti-HBc) 
       Lymphocytes 
    Hepatitis B core IgM antibody 
       Monocytes 
    HBV DNA b 
       Basophils 
Hepatis C virus (HCV) testing: 
       Eosinophils 
    HCV antibody 
   Platelets 
    HCV RNA b 
   Cell morphology (RBC and WBC) 
Hepatitis D virus (HDV) testing: 
Hepatic Clinical Chemistry Panel 
    HDV antibody 
   Total bilirubin 
Hepatitis E virus (HEV) testing: 
   Direct bilirubin 
    HEV IgG antibody 
   Alkaline phosphatase (ALP) 
    HEV IgM antibody 
   Alanine aminotransferase (ALT) 
    HEV RNA b 
   Aspartate aminotransferase (AST) 
Anti-nuclear antibody (ANA) 
   Gamma-glutamyl transferase (GGT) 
Anti-smooth muscle antibody (ASMA) a 
   Creatine kinase (CK) 
Anti-actin antibody c 
Hepatic Coagulation Panel 
Immunoglobulin IgA (quantitative) 
   Prothrombin time, INR (PT-INR) 
Immunoglobulin IgG (quantitative) 
Urine Chemistry 
Immunoglobulin IgM (quantitative) 
   Drug screen 
Epstein-Barr virus (EBV) testing: 
Haptoglobin 
    EBV antibody 
 
Tests assayed ONLY by investigator-designated local laboratory  
Acetaminophen 
Cytomegalovirus (CMV) testing: 
Acetaminophen protein adducts 
    CMV antibody 
Alkaline phosphatase isoenzymes 
    CMV DNA b 
Ceruloplasmin 
Herpes simplex virus (HSV) testing: 
Copper 
    HSV (Type 1 and 2) antibody 
Ethyl alcohol (EtOH) 
    HSV (Type 1 and 2) DNA b 
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Tests assayed ONLY by investigator-designated local laboratory  
Phosphatidylethanol (PEth) 
Liver kidney microsomal type 1 (LKM-1) antibody 
Urine Chemistry 
Microbiology  
    Ethyl glucuronide (EtG) 
Culture: 
Epstein-Barr virus (EBV) testing: 
    Blood 
    EBV DNA b 
    Urine 
 
a Not required if anti-actin antibody is tested. 
b Reflex/confirmation dependent on regulatory requirements, testing availability, or both. 
c Not required if anti-smooth muscle antibody (ASMA) is tested. 
 
 
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10.7. 
Appendix 7: Provisions for Changes in Study Conduct During 
Exceptional Circumstances 
Implementation of this appendix 
The changes to procedures described in this appendix are temporary measures intended to be used only 
during specific time periods as directed by the sponsor in partnership with the investigator. 
Exceptional circumstances 
Exceptional circumstances are rare events that may cause disruptions to the conduct of the study. 
Examples include pandemics or natural disasters. These disruptions may limit the ability of the 
investigators, participants, or both to attend on-site visits or to conduct planned study procedures. 
Implementing changes under exceptional circumstances 
In an exceptional circumstance, after receiving the sponsor’s written approval, sites may implement 
changes if permitted by local regulations. 
After approval by local Ethical Review Boards, regulatory bodies, and any other relevant local 
authorities, implementation of these exceptional circumstance changes will not typically require 
additional notification to these groups, unless they have specific requirements in which notification is 
required, for example, upon implementation and suspension of changes. All approvals and notifications 
must be retained in the study records. 
If the sponsor grants written approval for changes in study conduct, the sponsor will also provide 
additional written guidance, if needed. 
Considerations for making a change 
The prevailing consideration for making a change is ensuring the safety of study participants. Additional 
important considerations for making a change are compliance with GCP, enabling participants to continue 
safely in the study and maintaining the integrity of the study. 
Informed consent 
Additional consent from the participant will be obtained, if required, for 
 
participation in remote visits, as defined in Section “Remote Visits” 
 
dispensation of additional study intervention during an extended treatment period 
 
alternate delivery of study intervention and ancillary supplies, and 
 
provision of their personal or medical information required prior to implementation of these 
activities. 
Changes in study conduct during exceptional circumstances 
Changes in study conduct not described in this appendix, or not consistent with applicable local 
regulations, are not allowed. 
The following changes in study conduct will not be considered protocol deviations. 
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Remote visits 
Types of remote visits 
Telemedicine: Telephone or technology-assisted virtual visits, or both, are acceptable to 
complete appropriate assessments. Assessments to be completed in this manner include, but are 
not limited to 
 
