Clinical trial NCT05266586
Conditions: Dyslipidemias High Cholesterol Hypercholesterolemia
Keywords: obicetrapib statin LDL-C cholesterol atherosclerosis
Sponsor: NewAmsterdam Pharma
Start date: 2022-03-09; Completion date: 2022-09-08
Enrollment: 119 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will be a placebo-controlled, double-blind, randomized, phase 2 study to evaluate the efficacy, safety, and tolerability of obicetrapib 10 mg, both in combination with ezetimibe 10 mg and as monotherapy, as an adjunct to high-intensity statin therapy.

Detailed description:
This study will be a placebo-controlled, double-blind, randomized, phase 2 study to evaluate the efficacy, safety, and tolerability of obicetrapib 10 mg, both in combination with ezetimibe 10 mg and as monotherapy, as an adjunct to high-intensity statin therapy. The screening period for this study will take up to 2-weeks. Afterwards patients will be randomized to placebo, 10 mg obicetrapib monotherapy, or 10 mg obicetrapib + 10 mg ezetimibe combination therapy for a 12-week treatment period. After the treatment period, patients will continue for a 4-week safety follow-up.

Arms: arm 1: once-daily placebo tablet and placebo capsule arm 2: once-daily obicetrapib 10 mg tablet and placebo capsule arm 3: once-daily obicetrapib 10 mg tablet and ezetimibe 10 mg capsule
Interventions: intervention 1: Obicetrapib intervention 2: Ezetimibe 10mg intervention 3: Obicetrapib placebo intervention 4: Ezetimibe placebo
Intervention descriptions: intervention 1: tablets intervention 2: capsules; 10 mg ezetimibe tablets filled into capsule shells, 1 tablet per capsule. intervention 3: tablets; no active ingredient intervention 4: capsules; no active ingredient

Protocol documents:
Prot_000.pdf: 
CLINICAL STUDY PROTOCOL 
A Placebo-Controlled, Double-Blind, Randomized, Phase 2 Study to 
Evaluate the Effect of Obicetrapib 10 mg Daily in Combination 
With Ezetimibe 10 mg Daily as an Adjunct to High-Intensity Statin 
Therapy: The ROSE 2 Study 
Investigational Product: Obicetrapib 
Protocol Number: TA-8995-202 
Sponsor: 
NewAmsterdam Pharma BV  
Gooimeer 2-35 
1411 DC 
Naarden  
The Netherlands 
Telephone: +31 35 699 30 00 
Fax: +31 20 240 07 79 
Version Number: 1.0 
Date: 16 September 2021 
Confidentiality Statement 
The information in this document is confidential and is not to be disclosed without the written 
consent of NewAmsterdam Pharma BV except to the extent that disclosure would be required by 
law and for the purpose of evaluating and/or conducting a clinical study for NewAmsterdam 
Pharma BV. You are allowed to disclose the contents of this document only to your Institutional 
Review Board and study personnel directly involved with conducting this protocol. Persons to 
whom the information is disclosed must be informed that the information is confidential and 
proprietary to NewAmsterdam Pharma BV and that it may not be further disclosed to third 
parties. 
NCT number: NCT05266586
This NCT number has been applied to the document for the purposes of posting on clinicaltrials.gov


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INVESTIGATOR AGREEMENT 
By signing below I agree that: 
I have read this protocol. I approve this document and I agree that it contains all necessary details 
for carrying out the study as described. I will conduct this study in accordance with the design and 
specific provision of this protocol and will make a reasonable effort to complete the study within 
the time designated. I will provide copies of this protocol and access to all information furnished 
by NewAmsterdam Pharma BV to study personnel under my supervision. I will discuss this 
material with them to ensure they are fully informed about the study drug and study procedures. I 
will let them know that this information is confidential and proprietary to NewAmsterdam 
Pharma BV and that it may not be further disclosed to third parties. I understand that the study 
may be terminated or enrollment suspended at any time by NewAmsterdam Pharma BV, with or 
without cause, or by me if it becomes necessary to protect the best interests of the study 
participants. 
I agree to conduct this study in full accordance with Food and Drug Administration Regulations, 
Institutional Review Board Regulations, and International Council for Harmonisation Guidelines 
for Good Clinical Practices. 
 
 
 
 
 
 
______________________________________________  
____________________ 
Investigator’s Signature 
 
 
 
 
 
Date 
 
 
 
______________________________________________ 
Investigator’s Printed Name 
 


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SYNOPSIS 
TITLE: A Placebo-Controlled, Double-Blind, Randomized, Phase 2 Study to Evaluate the Effect 
of Obicetrapib 10 mg Daily in Combination With Ezetimibe 10 mg Daily as an Adjunct to 
High-Intensity Statin Therapy: The ROSE 2 Study 
PROTOCOL NUMBER: TA-8995-202 
INVESTIGATIONAL PRODUCT: Obicetrapib 
PHASE: 2 
INDICATION: Dyslipidemia 
OBJECTIVES: 
The 
primary 
objective 
of 
this 
study 
is 
to 
evaluate 
the 
effect 
of 
obicetrapib 10 mg  ezetimibe 10 mg combination therapy compared with placebo, when used as 
an adjunct to high-intensity statin therapy, on low-density lipoprotein cholesterol (LDL-C) at 
Day 84. 
The secondary objectives of this study include the following, in hierarchical order: 
 To evaluate the effect of obicetrapib 10 mg monotherapy compared with placebo, when used 
as an adjunct to high-intensity statin therapy, on LDL-C at Day 84; 
 To evaluate the effect of obicetrapib 10 mg  ezetimibe 10 mg combination therapy compared 
with placebo, when used as an adjunct to high-intensity statin therapy, on apolipoprotein B 
(ApoB) at Day 84; and 
 To evaluate the effect of obicetrapib 10 mg monotherapy compared with placebo, when used 
as an adjunct to high-intensity statin therapy, on ApoB at Day 84. 
The exploratory objectives of this study include the following: 
 To evaluate the effect of obicetrapib 10 mg  ezetimibe 10 mg combination therapy and 
obicetrapib 10 mg monotherapy, when used as an adjunct to high-intensity statin therapy, on 
non-high-density lipoprotein cholesterol (non-HDL-C), very low-density lipoprotein 
cholesterol (VLDL-C), high-density lipoprotein (HDL) cholesterol (HDL-C), triglycerides 
(TG), apolipoprotein E (ApoE), lipoprotein (a) (Lp[a]), and HDL-ApoE at Day 84;  
 To evaluate the effect of obicetrapib 10 mg  ezetimibe 10 mg combination therapy and 
obicetrapib 10 mg monotherapy, when used as an adjunct to high-intensity statin therapy, on 
the proportion of participants achieving predefined LDL-C targets at Day 84; 


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 To assess the mean trough plasma levels of obicetrapib 10 mg  ezetimibe 10 mg combination 
therapy and obicetrapib 10 mg monotherapy at steady state on Days 28, 84, and 112; and 
 To evaluate the safety and tolerability profiles of obicetrapib 10 mg  ezetimibe 10 mg 
combination therapy and obicetrapib 10 mg monotherapy, when used as an adjunct to 
high-intensity statin therapy, assessed by clinical laboratory values and incidence of adverse 
events (AEs). 
POPULATION: 
The population for this study includes men and women 18 to 75 years of age, inclusive, with a 
body mass index <40 kg/m2, fasting LDL-C levels >70 mg/dL, and TG levels <400 mg/dL at the 
Screening Visit, who are currently receiving high-intensity statin therapy. 
STUDY DESIGN AND DURATION: 
This study will be a placebo-controlled, double-blind, randomized, Phase 2 study to evaluate the 
efficacy, safety, and tolerability of obicetrapib 10 mg, both in combination with ezetimibe 10 mg 
and as monotherapy, as an adjunct to high-intensity statin therapy. This study will take place at 
approximately 20 sites in the United States. 
Screening Period 
At the Screening Visit, participants will be required to sign an informed consent form (ICF) before 
any study-related procedures are performed. After signing the ICF, participants will be assessed 
for study eligibility. 
Treatment Period 
Up to 2 weeks after the Screening Visit, participants will return to the site on Day 1 (Visit 2) and 
confirm 
study 
eligibility 
before 
being 
randomized 
and 
beginning 
treatment. 
Approximately 114 eligible participants (38 participants per treatment group) will be randomized 
in a 1:1:1 ratio to 1 of the following treatment groups: 
 Combination therapy: Obicetrapib 10 mg  ezetimibe 10 mg (administered as one 10 mg 
obicetrapib tablet and one 10 mg ezetimibe capsule); 
 Obicetrapib monotherapy: Obicetrapib 10 mg (administered as one 10 mg obicetrapib tablet 
and 1 placebo capsule); or 
 Placebo (administered as 1 placebo tablet and 1 placebo capsule). 
During the 12-week Treatment Period, the assigned study drugs will be administered by the 
participants orally with water, once daily on Day 1 to Day 84 at approximately the same time each 
morning. Participants will return to the site on Day 28 (2 days), Day 84 (2 days), and Day 112 
(2 days) for efficacy, safety, and pharmacokinetic (PK) assessments. Participants, Investigators, 
the Clinical Research Organization, and the Sponsor will be blinded to all lipid results from Day 1 
(Visit 2) for the first participant until all enrolled participants complete the Day 84 (End of 
Treatment) visit or are withdrawn from the study, in order to protect blinding to treatment 
assignment. 


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Safety Follow-Up Period 
Participants will return to the site for a Safety Follow-up Visit (Visit 5) approximately 4 weeks 
after the end of the Treatment Period for safety and PK assessments.  
DOSAGE FORMS AND ROUTE OF ADMINISTRATION: 
The study drugs include obicetrapib 10 mg, ezetimibe 10 mg, and matching placebo for each. 
Participants 
will 
be 
randomized 
to 
receive 
combination 
therapy 
(obicetrapib 10 mg  ezetimibe 10 mg [administered as one 10 mg obicetrapib tablet and 
one 10 mg ezetimibe capsule]); obicetrapib monotherapy (obicetrapib 10 mg [administered as 
one 10 mg obicetrapib tablet and 1 placebo capsule]), or placebo (administered as 1 placebo tablet 
and 1 placebo capsule) on Day 1 to Day 84. Study drugs (1 tablet and 1 capsule) will be 
administered by the participant orally with water, once daily on Day 1 to Day 84 at approximately 
the same time each morning. 
EFFICACY VARIABLES:  
The primary efficacy endpoint is the percent change from Day 1 to Day 84 in LDL-C for the 
obicetrapib 10 mg  ezetimibe 10 mg combination treatment group compared with the placebo 
group. 
The secondary efficacy endpoints include the following, in hierarchical order: 
 Percent change from Day 1 to Day 84 in LDL-C for the obicetrapib 10 mg monotherapy 
treatment group compared with the placebo group; 
 Percent change from Day 1 to Day 84 in ApoB for the obicetrapib 10 mg  ezetimibe 10 mg 
combination treatment group compared with the placebo group; and 
 Percent change from Day 1 to Day 84 in ApoB for the obicetrapib 10 mg monotherapy 
treatment group compared with the placebo group. 
The exploratory efficacy endpoints include the following: 
 Percent change from Day 1 to Day 84 in non-HDL-C, VLDL-C, HDL-C, TG, ApoE, Lp(a), 
and HDL-ApoE for the obicetrapib 10 mg  ezetimibe 10 mg combination treatment group 
compared with the placebo group and for the obicetrapib 10 mg monotherapy treatment group 
compared with the placebo group; and 
 Proportion of participants at Day 84 that achieve LDL-C <2.6 mmol/L (<100 mg/dL), LDL-C 
<1.8 mmol/L (<70 mg/dL), and LDL-C <1.3 mmol/L (<50 mg/dL) for the 
obicetrapib 10 mg  ezetimibe 10 mg combination treatment group compared with the 
placebo group and for the obicetrapib 10 mg monotherapy treatment group compared with the 
placebo group. 
PHARMACOKINETIC VARIABLES: 
Plasma obicetrapib concentrations, both in combination with ezetimibe and as monotherapy, will 
be assessed at the scheduled PK collection times. 


