A Phase 4, Multicenter, Randomized, Open-label, Active-controlled Study to Evaluate the Effectiveness and Safety of Early add-on of Ezetimibe With Atorvastatin in Very High-risk Patients
Phase: PHASE4
Conditions: Atherosclerotic Cardiovascular Disease
Sponsor: Organon and Co

CONFIDENTIAL
Protocol OG-KORATO-001, ver. 4.1
 
 
1 of 59 
[Organon] 소유권 
TITLE PAGE 
Protocol Title: A phase 4, multicenter, randomized, open-label, active-controlled study to 
evaluate the effectiveness and safety of early add-on of ezetimibe with 
atorvastatin in very high-risk patients. 
Protocol Number: OG-KORATO-001 
Amendment Number: Protocol OG-KORATO-001 ver.4.1 
Compound: ezetimibe/atorvastatin, atorvastatin 
Brief Title: Effectiveness and safety study of early add-on of ezetimibe with atorvastatin in 
very high-risk patients 
Study Phase: Phase 4 
Sponsor Name: Organon Korea Co. Ltd 
Legal Registered Address: 50, Jong-ro 1-gil, Jongno-gu, Seoul, Republic of Korea  
Regulatory Agency Identifier Number(s): not applicable 
Approval Date:  
Protocol OG-KORATO-001 ver.1.0 approved on 6-Dec-2022 
Protocol OG-KORATO-001 ver.2.0 approved on 16-Dec-2022 
Protocol OG-KORATO-001 ver.3.0 approved on 3-Jan-2023 
Protocol OG-KORATO-001 ver.4.0 approved on 21-Mar-2023 
Protocol OG-KORATO-001 ver.4.1 approved on 27-Jun-2024 
 
STATEMENT OF CONFIDENTIALITY 
This protocol contains confidential information that should only be disclosed to those persons responsible for 
execution and organization of the study and on condition that all such persons agree not to further disseminate it. 
 
 
 
 
 

CONFIDENTIAL
Protocol OG-KORATO-001, ver. 4.1
 
 
3 of 59 
[Organon] 소유권 
TABLE OF CONTENTS 
1.0 
PROTOCOL SUMMARY .......................................................................................... 7 
1.1 
Synopsis ............................................................................................................ 7 
1.2 
Schema ............................................................................................................ 10 
1.3 
Schedule of Activities .................................................................................... 11 
2.0 
STUDY RATIONALE AND BACKGROUND ...................................................... 13 
3.0 
OBJECTIVES AND ENDPOINTS .......................................................................... 15 
4.0 
STUDY DESIGN ....................................................................................................... 16 
4.1 
Overall Design ................................................................................................ 16 
4.2 
End of Study Definition ................................................................................. 17 
5.0 
STUDY POPULATION ............................................................................................ 18 
5.1 
Inclusion Criteria ........................................................................................... 18 
5.2 
Exclusion Criteria .......................................................................................... 18 
5.3 
Lifestyle Considerations ................................................................................ 19 
5.4 
Screen Failures ............................................................................................... 19 
5.5 
Criteria for Temporarily Delaying 
Enrollment/Randomization/Administration of Study 
Intervention .................................................................................................... 20 
6.0 
STUDY INTERVENTIONS AND CONCOMITANT THERAPY ...................... 21 
6.1 
Study Interventions Administered ............................................................... 21 
6.2 
Preparation, Handling, Storage, and Accountability ................................. 22 
6.3 
Measures to Minimize Bias: Randomization .............................................. 22 
6.3.1 
Stratified block randomization .......................................................... 22 
6.4 
Study Intervention Compliance ................................................................... 23 
6.5 
Continued Access to Study Intervention after the End of the 
Study ............................................................................................................... 23 
6.6 
Treatment of Overdose ................................................................................. 23 
6.7 
Concomitant Therapy ................................................................................... 24 
7.0 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ................................... 25 
7.1 
Discontinuation of Study Intervention ........................................................ 25 
7.2 
Participant Discontinuation/Withdrawal from the Study ......................... 25 
7.3 
Lost to Follow-up ........................................................................................... 26 
8.0 
STUDY ASSESSMENTS AND PROCEDURES .................................................... 27 
8.1 
Baseline characteristics ................................................................................. 27 

CONFIDENTIAL
Protocol OG-KORATO-001, ver. 4.1
 
 
4 of 59 
[Organon] 소유권 
8.1.1 
Demography ...................................................................................... 27 
8.1.2 
General medical history .................................................................... 27 
8.1.3 
Medical history related to dyslipidemia ............................................ 27 
8.2 
Effectiveness Assessments ............................................................................. 28 
8.2.1 
Lipid parameter laboratory test ......................................................... 28 
8.3 
Safety Assessments ........................................................................................ 28 
8.3.1 
Physical Examinations ...................................................................... 28 
8.3.2 
Vital Signs ......................................................................................... 28 
8.3.3 
12-Lead Electrocardiograms (ECG) ................................................. 28 
8.3.4 
Clinical Safety Laboratory Tests ....................................................... 28 
8.3.5 
Pregnancy Testing ............................................................................. 29 
8.4 
Adverse Events, Serious Adverse Events, and Other Safety 
Reporting ........................................................................................................ 29 
8.4.1 
Time Period and Frequency for Collecting AE and SAE 
Information ........................................................................................ 29 
8.4.2 
Method of Detecting AEs and SAEs ................................................. 30 
8.4.3 
Follow-up of AEs and SAEs ............................................................. 30 
8.4.4 
Regulatory Reporting Requirements for SAEs ................................. 31 
8.4.5 
Pregnancy .......................................................................................... 31 
8.4.6 
Adverse Events of Special Interest ................................................... 32 
8.4.7 
Special Situations .............................................................................. 32 
9.0 
STATISTICAL CONSIDERATIONS ..................................................................... 33 
9.1 
Statistical Hypotheses .................................................................................... 33 
9.2 
Analysis Sets ................................................................................................... 33 
9.3 
Statistical Analyses ........................................................................................ 33 
9.3.1 
General Considerations ..................................................................... 33 
9.3.2 
Primary Endpoint .............................................................................. 34 
9.3.3 
Secondary Endpoints ......................................................................... 34 
9.3.4 
Subgroup Analysis ............................................................................ 34 
9.3.5 
Safety Analysis.................................................................................. 35 
9.4 
Interim Analysis ............................................................................................. 35 
9.5 
Sample Size Determination ........................................................................... 35 
10.0 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ................................................................................................. 37 
10.1 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................... 37 
10.1.1 
Regulatory and Ethical Considerations ............................................. 37 
10.1.2 
Adequate Resources .......................................................................... 37 
10.1.3 
Financial Disclosure .......................................................................... 38 
10.1.4 
Insurance ........................................................................................... 38 
10.1.5 
Informed Consent Process................................................................. 38 
10.1.6 
Data Protection .................................................................................. 39 
10.1.7 
Dissemination of Clinical Study Data ............................................... 39 
10.1.8 
Data Quality Assurance ..................................................................... 39 

CONFIDENTIAL
Protocol OG-KORATO-001, ver. 4.1
 
 
5 of 59 
[Organon] 소유권 
10.1.9 
Source Documents ............................................................................ 40 
10.1.10 Study and Site Start and Closure ....................................................... 40 
10.1.11 Publication Policy ............................................................................. 41 
10.2 
Appendix 2: Clinical Laboratory Tests ....................................................... 43 
10.3 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting for Study 
Intervention .................................................................................................... 45 
10.3.1 
Definition of AE ................................................................................ 45 
10.3.2 
Definition of SAE ............................................................................. 46 
10.3.3 
Recording and Follow-Up of AE and/or SAE .................................. 47 
10.3.4 
Reporting of SAEs ............................................................................ 49 
10.4 
Appendix 4: Contraceptive and Barrier Guidance and 
Collection of Pregnancy Information .......................................................... 50 
10.4.1 
Definitions ......................................................................................... 50 
10.4.2 
Contraception Guidance .................................................................... 50 
10.4.3 
Collection of Pregnancy Information ................................................ 51 
10.4.4 
Reporting Pregnancy Information ..................................................... 52 
10.5 
Appendix 5: Abbreviations ........................................................................... 53 
10.6 
Appendix 6: Target Enroll Clarification ..................................................... 55 
11.0 
REFERENCES .......................................................................................................... 57 
 

CONFIDENTIAL
Protocol OG-KORATO-001, ver. 4.1
 
 
6 of 59 
[Organon] 소유권 
LIST OF TABLES 
Table 1–1 
Schedule of Activities ....................................................................................... 11 
Table 3–1 
Study objectives and endpoints ........................................................................ 15 
Table 6–1 
Study Interventions Administered .................................................................... 21 
Table 6–2 
Study Arms ....................................................................................................... 21 
Table 8–1 
Reporting Time Periods and Time Frames for Adverse Events, Serious Adverse 
Events, and other reportable safety events.  ............................................................................. 30 
Table 10–1 
Protocol-required Safety Laboratory Tests....................................................... 43 
 
LIST OF FIGURES 
Figure 1-1 
Study Schema ................................................................................................... 10 
 

CONFIDENTIAL
Protocol OG-KORATO-001, ver. 4.1
 
 
7 of 59 
[Organon] 소유권 
1.0 PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol Title: A phase 4, multicenter, randomized, open-label, active-controlled study to 
evaluate the effectiveness and safety of early add-on of ezetimibe with 
atorvastatin in very high-risk patients. 
Rationale: 
The 2019 dyslipidemia management guidelines from the European Society of Cardiology set 
an LDL-C target for very high-risk patients of less than 55 mg/dL (as well as at least a 50% 
cut from baseline), a class I recommendation. Accordingly, the Korean Society of Lipid and 
Atherosclerosis has also updated the treatment guidelines in 2022. However, the 2021 EAS 
practical guidance says that the new LDL-C goals for high and very-high risk group patients 
with dyslipidema are more demanding; in real-world practice, only 1/3 patients reach the 
LDL-C target (Averna M 2021). Therefore, this study aims to confirm the effectiveness of 
ezetimibe add-on therapy on LDL-C levels compared to atorvastatin monotherapy, especially 
in very high-risk patients. We intend to lay the foundation for a standard treatment for these 
patients through ezetimibe add on lipid-lowering therapy. 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
 
 
To evaluate the effectiveness of early add-on 
of ezetimibe with atorvastatin in very high-
risk patients 
 
Percentage change in LDL-C from baseline 
to week 6 
Secondary 
 
 
To evaluate the clinical effectiveness of 
early add-on of ezetimibe with atorvastatin 
in very high-risk patients. 
 