AE review 
 
concomitant medication review 
 
substance use (alcohol), and 
 
PCs (if applicable). 
Mobile healthcare: Healthcare visits may be performed by a mobile healthcare provider at 
locations other than the study site when participants cannot travel to the site due to an exceptional 
circumstance if written approval is provided by the sponsor. Procedures performed at such visits 
include, but are not limited to 
 
concomitant medications 
 
collection of blood samples 
 
physical assessments, and 
 
health information. 
Other alternative locations: A local laboratory may be used for laboratory draws. 
Assessments that may need to be delayed until the next on-site visit or missed, depending on the 
length of time that sites or participants are impacted and depending on when on-site visits are 
due, include 
 
vital signs 
 
weight 
 
symptom-directed physical examination, and 
 
laboratory tests if a local laboratory cannot be used. 
Data capture 
In source documents and the CRF, the study site should capture the visit method, with a specific 
explanation for any data missing because of missed in-person site visits. 
Safety reporting 
Regardless of the type of remote visits implemented, the protocol requirements regarding the reporting of 
AEs, SAEs, and PCs remain unchanged. 
Return to on-site visits 
Every effort should be made to enable participants to return to on-site visits as soon as reasonably 
possible, while ensuring the safety of both the participants and the site staff. 
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Local laboratory testing option 
Local laboratory testing may be conducted in lieu of Lilly-designated laboratory testing. The local 
laboratory must be qualified in accordance with applicable local regulations. 
Lilly-designated laboratory testing must be retained for PK, Lp(a), ApoB, hsCRP, plasminogen activity, 
and the lipid panel. 
Study intervention and ancillary supplies (including participant diaries) 
When a participant is unable to go to the site to receive study supplies during normal on-site visits, the 
site should work with the sponsor to determine appropriate actions. These actions may include 
 
asking the participant to go to the site and receive study supplies from site staff without 
completion of a full study visit 
 
asking the participant’s designee to go to the site and receive study supplies on a participant’s 
behalf, and 
 
arranging delivery of study supplies. 
These requirements must be met before action is taken: 
 
Alternate delivery of study intervention should be performed in a manner that does not 
compromise treatment blinding and ensures product integrity. The existing protocol 
requirements for product accountability remain unchanged, including verification of 
participant’s receipt of study supplies. 
 
When delivering supplies to a location other than the study site (for example, participant’s 
home), the investigator, sponsor, or both should ensure oversight of the shipping process to 
ensure accountability and product quality, that is, storage conditions maintained and intact 
packaging upon receipt. 
 
Instructions may be provided to the participant or designee on the final disposition of any 
unused or completed study supplies. 
Screening period guidance 
To ensure safety of study participants, laboratory values and other eligibility assessments taken at 
prescreening and screening visits are valid for a maximum of 60 days. The following rules will be applied 
for active, nonrandomized participants whose participation in the study must be paused due to exceptional 
circumstances: 
 
If screening is paused for less than 60 days from signing the ICF to randomization visit: the 
participant will proceed to the next study visit per the usual SoA, provided that randomization 
visit must be conducted within 45 days from the screening visit. 
o The site should conduct the next visit if the participant’s eligibility criteria are 
confirmed, and the site should document the reason for delay. 
o Due to the pause in screening, sites should also reconfirm the impacted participant’s 
consent and document this confirmation in the source documentation. 
 
If screening is paused for more than 60 days from screening visits to randomization visit: the 
participant must be discontinued because of screening interruption due to an exceptional 
circumstance. This is documented as a screen failure in the CRF. The participant can 
reconsent and be rescreened as a new participant. This rescreen is in addition to the one 
allowed by the main protocol. The screening procedures per the usual SoA should be 
followed, starting at screening visit to ensure participant eligibility by randomization visit. 
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Adjustments to visit windows 
Whenever possible and safe to do so, as determined by the investigator’s discretion, participants should 
complete the usual SoA. To maximize the possibility that these visits can be conducted as on-site visits, 
the windows for visits may be adjusted, upon further guidance from the sponsor. This minimizes missing 
data and preserves the intended conduct of the study. 
Documentation 
Changes to study conduct will be documented 
Sites will identify and document the details of how participants, visits types, and conducted activities 
were affected by exceptional circumstances. Dispensing or shipment records of study intervention and 
relevant communications, including delegation, should be filed with site study records. 
Source documents at alternate locations 
Source documents generated at a location other than the study site should be part of the 
investigator’s source documentation and should be transferred to the site in a secure and timely manner. 
 