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SAFETY VARIABLES: 
The safety and tolerability profile of obicetrapib 10 mg, both in combination with ezetimibe 10 mg 
and as monotherapy, will be assessed by clinical laboratory assessments (chemistry and 
hematology), vital signs, physical examinations, and the incidence of AEs. 
STATISTICAL ANALYSES: 
A Statistical Analysis Plan (SAP) will be finalized before database lock. Any changes to the 
methods described in the SAP will be described and justified as needed in the Clinical Study 
Report. All study-collected data will be summarized by treatment group using descriptive 
statistics, graphs, and/or raw data listings. Descriptive statistics for continuous variables will 
include number of participants (n), mean, standard deviation (SD), median, minimum, and 
maximum values. Analysis of categorical variables will include frequency and percentage. 
Analysis Populations 
The Intent-to-Treat (ITT) Population will include all participants randomized into the study. 
Treatment classification will be based on the randomized treatment.  
The Modified ITT (mITT) Population will include all participants in the ITT Population who 
receive at least 1 dose of any study drug and have a baseline value for the LDL-C assessment. Any 
efficacy measurement obtained during the Safety Follow-up Visit (Visit 5) after a participant 
permanently discontinues the study drug or after a participant receives an excluded medication 
and/or procedure will be removed from the mITT analysis. Treatment classification will be based 
on the randomized treatment. The mITT Population will be used for the primary analysis of all 
efficacy endpoints. 
The Per-Protocol (PP) Population will include all participants in the mITT Population who have 
a baseline value for the LDL-C assessment, have a Day 84 value for the LDL-C assessment, and 
who do not experience a major protocol deviation that could potentially impact the primary 
efficacy endpoint. The PP Population, along with the reason for exclusion, will be finalized prior 
to study unblinding. 
The PK Population will include all participants in the mITT Population who have sufficient blood 
samples collected for valid estimation of PK parameters. 
The Safety Population will include all participants who receive at least 1 dose of any study drug. 
Treatment classification will be based on the actual treatment received. The Safety Population will 
be the primary population used for the safety analyses. 
Analysis of Efficacy  
The mITT Population will be the primary population for the efficacy analyses. Efficacy will also 
be analyzed using the ITT Population and the PP Population as supportive analyses. 
The primary efficacy analysis of the percent change from Day 1 to Day 84 in LDL-C will be 
performed using a mixed model for repeated measures (MMRM) approach. The analysis will 
include fixed effects for treatment, visit, and treatment-by-visit interaction, along with a covariate 
of the baseline value as a continuous covariate. The Restricted Maximum Likelihood estimation 
approach will be used with an unstructured covariance matrix. The least squares means, standard 
errors, and 2-sided 95% confidence intervals for the combination group and for comparison of the 


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combination treatment group to the placebo group will be provided. Sensitivity analyses for 
various assumptions of missing data will be imputed using multiple imputation methodology. 
Results will be combined using Rubin’s method. Full details of the model(s) and imputation will 
be provided in the SAP.  
Similar MMRM models will be developed to examine the secondary efficacy endpoints. In order 
to maintain the overall Type I error rate, the secondary efficacy endpoints will be tested 
sequentially at the 0.05 significance level according to the order of hierarchy specified above. 
Similar MMRM models will be used for the percent change from Day 1 to Day 84 in non-HDL-C, 
VLDL-C, HDL-C, TG, ApoE, Lp(a), and HDL-ApoE. 
The proportion of participants at Day 84 that achieve LDL-C <2.6 mmol/L (<100 mg/dL), LDL-C 
<1.8 mmol/L (<70 mg/dL), and LDL-C <1.3 mmol/L (<50 mg/dL) will be examined through 
logistic regression models for binary variables with covariants of the treatment groups and the 
baseline variable.  
No adjustment will be made for multiplicity in testing the exploratory efficacy endpoints. Nominal 
p-values will be provided when applicable. Any additional sensitivity and/or supplemental 
analyses will be defined in the SAP. 
Analysis of Pharmacokinetics 
Plasma obicetrapib concentrations will be summarized with descriptive statistics based on the 
PK Population. Exploration of any relationships with obicetrapib exposure will be performed, as 
appropriate. 
Analysis of Safety 
The Safety Population will be the primary population for the safety analyses. All safety endpoints 
will be summarized descriptively. No statistical inference will be applied to the safety endpoints. 
SAMPLE SIZE DETERMINATION: 
A sample size of at least 108 evaluable participants (ie, 36 participants per treatment group) will 
provide >90% power to detect a 30% difference in LDL-C reduction at Day 84 (SD of 15%) for 
each of the obicetrapib treatment groups compared with the placebo group at a 1-sided significance 
level of 0.025. 
The sample size for this study was determined in order to provide sufficient power for the analyses 
of the primary and first secondary efficacy endpoints described above. Therefore, assuming an 
approximately 5% dropout rate, enrollment of approximately 114 participants (ie, 38 participants 
per treatment group) is planned for this study. This sample size will also contribute sufficient 
participant exposure and safety data. 
Participants will be stratified according to their Screening Visit LDL-C levels (100 or 
<100 mg/dL). 
SITES: Approximately 20 sites in the United States 


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SPONSOR: 
NewAmsterdam Pharma BV  
Gooimeer 2-35 
1411 DC 
Naarden  
The Netherlands 
Telephone: +31 35 699 30 00 
Fax: +31 20 240 07 79 


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TABLE OF CONTENTS 
Signature Page ................................................................................................................................ 2 
Investigator Agreement ................................................................................................................... 3 
Synopsis .......................................................................................................................................... 4 
Table of Contents .......................................................................................................................... 10 
List of Abbreviations and Definition of Terms............................................................................. 14 
1  Introduction and Background Information ............................................................................. 16 
1.1 
Cholesteryl Ester Transfer Protein Inhibitors ................................................................ 16 
1.2 
Obicetrapib (TA-8995) .................................................................................................. 17 
1.3 
Clinical Development of Obicetrapib ........................................................................... 17 
1.4 
Rationale ........................................................................................................................ 18 
1.4.1  Rationale for Obicetrapib and Ezetimibe Combination Therapy ...................... 18 
1.4.2  Dose Selection Rationale for Obicetrapib ......................................................... 19 
1.5 
Risk/Benefit ................................................................................................................... 19 
1.5.1  Coronavirus Disease 2019 Impacts ................................................................... 19 
2  Study Objectives ..................................................................................................................... 21 
2.1 
Primary Objective ......................................................................................................... 21 
2.2 
Secondary Objectives .................................................................................................... 21 
2.3 
Exploratory Objectives .................................................................................................. 21 
3  Study Description.................................................................................................................... 22 
3.1 
Summary of Study Design ............................................................................................ 22 
3.1.1  Screening Period ............................................................................................... 22 
3.1.2  Treatment Period ............................................................................................... 22 
3.1.3  Safety Follow-Up Period ................................................................................... 22 
3.1.4  Coronavirus Disease 2019 Contingency Measures ........................................... 22 
3.2 
Study Indication ............................................................................................................ 23 
4  Selection and Withdrawal of Participants ............................................................................... 24 
4.1 
Inclusion Criteria ........................................................................................................... 24 
4.2 
Exclusion Criteria .......................................................................................................... 25 
4.3 
Retesting ........................................................................................................................ 25 
4.4 
Rescreening ................................................................................................................... 26 


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4.5 
Withdrawal Criteria ....................................................................................................... 26 
5  Study Treatments .................................................................................................................... 27 
5.1 
Treatment Groups .......................................................................................................... 27 
5.2 
Rationale for Dosing ..................................................................................................... 27 
5.3 
Randomization and Blinding ......................................................................................... 27 
5.4 
Breaking the Blind ........................................................................................................ 27 
5.5 
Drug Supplies ................................................................................................................ 28 
5.5.1  Formulation and Packaging ............................................................................... 28 
5.5.2  Study Drug Preparation and Dispensing ........................................................... 29 
5.5.3  Study Drug Administration ............................................................................... 29 
5.5.4  Treatment Compliance ...................................................................................... 29 
5.5.5  Storage and Accountability ............................................................................... 30 
5.6 
Prior and Concomitant Medications and/or Procedures ................................................ 30 
5.6.1  Excluded Medications and/or Procedures ......................................................... 30 
5.6.2  Allowed Medications and/or Procedures .......................................................... 30 
5.6.3  Documentation of Prior and Concomitant Medication Use .............................. 30 
6  Study Procedures .................................................................................................................... 31 
7  Efficacy and Pharmacokinetic Assessments ........................................................................... 32 
7.1 
Efficacy Assessments .................................................................................................... 32 
7.2 
Pharmacokinetic Assessments ....................................................................................... 32 
7.3 
Serum Archive Sample .................................................................................................. 33 
8  Safety Assessments ................................................................................................................. 34 
8.1 
Adverse Events .............................................................................................................. 34 
8.1.1  Adverse (Drug) Reaction .................................................................................. 35 
8.1.2  Unexpected Adverse Drug Reaction ................................................................. 35 
8.1.3  Assessment of Adverse Events by the Investigator .......................................... 35 
8.2 
Serious Adverse Events ................................................................................................. 36 
8.3 
Serious Adverse Event Reporting − Procedures for Investigators ................................ 37 
8.4 
Pregnancy Reporting ..................................................................................................... 37 
8.5 
Expedited Reporting ...................................................................................................... 38 
8.6 
Special Situation Reports .............................................................................................. 38 
8.7 
Clinical Laboratory Evaluations .................................................................................... 39 


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8.7.1  Chemistry and Hematology Assessments ......................................................... 39 
8.7.2  Endocrinology Assessments .............................................................................. 39 
8.7.3  Aldosterone Assessment ................................................................................... 39 
8.8 
Vital Signs ..................................................................................................................... 39 
8.9 
Weight and Height ........................................................................................................ 40 
8.10  Demographics ................................................................................................................ 40 
8.11  Electrocardiograms ........................................................................................................ 40 
8.12  Physical Examinations .................................................................................................. 40 
9  Statistics .................................................................................................................................. 41 
9.1 
Analysis Populations ..................................................................................................... 41 
9.2 
Statistical Methods ........................................................................................................ 41 
9.2.1  Analysis of Efficacy .......................................................................................... 41 
9.2.1.1  Primary efficacy analysis .................................................................... 41 
9.2.1.2  Secondary efficacy analyses ............................................................... 42 
9.2.1.3  Exploratory analyses ........................................................................... 42 
9.2.2  Analysis of Pharmacokinetics ........................................................................... 42 
9.2.3  Analysis of Safety ............................................................................................. 42 
9.2.4  Interim Analysis ................................................................................................ 42 
9.2.5  Sample Size Determination ............................................................................... 42 
10  Data Management and Record Keeping ................................................................................. 44 
10.1  Data Management ......................................................................................................... 44 
10.1.1  Data Handling ................................................................................................... 44 
10.1.2  Computer Systems ............................................................................................. 44 
10.1.3  Data Entry ......................................................................................................... 44 
10.1.4  Medical Information Coding ............................................................................. 44 
10.1.5  Data Validation ................................................................................................. 44 
10.2  Record Keeping ............................................................................................................. 44 
10.3  End of Study .................................................................................................................. 45 
11  Investigator Requirements and Quality Control ..................................................................... 46 
11.1  Ethical Conduct of the Study ........................................................................................ 46 
11.2  Institutional Review Board ............................................................................................ 46 
11.3  Informed Consent .......................................................................................................... 46 


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11.4  Study Monitoring Requirements ................................................................................... 46 
11.5  Disclosure of Data ......................................................................................................... 47 
11.6  Retention of Records ..................................................................................................... 47 
11.7  Publication Policy ......................................................................................................... 47 
11.8  Financial Disclosure ...................................................................................................... 48 
12  Study Administrative Information .......................................................................................... 49 
12.1  Protocol Amendments ................................................................................................... 49 
13  References ............................................................................................................................... 50 
Appendix A: Schedule of Procedures ........................................................................................... 51 
Appendix B: Clinical Laboratory Analytes .................................................................................. 53 


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS  
Abbreviation 
Definition 
AE 
Adverse event 
ApoA1 
Apolipoprotein A1 
ApoB 
Apolipoprotein B 
ApoE 
Apolipoprotein E 
ASCVD 
Atherosclerotic cardiovascular disease 
CETP 
Cholesteryl ester transfer protein 
COVID-19 
Coronavirus Disease 2019 
CRA 
Clinical Research Associate 
CRO 
Clinical Research Organization 
CV 
Cardiovascular 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
EIU 
Exposure In Utero 
FDA 
Food and Drug Administration 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
HbA1c 
Glycosylated hemoglobin 
HDL 
High-density lipoprotein 
HDL-C 
High-density lipoprotein cholesterol 
HMGCR 
3-hydroxy-3-methylglutaryl-coenzyme A reductase 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IRB 
Institutional Review Board 
IRT 
Interactive response technology 
ITT 
Intent-to-Treat 
LDL 
Low-density lipoprotein 
LDL-C 
Low-density lipoprotein cholesterol 
Lp(a) 
Lipoprotein (a) 
mITT 
Modified Intent-to-Treat 
MMRM 
Mixed model for repeated measures 
non-HDL-C 
Non-high-density lipoprotein cholesterol 
PCSK9 
Proprotein convertase subtilisin kexin type 9 
PK 
Pharmacokinetic(s) 
PP 
Per-Protocol 
QTc 
Heart rate-corrected QT interval 
QTcF 
Heart rate-corrected QT interval using Fridericia’s formula 