Proportion of patients achieving LDL-C 
goal of <55 mg/dL after 6 weeks and 12 
weeks of treatment 
 
Proportion of patients achieving LDL-C 
goal of <70 mg/dL after 6 weeks and 12 
weeks of treatment   
 
Percentage change in LDL-C from baseline 
to week 12 
 
Percentage change in HDL-C, non-HDL-C, 
triglycerides, and total cholesterol from 
baseline to week 6 and week 12 
 
To evaluate the safety of early add-on of 
ezetimibe with atorvastatin in very high-risk 
patients. 
 
Treatment-emergent adverse events 
(TEAEs) at 6 weeks and 12 weeks 

CONFIDENTIAL
Protocol OG-KORATO-001, ver. 4.1
 
 
8 of 59 
[Organon] 소유권 
 
Dropout rate due to TEAEs at 6 weeks and 
12 weeks 
 
Abbreviations: LDL-C=Low-density lipoprotein cholesterol; HDL-C= High-density lipoprotein cholesterol 
Overall Design: 
This is Phase 4, multicenter, randomized, open-label, active-controlled study. The study has 
been designed to evaluate the effectiveness and safety of early add-on of ezetimibe with 
atorvastatin in very high-risk patients. 
In Visit 1, screening is conducted for patients in the very high-risk group. LDL-C needs to be 
above 70 mg/dL in patients (a) who failed to achieve their target LDL-C goals with mild to 
moderate intensity statin; (b) who are statin-naive or have not been on a stable statin regimen 
for at least 4 weeks prior to enrollment. However, by tracking the registration status of 
patients, (b) patients should be enrolled not to exceed 40% of each group. All laboratory tests 
are performed in the local laboratory and the Visit 1 results may be substituted if available 
within 2 weeks prior to the screening visit. The study participation is determined through the 
inclusion/exclusion criteria based on the test results conducted for Visit 1. In the case of the 
lipid parameter, Visit 1 results are used as the baseline. Individuals who do not meet the 
criteria for participation in this study (screen failure) may be rescreened once. 
In Visit 2, randomization is performed on patients who meet the inclusion criteria and do not 
meet any of the exclusion criteria and will be distributed 1:1 between test group (arm Eze/Ato) 
and control group (arm Ato). The results of laboratory tests at the Visit 2 are used as baseline 
except lipid parameters. Visit 1 and Visit 2 may be conducted on the same date. 
In Visit 2 and Visit 3, the appropriate investigational medical product (IMP) is given to each 
group. In principle, IMPs are administered orally once a day from the day of distribution.  
For participants whose LDL-C value has reached the target (LDL-C < 55 mg/dL) according to 
the lipid indicator test at Visit 3, they will continue treatment with the same dose for 6 weeks. 
If the LDL-C level has not reached target, the dose of atorvastatin should be increased to 
ezetimibe/atorvastatin 10/80 mg or atorvastatin 80 mg according to the group assigned. In 
principle, a morning visit is recommended so that the laboratory test results can be checked 
and the IMP can be prescribed and taken on the same day. However, if the test results are not 
confirmed on the same day and a participant has enough IMP to take until the next visit, IMP 
compliance is checked, and the same dose of IMP (ezetimibe/atorvastatin 10/40mg or 
atorvastatin 40mg) is continued. An additional visit is made within 1 week to return the 
remaining IMP and receive new IMP. If the test results are not confirmed on the same day and 
a participant does not have remaining IMP, the investigator prescribes the same dose of IMP 
(ezetimibe/atorvastatin 10/40mg or atorvastatin 40mg) that the participant was taking 

CONFIDENTIAL
Protocol OG-KORATO-001, ver. 4.1
 
 
9 of 59 
[Organon] 소유권 
previously, and an additional visit is made within 1 week to receive new IMP.  Visit 4 is the 
end of study visit, and tests for effectiveness and safety are conducted. 
Number of Participants: 
The number of patients in each treatment group is about 57 under the assumption of two-sided 
significance level α = 0.05, power 1-β = 0.80 with a randomization ratio λ = 1. Considering 
the dropout rate of 10%, 63 patients for each group and thus, a total of 126 patients will be 
randomized in this study. 
Intervention Groups and Duration: 
Arm Title 
Eze/Ato 
Ato 
Arm Type 
Experimental 
Active comparator 
[Arm Description] 
Participants will receive 
ezetimibe/atorvastatin 10/40 mg QD 
from Visit 2 (Day 1) to Visit 3 
(Week 6). If the LDL-C target is 
reached (LDL-C < 55 mg/dL) at 
Visit 3, maintain the dose to Visit 4 
(Week 12). If the LDL-C target level 
is not reached at Visit 3, dose is 
increased to ezetimibe/atorvastatin 
10/80 mg QD from Visit 3 to Visit 
4. 
Participants will receive atorvastatin 
40 mg QD from Visit 2 (Day 1) to 
Visit 3 (Week 6). If the LDL-C 
target is reached (LDL-C < 55 
mg/dL) at Visit 3, maintain the dose 
to Visit 4 (Week 12). If the LDL-C 
target is not reached at Visit 3, dose 
is increased to atorvastatin 80 mg 
QD from Visit 3 to Visit 4. 
Associated Intervention Labels 
Ezetimibe/Atorvastatin 
Atorvastatin 
Abbreviation: QD = once a day 
 

CONFIDENTIAL
Protocol OG-KORATO-001, ver. 4.1
 
 
10 of 59 
[Organon] 소유권 
1.2 
Schema 
Figure 1-1 Study Schema 
 
 

CONFIDENTIAL
Protocol OG-KORATO-001, ver. 4.1
 
11 of 59 
[Organon] 소유권 
1.3 
Schedule of Activities 
Table 1–1 presents the schedule of activities (SoA). 
Table 1–1 Schedule of Activities 
Procedure 
Screening a) 
Intervention Period 
 
E/D 
-D7~D1 
W0 
W6 
W12/EOS 
V1 
V2 
V3 
V4 
Visit window 
 
 
± 7 days 
± 7 days 
 
Informed consent b) 
X 
 
 
 
 
Inclusion and exclusion criteria  
X 
 
 
 
 
Demographics 
X 
 
 
 
 
Physical examination (height, weight) c) 
X 
X 
X 
X 
X 
Medical history related to dyslipidemia 
X 
 
 
 
 
General medical history  
X 
X 
 
 
 
Prior medication d)  
X 
 
 
 
 
Serum or urine pregnancy test (WOCBP only) 
X 
X 
X 
X 
X 
12-lead ECG 
X 
X 
X 
X 
X 
Vital signs e) 
X 
X 
X 
X 
X 
TLC f) 
X 
X 
X 
X 
X 
Randomization 
 
X 
 
 
 
IMP distribution and return g) 
 
X 
X 
X 
 
Concomitant therapy 
 
X 
X 
X 
X 
Lipid parameter laboratory tests h) 
X 
X 
X 
X 
X 
General laboratory tests 
X 
X 
X 
X 
X 