 
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10.8. 
Appendix 8: Abbreviations and Definitions 
Term 
Definition 
AC 
assessment committee 
ACC 
American College of Cardiology 
AE 
adverse event 
AHA 
American Heart Association 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANCOVA 
Analysis of covariance 
apo(a) 
apolipoprotein(a) 
ApoB 
apolipoprotein B 
ASCVD 
atherosclerotic cardiovascular disease 
AST 
aspartate aminotransferase 
blinding/masking 
A double-blind study is one in which neither the participant nor any of the investigator or 
sponsor staff who are involved in the treatment or clinical evaluation of the subjects are 
aware of the treatment received. 
CAD 
coronary artery disease 
CFR 
Code of Federal Regulations 
CIOMS 
Council for International Organizations of Medical Sciences 
CK 
creatine kinase 
CKD-EPI 
Chronic Kidney Disease Epidemiology Collaboration 
CMV 
cytomegalovirus 
Companion diagnostic  An in vitro diagnostic device (assay or test) that provides information that is essential for 
the safe and effective use of a corresponding therapeutic product. 
complaint 
A complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, quality, purity, durability, reliability, safety or effectiveness, or 
performance of a drug or drug delivery system. 
compliance 
Adherence to all study-related, good clinical practice (GCP), and applicable regulatory 
requirements. 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
case report form; a printed, optical, or electronic document designed to record all of the 
protocol-required information to be reported to the sponsor for each trial participant. 
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CSR 
clinical study report 
CT 
computerized tomography 
CTA 
Clinical Trial Agreement 
D. Bil 
direct bilirubin 
DNA 
deoxyribonucleic acid 
EAS 
Efficacy Analysis Set 
EBV 
Epstein-Barr virus 
ECG 
electrocardiogram 
ED 
early discontinuation 
EDC 
electronic data capture system 
eGFR 
estimated glomerular filtration rate 
Enroll 
The act of assigning a participant to a treatment. Participants who are enrolled in the study 
are those who have been assigned to a treatment. 
enter 
Participants entered into a study are those who sign the informed consent form directly or 
through their legally acceptable representatives. 
ERCP 
endoscopic retrograde cholangiopancreatography 
EU 
European Union 
FAS 
Full Analysis Set 
FSH 
follicle-stimulating hormone 
GCP 
good clinical practice 
GGT 
gamma-glutamyltransferase 
HbA1c 
hemoglobin A1c 
HBV 
hepatitis B virus 
HBcAb 
hepatitis B core antibody 
HBsAg 
hepatitis B surface antigen 
HCV 
hepatitis C virus 
HDV 
hepatitis D virus 
HIV 
human immunodeficiency virus 
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hsCRP 
high-sensitivity C-reactive protein 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committees 
informed consent 
A process by which a participant voluntarily confirms their willingness to participate in a 
particular study, after having been informed of all aspects of the study that are relevant to 
the participant’s decision to participate. Informed consent is documented by means of a 
written, signed, and dated informed consent form. 
interim analysis 
An interim analysis is an analysis of clinical study data, separated into treatment groups, 
that is conducted before the final reporting database is created or locked. 
INR 
international normalized ratio 
investigational 
product 
A pharmaceutical form of an active ingredient or placebo being tested or used as a 
reference in a clinical trial, including products already on the market when used or 
assembled (formulated or packaged) in a way different from the authorized form, or 
marketed products used for an unauthorized indication, or marketed products used to gain 
further information about the authorized form. 
IRB 
Institutional Review Board 
IWRS 
interactive web-response system 
LDL 
low-density lipoprotein 
Lp(a) 
lipoprotein(a) 
MACE 
major adverse cardiac events 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
mixed model for repeated measures 
MRCP 
magnetic resonance cholangiopancreatography 
NONMEM 
Nonlinear Mixed-Effects Modeling 
OTC 
over the counter 
participant 
equivalent to CDISC term “subject”: an individual who participates in a clinical trial, either 
as recipient of an investigational medicinal product or as a control 
PC 
product complaint 
PCSK9 
proprotein convertase subtilisin/kexin type 9 
PD 
pharmacodynamics 
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PI 
principle investigator 
PK 
pharmacokinetics 
PO 
by mouth 
PT-INR 
prothrombin time-INR 
QD 
once daily 
QTc 
corrected QT interval 
QTcF 
QT interval corrected using Fridericia’s formula 
QTL 
quality tolerance limit 
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
screen 
The act of determining if an individual meets minimum requirements to become part of a 
pool of potential candidates for participation in a clinical study.  
SCORE2 
Systematic COronary Risk Evaluation 2 
SNP 
single-nucleotide polymorphism 
SoA 
Schedule of Activities 
SS 
Safety Analysis Set 
TBL 
total bilirubin 
TEAE 
Treatment-emergent adverse event: An untoward medical occurrence that emerges during a 
defined treatment period, having been absent pretreatment, or worsens relative to the 
pretreatment state, and does not necessarily have to have a causal relationship with this 
treatment. 
TSH 
thyroid stimulating hormone 
UACR 
urinary albumin creatine ratio 
ULN 
upper limit of normal 
US 
United States 
WNOCBP 
women not of childbearing potential 
WOCBP 
women of childbearing potential 
 
 
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