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Abbreviation 
Definition 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
Standard deviation 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TG 
Triglyceride(s) 
ULN 
Upper limit of normal 
VLDL-C 
Very low-density lipoprotein cholesterol 
WHO 
World Health Organization 


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1 
INTRODUCTION AND BACKGROUND INFORMATION 
Dyslipidemias are disorders of lipoprotein metabolism, including lipoprotein overproduction or 
deficiency, which may be manifested by elevation of the levels of the serum total cholesterol, 
low-density lipoprotein (LDL) cholesterol (LDL-C) and triglyceride (TG) concentrations, and a 
decrease in the levels of high-density lipoprotein (HDL) cholesterol (HDL-C) concentration. These 
disorders are generally diagnosed by measuring the serum lipids and classified by the pattern of 
elevation/reduction in the lipid/lipoprotein fractions. Dyslipidemia itself does not generally cause 
any symptoms, but it can lead to symptomatic vascular disease including coronary artery disease 
and peripheral arterial disease. It is acknowledged that while there are a number of genetic and 
lifestyle factors which contribute to the development of vascular disease, dyslipidemia is 1 of the 
most prominent risk factors and normalization of the lipid profile has been a major target in 
cardiovascular (CV) protection strategies.1 
Statins are generally the drug of first choice in treating dyslipidemia. Statins are considered as the 
most potent, most effective, and best tolerated drugs for reducing LDL-C levels. Many patients, 
despite treatment with high-intensity statin therapy, do not achieve acceptable levels of LDL-C 
with statins alone.  
There is a need for chronic therapies which will robustly reduce elevated LDL-C levels when used 
adjunctive to high-intensity statin therapy.  
1.1 
Cholesteryl Ester Transfer Protein Inhibitors 
Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein produced in the liver and 
adipose tissue. It circulates in the blood, bound primarily to HDL-C, and is involved in the transfer 
of cholesteryl esters and TG between lipoproteins. In particular, it mediates the transfer of 
cholesteryl esters from HDL to apolipoprotein B (ApoB)-containing particles, eg, very low-density 
lipoprotein and LDL-C, in exchange for TG. As a result, cholesteryl ester from HDL can be taken 
up by the liver through scavenger receptor class B type 1; this action also leads to decreased 
HDL-C and ultimately to increased LDL-C.  
Inhibition of CETP activity reduces ApoB and LDL-C and increases HDL-C. CETP-inhibiting 
therapies were originally developed based on the premise that increasing HDL-C levels would 
prevent CV events. However, clinical study results and Mendelian randomization data have 
revealed that these effects are caused by changes in the concentration of ApoB-containing particles 
(including LDL particles) rather than changes in the HDL-C levels.2,3 Therefore, the LDL-C and 
ApoB-lowering effects, which arise from CETP inhibition and occur through upregulation of the 
LDL receptor, will benefit patients with elevated LDL-C and increased CV risk. 
Ference and colleagues have recently investigated the association between changes in LDL-C 
levels (and other lipoproteins) and the risk of CV events related to variants in the CETP gene alone 
and in combination with variants in the 3-hydroxy-3-methylglutaryl-coenzyme A reductase 
(HMGCR) gene.2 The results of these Mendelian randomization analyses demonstrate that 
treatment with a CETP inhibitor has the potential to effectively reduce the risk of CV events. Both 
genetic and therapeutic inhibition of CETP leads to quantitatively concordant changes in LDL-C 
and ApoB levels. A further Mendelian randomization analysis concluded that the clinical benefit 
of lower LDL-C levels per unit difference may specifically be related to the absolute reduction in 
ApoB-containing lipoprotein particles.4  


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1.2 
Obicetrapib (TA-8995) 
Obicetrapib (TA-8995) is a selective CETP inhibitor. Inhibition of CETP by obicetrapib blocks 
the transfer of cholesteryl ester from non-atherogenic HDL particles to particles in lipoprotein 
fractions (including LDL) that cause atherosclerosis and reduces the concentration of cholesterol 
in LDL, as well as other atherogenic lipoproteins. Obicetrapib also has several additional 
compound-specific activities that are hypothesized to be beneficial in patients. In a recent study, 
obicetrapib treatment not only reduced the number of ApoB-containing particles that constitute 
LDL-C, it also increased apolipoprotein E (ApoE), which led to the removal of cholesterol via the 
liver and also reduced lipoprotein (a) (Lp[a]).5 Finally, obicetrapib not only potently increases 
HDL-C and the concentration of apolipoprotein A1 (ApoA1)-containing lipoproteins but has been 
demonstrated to be a potent inducer of cholesterol efflux, which is the main driver of reverse 
cholesterol transport.6 This effect is considered important because it is expected to reduce 
established atheroma burden. 
1.3 
Clinical Development of Obicetrapib 
Both single ascending dose (TA-8995-01) and multiple ascending dose (TA-8995-02) studies of 
obicetrapib have been conducted in healthy volunteers. A formal, thorough QT/QTc study 
(TA-8995-04) demonstrated that obicetrapib has no effect on the QTcF. A drug-drug interaction 
study (TA-8995-05) showed no significant effect of obicetrapib on P-glycoprotein activity, but 
showed that obicetrapib is a mild inducer of cytochrome P450 3A4. A mass balance study in 
healthy males concluded that obicetrapib is steadily absorbed, and the principal route of excretion 
was in the feces (TA-8995-07). Finally, bioequivalence between obicetrapib capsule and tablet 
formulations was investigated (TA-8995-08). 
The first patient study conducted was a Phase 2 clinical study (TA-8995-03) in Denmark and The 
Netherlands where the aim was to evaluate the optimal dose of obicetrapib alone and in 
combination with statins in patients with mild dyslipidemia. This study concluded that a 10 mg 
daily dose of obicetrapib therapy resulted in an LDL-C reduction of 45.4%, an HDL-C increase of 
179.0%, an ApoA1 increase of 63.4%, and a significant increase of HDL-C efflux capacity. 
Furthermore, given on top of atorvastatin 20 mg, obicetrapib 10 mg resulted in an additional 
50.3% reduction in LDL-C. A second patient study (TA-8995-06) showed a statistically significant 
reduction in Lp(a) levels following 12 weeks of obicetrapib treatment. 
Two Phase 2 studies of obicetrapib (TA-8995-303 and TA-8995-201) are currently nearing 
completion. The first study, TA-8995-303, is evaluating the LDL-lowering effects of 
obicetrapib 5 mg in combination with ezetimibe 10 mg in participants with mild dyslipidemia. The 
second study, TA-8995-201, is evaluating the LDL-lowering effects of obicetrapib (both 5 mg and 
10 mg) as an adjunct to high intensity statin therapy in participants with dyslipidemia who are on 
high-intensity statins. 
Two Phase 3 studies of obicetrapib 10 mg investigating the treatment of elevated LDL-C levels in 
participants with established atherosclerotic CV disease (ASCVD), as well as heterozygous 
familial hypercholesterolemia, are currently in development. One study (TA-8995-301) will 
include participants on maximally tolerated lipid-lowering therapy, including maximally tolerated 
doses of statins with an LDL-C inclusion criterion of 100 mg/dL. The other study (TA-8995-302) 
will also include participants who are on maximally tolerated lipid-lowering therapy, including 
maximally tolerated doses of statins with an LDL-C inclusion criterion of 70 mg/dL and 


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<100 mg/dL. Together, these 2 pivotal studies will evaluate the effects of obicetrapib 10 mg in 
populations requiring further LDL-C reduction across a range of baseline LDL-C values relevant 
to contemporary clinical practice. 
A third Phase 3 study (TA-8995-304) will investigate the effect of obicetrapib 10 mg on clinical 
outcomes (ie, major adverse CV events, including CV death, non-fatal myocardial infarction, 
non-fatal stroke, or non-elective coronary revascularization). 
1.4 
Rationale 
Chronic LDL-C elevation leads to progressive accumulation of arterial atherosclerotic lesions that 
require long-term management. While lifestyle changes are the primary intervention, these 
measures seldom reduce plasma LDL-C by more than 15%, and pharmacologic treatments are 
required to adequately treat hyperlipidemia.7 
Statins are considered as first-line therapy for reducing LDL-C levels. However, despite lipid 
lowering therapy with statins, many patients are unable to achieve acceptable levels of LDL-C.  
Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors are one alternative to statins. 
However, there are several limitations with these therapies, including high costs, limited long-term 
outcome data relative to statins, and muscle-related events. In addition, because PCSK9 inhibitors 
are injectable, this poses a less attractive option for patients who prefer oral medications.  
Accordingly, there remains an unmet need for therapies to effectively reduce elevated LDL-C 
levels and CV risk at an acceptable cost, a convenient dosage form, and a more favorable safety 
profile to encourage long-term use and patient compliance. Obicetrapib, an oral CETP inhibitor, 
has demonstrated safety and efficacy in the reduction of LDL-C, in addition to other beneficial 
effects. The combination of obicetrapib and ezetimibe, an oral cholesterol absorption inhibitor, 
could be a valuable alternative to a PCSK9 inhibitor in patients who require additional LDL-C 
lowering despite high-intensity statin therapy. 
1.4.1 
Rationale for Obicetrapib and Ezetimibe Combination Therapy 
Ezetimibe selectively inhibits intestinal cholesterol absorption. Ezetimibe used as monotherapy 
for patients with hypercholesterolemia significantly reduces serum LDL-C levels, as evidenced by 
a meta-analysis of 8 randomized, double-blind, placebo-controlled studies, with a statistically 
significant mean reduction in LDL-C of 18.58% compared with placebo.8 Ezetimibe in 
combination with statin therapy further reduces LDL-C levels. A meta-analysis of 27 studies, 
including more than 21,000 patients, demonstrated a 15.1% greater reduction in LDL-C in patients 
treated with statin and ezetimibe in combination compared with statin alone.9 The IMPROVE-IT 
study,10 in which simvastatin 40 mg daily was compared with a combination of simvastatin 40 mg 
plus ezetimibe 10 mg in 18,144 patients with acute coronary syndrome, demonstrated a modest 
but statistically significant further reduction in future CV events (a 2% absolute risk reduction over 
7 years) in the combination group compared with statins alone. These large long-term studies have 
also demonstrated an excellent safety profile for ezetimibe. Importantly, additional Mendelian 
randomization studies have revealed that the CETP inhibitor HMGCR inhibitor interaction does 
not occur when a CETP inhibitor is combined with ezetimibe. 
A Phase 2 study is currently underway evaluating the LDL-lowering effects of obicetrapib 5 mg 
in combination with ezetimibe 10 mg in participants with mild dyslipidemia and no prior CV 
events (TA-8995-303).  


