Clinical trial NCT04753606
Conditions: Dyslipidemias High Cholesterol Hypercholesterolemia
Keywords: obicetrapib statin LDL-C cholesterol atherosclerosis
Sponsor: NewAmsterdam Pharma
Start date: 2021-02-18; Completion date: 2021-08-30
Enrollment: 120 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will be a placebo-controlled, double-blind, randomized, phase 2 dose-finding study to evaluate the efficacy, safety, and tolerability of obicetrapib as an adjunct to high-intensity statin therapy.

Detailed description:
This study will be a placebo-controlled, double-blind, randomized, phase 2 dose-finding study to evaluate the efficacy, safety, and tolerability of obicetrapib 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, 5 mg obicetrapib or 10 mg obicetrapib for an 8-week treatment period. After the treatment period, patients will continue for a 4-week safety follow-up and a 15-week PK follow-up.

Arms: arm 1: once-daily placebo arm 2: once-daily obicetrapib arm 3: once-daily obicetrapib
Interventions: intervention 1: Obicetrapib
Intervention descriptions: intervention 1: tablets

Protocol documents:
Prot_000.pdf: 
CLINICAL STUDY PROTOCOL 
A Placebo-Controlled, Double-Blind, Randomized, Phase 2 
Dose-Finding Study to Evaluate the Effect of Obicetrapib as an 
Adjunct to High-Intensity Statin Therapy 
Investigational Product: Obicetrapib 
Protocol Number: TA-8995-201 
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: 2.0 
Date: 26 January 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: NCT04753606
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 Dose-Finding Study to 
Evaluate the Effect of Obicetrapib as an Adjunct to High-Intensity Statin Therapy 
PROTOCOL NUMBER: TA-8995-201 
INVESTIGATIONAL PRODUCT: Obicetrapib 
PHASE: 2 
INDICATION: Dyslipidemia 
OBJECTIVES: 
The primary objective of this study is to evaluate the efficacy of obicetrapib, compared to placebo,
at Day 56 in decreasing low-density lipoprotein cholesterol (LDL-C) as an adjunct to 
high-intensity statin therapy. 
The secondary objectives of this study include the following: 
 To evaluate the effect of obicetrapib, compared to placebo, at Day 56 on apolipoprotein B 
(ApoB), non-high-density lipoprotein cholesterol (non-HDL-C), and high-density lipoprotein 
cholesterol (HDL-C), as an adjunct to high-intensity statin therapy; 
 To assess the mean plasma levels of obicetrapib at steady state on Days 56, 84, 112, and 161;
and 
 To evaluate the safety and tolerability profile of obicetrapib. 
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 triglyceride 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 dose-finding study to 
evaluate the efficacy, safety, and tolerability of obicetrapib 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 (Visit 1), 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. 


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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: 
 5 mg obicetrapib (one 5 mg obicetrapib tablet + 1 placebo tablet); 
 10 mg obicetrapib (two 5 mg obicetrapib tablets); or 
 Placebo (2 placebo tablets). 
During the 8-week Treatment Period, the assigned study drugs will be administered by the 
participants orally and once daily on Day 1 to Day 56. Participants will return to the site every 
4 weeks 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 through database lock in order to protect blinding to treatment 
assignment. 
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.  
Pharmacokinetic Period 
Participants will return to the site for 2 PK Visits (Visits 6 and 7) approximately 8 and 15 weeks, 
respectively, after the end of the Treatment Period for safety and PK assessments.  
DOSAGE FORMS AND ROUTE OF ADMINISTRATION: 
The study drugs used in this study are as follows: 
 5 mg obicetrapib tablet; and 
 Matching placebo tablet. 
The study drugs listed above will be packaged to provide doses of 5 or 10 mg obicetrapib or 
placebo only. Participants will be randomized to receive 1 of the 2 doses of obicetrapib or placebo
only. Two tablets of study drugs will be administered by the participant orally and once daily on 
Day 1 to Day 56 at approximately the same time each morning, with food. 
EFFICACY VARIABLES:  
The primary efficacy endpoint is the percent change from Day 1 to Day 56 in LDL-C for each 
obicetrapib group compared to the placebo group.  
The key secondary efficacy endpoints include the following: 
 Percent change from Day 1 to Day 56 in ApoB for each obicetrapib group compared to the 
placebo group; 
 Percent change from Day 1 to Day 56 in non-HDL-C for each obicetrapib group compared to 
the placebo group; and 
 Percent change from Day 1 to Day 56 in HDL-C for each obicetrapib group compared to the 
placebo group. 