CONFIDENTIAL
Protocol OG-KORATO-001, ver. 4.1
 
12 of 59 
[Organon] 소유권 
Procedure 
Screening a) 
Intervention Period 
 
E/D 
-D7~D1 
W0 
W6 
W12/EOS 
V1 
V2 
V3 
V4 
Visit window 
 
 
± 7 days 
± 7 days 
 
AE/SAE review  
 
X 
X 
X 
X 
Abbreviations: AE = adverse event; D = day; ECG = electrocardiogram; EOS = end of study; E/D = early discontinuation; IMP = investigational medical 
product; SAE = serious adverse event; TLC = therapeutic lifestyle change; V = visit; W = week; WOCBP = women of childbearing potential. 
a) 
Screening test (Visit 1) will be performed in the local laboratory and results may be substituted if available within 2 weeks prior to the screening visit. The 
Visit 1 and Visit 2 may be conducted on the same day. 
b) 
All procedures related to clinical trials must be carried out after obtaining written consent, and screening numbers are assigned in the order of written 
consent. 
c) 
Height is measured at screening only and body weight will be measured at each visit. 
d) 
Prior medication up to 1 month prior to enrollment will be collected. 
e) 
Heart rate and blood pressure will be assessed. Vital signs will be measured in a relax position after 5 minutes rest. 
f) 
Participants will receive education on TLC methods and perform during the clinical trial period. 
g) 
IMPs are distributed at Visit 2 and Visit 3, and the remaining IMPs are returned at Visit 3 and Visit 4, respectively. 
h) 
All tests will be performed in the local laboratory. 
 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
13 of 59 
[Organon] 소유권 
2.0 STUDY RATIONALE AND BACKGROUND 
Dyslipidemia is characterized by elevated total cholesterol, low density lipoprotein-cholesterol 
(LDL-C), triglyceride, and reduced high-density lipoprotein cholesterol (HDL-C), and is 
classified into hypercholesterolemia, hypertriglyceridemia and mixed dyslipidemia. 
Dyslipidemia is also a major risk factor that can lead to cardiovascular disease (CVD) along 
with smoking, hypertension, diabetes, and obesity (Keys A 1972). Therefore, it is important to 
manage blood lipids in these patients. Treatment methods for dyslipidemia include non-drug 
therapy and drug therapy (Rhee EJ 2019). Since the blood lipid, which is the target for the 
primary treatment of dyslipidemia, is affected by dietary factors such as excessive intake of 
saturated fatty acids or cholesterol, overeating, and drinking, an appropriate diet should be the 
basis. In addition, regular exercise not only reduces lipid levels but also affects body fat 
reduction, so it is effective to combine exercise therapy with it. Therefore, when managing 
dyslipidemia, a therapeutic lifestyle change (TLC) is essential, and it is important to treat 
optimal drug therapy in consideration of LDL-C and other risk factors (Rhee EJ 2019). 
According to the 2018 guideline for the management of dyslipidemia in Korea, patients with 
CVD are classified as a very high-risk group, and the treatment goal is to lower LDL-C levels 
to <70 mg/dL or by >50% from the baseline level for secondary prevention (Rhee EJ 2019). 
However, in a large-scale observational study of 10,661 patients in the Dyslipidemia 
International Study (DYSIS), only 29.4% and 18.9% patients with coronary heart disease and 
acute coronary syndrome respectively were under target LDL-C levels. (Gitt AK 2012). 
Statin is currently recommended as the first-line pharmacologic agent among other therapeutic 
agents, as it has relatively few adverse effects and clearly is beneficial for reducing CVD by 
lowering LDL-C (Rhee EJ 2019; Mihaylova B 2012). Therefore, for very high-risk patients, 
administration of statins is also recommended, and ezetimibe should be added if the target 
LDL-C goal is not met even with maximum tolerable dose of statin. Ezetimibe is commonly 
combined with statin therapy, as it lowers LDL-C by inhibiting cholesterol reabsorption in the 
small intestine. Although ezetimibe is also used alone, many studies have been conducted on 
its benefits when combined with statins. 
The IMPROVE-IT study (Špinar J 2014) is the first study powered for atherosclerotic 
cardiovascular disease (ASCVD) outcomes to show a benefit of a non-statin agent (ezetimibe) 
when added to a statin in patients post-acute coronary syndrome (ACS) (Cannon CP 2015). 
The primary endpoint of cardiovascular death/ myocardial infarction (MI)/ unstable angina 
(UA)/ coronary revascularization beyond 30 days/stroke was significantly lower in the 
ezetimibe/simvastatin arm compared with the simvastatin arm over the duration of follow-up 
(32.7% vs. 34.7%, hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.89-0.99; p = 0.016). 
These results offer important hope to patients who have unacceptable side effects from statin 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
14 of 59 
[Organon] 소유권 
therapy and to those who may not achieve adequate LDL-C reduction with statins (Jarcho JA 
2015). Moreover, this study results reinforce the LDL-C hypothesis and suggest that an LDL-
C closer to 50 mg/dl is even better (Špinar J 2014). Also, the large meta-analysis confirmed 
that 1 mmol/L reduction in LDL-C corresponded to a relative risk reduction of 19%, 
irrespective of baseline LDL-C concentration or drug class used (Berberich AJ 2020). The 
investigators now report that adding ezetimibe to statin reduces not only first cardiovascular 
events, but also additional and total cardiovascular events during the entire study period 
(relative risk reductions of 6%, 11%, and 8%, respectively) correlating with persistent lower 
LDL-C levels throughout the study period (Murphy SA 2016). In other words, approximately 
11 total cardiovascular events (MI, stroke and revascularizations) can be prevented for every 
100 patients treated for 10 years with ezetimibe and statin, which is essentially double the 
number of first cardiovascular events prevented. 
Furthermore, a study was conducted on the benefits of ezetimibe addition therapy when 
compared to high doses of statins. In the RACING study (Kim BK 2022), patients with 
ASCVD at 26 clinical centres in South Korea were randomly assigned (1:1) to receive either 
moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg with 
ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg). As a result, 
among patients with ASCVD, moderate-intensity statin with ezetimibe combination therapy 
was non-inferior to high-intensity statin monotherapy for the 3-year composite outcomes with 
a higher proportion of patients with LDL-C concentrations of less than 70 mg/dL and lower 
intolerance-related drug discontinuation or dose reduction (Kim BK 2022). Moreover, a 
pooled analysis of 17 double-blind trials of patients who were already on a statin showed that 
the largest percent reductions in LDL-C were seen with adding ezetimibe (Ambegaonkar BM 
2014). 
Based on these research results, the 2019 dyslipidemia management guidelines from the 
European Society of Cardiology set an LDL-C target for very high-risk people of less than 55 
mg/dL (as well as at least a 50% cut from baseline), a class I recommendation (Mach F 2020). 
Accordingly, the Korean Society of Lipid and Atherosclerosis has also updated the treatment 
guidelines. However, the 2021 EAS practical guidance says that the new LDL-C goals for 
high and very-high risk group patients with dyslipidema are more demanding; in real-world 
practice, only 1/3 patients reach the LDL-C target (Averna M 2021). Therefore, this study 
aims to confirm the effectiveness of ezetimibe add-on therapy on LDL-C levels compared to 
atorvastatin monotherapy, especially in very high-risk patients. We intend to lay the 
foundation for a standard treatment for these patients through ezetimibe add on lipid-lowering 
therapy. 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
15 of 59 
[Organon] 소유권 
3.0 OBJECTIVES AND ENDPOINTS 
Table 3–1 presents the objectives and corresponding endpoints of the study. 
 
Table 3–1 Study objectives and endpoints 
Objectives 
Endpoints 
Primary 
 
 
To evaluate the effectiveness of early add-on 
of ezetimibe with atorvastatin in very high-
risk patients. 
 
Percentage change in LDL-C from baseline 
to week 6 
Secondary 
 
 
To evaluate the clinical effectiveness of early 
add-on of ezetimibe with atorvastatin in very 
high-risk patients. 
 
Proportion of patients achieving LDL-C 
goal of <55 mg/dL after 6 weeks and 12 
weeks of treatment 
 
Proportion of patients achieving LDL-C 
goal of <70 mg/dL after 6 weeks and 12 
weeks of treatment 
 
Percentage change in LDL-C from baseline 
to week 12 
 
Percentage change in HDL-C, non-HDL-C, 
triglycerides, and total cholesterol from 
baseline to week 6 and week 12 
 
To evaluate the safety of early add-on of 
ezetimibe with atorvastatin in very high-risk 
patients. 
 
Treatment-emergent adverse events 
(TEAEs) at 6 weeks and 12 weeks 
 
Dropout rate due to TEAEs at 6 weeks and 
12 weeks 
Abbreviations: LDL-C=Low-density lipoprotein cholesterol; HDL-C= High-density lipoprotein cholesterol 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
16 of 59 
[Organon] 소유권 
4.0 STUDY DESIGN 
4.1 
Overall Design 
This is Phase 4, multicenter, randomized, open-label, active-controlled study. The study has 
been designed to evaluate the effectiveness and safety of early add-on of ezetimibe with 
atorvastatin in very high-risk patients. 
In Visit 1, screening is conducted for patients in the very high-risk group. LDL-C needs to be 
above 70 mg/dL in patients (a) who failed to achieve their target LDL-C goals with mild to 
moderate intensity statin; (b) who are statin-naive or have not been on a stable statin regimen 
for at least 4 weeks prior to enrollment. However, by tracking the registration status of 
patients, (b) patients should be enrolled not to exceed 40% of each group. All laboratory tests 
are performed in the local laboratory and the Visit 1 results may be substituted if available 
within 2 weeks prior to the screening visit. The study participation is determined through the 
inclusion/exclusion criteria based on the test results conducted for Visit 1. In the case of the 
lipid parameter, Visit 1 results are used as the baseline. Individuals who do not meet the 
criteria for participation in this study (screen failure) may be rescreened once. 
In Visit 2, randomization is performed on patients who meet the inclusion criteria and do not 
meet any of the exclusion criteria and will be distributed 1:1 between test group (arm Eze/Ato) 
and control group (arm Ato). The results of laboratory tests at the Visit 2 are used as baseline 
except lipid parameters. Visit 1 and Visit 2 may be conducted on the same date. 
In Visit 2 and Visit 3, the appropriate investigational medical product (IMP) is given to each 
group. In principle, IMPs are administered orally once a day from the day of distribution.  
For participants whose LDL-C value has reached the target (LDL-C < 55 mg/dL) according to 
the lipid indicator test at Visit 3, they will continue treatment with the same dose for 6 weeks. 
If the LDL-C level has not reached target, the dose of atorvastatin should be increased to 
ezetimibe/atorvastatin 10/80 mg or atorvastatin 80 mg according to the group assigned. In 
principle, a morning visit is recommended so that the laboratory test results can be checked 
and the IMP can be prescribed and taken on the same day. However, if the test results are not 
confirmed on the same day and a participant has enough IMP to take until the next visit, IMP 
compliance is checked, and the same dose of IMP (ezetimibe/atorvastatin 10/40mg or 
atorvastatin 40mg) is continued. An additional visit is made within 1 week to return the 
remaing IMP and receive new IMP. If the test results are not confirmed on the same day and a 
particpant does not have remaining IMP, the investigator prescribes the same dose of IMP 
(ezetimibe/atorvastatin 10/40mg or atorvastatin 40mg) that the participant was taking 
previously, and an additional visit is made within 1 week to receive new IMP. Visit 4 is the 
end of study visit, and tests for effectiveness and safety are conducted. 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
17 of 59 
[Organon] 소유권 
4.2 
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. 
A participant is considered to have completed the study if he/she has completed all periods of 
the study including the last visit. 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
18 of 59 
[Organon] 소유권 
5.0 STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known 
as protocol waivers or exemptions, are not permitted. 
5.1 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria apply: 
1. Patients who are ≥ 30 years old. 
2. Patients with very high-risk* 
*: clinical or unequivocal on imaging ASCVD. ASCVD includes previous ACS (MI 
or UA), stable angina, coronary revascularization (percutaneous coronary intervention 
(PCI), coronary artery bypass graft surgery (CABG), and other arterial 
revascularization procedures), stroke and transient ischaemic attack (TIA), and 
peripheral arterial disease (Mach F 2020). 
3. Patients (a) who failed to achieve LDL-C lower than 70 mg/dL with low and/or 
moderate intensity$ statin mono therapy for ≥ 4 weeks or (b) who are statin-naïve or 
have not been on a stable (unchanged) statin regimen for at least 4 weeks prior to 
enrollment. 
$: rosuvastatin < 20 mg, atorvastatin < 40 mg, and all dose of pitavastatin, simvastatin, 
lovastatin, pravastatin, and fluvastatin (Stone NJ 2014). 
4. Patients with LDL-C levels ≥ 70 mg/dL 
5. Patients who are willing to maintain TLC throughout the study. 
6. Patients who are willing to provide written informed consent prior to study 
enrollment. 
 