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To evaluate the potential of a higher dose of obicetrapib in combination with ezetimibe to augment 
reduction in LDL-C and ApoB, this study will evaluate the effect of obicetrapib 10 mg in 
combination with ezetimibe 10 mg in participants currently receiving high-intensity statin therapy 
(atorvastatin 40 or 80 mg or rosuvastatin 20 or 40 mg) as part of their guideline-directed medical 
therapy. 
1.4.2 
Dose Selection Rationale for Obicetrapib 
In clinical studies in healthy volunteers, obicetrapib was generally well tolerated in single doses 
up to 150 mg and multiple doses up to 25 mg/day for 21 days. In clinical studies in patients, 
obicetrapib was also well tolerated after daily dosing of 10 mg for 12 weeks, both alone and in 
combination with 2 different statins. Near maximal effects were observed with the 10 mg 
obicetrapib dose. At this dose level, CETP activity and concentrations were reduced, HDL-C levels 
were increased, and LDL-C levels were decreased. There were no dose-related adverse events 
(AEs) identified and no clinically significant changes in vital signs, electrocardiograms (ECGs), 
or hematology or biochemistry parameters in any clinical studies. A statistically significant 
reduction in Lp(a) levels from baseline was also observed at the 10 mg obicetrapib dose level. 
Therefore, the present study will utilize a dose of 10 mg obicetrapib in participants with ASCVD 
who are not adequately controlled despite maximally tolerated lipid-modifying therapies. 
1.5 
Risk/Benefit 
The primary pharmacology in in vitro, ex vivo, and in vivo studies have demonstrated that 
obicetrapib has the ability to inhibit CETP, decrease LDL-C levels, increase HDL-C levels, and 
importantly, reduce the number of atherogenic ApoB-containing particles in a way that is useful 
in the treatment of dyslipidemia. 
The safety pharmacology studies have demonstrated that obicetrapib has no adverse effect on 
critical physiological systems (eg, central nervous system, respiratory system, gastric emptying, 
urinary tract, and steroidal hormonal production [including aldosterone levels]) at doses up to 
300 mg/kg in rats. 
In clinical studies in patients, obicetrapib was also well tolerated after daily dosing of 10 mg for 
12 weeks, both alone and in combination with 2 different statins. There were no dose-related AEs 
identified and no clinically significant changes in vital signs, ECGs, or hematology or biochemistry 
parameters in any clinical studies. 
1.5.1 
Coronavirus Disease 2019 Impacts 
In March 2020, the Coronavirus Disease 2019 (COVID-19), caused by infection with severe acute 
respiratory syndrome coronavirus 2, was characterized as a pandemic by the World Health 
Organization (WHO). The COVID-19 pandemic has impacted clinical studies worldwide due to 
quarantines, site closures, travel limitations, diversion of resources, and/or general interruptions in 
study-related procedures. This study will be initiated during the ongoing COVID-19 pandemic. 
The Sponsor has reviewed guidance from regulatory authorities and reports from the literature 
while planning study start-up and conduct (ie, Food and Drug Administration [FDA] 2020).11  
The Sponsor will communicate with sites before study initiation and during the conduct of the 
study concerning the potential impact of COVID-19 on study-related procedures and overall 
conduct. The Sponsor will continue to monitor COVID-19 activity in the geographic areas and 


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institutions where the trial will be conducted and conduct an ongoing risk assessment throughout 
the study. The risk assessment will be documented on an ongoing basis in the Sponsor’s trial 
master file.  
This study protocol includes contingency measures to ensure participant safety while enabling sites 
to generate reliable data and maintain integrity of the study and study data (see Section 3.1.4). The 
impacts of these implemented contingency measures on the outcomes of this study, including any 
protocol deviations that result from COVID-19 illness and/or COVID-19 control measures, will 
be discussed in the Clinical Study Report. 
Treatment with standard of care and/or emergency use authorization medications, including 
vaccinations and boosters, for COVID-19 will be permitted during this study. There is no known 
negative impact of vaccination on obicetrapib efficacy and safety, nor any known negative impact 
of obicetrapib on vaccination efficacy and safety. 


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2 
STUDY OBJECTIVES 
2.1 
Primary Objective 
The 
primary 
objective 
of 
this 
study 
is 
to 
evaluate 
the 
effect 
of 
obicetrapib 10 mg  ezetimibe 10 mg combination therapy compared with placebo, when used as 
an adjunct to high-intensity statin therapy, on LDL-C at Day 84. 
2.2 
Secondary Objectives 
The secondary objectives of this study include the following, in hierarchical order: 
 To evaluate the effect of obicetrapib 10 mg monotherapy compared with placebo, when used 
as an adjunct to high-intensity statin therapy, on LDL-C at Day 84; 
 To evaluate the effect of obicetrapib 10 mg  ezetimibe 10 mg combination therapy compared 
with placebo, when used as an adjunct to high-intensity statin therapy, on ApoB at Day 84; 
and 
 To evaluate the effect of obicetrapib 10 mg monotherapy compared with placebo, when used 
as an adjunct to high-intensity statin therapy, on ApoB at Day 84. 
2.3 
Exploratory Objectives 
The exploratory objectives of this study include the following: 
 To evaluate the effect of obicetrapib 10 mg  ezetimibe 10 mg combination therapy and 
obicetrapib 10 mg monotherapy, when used as an adjunct to high-intensity statin therapy, on 
non-high-density lipoprotein cholesterol (non-HDL-C), very low-density lipoprotein 
cholesterol (VLDL-C), HDL-C, TG, ApoE, Lp(a), and HDL-ApoE at Day 84;  
 To evaluate the effect of obicetrapib 10 mg  ezetimibe 10 mg combination therapy and 
obicetrapib 10 mg monotherapy, when used as an adjunct to high-intensity statin therapy, on 
the proportion of participants achieving predefined LDL-C targets at Day 84; 
 To assess the mean trough plasma levels of obicetrapib 10 mg  ezetimibe 10 mg combination 
therapy and obicetrapib 10 mg monotherapy at steady state on Days 28, 84, and 112; and 
 To evaluate the safety and tolerability profiles of obicetrapib 10 mg  ezetimibe 10 mg 
combination therapy and obicetrapib 10 mg monotherapy, when used as an adjunct to 
high-intensity statin therapy, assessed by clinical laboratory values and incidence of AEs. 


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3 
STUDY DESCRIPTION 
3.1 
Summary of Study Design 
This study will be a placebo-controlled, double-blind, randomized, Phase 2 study to evaluate the 
efficacy, safety, and tolerability of obicetrapib 10 mg, both in combination with ezetimibe 10 mg 
and as monotherapy, as an adjunct to high-intensity statin therapy. This study will take place at 
approximately 20 sites in the United States. 
3.1.1 
Screening Period 
At the Screening Visit, participants will be required to sign an informed consent form (ICF) before 
any study-related procedures are performed. After signing the ICF, participants will be assessed 
for study eligibility. 
3.1.2 
Treatment Period 
Up to 2 weeks after the Screening Visit, participants will return to the site on Day 1 (Visit 2) and 
confirm study eligibility before being randomized and beginning treatment. Approximately 
114 eligible participants (38 participants per treatment group) will be randomized in a 1:1:1 ratio 
to 1 of the following treatment groups: 
 Combination therapy: Obicetrapib 10 mg  ezetimibe 10 mg (administered as one 10 mg 
obicetrapib tablet and one 10 mg ezetimibe capsule); 
 Obicetrapib monotherapy: Obicetrapib 10 mg (administered as one 10 mg obicetrapib tablet 
and 1 placebo capsule); or 
 Placebo (administered as 1 placebo tablet and 1 placebo capsule). 
During the 12-week Treatment Period, the assigned study drugs will be administered by the 
participants orally with water, once daily on Day 1 to Day 84 at approximately the same time each 
morning. Participants will return to the site on Day 28 (2 days), Day 84 (2 days), and Day 112 
(2 days) for efficacy, safety, and pharmacokinetic (PK) assessments. Participants, Investigators, 
the Clinical Research Organization (CRO), and the Sponsor will be blinded to all lipid results from 
Day 1 (Visit 2) for the first participant until all enrolled participants complete the Day 84 (End of 
Treatment) visit or are withdrawn from the study, in order to protect blinding to treatment 
assignment. 
3.1.3 
Safety Follow-Up Period 
Participants will return to the site for a Safety Follow-up Visit (Visit 5) approximately 4 weeks 
after the end of the Treatment Period for safety and PK assessments.  
3.1.4 
Coronavirus Disease 2019 Contingency Measures 
In cases of COVID-19 limitations, it is the Investigator’s responsibility to assure the safety of 
participants. If necessary, the Sponsor will implement and document mitigation strategies. At the 
Investigator’s discretion, the study visit(s) can be conducted in-clinic or virtually. If conducted 
virtually, the visit will include alternative methods for safety, efficacy, and distribution/collection 
of study drug, including but not limited to phone/video contact, alternative location for biologic 


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sample collection, alternative secure delivery of study drug, home health care (if available), and a 
secured way of transferring participant data from and to home health services and the site. 
If these contingency measures occur, the Sponsor will document the changes made, communicate 
recommendations about such changes in a timely fashion to minimize or prevent disruptions to the 
study, and support sites in implementing these changes. Documentation of these cases and the 
site’s management of participants should be recorded in the Investigator study files. In the absence 
of a COVID-19 impact, it is expected that Investigators and participants follow the protocol 
requirements as set forth. 
3.2 
Study Indication 
The indication for this study is dyslipidemia. 


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4 
SELECTION AND WITHDRAWAL OF PARTICIPANTS  
4.1 
Inclusion Criteria 
Participants who meet all of the following criteria will be eligible to participate in the study: 
1. Understanding of the study procedures, willingness to adhere to the study schedules, and 
agreement to participate in the study by giving written informed consent prior to screening 
procedures; 
2. Men or women 18 to 75 years of age, inclusive, at the Screening Visit;  
o Women may be enrolled if all 3 of the following criteria are met: 
 They are not pregnant; 
 They are not breastfeeding; and 
 They do not plan on becoming pregnant during the study. 
o Women of childbearing potential must have a negative urine pregnancy test at the 
Screening Visit. Note: Women are not considered to be of childbearing potential if they 
meet 1 of the following criteria as documented by the Investigator: 
 They have had a hysterectomy or tubal ligation at a minimum of 1 cycle prior to signing 
the ICF; or 
 They are postmenopausal, defined as 1 year since their last menstrual period for 
women 55 years of age or 1 year since their last menstrual period and have a 
follicle-stimulating hormone (FSH) level in the postmenopausal range for women 
<55 years of age. 
o Women of childbearing potential must agree to use an effective method of avoiding 
pregnancy from screening to 90 days after the last visit. Men whose partners are of 
childbearing potential must agree to use an effective method of avoiding pregnancy from 
screening to 90 days after the last visit. Effective methods of avoiding pregnancy are 
contraceptive methods with a Pearl index of <1 used consistently and correctly (including 
implantable contraceptives, injectable contraceptives, oral contraceptives, transdermal 
contraceptives, intrauterine devices, diaphragm with spermicide, male or female condoms 
with spermicide, or cervical cap) or a sterile sexual partner. 
3. Fasting LDL-C levels >70 mg/dL and TG levels <400 mg/dL at the Screening Visit; and 
4. Currently receiving high-intensity statin therapy (atorvastatin 40 or 80 mg or rosuvastatin 20 or 
40 mg) at a stable dose for 8 weeks prior to screening and intending to remain at the same 
stable dose throughout the study duration. 


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4.2 
Exclusion Criteria 
Participants who meet any of the following criteria will be excluded from participation in the study: 
1. Body mass index 40 kg/m2 at the Screening Visit; 
2. Current clinically significant CV disease, including but not limited to: 
o Major adverse CV event within 3 months prior to randomization; or 
Note: A major adverse CV event is defined as CV death, non-fatal myocardial infarction, 
non-fatal stroke, or non-elective coronary revascularization. 
o New York Heart Association Functional Classification Class III or IV heart failure. 
3. Glycosylated hemoglobin (HbA1c) 10% at the Screening Visit; 
4. Uncontrolled hypertension, ie, sitting systolic blood pressure >160 mmHg and/or sitting 
diastolic blood pressure >90 mmHg. One retest will be allowed, at which point if the retest 
result is no longer exclusionary, the participant may be randomized; 
5. Active muscle disease or persistent creatine kinase concentration >3 × the upper limit of 
normal (ULN). One retest will be allowed after 1 week to verify the result, at which point if 
the retest result is no longer exclusionary, the participant may be randomized; 
6. Estimated glomerular filtration rate <60 mL/min, calculated using the Chronic Kidney Disease 
Epidemiology Collaboration equation;12 
7. Hepatic dysfunction as evidenced by any laboratory abnormality as follows: gamma-glutamyl 
transferase, alanine aminotransferase, or aspartate aminotransferase >2 × ULN, or total 
bilirubin >1.5 × ULN; 
8. Anemia, defined as hemoglobin concentration <11 g/dL for men and hemoglobin 
concentration <9 g/dL for women; 
9. History of malignancy within 5 years prior to screening, with the exception of non-melanoma 
skin cancers; 
10. History of alcohol and/or drug abuse within 5 years prior to screening; 
11. Treatment with other investigational products or devices within 30 days or 5 half-lives, 
whichever is longer, prior to screening; 
12. History of participation in any clinical trial evaluating obicetrapib;  
13. Treatment with any PCSK9 inhibitor within 10 weeks prior to randomization or bempedoic 
acid within 2 weeks prior to randomization; 
14. Evidence of any other clinically significant, non-cardiac disease or condition that, in the opinion 
of the Investigator, would preclude participant in the study; or 
15. Known CETP inhibitor allergy or intolerance. 
4.3 
Retesting 
If laboratory abnormalities during screening are considered by the Investigator to be transient, then 
the laboratory tests may be repeated once during screening. The Investigator’s rationale for 


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retesting should be documented. If the retest result is no longer exclusionary, the participant may 
be randomized. 
4.4 
Rescreening 
A participant who is screened and does not meet the study eligibility criteria may be considered 
for rescreening upon Sponsor and/or Medical Monitor consultation and approval. Rescreened 
participants will be assigned a new participant number. Rescreening should occur no less than 
5 days after the last Screening Visit. 
4.5 
Withdrawal Criteria 
Participation in this study may be discontinued for any of the following reasons: 
 The participant withdraws consent or requests discontinuation from the study for any reason; 
 Occurrence of any medical condition or circumstance that exposes the participant to substantial 
risk and/or does not allow the participant to adhere to the requirements of the protocol; 
 Any serious AE (SAE), clinically significant AE, severe laboratory abnormality, intercurrent 
illness, or other medical condition, which indicates to the Investigator that continued 
participation is not in the best interest of the participant; 
 Pregnancy; 
 Requirement of prohibited concomitant medication; 
 Participant failure to comply with protocol requirements or study-related procedures; or 
 Termination of the study by the Sponsor or the regulatory authority. 
Unless the participant withdraws consent, participants who discontinue study drug early should be 
encouraged to complete the full panel of assessments scheduled for the Early Termination Visit 
promptly and complete a Safety Follow-up Visit (Visit 5) 4 weeks after the last dose of study drug. 
PK samples will not be collected during the Safety Follow-up Visit for participants who 
discontinue study drug early without withdrawing consent or for participants who withdraw 
prematurely from the study. The reason for participant withdrawal must be documented in the 
electronic case report form (eCRF). 
In the case of a participant lost to follow-up, attempts to contact the participant must be made and 
documented in the participant’s medical records. 
Withdrawn participants will not be replaced. 