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SAFETY VARIABLES: 
The safety and tolerability profile of obicetrapib will be assessed by clinical laboratory 
assessments (chemistry and hematology), vital signs, physical examinations, and the incidence of 
adverse events. 
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 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 56 value for the LDL-C assessment, and 
who did not experience a major protocol deviation that potentially impacted 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 56 in LDL-C will be 
performed using a mixed model for repeated measures approach. The analysis will include fixed 
effects for treatment, visit, and treatment-by-visit interaction, along with a covariate of the baseline 
value. 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 each treatment group and for the pairwise comparisons of each dose of obicetrapib to the 


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placebo group will be provided. Adjustment for multiple comparisons will be made using 
Dunnett’s test in accordance with the power and sample size calculations utilized for the study. 
Missing data will be imputed using multiple imputation methodology. Results will be combined 
using Rubin’s method. Full details of the model and imputation will be provided in the SAP.  
Similar models as described for the primary efficacy analyses will be used to analyze the 
secondary efficacy endpoints. No adjustment will be made for multiplicity in testing the secondary 
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 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.
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. 
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 56 (SD of 15%) for 
each of the obicetrapib groups compared to the placebo group at a 2-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 efficacy endpoint 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 (Visit 1) LDL-C levels (100 or 
<100 mg/dL). 
SITES: Approximately 20 sites in the United States 
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 ............................................................................................................................ 8 
List of Abbreviations and Definition of Terms............................................................................. 12 
1  Introduction and Background Information ............................................................................. 14 
1.1 
Cholesteryl Ester Transfer Protein Inhibitors ................................................................ 14 
1.2 
Obicetrapib .................................................................................................................... 14 
1.3 
Clinical Development of Obicetrapib ........................................................................... 15 
1.4 
Rationale ........................................................................................................................ 15 
1.5 
Risk/Benefit ................................................................................................................... 15 
1.6 
Coronavirus Disease 2019 Impacts ............................................................................... 16 
2  Study Objectives ..................................................................................................................... 17 
2.1 
Primary Objective ......................................................................................................... 17 
2.2 
Secondary Objectives .................................................................................................... 17 
3  Study Description.................................................................................................................... 18 
3.1 
Summary of Study Design ............................................................................................ 18 
3.1.1  Screening Period ............................................................................................... 18 
3.1.2  Treatment Period ............................................................................................... 18 
3.1.3  Safety Follow-Up Period ................................................................................... 18 
3.1.4  Pharmacokinetic Period ..................................................................................... 18 
3.1.5  Coronavirus Disease 2019 Contingency Measures ........................................... 18 
3.2 
Study Indication ............................................................................................................ 19 
4  Selection and Withdrawal of Participants ............................................................................... 20 
4.1 
Inclusion Criteria ........................................................................................................... 20 
4.2 
Exclusion Criteria .......................................................................................................... 21 
4.3 
Retesting ........................................................................................................................ 21 
4.4 
Rescreening ................................................................................................................... 22 
4.5 
Withdrawal Criteria ....................................................................................................... 22 
5  Study Treatments .................................................................................................................... 23 