5.2 
Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
1. Patients with hypersensitivity to ezetimibe, atorvastatin or any of its inactive 
ingredients. 
2. Patients with active liver disease or unexplained persistent elevations of hepatic 
transaminase levels. (aspartate transaminase (AST) or alanine transaminase (ALT) > 3 
x upper limit of normal (ULN)). 
3. Patients who have predisposing conditions with muscle disease (i.e., rhabdomyolysis 
or myopathy) or neuromuscular disease. 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
19 of 59 
[Organon] 소유권 
4. Patients with myasthenia gravis. 
5. If female,  patient is a pregnant woman or a women intending to become pregnant 
within a year. 
6. Patients who are taking glecaprevir and pibrentasvir. 
7. Patients with hereditary problems of galactose intolerance, lapp lactase deficiency, or 
of glucose-galactose malabsorption. 
8. Patients with disease known to influence serum lipids or lipoproteins excluding 
dyslipidemia. 
9. Patients with a history of cancer within 5 years. 
10. Patients whose life expectancy is less than 6 months due to their medical conditions. 
11. Patients with any condition or situation that might pose a risk to the participant or 
interfere with participation in the study. 
12. Patients who have received any investigational medicine within 12 weeks of written 
informed consent or are going to receive during the clinical trial period. 
13. Patients who are judged to be difficult to conduct clinical trials according to the 
judgment of the investigator 
 
5.3 
Lifestyle Considerations 
Participants should be educated on TLC to be conducted during the entire clinical trial period. 
TLC includes diet, weight loss, and exercise therapy and is performed according to the 
standard guide of each site.  
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 a study intervention. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants to meet 
the Consolidated Standards of Reporting Trials publishing requirements and to respond to 
queries from institutional review boards (IRBs)/ independent ethics committees (IECs). 
Minimal information includes demography, screen failure details, eligibility criteria, and any 
medical history/current medical conditions. 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened once. Rescreened participants should be given a new participant number. Re-

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
20 of 59 
[Organon] 소유권 
screening is decided at the discretion of the investigator, and is performed after consulting 
with the sponsor. 
5.5 
Criteria for Temporarily Delaying 
Enrollment/Randomization/Administration of Study Intervention 
Enrollment and randomization can be paused, at the Sponsor’s discretion, in the event of 
restrictions related to the coronavirus disease 2019 (COVID-19) pandemic or a similar 
national emergency. 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
21 of 59 
[Organon] 소유권 
6.0 STUDY INTERVENTIONS AND CONCOMITANT 
THERAPY 
Study intervention is defined as any investigational interventions, marketed products, placebo, 
or medical devices intended to be administered to a study participant according to the study 
protocol. 
6.1 
Study Interventions Administered 
Details of the treatments administered in this study are presented in Table 6–1 and Table 6–2. 
Table 6–1 Study Interventions Administered 
Intervention Label 
Ezetimibe/Atorvastatin 
Atorvastatin 
Intervention Name 
Atozet 
Lipitor 
Type  
Drug 
Drug 
Dose Formulation 
Tablet 
Tablet 
Unit Dose Strength(s) 
10/40 mg 
10/80 mg 
40 mg 
80 mg 
Dosage Level(s) 
QD 
QD 
Route of Administration 
Oral 
Oral 
Use 
Experimental 
Active comparator 
IMP and NIMP/AMP. 
IMP 
IMP 
Sourcing 
Provided centrally by the Sponsor.  
Provided centrally by the Sponsor.  
Packaging and Labeling 
Do not include a sample of 
the label text or details of 
pack design in the protocol. 
Study intervention will be provided in 
bag. Each bag will be labeled as required 
per country requirement. 
 
Study intervention will be provided 
in bag. Each bag will be labeled as 
required per country requirement. 
Abbreviations: QD = once a day; IMP = investigational medical product 
Table 6–2 Study Arms 
Arm Title 
Eze/Ato 
Ato 
Arm Type 
Experimental 
Active comparator 
Arm Description 
Participants will receive 
ezetimibe/atorvastatin 10/40 mg QD 
from Visit 2 (Day 1) to Visit 3 
(Week 6). If the LDL-C target is 
reached (LDL-C < 55 mg/dL) at 
Visit 3, maintain the dose to Visit 4 
(Week 12). If the LDL-C target level 
is not reached at Visit 3, dose is 
increased to ezetimibe/atorvastatin 
10/80 mg QD from Visit 3 to Visit 
4. 
Participants will receive atorvastatin 
40 mg QD from Visit 2 (Day 1) to 
Visit 3 (Week 6). If the LDL-C 
target is reached (LDL-C < 55 
mg/dL) at Visit 3, maintain the dose 
to Visit 4 (Week 12). If the LDL-C 
target is not reached on at Visit 3, 
dose is increased to atorvastatin 80 
mg QD from Visit 3 to Visit 4. 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
22 of 59 
[Organon] 소유권 
Associated Intervention Labels 
Ezetimibe/Atorvastatin 
Atorvastatin 
Abbreviations: QD = once a day 
6.2 
Preparation, Handling, Storage, and Accountability 
The investigator or authorized study site staff must confirm appropriate temperature 
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, and only authorized 
study site staff may supply 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 site staff. 
The investigator, site, or the head of the medical institution (where applicable) is responsible 
for study intervention accountability, reconciliation, and record maintenance (ie, receipt, 
reconciliation, and final disposition records). 
The investigator, a member of the study site staff, or a hospital pharmacist must maintain an 
adequate record of the receipt and distribution of all study intervention using the Drug 
Accountability Form. These forms must be available for inspection at any time. 
Further guidance and information for the final disposition of unused study interventions are 
provided in a separate document. 
6.3 
Measures to Minimize Bias: Randomization 
All participants will be centrally assigned to randomized study intervention using an 
interactive web response system (IWRS). Before the study is initiated, the log-in information 
and directions for the IWRS will be provided to each study site. 
Study intervention will be dispensed at the study visits as summarized in the Section 1.3.  
Returned study intervention should not be redispensed to the participants. 
If the IWRS system is unavailable, contact the medical monitor in charge of the site to solve 
the problem. 
6.3.1 
Stratified block randomization 
The randomization code will be set so that the test group and control group can be assigned in 
a 1:1 ratio by the stratified block randomization method for each institution and using statin 
administration history as a stratification factor. 
Inclusion criterion No. 3 is the stratification factor, and the classification is as follows: 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
23 of 59 
[Organon] 소유권 
(a) patients who failed to achieve their target LDL-C goals with low and/or moderate intensity 
statin mono therapy for ≥ 4 weeks 
(b) patients who are statin-naïve or have not been on a stable (unchanged) statin regimen for at 
least 4 weeks prior to enrollment 
However, in the case of (b) patients, less than 40% of each group should be recruited. 
6.4 
Study Intervention Compliance 
The prescribed dosage and regimen of administration may not be changed. Any departures 
from the intended regimen must be recorded in the electronic case report form (eCRF). 
Participants exhibiting poor compliance as assessed by tablet counts should be counseled on 
the importance of good compliance to the study dosing regimen. 
Noncompliance is defined as taking less than 80% or more than 120% of study intervention 
during any evaluation period (visit to visit). 
When participants self-administer study interventions at home, compliance with study 
intervention will be assessed at each visit. Compliance will be assessed by direct questioning 
and counting returned tablets during the study site visits and documented in the source 
documents and relevant form. Deviation(s) from the prescribed dosage regimen should be 
recorded. 
A record of the quantity of study interventions dispensed to and administered by each 
participant must be maintained and reconciled with study intervention and compliance 
records. Intervention start and stop dates, including dates for intervention delays and/or dose 
reductions will also be recorded. 
6.5 
Continued Access to Study Intervention after the End of the Study 
The Sponsor will not provide any additional care to participants after they leave the study. 
6.6 
Treatment of Overdose 
In the event of an overdose, the investigator should: 
 Contact the medical monitor immediately (see Section 8.4.7). 
 Evaluate the participant to determine, in consultation with the medical monitor, whether 
study intervention should be interrupted or whether the dose should be reduced. 
 Closely monitor the participant for any AE/serious adverse event (SAE) and laboratory 
abnormalities until end of study. 
 Document the quantity of the excess dose as well as the duration of the overdose. 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
24 of 59 
[Organon] 소유권 
6.7 
Concomitant Therapy 
The Investigator must instruct the participant to notify the study site about any new 
medications he/she takes after signing the study informed consent. All medications, 
procedures, and significant non-drug therapies (including physical therapy and blood 
transfusions) administered after the participant was enrolled into the study must be recorded 
on the appropriate eCRFs. 
Any therapy that the participant is receiving at the time of enrollment or receives during the 
study must be recorded along with: 
 Concomitant therapy name 
 Reason for use 
 Period including start and end dates 
In particular, in the case of medication, the following items are also collected: 
 Route of administration 
 Dosage information including dose and frequency 
Prior medication up to 1 month prior to enrollment is also collected. 
 