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5 
STUDY TREATMENTS 
5.1 
Treatment Groups 
Participants will be randomized in a 1:1:1 ratio to 1 of the following treatment groups: 
 Combination therapy: Obicetrapib 10 mg  ezetimibe 10 mg (administered as one 10 mg 
obicetrapib tablet and one 10 mg ezetimibe capsule); 
 Obicetrapib monotherapy: Obicetrapib 10 mg (administered as one 10 mg obicetrapib tablet 
and 1 placebo capsule); or 
 Placebo (administered as 1 placebo tablet and 1 placebo capsule). 
5.2 
Rationale for Dosing 
In clinical studies in healthy volunteers, obicetrapib was generally well tolerated in single doses 
up to 150 mg and multiple doses up to 25 mg/day for 21 days. In clinical studies in patients, 
obicetrapib was also well tolerated after daily dosing of 10 mg for 12 weeks, both alone and in 
combination with 2 different statins. Near maximal effects were observed with the 10 mg 
obicetrapib dose. At this dose level, CETP activity and concentrations were reduced, HDL-C levels 
were increased, and LDL-C levels were decreased. There were no dose-related AEs identified and 
no clinically significant changes in vital signs, ECGs, or hematology or biochemistry parameters 
in any clinical studies. A statistically significant reduction in Lp(a) levels from baseline was also 
observed at the 10 mg obicetrapib dose level. Therefore, the present study will utilize a dose of 
10 mg obicetrapib in participants with ASCVD who are not adequately controlled despite 
maximally tolerated lipid-modifying therapies. 
The ezetimibe dose of 10 mg is the current FDA-approved dose.  
5.3 
Randomization and Blinding 
Participants who meet all eligibility criteria will be randomized into the study. Participants will be 
randomized in a 1:1:1 ratio to receive combination therapy (obicetrapib 10 mg  ezetimibe 10 mg 
[administered as one 10 mg obicetrapib tablet and one 10 mg ezetimibe capsule]), obicetrapib 
monotherapy (obicetrapib 10 mg [administered as one 10 mg obicetrapib tablet and 1 placebo 
capsule]); or placebo (administered as 1 placebo tablet and 1 placebo capsule). 
At randomization, participants will be stratified according to their Screening Visit LDL-C level 
(100 or <100 mg/dL). An automated interactive response technology (IRT) system will be used 
to assign the participant to 1 of the 3 treatment groups. 
Participants, Investigators, the CRO, and the Sponsor will be blinded to all lipid results from Day 1 
(Visit 2) for the first participant until all enrolled participants complete the Day 84 (End of 
Treatment) visit or are withdrawn from the study, in order to protect blinding to treatment 
assignment. 
5.4 
Breaking the Blind 
Unblinding by request of an Investigator should occur only in the event of an emergency or AE, 
for which it is necessary to know the study drugs to determine an appropriate course of therapy for 
the participant. If the Investigator or qualified designee must identify the treatment assignment of 




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The physical, chemical, and pharmaceutical formulation properties and characteristics of the 
obicetrapib tablets are described in the Investigator’s Brochure. 
All study drugs will be labelled in accordance with all applicable local regulatory requirements. 
5.5.2 
Study Drug Preparation and Dispensing 
The study drugs include obicetrapib 10 mg, ezetimibe 10 mg, and matching placebo for each. 
Participants 
will 
be 
randomized 
to 
receive 
combination 
therapy 
(obicetrapib 10 mg  ezetimibe 10 mg [administered as one 10 mg obicetrapib tablet and 
one 10 mg ezetimibe capsule]); obicetrapib monotherapy (obicetrapib 10 mg [administered as one 
10 mg obicetrapib tablet and 1 placebo capsule]), or placebo (administered as 1 placebo tablet and 
1 placebo capsule) on Day 1 to Day 84. Study drugs (1 tablet and 1 capsule) will be administered 
by the participant orally with water, once daily on Day 1 to Day 84 at approximately the same time 
each morning. 
At Visit 2 (Day 1), participants will receive 1 kit (containing 32 obicetrapib tablets or matching 
placebo tablets and 32 ezetimibe capsules or matching placebo capsules totaling 
64 tablets/capsules per kit) with the study drugs appropriate for the participant’s treatment group. 
At Visit 3 (Day 28), participants will receive 2 kits as described above. Each kit will provide a 
sufficient supply for 28 days of dosing, with enough for an extra 4 days of dosing in case the 
participant needs to postpone the next visit. Participants will be instructed to take 2 units from the 
kit each day. The kit will be clearly labelled to indicate which tablets/capsules to use on each day. 
Participants will be instructed to bring all unused study drugs to the site at the next visit. 
This study protocol includes contingency measures to manage disruptions due to COVID-19 
control measures, including modifications to study drug dispensation specific to situations where 
COVID-19 is impacting study conduct. See Section 3.1.4 for details of COVID-19 contingency 
measures. In the absence of a COVID-19 impact, it is expected that Investigators and participants 
follow the protocol requirements as set forth. 
5.5.3 
Study Drug Administration 
Study drugs (1 tablet and 1 capsule) will be administered by the participant orally with water, once 
daily on Day 1 to Day 84 at approximately the same time each morning. On days with visits 
scheduled, study drugs should be administered with water following all fasted blood samples. At 
Visits 3 and 4, participants will dose from the kit received at the previous visit (Visits 2 and 3, 
respectively).  
If a participant forgets to take study drug on a given day, they should take the next dose as normal 
and should not take a double dose to make up for the forgotten dose. 
5.5.4 
Treatment Compliance 
Compliance to the study drug regimen will be evaluated by counting unused tablets and capsules. 
Participants will be instructed to bring all unused study drugs to the site at Visits 3 and 4. During 
the Treatment Period, if compliance is not between 80% and 120%, inclusive, the participant will 
be counselled about the importance of compliance to the regimen. If the limits are exceeded at 
2 consecutive visits, a decision will be made by the Investigator and Sponsor as to whether the 
participant should be withdrawn from the study. 


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5.5.5 
Storage and Accountability 
All study drugs must be stored below 25°C (77°F) in a secure area with access limited to the 
Investigator and authorized site personnel. 
In accordance with regulatory requirements, the Investigator or designated site personnel must 
document the amount of study drug dispensed and/or administered to participants, the amount 
returned by participants, and the amount received from and returned to the Sponsor (or 
representative) when applicable. Study drug accountability records must be maintained throughout 
the course of the study. The accountability unit for this study is a tablet or capsule. Discrepancies 
are to be reconciled or resolved. Procedures for final disposition of unused study drug will be 
provided in the appropriate study manual. 
5.6 
Prior and Concomitant Medications and/or Procedures 
5.6.1 
Excluded Medications and/or Procedures 
Participants must not receive treatment with other investigational products or devices within 
30 days or 5 half-lives, whichever is longer, prior to screening. 
Participants must abstain from taking any PCSK9 inhibitor within 10 weeks prior to randomization 
or bempedoic acid within 2 weeks prior to randomization.  
5.6.2 
Allowed Medications and/or Procedures 
Participants must be currently receiving high-intensity statin therapy (atorvastatin 40 or 80 mg or 
rosuvastatin 20 or 40 mg) at a stable dose for 8 weeks prior to screening and intending to remain 
at the same stable dose throughout the study duration. 
5.6.3 
Documentation of Prior and Concomitant Medication Use 
Medications used within 28 days prior to the Screening Visit will be recorded. Any medications 
administered in addition to the study drugs, whether allowed per the protocol or not, must be 
documented on the concomitant medication eCRF. 


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6 
STUDY PROCEDURES 
Study procedures will follow the Schedule of Procedures (Appendix A).  


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7 
EFFICACY AND PHARMACOKINETIC ASSESSMENTS 
7.1 
Efficacy Assessments 
The primary efficacy endpoint is the percent change from Day 1 to Day 84 in LDL-C for the 
obicetrapib 10 mg  ezetimibe 10 mg combination treatment group compared with the placebo 
group. 
The secondary efficacy endpoints include the following, in hierarchical order: 
 Percent change from Day 1 to Day 84 in LDL-C for the obicetrapib 10 mg monotherapy 
treatment group compared with the placebo group; 
 Percent change from Day 1 to Day 84 in ApoB for the obicetrapib 10 mg  ezetimibe 10 mg 
combination treatment group compared with the placebo group; and 
 Percent change from Day 1 to Day 84 in ApoB for the obicetrapib 10 mg monotherapy 
treatment group compared with the placebo group. 
The exploratory efficacy endpoints include the following: 
 Percent change from Day 1 to Day 84 in non-HDL-C, VLDL-C, HDL-C, TG, ApoE, Lp(a), 
and HDL-ApoE for the obicetrapib 10 mg  ezetimibe 10 mg combination treatment group 
compared with the placebo group and for the obicetrapib 10 mg monotherapy treatment group 
compared with the placebo group; and 
 Proportion of participants at Day 84 that achieve LDL-C <2.6 mmol/L (<100 mg/dL), LDL-C 
<1.8 mmol/L (<70 mg/dL), and LDL-C <1.3 mmol/L (<50 mg/dL) for the 
obicetrapib 10 mg  ezetimibe 10 mg combination treatment group compared with the placebo 
group and for the obicetrapib 10 mg monotherapy treatment group compared with the placebo 
group. 
Blood samples for the lipid profile must be obtained under fasting conditions (ie, after the 
participant has fasted for approximately 10 hours). For the purposes of this study, fasting will be 
defined as nothing by mouth except water and any essential medications. If a participant is not 
fasting, the Investigator should reschedule the visit as soon as possible. LDL-C level will be 
calculated using the Friedewald equation unless TG 400 mg/dL or LDL-C 50 mg/dL; in both 
cases, LDL-C level will be measured directly by preparative ultracentrifugation, also referred to 
as beta quantification.13 Additionally, LDL-C will be measured by preparative ultracentrifugation, 
also referred to as beta quantification, at baseline (Visit 2) and at the end of the 12-week Treatment 
Period (Visit 4) for all participants. 
7.2 
Pharmacokinetic Assessments 
Plasma obicetrapib concentrations, both in combination with ezetimibe and as monotherapy, will 
be assessed at the scheduled PK collection times as indicated in Appendix A. At visits with dosing 
scheduled (ie, Visits 2, 3, and 4), PK samples will be collected with fasting laboratory samples 
(pre-dose). At Visits 3 and 4, the time between the last dose of study drug and PK sampling will 
be >24 hours. The subsequent post-dose PK sample at Visit 5 should be collected at approximately 
the same time as the previous visits. 


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7.3 
Serum Archive Sample 
A serum archive sample will be obtained at visits specified in the Schedule of Procedures 
(Appendix A) and stored for future analysis. If the sample is analyzed, it will be for non-genetic 
tests.  