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5.1 
Treatment Groups .......................................................................................................... 23 
5.2 
Rationale for Dosing ..................................................................................................... 23 
5.3 
Randomization and Blinding ......................................................................................... 23 
5.4 
Breaking the Blind ........................................................................................................ 23 
5.5 
Drug Supplies ................................................................................................................ 24 
5.5.1  Formulation and Packaging ............................................................................... 24 
5.5.2  Study Drug Preparation and Dispensing ........................................................... 24 
5.5.3  Study Drug Administration ............................................................................... 25 
5.5.4  Treatment Compliance ...................................................................................... 25 
5.5.5  Storage and Accountability ............................................................................... 25 
5.6 
Prior and Concomitant Medications and/or Procedures ................................................ 25 
5.6.1  Excluded Medications and/or Procedures ......................................................... 25 
5.6.2  Allowed Medications and/or Procedures .......................................................... 25 
5.6.3  Documentation of Prior and Concomitant Medication Use .............................. 25 
6  Study Procedures .................................................................................................................... 26 
7  Efficacy Assessments .............................................................................................................. 27 
8  Safety Assessments ................................................................................................................. 28 
8.1 
Adverse Events .............................................................................................................. 28 
8.1.1  Adverse (Drug) Reaction .................................................................................. 28 
8.1.2  Unexpected Adverse Drug Reaction ................................................................. 29 
8.1.3  Assessment of Adverse Events by the Investigator .......................................... 29 
8.2 
Serious Adverse Events ................................................................................................. 30 
8.3 
Serious Adverse Event Reporting − Procedures for Investigators ................................ 31 
8.4 
Pregnancy Reporting ..................................................................................................... 31 
8.5 
Expedited Reporting ...................................................................................................... 32 
8.6 
Special Situation Reports .............................................................................................. 32 
8.7 
Clinical Laboratory Evaluations .................................................................................... 33 
8.8 
Vital Signs ..................................................................................................................... 33 
8.9 
Weight and Height ........................................................................................................ 33 
8.10  Demographics ................................................................................................................ 33 
8.11  Electrocardiograms ........................................................................................................ 33 
8.12  Physical Examinations .................................................................................................. 34 


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9  Statistics .................................................................................................................................. 35 
9.1 
Analysis Populations ..................................................................................................... 35 
9.2 
Statistical Methods ........................................................................................................ 35 
9.2.1  Analysis of Efficacy .......................................................................................... 35 
9.2.1.1  Primary efficacy analysis .................................................................... 35 
9.2.1.2  Secondary efficacy analysis ................................................................ 36 
9.2.2  Analysis of Safety ............................................................................................. 36 
9.2.3  Analysis of Pharmacokinetics ........................................................................... 36 
9.2.4  Interim Analysis ................................................................................................ 36 
9.2.5  Sample Size Determination ............................................................................... 36 
10  Data Management and Record Keeping ................................................................................. 37 
10.1  Data Management ......................................................................................................... 37 
10.1.1  Data Handling ................................................................................................... 37 
10.1.2  Computer Systems ............................................................................................. 37 
10.1.3  Data Entry ......................................................................................................... 37 
10.1.4  Medical Information Coding ............................................................................. 37 
10.1.5  Data Validation ................................................................................................. 37 
10.2  Record Keeping ............................................................................................................. 38 
10.3  End of Study .................................................................................................................. 38 
11  Investigator Requirements and Quality Control ..................................................................... 39 
11.1  Ethical Conduct of the Study ........................................................................................ 39 
11.2  Institutional Review Board ............................................................................................ 39 
11.3  Informed Consent .......................................................................................................... 39 
11.4  Study Monitoring Requirements ................................................................................... 39 
11.5  Disclosure of Data ......................................................................................................... 40 
11.6  Retention of Records ..................................................................................................... 40 
11.7  Publication Policy ......................................................................................................... 40 
11.8  Financial Disclosure ...................................................................................................... 41 
12  Study Administrative Information .......................................................................................... 42 
12.1  Protocol Amendments ................................................................................................... 42 
13  References ............................................................................................................................... 43 
Appendix A: Schedule of Procedures ........................................................................................... 44 


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Appendix B: Clinical Laboratory Analytes .................................................................................. 46 