The following drugs are not allowed to be administered during the clinical trial period. 
However, partial permission is possible at the discretion of the investigator. 
1. Lipid modulating agents other than IMP. 
- 
statin, fibric acid derivatives, ezetimibe, bile acid sequestrants, PCSK9 inhibitor, 
nicotinic acid (niacin) 
- 
alipogene tiparvovec, bempedoic acid, dextrothyroxine, inclisiran, lomitapide, 
magnesium pyridoxal 5-phosphate glutamate, meglutol, mipomersen, omega-3-
triglycerides incl. other esters and acids, policosanol, probucol, tiadenol 
2. Other drugs or foods that may affect blood lipids. 
- 
systemic steroids, lipolytic enzyme inhibitors (e.g., orlistat), hormone replacement 
therapy, thyroid therapy (e.g., levothyroxine, benzylthiouracil), fish oil, fiber-based 
laxatives, cholestine, phytosterol margarines, grapefruit. 
3. Drugs with known drug interactions with IMP according to label. 
- 
cyclosporine, HIV protease inhibitors, hepatitis C protease inhibitors, gemfibrozil, 
fusidic acid.  
4. Drugs or foods described in the label precautions. 
 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
25 of 59 
[Organon] 소유권 
7.0 DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
Discontinuation of specific study sites or of the study as a whole are detailed in 
Section 10.1.10. 
7.1 
Discontinuation of Study Intervention 
It may be necessary for a participant to permanently discontinue study intervention. If study 
intervention is permanently discontinued, the participant will remain in the study to be 
evaluated for lipid profile. See the SoA in Section 1.3 for data to be collected at the time of 
discontinuation of study intervention and follow-up and for any further evaluations that need 
to be completed. 
The following criteria should be considered for discontinuation: 
- 
Protocol deviation 
- 
Lost to follow-up 
- 
AST or ALT level > 3 × ULN for 2 consecutive times 
- 
CK > 10 × ULN for 2 consecutive times 
- 
Pregnancy 
- 
Termination of the study by the investigator or Sponsor 
- 
Difficult to continue the study according to the judgment of the investigator 
- 
Adverse event 
- 
Withdrew informed consent 
If a participant who does not meet enrollment criteria is inadvertently enrolled, that participant 
must be discontinued from study intervention and the Sponsor or designee, must be contacted. 
An exception may be granted in rare circumstances for which there is a compelling safety 
reason to allow the participant to continue. In these rare cases, the investigator must obtain 
documented approval from the Sponsor or designee, to allow the participant to continue in the 
study. 
Participants who discontinue study intervention will not be replaced. 
7.2 
Participant Discontinuation/Withdrawal from the Study 
A participant may withdraw from the study at any time at his/her own request or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, or 
compliance, positive COVID-19 test or suspected Severe acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2) infection, or administrative reasons. This is expected to be 
uncommon. 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
26 of 59 
[Organon] 소유권 
At the time of discontinuing from the study, if possible, an early discontinuation visit should 
be conducted, as shown in the SoA (Section 1.3). See SoA for data to be collected at the time 
of study discontinuation and follow-up and for any further evaluations that need to be 
completed.  
The participant will be permanently discontinued from the study intervention and the study at 
that time. 
If the participant withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the investigator must document this in the study site study records. 
7.3 
Lost to Follow-up 
A participant will be considered lost to follow-up if he/she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the site for a required 
study visit: 
 The study site must attempt to contact the participant and reschedule the missed visit as 
soon as possible, counsel the participant on the importance of maintaining the assigned 
visit schedule and ascertain whether the participant wishes to and/or should continue in the 
study. 
 Before a participant is deemed lost to follow-up, the investigator or authorized study site 
staff must make every effort to regain contact with the participant (where possible, 
telephone calls, and if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented in the 
participant’s medical record. 
 Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study.  

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
27 of 59 
[Organon] 소유권 
8.0 STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the SoA (Section 1.3). Protocol waivers 
or exemptions are not allowed. 
Immediate safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue study 
intervention. 
Adherence to the study design requirements, including those specified in the SoA 
(Section 1.3), is essential and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
Procedures conducted as part of the participant’s routine clinical management (e.g., blood 
count) and obtained before signing of the informed consent form (ICF) may be utilized for 
screening or baseline purposes provided the procedures met the protocol-specified criteria and 
were performed within the timeframe defined in the SoA (Section 1.3). 
8.1 
Baseline characteristics 
8.1.1 
Demography 
Demographics will be evaluated at screening visit and include age, sex, smoking history, 
alcohol history. 
8.1.2 
General medical history 
Medical history including disease name, severity, period will be presented by Medical 
dictionary for regulatory activities (MedDRA) terminology. At the time of randomization, 
past/present disease is determined according to whether it is ongoing or not. 
8.1.3 
Medical history related to dyslipidemia 
Medical history related to dyslipidemia includes risk classification factors (ACS (MI or UA), 
stable angina, coronary revascularization (PCI, CABG, and other arterial revascularization 
procedures), stroke and TIA, and peripheral arterial disease), statin administration history, 
family history, dyslipidemia diagnosis date. 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
28 of 59 
[Organon] 소유권 
8.2 
Effectiveness Assessments 
8.2.1 
Lipid parameter laboratory test 
Lipid laboratory tests for efficacy evaluation include LDL-C, HDL-C, triglycerides, and total 
cholesterol. 
8.3 
Safety Assessments 
8.3.1 
Physical Examinations 
A physical examination will include, at a minimum, assessments of height and weight. Height 
is measured at screening only and body weight is measured at each visit.  
Investigators should pay special attention to clinical signs related to previous serious illnesses. 
8.3.2 
Vital Signs 
Heart rate and blood pressure will be assessed. 
Heart rate and blood pressure measurements will be assessed with a completely automated 
device. Manual techniques will be used only if an automated device is not available. 
Vital signs will be measured in a relax position after 5 minutes rest. Three readings of heart 
rate and blood pressure will be taken. The first reading should be rejected. The second and 
third readings should be averaged to give the measurement to be recorded. 
8.3.3 
12-Lead Electrocardiograms (ECG) 
Single 12-lead ECG will be obtained using an ECG machine that automatically calculates the 
heart rate and measures PR, QRS, QT, and QTc intervals. 
8.3.4 
Clinical Safety Laboratory Tests  
See Section 10.2 for the list of clinical laboratory tests to be performed. 
The investigator must review the laboratory report, document this review, and record any 
clinically significant changes occurring during the study as an AE. The laboratory reports 
must be filed with the source documents.  
Abnormal laboratory findings associated with the underlying disease are not considered 
clinically significant 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 should be repeated until the values return to normal or baseline or 
are no longer considered clinically significant by the investigator or medical monitor. 
However, abnormal lab result will not be followed up after study completion. 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
29 of 59 
[Organon] 소유권 
If clinically significant values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified, and the Sponsor or designee 
notified. 
If laboratory values from non-protocol-specified laboratory tests performed at the site’s local 
laboratory require a change in participant management or are considered clinically significant 
by the investigator (e.g., SAE or AE or dose modification), then the results must be recorded. 
8.3.5 
Pregnancy Testing 
Women of childbearing potential (WOCBP) should only be included after a confirmed 
menstrual period and a negative highly sensitive urine or serum pregnancy test. 
Additional pregnancy testing should be performed at each visit during the treatment period 
and as required locally. 
Pregnancy testing will be performed whenever a menstrual cycle is missed or when pregnancy 
is otherwise suspected. 
8.4 
Adverse Events, Serious Adverse Events, and Other Safety Reporting 
The definitions of AEs and SAEs can be found in Section 10.3. Treatment-emergent adverse 
events (TEAEs) are defined as AEs that first occurred or worsened in severity after the first 
administration of the study treatment during the treatment period. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant’s legally authorized representative). The investigator who is a 
qualified physician, will assess events that meet the definition of an AE or SAE with respect 
to seriousness, severity and causality. The investigator and authorized study site staffs are 
responsible for detecting, documenting, and recording events that meet the definition of an AE 
or SAE and remain responsible for following up all AEs (see Section 10.3). For any guidance 
regarding AE/SAE reporting, the Investigator should contact the medical monitor. 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 10.3. 
8.4.1 
Time Period and Frequency for Collecting AE and SAE Information 
From the time of screening to the last visit, all AEs, SAEs, and other reportable safety events 
must be recorded and reported by the investigator to the Sponsor or designee within the time 
frames indicated in Table 8–1.  
Additionally, any SAE brought to the attention of the investigator at any time outside the 
period specified in the previous paragraph must be reported immediately. 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
30 of 59 
[Organon] 소유권 
Table 8–1 Reporting Time Periods and Time Frames for Adverse Events, Serious Adverse 
Events, and other reportable safety events.  
Type of Event 
Reporting Time Period: 
Treatment Allocation 
Through End of Study 
Time Frame to Report Event and 
Follow-up Information to Sponsor 
or designee 
Adverse Event (AE) 
Report all 
Per study manual  
Serious Adverse Event (SAE) 
Report all 
Within 24 hours of learning of event 
Pregnancy/Lactation Exposure 
Report all 
Within 24 hours of learning of event 
All AE/SAEs will be collected from the study participation until the last visit. However, if 
events are collected up to a period of 14 days after the intake of study treatment, it is recorded 
as AEs. 
All SAEs will be recorded and reported to the Sponsor or designee immediately and under no 
circumstance should this exceed 24 hours of the investigator’s awareness of the event, as 
indicated in Section 10.3. The investigator will submit any updated SAE data to the Sponsor 
or designee within 24 hours of their awareness of the updated information. 
Investigators are not obligated to actively seek information on AEs or SAEs after conclusion 
of the study participation. However, if the investigator learns of any SAE, including a death, at 
any time after a participant has been discharged from the study, and he/she considers the 
event/cause of death to be reasonably related to the study intervention or study participation, 
the investigator must promptly notify the Sponsor or designee. 
The method of recording, evaluating, and assessing causality of AE and SAE and the 
procedures for completing and transmitting safety reports are provided in Section 10.3. 
AEs that are reported after the AE reporting time period of study should be forwarded to 
Sponsor or designee and reported as spontaneous cases. 
8.4.2 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about AE 
occurrences. 
8.4.3 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All AEs, SAEs, and other reportable events, 
including pregnancy complications/outcomes and exposure during breastfeeding will be 
followed. Further information on follow-up procedures is provided in Section 10.3. Also, the 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
31 of 59 
[Organon] 소유권 
investigator will make every attempt to follow all non-serious AEs that occur in eligible 
participants for outcome. 
Investigators remain responsible for following up on final event outcomes and events that are 
serious, considered related to the study treatment or study procedures, or that caused the 
participant to discontinue the study treatment or withdraw from the study. 
8.4.4 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the Sponsor or designee of an SAE is essential so 
that legal obligations and ethical responsibilities toward the safety of participants and the 
safety of a study intervention under clinical investigation are met. 
The Sponsor or designee 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 or designee will comply with country-specific regulatory 
requirements relating to safety reporting to the corresponding regulatory authority, IRB/IEC, 
and investigators. 
An investigator who receives an investigator safety report describing an SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the Sponsor or designee will 
review and then file it along with the package insert and will notify the IRB/IEC, if 
appropriate according to local requirements. 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSARs) according to local regulatory requirements and Sponsor policy and 
forwarded to investigators as necessary. 
8.4.5 
Pregnancy 
Details of all pregnancies in female participants will be collected after the start of study 
intervention and until 1 month after the estimated date of delivery (EDD) (see Section 10.4). 
If a pregnancy is reported, the investigator will record pregnancy information on the 
appropriate form and submit it to the Sponsor or designee within 24 hours of learning of the 
female participant pregnancy and should follow the procedures outlined in Section 10.3. 
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. 
If the outcome of the pregnancy meets the criteria for immediate classification as an SAE (ie, 
spontaneous abortion, stillbirth, neonatal death, or congenital anomaly including that in an 
ectopic pregnancy, aborted fetus, stillbirth, or fetal death) the investigator will report 
according to the SAE reporting procedures described in Section 10.3. 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
32 of 59 
[Organon] 소유권 
The female participant will be followed to determine the outcome of the pregnancy (e.g., until 
delivery of baby or for longevity). The investigator will collect follow-up information on the 
female participant and the neonate and the information will be forwarded to the Sponsor or 
designee. 
Any post-study pregnancy-related SAE considered reasonably related to the study intervention 
by the investigator will be reported to the Sponsor or designee as described in Section 10.3. 
While the investigator is not obligated to actively seek this information in former female 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. 
8.4.6 
Adverse Events of Special Interest 
Not applicable 
8.4.7 
Special Situations 
The following special situations are considered important safety information and can be 
reported, regardless of seriousness or causality, if the investigator becomes aware of them: 
• Overdose 
Note: In this study, an overdose is defined as the patient has taken, accidentally or 
intentionally, a dose exceeding the dose as stated in the local label. 
• Lack of therapeutic effect 
• Off-label use, medication error, misuse, abuse, or occupational exposure 
• Suspected transmission via a medicinal product of an infectious agent 
These special situations are not considered as AEs, but do require to be reported to Sponsor or 
designee on the same timeline as the AE.If special situation is associated with, or results in, an 
AE, the AE is to be assessed separately from the special situation and captured as an AE in 
eCRF. 
 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
33 of 59 
[Organon] 소유권 
9.0 STATISTICAL CONSIDERATIONS 
The statistical analysis plan will be finalized prior to database lock 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 key secondary endpoints. 
9.1 
Statistical Hypotheses 
The primary endpoint of the study is the percentage change in LDL-C from baseline to 6 
weeks. The primary hypothesis is that the addition of ezetimibe to atorvastatin would result in 
a significantly greater reduction in percentage change in LDL-C compared with atorvastatin 
monotherapy. 
9.2 
Analysis Sets 
The safety analysis set (SAS) includes all randomized patients who received at least one dose 
of study treatment. Patients in the SAS will be included in the actual treatment group, 
regardless of their randomized treatment. 
The full analysis set (FAS) comprises all randomized patients who had a baseline assessment 
of LDL-C and received at least one dose of study treatment. Patients in the FAS will be 
included in their randomized treatment group, regardless of their actual treatment. The FAS is 
the primary analysis set for efficacy analyses. 
The per-protocol set (PPS) is a subset of the FAS who completed the 6-week follow-up 
observation with no major protocol deviations. The efficacy analysis based on the PPS will be 
considered supportive. 
9.3 
Statistical Analyses 
9.3.1 
General Considerations 
All analyses will be performed by a designated CRO using SAS 9.4 or above. 
Descriptive statistics will include n, mean, standard deviation (SD), median, minimum, and 
maximum for continuous variables and the number and percentage of patients for categorical 
variables. If necessary, more detailed information will be provided.  
For continuous efficacy variables, the statistical comparisons between treatment groups are 
performed using an analysis of covariance (ANCOVA) with treatment group as a factor and 
the corresponding baseline and history of statin administration as the covariate. For 
categorical efficacy variables, the statistical significance of the differences between treatment 
groups is tested using Chi-square test or Fisher's exact test. All the statistical tests use a two-
sided test at the significance level of 0.05. 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
34 of 59 
[Organon] 소유권 
Unless otherwise specified, missing for all efficacy parameters will be imputed by last 
observation carried forward (LOCF) method. For patients with no post-baseline value, the 
baseline values are carried forward. 
9.3.2 
Primary Endpoint 
The primary endpoint analysis will be performed on the FAS and PPS, and the primary 
analysis set is the FAS. The primary endpoint is defined as 100 x (LDL-C value at 6 weeks – 
LDL-C value at baseline) / LDL-C value at baseline. 
The statistical significance of the difference in the percentage change between treatment 
groups will be analyzed by fitting ANCOVA model with treatment group as a factor and the 
baseline LDL-C and history of statin administration as the covariate. Estimates of least 
squares (LS) mean and standard error (SE) for within-treatment effects and treatment 
differences along with corresponding two-sided 95% CI and p-value will be provided. If the 
upper limit of the 95% two-sided CI for the corresponding treatment difference 
(ezetimibe/atorvastatin 10/40 mg - atorvastatin 40 mg) is less than 0, ezetimibe/atorvastatin 
10/40 mg is considered superior to atorvastatin 40 mg.  
In addition, descriptive statistics will be presented for LDL-C at each visit and for percentage 
change from baseline. 
9.3.3 
Secondary Endpoints 
All secondary endpoint analyses will be performed on the FAS and PPS.  
The number and percentage of patients achieving LDL-C goal of < 55 mg/dL and LDL-C goal 
of < 70 mg/dL at 6 weeks and 12 weeks will be presented by treatment group and tested using 
Chi-square test or Fisher’s exact test as appropriate. The difference in the percentage will be 
presented with its corresponding 95% CI and p-value. 
For continuous secondary variables, the percentage change from baseline at time point of 
interest will be analyzed by fitting ANCOVA model with treatment group as a factor and its 
corresponding baseline and history of statin administration as a covariate. Estimates of LS 
mean and SE for within-treatment effects and treatment differences along with corresponding 
two-sided 95% CI and p-value will be provided. In addition, descriptive statistics will be 
presented for outcome of interest at each visit and for percentage change from baseline. 
9.3.4 
Subgroup Analysis 
If possible, subgroup analysis will be performed on the primary endpoint and all secondary 
endpoins at 6 and/or 12 weeks to assess the homogeneity of the treatment effect across various 
subgroups including history of statin administration, age, sex and status of a dose up-titration.   