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8 
SAFETY ASSESSMENTS 
The safety and tolerability profile of obicetrapib 10 mg, both in combination with ezetimibe 10 mg 
and as monotherapy, will be assessed by clinical laboratory assessments (chemistry and 
hematology), vital signs, physical examinations, and the incidence of AEs. 
8.1 
Adverse Events 
An AE is defined as any untoward medical occurrence in a clinical investigation participant 
administered a pharmaceutical product, which does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and/or unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of an 
investigational medicinal product, whether or not related to the investigational medicinal product. 
All AEs, including observed or volunteered problems, complaints, or symptoms, are to be recorded 
on the appropriate eCRF. 
AEs, which include clinical laboratory assessment variables, will be monitored and documented 
from the time of first dose of study treatment until completion of Visit 5. Participants should be 
instructed to report any AE that they experience to the Investigator, whether or not they think the 
event is due to study drug. Beginning at the date of the first dose of study treatment, Investigators 
should make an assessment for AEs at each visit and record the event on the appropriate AE eCRF. 
Wherever possible, a specific disease or syndrome rather than individual associated signs and 
symptoms should be identified by the Investigator and recorded on the eCRF. However, if an 
observed or reported sign or symptom is not considered a component of a specific disease or 
syndrome by the Investigator, it should be recorded as a separate AE on the eCRF. Additionally, 
the condition that led to a medical or surgical procedure (eg, surgery, endoscopy, tooth extraction, 
or transfusion) should be recorded as an AE, not the procedure itself.  
Any medical condition already present at the date of the first dose of study treatment should be 
recorded as medical history and not be reported as an AE unless the medical condition or signs or 
symptoms present at baseline changes in severity, frequency, or seriousness at any time during the 
study. In this case, it should be reported as an AE. 
Clinically significant abnormal laboratory or other examination findings (eg, ECG) that are 
detected during the study or are present at the date of the first dose of study treatment and 
significantly worsen during the study should be reported as AEs, as described below. The 
Investigator will exercise his or her medical and scientific judgment in deciding whether an 
abnormal laboratory finding or other abnormal assessment is clinically significant. Clinically 
significant abnormal laboratory values occurring during the study will be followed until repeat 
tests return to normal, stabilize, or are no longer clinically significant. Abnormal test results that 
are determined to be an error should not be reported as an AE. Laboratory abnormalities or other 
abnormal clinical findings (eg, ECG abnormalities) should be reported as an AE if any of the 
following are applicable: 
 If an intervention is required as a result of the abnormality; 
 If action taken with the study drug is required as a result of the abnormality; or  
 Based on the clinical judgment of the Investigator. 


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8.1.1 
Adverse (Drug) Reaction 
All noxious and unintended responses to a medicinal product related to any dose should be 
considered an adverse drug reaction. “Responses” to a medicinal product means that a causal 
relationship between a medicinal product and an AE is at least a reasonable possibility, ie, the 
relationship cannot be ruled out. 
8.1.2 
Unexpected Adverse Drug Reaction 
An Unexpected Adverse Drug Reaction is defined as an adverse reaction, the nature or severity of 
which is not consistent with the applicable product information.  
8.1.3 
Assessment of Adverse Events by the Investigator 
The Investigator will assess the severity (intensity) of each AE as mild, moderate, or severe, and 
will also categorize each AE as to its potential relationship to study drug using the categories of 
yes or no. 
Assessment of severity 
Mild – An event that is easily tolerated and generally not interfering with normal daily activities. 
Moderate – An event that is sufficiently discomforting to interfere with normal daily activities. 
Severe – An event that is incapacitating with inability to work or perform normal daily activities. 
Causality assessment 
The relationship of an AE to the administration of the study drug is to be assessed according to the 
following definitions: 
No (unrelated, not related, unlikely to be related) – The time course between the administration of 
study drug and the occurrence or worsening of the AE rules out a causal relationship and another 
cause (concomitant drugs, therapies, complications, etc) is suspected. 
Yes (possibly, probably, or definitely related) – The time course between the administration of 
study drug and the occurrence or worsening of the AE is consistent with a causal relationship and 
no other cause (concomitant drugs, therapies, complications, etc) can be identified. 
The definition implies a reasonable possibility of a causal relationship between the event and the 
study drug. This means that there are facts (evidence) or arguments to suggest a causal relationship. 
The following factors should also be considered: 
 The temporal sequence from study drug administration- 
The event should occur after the study drug is given. The length of time from study drug 
exposure to event should be evaluated in the clinical context of the event. 
 Underlying, concomitant, intercurrent diseases- 
Each report should be evaluated in the context of the natural history and course of the disease 
being treated and any other disease the participant may have. 


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 Concomitant drug- 
The other drugs the participant is taking or the treatment the participant receives should be 
examined to determine whether any of them might be recognized to cause the event in question. 
 Known response pattern for this class of study drug- 
Clinical and/or preclinical data may indicate whether a particular response is likely to be a 
class effect. 
 Exposure to physical and/or mental stresses- 
The exposure to stress might induce adverse changes in the recipient and provide a logical and 
better explanation for the event. 
 The pharmacology and PK of the study drug- 
The known pharmacologic properties (absorption, distribution, metabolism, and excretion) of 
the study drug should be considered. 
8.2 
Serious Adverse Events 
An AE or adverse reaction is considered serious if, in the view of either the Investigator or Sponsor, 
it results in any of the following outcomes: 
 Death; 
 A life-threatening AE; 
Note: An AE or adverse reaction is considered “life-threatening” if, in view of either the 
Investigator or Sponsor, its occurrence places the participant at immediate risk of death. It does 
not include an event that, had it occurred in a more severe form, might have caused death. 
 Requires hospitalization or prolongation of existing hospitalizations; 
Note: Any hospital admission with at least 1 overnight stay will be considered an inpatient 
hospitalization. An emergency room or urgent care visit without hospital admission will not 
be recorded as a SAE under this criterion, nor will hospitalization for a procedure scheduled 
or planned before signing of informed consent, or elective treatment of a pre-existing condition 
that did not worsen from baseline. However, unexpected complications and/or prolongation of 
hospitalization that occur during elective surgery should be recorded as AEs and assessed for 
seriousness. Admission to the hospital for social or situational reasons (ie, no place to stay, live 
too far away to come for hospital visits, respite care) will not be considered inpatient 
hospitalizations.  
 A persistent or significant disability/incapacity or substantial disruption of the ability to 
conduct normal life functions; 
 A congenital anomaly/birth defect; or 
 An important medical event. 
Note: Important medical events that do not meet any of the above criteria may be considered 
an SAE when, based upon appropriate medical judgment, they may jeopardize the participant 
and may require medical or surgical intervention to prevent 1 of the outcomes listed above. 
Examples of such medical events include allergic bronchospasm requiring intensive treatment 


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in an emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalizations, or the development of drug dependency. 
8.3 
Serious Adverse Event Reporting − Procedures for Investigators 
Initial reports 
All SAEs occurring from the time of the first dose of study treatment until 30 days following the 
last administration of study drug must be reported to 
 within 24 hours of 
the knowledge of the occurrence. After the 30-day reporting window, any SAE that the 
Investigator considers related to study drug must be reported to 
 or the 
Sponsor/designee. 
To report the SAE, complete the SAE form electronically in the electronic data capture (EDC) 
system for the study. When the form is completed, 
 personnel will be notified 
electronically by the EDC system and will retrieve the form. If the event meets serious criteria and 
it is not possible to access the EDC system, send an email to 
 at 
 or call the 
 reporting line (phone 
number listed below), and fax/email the completed paper SAE form to 
(contact 
information listed in Section 8.6) within 24 hours of awareness. When the EDC system becomes 
available, the SAE information must be entered within 24 hours of the system becoming available. 
Follow-up reports 
The Investigator must continue to follow the participant until the SAE has subsided or until the 
condition becomes chronic in nature, stabilizes (in the case of persistent impairment), or the 
participant dies. 
Within 24 hours of receipt of follow-up information, the Investigator must update the SAE form 
electronically in the EDC system for the study and submit any supporting documentation 
(eg, participant discharge summary or autopsy reports) to 
 via fax or 
email. If it is not possible to access the EDC system, refer to the procedures outlined above for 
initial reporting of SAEs.  
8.4 
Pregnancy Reporting 
If a participant becomes pregnant during the study or within the Safety Follow-up Period defined 
in the protocol, the Investigator is to stop dosing with study drug(s) immediately and the participant 
should be withdrawn from the study. Early termination procedures should be implemented at that 
time.  
A pregnancy is not considered to be an AE or SAE; however, it must be reported to 
 
 within 24 hours of knowledge of the event. 
 will then 
provide the Investigator/site the Exposure In Utero (EIU) form for completion. The 
Investigator/site must complete the EIU form and fax/email it back to 
.  
If the female partner of a male participant becomes pregnant while the participant is receiving 
study drug or within the Safety Follow-up Period defined in the protocol, the Investigator should 
notify
 as described above.  
The pregnancy should be followed until the outcome of the pregnancy, whenever possible. Once 
the outcome of the pregnancy is known, the EIU form should be completed and faxed/emailed to 


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. If the outcome of the pregnancy meets the criteria for immediate 
classification as an SAE (ie, postpartum complication, spontaneous abortion, stillbirth, neonatal 
death, or congenital anomaly), the Investigator should follow the procedures for reporting an SAE. 
8.5 
Expedited Reporting 
The Sponsor/designee will report all relevant information about Suspected Unexpected Serious 
Adverse Reactions (SUSARs) that are fatal or life-threatening as soon as possible to the FDA, and 
in any case no later than 7 days after knowledge by the Sponsor/designee of such a case. Relevant 
follow-up information will subsequently be communicated within an additional 8 days.  
All other SUSARs will be reported to the FDA, applicable competent authorities concerned, and 
to the Central Ethics Committee concerned as soon as possible but within a maximum of 15 days 
of first knowledge by the Sponsor/designee.  
The Sponsor/designee will also report any additional expedited safety reports required in 
accordance with the timelines outlined in country-specific legislation.  
The Sponsor/designee will also inform all Investigators as required per local regulation. 
The requirements above refer to the requirements relating to study drug. 
8.6 
Special Situation Reports 
Special situation reports include reports of overdose, misuse, abuse, medication error, and reports 
of adverse reactions associated with product complaints. 
 Overdose: Refers to the administration of a quantity of a medicinal product given per 
administration or cumulatively (accidentally or intentionally), which is above the maximum 
recommended dose according to the protocol. Clinical judgement should always be applied. In 
cases of a discrepancy in the drug accountability, overdose will be established only when it is 
clear that the participant has taken additional dose(s) or the Investigator has reason to suspect 
that the participant has taken additional dose(s).  
 Misuse: Refers to situations where the medicinal product is intentionally and inappropriately 
used not in a way that is not in accordance with the protocol instructions or local prescribing 
information and may be accompanied by harmful physical and/or psychological effects.  
 Abuse: Is defined as persistent or sporadic, intentional excessive use of a medicinal product, 
which is accompanied by harmful physical or psychological effects. 
 Medication error: Is any unintentional error in the prescribing, dispensing, or administration 
of a medicinal product by a healthcare professional, participant, or consumer, respectively. The 
administration or consumption of the unassigned treatment and administration of an expired 
product are always reportable as medication errors, cases of participants missing doses of 
investigational product are not considered reportable as medication error. 
 Product complaint: Is defined as any written, electronic, or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or 
performance of a drug or device after it is released for distribution. A special situations form 
will only be completed if a complaint is associated with an adverse drug reaction.  




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8.9 
Weight and Height 
Weight and height will be measured at the Screening Visit and will be used to calculate body mass 
index. Measurement of weight should be performed with the participant dressed in indoor clothing, 
with shoes removed, and bladder empty. 
8.10 
Demographics 
Participant demographic data (eg, gender, race, ethnicity, and birth date/year) will be collected at 
the Screening Visit. 
8.11 
Electrocardiograms 
A single, standard 12-lead ECG will be performed by the Investigator or trained site personnel at 
the Screening Visit and read locally. 
8.12 
Physical Examinations 
A physical examination will be performed as indicated in Appendix A.  


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9 
STATISTICS 
9.1 
Analysis Populations 
The Intent-to-Treat (ITT) Population will include all participants randomized into the study. 
Treatment classification will be based on the randomized treatment.  
The Modified ITT (mITT) Population will include all participants in the ITT Population who 
receive at least 1 dose of any study drug and have a baseline value for the LDL-C assessment. Any 
efficacy measurement obtained during the Safety Follow-up Visit (Visit 5) after a participant 
permanently discontinues the study drug or after a participant receives an excluded medication 
and/or procedure will be removed from the mITT analysis. Treatment classification will be based 
on the randomized treatment. The mITT Population will be used for the primary analysis of all 
efficacy endpoints. 
The Per-Protocol (PP) Population will include all participants in the mITT Population who have a 
baseline value for the LDL-C assessment, have a Day 84 value for the LDL-C assessment, and 
who do not experience a major protocol deviation that could potentially impact the primary 
efficacy endpoint. The PP Population, along with the reason for exclusion, will be finalized prior 
to study unblinding. 
The PK Population will include all participants in the mITT Population who have sufficient blood 
samples collected for valid estimation of PK parameters. 
The Safety Population will include all participants who receive at least 1 dose of any study drug. 
Treatment classification will be based on the actual treatment received. The Safety Population will 
be the primary population used for the safety analyses. 
9.2 
Statistical Methods 
A Statistical Analysis Plan (SAP) will be finalized before database lock. Any changes to the 
methods described in the SAP will be described and justified as needed in the Clinical Study 
Report. All study-collected data will be summarized by treatment group using descriptive 
statistics, graphs, and/or raw data listings. Descriptive statistics for continuous variables will 
include number of participants (n), mean, standard deviation (SD), median, minimum, and 
maximum values. Analysis of categorical variables will include frequency and percentage. 
9.2.1 
Analysis of Efficacy 
The mITT Population will be the primary population for the efficacy analyses. Efficacy will also 
be analyzed using the ITT Population and the PP Population as supportive analyses. 
9.2.1.1 
Primary efficacy analysis 
The primary efficacy analysis of the percent change from Day 1 to Day 84 in LDL-C will be 
performed using a mixed model for repeated measures (MMRM) approach. The analysis will 
include fixed effects for treatment, visit, and treatment-by-visit interaction, along with a covariate 
of the baseline value as a continuous covariate. The Restricted Maximum Likelihood estimation 
approach will be used with an unstructured covariance matrix. The least squares means, standard 
errors, and 2-sided 95% confidence intervals for the combination group and for comparison of the 
combination treatment group to the placebo group will be provided. Sensitivity analyses for 
various assumptions of missing data will be imputed using multiple imputation methodology. 


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Results will be combined using Rubin’s method. Full details of the model(s) and imputation will 
be provided in the SAP.  
9.2.1.2 
Secondary efficacy analyses 
Similar MMRM models will be developed to examine the secondary efficacy endpoints. In order 
to maintain the overall Type I error rate, the secondary efficacy endpoints will be tested 
sequentially at the 0.05 significance level according to the order of hierarchy specified in 
Section 7.1. 
9.2.1.3 
Exploratory analyses 
Similar MMRM models will be used for the percent change from Day 1 to Day 84 in non-HDL-C, 
VLDL-C, HDL-C, TG, ApoE, Lp(a), and HDL-ApoE. 
The proportion of participants at Day 84 that achieve LDL-C <2.6 mmol/L (<100 mg/dL), LDL-C 
<1.8 mmol/L (<70 mg/dL), and LDL-C <1.3 mmol/L (<50 mg/dL) will be examined through 
logistic regression models for binary variables with covariants of the treatment groups and the 
baseline variable.  
No adjustment will be made for multiplicity in testing the exploratory efficacy endpoints. Nominal 
p-values will be provided when applicable. Any additional sensitivity and/or supplemental 
analyses will be defined in the SAP. 
9.2.2 
Analysis of Pharmacokinetics  
Plasma obicetrapib concentrations will be summarized with descriptive statistics based on the 
PK Population. Exploration of any relationships with obicetrapib exposure will be performed, as 
appropriate. 
9.2.3 
Analysis of Safety 
The Safety Population will be the primary population for the safety analyses. All safety endpoints 
will be summarized descriptively. No statistical inference will be applied to the safety endpoints. 
AEs will be categorized by primary system organ class and preferred term as coded using the 
Medical Dictionary for Regulatory Activities category designations. Summaries of AEs, including 
the number and percentage of participants who experience an AE, will be provided. 
Laboratory values will be summarized descriptively, including the change from baseline, by 
treatment group, and overall. In addition, shift tables will be presented to describe the change in 
laboratory parameter values at post-baseline visits using normal range categories (low, normal, 
and high). 
9.2.4 
Interim Analysis 
No interim analysis is planned for this study. 
9.2.5 
Sample Size Determination 
A sample size of at least 108 evaluable participants (ie, 36 participants per treatment group) will 
provide >90% power to detect a 30% difference in LDL-C reduction at Day 84 (SD of 15%) for 
each of the obicetrapib treatment groups compared with the placebo group at a 1-sided significance 
level of 0.025. 


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The sample size for this study was determined in order to provide sufficient power for the analyses 
of the primary and first secondary efficacy endpoints described in Section 7.1. Therefore, assuming 
an 
approximately 
5% 
dropout 
rate, 
enrollment 
of 
approximately 
114 participants 
(ie, 38 participants per treatment group) is planned for this study. This sample size will also 
contribute sufficient participant exposure and safety data. 
Participants will be stratified according to their Screening Visit LDL-C levels (100 or 
<100 mg/dL). 


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10 
DATA MANAGEMENT AND RECORD KEEPING 
10.1 
Data Management 
10.1.1 
Data Handling 
Data will be recorded at the site on eCRFs and reviewed by the Clinical Research Associate (CRA) 
during monitoring visits. The CRAs will verify data recorded in the EDC system with source 
documents. All corrections or changes made to any study data must be appropriately tracked in an 
audit trail in the EDC system. An eCRF will be considered complete when all missing, incorrect, 
and/or inconsistent data has been accounted for. 
10.1.2 
Computer Systems 
Data will be processed using a validated computer system conforming to regulatory requirements. 
10.1.3 
Data Entry 
Data must be recorded using the EDC system as the study is in progress. All site personnel must 
log into the system using their secure username and password in order to enter, review, or correct 
study data. These procedures must comply with Title 21 of the Code of Federal Regulations Part 11 
and other appropriate international regulations. All passwords will be strictly confidential. 
10.1.4 
Medical Information Coding 
For medical information, the following thesauri will be used: 
 Medical Dictionary for Regulatory Activities (latest) for medical history and AEs; and  
 WHO Drug Dictionary for prior and concomitant medications. 
10.1.5 
Data Validation 
Validation checks programmed within the EDC system, as well as supplemental validation 
performed via review of the downloaded data, will be applied to the data in order to ensure 
accurate, consistent, and reliable data. Data identified as erroneous, or data that are missing, will 
be referred to the site for resolution through data queries. 
The eCRFs must be reviewed and electronically signed by the Investigator. 
10.2 
Record Keeping 
Records of participants, source documents, monitoring visit logs, eCRFs, inventory of study drug, 
regulatory documents, and other Sponsor correspondence pertaining to the study must be kept in 
the appropriate study files at the site. Source data are defined as all information in original records 
and certified copies of original records of clinical findings, observations, or other activities in a 
clinical study necessary for the evaluation and reconstruction of the clinical study. Source data are 
contained in source documents (original records or certified copies). These records will be retained 
in a secure file for the period as set forth in the Clinical Study Agreement. Prior to transfer or 
destruction of these records, the Sponsor must be notified in writing and be given the opportunity 
to further store such records.  


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10.3 
End of Study 
The end of the study (“study completion”) is defined as the date of the last protocol-specified 
visit/assessment (including telephone contact) for the last participant in the study.  


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11 
INVESTIGATOR REQUIREMENTS AND QUALITY CONTROL 
11.1 
Ethical Conduct of the Study 
Good Clinical Practice (GCP) is an international ethical and scientific quality standard for 
designing, conducting, recording, and reporting studies that involve human participants. 
Compliance with this standard provides public assurance that the rights, safety, and wellbeing of 
study participants are protected, consistent with the principles that have their origin in the 
Declaration of Helsinki, and that the clinical study data are credible. 
11.2 
Institutional Review Board 
The Institutional Review Board (IRB) will review all appropriate study documentation in order to 
safeguard the rights, safety, and well-being of participants. The study will only be conducted at 
sites where IRB approval has been obtained. The protocol, Investigator’s Brochure, ICF, 
advertisements (if applicable), written information given to the participants, safety updates, annual 
progress reports, and any revisions to these documents will be provided to the IRB by the 
Investigator. 
Federal regulations and ICH Guidelines require that approval be obtained from an IRB prior to 
participation of participants in research studies. Prior to study onset, the protocol, any protocol 
amendments, ICFs, advertisements to be used for participant recruitment, and any other written 
information regarding this study to be provided to a participant or participant’s legal guardian must 
be approved by the IRB. 
No study drug will be released to the site for dosing until written IRB authorization has been 
received by the Sponsor. 
11.3 
Informed Consent 
The ICF and any changes to the ICF made during the course of the study must be agreed to by the 
Sponsor or designee and the IRB prior to its use and must be in compliance with all ICH GCP, 
local regulatory requirements, and legal requirements.  
The Investigator must ensure that each study participant is fully informed about the nature and 
objectives of the study and possible risks associated with participation and must ensure that the 
participant has been informed of his/her rights to privacy. The Investigator will obtain written 
informed consent from each participant before any study-related activity is performed and should 
document in the source documentation that consent was obtained prior to enrollment in the study. 
The original signed copy of the ICF must be maintained by the Investigator and is subject to 
inspection by a representative of the Sponsor, their representatives, auditors, the IRB, and/or 
regulatory agencies. A copy of the signed ICF will be given to the participant. 
11.4 
Study Monitoring Requirements 
It is the responsibility of the Investigator to ensure that the study is conducted in accordance with 
the protocol, Declaration of Helsinki, ICH GCP, and applicable regulatory requirements, and that 
valid data are entered into the eCRFs. 
To achieve this objective, the CRA’s duties are to aid the Investigator and, at the same time, the 
Sponsor in the maintenance of complete, legible, well organized, and easily retrievable data. 
Before the enrollment of any participant in this study, the Sponsor or their designee will review 


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with the Investigator and site personnel the following documents: protocol, Investigator’s 
Brochure, eCRFs and procedures for their completion, informed consent process, and the 
procedure for reporting SAEs. 
The Investigator will permit the Sponsor or their designee to monitor the study as frequently as 
deemed necessary to determine that data recording and protocol adherence are satisfactory. During 
the monitoring visits, information recorded on the eCRFs will be verified against source 
documents and requests for clarification or correction may be made. After the eCRF data is entered 
by the site, the CRA will review the data for safety information, completeness, accuracy, and 
logical consistency. Computer programs that identify data inconsistencies may be used to help 
monitor the clinical study. If necessary, requests for clarification or correction will be sent to 
Investigators. The Investigator and his/her staff will be expected to cooperate with the Sponsor or 
their designee and provide any missing information, whenever possible. 
All monitoring activities will be reported and archived. In addition, monitoring visits will be 
documented at the investigational site by signature and date on the study-related monitoring log. 
11.5 
Disclosure of Data 
Data generated by this study must be available for inspection by the FDA, the Sponsor or their 
designee, applicable foreign health authorities, and the IRB as appropriate. Participants or their 
legal representatives may request their medical information be given to their personal physician or 
other appropriate medical personnel responsible for their welfare. 
Participant medical information obtained during the study is confidential and disclosure to 
third parties other than those noted above is prohibited. 
11.6 
Retention of Records 
To enable evaluations and/or audits from regulatory authorities or the Sponsor, the Investigator 
will keep records, including the identity of all participants (sufficient information to link records, 
eg, eCRFs and hospital records), all original signed ICFs, copies of all eCRFs, SAE forms, source 
documents, and detailed records of treatment disposition. The records should be retained by the 
Investigator according to specifications in the ICH guidelines, local regulations, or as specified in 
the Clinical Study Agreement, whichever is longer. The Investigator must obtain written 
permission from the Sponsor before disposing of any records, even if retention requirements have 
been met. 
If the Investigator relocates, retires, or for any reason withdraws from the study, the Sponsor should 
be prospectively notified. The study records must be transferred to an acceptable designee, such 
as another Investigator, another institution, or to the Sponsor.  
11.7 
Publication Policy 
Following completion of the study, the data may be considered for publication in a scientific 
journal or for reporting at a scientific meeting. Each Investigator is obligated to keep data 
pertaining to the study confidential. The Investigator must consult with the Sponsor before any 
study data are submitted for publication. The Sponsor reserves the right to deny publication rights 
until mutual agreement on the content, format, interpretation of data in the manuscript, and journal 
selected for publication are achieved. 


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11.8 
Financial Disclosure 
Investigators are required to provide financial disclosure information to the Sponsor to permit the 
Sponsor to fulfill its obligations under 21 Code of Federal Regulations Part 54. In addition, 
Investigators must commit to promptly updating this information if any relevant changes occur 
during the study and for a period of 1 year after the completion of the study. 


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12 
STUDY ADMINISTRATIVE INFORMATION 
12.1 
Protocol Amendments 
Any amendments to the study protocol will be communicated to the Investigators by 
 or 
the Sponsor. All protocol amendments will undergo the same review and approval process as the 
original protocol. A protocol amendment may be implemented after it has been approved by the 
IRB, unless immediate implementation of the change is necessary for participant safety. In this 
case, the situation must be documented and reported to the IRB within 5 working days. 


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13 
REFERENCES 
1. 
de Grooth GJ, Klerkx AH, Stroes ES, et al. A review of CETP and its relation to 
atherosclerosis. J Lipid Res. 2004;45(11):1967-1974. 
2. 
Ference BA, Kastelein JJ, Ginsberg HN, et al. Association of genetic variants related to 
CETP inhibitors and statins with lipoprotein levels and cardiovascular risk. JAMA. 
2017;318(10):947-956. 
3. 
Tall AR, Rader DJ. Trials and tribulations of CETP inhibitors. Circ Res. 
2018;122(1):106-112. 
4. 
Ference BA, Kastelein JJP, Ray KK, et al. Association of triglyceride-lowering LPL 
variants and LDL-C-lowering LDLR variants with risk of coronary heart disease. JAMA. 
2019;321(4):364-373. 
5. 
Hovingh GK, Kastelein JJ, van Deventer SJ, et al. Cholesterol ester transfer protein 
inhibition by TA-8995 in patients with mild dyslipidaemia (TULIP): a randomised, 
double-blind, placebo-controlled phase 2 trial. Lancet. 2015;386(9992):452-460. 
6. 
van Capelleveen JC, Kastelein JJ, Zwinderman AH, et al. Effects of the cholesteryl ester 
transfer protein inhibitor, TA-8995, on cholesterol efflux capacity and high-density 
lipoprotein particle subclasses. J Clin Lipidol. 2016;10(5):1137-1144.e3. 
7. 
Cholesterol Treatment Trialists’ (CTT) Collaboration. Baigent C, Blackwell L, 
Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a 
meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 
2010;376(9753):1670-1681. 
8. 
Pandor A, Ara RM, Tumur I, et al. Ezetimibe monotherapy for cholesterol lowering in 
2,722 people: systematic review and meta-analysis of randomized controlled trials. J Intern 
Med. 2009;265(5):568-580.  
9.  
Morrone D, Weintraub WS, Toth PP, et al. Lipid-altering efficacy of ezetimibe plus statin 
and statin monotherapy and identification of factors associated with treatment response: a 
pooled analysis of over 21,000 subjects from 27 clinical trials. Atherosclerosis. 
2012;223(2):251-261. 
10.  
Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute 
coronary syndromes. N Engl J Med. 2015;372(25):2387-2397. 
11. 
United States Food and Drug Administration. FDA guidance on conduct of clinical trials 
of medical products during the COVID-19 public health emergency. Guidance for 
Industry, Investigators, and Institutional Review Boards. March 2020, updated 
27 January 2021. 
https://www.fda.gov/media/136238/download. 
Accessed 
04 August 2021. 
12. 
Levey AS. CKD-EPI equations for glomerular filtration rate (GFR). MDCalc. 
https://www.mdcalc.com/ckd-epi-equations-glomerular-filtration-rate-gfr. 
Accessed 
09 November 2020. 
13. 
Friedewald W. LDL calculated. MDCalc. https://www.mdcalc.com/ldl-calculated. 
Accessed 10 August 2021. 
 


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APPENDIX A: SCHEDULE OF PROCEDURES 
 
Screeninga,b 
Treatment Period 
Safety Follow-Up 
Early Termination Visit 
Visit 
1 
2 (Baseline) 
3 
4 (EOT) 
5 
Week 
Up to -2 
0 
4 
12 
16 
Day (Visit Window) 
-14 to -1 
1 
28 (2) 
84 (2) 
112 (2) 
Unscheduled 
Informed consentc 
X 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
Xd 
 
 
 
 
Demographic information 
X 
 
 
 
 
 
Medical/surgical history 
X 
 
 
 
 
 
Prior/concomitant medications 
X 
X 
X 
X 
X 
X 
Weight and heighte 
X 
 
 
 
 
 
Physical examination 
X 
 
 
X 
 
 
Vital signsf 
X 
X 
X 
X 
X 
X 
12-lead ECGg 
X 
 
 
 
 
 
Urine pregnancy testh 
X 
 
 
 
 
X 
FSH testi 
X 
 
 
 
 
 
Fasting (approximately 10 hours) 
chemistry and hematologyj 
X 
X 
X 
X 
X 
X 
Fasting (approximately 10 hours) 
lipid profilek 
X 
X 
X 
X 
 
X 
PK samplel 
 
X 
X 
X 
Xm 
X 
Fasting (approximately 10 hours) 
aldosterone 
 
X 
X 
X 
X 
X 
Fasting (approximately 10 hours) 
Lp(a) 
 
X 
 
X 
 
 
Serum archive samplen 
 
X 
 
X 
 
 
Randomization 
 
X 
 
 
 
 
Dispense study drugo 
 
X 
X 
 
 
 
Study drug administrationp 
 
-----------------------------X--------------------------- 
 
 
Study drug compliance  
 
 
X 
X 
 
 
Register visit in IRT 
X 
X 
X 
X 
 
X 
Adverse events 
 
X 
X 
X 
X 
X 
Note: When several assessments are required at the same visit, samples for clinical laboratory assessments should be collected after completing other assessments, such as physical 
examinations, vital signs, and 12-lead ECGs. 
Note: In cases of COVID-19 limitations, it is the Investigator’s responsibility to assure the safety of participants. If necessary, the Sponsor will implement and document mitigation 
strategies as described in Section 3.1.4. In the absence of a COVID-19 impact, it is expected that Investigators and participants follow the protocol requirements as set forth. 


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Note: For the purposes of this study, fasting will be defined as nothing by mouth except water and any essential medications. 
a. 
If laboratory abnormalities during screening are considered by the Investigator to be transient, then the laboratory tests may be repeated once during screening. The Investigator’s 
rationale for retesting should be documented. If the retest result is no longer exclusionary, the participant may be randomized. 
b. 
A participant who is screened and does not meet the study eligibility criteria may be considered for rescreening upon Sponsor and/or Medical Monitor consultation and approval. 
Rescreened participants will be assigned a new participant number. Rescreening should occur no less than 5 days after the last Screening Visit. 
c. 
Participants will be required to sign an ICF before any study-related procedures are performed. 
d. 
Confirm the participant continues to meet the inclusion and exclusion criteria and assess any updates since the Screening Visit. 
e. 
Weight and height will be measured at the Screening Visit and will be used to calculate body mass index. Measurement of weight should be performed with the participant 
dressed in indoor clothing, with shoes removed, and bladder empty. 
f. 
Vital signs will include body temperature, heart rate, and triplicate blood pressure (systolic and diastolic) measurements. Participants should be in the supine position after at 
least 10 minutes rest prior to the vital sign measurements. 
g. 
A single, standard 12-lead ECG will be performed by the Investigator or trained site personnel at the Screening Visit and read locally. 
h. 
For women of childbearing potential only. 
i. 
FSH test will be performed in women <55 years of age for whom it has been 1 year since their last menstrual period. 
j. 
At the Screening Visit only, chemistry panel will include HbA1c. 
k. 
LDL-C level will be calculated using the Friedewald equation unless TG 400 mg/dL or LDL-C 50 mg/dL; in both cases, LDL-C level will be measured directly by preparative 
ultracentrifugation, also referred to as beta quantification (Source: LDL calculated. MDCalc. https://www.mdcalc.com/ldl-calculated. Accessed 10 August 2021). Additionally, 
LDL-C will be measured by preparative ultracentrifugation, also referred to as beta quantification, at baseline (Visit 2) and at the end of the 12-week Treatment Period (Visit 4) 
for all participants. 
l. 
At visits with dosing scheduled (ie, Visits 2, 3, and 4), PK samples will be collected with fasting laboratory samples (pre-dose). At Visits 3 and 4, the time between the last dose 
of study drug and PK sampling will be >24 hours. The subsequent post-dose PK sample at Visit 5 should be collected at approximately the same time as the previous visits.  
m. PK samples will not be collected during the Safety Follow-up Visit for participants who discontinue study drug early without withdrawing consent or for participants who 
withdraw prematurely from the study. 
n. 
A serum archive sample will be obtained and stored for future analysis. If the sample is analyzed, it will be for non-genetic tests.  
o. 
At Visit 2 (Day 1), participants will receive 1 kit (containing 32 obicetrapib tablets or matching placebo tablets and 32 ezetimibe capsules or matching placebo capsules totaling 
64 tablets/capsules per kit) with the study drugs appropriate for the participant’s treatment group. At Visit 3 (Day 28), participants will receive 2 kits as described above. Each 
kit will provide a sufficient supply for 28 days of dosing, with enough for an extra 4 days of dosing in case the participant needs to postpone the next visit. Participants will be 
instructed to take 2 units from the kit each day. The kit will be clearly labelled to indicate which tablets/capsules to use on each day. Participants will be instructed to bring all 
unused study drugs to the site at the next visit. 
p. 
Study drugs (1 tablet and 1 capsule) will be administered by the participant orally with water, once daily on Day 1 to Day 84 at approximately the same time each morning. On 
days with visits scheduled, study drugs should be administered with water following all fasted blood samples. At Visits 3 and 4, participants will dose from the kit received at 
the previous visit (Visits 2 and 3, respectively).  
COVID-19 = Coronavirus Disease 2019; ECG = electrocardiogram; EOT = End of Treatment; FSH = follicle-stimulating hormone; HbA1c = glycosylated hemoglobin; 
ICF = informed consent form; IRT = interactive response technology; LDL-C = low-density lipoprotein cholesterol; Lp(a) = lipoprotein (a); PK = pharmacokinetic; 
TG = triglyceride(s). 
 


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APPENDIX B: CLINICAL LABORATORY ANALYTES 
Standard Safety Chemistry Panel 
Alanine aminotransferase 
Albumin 
Alkaline phosphatase 
Amylase 
Aspartate aminotransferase 
Bicarbonate 
Blood urea nitrogen 
Calcium 
Chloride 
Creatine kinase 
Creatinine 
Estimated glomerular filtration rate [1] 
Gamma-glutamyl transferase 
Glucose (fasting) 
Glycosylated hemoglobin [2] 
High-sensitivity C-reactive protein 
Inorganic phosphorus 
Lactate dehydrogenase 
Lipase 
Potassium 
Sodium 
Total bilirubin 
Total protein 
Uric acid 
1. 
Calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. (Source: CKD-EPI equations for 
glomerular filtration rate [GFR]. MDCalc. https://www.mdcalc.com/ckd-epi-equations-glomerular-filtration-rate-gfr. 
Accessed 09 November 2020). 
2. 
Screening Visit only. 
 
Endocrinology 
Aldosterone 
Follicle-stimulating hormone [1] 
Urine pregnancy test [2] 
 
1. 
Follicle-stimulating hormone test will be performed in women <55 years of age for whom it has been 1 year since their 
last menstrual period. 
2. 
For women of childbearing potential only. 
 
Hematology 
Hematocrit 
Hemoglobin 
Platelets 
Red blood cell count 
White blood cell count and differential [1] 
 
1. 
Manual microscopic review is performed only if white blood cell count and/or differential values are out of reference 
range. 
 
Lipid Profile 
Apolipoprotein B 
Apolipoprotein E (Apo E) 
High-density lipoprotein-ApoE 
High-density lipoprotein cholesterol 
Low-density lipoprotein cholesterol [1] 
Non-high-density lipoprotein cholesterol 
Triglycerides 
Very low-density lipoprotein cholesterol 
1. 
LDL-C will be calculated using the Friedewald equation unless triglycerides 400 mg/dL or low-density lipoprotein 
cholesterol (LDL-C) 50 mg/dL; in both cases, LDL-C level will be measured directly by preparative ultracentrifugation, 
also referred to as beta quantification (Source: LDL calculated. MDCalc. https://www.mdcalc.com/ldl-calculated. 
Accessed 10 August 2021). In addition, for all participants, LDL-C will be measured by preparative ultracentrifugation, 
also referred to as beta quantification, at baseline (Visit 2) and at the end of the 12-week Treatment Period (Visit 4). 
 


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Other Laboratory Analytes 
Lipoprotein (a) 
 
 

SAP_001.pdf: 




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