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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 
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 
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 
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 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
Standard deviation 


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Abbreviation 
Definition 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TEAE 
Treatment-emergent adverse event 
TG 
Triglyceride(s) 
ULN 
Upper limit of normal 


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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. Some 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 occurs through upregulation of the 
LDL receptor, would lead to large reductions in CV events and would be of great clinical 
importance for patients who are unable to tolerate statins. 
1.2 
Obicetrapib  
Obicetrapib has been shown to be 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 not only in LDL, but also in other atherogenic lipoproteins. On top of this, obicetrapib 
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 


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removal of cholesterol via the liver and also reduced lipoprotein (a) (Lp[a]).4 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.5 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 have 
been conducted in healthy volunteers. A formal, thorough QT/QTc study (TA-8995-04) has been 
completed and obicetrapib was shown to have no effect on QTcF. A drug-drug interaction study 
(TA-8995-05) has also been conducted; this study showed no significant effect of obicetrapib on 
P-glycoprotein activity, but this study showed that obicetrapib is a mild inducer of cytochrome 
P450 3A4. A mass balance study (TA-8995-07) in healthy males concluded that obicetrapib is 
steadily absorbed, and the principal route of excretion was in the feces. Finally, bioequivalence 
between obicetrapib capsule and tablet formulations was investigated (TA-8995-08) and 
established. 
A Phase 2 patient study (TA-8995-03) was conducted in Denmark and the Netherlands to evaluate 
the optimal dose of obicetrapib alone and in combination with medium-intensity statins in patients 
with mild dyslipidemia. This study concluded that a daily dose of 10 mg obicetrapib in 
combination with medium-intensity statins resulted in an incremental LDL-C reduction of up to 
50.2% and a total LDL-C reduction of 63.7%, while statin monotherapy or obicetrapib 
monotherapy achieved an LDL-C reduction of only 46.4%.4 When compared with statin 
treatment alone at the end of the 12-week Treatment Period, all treatment groups with obicetrapib 
in combination with medium-intensity statins had significantly higher mean HDL-C levels; had a 
significantly greater increase in ApoA1 and ApoE levels; and a greater decrease in ApoB, Lp(a), 
and non-high-density lipoprotein cholesterol (non-HDL-C) levels.4 However, there is a lack of 
data for the safety and efficacy of obicetrapib used as an adjunct to high-intensity statin therapy, 
which is commonly used in patients with dyslipidemia.  
Another patient study (TA-8995-06) was conducted where obicetrapib was found to result in a 
statistically significant reduction in Lp(a) levels following 12 weeks of treatment; however, the 
magnitude of the changes (approximately a 10% reduction) was not likely to be clinically relevant. 
1.4 
Rationale 
The safety and efficacy data following 56 days of single daily dose administrations of obicetrapib 
as an adjunct to high-intensity statin therapy in this study will support dose selection for subsequent 
studies. 
1.5 
Risk/Benefit 
Obicetrapib has undergone extensive nonclinical testing in the standard battery of tests according 
to International Council for Harmonisation (ICH) guidelines, including repeat-dose toxicity 
studies of up to 39 weeks duration. In addition, obicetrapib has been investigated in 8 completed 
clinical studies, of which 6 studies were in Phase 1 of clinical development and 2 studies were in 
Phase 2. A total of approximately 500 subjects have been exposed to obicetrapib in these studies. 
In Phase 1, a total of 159 subjects received single oral doses between 5 and 150 mg of obicetrapib, 