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
35 of 59 
[Organon] 소유권 
9.3.5 
Safety Analysis 
All safety analyses will be performed on the SAS. 
The number and percentage of patients experiencing TEAEs, treatment-emergent serious 
adverse events (TESAE)s, Treatment-related adverse events (TRAEs) and TEAEs leading to 
the premature discontinuation of the study at 6 weeks and 12 weeks will be presented by 
treatment group and tested using Chi-square test or Fisher’s exact test as appropriate. The 
difference in the percentages will be presented with its corresponding 95% CI and p-value. 
The numbers and percentages of patients experiencing TEAEs will be summarized by system 
organ class (SOC) and preferred term (PT) according to the MedDRA dictionary for each 
treatment group.  
Individual TESAEs and TEAEs leading to the premature discontinuation of the study will be 
listed with details including reported term, SOC, PT, start and stop date, severity, seriousness 
with criteria, causality, action taken and outcome.  
For continuous other variables such as weight and vital signs parameters, descriptive statistics 
will be presented for outcome of interest at each visit and for change from baseline by 
treatment group.  
Individual clinically significant changes in 12-lead ECG will be listed. 
9.4 
Interim Analysis 
No interim analysis is planned. 
9.5 
Sample Size Determination 
The statistical hypothesis of this study is as follows. 
0:  -  = 0 vs. 1:  -  ≠ 0 

= Percentage change in LDL-C from baseline to 6 weeks in 
ezetimibe/atorvastatin 10/40 mg 

= Percentage change in LDL-C from baseline to 6 weeks in atorvastatin 
40 mg 
Azar et al. reported that the between-treatment difference in percentage change in LDL-C at 8 
weeks was -10% in favor of ezetimibe/atorvastatin 10/40 mg compared to atorvastatin 40 mg 
(-20% vs -10%; p-value=0.01) (Azar RR 2010). This is the only study that has assessed the 
efficacy of ezetimibe/atorvastatin 10/40 mg versus atorvastatin 40 mg among very high-risk 
patients with stable CAD or CAD equivalent (coronary stenosis >50%, previous myocardial 
infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, diabetes 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
36 of 59 
[Organon] 소유권 
mellitus, stroke, peripheral vascular disease) who were taking the potency of the background 
statins ≤ 20 mg/day of atorvastatin prior to the randomization. Although the evaluation time 
point for the LDL-C lowering effect in Azar et al. study is at 8 weeks, it is noted that a 
reduction in LDL-C is usually achieved with all statins as well as ezetimibe as early as 2 
weeks, with a maximum response occurring by 4 weeks and maintaining thereafter during 
continued therapy (ACH-Ezetimibe Product Monograph 2019; Shankar PR 2019). Given that, 
this study sets -10% as the expected difference in percentage change in LDL-C from baseline 
to 6 weeks between the treatment groups.  
The pooled standard deviation of 19.0% was obtained from the p-value of 0.01 and a total of 
50 patients per treatment group reported in the study of Azar et al.; The t-value that 
corresponds with a p-value of 0.01 and 50 + 50 – 2 = 98 degrees of freedom is t=2.627, 
considering that the degrees of freedom are given N1 + N2 – 2, where N1 and N2 are the 
number of study patients per each treatment group. As the t-value is the ratio of the difference 
in means to the standard error of the difference in means, the standard error is therefore 
obtained by dividing 10 (treatment difference in percentage change in LDL-C) by 2.627, 
which gives 3.8066. In turn, the standard deviation obtained from standard error is 19% 
(3.8066 / SQRT (1/50 + 1/50)). 
Based on this, the number of patients in each treatment group calculated by the formula below 
is about 57 under the assumption of two-sided significance level α = 0.05, power 1-β = 0.80 
with a randomization ratio λ = 1. Considering the dropout rate of 10%, 63 patients for each 
group and thus, a total of 126 patients will be randomized in this study. 
 = (	 + 1) + 

	(μ −μ)
=
(1 + 1)(1.96 + 0.842)(19)
(−10)
= 56.69 
 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
37 of 59 
[Organon] 소유권 
10.0 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 
international ethical guidelines 
 Applicable ICH good clinical practice (GCP) guidelines 
 Applicable laws and regulations. 
The protocol, protocol amendments, ICF, product information, and other relevant documents 
(e.g., advertisements) must be submitted to an IRB/IEC by the investigator and reviewed and 
approved by the IRB/IEC before the study is initiated. 
Any 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.  
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 the conduct of the study at the study site 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), European Medical 
Device Regulation 2017/745 for clinical device research (if applicable), and all other 
applicable local regulations. 
After reading the protocol, each investigator will sign the protocol signature page and send a 
copy of the signed page to the Sponsor or designee. The study will not start at any study site at 
which the investigator has not signed the protocol. 
10.1.2 
Adequate Resources 
The investigator is responsible for supervising any individual or party to whom the 
investigator delegates study-related duties and functions conducted at the study site. 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
38 of 59 
[Organon] 소유권 
If the investigator/site retains the services of any individual or party to perform study-related 
duties and functions, the investigator/site should ensure this individual or party is qualified to 
perform those study-related duties and functions and should implement procedures to ensure 
the integrity of the study-related duties and functions performed and any data generated. 
10.1.3 
Financial Disclosure 
Investigators and authorized study site staffs 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. 
10.1.4 
Insurance 
Sponsor will provide insurance in accordance with local guidelines and requirements as a 
minimum for the participants in this study. The terms of the insurance will be kept in the study 
files. 
10.1.5 
Informed Consent Process 
The investigator or authorized study site staff will explain the nature of the study, including 
the risks and benefits, to the participant or their legally authorized representative and answer 
all questions regarding the study. 
Participants must be informed that their participation is voluntary. Participants or their legally 
authorized representatives 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 site. 
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was obtained. 
The authorized person obtaining the informed consent must also sign the ICF. 
Participants must be reconsented to the most current version of the ICF during their 
participation in the study. 
A copy of the ICF must be provided to the participant or their legally authorized 
representative. 
A participant who is rescreened is not required to sign another ICF if the rescreening occurs 
within 7 days from the previous ICF signature date. 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
39 of 59 
[Organon] 소유권 
10.1.6 
Data Protection 
 Participants will be assigned a unique identifier by the Sponsor. Any participant records or 
datasets that are transferred to the Sponsor will contain the identifier only; participant 
names or any information which would make the participant identifiable will not be 
transferred. 
 The participant must be informed that his/her personal study-related data will be used by 
the Sponsor in accordance with local data protection law. The level of disclosure must also 
be explained to the participant 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 his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
Sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
10.1.7 
Dissemination of Clinical Study Data 
The results of the study should be reported within 1 year from the end of the clinical study. 
Irrespective of the outcome, the Sponsor will submit to any relevant database a summary of 
the results of the clinical study within 1 year from the end of the global clinical study. It shall 
be accompanied by a summary written in a manner that is understandable to laypersons. 
10.1.8 
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 (e.g., laboratory data). The 
investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the CRF. 
 Guidance on completion of CRFs will be provided in a separate document. 
 The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents. 
 Quality tolerance limits will be predefined in the Study Monitoring Plan to identify 
systematic issues that can impact participant safety and/or reliability of study results. 
These predefined parameters will be monitored during the study, and important deviations 
from the quality tolerance limits and remedial actions taken will be summarized in the 
clinical study report. 
 Monitoring details describing strategy, including definition of study critical data items and 
processes (e.g., risk-based initiatives in operations and quality such as risk management 
and mitigation strategies and analytical risk-based monitoring), methods, responsibilities, 
and requirements, including handling of noncompliance issues and monitoring techniques 
(central, remote, or on-site monitoring) are provided in the Study Monitoring Plan. 
 Details of study monitoring, including action required due to SARS-CoV-2 (COVID-19), 
will be included in a separate Study Monitoring Plan. 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
40 of 59 
[Organon] 소유권 
 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 (e.g., 
contract research organizations (CROs)). 
 Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the investigator for 10 years after study completion 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. 
10.1.9 
Source Documents 
The investigator/site should maintain adequate and accurate source documents and study 
records that include all pertinent observations on each of the study site’s participants. Source 
data should be attributable, legible, contemporaneous, original, accurate, and complete. 
Changes to source data should be traceable, should not obscure the original entry, and should 
be explained if necessary (e.g., via an audit trail). 
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 the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available. 
Definition of what constitutes source data and its origin can be found in source data 
acknowledgment or monitoring guidelines or eCRF completion guidelines.  
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the CRF by authorized study 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. 
10.1.10 
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. 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
41 of 59 
[Organon] 소유권 
The first study site open is considered the first act of recruitment and will be the study start 
date. 
Study/Site Termination 
The Sponsor or designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or investigator may include but are 
not limited to: 
For study termination: 
 Discontinuation of further study intervention development. 
For study site termination: 
 Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the Sponsor’s procedures, or GCP guidelines 
 Inadequate or no recruitment (evaluated after a reasonable amount of time) of participants 
by the investigator 
 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, and any CRO(s) used in the study of the reason for termination 
or suspension, as specified by the applicable regulatory requirements. The investigator shall 
promptly inform the participant and should assure appropriate participant therapy and/or 
follow-up. 
10.1.11 
Publication Policy 
The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before 
submission. This allows the Sponsor to protect proprietary information and to provide 
comments. 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual study site data. In this case, a 
coordinating investigator will be designated by mutual agreement. 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
42 of 59 
[Organon] 소유권 
Authorship will be determined by mutual agreement and in line with International Committee 
of Medical Journal Editors authorship requirements. 
 
 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
43 of 59 
[Organon] 소유권 
10.2 Appendix 2: Clinical Laboratory Tests 
The tests detailed in Table 10–1 will be performed by the local laboratory. 
Additional tests may be performed at any time during the study as determined necessary by 
the investigator or required by local regulations. 
Table 10–1 Protocol-required Safety Laboratory Tests 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet count  
White blood cell count with differential: 
 
Red blood cell count 
Neutrophils 
 
Hemoglobin 
Lymphocytes 
 
Hematocrit 
Monocytes 
 
 
Eosinophils 
 
 
Basophils 
Clinical Chemistrya 
Blood urea nitrogen (BUN) 
Aspartate aminotransferase (AST)/Serum 
glutamic-oxaloacetic transaminase (SGOT) 
 
Creatinine 
Alanine aminotransferase (ALT)/serum 
glutamic-pyruvic transaminase (SGPT) 
 
Glucose  
Alkaline phosphatase (ALP) 
 
Gamma glutamyl transferase 
(GGT) 
Creatine kinase (CK) 
 
Potassium 
Chloride 
 
Sodium 
Total and direct bilirubin 
 
Calcium 
Total protein 
 
Albumin 
Phosphate 
 
Lactate Dehydrogenase (LDH) 
C-reactive protein 
 
Uric acid 
HbA1c b 
Lipid parameter 
LDL-C 
Triglycerides 
 
HDL-C 
Total cholesterol 
Urinalysis 
Leucocytes 
Red blood cells 
 
Protein 
pH 
 
Bilirubin 
Nitrite 
 
Urobilinogen 
Specific gravity 
 
Ketones 
Glucose 
Other screening tests 
Follicle Stimulating Hormone (FSH) and estradiol (as needed in women of 
non-childbearing potential only). 
Serum or urine human chorionic gonadotropin (hCG) pregnancy test (as 
needed for women of childbearing potential)c. 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
44 of 59 
[Organon] 소유권 
Laboratory 
Assessments 
Parameters 
<<NOTES: 
a  All events of ALT or AST 3 × upper limit of normal (ULN) and bilirubin 2 × ULN (>35% direct 
bilirubin) or ALT or AST 3 × ULN and international normalized ratio (INR) >1.5, if INR measured, 
may indicate severe liver injury (possible Hy’s Law) and must be reported as an SAE (excluding studies 
of hepatic impairment or cirrhosis). 
b  The test is performed in participants with confirmed history of diabetes at V1 and V4. However, there 
will not be a separate testing to confirm diabetes in patients as part of this study. If participants already 
have diabetes in their current medical history, they will be classified as participants with confirmed 
diabetes. 
c  Local urine testing will be standard for the protocol unless serum testing is required by local regulation 
or IRB/IEC. 
Investigators must document their review of each laboratory safety report. The results of each 
test must be entered into the (e)CRF. 
 
 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
50 of 59 
[Organon] 소유권 
10.4 Appendix 4: Contraceptive and Barrier Guidance and Collection of 
Pregnancy Information 
10.4.1 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below). 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
a) Documented hysterectomy. 
b) Documented bilateral salpingectomy. 
c) Documented bilateral oophorectomy. 
NOTE: Documentation can come from the study site personnel’s: review of the participant’s 
medical records, medical examination, or medical history interview. 
3. Postmenopausal female: 
a) A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 
12 months of amenorrhea, a single FSH measurement is insufficient.  
b) Females on HRT and whose menopausal status is in doubt will be required to use 1 of 
the non-estrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
10.4.2 
Contraception Guidance 
Female participants 
Female participants of childbearing potential are eligible to participate if they agree to use a 
highly effective method of contraception consistently and correctly as described in the table 
below. 
Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User Dependenta  
Failure rate of <1% per year when used consistently and correctly.  
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of 
ovulationb  
 
Oral. 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
51 of 59 
[Organon] 소유권 
 
Intravaginal. 
 
Transdermal. 
Progestogen only hormonal contraception associated with inhibition of ovulation 
 
Oral. 
 
Injectable.  
Highly Effective Methods That Are User Independenta  
Implantable progestogen only hormonal contraception associated with inhibition of ovulationb 
 
Intrauterine device. 
 
Intrauterine hormone-releasing system. 
 
Bilateral tubal occlusion. 
Vasectomized partner  
A vasectomized partner is a highly effective birth control method provided that the partner is the sole male 
sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional highly effective 
method of contraception should be used.  
Sexual abstinence  
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study intervention. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of 
the participant.  
NOTES:  
a Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for participants participating in clinical 
studies.  
b Hormonal contraception may be susceptible to interaction with the study intervention, which may reduce the 
efficacy of the contraceptive method. In this case, 2 highly effective methods of contraception should be 
utilized during the treatment period and for at least 30 days after the last dose of study intervention.  
 