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and 76 subjects received consecutive doses between 1 and 25 mg of obicetrapib for periods up to 
28 days. In Phase 2, a total of 268 patients received 1 to 10 mg of obicetrapib for up to 12 weeks. 
In healthy volunteer studies, single doses of obicetrapib up to 150 mg and multiple doses up to 
25 mg/day over 28 days were generally well tolerated. In patient studies, 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 adverse events (AEs) identified and no clinically significant 
changes in vital signs, 12-lead electrocardiograms (ECGs), hematology, or biochemistry in any 
clinical trials. Most treatment-emergent AEs (TEAEs) were mild or moderate in severity. None of 
the severe TEAEs were considered related to study drug. The number of patients experiencing 
TEAEs and their severity were similar across all treatment groups. Incidence rates of drug-related 
TEAEs were also comparable for all treatment groups; the number of TEAEs in the obicetrapib 
treatment groups did not display a dose-dependent effect. There were 7 patients, who were 
randomized to receive obicetrapib alone or in combination with statin, with a treatment-emergent 
serious AE (SAE), none of which were suspected to be related to study drug. One patient had a 
treatment-emergent SAE that resulted in study discontinuation. 
1.6 
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. 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 protocol includes contingency measures to manage disruptions due to COVID-19 
control measures, see Section 3.1.5 for details. 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. 
 


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2 
STUDY OBJECTIVES 
2.1 
Primary Objective 
The primary objective of this study is to evaluate the efficacy of obicetrapib, compared to placebo, 
at Day 56 in decreasing LDL-C as an adjunct to high-intensity statin therapy. 
2.2 
Secondary Objectives 
The secondary objectives of this study include the following: 
 To evaluate the effect of obicetrapib, compared to placebo, at Day 56 on ApoB, non-HDL-C, 
and HDL-C, as an adjunct to high-intensity statin therapy; 
 To assess the mean plasma levels of obicetrapib at steady state on Days 56, 84, 112, and 161; 
and 
 To evaluate the safety and tolerability profile of obicetrapib. 


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STUDY DESCRIPTION 
3.1 
Summary of Study Design 
This study will be a placebo-controlled, double-blind, randomized, Phase 2 dose-finding study to 
evaluate the efficacy, safety, and tolerability of obicetrapib 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 (Visit 1), 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: 
 5 mg obicetrapib (one 5 mg obicetrapib tablet + 1 placebo tablet); 
 10 mg obicetrapib (two 5 mg obicetrapib tablets); or 
 Placebo (2 placebo tablets). 
During the 8-week Treatment Period, the assigned study drugs will be administered by the 
participants orally and once daily on Day 1 to Day 56. Participants will return to the site every 
4 weeks 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 through database lock 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 
Pharmacokinetic Period 
Participants will return to the site for 2 PK Visits (Visits 6 and 7) approximately 8 and 15 weeks, 
respectively, after the end of the Treatment Period for safety and PK assessments.  
3.1.5 
Coronavirus Disease 2019 Contingency Measures 
In cases of COVID-19 limitations, it is the Investigator’s responsibility to assure the safety of 
participants, including phone or video contact to assess the participant’s well-being including any 
AE, collection of study samples and clinical data as best as possible, and direct shipment of study 
drug to participant, if necessary. Where available and appropriate, home health care may be 
considered to facilitate monitoring of safety and study continuity. Documentation of these cases 
and the site’s management of participants should be recorded in the Investigator study files. In the 


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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; and 
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 
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;6 
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. Treatment with any proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor within 
10 weeks prior to randomization or bempedoic acid within 2 weeks prior to randomization; 
13. 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 
14. 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 
retesting should be documented. If the retest result is no longer exclusionary, the participant may 
be randomized. 


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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 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 4 weeks after the last dose. If a participant 
withdraws prematurely from the study due to the above criteria or any other reason, study staff 
should make every effort to complete the full panel of assessments scheduled for the Early 
Termination Visit and complete a Safety Follow-up Visit 4 weeks after the last dose. 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 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: 
 5 mg obicetrapib (one 5 mg obicetrapib tablet + 1 placebo tablet); 
 10 mg obicetrapib (two 5 mg obicetrapib tablets); or 
 Placebo (2 placebo tablets). 
5.2 
Rationale for Dosing 
In previous clinical studies of obicetrapib in healthy volunteers and patients, near maximal effects 
were observed at the 5 mg obicetrapib dose level with increased HDL-C levels and decreased 
LDL-C levels. 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 doses of 5 and 10 mg 
obicetrapib in participants currently receiving high-intensity statin therapy. 
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 the 5 mg obicetrapib, 10 mg obicetrapib, or placebo treatment 
groups. At randomization, participants will be stratified according to their Screening Visit (Visit 1) 
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 through database lock 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 
an individual participant, the Investigator or qualified designee should request the treatment 
assignment from the IRT system. The Investigator is advised not to reveal the treatment assignment 
to other sites or Sponsor personnel. 
Prior to unblinding, and if the situation allows, the Investigator should consult with the Sponsor’s 
Medical Monitor. If this is impractical, the Investigator must notify the Sponsor’s Medical Monitor 
as soon as possible, without revealing the treatment assignment of the unblinded participant. The 
Investigator must document the participant identification and the date and time for breaking the 
blind and must clearly explain the reasons for breaking the blind. 
Medically necessary care should not be delayed for unblinding information (ie, the Investigator 
should treat the participant based on the participant’s signs/symptoms without waiting for the 
unblinding process to be completed). 




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5.5.3 
Study Drug Administration 
Two tablets of study drugs will be administered by the participant orally and once daily on Day 1 
to Day 56. Study drugs should be administered at approximately the same time each morning, with 
food. On days with visits scheduled, study drugs should be administered with food following all 
fasted blood samples. 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. 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. 
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. 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).  
This study protocol includes contingency measures to manage disruptions due to COVID-19 
control measures, including modifications to visit schedules and procedures specific to situations 
where COVID-19 is impacting study conduct. See Section 3.1.5 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. 


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7 
EFFICACY ASSESSMENTS 
The primary efficacy endpoint is the percent change from Day 1 to Day 56 in LDL-C for each 
obicetrapib group compared to the placebo group.  
The key secondary efficacy endpoints include the following: 
 Percent change from Day 1 to Day 56 in ApoB for each obicetrapib group compared to the 
placebo group; 
 Percent change from Day 1 to Day 56 in non-HDL-C for each obicetrapib group compared to 
the placebo group; and 
 Percent change from Day 1 to Day 56 in HDL-C for each obicetrapib group compared to 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.7 In addition, for all patients, LDL-C will be measured by preparative 
ultracentrifugation, also referred to as beta quantification, at baseline (Visit 2) and at the end of 
the 8-week Treatment Period (Visit 4). 


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8 
SAFETY ASSESSMENTS 
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 7. 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. 
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 


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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. 
 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. 


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 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 
in an emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalizations, or the development of drug dependency. 




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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 Food and 
Drug Administration (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 investigational medicinal product. 
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.  
All special situation events as described above must be reported on the Special Situations Report 
form and faxed/emailed to 
 (contact information listed below) within 
24 hours of knowledge of the event. All AEs associated with these Special Situation reports should 
be reported as AEs or SAEs as well as recorded on the AE eCRF and/or the SAE report form. 




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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 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 56 value for the LDL-C assessment, and 
who did not experience a major protocol deviation that potentially impacted 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 56 in LDL-C will be 
performed using a mixed model for repeated measures approach. The analysis will include fixed 
effects for treatment, visit, and treatment-by-visit interaction, along with a covariate of the baseline 
value. 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 each treatment group and for the pairwise comparisons of each dose of obicetrapib to the 
placebo group will be provided. Adjustment for multiple comparisons will be made using 
Dunnett’s test in accordance with the power and sample size calculations utilized for the study. 


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Missing data will be imputed using multiple imputation methodology. Results will be combined 
using Rubin’s method. Full details of the model and imputation will be provided in the SAP. 
9.2.1.2 
Secondary efficacy analysis 
Similar models as described for the primary efficacy analyses will be used to analyze the secondary 
efficacy endpoints. No adjustment will be made for multiplicity in testing the secondary 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 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). 
9.2.3 
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. 
9.2.4 
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 56 (SD of 15%) for 
each of the obicetrapib groups compared to the placebo group at a 2-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 efficacy endpoint described in Section 7. 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 (Visit 1) 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  
 World Health Organization 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 investigative site for resolution through data queries. 
The eCRFs must be reviewed and electronically signed by the Investigator. 