10.4.3 
Collection of Pregnancy Information 
Female Participants who become pregnant  
 The investigator will collect pregnancy information on any female participant who 
becomes pregnant while participating in this study. Information will be recorded on the 
appropriate form and submitted to the Sponsor or designee 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 or designee. Generally, 
follow-up is required by 1 month after the EDD. Any termination of pregnancy will be 
reported, regardless of fetal status (presence or absence of anomalies) or indication for the 
procedure. 
 While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication 
will be reported as an AE or SAE. If the outcome of the pregnancy meets the criteria for 
immediate classification as an SAE (ie, spontaneous abortion, stillbirth, fetal death, or 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
52 of 59 
[Organon] 소유권 
congenital anomalies, ectopic pregnancy), the investigator will report according to the 
SAE reporting procedures described in Section 10.3. 
 Any post-study pregnancy-related SAE considered reasonably related to the study 
treatment by the investigator will be reported to the Sponsor or designee as described in 
Section 10.3. While the investigator is not obligated to actively seek this information in 
former 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 treatment or be withdrawn from the study. 
10.4.4 
Reporting Pregnancy Information 
Email transmission of the paper Pregnancy Report Form is the preferred method to transmit 
safety event information to Organon or IQVIA with facsimile as a back-up method, if necessary. 
Safety events should be reported to:  
Email: 
 
Fax: 
 
 
 
PPD
PPD

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
53 of 59 
[Organon] 소유권 
10.5 Appendix 5: Abbreviations  
Abbreviation 
Definition 
ACS 
Acute coronary syndrome 
ADL 
Activities of daily living 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
ASCVD 
Atherosclerotic cardiovascular disease 
AST 
Aspartate aminotransferase 
BUN 
Blood urea nitrogen 
CABG 
Coronary artery bypass graft surgery 
CFR 
Code of federal regulations 
CI 
Confidence interval 
CK 
Creatine kinase 
COVID-19 
Coronavirus disease 2019 
CRF 
Case report form 
CRO 
Contract research organization 
CVD 
Cardiovascular disease 
eCRF 
Electronic case report form 
EDD 
Estimated date of delivery 
FAS 
Full analysis set 
FSH 
Follicle stimulating hormone 
GCP 
Good clinical practice 
GGT 
Gamma glutamyl transferase 
HbA1c 
Hemoglobin A1c 
hCG 
Human chorionic gonadotropin 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
IEC 
Independent ethics committee 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
54 of 59 
[Organon] 소유권 
Abbreviation 
Definition 
IMP 
Investigational medicinal product 
INR 
International normalized ratio 
IRB 
Institutional review board 
IWRS 
Interactive web response system 
LDH 
Lactate dehydrogenase 
LOCF 
Last observation carried forward 
LS 
Least squares 
MedDRA 
Medical dictionary for regulatory activities 
MI 
Myocardial infarction 
PCI 
Percutaneous coronary intervention 
PPS 
Per-protocol set 
PT 
Preferred term 
SAE 
Serious adverse event 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SAS 
Safety analysis set 
SD 
Standard deviation 
SE 
Standard error 
SGOT 
Serum glutamic-oxaloacetic transaminase 
SGPT 
Serum glutamic-pyruvic transaminase 
SoA 
Schedule of activities 
SOC 
System organ class 
SUSAR 
Suspected unexpected serious adverse reactions 
TEAE 
Treatment-emergent adverse event 
TESAE 
Treatment-emergent serious adverse event 
TIA 
Transient ischaemic attack 
TLC 
Therapeutic lifestyle change 
TRAE 
Treatment-related adverse event 
UA 
Unstable angina 
ULN 
Upper limit of normal 
WOCBP 
Women of childbearing potential 
 
 
 
 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
56 of 59 
[Organon] 소유권 
(a) patients who failed to achieve their target LDL-C goals with low 
and/or moderate intensity statin mono therapy for ≥ 4 weeks 
(b) patients who are statin-naïve or have not been on a stable 
(unchanged) statin regimen for at least 4 weeks prior to enrollment 
However, in the case of (b) patients, less than 40% of each group 
should be recruited. 
 
 
 
 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
57 of 59 
[Organon] 소유권 
11.0 REFERENCES 
ACH-Ezetimibe Product Monograph. 2019 July 3 
Ambegaonkar BM, Tipping D, Polis AB, Tomassini JE, Tershakovec AM. Achieving goal 
lipid levels with ezetimibe plus statin add-on or switch therapy compared with doubling the 
statin dose. A pooled analysis. Atherosclerosis. 2014 Dec 1;237(2):829-37. 
Averna M, Banach M, Bruckert E, Drexel H, Farnier M, Gaita D, Magni P, März W, Masana 
L, e Silva AM, Reiner Z. Practical guidance for combination lipid-modifying therapy in high-
and very-high-risk patients: A statement from a European Atherosclerosis Society Task Force. 
Atherosclerosis. 2021 May 1;325:99-109. 
Azar RR, Badaoui G, Sarkis A, Azar M, Aydanian H, Harb S, Achkouty G, Kassab R. Effect 
of ezetimibe/atorvastatin combination on oxidized low density lipoprotein cholesterol in 
patients with coronary artery disease or coronary artery disease equivalent. The American 
journal of cardiology. 2010 Jul 15;106(2):193-7. 
Berberich AJ, Hegele RA. LDL cholesterol: lower, faster, younger?. The Lancet Diabetes & 
Endocrinology. 2020 Jan 1;8(1):5-7. 
Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, Darius H, Lewis 
BS, Ophuis TO, Jukema JW, De Ferrari GM. Ezetimibe added to statin therapy after acute 
coronary syndromes. New England Journal of Medicine. 2015 Jun 18;372(25):2387-97. 
Gitt AK, Lautsch D, Ferrières J, Ferrari GM, Vyas A, Baxter CA, Bash LD, Ashton V, Horack 
M, Almahmeed W, Chiang FT, Poh KK, Brudi P, Ambegaonkar B. Cholesterol target value 
attainment and lipid-lowering therapy in patients with stable or acute coronary heart disease: 
Results from the Dyslipidemia International Study II. 2017 Nov; 266:157-166.Jarcho JA, 
Keaney Jr JF. Proof that lower is better--LDL cholesterol and IMPROVE-IT 2015. 
Keys A, Aravanis C, Blackburn H, Van Buchem FS, Buzina R, Djordjevic BS, FIDANZA F, 
KARVONEN MJ, MENOTTI A, PUDDU V, TAYLOR HL. Probability of middle-aged men 
developing coronary heart disease in five years. Circulation. 1972 Apr;45(4):815-28. 
Kim BK, Hong SJ, Lee YJ, Hong SJ, Yun KH, Hong BK, Heo JH, Rha SW, Cho YH, Lee SJ, 
Ahn CM. Long-term efficacy and safety of moderate-intensity statin with ezetimibe 
combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic 
cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial. The Lancet. 
2022 Jul 30;400(10349):380-90. 
Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De 
Backer GG, Delgado V, Ference BA, Graham IM. 2019 ESC/EAS Guidelines for the 
management of dyslipidaemias: lipid modification to reduce cardiovascular risk: the Task 
Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) 
and European Atherosclerosis Society (EAS). European heart journal. 2020 Jan 1;41(1):111-
88. 
Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, Voysey M, Gray A, 
Collins R, Baigent C. The effects of lowering LDL cholesterol with statin therapy in people at 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
58 of 59 
[Organon] 소유권 
low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. 
Lancet (London, England). 2012 May 17;380(9841):581-90. 
Murphy SA, Cannon CP, Blazing MA, Giugliano RP, White JA, Lokhnygina Y, Reist C, Im 
K, Bohula EA, Isaza D, Lopez-Sendon J. Reduction in total cardiovascular events with 
ezetimibe/simvastatin post-acute coronary syndrome: the IMPROVE-IT trial. Journal of the 
American College of Cardiology. 2016 Feb 2;67(4):353-61. 
Rhee EJ, Kim HC, Kim JH, Lee EY, Kim BJ, Kim EM, Song Y, Lim JH, Kim HJ, Choi S, 
Moon MK. 2018 Guidelines for the management of dyslipidemia in Korea. Journal of lipid 
and atherosclerosis. 2019 Sep 1;8(2):78-131. 
Shankar PR, Alshakka MA. Clinical Pharmacy and Therapeutics Sixth Edition. Journal of 
Chitwan Medical College. 2019 Sep 25;9(3):104-. 
Špinar J, Špinarová L, Vítovec J. IMProved reduction of outcomes: Vytorin efficacy 
international trial (studie IMPROVE-IT). Vnitřní lékařství. 2014 Dec 1;60(12):1095-101. 
Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg 
AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, 
Watson K, Wilson PW; American College of Cardiology/American Heart Association Task 
Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol 
to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of 
Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll 
Cardiol. 2014 Jul 1;63(25 Pt B):2889-934. 
 

CONFIDENTIAL 
 
Protocol OG-KORATO-001, ver. 4.1
 
 
 
[Organon] 소유권 
Signature of Investigator 
PROTOCOL TITLE: A phase 4, multicenter, randomized, open-label, active-controlled study 
to evaluate the effectiveness and safety of early add-on of ezetimibe with atorvastatin in very 
high-risk patients.  
PROTOCOL NO: 
OG-KORATO-001 
VERSION:  
 
4.1 dated 27-Jun-2024 
This protocol is a confidential communication of Organon. I confirm that I have read this 
protocol, I understand it, and I will work according to this protocol. I will also work 
consistently with the ethical principles that have their origin in the Declaration of Helsinki and 
that are consistent with Good Clinical Practices (GCP) and the applicable laws and 
regulations. Acceptance of this document constitutes my agreement that no unpublished 
information contained herein will be published or disclosed without prior written approval 
from the Sponsor. 
Instructions to the investigator: Please SIGN and DATE this signature page. PRINT your name, title, and the name of the 
study center in which the study will be conducted. Return the signed copy to Organon or IQVIA. 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
Signature of Investigator:      __________________________            Date:  ________ 
Printed Name:                                ___________________________ 
Investigator Title:                           ___________________________ 
 
Name/Address of Center:               
___________________________ 
 
 
 
 
 
___________________________ 
 
 
 
 
 
___________________________