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10.2 
Record Keeping 
Records of participants, source documents, monitoring visit logs, eCRFs, inventory of study 
product, 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.  
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 monitor’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 monitor 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. 
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. 
5. 
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. 
6. 
CKD-EPI 
equations 
for 
glomerular 
filtration 
rate 
(GFR). 
MDCalc. 
https://www.mdcalc.com/ckd-epi-equations-glomerular-filtration-rate-gfr. 
Accessed 
09 November 2020. 
7. 
LDL 
calculated. 
MDCalc. 
https://www.mdcalc.com/ldl-calculated. 
Accessed 
09 November 2020. 
 


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APPENDIX A: SCHEDULE OF PROCEDURES 
 
Screeninga,b 
Treatment Period 
Safety Follow-Up 
PK 
Early 
Termination 
Visit 
Visit 
1 
2 
3 
4 
5 
6 
7 
Week 
Up to -2 
0 
4 
8 
12 
16 
23 
Day ( Visit Window) 
-14 to -1 
1 
28 (2) 
56 (2) 
84 (2) 
112 (2) 
161 (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
X
FSH testi 
X
 
Fasting (approximately 10 hours) 
chemistry and hematologyj 
X
X
X
X
X 
X
X
X
Fasting (approximately 10 hours) 
lipid profilek 
X
X
X
X
 
X
PK samplel 
X
X
X
Xm 
X
X
X
Randomization 
X
 
Dispense study drug 
X
X
 
Study drug administrationn 
X
X
X
 
Study drug compliance  
X
X
 
Register visit in IRT 
X
X
X
X
 
X
Adverse events 
X
X
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, including phone or video contact to assess the participant’s well-being 
including any adverse event, collection of study samples and clinical data as best as possible, and direct shipment of study drug to participant, if necessary. Where available and 
appropriate, home health care may be considered to facilitate monitoring of safety and study continuity. 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. 
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. 


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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. 
Signed informed consent must be obtained 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 09 November 2020.) In 
addition, for all patients, LDL-C will be measured by preparative ultracentrifugation, also referred to as beta quantification, at baseline (Visit 2) and at the end of the 8-week 
Treatment Period (Visit 4). 
l. 
On Day 1, a PK sample will be collected pre-dose. The subsequent post-dose PK samples should be collected once at approximately the same time at each visit. 
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. 
Two tablets of study drugs will be administered by the participant orally and once daily on Day 1 to Day 56. Study drugs should be administered at approximately the same 
time each morning, with food. On days with visits scheduled, study drugs should be administered with food following all fasted blood samples. 
COVID-19 = Coronavirus Disease 2019; ECG = electrocardiogram; FSH = follicle-stimulating hormone; HbA1c = glycosylated hemoglobin; IRT = interactive response technology; 
LDL-C = low-density lipoprotein cholesterol; PK = pharmacokinetic; TG = triglycerides. 
 


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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 
Follicle-stimulating hormone [1] 
 
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. 
 
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. 
 
Pregnancy Test 
Urine [1] 
 
1. 
For women of childbearing potential only.
 


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Lipid Profile 
Apolipoprotein B 
Apolipoprotein E (ApoE) 
High-density lipoprotein-ApoE [1]  
High-density lipoprotein cholesterol 
Low-density lipoprotein cholesterol [2] 
Non-high-density lipoprotein cholesterol 
Triglycerides 
Very low-density lipoprotein cholesterol 
1. 
With and without apolipoprotein C3. 
2. 
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 
09 November 2020.) In addition, for all patients, LDL-C will be measured by preparative ultracentrifugation, also 
referred to as beta quantification, at baseline (Visit 2) and at the end of the 8-week Treatment Period (Visit 4). 
 
 
 
 

SAP_001.pdf: