Conditions: Hypercholesterolemia
Keywords: Cholesterol PCSK9 Repatha evolocumab LDL-C
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 59
Healthy volunteers: no

Brief summary:
The purpose of this study is to determine if bempedoic acid (ETC-1002) 180mg added to PCSK9 inhibitor (evolocumab) therapy is effective and safe in patients with elevated LDL cholesterol.

Detailed description:

Arms:
arm 1: Bempedoic acid 180mg tablet taken orally, once daily plus evolocumab (Repatha) 420mg injection once monthly arm 2: Matching placebo tablet taken orally, once daily plus evolocumab (Repatha) 420mg injection once monthly

Interventions: intervention 1: bempedoic acid 180mg intervention 2: placebo intervention 3: evolocumab
Intervention descriptions: intervention 1: Daily bempedoic acid 180mg tablet in addition to monthly PCSK9i (evolocumab) background therapy intervention 2: Daily matching placebo tablet in addition to monthly PCSK9i (evolocumab) background therapy intervention 3: Monthly PCSK9i (evolocumab) background therapy

Protocol document:
Prot_000.pdf: 
Confidential 
Page 1 of 114 
1.
TITLE PAGE
BEMPEDOIC ACID (ETC-1002) 
1002-039 
A RANDOMIZED, DOUBLE-BLIND, PARALLEL GROUP, 
MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY 
OF BEMPEDOIC ACID (ETC-1002) 180 MG QD WHEN ADDED TO 
PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 
(PCSK9)-INHIBITOR THERAPY 
Study Phase: 
2 
IND Number: 
106,654 
EudraCT Number: 
n/a 
Indication: 
Treatment of hyperlipidemia 
Investigators: 
Approximately 20-30 sites located in North America 
Sponsor: 
Esperion Therapeutics, Inc. 
3891 Ranchero Drive, Suite 150 
Ann Arbor, MI 48108 
Phone: 734-862-4840 
Fax: 734-582-9720 
Sponsor Contact: 
Medical Monitor: 
Version 
Date 
Original Protocol 
22 November 2016 
Protocol Amendment 1: 
05 March 2017 
Confidentiality Statement 
THIS CONFIDENTIAL INFORMATION IS ABOUT AN INVESTIGATIONAL DRUG PROVIDED FOR THE EXCLUSIVE USE OF INVESTIGATORS OF 
THIS DRUG AND IS SUBJECT TO RECALL AT ANY TIME. THE INFORMATION IN THIS DOCUMENT MAY NOT BE DISCLOSED UNLESS SUCH 
DISCLOSURE IS REQUIRED BY FEDERAL OR STATE LAW OR REGULATIONS. SUBJECT TO THE FOREGOING, THIS INFORMATION MAY BE
DISCLOSED ONLY TO THOSE PERSONS INVOLVED IN THE STUDY WHO HAVE NEED TO KNOW, WITH THE OBLIGATION NOT TO FURTHER
DISSEMINATE THIS INFORMATION. THESE RESTRICTIONS ON DISCLOSURE WILL APPLY EQUALLY TO ALL FUTURE ORAL OR WRITTEN
INFORMATION, SUPPLIED TO YOU BY ESPERION THERAPEUTICS, INC., WHICH IS DESIGNATED AS “PRIVILEGED” OR “CONFIDENTIAL.” 
NCT number: NCT03193047
This NCT number has been applied to the document
for purposes of posting on clinicaltrials.gov


Bempedoic Acid 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
Amendment 1, 05 March 2017 
Confidential 
Page 2 of 114 
2.
SYNOPSIS
Name of Sponsor:  Esperion Therapeutics, Inc.  
Name of Investigational Product:  Bempedoic acid (ETC-1002) film-coated tablets 
Name of Active Ingredient:  Bempedoic acid 
Title of Study: 
A Randomized, Double-Blind, Parallel Group, Multicenter Study to Evaluate the Efficacy and Safety of 
Bempedoic Acid (ETC-1002) 180 mg QD when added to PCSK9-Inhibitor Therapy   
Study Number:  1002-039 
Phase of Development:  2 
Clinical Sites:  Approximately 20 sites located in North America 
Objectives: 
Primary: 
•
To assess the 2-month efficacy of bempedoic acid 180 mg/day vs placebo in the reduction of low-
density lipoprotein cholesterol (LDL-C) in patients on proprotein convertase subtilisin/kexin
type 9 inhibitor (PCSK9i) therapy
Secondary: 
•
To assess the 1-month efficacy of bempedoic acid 180 mg/day vs placebo in the reduction of
LDL-C in patients on PCSK9i therapy
•
To evaluate the effect of bempedoic acid 180 mg/day vs placebo on apolipoprotein B (ApoB),
non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), and high-
sensitivity C-reactive protein (hs-CRP) after 1 and 2 months of treatment
•
To evaluate the safety and tolerability of bempedoic acid 180 mg/day compared to placebo in
patients on PCSK9i therapy
Exploratory: 


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Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 4 of 114 
Primary Endpoint 
The primary efficacy endpoint for this study is the percent change from baseline to Month 2 in LDL-C. 
Secondary Endpoints 
1. Percent change from baseline to Month 1 in LDL-C 
2. Change from baseline to Month 1 and Month 2 in LDL-C 
3. Percent change from baseline to Month 1 and Month 2 in ApoB, non-HDL-C, TC, and hs-CRP  
4. Safety and tolerability of bempedoic acid in this patient population over 2 months, as assessed by 
adverse events (AEs) and clinical laboratory values 
Exploratory Endpoints 
For details of study assessments, see the Schedule of Events (Appendix 1). 
Number of patients (planned):  Approximately 52 adult male and female patients  
Diagnosis and Criteria for Inclusion: 
 
Key inclusion criteria 
1. Provision of written informed consent must be obtained prior to any study-specific procedure. 
2. Age ≥18 years or legal age of majority depending on regional law, whichever is greater at Month -4.5 
(Visit S1) 
3. Fasting, calculated LDL-C at screening (Visit S2) ≥160 mg/dL and ≥70 mg/dL at Visit S4 
Note:  A single repeat of LDL-C may be completed.  For those patients who have a repeat LDL-C, 
the average of the 2 values will be used to determine eligibility. 
4. Men and nonpregnant, nonlactating women.  Women must be: 
a. Naturally postmenopausal defined as ≥1 year without menses and:  
− 
≥55 years, or  
− 
<55 years with follicle-stimulating hormone (FSH) ≥40.0 IU/L; or 
b. Surgically sterile including hysterectomy, bilateral oophorectomy, and/or tubal ligation; or 
c. Women of childbearing potential willing to use 2 acceptable methods of birth control including: 
− 
oral, implanted, topical or injectable birth control medications 
− 
placement of an intrauterine device with or without hormones 
− 
barrier methods including condom or occlusive cap with spermicidal foam or spermicidal 
jelly 
− 
vasectomized male partner who is the sole partner for this patient  
− 
true abstinence:  when this is in line with the preferred and usual lifestyle of the subject. 
(Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], 
declaration of abstinence for the duration of a trial, and withdrawal are not acceptable 
methods of contraception) 
There are no protocol-specific birth control requirements for men with partners who are able to 
become pregnant. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 5 of 114 
Key exclusion criteria 
1. Homozygous Familial Hypercholesterolemia (HoFH) 
2. Total fasting TG ≥500 mg/dL (5.6 mmol/L at Month -3 (Visit S2). 
Note:  A single repeat of TG may be completed.  For those patients who have a repeat TG, the 
average of the 2 values will be used to determine eligibility. 
3. Renal dysfunction or a glomerulonephropathy defined as either nephritic or nephrotic syndrome, 
including estimated glomerular filtration rate (eGFR; using central laboratory determined 
Modification of Diet in Renal Disease [MDRD] formula) <30 mL/min/1.73 m2 at Month -4.5 
(Visit S1). 
Note:  A single repeat of eGFR may be completed prior to randomization.  For those patients who 
have a repeat eGFR, the average of the 2 values will be used to determine eligibility. 
4. All patients with known cardiovascular disease (CVD) or peripheral arterial disease (PAD) or 
cerebrovascular disease (CD).   
5. History of type 1 or type 2 diabetes or laboratory evidence of diabetes (fasting blood glucose [FBG] 
>126 mg/dL or glycosylated hemoglobin, Type A1C [HbA1C] >6.5%) without prior diagnosis of 
diabetes at Month -4.5 (Visit S1)  
6. Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) >160 mmHg or diastolic 
blood pressure (DBP) >100 mmHg at Month -4.5 (Visit S1). 
7. Uncontrolled hypothyroidism, including thyroid-stimulating hormone (TSH) >1.5 × the upper limit of 
normal (ULN) at Month -4.5 (Visit S1).   
8. Liver disease or dysfunction, including: 
a. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≥2.0 × ULN at 
Month -4.5 (Visit S1). 
b. Positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies 
(HCV-ABVivi) at Month -4.5 (Visit S1). 
Note:  If total bilirubin (TB) ≥1.2 × ULN, a reflex indirect (unconjugated) bilirubin will be 
obtained and if consistent with Gilbert’s disease, the patient may be enrolled in the study.   
Note:  At the discretion of the investigator, a single repeat of ALT and/or AST may be 
completed.  For those patients who have a repeat ALT and/or AST, the average of the 
2 values will be used to determine eligibility.  Also, if test for hepatitis C antibody is positive, 
but reflexive test for Hepatitis C ribonucleic acid (RNA) is negative, patient can be enrolled.  
9. Gastrointestinal conditions or procedures (including weight loss surgery; eg, Lap-Band® or gastric 
bypass) that may affect drug absorption. 
10. History of hematologic or coagulation disorders or a hemoglobin (Hgb) level <10 g/dL at Month -4.5 
(Visit S1)  
11. History of malignancy (except non-metastatic basal or squamous cell carcinoma of the skin and 
cervical carcinoma in situ). 
12. Unexplained creatine kinase (CK) >3 × ULN at screening up to randomization (ie, not associated with 
recent trauma or physically strenuous activity).  Patients with an explained CK elevation must have 
single repeat CK ≤3 × ULN prior to randomization.   
13. History within the last 2 years of drug, alcohol, amphetamine and derivatives, or cocaine abuse.  
Patients taking  amphetamine derivatives for medical reasons such as attention deficit disorder or 
taking prescription opioids or other meds for chronic pain that have been stable, without evidence of 
abuse prescribed by and under the care of a health care practitioner can be enrolled after evaluation by 
the Investigator. 
14. Blood donation, participation in a clinical study with multiple blood draws, major trauma, blood 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 6 of 114 
transfusion, or major surgery with or without blood loss within 30 days prior to randomization 
15. Use of any experimental or investigational drugs within 30 days or 5 half-lives, whichever is longer 
16. Previous enrollment in a Esperion Phase 3 bempedoic acid (ETC-1002) clinical study 
17. Use of a cholesterylester transfer protein (CETP) inhibitor in the last 12 months prior to screening, 
such as: anacetrapib, dalcetrapib, or evacetrapib. 
18. Use of, or a plan to initiate, these prohibited therapies/supplements during the study: 
• 
Mipomersen (must be stopped at least 6 months prior to Month -4.5 [Visit S1]), 
• 
Lomitapide or apheresis therapy (must be stopped at least 3 months prior to Month -4.5 
[Visit S1]),  
• 
Red yeast rice containing products (must be stopped on or before Month -4.5 [Visit S1]),  
• 
Lipid-regulating drugs or supplements (must be stopped on or before Month -4.5[Visit S1]) 
19. Planned initiation or changes to the following drugs prior to Month -4.5: 
• 
Hormone replacement (6 weeks prior to Month -4.5) 
• 
Thyroid replacement (6 weeks prior to Month -4.5) 
• 
Obesity medication (3 months prior to Month -4.5) 
20. A medical or situational (ie, geographical) finding that in the investigator’s opinion may compromise 
the patient’s safety or ability to complete the study. 
21. Patient is pregnant or breast feeding, or planning to become pregnant during treatment and/ or within 
30 days after the end of treatment 
22. An employee or contractor of the facility conducting the study, or a family member of the Principal 
Investigator, Co-Investigator, or Sponsor. 
23. Heterozygous familial hypercholesterolemia (HeFH) 
24. Concomitant use of a PCSK9 inhibitor (Praluent® [alirocumab] or Repatha® [evolocumab]) at 
(Visit S1) or prior use within the past 16 weeks of Visit S1 
Test product, dose, and mode of administration:   
• 
Bempedoic acid 180-mg tablets/once per day 
• 
Matching placebo tablets/once per day 
• 
PCSK9i – Repatha 420 mg injection once monthly 
All study drug (bempedoic acid or placebo) will be ingested once daily with or without food.  On clinic 
days patients will come to the clinic in the fasted state and the PCSK9i and study drug will be 
administered after all study procedures have been conducted.  PCSK9i injections must be administered 
consistently throughout the trial within 30 ± 3 days from the previous dose.  Efficacy will vary if the 
doses are not consistently administered. 
Duration of treatment: 
The duration of treatment will be composed of a 1.5-month screening period, a 3-month PCSK9i lipid 
stabilization period, and a 2-month treatment period. 
Criteria for evaluation: 
Efficacy: 
Lipid and Cardiometabolic Assessments: 
• 
Calculated LDL-C,
non-HDL-C, TC, 
 ApoB,
 and hs-CRP 
− 
If TG exceeds 400 mg/dL (4.5 mmol/L) or LDL-C is ≤50 mg/dL (1.3 mmol/L), direct 
measure of LDL-C will be conducted. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 7 of 114 
Other biomarker and PK samples: 
Pharmacokinetics 
Three pharmacokinetic (PK) samples will be collected (see lab manual).  Plasma concentrations of 
bempedoic acid and its metabolite ESP15228 will be determined in patients who are receiving bempedoic 
acid, who have compliance ≥80%, and who have taken a dose of bempedoic acid within 2 days of the 
sample collection.  All patients, site personnel, and study personnel will remain blinded to treatment 
assignment throughout the duration of the study.  Personnel performing the bioanalytical analysis of 
bempedoic acid concentrations will be unblinded in order to assay the appropriate samples during the 
study.  Plasma concentrations of bempedoic acid and ESP15228 will be summarized using descriptive 
statistics by time point. 
 
Safety: 
Safety Assessments: 
• 
Adverse events and serious adverse events (SAEs) will be collected and reported.  Other safety 
assessments will include clinical safety laboratories (including hematology, blood chemistry, 
HbA1C, fasting glucose, and urinalysis), physical examination (PE) findings, vital signs, and 
weight. 
Clinical Laboratory Assessments: 
• 
Hematology:  Hematocrit (Hct), Hgb, mean corpuscular hemoglobin (MCH), mean corpuscular 
hemoglobin concentration (MCHC), mean corpuscular volume (MCV), platelet count, red blood 
cell (RBC) count, white blood cell (WBC) count with differential (absolute values only) 
• 
Urinalysis (Dipstick):  Clarity, bilirubin, color, glucose, ketones, leukocyte esterase, nitrite, occult 
blood, pH, protein, specific gravity, urobilinogen 
• 
Urinalysis (Microscopic):  Obtain centrally only if positive urine dipstick; bacteria, casts, crystals, 
epithelial cells, RBC, and WBC 
• 
In patients receiving anticoagulant therapy that in the investigator’s judgement require 
monitoring, PT/international normalized ratio (INR) will be evaluated at Visit T1 and 3 to 5 days 
post Visit T1 using a local or central lab  
• 
Serum Chemistry (fasting):  Albumin (ALB), alkaline phosphatase (ALK-P), ALT (or serum 
glutamic pyruvic transaminase [SGPT]), AST (or serum glutamic oxaloacetic transaminase 
[SGOT]), blood urea nitrogen (BUN), calcium (Ca), carbon dioxide (CO2), chloride (Cl), 
creatinine, CK, glucose, lactate dehydrogenase (LDH), phosphorus, potassium (K), sodium (Na), 
total and direct bilirubin, total protein, uric acid  
• 
HbA1C 
Other Screening Laboratories: 
• 
Serum pregnancy test (only for females who are of childbearing potential), TSH, FSH (in females 
naturally postmenopausal, females <55 years of age at screening) 
Safety and Monitoring: 
Post-randomization, lipid results will be masked in order to maintain the blind. 
Monitoring and Management of Potential AEs and Adverse Events of Special Interest (AESI) 
Adverse Events Associated with Experience with bempedoic acid to date: 
Potential AEs: 
Based on findings in nonclinical models, potential AEs include reversible hypoglycemia and 
metabolic acidosis.  Potential cases of reversible hypoglycemia and metabolic acidosis will be 
identified by routine safety monitoring of AEs and clinical safety laboratories. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 8 of 114 
Musculoskeletal Safety: 
Patients with CK abnormalities will also be reviewed for any other lab changes, such as creatinine, 
and any reported AEs or SAEs.  Musculoskeletal events will be identified and evaluated by routine 
safety monitoring of PE findings and AEs.  
Hepatic:  
Hepatic function will be monitored throughout with the clinical safety labs.  More detailed 
investigation will occur if the safety clinical laboratory results are 3 times or more than the ULN.  
Further details on occurrence and monitoring are available in the Investigator’s Brochure (IB) and 
protocol.  
Statistical methods: 
Sample Size 
The planned total sample size for this study is 52 with 26 patients in the bempedoic acid 180 mg group 
and 26 in the placebo group.  This sample size is expected to 
 
  
Analysis Populations 
The Full Analysis Set (FAS), used for all of the efficacy analyses, is defined as all randomized patients 
with a baseline lipid value, at least 1 postbaseline lipid value, and having taken their study drug within 
2 days of the lipid measurement.  The FAS is also known as the modified intention-to-treat (mITT) set of 
patients.  Patients in the FAS will be included in their randomized treatment group, regardless of the 
treatment they actually received.  Other subsets of the FAS will be considered to evaluate primary and 
secondary endpoints as sensitivity analyses and the details will be described in the statistical analysis plan 
(SAP). 
The Safety Population (SP), used for all of the safety summaries, is defined as all randomized patients 
who received at least 1 dose of study medication.  Patients in the SP will be included in the treatment 
group that they actually received, regardless of their randomized treatment.   
Primary Endpoint  
The primary efficacy endpoint is the percent change from baseline to Month 2 in LDL-C.  The primary 
efficacy endpoint will be analyzed using analysis of covariance (ANCOVA), with treatment group as a 
factor and baseline LDL-C as a covariate.  The details of the ANCOVA model and options to correct for 
unequal variances will be described in the SAP.  Baseline LDL-C is defined as the average of S4 and 
Day 1 values, if only 1 value is available, then that single value will be used as baseline.  The ANCOVA 
will be performed using the FAS, with patients included in their randomized treatment group regardless 
of the treatment they actually received.  Patients who are missing their Month 2 LDL-C will have their 
Month 2 value imputed by last observation carried forward (LOCF).  The least squares mean (LSM) and 
standard error (SE) will be provided for both treatment groups, along with the placebo-corrected LSM, its 
95% confidence interval (CI) and associated p-value. 
Secondary and Exploratory Efficacy Endpoints 
Secondary endpoints based on lipid parameters will be analyzed in the similar fashion as for the primary 
endpoint. 
Safety Analyses 
Descriptive summary will be provided for the safety data in this study.   
The subject incidence of all treatment-emergent AEs (TEAE), SAEs, related AEs, AEs leading to 
withdrawal of study drug and/or study, fatal AEs, and AEs of special interest (AESI) will be tabulated by 
system organ class (SOC) and preferred term in descending order of frequency and by treatment group. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 9 of 114 
Clinical safety laboratories, including hematology, blood chemistry, HbA1C, glucose, and urinalysis; PE 
findings; vital signs; and weight will be summarized by the value and by change from baseline in the 
value (where appropriate) at each postbaseline time point. 
Hepatic Safety 
For liver-associated enzymes and TB, the number and percent of patients with abnormal values for ALT, 
AST, and TB will be summarized.  All liver-associated laboratory abnormalities will be assessed for Hy’s 
Law criteria (≥3 × ULN for either ALT or AST, with accompanying TB >2 × ULN in the absence of 
other known causes). 
Musculoskeletal Safety 
AEs of muscle related symptoms will be summarized by treatment group.  In addition, the number and 
percent of patients with abnormal CK values will be summarized.  Finally, muscle-related AEs will be 
summarized by treatment group and by baseline eGFR category. 
Diabetes/Hyperglycemia 
Cases of new onset of diabetes will be recorded as AEs and will be summarized using the appropriate 
SOC.  These events will be summarized by severity and relationship to study drug for each treatment 
group. 
Renal Safety 
Baseline eGFR and values of CK will be summarized by treatment group and by baseline eGFR 
categories.  Shift tables of eGFR category from baseline over the study, will be provided by treatment 
group.   
Neurocognitive Events 
Neurocognitive events will be identified and evaluated by routine safety monitoring of PE findings and 
AEs.  Summarization of neurocognitive events will occur using prespecified Medical Dictionary for 
Regulatory Activities (MedDRA) terms and will be performed by treatment group. 
 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
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Page 10 of 114 
TABLE OF CONTENTS 
1. 
TITLE PAGE ................................................................................................................1 
2. 
SYNOPSIS ...................................................................................................................2 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................15 
4. 
INTRODUCTION ......................................................................................................19 
4.1. 
Overview of the Disease Under Study ........................................................................19 
4.2. 
Background on Bempedoic Acid ................................................................................19 
4.2.1. 
Mechanism of Action .................................................................................................19 
4.2.2. 
Nonclinical Experience ...............................................................................................20 
4.2.3. 
Previous Human Experience .......................................................................................21 
4.2.4. 
Dose Selection ............................................................................................................22 
4.2.5. 
Background Therapy ..................................................................................................22 
4.2.6. 
Risk Benefit Summary ................................................................................................22 
5. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................23 
5.1. 
Study Objectives .........................................................................................................23 
5.1.1. 
Primary Objective .......................................................................................................23 
5.1.2. 
Secondary Objectives .................................................................................................23 
5.1.3. 
Exploratory Objectives ...............................................................................................23 
5.1.4. 
Primary Endpoint ........................................................................................................23 
5.1.5. 
Secondary Endpoints ..................................................................................................23 
5.1.6. 
Exploratory Endpoints ................................................................................................23 
6. 
INVESTIGATIONAL PLAN .....................................................................................25 
6.1. 
Overall Study Design ..................................................................................................25 
6.2. 
Study Hypothesis ........................................................................................................26 
6.3. 
Study Duration and Period ..........................................................................................26 
6.4. 
End of Study ...............................................................................................................26 
6.5. 
Number of Patients .....................................................................................................26 
6.6. 
Patient Identification Numbers ...................................................................................26 


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6.6.1. 
Screening and 1 Month PCSK9i Run-in Period .........................................................27 
6.6.2. 
Randomization and Treatment Period ........................................................................27 
7. 
SELECTION AND WITHDRAWAL OF PATIENTS ..............................................28 
7.1. 
Subject Inclusion Criteria ...........................................................................................28 
7.2. 
Subject Exclusion Criteria ..........................................................................................28 
7.3. 
Investigator/Sponsor Suspension or Termination of Patient Enrollment ...................31 
8. 
TREATMENT OF PATIENTS ..................................................................................32 
8.1. 
Description of Investigational Medicinal Product ......................................................32 
8.2. 
Concomitant Medications ...........................................................................................32 
8.2.1. 
Prohibited Lipid-Regulating Medications and Dietary Supplements .........................33 
8.2.2. 
Allowable Medications ...............................................................................................33 
8.3. 
Blinding ......................................................................................................................33 
8.4. 
Overdose .....................................................................................................................34 
9. 
INVESTIGATIONAL MEDICINAL PRODUCT .....................................................35 
9.1. 
Investigational Medicinal Product Supply and Control ..............................................35 
9.2. 
Administration of Investigational Medicinal Product ................................................35 
9.3. 
Investigational Medicinal Product Accountability .....................................................36 
9.4. 
Investigational Medicinal Product Handling and Disposal ........................................36 
10. 
STUDY PROCEDURES ............................................................................................37 
10.1. 
Informed Consent .......................................................................................................37 
10.2. 
Procedures and Schedule of Assessments ..................................................................37 
10.2.1. 
Screening Month -4.5 (Visit S1) .................................................................................37 
10.2.2. 
PCSK9i Run-in Month -3 (Visit S2) ..........................................................................38 
10.2.3. 
PCSK9i Run-in Month -2 (Visit S3) ..........................................................................39 
10.2.4. 
PCSK9 Run-in Month -1 (Visit S4)............................................................................39 
10.2.5. 
Treatment Week 0 (Visit T1; Day 1) ..........................................................................39 
10.2.6. 
Treatment Month 1 (Visit T2 ±3 days) .......................................................................40 
10.2.7. 
Treatment Month 2 (Visit T3 ±3 days)/EOS ..............................................................41 


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10.3. 
Subject Withdrawal Criteria .......................................................................................42 
10.3.1. 
Early Withdrawal from the Study ...............................................................................42 
10.3.2. 
Procedures for Early Withdrawal ...............................................................................42 
11. 
ASSESSMENT OF SAFETY .....................................................................................44 
11.1. 
Safety Parameters .......................................................................................................44 
11.1.1. 
Demographic/Medical History ...................................................................................44 
11.1.2. 
Vital Signs ..................................................................................................................44 
11.1.3. 
Weight, Height, and Body Mass Index .......................................................................44 
11.1.4. 
Physical Examination .................................................................................................45 
11.1.5. 
Clinical Laboratory Tests ...........................................................................................45 
11.1.5.1. 
Laboratory Parameters (Safety) ..................................................................................45 
11.1.5.2. 
Clinical Laboratory Tests (PK) ...................................................................................47 
11.1.5.3. 
Sample Collection, Storage, and Shipping .................................................................47 
11.1.5.4. 
General Monitoring and Management of Abnormal Clinical Labs ............................47 
11.1.5.5. 
Monitoring and Management of Potential Hypoglycemia and Metabolic 
Acidosis ......................................................................................................................50 
12. 
ADVERSE AND SERIOUS ADVERSE EVENTS ...................................................51 
12.1. 
Adverse Events ...........................................................................................................51 
12.1.1. 
Definition of Adverse Events .....................................................................................51 
12.1.2. 
Adverse Drug Reaction ...............................................................................................51 
12.1.3. 
Reporting for Adverse Events ....................................................................................51 
12.1.4. 
Severity .......................................................................................................................53 
12.1.5. 
Relationship ................................................................................................................53 
12.1.6. 
Monitoring and Follow-up of Adverse Events ...........................................................53 
12.1.7. 
Treatment-Emergent Adverse Events .........................................................................54 
12.2. 
Serious Adverse Events ..............................................................................................54 
12.2.1. 
Definition of Serious Adverse Event ..........................................................................54 
12.2.2. 
Reporting Serious Adverse Events .............................................................................55 


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12.2.3. 
Reporting of Patient Death .........................................................................................56 
12.2.4. 
Reports of Pregnancy and Lactation ...........................................................................56 
12.3. 
Adverse Events of Special Interest .............................................................................56 
12.4. 
Data Monitoring Committee .......................................................................................57 
12.5. 
Assessment of Lipid Endpoints ..................................................................................57 
12.5.1. 
Lipid Parameters .........................................................................................................57 
12.5.2. 
Clinical Laboratory Tests (Lipids) ..............................................................................57 
13. 
STATISTICS ..............................................................................................................59 
13.1. 
General Considerations ...............................................................................................59 
13.2. 
Determination of Sample Size ....................................................................................59 
13.3. 
Analysis Populations ..................................................................................................59 
13.4. 
Disposition, Demographics, and Baseline Characteristics .........................................59 
13.5. 
Primary Endpoint ........................................................................................................59 
13.6. 
Secondary and Exploratory Efficacy Endpoints .........................................................60 
13.7. 
Safety Endpoints .........................................................................................................60 
13.8. 
Pharmacokinetics ........................................................................................................61 
14. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.........................................62 
14.1. 
Study Monitoring ........................................................................................................62 
14.2. 
Audits and Inspections ................................................................................................62 
15. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................63 
16. 
ETHICS ......................................................................................................................64 
16.1. 
Institutional Review Board/Independent Ethics Committee Approval ......................64 
16.2. 
Ethical Conduct of the Study ......................................................................................64 
16.3. 
Written Informed Consent ..........................................................................................65 
16.4. 
Patient Confidentiality ................................................................................................65 
17. 
DATA HANDLING AND RECORDKEEPING .......................................................66 
17.1. 
Inspection of Records .................................................................................................66 
17.2. 
Retention of Records ..................................................................................................66 


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17.3. 
Case Report Forms and Study Records ......................................................................66 
18. 
ADMINISTRATIVE CONSIDERATIONS ..............................................................68 
18.1. 
Investigators ................................................................................................................68 
18.2. 
Amendments ...............................................................................................................69 
18.3. 
Financial Disclosure ...................................................................................................69 
19. 
PUBLICATION AND DISCLOSURE POLICY .......................................................70 
20. 
LIST OF REFERENCES ............................................................................................71 
21. 
APPENDICES ............................................................................................................72 
APPENDIX 1. SCHEDULE OF EVENTS (SUBJECT VISIT SCHEDULE) ...........................73 
APPENDIX 2. SPONSOR’S SIGNATURE ...............................................................................76 
APPENDIX 3. INVESTIGATOR’S SIGNATURE....................................................................78 
APPENDIX 4. SUMMARY OF CHANGES IN AMENDMENT 1 ..........................................79 
 
LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................15 
Table 2: 
Investigational Medicinal Products ............................................................................32 
Table 3: 
Clinical Laboratory Parameters (Safety) ....................................................................46 
Table 4: 
Clinical Laboratory Parameters (Lipids) and Cardiometabolic Biomarkers ..............58 
 
LIST OF FIGURES 
Figure 1. 
Study 1002-039 Study Design ....................................................................................26 
 
 


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3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 1: 
Abbreviations and Specialist Terms  
Abbreviation or Specialist Term 
Explanation 
ACL 
Adenosine triphosphate-citrate lyase 
ADR 
Adverse drug reaction 
AE 
Adverse event 
AESI 
Adverse events of special interest 
ALB 
Albumin 
ALK-P 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
ApoB 
Apolipoprotein B 
ASCVD 
Atherosclerotic cardiovascular diseases 
AST 
Aspartate aminotransferase 
ATP 
Adenosine triphosphate 
AUC 
Area under the concentration-time curve 
AUC0-24 
Area under the curve during 24 hours 
BMI 
Body mass index 
BP 
Blood pressure 
BUN 
Blood urea nitrogen 
Ca 
Calcium 
CD 
Cerebrovascular disease 
CETP 
Cholesterol ester transfer protein 
CFR 
Code of Federal Regulations 
CHD 
Coronary heart disease 
CI 
Confidence interval 
CK 
Creatine kinase 
Cl 
Chloride 
Cmax 
Time to peak maximum concentrations 
CNS 
Central nervous system 
CoA 
Acetyl-coenzyme A 
CO2 
Carbon dioxide 
CRO 
Contract research organization 
CV 
Cardiovascular 


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Abbreviation or Specialist Term 
Explanation 
CVD 
Cardiovascular disease 
CYP 
Cytochrome P450 
DBP 
Diastolic blood pressure 
DMC 
Data Monitoring Committee 
eCRF 
Electronic case report form 
eGFR 
Estimated glomerular filtration rate 
EMA 
European Medicines Agency 
EOS 
End of Study 
ETC-1002 
Bempedoic acid 
EU 
European Union 
FAS 
Full analysis set 
FBG 
Fasting blood glucose 
FDA 
Food and Drug Administration 
FPFV 
First patient first visit 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GI 
Gastrointestinal 
HbA1C 
Glycosylated hemoglobin, Type A1C 
HBsAg 
Hepatitis B surface antigen 
Hct 
Hematocrit 
HCV 
Hepatitis C virus 
HCV-AB 
Hepatitis C antibodies 
HeFH 
Heterozygous familial hypercholesterolemia 
Hgb 
Hemoglobin 
HMG-CoA 
3-hydroxy-3-methylglutaryl-coenzyme A 
HoFH 
Homozygous familial hypercholesterolemia 
hs-CRP 
High-sensitivity C-reactive protein 
IB 
Investigator’s Brochure 
ICD 
Informed Consent Document 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IMP 
Investigational medicinal product 
IND 
Investigational New Drug Application 
INR 
International normalized ratio 
IRB 
Institutional Review Board 


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Abbreviation or Specialist Term 
Explanation 
IWRS 
Interactive web response system 
K 
Potassium 
LDH 
Lactate dehydrogenase 
LDL-C 
Low-density lipoprotein cholesterol 
LDLR 
LDL receptor 
LFT 
Liver function test 
LOCF 
Last observation carried forward 
LPLV 
Last patient last visit 
LS 
Least square 
LSM 
Least square mean 
MCH 
Mean corpuscular hemoglobin 
MCHC 
Mean corpuscular hemoglobin concentration 
MCV 
Mean corpuscular volume 
MDRD 
Modification of diet in renal disease 
MED ID 
Medication identification 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
Modified intent-to-treat 
MRI 
Magnetic resonance imaging 
Na 
Sodium 
NA 
Not applicable 
NLA 
National Lipid Association 
NOAEL 
No-observed-adverse-effect level 
non-HDL-C 
Non-high-density lipoprotein cholesterol 
PAD 
Peripheral arterial disease 
PCSK9 
Proprotein convertase subtilisin/kexin type 9 
PCSK9i 
PCSK9 inhibitor 
PE 
Physical examination 
PK 
Pharmacokinetic(s) 
PT 
Prothrombin time 
QM 
Once monthly 
RBC 
Red blood cell 
RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SBP 
Systolic blood pressure 


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Abbreviation or Specialist Term 
Explanation 
SE 
Standard error 
SGOT 
Serum glutamic oxaloacetic transaminase 
SGPT 
Serum glutamic pyruvic transaminase 
SOC 
System organ class 
SOP 
Standard operating procedures 
SP 
Safety population 
SUSARS 
Suspected and unexpected serious adverse reactions 
t½  
Terminal elimination half-live 
T2DM 
Type 2 diabetes mellitus 
TB 
Total bilirubin 
TC 
Total cholesterol 
TEAE 
Treatment-emergent adverse event 
TG 
Triglycerides 
TSH 
Thyroid-stimulating hormone 
TQT 
Thorough QT/QTc 
ULN 
Upper limit of normal 
US 
United States 
WBC 
White blood cell 
WHO 
World Health Organization 


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4. 
INTRODUCTION 
4.1. 
Overview of the Disease Under Study  
Bempedoic acid (ETC-1002) is an inhibitor of adenosine triphosphate-citrate lyase (ACL) 
(adenosine triphosphate [ATP] citrate lyase), an enzyme upstream of 3-hydroxy-3-methylglutaryl 
coenzyme A (HMG-CoA) reductase in the cholesterol biosynthesis pathway.  It is an oral first-
in-class small molecule designed to lower low-density lipoprotein cholesterol (LDL-C) levels in 
patients with high cardiovascular (CV) risk unable to meet their treatment goals with currently 
available lipid-lowering therapies. 
Proprotein convertase subtilisin kexin type 9 (PCSK9) reduces LDL receptor recycling to the 
hepatic surface, thereby limiting removal of LDL particles from the circulation.  Monoclonal 
antibodies neutralize PCSK9 and reduce LDL-C levels when administered alone or in 
combination with other background therapies.   
Elevated LDL-C is a major modifiable risk factor for the development of atherosclerosis and 
atherosclerotic cardiovascular diseases (ASCVD) (Sharrett 2001).  Despite aggressive 
interventional and pharmacologic therapies, CV disease is the number 1 cause of death globally 
(WHO 2015).  An estimated 17.5 million people died from CV diseases in 2012, representing 
31% of all global deaths. Of these deaths, an estimated 7.4 million were due to coronary heart 
disease (CHD) and 6.7 million were due to stroke (WHO 2015). Cardiovascular disease remains 
the leading cause of death among Europeans, Americans, and around the world.  The Global 
Burden of Disease study estimated that 29.6% of all deaths worldwide (approximately 
15.6 million deaths) were caused by CV disease in 2010, more than all communicable, maternal, 
neonatal and nutritional disorders combined, and double the number of deaths caused by cancers 
(Nichols 2014).  In the United States (US), based on 2011 death rate data, more than 
2150 Americans die from CV diseases daily, an average of 1 death every 40 seconds.  
Approximately 155,000 Americans dying from CV disease are less than 65 years of age.  In 
2011, 34% of deaths due to CV disease occurred prior to the age of 75 years, less than the 
current 78.7-year average life expectancy (Mozffarian 2015). As such new therapies to combat 
this global public health problem are needed. 
Global guidelines recommend lowering of LDL-C to levels below 100 mg/dL and often under 
70 mg/dL (Jacobson 2014) or reduction of ≥50% (Stone 2013).  In order to reach these goals, 
lipid-lowering therapies are often taken in combination.  The combination of bempedoic acid and 
a PCSK9 inhibitor (PCSK9i) may offer an additional treatment option in the future for 
physicians. 
4.2. 
Background on Bempedoic Acid 
4.2.1. 
Mechanism of Action 
Bempedoic acid is a first-in-class small molecule inhibitor of ACL, an enzyme upstream of 
HMG-CoA in the cholesterol biosynthesis pathway.  Bempedoic acid is a prodrug that requires 
activation in liver to ETC-1002-co-enzyme A (ETC-1002-CoA), which mediates competitive 


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inhibition of ACL.  Inhibition of ACL by ETC-1002-CoA decreases cholesterol synthesis in liver 
leading to increased LDL receptor (LDLR) expression and LDL particle clearance from the 
blood.  Therefore, inhibition of ACL by ETC-1002-CoA reduces LDL-C via the same pathway 
as HMG-CoA reductase inhibition by statins. 
An important differentiating feature of bempedoic acid is that it does not inhibit cholesterol 
synthesis in skeletal muscle.  In addition to preliminary data suggesting that only minor amounts 
of bempedoic acid enter skeletal muscle (<5% of systemic exposure), skeletal muscle does not 
express the enzyme required to activate bempedoic acid to ETC-1002-CoA and inhibit ACL.  
Therefore, bempedoic acid is not anticipated to mediate the adverse effects associated with 
inhibition of biological intermediates within the cholesterol biosynthesis pathway in skeletal 
muscle.  The long-term safety of bempedoic acid and its metabolites regarding human skeletal 
muscle is not yet established.   
4.2.2. 
Nonclinical Experience 


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4.2.3. 
Previous Human Experience 


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4.2.4. 
Dose Selection 
4.2.5. 
Background Therapy 
Bempedoic acid in this study is currently being evaluated as an add-on to PCSK9i therapy.  
4.2.6. 
Risk Benefit Summary 
To date, the nonclinical and clinical data indicate that bempedoic acid has a favorable risk-
benefit profile.  The ability of bempedoic acid to achieve clinically meaningful LDL-C-lowering 
responses while demonstrating a favorable tolerability profile in a variety of patient populations 
supports continued development of bempedoic acid, an oral ACL inhibitor, in Phase 3 studies. 
Please refer to the most recent IB for additional information regarding previous human 
experience. 


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5. 
TRIAL OBJECTIVES AND PURPOSE 
5.1. 
Study Objectives 
5.1.1. 
Primary Objective 
• To assess the 2-month efficacy of bempedoic acid 180 mg/day vs placebo in the 
reduction of LDL-C in patients on PCSK9i therapy 
5.1.2. 
Secondary Objectives 
• To assess the 1-month efficacy of bempedoic acid 180 mg/day vs placebo in the 
reduction of LDL-C in patients on PCSK9i therapy 
• To evaluate the effect of bempedoic acid 180 mg/day vs placebo on apolipoprotein B 
(ApoB), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol 
(TC), and high-sensitivity C-reactive protein (hs-CRP) after 1 and 2 months in 
patients on PCSK9i therapy 
• To evaluate the safety and tolerability of bempedoic acid 180 mg/day compared to 
placebo in patients on PCSK9i therapy 
5.1.3. 
Exploratory Objectives 
5.1.4. 
Primary Endpoint 
The primary efficacy endpoint for this study is the percent change from baseline to Month 2 in 
LDL-C. 
5.1.5. 
Secondary Endpoints 
• Percent change from baseline to Month 1 in LDL-C 
• Change from baseline to Months 1 and 2 in LDL-C 
• Percent change from baseline to Months 1 and 2 in ApoB, non-HDL-C, TC, and 
hs-CRP  
• Safety and tolerability of bempedoic acid in this patient population over 2 months, as 
assessed by AEs and clinical laboratory values 
5.1.6. 
Exploratory Endpoints 


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6. 
 
INVESTIGATIONAL PLAN 
6.1. 
Overall Study Design 
This is a Phase 2, randomized, double-blind, placebo-controlled, parallel group multicenter study 
that will be conducted at approximately 20 clinical sites in North America.  Screening 
Month -4.5 (Visit S1) will occur approximately 18 weeks prior to randomization.  After 
providing informed consent at Visit S1, patients will stop all background lipid-lowering therapy 
and lipid-modifying nutritional supplements, if applicable.  All patients will return to the clinic 
on Month -3 (Visit S2).  During this visit, patients with an LDL-C value ≥160 mg/dL (via central 
or local lab) and triglycerides <500 mg/dL (via central or local lab) will initiate PCSK9 
background therapy (Repatha 420 mg once montly [QM]).  Sites that do not use a local lab may 
need to bring patients back for another visit to administer PCSK9 background therapy, as a 
qualifying LDL value is required prior to initiating the 3-month PCSK9i run-in period.  No other 
background lipid-modifying therapy except study provided PCSK9i will be permitted during the 
trial.  After 1 month (at least 30 ± 3 days), patients will return to the clinic for Month -2 
(Visit S3) followed by Month -1 (Visit S4) 30 ± 3 days later.  During these visits, Repatha will 
be administered, labs will be collected, and safety assessed.  At Visit S4, LDL-C will be checked 
a second time prior to randomization.  Patients with an LDL-C ≥70 mg/dL (via central lab only) 
at this visit will qualify for randomization.  Patients with LDL-C <70 mg/dL at Visit S4 will be 
screen failed and no further PCSK9i therapy will be administered.  Day 1 should occur 30 days ± 
3 days after Visit S4, once LDL-C eligibility is established.  On Day 1, qualified patients will be 
randomized 1:1 to bempedoic acid 180 mg/day (n = 26) or matching placebo (n = 26).  
Randomized patients will return for clinic visits at Month 1 (Visit T2) and Month 2 (Visit T3).  
Both study drug and PCSK9i doses will be administered on site during clinic visits after all 
procedures have been completed.   
An independent expert Data Monitoring Committee (DMC) will formally review accumulating 
unblinded safety and efficacy data across the bempedoic acid program.  


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6.6.1. 
Screening and 1 Month PCSK9i Run-in Period  
Screening will occur approximately 18 weeks prior to Day 1 (Visit T1).  Eligible patients will 
return to the clinical site at Month -3 (Visit S2).  During this visit, patients with an LDL-C value 
≥160 mg/dL (via central or local lab) and triglycerides <500 mg/dL (via central or local lab) will 
initiate study-provided PCSK9i background therapy (Repatha 420 mg QM).  No other 
background lipid-modifying therapy except study provided PCSK9i will be permitted during the 
trial.  
Patients who are deemed not eligible for randomization at any point during screening will be 
notified by clinical site personnel regarding their eligibility status and considered screen failures.  
As necessary, for reasons of safety if a patient begins the run-in period but screen fails prior to 
randomization, the patient may be asked to return to the clinical site for further evaluation and 
follow-up of AEs. 
6.6.2. 
Randomization and Treatment Period 
Patients who satisfy all entry criteria, complete the 1.5-month screening period and 3-month 
PCSK9i run-in period, and have an LDL-C ≥70 mg/dL at S4 will be randomized.  
Randomization numbers will be assigned via IWRS on Day 1 (Visit T1).  Patients will be 
randomized in a ratio of 1:1 to receive 1 of the following 2 treatments in a double-blind fashion 
in addition to monthly PCSK9i background therapy: 
• Bempedoic acid 180-mg tablet 
• Matching placebo tablet 


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7. 
SELECTION AND WITHDRAWAL OF PATIENTS 
7.1. 
Subject Inclusion Criteria 
1. Provision of written informed consent must be obtained prior to any study-specific 
procedure. 
2. Age ≥18 years or legal age of majority depending on regional law, whichever is greater at 
Month -4.5 (Visit S1) 
3. Fasting, calculated LDL-C at screening ( Visit S2) ≥160 mg/dL and ≥70 mg/dL at 
Visit S4 
Note:  A single repeat of LDL-C may be completed.  For those patients who have a repeat 
LDL-C, the average of the 2 values will be used to determine eligibility. 
4. Men and nonpregnant, nonlactating women.  Women must be: 
a. Naturally postmenopausal defined as ≥1 year without menses and:  
−  
≥55 years, or  
−  
<55 years with follicle-stimulating hormone (FSH) ≥40.0 IU/L; or 
b. Surgically sterile including hysterectomy, bilateral oophorectomy, and/or tubal 
ligation; or 
c. Women of childbearing potential willing to use 2 acceptable methods of birth control 
including: 
− oral, implanted, topical or injectable birth control medications 
− placement of an intrauterine device with or without hormones 
− barrier methods including condom or occlusive cap with spermicidal foam or 
spermicidal jelly 
− vasectomized male partner who is the sole partner for this patient  
− true abstinence:  when this is in line with the preferred and usual lifestyle of the 
subject.  (Periodic abstinence [eg, calendar, ovulation, symptothermal, 
postovulation methods], declaration of abstinence for the duration of a trial, and 
withdrawal are not acceptable methods of contraception.) 
There are no protocol-specific birth control requirements for men with partners who are 
able to become pregnant. 
7.2. 
Subject Exclusion Criteria 
Patients who meet any of the following criteria will not be randomized: 
1. Homozygous Familial Hypercholesterolemia (HoFH) 


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2. Total fasting TG ≥500 mg/dL (5.6 mmol/L) at Month -3 (Visit S2) 
Note:  A single repeat of TG may be completed prior to initiation of the single-blind Run-
in period.  For those patients who have a repeat TG, the average of the 2 values will be 
used to determine eligibility. 
3. Renal dysfunction or a glomerulonephropathy defined as either nephritic or nephrotic 
syndrome, including estimated glomerular filtration rate (eGFR; using central laboratory 
determined Modification of Diet in Renal Disease [MDRD] formula) 
<30 mL/min/1.73 m2 at Month -4.5 (Visit S1) 
Note:  A single repeat of eGFR may be completed prior to randomization.  For those 
patients who have a repeat eGFR, the average of the 2 values be used to determine 
eligibility. 
4. All patients with known cardiovascular disease (CVD) or peripheral arterial disease 
(PAD) or cerebrovascular disease (CD) 
5. History of type 1 or type 2 diabetes or laboratory evidence of diabetes (fasting blood 
glucose [FBG] >126 mg/dL or glycosylated hemoglobin, Type A1C (HbA1C) >6.5%) 
without prior diagnosis of diabetes at Month -4.5 (Visit S1) 
6. Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) >160 mmHg 
or diastolic blood pressure (DBP) >100 mmHg at Month -4.5 (Visit S1) 
7. Uncontrolled hypothyroidism, including thyroid-stimulating hormone (TSH) >1.5 × the 
upper limit of normal (ULN) at Month -4.5 (Visit S1) 
8. Liver disease or dysfunction, including: 
a. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≥2.0 × 
ULN at Month -4.5 (Visit S1). 
b. Positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C 
antibodies (HCV-ABVivi) at Month -4.5 (Visit S1). 
Note:  If total bilirubin (TB) ≥1.2 × ULN, a reflex indirect (unconjugated) bilirubin 
will be obtained and if consistent with Gilbert’s disease, the patient may be enrolled 
in the study.   
Note: At the discretion of the investigator, a single repeat of ALT and/or AST may be 
completed.  For those patients who have a repeat ALT and/or AST, the average of the 
2 values will be used to determine eligibility.  Also, if test for hepatitis C antibody is 
positive, but reflexive test for Hepatitis C ribonucleic acid (RNA) is negative, patient 
can be enrolled.  
9. Gastrointestinal conditions or procedures (including weight loss surgery; eg, Lap-Band® 
or gastric bypass) that may affect drug absorption 
10. History of hematologic or coagulation disorders or a hemoglobin (Hgb) level <10 g/dL at 
Month -4.5 (Visit S1) 
11. History of malignancy (except non-metastatic basal or squamous cell carcinoma of the 
skin and cervical carcinoma in situ) 


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12. Unexplained creatine kinase (CK) >3 × ULN at screening up to randomization (ie, not 
associated with recent trauma or physically strenuous activity).  Patients with an 
explained CK elevation must have single repeat CK ≤3 × ULN prior to randomization. 
13. History within the last 2 years of drug, alcohol, amphetamine and derivatives, or cocaine 
abuse.  Patients taking  amphetamine derivatives for medical reasons such as attention 
deficit disorder or taking prescription opioids or other meds for chronic pain that have 
been stable, without evidence of abuse prescribed by and under the care of a health care 
practitioner can be enrolled after evaluation by the Investigator. 
14. Blood donation, participation in a clinical study with multiple blood draws, major trauma, 
blood transfusion, or major surgery with or without blood loss within 30 days prior to 
randomization 
15. Use of any experimental or investigational drugs within 30 days or 5 half-lives, 
whichever is longer 
16. Previous enrollment in an Esperion Phase 3 bempedoic acid (ETC-1002) clinical study 
17. Use of a cholesterylester transfer protein (CETP) inhibitor in the last 12 months prior to 
screening, such as: anacetrapib, dalcetrapib or evacetrapib 
18. Use of, or a plan to initiate, these prohibited therapies/supplements during the study: 
• Mipomersen (must be stopped at least 6 months prior to Month -4.5 [Visit S1]), 
• Lomitapide or apheresis therapy (must be stopped at least 3 months prior to 
Month -4.5 [Visit S1]),  
• Red yeast rice containing products (must be stopped on or before Month -4.5 
[Visit S1]),  
• Lipid regulating drugs or supplements (must be stopped on or before Month -4.5 
[Visit S1]) 
19. Planned initiation or changes to the following drugs prior to Month -4.5: 
• Hormone replacement (6 weeks prior to Month -4.5) 
• Thyroid replacement (6 weeks prior to Month -4.5) 
• Obesity medication (3 months prior to Month -4.5) 
20. A medical or situational (ie, geographical) finding that in the investigator’s opinion may 
compromise the patient’s safety or ability to complete the study 
21. Patient is pregnant or breast feeding, or planning to become pregnant during treatment 
and/ or within 30 days after the end of treatment 
22. An employee or contractor of the facility conducting the study, or a family member of the 
Principal Investigator, Co-Investigator, or Sponsor. 
23. Heterozygous familial hypercholesterolemia (HeFH) 
24. Concomitant use of a PCSK9 inhibitor (Praluent® [alirocumab] or Repatha® 
[evolocumab]) at (Visit S1) or prior use within the past 16 weeks of Visit S1 


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7.3. 
Investigator/Sponsor Suspension or Termination of Patient 
Enrollment 
If, in the opinion of the Investigator, the clinical observations in the study suggest that it may be 
unwise to continue, the Investigator may suspend or terminate the study after consultation with 
the Sponsor (or designee).  A written statement fully documenting the reasons for such a 
termination will be provided to the Sponsor (or designee) and the Institutional Review Board 
(IRB) or Independent Ethics Committee (IEC).  
The Sponsor has the right to terminate the study or to close a site and remove all study materials 
from the clinical site. A written statement will be provided to the Investigator, the IRB or IEC, 
and regulatory authorities, if required.  
Possible reasons for termination of the study at a clinical site include, but are not limited to: 
• Unsatisfactory enrollment with respect to quantity or quality 
• Inaccurate or incomplete data collection on a chronic basis 
• Falsification of records 
• Failure to adhere to the protocol 
• Lack of study oversight by the Principal Investigator and/or designee 
If any serious or nonserious AEs have occurred at such a clinical site, all documentation relating 
to the event(s) must be obtained. 


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8. 
TREATMENT OF PATIENTS 
8.1. 
Description of Investigational Medicinal Product 
Table 2: 
Investigational Medicinal Products 
Product Name: 
Bempedoic acid 
Placebo to Match Bempedoic Acid 
Dosage Form: 
Film-coated tablets 
Film-coated tablets 
Unit Dose: 
180 mg 
Not applicable 
Container/Closurea 
35-count bottle with screw on 
childproof cap 
35-count bottle with screw on 
childproof cap 
Route of Administration: 
Oral, daily at approximately the 
same time, with or without food 
Oral, daily at approximately the same 
time, with or without food 
Physical Description: 
Manufacturer 
(Fill/Finish): 
 
Study drug should be taken once a day (once every 24 hours) at approximately the same time 
every day and may be taken with or without food.  Patients will fast for a minimum of 10 hours 
prior to collection of all laboratory samples. 
Please see Pharmacy Manual for detailed storage requirements and instructions. 
8.2. 
Concomitant Medications 
Patients will be questioned about their concomitant medication use at each clinic visit.  All 
concomitant medication taken chronically or intermittently during the study must be recorded 
with indication, total daily dose, and start and stop dates of administration.  
The Prior/Concomitant electronic case report form (eCRF) will be used to record medications, 
herbal remedies, vitamins, other supplements, and over-the-counter medications taken within 
3 months prior to screening and during the study.  


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8.2.1. 
Prohibited Lipid-Regulating Medications and Dietary Supplements 
• Patients will be required to stop taking all prescription or nonprescription drugs or 
dietary supplements taken for the purpose of lipid regulation at Month -4.5.  With the 
exception of the study provided PCSK9i (Repatha 420 mg QM), no other lipid-
modifying therapies or supplements will be permitted. 
8.2.2. 
Allowable Medications 
• Hormone replacement (if stable 6 weeks prior to Month -4.5) 
• Thyroid replacement (if stable 6 weeks prior to Month -4.5) 
• Obesity medication (if stable 3 months prior to Month -4.5) 
8.3. 
Blinding 
Patients who satisfy all entry criteria during the screening phase and complete the PCSK9i run-in 
period will be randomized to a treatment group at Day 1 (Visit T1).  The Investigator or designee 
will contact IWRS at this visit to randomize the patient into the study.  The IWRS will determine 
the randomized treatment assignment number and the appropriate study drug container via 
medication identification numbers (MED ID).  A patient is considered to be randomized when 
they have been assigned a MED ID number by IWRS. 
After patients have been randomized, study drug, which is assigned by the IWRS, will be 
administered in a double-blind fashion.  The Sponsor, all clinical site personnel (Investigator, 
pharmacist, etc), and other vendor personnel will be blinded to the treatment group for each 
patient.  Patients will also be blinded to the treatment they receive.  Unblinded User(s) will be 
designated for each clinical site and at the sponsor (or designee) as needed.  Unblinded 
individuals will be provided IWRS access allowing them the ability to perform emergency 
unblinding of treatment for an individual patient.  An affirmative entry of the user’s login details 
will be required before the treatment group is displayed.  Unblinding at the clinical site for any 
other reason will be considered a protocol deviation.  Unblinded treatments for patients will 
NOT automatically discontinue the patient from the study.  To discontinue the patient from the 
study, the appropriate clinical site personnel will need to register the ‘discontinuation’ visit 
separately.  
Blinding of treatment must be maintained for all patients unless, in the opinion of the 
Investigator, the safety of the patient may be at risk.  Only under the rarest of circumstances 
should the Investigator consider breaking the blind and only when medical/supportive care 
cannot be provided without determining if the patient is receiving active drug treatment.  In the 
event that the blind needs to be broken prior to completion of the study, the Investigator should 
contact the appropriate Medical Monitor by telephone.  If the blind must be broken prior to 
consultation with the Medical Monitor, contact must be made within 24 hours of breaking the 
blind.  At the initiation of the study, the clinical site will be instructed on procedures for breaking 
the blind via the IWRS.  In all cases of breaking the blind, the Investigator must document in the 
patient’s medical record the date, time, and reason for breaking the blind, and the names of 
personnel involved.  


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Limited vendors (ie, the bioanalytical laboratory and other vendor personnel, if any, that are 
responsible for PK analysis) will have access to the randomization codes to facilitate PK 
analytical work, and will be instructed to not communicate in any manner information associated 
with treatment assignment to any personnel at the clinical site, the Sponsor, or contract research 
organization (CRO).  
Post-randomization values for individual laboratory measures for LDL-C,
TC,
non-HDL, ApoB,
and hs-CRP, including any plasma concentration of bempedoic acid and 
its metabolite that may inadvertently suggest treatment assignment will not be available to 
personnel from the clinical site, the patient, the Sponsor, and CRO. 
An independent DMC will monitor unblinded accumulating patient safety and efficacy data until 
the last patient has completed study treatment.  In addition, data on SAEs and deaths will be 
monitored by the DMC during this period.  At each DMC review, relevant unblinded safety and 
efficacy information from ongoing studies will be provided to the DMC by an independent, 
unblinded
programmer and statistician.  Additional details will be provided in a DMC 
Charter. 
8.4. 
Overdose 
There is no specific antidote for an overdose of bempedoic acid.  Management of an overdose 
should be focused on the treatment of symptoms.  These symptoms should be managed 
according to current standards of care with appropriate supportive measures.  Also 
discontinuation of study drug should be considered, based on medical judgement. 


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9. 
INVESTIGATIONAL MEDICINAL PRODUCT  
9.1. 
Investigational Medicinal Product Supply and Control 
The Sponsor will supply the investigational medicinal product (IMP) for this study.  The IMP for 
this study includes bempedoic acid (180-mg film-coated tablets) and matching placebo (film-
coated tablets).  IMP will be distributed and released in accordance with regional and local 
requirements during the conduct of the study. 
PCSK9i will be provided as background therapy.  This will be dispensed and administered 
during clinic visits and will be stored and taken as commercially labeled.   
The MED ID number (an identifier on the study drug packaging) will be obtained via IWRS and 
used to select PCSK9i and double-blind IMP for the treatment period from available clinical 
supplies at the clinical site.  
Double-blind IMP will be dispensed in 35-day supply increments to patients by appropriate 
clinical site personnel.  Patients will receive one 35-day supply bottle at Day 1 (Visit T1) and at 
Month 1 (Visit T2).  
Please see Pharmacy Manual for detailed storage requirements and management instructions. 
9.2. 
Administration of Investigational Medicinal Product 
Patients will be instructed to ingest IMP starting at Visit T1 for the duration of treatment period 
orally once daily (once every 24 hours) at approximately the same time each day with water.  
IMP may be taken with or without food.  On clinic visit days, patients will be instructed to delay 
ingestion of IMP until all study procedures have been completed.  If a patient arrives at clinic on 
Visits T1, T2, or T3 without having fasted or having taken IMP before arriving at the clinic, 
reschedule the visit (the next day or as soon as possible) so that the fasting and dosing 
requirements have been met.  Patients will be instructed to return all packaging and unused IMP 
at each clinic visit.  
If the patient forgets to take IMP at the usual time on nonclinic visit days, it may be taken up to 
12 hours later the same day.  After that time, the patient should not take IMP that day and should 
resume ingestion of IMP the following day.  If a patient fails to take IMP, details describing the 
reasons for nondosing should be documented in the patient’s medical records and eCRF.  Extra 
IMP (7 extra days per bottle) is provided and can be used, if needed, prior to the next visit or to 
replace a dose of IMP that cannot be used because it is lost or damaged. 
PCSK9i will be administered on site at Visits S2, S3, S4, T1, and T2.  Doses will be stored and 
administered as required in prescribing information 


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9.3. 
Investigational Medicinal Product Accountability 
Accurate records of the receipt of all IMP and PCSK9i shipped by the Sponsor (or designee) and 
the disposition of the IMP and PCSK9 must be maintained.  
IMP records or logs must comply with applicable regulations, local law, and guidelines, and 
should include: 
• Amount received/placed in storage area 
• Amount currently in storage area 
• MED ID number for all IMP 
• Dates and initials of person(s) responsible for IMP/PCSK9i inventory (including 
entry/movement/disposition) 
• Date and amount of IMP/PCSK9i dispensed to each patient, including unique patient 
identifiers 
• Date that IMP/PCSK9i was returned by patient, assessment of compliance, and 
relevant documentation of discrepancies 
• Nonstudy disposition (eg, lost, broken, wasted) 
• Amount returned to Sponsor/Sponsor’s designee/destroyed or amount destroyed per 
local standard operating procedure (SOP) following accountability by site monitor. 
9.4. 
Investigational Medicinal Product Handling and Disposal 
Upon completion or termination of the study, all used and unused IMP with the IMP packaging 
must be returned to the Sponsor (or designee) for eventual destruction unless otherwise 
authorized by the Sponsor.  All IMP returns must be accompanied by the appropriate 
documentation. 


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10. 
STUDY PROCEDURES 
10.1. 
Informed Consent 
The patient must be adequately informed of the nature and risks of the study and understand the 
informed consent document (ICD).  No study-related procedure will be performed until the 
patient has been completely informed of the study, has freely consented to take part in the study, 
and has signed and dated an ICD approved by the Sponsor (or designee) and the IRB or IEC.   
10.2. 
Procedures and Schedule of Assessments 
Patients who provide informed consent and sign the ICD will be eligible to begin screening for 
the study.  The study is comprised of 3 distinct periods:  screening, PCSK9i run-in and double-
blind treatment.  
The schedule of study events is provided in Appendix 1.  However, a patient can be seen at any 
time for reasons of safety.  
Data will be captured on eCRFs.  Randomization, drug supply (re)ordering, and patient tracking 
will occur via IWRS.  Instructions for these systems will be provided separately. 
10.2.1. 
Screening Month -4.5 (Visit S1) 
The screening period will begin with a screening visit that will occur approximately 18 weeks 
prior to randomization.  Visit S1 will allow the Investigator to assess the patient’s preliminary 
eligibility.  After the patient provides written informed consent (see Section 10.1), the patient 
will undergo the following assessments and procedures at Visit S1: 
• Demographics 
• Clinically relevant medical history  
• Concomitant and prohibited medication review 
• Height (cm), weight (kg), body mass index (BMI)  
• Vital signs  
• Clinical laboratory evaluations:  
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, 
, non-HDL-C, 
, and 
) 
− HbA1C 
− TSH 
− FSH (in appropriate female patients) 
− Serum pregnancy test (on appropriate female patients) 
• Serology (including HBsAg, Hepatitis C virus [HCV])  


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• Review of all inclusion/exclusion criteria that can be assessed at this time 
• Conduct diet and exercise counseling 
• Contact IWRS to register the patient  
Patients who meet all enrollment criteria that can be assessed following review of the S1 central 
clinical laboratory results (available several days after Visit S1) will be instructed to washout of 
all lipid-regulating drugs and supplements and to maintain consistent diet and exercise patterns 
throughout the study.  Patients who fail to meet any entry criterion that can be assessed at 
Visit S1 are considered to be screen failures and are not required to return for additional visits 
(although a patient can be seen at any time for safety reasons). 
10.2.2. 
PCSK9i Run-in Month -3 (Visit S2) 
Prior to scheduling Visit S2, review the screening clinical results to evaluate whether the patient 
continues to meet eligibility criteria. 
• If the patient meets eligibility criteria, then schedule the Visit S2 and proceed with the 
Visit S2 procedures 
The patient will undergo the following assessments and procedures at (Visit S2) 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs (starting from signing of the informed consent document) 
• Physical examination (PE) 
• Vital signs 
• Basic fasting lipids (TC, calculated LDL-C, 
, non-HDL-C, 
, and 
) 
• ApoB and hs-CRP  
• First PCSK9i monthly injection.  Verification of lipid entry criteria (LDL-C value of 
>160 mg/dL and triglycerides <500 mg/dL) must be obtained before starting PCSK9i 
• Schedule next visit (S3 has to be at least 30 days ± 3 days from the first dose of 
PCSK9)  
− PCSK9i injections must be administered consistently throughout the trial within 
30 ± 3 days from the previous dose.  Efficacy will vary if the doses are not 
consistently administered. 
Note:  Local labs can be used to assess LDL-C and TGs for entry.  All other labs must be 
run via the central lab.  If using a central lab or a local lab with a delay in obtaining 
results, an optional visit to administer PCSK9 may be scheduled.  Patients need to be on 
Repatha 420 mg for at least 30 days ± 3 days before conducting Visit S3. 


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10.2.3. 
PCSK9i Run-in Month -2 (Visit S3) 
Prior to scheduling Visit S3, review the screening clinical results to evaluate whether the patient 
continues to meet eligibility criteria. 
• If the patient continues to meet eligibility criteria, then schedule Visit S3 and proceed 
with Visit S3 procedures 
The patient will undergo the following assessments and procedures at (Visit S3) 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs (starting from signing of the informed consent document) 
• Vital signs 
• Basic fasting lipids (TC, calculated LDL C, 
 non-HDL C, 
, and 
) 
• PCSK9i monthly injection must be given at the end of procedures 
10.2.4. 
PCSK9 Run-in Month -1 (Visit S4)  
One month (30 ± 3 days) from S3, patients will have their LDL-C evaluated a second time via 
central lab only prior to randomization on Day 1. 
The patient will undergo the following assessments and procedures at (Visit S4) 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs (starting from signing of the informed consent document) 
• Vital signs 
• Basic fasting lipids (TC, calculated LDL C, 
, non-HDL C, 
, and 
) 
• Schedule next visit Day 1 (Day 1 should occur 30 ± 3 days after S4, once LDL-C 
eligibility [≥70 mg/dL] is established) 
• PCSK9i monthly injection  must be given at the end of procedures 
10.2.5. 
Treatment Week 0 (Visit T1; Day 1) 
Prior to scheduling Visit T1, review S1, S2, S3, and S4 clinical results to evaluate whether the 
patient continues to meet eligibility criteria. 
• If the patient meets eligibility criteria, then schedule the Visit T1 and proceed with 
the Visit T1 procedures 
If the patient has met all inclusion criteria, none of the exclusion criteria, and has been on 
Repatha 420 mg for 30 ± 3 days during each month of the PCSK9 run-in period, the patient 
may be randomized into the double-blind treatment period.  Patients who fail to meet any entry 
criterion prior to randomization are considered to be screen failures, will not be randomized into 
a treatment group, and are not required to return for additional visits.  Patients are considered 
randomized once all eligibility criteria are confirmed and a randomization number is obtained by 
the IWRS on the day of first dose.  


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The patient will undergo the following assessments and procedures at (Visit T1) 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs (starting from signing of the informed consent document) 
• Weight 
• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
Note:  Urine pregnancy test (for females of childbearing potential) 
− Basic fasting lipids (TC, calculated LDL-C, 
, non-HDL-C, 
, and 
) 
− ApoB and hs-CRP 
− HbA1C  
• Predose PK 
• Review inclusion/exclusion criteria to establish patient eligibility.  Patient must have 
an LDL-C ≥70 mg/dL at S4 before they can be randomized on Day 1. 
• Conduct diet and exercise counseling 
• IWRS contact to obtain the patient randomization number and MED ID number for 
double-blind study drug 
• Dispense IMP and provide dosing instructions (35-day supply bottles) 
− Subject should be randomized and receive IMP within 30 ± 3 days of S4, as 
soon as the final LDL-C entry criterion is met 
• PCSK9i injection and IMP must be given at the end of procedures 
• Schedule next visit 
10.2.6. 
Treatment Month 1 (Visit T2 ±3 days) 
If the patient is withdrawing early from the study at this visit, proceed to Section 10.3.2 for the 
list of the required assessments. 
If the patient is withdrawing from IMP treatment at this visit, proceed to Section 10.3.2 for the 
list of the required assessments.  
Patients will undergo the following assessments and procedures at Month 1 (Visit T2): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs since last visit (ongoing) 
• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 


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− Basic fasting lipids (TC, calculated LDL-C, 
, non-HDL-C, 
, and 
) 
− ApoB and hs-CRP 
• Predose PK.  Should be taken ideally within 4 hours of the patient’s normal time of 
dosing 
• Conduct diet and exercise counseling 
• Return of IMP; assessment and recording of IMP compliance 
• Dispense IMP and provide dosing instructions (35-day supply bottles) 
• PCSK9i injection and IMP must be given at the end of procedures 
• Schedule next visit 
10.2.7. 
Treatment Month 2 (Visit T3 ±3 days)/EOS 
If the patient is withdrawing early from the study at this visit, proceed to Section 10.3.2 for the 
list of the required assessments.  
If the patient is withdrawing from IMP treatment at this visit, proceed to Section 10.3.2 for the 
list of the required assessments.    
Patients will undergo the following assessments and procedures at Month 2 (Visit T3): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs since last visit (ongoing) 
• PE 
• Weight 
• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, 
, non-HDL-C, 
, and 
) 
− ApoB and hs-CRP 
− HbA1C 
• Predose PK.  Should be taken ideally within 4 hours of the patient’s normal time of 
dosing 
• Conduct diet and exercise counseling 
• Return of IMP; assessment and recording of IMP compliance 
• Complete study status in IWRS (ie, completed study). 


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10.3. 
Subject Withdrawal Criteria 
10.3.1. 
Early Withdrawal from the Study 
Patients must remain in the study until the last scheduled visit at Month 2 (Visit T3) to be 
considered as having completed participation in the study.  
Patients who temporarily withdraw from IMP prior to Month 2 (Visit T3) for any reason may 
restart IMP providing that 1) the patient and the investigator are in agreement regarding this 
course of action, 2) the patient has been off of IMP for 2 weeks or less; and 3) IMP can be started 
as soon as possible.  For cases where the patient has been off of IMP for more than 4 weeks, the 
investigator must contact the medical monitor for approval prior to restarting IMP. 
The patient’s decision to participate in the clinical study is voluntary.  Patients may refuse to 
continue in the study and/or withdraw from participation in this study at any time, for any reason, 
specified or unspecified, and without penalty or loss of benefits to which the patient is otherwise 
entitled.  
It is the right and duty of the Investigator to interrupt the treatment of any patient whose health or 
well-being may be threatened by continuation in this study.  Such patients should be withdrawn 
from the study and should not be continued under a modified regimen. 
Patients who are withdrawn from the study may not re-enter.  The reasons for withdrawal from 
this study may include: 
• Patient’s withdrawal of consent 
• Failure to comply with the protocol 
• Lost to follow-up 
• Illness, condition, or procedural complication (including AEs) affecting the patient’s 
ability to participate or requiring prohibited medication 
• The Sponsor or Investigator terminates the study  
• In the Investigator’s judgment, it is deemed in the best interest of the patient to 
discontinue his/her participation in the study 
• Any other reason 
If a patient is lost to follow-up, every reasonable effort must be made by the clinical site 
personnel to contact the patient and determine the reason for discontinuation/withdrawal.  The 
measures taken to follow-up must be documented. 
10.3.2. 
Procedures for Early Withdrawal 
If a patient withdraws or is removed from the study for any reason, all End of Study procedures 
should be completed.  Reason for withdrawal, date of the discontinuation, and date of the last 
dose of study drug should be recorded in the appropriate section of the eCRF.  Additionally, the 
discontinuation visit date must be registered in IWRS.  Study drug assigned to the withdrawn 
patient may not be assigned to another patient. 


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All effort should be made to have each patient complete all study visits on schedule according to 
the protocol.  Accommodations for early or late visits in special circumstances will be considered 
by the Sponsor to prevent early withdrawal.  Written notice (regardless of cause) is to be 
provided within 48 hours of the withdrawal to the Sponsor personnel or the Medical Monitor.  At 
the time of discontinuation, every effort should be made to ensure all relevant procedures and 
evaluations scheduled for the final study visit are performed.  Except in the case of a medical 
emergency, the procedures and assessments detailed in Section 10.2.7 will be performed upon 
the discontinuation of the study. 


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11. 
ASSESSMENT OF SAFETY 
11.1. 
Safety Parameters 
At all clinic visits, investigators will review all safety information including vital signs, AEs, and 
concomitant medications and will ensure that the collected data are recorded into the appropriate 
eCRF.  Additionally, clinical laboratory samples will be collected and sent for analysis and the 
investigator will review the results to ensure continued patient safety while participating in the 
study.  
11.1.1. 
Demographic/Medical History 
Demographic data and a complete medical history will be obtained from the patient.  For medical 
history, conditions that are relevant and/or clinically significant should be captured with at least a 
start date (month and year) and whether the condition is ongoing or resolved.  All surgeries 
regardless of date should be reported.  
11.1.2. 
Vital Signs 
Vital signs will include DBP and SBP as well as heart rate. 
The patient should sit quietly for 5 minutes prior to collection of vital signs.  At all time points, 
vitals will be collected prior to blood collection.  Blood pressure (BP) and heart rate will be 
measured using a calibrated, fully automated machine with a cuff that is appropriate to the size 
of the upper arm.  If a fully automated machine is not available, BP may be measured manually.  
The same method (either automated or manual) and the same arm (right or left) must be used 
throughout the study.  The patient should be in a seated position with feet touching the floor.  
Patients should be seated quietly for at least 5 minutes in a chair with their backs supported, their 
feet flat on the ground, and their arms bared and supported at heart level. 
11.1.3. 
Weight, Height, and Body Mass Index 
Weight will be measured on a calibrated scale while fasted and after voiding.  Body weight will 
be measured while fasting, using consistent scales, after voiding, and without shoes and 
outerwear (eg, coats).  
Height will be measured using standard clinic procedures.  
BMI will be calculated using the formula:  
BMI (kg/m2) = weight in kg / (height in meters)2 


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11.1.4. 
Physical Examination 
PEs will include an assessment of the following: 
• General appearance 
• Skin 
• Eyes, ears, nose, and throat 
• Head and neck 
• Extremities 
• Musculoskeletal examination 
• Respiratory examination 
• Cardiovascular assessment, including rhythm and presence of cardiac abnormalities 
• Abdominal examination 
• Neurologic examination including documentation of the presence of abnormalities in 
mental status and motor and sensory function 
• Any additional assessments necessary to establish baseline status or evaluate 
symptoms or adverse experiences 
Documentation of the PE findings will be included in the source documentation at the clinical 
site.  Significant findings prior to the time of ICF signature will be recorded on the Medical 
History/Current Medical Conditions page of the eCRF.  Only changes from baseline PE findings 
that meet the definition of an AE will be recorded on the AE page of the eCRF. 
Note:  Additional information will be collected regarding muscle-related AEs.  See Section 12.3. 
11.1.5. 
Clinical Laboratory Tests 
11.1.5.1. Laboratory Parameters (Safety) 
Patients will be in a seated position during the blood collection.  Clinical laboratory parameters 
and tests will include those listed in Table 3.  Collection schedule, schedule of laboratory 
parameters by visit, and instructions are in the Clinical Laboratory Manual provided by Central 
Laboratory. 


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Table 3: 
Clinical Laboratory Parameters (Safety) 
Clinical Laboratory Test 
Clinical Laboratory Test 
Hematology 
• 
Hematocrit (Hct) 
• 
Hemoglobin (Hgb) 
• 
Mean corpuscular hemoglobin (MCH) 
• 
Mean corpuscular hemoglobin 
concentration (MCHC) 
• 
Mean corpuscular volume (MCV) 
• 
Platelet count 
• 
Red blood (RBC) cell count 
• 
White blood (WBC) cell count with 
differential (absolute and %) 
Blood Chemistry (serum, fasting) 
• 
Albumin (Alb) 
• 
Alkaline phosphatase (ALK-P) 
• 
Alanine aminotransferase (ALT; SGPT) 
• 
Aspartate aminotransferase (AST; SGOT) 
• 
Blood urea nitrogen (BUN) 
• 
Calcium (Ca) 
• 
Carbon dioxide (CO2) 
• 
Chloride (Cl) 
• 
Creatinine 
• 
Creatine kinase (CK) 
• 
Glucose 
• 
Lactate dehydrogenase (LDH) 
• 
Phosphorus 
• 
Potassium (K) 
• 
Sodium (Na) 
• 
Total and direct bilirubin (TB)a 
• 
Total protein 
• 
Uric acid 
Coagulation—only in patients receiving anticoagulant 
therapy that in the investigator’s judgment require 
monitoring at T1 and 3 to 5 days post-T1 
• 
Prothrombin time (PT) 
• 
International normalized ration (INR) 
Urinalysis (Dipstick) 
• 
Clarity 
• 
Bilirubin 
• 
Color 
• 
Glucose 
• 
Ketones 
• 
Leukocyte esterase 
• 
Nitrate 
• 
Occult blood 
• 
pH 
• 
Protein 
• 
Specific gravity 
• 
Urobilinogen 
Urinalysis (Microscopic)-only if urine dipstick 
abnormal 
• 
Bacteria 
• 
Casts 
• 
Crystals 
• 
Epithelial cells 
• 
Red blood cell (RBC) 
• 
WBC 
Additional samples 
• 
Hemoglobin A1C (HbA1C) 
• 
PK 


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Table 3: 
Clinical Laboratory Parameters (Safety) 
Clinical Laboratory Test 
Clinical Laboratory Test 
Other Screening Labs 
 
• 
Hepatitis B surface antigen (HBsAg), 
hepatitis C virus (HCV)b 
• 
Serum pregnancy test (only for females of 
childbearing potential) 
• 
Follicle-stimulating hormone (FSH; 
Females <55 years and >1 year without 
menses) 
• 
Urine pregnancy test prior to 
randomization (for female of child bearing 
potential) 
• 
Thyroid-stimulating hormone (TSH) 
a If TB ≥1.2 × ULN, a reflex indirect (unconjugated) bilirubin will be obtained. 
b If HCV-AB is positive, a reflex HCV RNA will be performed to rule out active disease. 
11.1.5.2. Clinical Laboratory Tests (PK) 
Trough PK plasma concentrations of bempedoic acid and its metabolite ESP15228 will be 
collected prior to dosing at Visits T1, T2, and T3.  See lab manual for additional details. 
Patients will be in a seated position during the blood collection.  Collection schedule and 
instructions are provided in the Clinical Laboratory Manual.  A description of the sample 
collection, storage, and shipping are described in Section 11.1.5.3. 
11.1.5.3. Sample Collection, Storage, and Shipping 
Clinical laboratory samples will be collected by appropriate clinical site personnel and then 
shipped according to a separate laboratory manual provided by the Central Laboratory.  Samples 
will be processed by the Central Laboratory, and PK samples will be forwarded to the 
Bioanalytical Laboratory for analysis.   
Blood draws for lipids, 
, and glucose must meet the criteria listed below.  If these criteria 
have not been met, these blood samples will NOT be collected.  If these criteria can be met by 
rescheduling the clinic visit to occur within 3 days, the lipid, 
, and/or glucose blood samples 
will be collected at the rescheduled clinic visit only.  
• Blood samples will be drawn after a minimum 10-hour fast (water is allowed) 
11.1.5.4. General Monitoring and Management of Abnormal Clinical Labs 
It is the Investigator’s responsibility to review the results of all laboratory tests as they become 
available and to sign and date the report to document their review.  For each laboratory test 
outside of the laboratory normal range, the Investigator needs to ascertain if this is a clinically 
significant change from baseline for the individual patient.  The Investigator may repeat the 
laboratory test or request additional tests to verify the results of the original laboratory test. 


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If a laboratory value is determined to be an abnormal and clinically significant change from 
baseline for the patient, the Investigator should determine if it qualifies as an AE, and if yes, an 
appropriate eCRF will be completed.  All clinically significant laboratory abnormalities 
occurring during the study that were not present at baseline should be followed and evaluated 
with additional tests if necessary, until diagnosis of the underlying cause or resolution.  Specific 
monitoring and management guidelines for laboratories of special interest are outlined in the 
sections below. 
11.1.5.4.1. Monitoring and Management of Elevated Liver Function Tests 
If at any time after randomization a patient experiences a new ALT and/or AST >3 × ULN, the 
patient will undergo repeat confirmatory liver function test (LFT) assessment as soon as is 
reasonably possible, preferably within 3 to 7 days of the laboratory result becoming available.  
Repeat LFT assessment will include:  1) measurement of ALT, AST, alkaline phosphatase, total 
and direct bilirubin, prothrombin time (PT)/international normalized ratio (INR), eosinophil 
count, CK, antihepatitis A virus (total), HBsAg (confirmation of screening measurement), HCV 
(confirmation of screening measurement), and anticytomegalovirus/immunoglobulin M; 
2) history of concomitant medication use; 3) history of exposure to environmental chemical 
agents, including ethanol; and 4) query for related symptoms.  Additionally, further testing such 
as liver ultrasound or magnetic resonance imaging (MRI) scanning may be warranted to rule out 
additional pathology depending on clinical presentation and should be discussed with the 
Sponsor personnel or the authorized Medical Monitor.  
• If repeat LFT assessment confirms ALT and/or AST >3 × ULN, consideration should 
be given to withdrawing the patient and administering no further doses of study drug.  
At the investigator’s discretion, study drug may be interrupted and the patient 
rechallenged with study drug after LFTs have returned to baseline levels.  
• If repeat LFT assessment confirms ALT and/or AST >5 × ULN, patient should be 
withdrawn from IMP treatment, but will be asked to continue to be followed for 
safety using the protocol-specified visit schedule (see Appendix 1). 
• If repeat LFT assessment confirms ALT and/or AST >3 × ULN in addition to any of 
the following, the patient should be given no further IMP treatment, but will be asked 
to continue to be followed for safety using the protocol-specified visit schedule (see 
Appendix 1): 
− TB >2 × ULN 
Note:  In the case of patients with Gilbert’s disease, TB will be fractionated and 
the determination of 2 × ULN will be based upon direct (conjugated) bilirubin. 
− INR >1.5 × ULN (unless the patient is on stable dose of anticoagulation 
medication) 
− Appearance or worsening of right upper abdominal discomfort, anorexia, fatigue, 
nausea, vomiting, fever, rash, or eosinophilia 


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11.1.5.4.2. Monitoring and Management of Elevated Serum Creatinine 
If at any time after randomization, a patient experiences a decrease in eGFR to the level of 
15 mL/min/1.73 m2) or if the patient experiences acute renal failure, the patient should be 
withdrawn from IMP treatment but will be asked to continue to be followed for safety using the 
protocol-specified visit schedule (see Appendix 1) 
11.1.5.4.3. Monitoring and Management of Elevated Creatine Kinase 
If at any time after randomization a patient experiences a marked CK elevation >5 × ULN, the 
patient will undergo repeat confirmatory assessment as soon as is reasonably possible, preferably 
within 3 to 7 days of the laboratory result becoming available.  
Repeat CK assessment will include query for related symptoms.  
• If the repeat CK assessment confirms an unexplained (ie, not associated with recent 
trauma or physically strenuous activity) CK abnormality >5 × ULN, if asymptomatic, 
the patient should receive further assessment and investigation into the cause, assess 
whether there is renal injury, and measure CK approximately weekly or more 
frequently if clinically indicated until resolution.  If CK levels continue to rise; IMP 
should be discontinued.  
• If symptomatic, the following should be completed: 
− Hold IMP 
− Clarification of the nature, duration, and intensity of muscle symptoms 
− Review possible predisposing factors, such as unaccustomed exercise, heavy 
alcohol intake, viral illness (consider performing serology)  
− Evaluation for additional diagnoses or other conditions which can cause 
myopathy including muscle tenderness (by PE), weakness, rash, measurement of 
serum creatinine, dipstick urinalysis with microscopy if indicated 
− Obtain clinical chemistries to assess the possibility of lactic acidosis 
− Follow symptoms and CK until the abnormality has resolved 
− If based on the above evaluation an alternative explanation is suspected, 
consideration can be given to resuming IMP once CK returns to baseline levels 
− If no alternative explanation exists, consideration should be given to withdrawing 
the patient from IMP treatment.  
• If the repeat CK assessment confirms an unexplained (ie, not associated with recent 
trauma or physically strenuous activity) CK abnormality as listed below, the patient 
should be withdrawn and given no further doses of study drug:  
− >10 × ULN, even in the absence of symptoms.  
− In all cases, evaluate the signs/symptoms and laboratory evaluations as outlined 
above. 


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• If the patient is withdrawn from IMP treatment, the patient should be asked to 
continue being followed for safety using the protocol-specified visit schedule (see 
Appendix 1). 
11.1.5.5. Monitoring and Management of Potential Hypoglycemia and Metabolic Acidosis 
Patients will be educated on the signs and symptoms of hypoglycemia.  If such signs and 
symptoms are experienced, patients will be instructed to report these signs and symptoms to the 
investigator.  
During each study visit, patients will be reminded to report all signs and symptoms associated 
with hypoglycemia to the investigator.  For each occurrence of patient-reported signs and 
symptoms associated with hypoglycemia, the investigator will discuss these symptoms with the 
patient and assess whether they are attributable to hypoglycemia or to another potential cause.  
All investigator-confirmed occurrences of hypoglycemia will be recorded as an AE.  All 
occurrences of signs and symptoms that are not confirmed by the investigator to be attributable 
to hypoglycemia will be reported using the appropriate diagnosis. 
Clinical laboratories will be assessed to determine any signs of anion gap metabolic acidosis.  If 
laboratories are consistent with metabolic acidosis, immediate follow up with the patient for 
further medical evaluation of the acidosis will occur.  This event should be captured as an AE.  


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12. 
ADVERSE AND SERIOUS ADVERSE EVENTS 
12.1. 
Adverse Events 
12.1.1. 
Definition of Adverse Events 
An AE is defined as any untoward medical occurrence in a clinical investigation patient 
administered a pharmaceutical product, including control, and which does not necessarily have a 
causal relationship with treatment.  The investigator is responsible for ensuring that any adverse 
events observed by the investigator or reported by the patient are recorded in the patient’s 
medical record.  
An AE can be: 
• Any unfavorable and unintended sign/symptom, including an abnormal laboratory 
finding, or disease temporally associated with the use of a medicinal product, whether 
or not considered related to the medicinal product 
• Any new disease or exacerbation of an existing disease 
• Laboratory abnormality or diagnostic test abnormalities (eg, x-ray) should be reported 
as an AE if one of the following occurs   
− Treatment required due to the abnormality 
− Discontinuation of IMP 
− Per Investigator judgement 
• TEAEs are defined as AEs that begin or worsen after the first dose of study drug 
administration, as defined in the Statistical Analysis Plan (SAP). 
12.1.2. 
Adverse Drug Reaction 
All noxious and unintended responses to a medicinal product related to any dose should be 
considered an adverse drug reaction (ADR).  “Responses” to a medicinal product means that a 
causal relationship between the medicinal product and an AE is at least a reasonable possibility 
(ie, the relationship cannot be ruled out). 
An unexpected ADR is defined as an adverse reaction, the nature or severity of which is not 
consistent with the applicable product information (eg, IB for an unapproved investigational 
product or package insert/summary of product characteristics for an approved product). 
12.1.3. 
Reporting for Adverse Events 
All AEs occurring during the course of the study (starting from signing informed consent 
through 30 days after last dose of study treatment) will be collected on the AE eCRF.  Patients 
should be instructed to report any AE that they experience to the investigator.  Investigators 
should make an assessment for AEs at each visit and record the event on the appropriate AE 
eCRF.  


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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.  A cluster of signs 
and symptoms that results from a single cause should be reported as a single AE (eg, fever, 
elevated white blood cells [WBC], cough, abnormal chest x-ray, etc, can all be reported as 
“pneumonia” if that is the final diagnosis).  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 should be recorded as the AE, not the procedure itself.  
Any medical condition already present at screening or baseline should not be reported as an AE 
unless the medical condition or signs or symptoms present at baseline worsens in severity 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 that are detected during 
the study or are present at baseline 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.  Significant abnormal laboratory values occurring during the clinical study 
will be followed until repeat tests return to normal, stabilize, or are no longer clinically 
significant.  Any abnormal test that is determined to be an error does not require reporting as an 
AE. 
An abnormal laboratory value that is not already associated with an AE is to be recorded as an 
AE only if any one of the following criteria is met: 
• an action on the study drug is made as a result of the abnormality 
• intervention for management of the abnormality is required 
• at the discretion of the investigator should the abnormality be deemed clinically 
significant 
Each AE is to be evaluated for duration, severity, seriousness, and causal relationship to the IMP.  
For each AE, the following information will be recorded: 
• Description of the event (eg, headache) 
• Date of onset 
• Date of resolution (or that the event is continuing) 
• Action taken as a result of the event 
• Seriousness of the event 
• Severity of the event 
• Outcome of the event 
• Investigator’s assessment of relationship to IMP or PCSK9i. 
The investigator will carefully evaluate the comments of the patient and the response to 
treatment in order that he/she may judge the true nature and severity of the AE.  The question of 


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the relationship of AEs to IMP administration should be determined by the investigator or study 
physician after thorough consideration of all facts that are available. 
12.1.4. 
Severity 
It is the investigator’s responsibility to assess the intensity (severity) of an AE.  
The severity of the AE will be characterized as mild, moderate, or severe according to the 
following definitions: 
• Mild:  Events are usually transient and do not interfere with the patient’s daily 
activities 
• Moderate:  Events introduce a low level of inconvenience or concern to the patient 
and may interfere with daily activities  
• Severe:  Events interrupt the patient’s usual daily activity, are incapacitating with 
inability to do usual activities, or significantly affect clinical status and warrant 
intervention and/or close follow-up  
Note:  A severe AE need not be serious and an SAE need not, by definition, be severe. 
12.1.5. 
Relationship 
It is the investigator’s responsibility to assess the relationship between the IMP and the AE.  The 
degree of “relatedness” of the AE to the IMP may be described using the following scale: 
• Not Related:  No temporal association and other etiologies are likely the cause  
• Unlikely:  While cannot be definitively ruled as not related to IMP, a causal 
association is remote, and other etiologies are more likely to be the cause.  For 
reporting and summarization, events assessed as Unlikely to be related to IMP will be 
considered as Not Related to IMP. 
• Possible:  Temporal association, but other etiologies are likely the cause.  However, 
involvement of the IMP cannot be excluded. 
• Probable:  Temporal association, other etiologies are possible but unlikely.  The event 
may respond if the IMP is discontinued. 
• Definite:  Established temporal association with administration of the IMP with no 
other more probable cause.  Typically, the event should resolve when the IMP is 
discontinued and recur on rechallenge. 
12.1.6. 
Monitoring and Follow-up of Adverse Events 
Patients having AEs will be monitored with relevant clinical assessments and laboratory tests, as 
determined by the investigator.  All follow-up results are to be reported to the Sponsor personnel 
or the authorized Medical Monitor.  Any actions taken and follow up results must be recorded 
either on the appropriate page of the eCRF or in appropriate follow-up written correspondence, 
as well as in the patient’s source documentation.  Follow-up laboratory results should be filed 
with the patient’s source documentation. 


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For all AEs that require the patient to be discontinued from the study, relevant clinical 
assessments and laboratory tests must be repeated at appropriate intervals until final resolution or 
stabilization of the event(s). 
Patients with AEs related to IMP that are ongoing at study discontinuation or completion must be 
followed until resolution, until deemed stable/chronic, or for 30 days after study completion, 
whichever comes first, with the exception of patients reporting SAEs (see Section 12.2.2). 
12.1.7. 
Treatment-Emergent Adverse Events 
TEAE are defined as AEs that begin or worsen after the first dose of study drug administration, 
as defined in the SAP. 
12.2. 
Serious Adverse Events 
12.2.1. 
Definition of Serious Adverse Event  
An SAE is defined as any AE occurring at any dose that results in any of the following 
outcomes:  
• Results in death 
• Is life threatening 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Results in persistent or significant disability/incapacity, or substantial disruption of 
the ability to conduct normal life functions 
• Is a congenital anomaly/birth defect 
• An important medical event 
NOTE:  An emergency room visit without hospital admission does not meet inpatient 
hospitalization criteria, nor does hospitalization for an elective or outpatient procedure scheduled 
or planned before signing of informed consent.  However, unexpected complications and/or 
prolongation of hospitalization that occur during elective or outpatient surgery should be 
recorded as AEs and assessed for seriousness.  Admission to the hospital for social or situational 
reasons (eg, no place to stay, live too far away to come for hospital visits) will not be considered 
inpatient hospitalizations.  
Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, they 
may jeopardize the patient and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition.  Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room, blood dyscrasias, 
convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 


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Events or Outcomes Not Qualifying as Serious Adverse Events 
The following are not considered SAEs and therefore do not need to be reported as such: 
• Preplanned or elective hospitalization, including social and/or convenience situations 
(eg, due to inclement weather) 
• Overdose of either Esperion study drug or concomitant medication unless the event 
meets SAE criteria (eg, hospitalization).  However, the event should still be captured 
as a nonserious AE on the appropriate eCRF page 
12.2.2. 
Reporting Serious Adverse Events 
All SAEs occurring from the time of informed consent until 30 days following study completion/ 
discontinuation must be reported by the Principal Investigator or designee to the designated 
Safety contact within 24 hours of knowledge of the event.  All SAEs that the investigator 
considers related to IMP that occur after the 30-day follow-up period of the study period must be 
also reported to the Sponsor.  
To report the SAE, the SAE information should be entered on to the AE eCRF in the EDC 
database within 24 hours of becoming aware of the event.  If you have questions, please call the 
designated Safety contact for assistance.  
Detailed instructions and contact information for the Safety designee will be provided in the SAE 
Completion Guidelines.  
The investigator is required to submit SAE reports to their IRB/IEC in accordance with local 
requirements.  All investigators involved in studies using the same investigational product will 
receive any safety alert notifications for onward submission to their local IRB as required.  All 
reports sent to investigators will be blinded. 
All SAEs should be recorded on the eCRF and source documents.  Criteria for documenting the 
relationship to IMP and severity will be the same as those previously described. 
The investigator must continue to follow the patient until the SAE has subsided or until the 
condition becomes chronic in nature, stabilizes (in the case of persistent impairment), or the 
patient dies. 
Within 24 hours of receipt of follow-up information, the investigator must update the SAE 
information on the AE eCRF and submit any supporting documentation (eg, patient discharge 
summary or autopsy reports) to designated Safety contact.  
The Sponsor (and/or legally transferred designee) will report SAEs and suspected and 
unexpected serious adverse reactions (SUSARs) as required by global regulatory authorities, 
IECs/IRBs, and/or investigators/institutions in compliance with all reporting requirements 
according to local regulations, laws, and Good Clinical Practices (GCPs).  The investigator 
should notify their IEC/IRB of SAEs occurring at their site and other SAE reports received from 
the Sponsor, in accordance with local procedures and statutes.  


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12.2.3. 
Reporting of Patient Death 
The death of any patient during the study or within 30 days after the last dose of study treatment 
must be reported as an SAE. 
12.2.4. 
Reports of Pregnancy and Lactation 
Although not considered an SAE (unless an event occurs with a serious outcome), any event of 
pregnancy will be collected by the designated Safety contact.  If a female patient should become 
pregnant during the course of the study or within 30 days after last dose of study treatment, the 
Principal Investigator or designee must contact the designated Safety contact within 24 hours of 
knowledge of the pregnancy.  In addition, a paper Pregnancy Report Form must be completed 
and submitted to the Safety contact. 
Patients who become pregnant must discontinue study medication immediately and will continue 
to be followed until the pregnancy is completed.  Once the outcome of the pregnancy is known, 
the paper Pregnancy Outcome Report Form must be completed and submitted to the Safety 
contact.  Patients who are breastfeeding are excluded from this study and should discontinue 
study medication. 
12.3. 
Adverse Events of Special Interest 
Muscle:  Muscle events have been associated with statins (Thompson 2003) and other lipid-
lowering therapies and are mentioned in the product information for these therapies.  Muscle 
symptoms through AE review, CK elevations, and symptoms of potential myopathy will be 
closely monitored.  
Hepatic:  Hepatic function will be monitored throughout with the clinical safety labs.  More 
detailed investigation will occur if the safety clinical laboratory results are >3 × ULN. 
Neurocognitive Events:  Theoretically, it is possible that lipid-lowering agents that disrupt 
cholesterol homeostasis in the brain could impact neurological function, and there have been 


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reports of cognitive impairment (eg, memory loss) associated with the use of statin drugs 
(FDA 2012).  Summarization of events will occur using prespecified Medical Dictionary for 
Regulatory Activities (MedDRA) terms outlined in the SAP. 
12.4. 
Data Monitoring Committee 
An independent DMC will monitor unblinded accumulating patient safety and efficacy data until 
the last patient has completed study treatment.  In addition, data on SAEs and deaths, including 
clinical endpoints, will be monitored by the DMC during this period.  At each DMC review, 
relevant unblinded safety and efficacy information from ongoing studies of bempedoic acid will 
be provided to the DMC by an independent unblinded statistician and programmer.  Additional 
details will be provided in a DMC Charter. 
12.5. 
Assessment of Lipid Endpoints 
12.5.1. 
Lipid Parameters 
After randomization, patients will return to clinic every month.  Clinical laboratory samples will 
be collected and analyzed for calculated LDL-C and lipid and cardiometabolic biomarkers 
including non-HDL-C,
 TC, ApoB,
 and
 at baseline and all clinic visits for 
evaluation of bempedoic acid effects on lipids and cardiometabolic parameters.  
12.5.2. 
Clinical Laboratory Tests (Lipids) 
Clinical laboratory samples will be collected at all clinic visits.  
Blood draws for lipids (and glucose) must meet the criteria below.  If these criteria have not been 
met, these blood samples will NOT be collected.  If these criteria can be met by rescheduling 
clinic visit to occur within 3 days, these blood samples will be collected at the rescheduled 
clinic visit only.  
• Blood samples will be drawn after a minimum 10-hour fast (water is allowed)  
Patients are encouraged to be in a seated position during the blood collection.  Clinical laboratory 
parameters and tests will include those listed in Table 4.  Collection schedule and instructions are 
provided in the Clinical Laboratory Manual.  A description of the sample collection, storage, and 
shipping as well as monitoring and management of abnormal laboratories are described in 
Section 11.1.5. 
When vital signs and laboratory samples are to be collected at the same time point, vital sign 
measurements will precede laboratory sample collection.  


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Table 4: 
Clinical Laboratory Parameters (Lipids) and Cardiometabolic Biomarkers 
Clinical Laboratory Test  
Clinical Laboratory Test 
Basic Lipid Parameters 
Other Parameters 
• 
Total cholesterol (TC) 
• 
low-density lipoprotein cholesterol (LDL-C) 
and non-HDL-C 
• 
• 
• 
High-sensitivity C-reactive protein (hs-CRP) 
• 
ApoB 
• 


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13. 
STATISTICS 
13.1. 
General Considerations 
The statistical analyses described in this section will be performed as further outlined in a 
separate SAP.  The SAP will supersede the protocol in the event of any differences between the 
2 documents in the plans for data analysis, and the protocol will be amended if appropriate.  The 
SAP will be included as an appendix in the clinical study report for this protocol. 
Summary statistics for continuous variables will include the number of patients, mean, median, 
standard deviation or standard error, minimum, and maximum. For categorical variables, the 
frequency and percentage will be given. 
13.2. 
Determination of Sample Size 
The planned total sample size for this study is 52 with 26 patients in the bempedoic acid 180 mg 
group and 26 in the placebo group.  This sample size is expected to
 
 
  
13.3. 
Analysis Populations  
The Full Analysis Set (FAS), used for all of the efficacy analyses, is defined as all randomized 
patients with a baseline lipid value, at least 1 postbaseline lipid value, and having taken their 
study drug within 2 days of the lipid measurement.  The FAS is also known as the modified 
intention-to-treat (mITT) set of patients.  Patients in the FAS will be included in their 
randomized treatment group, regardless of the treatment they actually received.  Other subsets of 
the FAS will be considered to evaluate primary and secondary endpoints as sensitivity analyses 
and the details will be described in the SAP. 
The Safety Population (SP), used for all of the safety summaries, is defined as all randomized 
patients who received at least 1 dose of study medication.  Patients in the SP will be included in 
the treatment group that they actually received, regardless of their randomized treatment.  
13.4. 
Disposition, Demographics, and Baseline Characteristics 
Disposition, including reason for withdrawal from the study drug and/or study, will be 
summarized by treatment group.  Demographic information and patient characteristics including, 
but not limited to, gender, race, age, and baseline vital signs will also be summarized by 
treatment group. 
13.5. 
Primary Endpoint 
The primary efficacy endpoint is the percent change from baseline to Month 2 in LDL-C.  The 
primary efficacy endpoint will be analyzed using analysis of covariance (ANCOVA), with 


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treatment group as a factor and baseline LDL-C as a covariate.  The details of the ANCOVA 
model and options to correct for unequal variances will be described in the SAP.  Baseline 
LDL-C is defined as the average of S4 and Day 1 values, if only 1 value is available, then that 
single value will be used as baseline.  The ANCOVA will be performed using the FAS, with 
patients included in their randomized treatment group regardless of the treatment they actually 
received.  Patients who are missing their Month 2 LDL-C will have their Month 2 value imputed 
by last observation carried forward (LOCF).  The least squares mean (LSM) and standard error 
(SE) for percent change estimate will be provided for both treatment groups, along with the 
placebo-corrected LSM, its 95% confidence interval (CI) and associated p-value.   
The ANCOVA assumptions will be examined and nonparametric test or transformation of the 
data will be considered if these assumptions are not met. 
13.6. 
Secondary and Exploratory Efficacy Endpoints 
The secondary efficacy endpoints (percent change from baseline to Month 1 in LDL-C; change 
from baseline to Months 1 and 2 in LDL-C; percent change from baseline to Months 1 and 2 in 
ApoB, non-HDL-C,TC, hs-CRP 
and 
), will be analyzed using the ANCOVA method 
similar to the primary endpoint.  Baseline value for TC, non-HDL-C,
will 
be the average of S4 and Day 1 values; ApoB and hs-CRP will be the Day 1 value, if only 
1 value is available, the single value will be used as the baseline.  Each ANCOVA will be 
performed using the FAS, with patients included in their randomized treatment group regardless 
of the treatment they actually received.  Missing values will be imputed using LOCF, where 
applicable.  For each parameter and analysis time point, the LSM and SE will be provided for 
both treatment groups, along with the placebo-corrected LSM, its 95% CI and associated p value. 
All efficacy endpoints will be analyzed at a significance level of 0.05, no multiplicity adjustment 
will be implemented. 
Exploratory endpoints will be summarized by descriptive statistics. 
13.7. 
Safety Endpoints 
The safety analyses for this study will be descriptive in nature, no statistical inferences are 
planned 
The subject incidence of all TEAE, SAEs, related AEs, AEs leading to withdrawal of study drug 
and/or study, fatal AEs, and AESI will be tabulated by system organ class (SOC) and preferred 
term in descending order of frequency and by treatment group.  
Clinical safety laboratories, including hematology, blood chemistry, HbA1C, glucose, and 
urinalysis; PE findings; vital signs; and weight will be summarized by the value and by change 
from baseline in the value (where appropriate) at each postbaseline time point. 
Hepatic Safety 
For liver-associated enzymes and TB, the number and percent of patients with abnormal values 
for ALT, AST, and TB will be summarized.  All liver-associated laboratory abnormalities will be 
assessed for Hy’s Law criteria (≥3 × ULN for either ALT or AST, with accompanying TB >2 × 


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ULN in the absence of other known causes) will also be applied to the data; any potential Hy’s 
law cases will be listed separately. 
Musculoskeletal Safety 
AEs of muscle-related symptoms will be summarized by treatment group.  In addition, the 
number and percent of patients with abnormal CK values will be summarized.  Finally, muscle-
related AEs will be summarized by treatment group and by baseline eGFR category. 
Diabetes/Hyperglycemia 
Cases of new onset of diabetes will be recorded as AEs and will be summarized using the 
appropriate SOC.  These events will be summarized by severity and relationship to study drug 
for each treatment group. 
Renal Safety 
Baseline eGFR and values of CK will be summarized by treatment group and by baseline eGFR 
categories.  Shift tables of eGFR category from baseline over the study, will be provided by 
treatment group. 
Neurocognitive Events 
Neurocognitive events will be identified and evaluated by routine safety monitoring of PE 
findings and AEs.  Summarization of neurocognitive events will occur using prespecified 
MedDRA terms and will be performed by treatment group. 
13.8. 
Pharmacokinetics 
Three trough plasma concentrations of bempedoic acid and ESP15228 will be collected and 
summarized from patients at predose (T1), T2, and T3 for use in further developing the 
population PK model. 


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14. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
14.1. 
Study Monitoring 
The Sponsor (or its authorized representative) has the obligation to follow this study closely to 
ensure that the study is conducted in accordance with the protocol, International Conference on 
Harmonisation (ICH) and GCP guidelines, national and international regulatory requirements, 
and the current Declaration of Helsinki throughout its duration by means of personal visits to the 
Investigator’s facilities and other communications.  
These visits will be conducted to evaluate the progress of the study, verify the rights and 
well-being of the patients are protected, and verify the reported clinical study data are accurate, 
complete, and verifiable from source documents.  This includes review of ICDs, results of tests 
performed as a requirement for participation in this study, and any other medical records 
(eg, laboratory reports, clinic notes, study drug dispensing log, pharmacy records, patient sign-in 
sheets, patient-completed questionnaires, telephone logs) required to confirm information 
contained in the eCRFs. 
A monitoring visit should include a review of the essential clinical study documents (regulatory 
documents, case report forms, medical records and source documents, drug disposition records, 
patient informed consent forms, etc) as well as discussion on the conduct of the study with the 
Investigator and staff. 
The monitor should conduct these visits as frequently as appropriate for the clinical study.  The 
Investigator and staff should be available during these visits for discussion of the conduct of the 
study as well as to facilitate the review of the clinical study records and resolve/document any 
discrepancies found during the visit.  
All monitoring activities will be reported and archived.  In addition, monitoring visits will be 
documented at the clinical site by signature and date on the study-specific monitoring log. 
14.2. 
Audits and Inspections 
Representatives of the Sponsor or its authorized clinical quality assurance group may visit a 
clinical site at any time during the study to conduct an audit of the study in compliance with 
regulatory guidelines and company policy.  These audits will require access to all study records, 
including source documents, for inspection and comparison with the eCRFs.  Patient privacy 
must be respected.  The Investigator and clinical site personnel are responsible for being present 
and available for consultation during routinely scheduled site audit visits conducted by the 
Sponsor or its authorized representative.  
The clinical study may also be inspected by the FDA or EMA (or other regulatory authority) to 
verify that the study was conducted in accordance with protocol requirements, as well as the 
applicable regulations and guidelines. 
In the event the Investigator is contacted by regulatory authorities who wish to conduct an 
inspection of the clinical site, the Investigator will promptly notify the Sponsor of all such 
requests and will promptly forward a copy of all such inspection reports. 


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15. 
QUALITY CONTROL AND QUALITY ASSURANCE 
To ensure compliance with GCP and all applicable regulatory requirements, the Sponsor / 
designee may conduct a quality assurance audit.  Please see Section 14.2 for more details 
regarding the audit process. 


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16. 
ETHICS 
16.1. 
Institutional Review Board/Independent Ethics Committee Approval 
Before initiation of the study, the Investigator must obtain approval or favorable opinion of the 
research protocol, ICD, and any material related to patient recruitment from an IRB or IEC.  For 
locations participating within the US, the IRB must comply with the provisions specified in 
21 Code of Federal Regulations (CFR) Part 56, ICH and GCP guidelines, and applicable 
pertinent state and federal requirements.  For locations participating outside of the US, the IRB 
or IEC must comply with the applicable requirements of each participating location, including 
ICH and GCP guidelines, except where a waiver is applicable. 
IRBs and IECs must be constituted according to the applicable laws.  It is the responsibility of 
each clinical site to submit the protocol, IB, patient informed consent, patient recruitment 
materials (if applicable), and other documentation as required by the IRB or IEC for review and 
approval.  A copy of the written approval must be provided to the Sponsor.  
The documentation should clearly mention the approval/favorable opinion of the protocol, the 
patient informed consent form, and patient recruitment materials (if applicable), including 
respective version dates.  The written approval and a list of the voting members, their titles or 
occupations, and their institutional affiliations must be obtained from the IRBs or IECs and 
provided to the Sponsor prior to the release of clinical study supplies to the clinical site and 
commencement of the study.  If any member of the IRB or IEC has direct participation in this 
study, written notification regarding his or her abstinence from voting must also be obtained. 
Clinical sites must adhere to all requirements stipulated by their respective IRB or IEC.  This 
includes notification to the IRB or IEC regarding: protocol amendments, updates to the ICD, 
recruitment materials intended for viewing by patients, aggregate safety reports required by 
regulatory competent authorities, serious and unexpected AEs, reports and updates regarding the 
ongoing review of the study at intervals specified by the respective IRB or IEC, and submission 
of final study reports and summaries to the IRB or IEC. 
It is the responsibility of each clinical site to submit information to the appropriate IRB or EC for 
annual review and annual re-approval. 
The Investigator must promptly inform their IRB or IEC of all SAEs or other safety information 
reported from the patient or the Sponsor. 
16.2. 
Ethical Conduct of the Study 
The investigator agrees, when signing the protocol, to conduct the study in accordance with 
ethical principles that have their origin in the current revision of the Declaration of Helsinki and 
are consistent with ICH/GCP, applicable regulatory requirements, and policies and procedures as 
outlined by the ethical requirements for IRB or IEC review and ICDs. 
The Investigator agrees to allow monitoring and auditing of all essential clinical study 
documents by the Sponsor or its authorized representatives and inspection by the FDA, EMA, or 
other appropriate regulatory authorities.  Monitoring and auditing visits by the Sponsor or 


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authorized designee will be scheduled with the appropriate staff at mutually agreeable times 
periodically throughout the study. 
The Investigator will assure proper implementation and conduct of the study, including those 
study-related duties delegated to other appropriately qualified individuals.  The Investigator will 
assure that study staff cooperates with monitoring and audits, and will demonstrate due diligence 
in recruiting and screening study patients.  The Investigator must sign and return to the Sponsor 
the “Investigator’s Signature” page (see Appendix 3) and provide a copy of current curriculum 
vitae.  For this study and all studies conducted under an IND, the Investigator must sign and 
return a completed Form FDA 1572 “Statement of Investigator” to the Sponsor (or designee).  
For European Union (EU) investigators, equivalent information contained within the FDA 1572 
form may be requested unless a waiver has been requested and received by the Sponsor from the 
FDA. 
16.3. 
Written Informed Consent 
The Principal Investigator(s) at each center will ensure that the patient is given full and adequate 
oral and written information about the nature, purpose, possible risk and benefit of the study.  
Patients must also be notified that they are free to discontinue from the study at any time.  The 
patient should be given the opportunity to ask questions and allowed time to consider the 
information provided. 
The patient’s signed and dated informed consent must be obtained before conducting any study 
procedures. 
The Principal Investigator(s) must maintain the original, signed ICD.  A copy of the signed ICD 
must be given to the patient. 
16.4. 
Patient Confidentiality 
The names and identities of all research patients will be kept in strict confidence and will not 
appear on eCRFs or other records provided to or retained by the Sponsor (or the Sponsor’s 
authorized representative).  If a patient’s name appears on any document, it must be redacted and 
replaced with the patient identifier before a copy of the document is supplied to the Sponsor or 
Sponsor’s authorized representative.  The ICD must include appropriate statements explaining 
that patient data will be confidential and what actions will be taken to ensure patient 
confidentiality. 
Any other confidentiality requirements specified by the site, IRB or IEC, or national or local 
regulations will be adhered to and detailed appropriately in the ICD. 


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17. 
DATA HANDLING AND RECORDKEEPING 
17.1. 
Inspection of Records 
Applicable regulations require the Sponsor (or the Sponsor’s authorized representative) to 
inspect all documents and records to be maintained by the Investigator, including but not limited 
to, medical records (office, clinic, or hospital) for the patients in this study.  These regulations 
also allow the Sponsor’s records to be inspected by authorized representatives of the regulatory 
agencies.  The Investigator will permit study-related monitoring, audits, IRB or IEC review, and 
regulatory inspections by providing direct access to source data/documents.  Direct access 
includes permission to examine, analyze, verify, and reproduce any records and reports that are 
important to the evaluation of a clinical study. 
17.2. 
Retention of Records 
In compliance with the ICH/GCP guidelines, the Investigator/Institution agrees to retain and 
maintain all study records that support the data collected from each patient, as well as all study 
documents as specified in ICH/GCP, Section 8 Essential Documents for the Conduct of a 
Clinical Trial.  The Investigator agrees to contact the Sponsor before destroying or relocating any 
study documentation and is expected to take measures to prevent accidental or premature 
destruction of these documents.  
If the Investigator retires, relocates, or for other reasons withdraws from the responsibility of 
keeping the study records, custody must be transferred to a person who will accept responsibility.  
The Sponsor must be contacted in writing regarding the name and address of the new person 
responsible as well as the disposition of document storage.  Under no circumstances shall the 
Investigator relocate or dispose of any study documents before having obtained written approval 
from the Sponsor. 
Essential records (including eCRFs, source documents, study drug disposition records, signed 
patient ICDs, AE reports, and other regulatory documents) as required by the applicable 
regulations, must be maintained for 2 years after a marketing application is approved for the drug 
for the indication for which it is being investigated; or, if no application is to be filed or if the 
application is not approved for such indication, until 2 years after formal discontinuation of 
clinical development of the investigational product. 
It is the responsibility of the Sponsor to inform the Investigator/Institution as to when these 
documents no longer need to be retained. 
17.3. 
Case Report Forms and Study Records 
Access to eCRFs will be provided to the clinical site. As part of the responsibilities assumed by 
participating in the study, the Investigator agrees to maintain adequate case histories for the 
patients treated as part of the research under this protocol.  The Investigator agrees to maintain 
accurate source documentation and eCRFs as part of the case histories.  


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Study records are comprised of source documents, eCRFs, and all other administrative 
documents (eg, IRB or IEC correspondence, clinical study materials and supplies shipment 
manifests, monitoring logs, and correspondence).  A study-specific binder will be provided with 
instructions for the maintenance of study records. 
Source documentation is defined as any handwritten or computer-generated document that 
contains medical information or test results that have been collected for or in support of the 
protocol specifications (eg, laboratory reports, clinic notes, study drug disposition log, pharmacy 
records, patient sign-in sheets, patient completed questionnaires, telephone logs, and x-rays).  All 
draft, preliminary, and pre/final iterations of a final report are also considered to be source 
documents (eg, faxed and hard copy of laboratory reports, faxed and hard copy of initial results, 
and final report).  
The Investigator agrees to allow direct access to all essential clinical study documents for the 
purpose of monitoring and/or auditing by the Sponsor or its authorized representatives and 
inspection by the appropriate regulatory authorities. 
Data reflecting the patient’s participation with the study drug under investigation are to be 
reported to the Sponsor.  The data are to be recorded on the eCRFs and/or other media provided 
or approved by the Sponsor.  
A completed eCRF must be submitted for each patient who receives study drug, regardless of 
duration.  All supportive documentation submitted with the eCRF, such as laboratory or hospital 
records, should be clearly identified with the study and patient number.  Any personal 
information, including patient name, should be removed or rendered illegible to preserve 
individual confidentiality.  The eCRF should not be used as a source document unless otherwise 
specified by the Sponsor.  
Neither the Sponsor nor a service provider contracted to analyze data and complete the study 
report is permitted to interpret a blank answer; therefore, all fields should be completed.  All 
requested information must be entered on the eCRFs. If an item is not available or is not 
applicable, this fact should be indicated as not available (N/A) or not done (N/D); do not leave a 
field blank.  
Each set of completed eCRFs must be signed and dated by the Investigator acknowledging 
review and that the data are accurate and complete.  The completed database is to be returned to 
the Sponsor as soon as practical after completion by the mechanism prescribed for the protocol. 
It is essential that all dates appearing on the Sponsor’s patient data collection forms for 
laboratory tests, cultures, etc, be the dates on which the specimens were obtained or the 
procedures performed.  The eCRFs will be electronically signed by the Investigator and dated as 
verification of the accuracy of the recorded data.  All data collection forms should be completed 
within a timely manner according to the eCRF completion guidelines following the evaluation. 


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18. 
ADMINISTRATIVE CONSIDERATIONS 
18.1. 
Investigators 
The Investigator must agree to the responsibilities and obligations listed below, as specified by 
the appropriate FDA/EMA regulatory requirements or ICH/GCP guidelines: 
• Agree to conduct the study in accordance with the relevant current protocol 
• Agree to personally conduct or supervise the described investigation(s) 
• Agree to inform any patients, or persons used as controls, that the study drugs are 
being used for investigational purposes and ensure that the requirements relating to 
obtaining informed consent and IRB/IEC review and approval are met  
• Agree to report adverse experiences that occur during the course of the 
investigation(s)  
• Read and understand the information in the IB, including the potential risks and side 
effects of the study drug 
• Ensure that all associates, colleagues, and employees assisting in the conduct of the 
study are informed about their obligations in meeting the above commitments 
• Maintain adequate and accurate records and make those records available for 
inspection  
• Ensure that an appropriate IRB/IEC will be responsible for the initial and continuing 
review and approval of the clinical investigation 
• Agree to promptly report to the IRB/IEC all changes in the research activity and all 
unanticipated problems involving risks to patients or others 
• Agree to not make changes in the research without IRB/IEC approval, except where 
necessary to eliminate apparent hazards to patients 
• Comply with all other requirements regarding the obligations of clinical Investigators 
and all other pertinent requirements. 
• Refer also to: 
− FDA Regulations Related to GCP and Clinical Trials: 
http://www.fda.gov/oc/gcp/regulations.html 
− Guidance and Information Sheets on GCP in FDA-Regulated Clinical Trials: 
http://www.fda.gov/oc/gcp/guidance.html 
− Guidance for IRBs and Clinical Investigators: 
http://www.fda.gov/oc/ohrt/irbs/default.htm 
− DIRECTIVE 2001/20/EC:  
http://ec.europa.eu/health/files/eudralex/vol-1/dir_2001_20/dir_2001_20_en.pdf 


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− Guidance for Industry – E6 Good Clinical Practice: Consolidated Guidance: 
http://www.fda.gov/cder/guidance/959fnl.pdf 
18.2. 
Amendments 
Changes to the research covered by this protocol must be implemented by formal protocol 
amendment.  All amendments to the protocol must be initiated by the Sponsor and signed and 
dated by the Investigator.  Protocol amendments must not be implemented without prior IRB or 
IEC approval.  Documentation of amendment approval by the Investigator and IRB or IEC must 
be provided to the Sponsor or its authorized representative.  When the change(s) involve only 
logistic or administrative aspects of the study, the IRB or IEC only needs to be notified.  
During the course of the study, in situations where a departure from the protocol is unavoidable, 
the Investigator will contact the Medical Monitor.  Except in emergency situations, this contact 
should be made before implementing any departure from the protocol.  In all cases, contact with 
the Medical Monitor must be made as soon as possible to discuss the situation and agree on an 
appropriate course of action.  The data recorded on the eCRF and source documents will reflect 
any departure from the protocol and the source documents will describe the departure and the 
circumstances requiring it. 
18.3. 
Financial Disclosure 
Prior to the start of the study, Investigators will release sufficient and accurate financial 
information that permits the Sponsor to demonstrate that an Investigator and all study relevant 
assigned personnel have no personal or professional financial incentive regarding the future 
approval or disapproval of the study drug such that his or her research might be biased by such 
incentive. 


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19. 
PUBLICATION AND DISCLOSURE POLICY 
It is understood by the Investigator that the information and data included in this protocol may be 
disclosed to and used by the Investigator’s staff and associates as may be necessary to conduct 
this clinical study. 
All information derived from this clinical study will be used by the Sponsor (or designee) and 
therefore, may be disclosed by the Sponsor (or designee) as required to other clinical 
Investigators, to the FDA, EMA, and to other government agencies, or in connection with 
intellectual property filings or publications.  In order to allow for the use of the information 
derived from this clinical study, it is understood by the Investigator that there is an obligation to 
provide the Sponsor with complete test results and all data from this clinical study.  The 
Investigator agrees to maintain this information in confidence, to use the information only to 
conduct the study, and to use the information for no other purpose without the Sponsor’s prior 
written consent (or as otherwise may be permitted pursuant to a written agreement with the 
Sponsor or its designee). 
The results of the study will be reported in a clinical study report prepared by the Sponsor (or 
designee), which will contain eCRF data from all clinical sites that conducted the study. 
The Sponsor shall have the right to publish data from the study without approval from the 
Investigator.  Manuscript(s) and abstract(s) may only be prepared through cooperation between 
the Sponsor (or designee) and the study Investigator(s).  If an Investigator wishes to publish 
information from the study, a copy of the manuscript must be provided to the Sponsor for review 
in accordance with the provisions of such Investigator’s written agreement with the Sponsor (or 
designee) before submission for publication or presentation.  If requested by the Sponsor in 
writing, the Investigator will withhold such publication in accordance with the provisions of such 
agreement. 


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20. 
LIST OF REFERENCES 
Food and Drug Administration (2012). FDA announces safety changes in labeling for some 
cholesterol-lowering drugs [Press release]. Retrieved from 
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm293623.htm  
Jacobson TA for the NLA Task Force on Statin Safety - 2014 update. J Clin Lipidol. 
2014;8:S1-4.  
Mozffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al, for the writing 
group Members. Heart Disease and Stroke Statistics—2015 Update. A Report from the 
American Heart Association. Circ. 2015;131:e29-322. 
Nichols M, Townsend N, Scarborough P, Rayner M. Cardiovascular disease in Europe 2014: 
epidemiological update. Eur Heart J. 2014; 35:2950-9. 
Sharrett AR, Ballantyne CM, Coady SA, Heiss G, Sorlie PD, Catellier D, et al. Atherosclerosis 
Risk in Communities Study Group. Coronary heart disease prediction from lipoprotein 
cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density 
subfractions. The Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 
2001;104:1108-13. 
Stone NJ, Robinson J, Lichtenstein AH, Bairey Merc CN, Blum CB, Eckel RH, et al. 
2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic 
cardiovascular risk in adults: a report of the American College of Cardiology/American Heart 
Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24;129(25 Suppl 2):S1-45. 
doi: 10.1161/01.cir.0000437738.63853.7a 
Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA. 2003:289:1681-90. 
World Health Organization (WHO) Fact Sheet No 317 Updated January 2015. 
 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 72 of 114 
21. 
APPENDICES 
Appendix 1: 
Schedule of Events (Subject Visit Schedule) 
Appendix 2: 
Sponsor’s Signature 
Appendix 3: 
Investigator’s Signature 
Appendix 4: 
Summary of Changes in Amendment 1 
 
 
 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 73 of 114 
APPENDIX 1. SCHEDULE OF EVENTS (SUBJECT VISIT SCHEDULE) 
 
Schedule of Events 
Visit 
S11,2 
S2 
S3 
S4 
T1 
T2 
T3/EOS)3 
Month 
Month -4.5 
Month -3 
Month -2 
Month -1 
Week 0 
Month 1 
Month 2 
Day 
Procedure 
Day -135 
Day-90 ±3 
Day -60 ±3 
Day -30 ±3 
Day 
1* 
Day31 ±3 
Day61 ±3 
Informed Consent 
X 
 
 
 
 
 
 
Enrollment Criteria 
X 
X 
X 
X 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
Adverse Event Recording 
 
X 
X 
X 
X 
X 
X 
Physical Exam 
 
X 
 
 
 
 
X 
Weight4 
X 
 
 
 
X 
 
X 
Height 
X 
 
 
 
 
 
 
Vital Signs6 
X 
X 
X 
X 
X 
X 
X 
Serology7 
X 
 
 
 
 
 
 
Serum Pregnancy/FSH8  
X 
 
 
 
 
 
 
Urine pregnancy test for 
women of childbearing 
potential only 
 
 
 
 
X 
 
 
TSH 
X 
 
 
 
 
 
 
Clinical Safety Labs9 
X 
 
 
 
X 
X 
X 
Basic Fasting Lipids10 
X 
X** 
X 
X*** 
X 
X 
X 
ApoB and hs-CRP 
 
X 
 
 
X 
X 
X 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 74 of 114 
 
Schedule of Events 
Visit 
S11,2 
S2 
S3 
S4 
T1 
T2 
T3/EOS)3 
Month 
Month -4.5 
Month -3 
Month -2 
Month -1 
Week 0 
Month 1 
Month 2 
Day 
Procedure 
Day -135 
Day-90 ±3 
Day -60 ±3 
Day -30 ±3 
Day 
1* 
Day31 ±3 
Day61 ±3 
HbA1C 
X 
 
 
 
X 
 
X 
PK – predose trough 
 
 
 
 
X 
X 
X 
Diet and exercise counseling11 
X 
X 
 
 
X 
X 
X 
Establish Patient Eligibility 
 
 
 
 
X 
 
 
Randomization 
 
 
 
 
X 
 
 
IWRS Contact12 
X 
 
 
 
X 
X 
X 
PCSK9i administered at site 
 
X 
X 
X 
X 
X 
 
Double-blind Drug Dispensing 
 
 
 
 
X 
X 
 
IMP Return/Compliance 
 
 
 
 
 
X 
X 
PCSK9i Return/Accountability 
 
X 
X 
X 
X 
X 
 
NOTE: For patients who withdraw from study drug treatment, but consent to be followed for safety assessments and return to clinic for these visit, the visits will occur according 
to the protocol schedule.  Safety assessments should include clinical safety and basic lipid laboratories, adverse events (AEs), physical examination (PE), and vital signs.  For 
patients who withdraw from study drug treatment, but consent to be followed for safety assessments by phone, the telephone contacts will occur according the protocol schedule 
with information regarding current health status and to collect information on AEs (eg, recent procedures, hospitalizations, and if the patient has died, the cause of death).  If a 
patient does not provide consent to be followed for safety assessments per the protocol (either by returning to clinic or by phone), Visit T4 will be considered the End of Study 
(EOS)/Early Withdrawal from study and no further visits will be scheduled. 
1 An optional basic fasting lipid MAY be completed prior to S2, but must occur just prior to the next witnessed PCSK9i dose if patient fails to meet lipid entry criterion at 
Visit S1.  If this optional basic fasting lipid is completed, the average of the 2 lipid values will be used to determine eligibility. 
2 A recheck of blood pressure may be completed prior to T1 if the patient’s diastolic blood pressure (DBP) and/or systolic blood pressure (SBP) meet the exclusion criteria levels.  
Patients may randomize after blood pressure medications have been adjusted, the patients have been on stable doses of blood pressure medications for at least 2 weeks, and the 
repeat blood pressure values (DBP and/or SBP) do not meet exclusionary values.  Repeat labs may be completed prior to T1 to determine eligibility if the patient’s estimated 
glomerular filtration rate (eGFR), alanine aminotransferase (ALT), aspartate aminotransferase (AST) or other labs meet exclusion criteria levels.  If this optional lab is 
completed, the repeated value will be used to determine eligibility. 
3 All procedures will be completed for all patients at either T3/EOS if completing the study or early withdrawal. 
4 Body weight will be measured while fasting, using consistent scales, after voiding, and without shoes and outerwear (eg, coats).   
6 Vital signs will include DBP, SBP, heart rate (HR) and will be collected prior to any blood sample collection.  Patient will rest for 5 minutes prior to assessments 
7 Serology for HBsAg, HCV-ABVivi 
8 Pregnancy test completed in women of child-bearing age only. FSH in naturally postmenopausal women ≥1 year without menses and <55 years; 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 75 of 114 
9 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits.  Please refer to laboratory manual for detailed schedule of tests. 
10 Basic fasting lipids include total cholesterol (TC), calculated low-density lipoprotein cholesterol (LDL-C),
 non-HDL-C,), and 
).   
11 Diet and exercise counseling per local and/or regional guidelines for the management of hyperlipidemia. 
12 Interactive web response system (IWRS) contact at either an early withdrawal or an EOS visit to register study discontinuation visit date. 
* Patients must be on PCSK9 for 30 ± 3 days during each month of the PCSK9 run-in period before initiating Day 1.   
** LDL-C must be ≥160 mg/dL and TG <500 mg/dL before initiating PCSK9i.  A local lab may be used to assess LDL-C and TG for eligibility prior to initiating Repatha, but a 
central lab must also be conducted at this visit.  
*** LDL-C must be ≥70 mg/dL to qualify for randomization.  Only a central lab may be used to assess entry LDL-C. 


Bempedoic Acid 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
Amendment 1, 05 March 2017 
APPENDIX 2. SPONSOR'S SIGNATURE 
Study Title: 
A Randomized, Double-Blind, Parallel Group, Multicenter Study to 
Evaluate the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180 mg 
QD when added to PCSK9-Inhibitor Therapy 
Study Number: 
1002-039 
Final Date: 
05 March 2017 
This clinical study protocol was subject to critical review and has been approved by the Sponsor. 
The following personnel contributed to writing and/or approving this protocol: 
Signed:
-
Confidential 
Page 76 of 114 


Bempedoic Acid 
Esperion Therapeutics, Inc. 
Clinical Study Protocol I 002-039 
Amendment 1, 05 March 2017 
Study Title: 
A Randomized, Double-Blind, Parallel Group, Multicenter Study to 
Evaluate the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180 mg 
QD when added to PCSK9-Inhibitor Therapy 
Study Number: 
1002-039 
Final Date: 
05 March 2017 
This clinical study protocol was subject to critical review and has been approved by the Sponsor. 
The following personnel contributed to writing and/or approving this protocol: 
Signed:
-------
Confidential 
Page 77 of 114 
Date: 
9-March-2017 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 78 of 114 
APPENDIX 3. INVESTIGATOR’S SIGNATURE 
Study Title: 
A Randomized, Double-Blind, Parallel Group, Multicenter Study to 
Evaluate the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180 mg 
QD when added to PCSK9-Inhibitor Therapy  
Study Number: 
1002-039 
Final Date: 
05 March 2017 
 
I have read the protocol described above.  I agree to comply with all applicable regulations and 
to conduct the study as described in the protocol.  
 
 
Signed:  
Date:  
 
Name and Credentials:  
Title:  
Affiliation:  
Address:  
Phone Number:  
 
 
 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 79 of 114 
APPENDIX 4. SUMMARY OF CHANGES IN AMENDMENT 1 
SUMMARY OF CHANGES 
CLINICAL STUDY PROTOCOL 
Study Number: 
1002-039 
Study Title: 
A Randomized, Double-Blind, Parallel Group, 
Multicenter Study to Evaluate the Efficacy and Safety of 
Bempedoic Acid (ETC-1002) 180 mg QD When added to 
proprotein convertase subtilisin/kexin type 9 
(PCSK9)-inhibitor Therapy 
Protocol Version Incorporating 
Current Summary of Changes: 
Amendment 1, 05 March 2017 
Preceding Protocol Version: 
Original Protocol, 22 November 2016 
Investigational Product Name: 
ETC-1002 
Conventions used in this Summary of Changes Document 
1. The text immediately preceding and following a change to the protocol is included for 
each change in order to provide the reviewer with a reference point to identify the change 
in the protocol. 
2. All locations (ie, section numbers and/or header text) refer to the current protocol 
version, which incorporates the items specified in this Summary of Changes document. 
3. The original text is from the preceding protocol version. 
4. In the “New Text”, all substantive text added to the protocol is bolded and italicized. 
5. In the “New Text”, text deleted from the protocol is indicated in strikethrough font. 
Summary and Justification of Changes 
Below are the main protocol changes: 
• The PCSK9 run-in was extended from 1 month to 3 months in order to ensure all 
patients reach steady state prior to randomization.  
• Added/revised the following subject exclusion criteria to exclude patients that were 
recently on PCSK9 inhibitors as well as HeFH patients (this population will be 
studied in P3 trials): 
− Heterozygous Familial Hypercholesterolemia (HeFH) 
− Concomitant use of a PCSK9 inhibitor (Praluent® [alirocumab] or Repatha® 
[evolocumab]) at (Visit S1) or prior use within the past 16 weeks of Visit S1 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 80 of 114 
− Use of any experimental or investigational drugs within 30 days or 5 half-lives, 
whichever is longer 
• Updated contraception language to align with other P3 ETC-1002 clinical trials.  
− Added requirement that women use 2 rather than 1 form of acceptable 
contraception; expanded definition of true abstinence. 
• Removed remnant ECG language.  There are no ECG assessments, these were 
inadvertently added to the original protocol  
• Removed evaluation of PCSK9 levels from exploratory objectives and endpoints 
• Specified that LDL-C levels used for evaluation for study inclusion can use a local 
lab at S3, but that S4 evaluation can only use a central lab 
 
CHANGE 1 
REVISION OF PROTOCOL TITLE AND TITLE PAGE VERSION 
INFORMATION 
Location: 
Protocol title 
Original Text: 
A Randomized, Double-Blind, Parallel Group, Multicenter Study to Evaluate the Efficacy and 
Safety of Bempedoic Acid (ETC-1002) 180 mg QD when added to PCSK9-Inhibitor Therapy 
New Text: 
A Randomized, Double-Blind, Parallel Group, Multicenter Study to Evaluate the Efficacy and 
Safety of Bempedoic Acid (ETC-1002) 180 mg QD when added to Proprotein Convertase 
Subtilisin/Kexin Type 9 (PCSK9)-Inhibitor Therapy 
Location: 
Title page 
Original Text: 
 
Version 
Date 
 
 
Original Protocol: 
22 November 2016 
 
New Text: 
 
Version 
Date 
 
 
Original Protocol 
22 November 2016 
 
 
Protocol Amendment 1: 
05 March 2017 
 
 


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Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 82 of 114 
CHANGE 3 
STUDY OBJECTIVES REVISIONS 
Location: 
Section 2, Synopsis; 
Section 5.1.3, Exploratory Objectives;  
Section 5.1.6, Exploratory Endpoints 
Original Text: 
New Text: 
 
CHANGE 4 
STUDY METHODOLOGY REVISIONS 
Location: 
Section 2, Synopsis; 
Section 6.1, Overall Study Design 
Original Text: 
This is a Phase 2, randomized, double-blind, placebo-controlled, parallel group multicenter study 
that will be conducted at approximately 20 clinical sites in North America.  Screening 
Month -2.5 (Visit S1) will occur approximately 10 weeks prior to randomization.  After 
providing informed consent at Visit S1, patients will stop all background lipid-lowering therapy 
and lipid-modifying nutritional supplements, if applicable.  All patients will return to the clinic 
on Week -4 (Visit S2).  During this visit, patients with an LDL-C value ≥160 mg/dL (via central 
or local lab) and triglycerides <500 mg/dL (via central or local lab) will initiate PCSK9 
background therapy (Repatha 420 mg QM).  Sites that do not use a local lab may need to bring 
patients back for another visit to administer PCSK9 background therapy, as a qualifying LDL 
value is required prior to initiating background therapy.  No other background lipid-modifying 
therapy except study provided PCSK9 will be permitted during the trial.  After a 1-month (at 
least 30 days) PCSK9i lipid-stabilization period, patients will return to the clinic for Visit S3.  
The sole purpose of this visit is to determine entry LDL-C prior to randomization.  Patients with 
an LDL-C ≥70 mg/dL (via central or local lab) at this visit will qualify for randomization.  
Patients with LDL-C <70 mg/dL at Visit S3 will be screen failed and no further PCSK9i therapy 
will be administered.  Day 1 should occur immediately (ideally within 3 days) after Visit S3, 
once LDL-C eligibility is established.  On Day 1, qualified patients will be randomized 1:1 to 
bempedoic acid 180 mg/day (n = 26) or matching placebo (n = 26).  Randomized patients will 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 83 of 114 
return for clinic visits at Month 1 (Visit T2) and Month 2 (Visit T3).  Both study drug and 
PCSK9i doses will be administered on site during clinic visits after all procedures have been 
completed. 
New Text: 
This is a Phase 2, randomized, double-blind, placebo-controlled, parallel group multicenter study 
that will be conducted at approximately 20 clinical sites in North America.  Screening Visit S1 
will occur approximately 2.54.5 months prior to randomization.  After providing informed 
consent at Visit S1, patients will stop all background lipid-lowering therapy and lipid-modifying 
nutritional supplements, if applicable.  All patients will return to the clinic on Month -31 
(Visit S2).  During this visit, patients with an LDL-C value ≥160 mg/dL (via central or local lab) 
and triglycerides <500 mg/dL (via central or local lab) will initiate PCSK9i background therapy 
(Repatha 420 mg once monthly [QM]).  Sites that do not use a local lab may need to bring 
patients back for another visit to administer PCSK9i background therapy, as a qualifying LDL-C 
value is required prior to initiating the 3-month PCSK9i run-in periodinitial background 
therapy.  No other background lipid-modifying therapy except study-provided PCSK9i will be 
permitted during the trial.  After a 1 month (at least 30 days ±3 days) PCSK9i lipid stabilization 
period, patients will return to the clinic for Month -2 (Visit S3) followed by Month -1 (Visit S4) 
30 days ± 3 days later.  During these visits, Repatha will be administered, labs will be collected, 
and safety assessed. The sole purpose of this At visit S4, is to determine entry LDL-C will be 
checked a second time prior to randomization.  The sole purpose of this visit is to determine 
entry LDL-C prior to randomization. Patients with an LDL-C ≥70 mg/dL (via central or local 
lab) at this visit will qualify for randomization. Patients with LDL-C <70 mg/dL at Visit S4 will 
be screen failed and no further PCSK9i therapy will be administered.  Day 1 should occur 
immediately (ideally within 3 days) 30 days ±3 days after Visit S4, once LDL-C eligibility is 
established.  On Day 1, qualified patients will be randomized 1:1 to bempedoic acid 180 mg/day 
(n = 26) or matching placebo (n = 26).  Randomized patients will return for clinic visits at 
Month 1 (Visit T2) and Month 2 (Visit T3).  Both study drug and PCSK9i doses will be 
administered on site during clinic visits after all procedures have been completed. 
 
CHANGE 5 
SUBJECT INCLUSION CRITERIA REVISIONS 
Location: 
Section 2, Synopsis; 
Section 7.1, Subject Inclusion Criteria 
Original Text: 
1. Provision of written informed consent must be obtained prior to any study-specific 
procedure. 
2. Age ≥18 years or legal age of majority depending on regional law, whichever is greater at 
Month -2.5 (Visit S1) 
3. Fasting, calculated LDL-C at screening (Month -1) ≥160 mg/dL and ≥70 mg/dL at 
Visit S3 


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Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
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Page 84 of 114 
Note:  A single repeat of LDL-C may be completed.  For those patients who have a repeat 
LDL-C, the average of the 2 values will be used to determine eligibility. 
4. Men and nonpregnant, nonlactating women.  Women must be: 
a. Naturally postmenopausal defined as ≥1 year without menses and:  
−  
≥55 years, or  
−  
<55 years with follicle-stimulating hormone (FSH) ≥40.0 IU/L; or 
b. Surgically sterile including hysterectomy, bilateral oophorectomy, and/or tubal 
ligation; or 
c. Women of childbearing potential willing to use 1 acceptable method of birth control 
including: 
− oral, implanted, topical or injectable birth control medications 
− placement of an intrauterine device with or without hormones 
− barrier methods including condom or occlusive cap with spermicidal foam or 
spermicidal jelly 
− vasectomized male partner who is the sole partner for this patient  
− true abstinence (not including periodic abstinence such as calendar, ovulation, 
symptothermal, postovulation methods, or withdrawal) 
There are no protocol-specific birth control requirements for men with partners who are 
able to become pregnant. 
New Text: 
1. Provision of written informed consent must be obtained prior to any study-specific 
procedure. 
2. Age ≥18 years or legal age of majority depending on regional law, whichever is greater at 
Month -24.5 (Visit S1) 
3. Fasting, calculated LDL-C at screening (Month -1Visit S2) ≥160 mg/dL and ≥70 mg/dL 
at Visit S3S4 
Note:  A single repeat of LDL-C may be completed.  For those patients who have a repeat 
LDL-C, the average of the 2 values will be used to determine eligibility. 
4. Men and nonpregnant, nonlactating women.  Women must be: 
a. Naturally postmenopausal defined as ≥1 year without menses and:  
−  
≥55 years, or  
−  
<55 years with follicle-stimulating hormone (FSH) ≥40.0 IU/L; or 
b. Surgically sterile including hysterectomy, bilateral oophorectomy, and/or tubal 
ligation; or 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
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Page 85 of 114 
c. Women of childbearing potential willing to use 12 acceptable methods of birth 
control including: 
− oral, implanted, topical or injectable birth control medications 
− placement of an intrauterine device with or without hormones 
− barrier methods including condom or occlusive cap with spermicidal foam or 
spermicidal jelly 
− vasectomized male partner who is the sole partner for this patient  
− true abstinence (not including periodic abstinence such as calendar, ovulation, 
symptothermal, postovulation methods, or withdrawal) 
− true abstinence:  when this is in line with the preferred and usual lifestyle of the 
subject.  (Periodic abstinence [eg, calendar, ovulation, symptothermal, 
postovulation methods], declaration of abstinence for the duration of a trial, 
and withdrawal are not acceptable methods of contraception.)(not including 
periodic abstinence such as calendar, ovulation, symptothermal, postovulation 
methods, or withdrawal) 
There are no protocol-specific birth control requirements for men with partners who are 
able to become pregnant. 
 
CHANGE 6 
SUBJECT EXCLUSION CRITERIA REVISIONS 
Location: 
Section 2, Synopsis; 
Section 7.2, Subject Exclusion Criteria 
Original Text: 
1. Homozygous Familial Hypercholesterolemia (HoFH) 
2. Total fasting TG ≥500 mg/dL (5.6 mmol/L) at Month -1 (Visit S2) 
Note:  A single repeat of TG may be completed prior to initiation of the single-blind Run-
in period.  For those patients who have a repeat TG, the average of the 2 values will be 
used to determine eligibility. 
3. Renal dysfunction or a glomerulonephropathy defined as either nephritic or nephrotic 
syndrome, including estimated glomerular filtration rate (eGFR; using central laboratory 
determined Modification of Diet in Renal Disease [MDRD] formula) 
<30 mL/min/1.73 m2 at Month -2.5 (Visit S1) 
Note:  A single repeat of eGFR may be completed prior to randomization.  For those 
patients who have a repeat eGFR, the average of the 2 values be used to determine 
eligibility. 
4. All patients with known cardiovascular disease (CVD) or peripheral arterial disease 
(PAD) or cerebrovascular disease (CD) 


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Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
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5. History of type 1 or type 2 diabetes or laboratory evidence of diabetes (fasting blood 
glucose [FBG] >126 mg/dL or glycosylated hemoglobin, Type A1C (HbA1C) >6.5%) 
without prior diagnosis of diabetes at Month -2.5 (Visit S1) 
6. Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) >160 mmHg 
or diastolic blood pressure (DBP) >100 mmHg at Month -2.5 (Visit S1) 
7. Uncontrolled hypothyroidism, including thyroid-stimulating hormone (TSH) >1.5 × the 
upper limit of normal (ULN) at Month -2.5 (Visit S1) 
8. Liver disease or dysfunction, including: 
a. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≥2.0 × 
ULN at Month -2.5 (Visit S1). 
b. Positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C 
antibodies (HCV-ABVivi) at Month -2.5 (Visit S1). 
Note:  If total bilirubin (TB) ≥1.2 × ULN, a reflex indirect (unconjugated) bilirubin 
will be obtained and if consistent with Gilbert’s disease, the patient may be enrolled 
in the study.   
Note: At the discretion of the investigator, a single repeat of ALT and/or AST may be 
completed.  For those patients who have a repeat ALT and/or AST, the average of the 
2 values will be used to determine eligibility.  Also, if test for hepatitis C antibody is 
positive, but reflexive test for Hepatitis C ribonucleic acid (RNA) is negative, patient 
can be enrolled.  
9. Gastrointestinal conditions or procedures (including weight loss surgery; eg, Lap-Band® 
or gastric bypass) that may affect drug absorption 
10. History of hematologic or coagulation disorders or a hemoglobin (Hgb) level <10 g/dL at 
Month -2.5 (Visit S1) 
11. History of malignancy (except non-metastatic basal or squamous cell carcinoma of the 
skin and cervical carcinoma in situ) 
12. Unexplained creatine kinase (CK) >3 × ULN at screening up to randomization (ie, not 
associated with recent trauma or physically strenuous activity).  Patients with an 
explained CK elevation must have single repeat CK ≤3 × ULN prior to randomization. 
13. History within the last 2 years of drug, alcohol, amphetamine and derivatives, or cocaine 
abuse.  Patients taking  amphetamine derivatives for medical reasons such as attention 
deficit disorder or taking prescription opioids or other meds for chronic pain that have 
been stable, without evidence of abuse prescribed by and under the care of a health care 
practitioner can be enrolled after evaluation by the Investigator. 
14. Blood donation, participation in a clinical study with multiple blood draws, major trauma, 
blood transfusion, or major surgery with or without blood loss within 30 days prior to 
randomization 
15. Use of any experimental or investigational drugs within 30 days 
16. Previous enrollment in an Esperion Phase 3 bempedoic acid (ETC-1002) clinical study 


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Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
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Page 87 of 114 
17. Use of a cholesterylester transfer protein (CETP) inhibitor in the last 12 months prior to 
screening, such as: anacetrapib, dalcetrapib or evacetrapib 
18. Use of, or a plan to initiate, these prohibited therapies/supplements during the study: 
• Mipomersen (must be stopped at least 6 months prior to Month -2.5 [Visit S1]), 
• Lomitapide or apheresis therapy (must be stopped at least 3 months prior to 
Month -2.5 [Visit S1]),  
• Red yeast rice containing products (must be stopped on or before Month -2.5 
[Visit S1]),  
• Lipid regulating drugs or supplements (must be stopped on or before Month -2.5 
[Visit S1]) 
19. Planned initiation or changes to the following drugs prior to Month -2.5: 
• Hormone replacement (6 weeks prior to Month -2.5) 
• Thyroid replacement (6 weeks prior to Month -2.5) 
• Obesity medication (3 months prior to Month -2.5) 
20. A medical or situational (ie, geographical) finding that in the investigator’s opinion may 
compromise the patient’s safety or ability to complete the study 
21. Patient is pregnant or breast feeding, or planning to become pregnant during treatment 
and/ or within 12 weeks after the end of treatment 
22. An employee or contractor of the facility conducting the study, or a family member of the 
Principal Investigator, Co-Investigator, or Sponsor. 
New Text: 
1. Homozygous Familial Hypercholesterolemia (HoFH) 
2. Total fasting TG ≥500 mg/dL (5.6 mmol/L) at Month -13 (Visit S2) 
Note:  A single repeat of TG may be completed prior to initiation of the single-blind Run-
in period.  For those patients who have a repeat TG, the average of the 2 values will be 
used to determine eligibility. 
3. Renal dysfunction or a glomerulonephropathy defined as either nephritic or nephrotic 
syndrome, including estimated glomerular filtration rate (eGFR; using central laboratory 
determined Modification of Diet in Renal Disease [MDRD] formula) 
<30 mL/min/1.73 m2 at Month -24.5 (Visit S1) 
Note:  A single repeat of eGFR may be completed prior to randomization.  For those 
patients who have a repeat eGFR, the average of the 2 values be used to determine 
eligibility. 
4. All patients with known cardiovascular disease (CVD) or peripheral arterial disease 
(PAD) or cerebrovascular disease (CD) 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
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Page 88 of 114 
5. History of type 1 or type 2 diabetes or laboratory evidence of diabetes (fasting blood 
glucose [FBG] >126 mg/dL or glycosylated hemoglobin, Type A1C (HbA1C) >6.5%) 
without prior diagnosis of diabetes at Month -24.5 (Visit S1) 
6. Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) >160 mmHg 
or diastolic blood pressure (DBP) >100 mmHg at Month -24.5 (Visit S1) 
7. Uncontrolled hypothyroidism, including thyroid-stimulating hormone (TSH) >1.5 × the 
upper limit of normal (ULN) at Month -24.5 (Visit S1) 
8. Liver disease or dysfunction, including: 
a. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≥2.0 × 
ULN at Month -24.5 (Visit S1). 
b. Positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C 
antibodies (HCV-ABVivi) at Month -24.5 (Visit S1). 
Note:  If total bilirubin (TB) ≥1.2 × ULN, a reflex indirect (unconjugated) bilirubin 
will be obtained and if consistent with Gilbert’s disease, the patient may be enrolled 
in the study.   
Note: At the discretion of the investigator, a single repeat of ALT and/or AST may be 
completed.  For those patients who have a repeat ALT and/or AST, the average of the 
2 values will be used to determine eligibility.  Also, if test for hepatitis C antibody is 
positive, but reflexive test for Hepatitis C ribonucleic acid (RNA) is negative, patient 
can be enrolled.  
9. Gastrointestinal conditions or procedures (including weight loss surgery; eg, Lap-Band® 
or gastric bypass) that may affect drug absorption 
10. History of hematologic or coagulation disorders or a hemoglobin (Hgb) level <10 g/dL at 
Month -24.5 (Visit S1) 
11. History of malignancy (except non-metastatic basal or squamous cell carcinoma of the 
skin and cervical carcinoma in situ) 
12. Unexplained creatine kinase (CK) >3 × ULN at screening up to randomization (ie, not 
associated with recent trauma or physically strenuous activity).  Patients with an 
explained CK elevation must have single repeat CK ≤3 × ULN prior to randomization. 
13. History within the last 2 years of drug, alcohol, amphetamine and derivatives, or cocaine 
abuse.  Patients taking  amphetamine derivatives for medical reasons such as attention 
deficit disorder or taking prescription opioids or other meds for chronic pain that have 
been stable, without evidence of abuse prescribed by and under the care of a health care 
practitioner can be enrolled after evaluation by the Investigator. 
14. Blood donation, participation in a clinical study with multiple blood draws, major trauma, 
blood transfusion, or major surgery with or without blood loss within 30 days prior to 
randomization 
15. Use of any experimental or investigational drugs within 30 days or 5 half-lives, 
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16. Previous enrollment in an Esperion Phase 3 bempedoic acid (ETC-1002) clinical study 
17. Use of a cholesterylester transfer protein (CETP) inhibitor in the last 12 months prior to 
screening, such as: anacetrapib, dalcetrapib or evacetrapib 
18. Use of, or a plan to initiate, these prohibited therapies/supplements during the study: 
• Mipomersen (must be stopped at least 6 months prior to Month -24.5 [Visit S1]), 
• Lomitapide or apheresis therapy (must be stopped at least 3 months prior to 
Month -24.5 [Visit S1]),  
• Red yeast rice containing products (must be stopped on or before Month -24.5 
[Visit S1]),  
• Lipid regulating drugs or supplements (must be stopped on or before Month -24.5 
[Visit S1]) 
19. Planned initiation or changes to the following drugs prior to Month -24.5: 
• Hormone replacement (6 weeks prior to Month -24.5) 
• Thyroid replacement (6 weeks prior to Month -24.5) 
• Obesity medication (3 months prior to Month -24.5) 
20. A medical or situational (ie, geographical) finding that in the investigator’s opinion may 
compromise the patient’s safety or ability to complete the study 
21. Patient is pregnant or breast feeding, or planning to become pregnant during treatment 
and/ or within 30 days12 weeks after the end of treatment 
22. An employee or contractor of the facility conducting the study, or a family member of the 
Principal Investigator, Co-Investigator, or Sponsor. 
23. Heterozygous familial hypercholesterolemia (HeFH) 
24. Concomitant use of a PCSK9 inhibitor (Praluent® [alirocumab] or Repatha® 
[evolocumab]) at (Visit S1) or prior use within the past 16 weeks of Visit S1 
 
CHANGE 7 
PCSK9 INHIBITOR ADMINISTRATION CLARIFICATION 
Location: 
Section 2, Synopsis 
Original Text: 
Test product, dose, and mode of administration:   
• Bempedoic acid 180-mg tablets/day 
• Matching placebo tablets 
• PCSK9i – Repatha 420 mg QM 


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All study drug (bempedoic acid or placebo) will be ingested once daily with or without food.  On 
clinic days patients will come to the clinic in the fasted state and the PCSK9i and study drug will 
be administered after all study procedures have been conducted. 
New Text: 
Test product, dose, and mode of administration:   
• Bempedoic acid 180-mg tablets/once per day 
• Matching placebo tablets/once per day 
• PCSK9i – Repatha 420 mg QMinjection once monthly 
All study drug (bempedoic acid or placebo) will be ingested once daily with or without food.  On 
clinic days patients will come to the clinic in the fasted state and the PCSK9i and study drug will 
be administered after all study procedures have been conducted.  PCSK9i injections must be 
administered consistently throughout the trial within 30 ± 3 days from the previous dose.  
Efficacy will vary if the doses are not consistently administered. 
 
CHANGE 8 
REMOVAL OF ECG FROM SAFETY ASSESSMENTS 
Location: 
Section 2, Synopsis.  This change also made as applicable in Sections 1.11, Safety Parameters; 
13.7, Safety Endpoints; 14.1, Safety Monitoring; 17.3, Case Report Forms and Study Records; 
and Appendix 1 Schedule of Events (Subject Visit Schedule) 
Original Text: 
Adverse events and serious adverse events (SAEs) will be collected and reported.  Other safety 
assessments will include clinical safety laboratories (including hematology, blood chemistry, 
HbA1C, fasting glucose, and urinalysis), physical examination (PE) findings, vital signs, 
electrocardiogram (ECG) readings, and weight. 
New Text: 
Adverse events and serious adverse events (SAEs) will be collected and reported.  Other safety 
assessments will include clinical safety laboratories (including hematology, blood chemistry, 
HbA1C, fasting glucose, and urinalysis), physical examination (PE) findings, vital signs, 
electrocardiogram (ECG) readings, and weight. 
 


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CHANGE 9 
STATISTICAL METHODS REVISIONS 
Location: 
Section 2, Synopsis 
Section 13.2, Determination of Sample Size 
Original Text: 
Sample Size 
The planned total sample size for this study is 52 with 26 patients in the bempedoic acid 180 mg 
group and in the placebo group.  This sample size is expected to
 
 
  
New Text: 
Sample Size 
The planned total sample size for this study is 52 with 26 patients in the bempedoic acid 180 mg 
group and 26 in the placebo group.  This sample size is expected to
 
 
  
 
CHANGE 10 
REVISIONS TO STATISTICAL METHODS 
Location: 
Section 2, Synopsis 
Section 13.5, Primary Endpoint 
Original Text: 
Primary Endpoint 
The primary efficacy endpoint is the percent change from baseline to Month 2 in LDL-C.  The 
primary efficacy endpoint will be analyzed using analysis of covariance (ANCOVA), with 
treatment group as a factor and baseline LDL-C as a covariate.  Baseline LDL-C is defined as the 
Day 1 value.  The ANCOVA will be performed using the FAS, with patients included in their 
randomized treatment group regardless of the treatment they actually received.  Patients who are 
missing their Month 2 LDL-C will have their Month 2 value imputed by last observation carried 
forward (LOCF).  The least squares mean (LSM) and standard error (SE) for percent change 
estimate will be provided for both treatment groups, along with the placebo-corrected LSM, its 
95% confidence interval (CI) and associated p-value. 
New Text: 
Primary Endpoint 
The primary efficacy endpoint is the percent change from baseline to Month 2 in LDL-C.  The 
primary efficacy endpoint will be analyzed using analysis of covariance (ANCOVA), with 
treatment group as a factor and baseline LDL-C as a covariate.  The details of the ANCOVA 


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model and options to correct for unequal variances will be described in the SAP.  Baseline 
LDL-C is defined as the average of S4 and Day 1 values, if only 1 value is available, then that 
single value will be used as baseline.  The ANCOVA will be performed using the FAS, with 
patients included in their randomized treatment group regardless of the treatment they actually 
received.  Patients who are missing their Month 2 LDL-C will have their Month 2 value imputed 
by last observation carried forward (LOCF).  The least squares mean (LSM) and standard error 
(SE) for percent change estimate will be provided for both treatment groups, along with the 
placebo-corrected LSM, its 95% confidence interval (CI) and associated p-value. 
Location: 
Section 13.6, Secondary and Exploratory Efficacy Endpoints 
Original Text: 
The secondary efficacy endpoints (percent change from baseline to Month 1 in LDL-C; change 
from baseline to Months 1 and 2 in LDL-C; percent change from baseline to Months 1 and 2 in 
ApoB, non-HDL-C,TC, hs-CRP
and
, will be analyzed using the ANCOVA method 
similar to the primary endpoint.  Baseline value for TC, non-HDL-C,
 ApoB, and 
hs-CRP will be Day 1 value.  Each ANCOVA will be performed using the FAS, with patients 
included in their randomized treatment group regardless of the treatment they actually received.  
Missing values will be imputed using LOCF, where applicable.  For each parameter and analysis 
time point, the LSM and SE will be provided for both treatment groups, along with the placebo-
corrected LSM, its 95% CI and associated p value. 
New Text: 
The secondary efficacy endpoints (percent change from baseline to Month 1 in LDL-C; change 
from baseline to Months 1 and 2 in LDL-C; percent change from baseline to Months 1 and 2 in 
ApoB, non-HDL-C,TC, hs-CRP
and 
, will be analyzed using the ANCOVA method 
similar to the primary endpoint.  Baseline value for TC, non-HDL-C,
 will be 
the average of S4 and Day 1 values; ApoB, and hs-CRP will be the Day 1 value, if only 1 value 
is available, the single value will be used as the baseline.  Each ANCOVA will be performed 
using the FAS, with patients included in their randomized treatment group regardless of the 
treatment they actually received.  Missing values will be imputed using LOCF, where applicable.  
For each parameter and analysis time point, the LSM and SE will be provided for both treatment 
groups, along with the placebo-corrected LSM, its 95% CI and associated p value. 
 
CHANGE 11 
SAFETY ENDOINT REVISIONS 
Location: 
Section 2, Synopsis;  
Section 13.7, Safety Endpoints 
Original Text: 
Musculoskeletal Safety 
AEs of muscle-related symptoms will be summarized by treatment group.  In addition, the 
number and percent of patients with abnormal CK values will be summarized.   


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Diabetes/Hyperglycemia 
Cases of new onset of diabetes will be recorded as AEs and will be summarized using the 
appropriate SOC.  These events will be summarized by severity and relationship to study drug 
for each treatment group. 
Renal Safety 
Baseline eGFR and values of CK will be summarized by treatment group and by baseline eGFR 
categories.  Shift tables of eGFR category from baseline over the study, will be provided by 
treatment group.  Finally, muscle-related AEs will be summarized by treatment group and by 
baseline eGFR category. 
New Text: 
Musculoskeletal Safety 
AEs of muscle-related symptoms will be summarized by treatment group.  In addition, the 
number and percent of patients with abnormal CK values will be summarized.  Finally, muscle-
related AEs will be summarized by treatment group and by baseline eGFR category. 
Diabetes/Hyperglycemia 
Cases of new onset of diabetes will be recorded as AEs and will be summarized using the 
appropriate SOC.  These events will be summarized by severity and relationship to study drug 
for each treatment group. 
Renal Safety 
Baseline eGFR and values of CK will be summarized by treatment group and by baseline eGFR 
categories.  Shift tables of eGFR category from baseline over the study, will be provided by 
treatment group.  Finally, muscle-related AEs will be summarized by treatment group and by 
baseline eGFR category. 
 
CHANGE 12 
INVESTIGATIONAL PLAN REVISIONS 
Location: 
Section 6.3, Study Duration and Period 
Section 6.4, End of Study 
Original Text: 
6.3  
Study Duration and Period 
The duration of treatment will be 18 weeks (2.5-month screening period, a 1-month lipid-
stabilization period, and 2-month treatment period). 
6.4  
End of Study 
The study will end when the last randomized patient completes the Month 2 visit.  The estimated 
overall duration of the study (first patient first visit [FPFV] to last patient last visit [LPLV]) is 
approximately 8 months. 


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New Text: 
6.3  
Study Duration and Period 
The duration of treatment will be 2618 weeks (12.5-month screening period, a 31-month lipid-
stabilization period, and 2-month treatment period). 
6.4  
End of Study 
The study will end when the last randomized patient completes the Month 2 visit.  The estimated 
overall duration of the study (first patient first visit [FPFV] to last patient last visit [LPLV]) is 
approximately 10.58 months. 
Location: 
Section 6.6.1, Screening and 1 Month PCSK9i Run-in Period 
Original Text: 
Screening will occur approximately 10 weeks prior to Day 1 (Visit T1).  Eligible patients will 
return to the clinical site at Month -1 (Visit S2).  During this visit, patients with an LDL-C value 
≥160 mg/dL (via central or local lab) and triglycerides <500 mg/dL (via central or local lab) will 
initiate PCSK9i background therapy (Repatha 420 mg QM).  No other background lipid-
modifying therapy except study provided PCSK9i will be permitted during the trial.  
New Text: 
Screening will occur approximately 1810 weeks prior to Day 1 (Visit T1).  Eligible patients will 
return to the clinical site at Month -13 (Visit S2).  During this visit, patients with an LDL-C 
value ≥160 mg/dL (via central or local lab) and triglycerides <500 mg/dL (via central or local 
lab) will initiate study-provided PCSK9i background therapy (Repatha 420 mg QM).  No other 
background lipid-modifying therapy except study provided PCSK9i will be permitted during the 
trial.  
Location: 
Section 6.6.2, Randomization and Treatment Period;  
Original Text: 
Patients who satisfy all entry criteria, complete the 2.5-month screening period and 1-month (at 
least 30 days) PCSK9i run-in period and have an LDL-C ≥70 mg/dL at S3 will be randomized.  
Randomization numbers will be assigned via IWRS on Day 1 (Visit T1).  Patients will be 
randomized in a ratio of 1:1 to receive 1 of the following 2 treatments in a double-blind fashion: 
• Bempedoic acid 180-mg tablet 
• Matching placebo tablet 
New Text: 
Patients who satisfy all entry criteria, complete the 1.52.5-month screening period and 31-month 
(at least 30 days) PCSK9i run-in period and have an LDL-C ≥70 mg/dL at S43 will be 
randomized.  Randomization numbers will be assigned via IWRS on Day 1 (Visit T1).  Patients 


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will be randomized in a ratio of 1:1 to receive 1 of the following 2 treatments in a double-blind 
fashion in addition to monthly PCSK9i background therapy: 
• Bempedoic acid 180-mg tablet 
• Matching placebo tablet 
 
CHANGE 13 
ADMINISTRATION OF MEDICINAL PRODUCT REVISION 
Location: 
Section 9.2, Administration of Investigational Medicinal Product  
Original Text: 
PCSK9i will be administered on site at Visits S2, T1, and T2.  Doses will be stored and 
administered as required in prescribing information 
New Text: 
PCSK9i will be administered on site at Visits S2, S3, S4, T1, and T2.  Doses will be stored and 
administered as required in prescribing information 
 
CHANGE 14 
STUDY PROCEDURES REVISIONS 
Location:  
Section 10.2, Procedures and Schedule of Assessments 
Original Text: 
10.2.1 Screening Month -2.5 (Visit S1) 
The screening period will begin with a screening visit that will occur approximately 10 weeks 
prior to randomization.  Visit S1 will allow the Investigator to assess the patient’s preliminary 
eligibility.  After the patient provides written informed consent (see Section 10.1), the patient 
will undergo the following assessments and procedures at Visit S1: 
• Demographics 
• Clinically relevant medical history  
• Concomitant and prohibited medication review 
• Height (cm), weight (kg), body mass index (BMI)  
• Vital signs  
• Clinical laboratory evaluations:  
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, 
, non-HDL-C, 
, and 
) 
− ApoB and hs-CRP 
− 
HbA1C 


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− PCSK9i 
− TSH 
− FSH (in appropriate female patients) 
− Serum pregnancy test (on appropriate female patients) 
• Serology (including HBsAg, Hepatitis C virus [HCV])  
• Review of all inclusion/exclusion criteria that can be assessed at this time 
• Conduct diet and exercise counseling 
• Contact IWRS to register the patient  
Patients who meet all enrollment criteria that can be assessed following review of the SI central 
clinical laboratory results (available several days after Visit S1) will be instructed to washout of 
all lipid-regulating drugs and supplements and to maintain consistent diet and exercise patterns 
throughout the study.  Patients who fail to meet any entry criterion that can be assessed at 
Visit S1 are considered to be screen failures and are not required to return for additional visits 
(although a patient can be seen at any time for safety reasons). 
10.2.2 
PCSK9i Run-in Month -1 (Visit S2) 
Prior to scheduling Visit S2, review the screening clinical results to evaluate whether the patient 
continues to meet eligibility criteria. 
• If the patient meets eligibility criteria, then schedule the Visit S2 and proceed with the 
Visit S2 procedures 
The patient will undergo the following assessments and procedures at (Visit S2) 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs (starting from signing of the informed consent document) 
• Physical examination (PE) 
• Vital signs 
• Basic fasting lipids (TC, calculated LDL-C, 
, non-HDL-C, 
, and 
) 
• ApoB and hs-CRP 
• PCSK9i  
• First PCSK9i injection.  Verification of lipid entry criteria (LDL-C value of 
>160 mg/dL and triglycerides <500 mg/dL) must be obtained before starting PCSK9i 
• Schedule next visit (S3 has to be at least 30 days from first dose of PCSK9i) 
Note:  Local labs can be used to assess LDL-C and TGs for entry.  If using a central lab 
or a local lab with a delay in obtaining results, an optional visit to administer PCSK9i 
may be scheduled.  Patients need to be on Repatha 420 mg for at least 30 days during 
the lipid stabilization period before conducting Visit S3. 


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10.2.3 
Screening/Prerandomization (Visit S3)  
One month (30 days) from S2, patients will have their LDL-C evaluation (local or central) prior 
to randomization. 
The patient will undergo the following assessments and procedures at (Visit S3) 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs (starting from signing of the informed consent document) 
• Obtain fasting LDL-C 
• Schedule next visit Day 1 (Day 1 should occur immediately [ideally within 3 days] 
after S3, once LDL-C eligibility [≥70 mg/dL] is established) 
Note:  Central lab LDL-C results may take up to 3 days to obtain, so please plan 
accordingly if using the central lab.  
10.2.4. 
Treatment Week 0 (Visit T1; Day 1) 
Prior to scheduling Visit T1, review S1, S2, and S3clinical results to evaluate whether the patient 
continues to meet eligibility criteria. 
• If the patient meets eligibility criteria, then schedule the Visit T1 and proceed with 
the Visit T1 procedures 
If the patient has met all inclusion criteria, none of the exclusion criteria, and has been on 
Repatha 420 mg for at least 30 days, the patient may be randomized into the double-blind 
treatment period.  Patients who fail to meet any entry criterion prior to randomization are 
considered to be screen failures, will not be randomized into a treatment group, and are not 
required to return for additional visits.  Patients are considered randomized once all eligibility 
criteria are confirmed and a randomization number is obtained by the IWRS on the day of first 
dose.  
The patient will undergo the following assessments and procedures at (Visit T1) 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs (starting from signing of the informed consent document) 
• Weight 
• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
Note:  Urine pregnancy test (for females of childbearing potential) 
− Basic fasting lipids (TC, calculated LDL-C, 
, non-HDL-C, 
, and 
) 
− ApoB and hs-CRP 
− HbA1C  
• Predose PCSK9i and PK 


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• Review inclusion/exclusion criteria to establish patient eligibility.  Patient must have 
an LDL-C ≥70 mg/dL on S3 before they can be randomized on Day 1. 
• Conduct diet and exercise counseling 
• IWRS contact to obtain the patient randomization number and MED ID number for 
double-blind study drug 
• Dispense IMP and provide dosing instructions (two 35-day supply bottles) 
− Subject should be randomized and receive IMP within 3 days of S3, as soon 
as the final LDL-C entry criterion is met 
• PCSK9i injection and IMP must be given at the end of procedures 
• Schedule next visit 
10.2.5 
Treatment Month 1 (Visit T2 ±3 days) 
If the patient is withdrawing early from the study at this visit, proceed to Section 10.3.2 for the 
list of the required assessments. 
If the patient is withdrawing from IMP treatment at this visit, proceed to Section 10.3.2 for the 
list of the required assessments.  
Patients will undergo the following assessments and procedures at Month 1 (Visit T2): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs since last visit (ongoing) 
• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, 
, non-HDL-C, 
, and 
) 
• Predose PCSK9 and PK.  Should be taken ideally within 4 hours of the patient’s 
normal time of dosing 
• Conduct diet and exercise counseling 
• Return of IMP; assessment and recording of IMP compliance 
• Re-dispense IMP container from Visit T1 to patient for continued dosing and provide 
dosing instruction 
• PCSK9i injection and IMP must be given at the end of procedures 
• Schedule next visit 


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10.2.6 
Treatment Month 2 (Visit T3 ±3 days) 
If the patient is withdrawing early from the study at this visit, proceed to Section 10.3.2 for the 
list of the required assessments. 
New Text: 
10.2.1. 
Screening Month -2.5 −4.5 (Visit S1) 
The screening period will begin with a screening visit that will occur approximately 1018 weeks 
prior to randomization.  Visit S1 will allow the Investigator to assess the patient’s preliminary 
eligibility.  After the patient provides written informed consent (see Section 10.1), the patient 
will undergo the following assessments and procedures at Visit S1: 
• Demographics 
• Clinically relevant medical history  
• Concomitant and prohibited medication review 
• Height (cm), weight (kg), body mass index (BMI)  
• Vital signs  
• Clinical laboratory evaluations:  
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, 
, non-HDL-C, 
, and 
) 
− ApoB and hs-CRP 
− 
HbA1C 
− PCSK9i 
− TSH 
− FSH (in appropriate female patients) 
− Serum pregnancy test (on appropriate female patients) 
• Serology (including HBsAg, Hepatitis C virus [HCV])  
• Review of all inclusion/exclusion criteria that can be assessed at this time 
• Conduct diet and exercise counseling 
• Contact IWRS to register the patient  
Patients who meet all enrollment criteria that can be assessed following review of the S1 central 
clinical laboratory results (available several days after Visit S1) will be instructed to washout of 
all lipid-regulating drugs and supplements and to maintain consistent diet and exercise patterns 
throughout the study.  Patients who fail to meet any entry criterion that can be assessed at 
Visit S1 are considered to be screen failures and are not required to return for additional visits 
(although a patient can be seen at any time for safety reasons). 


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10.2.2. 
PCSK9i Run-in Month -13 (Visit S2) 
Prior to scheduling Visit S2, review the screening clinical results to evaluate whether the patient 
continues to meet eligibility criteria. 
• If the patient meets eligibility criteria, then schedule the Visit S2 and proceed with the 
Visit S2 procedures 
The patient will undergo the following assessments and procedures at (Visit S2) 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs (starting from signing of the informed consent document) 
• Physical examination (PE) 
• Vital signs 
• Basic fasting lipids (TC, calculated LDL-C, 
, non-HDL-C, 
, and 
) 
• ApoB and hs-CRP 
• PCSK9i  
• First PCSK9i monthly injection.  Verification of lipid entry criteria (LDL-C value of 
>160 mg/dL and triglycerides <500 mg/dL) must be obtained before starting PCSK9i 
• Schedule next visit (S3 has to be at least 30 days ±3 days from the first dose of 
PCSK9i) 
− PCSK9i injections must be administered consistently throughout the trial within 
30 ± 3 days from the previous dose.  Efficacy will vary if the doses are not 
consistently administered. 
Note:  Local labs can be used to assess LDL-C and TGs for entry.  All other labs must 
be run via the central lab.  If using a central lab or a local lab with a delay in obtaining 
results, an optional visit to administer PCSK9i may be scheduled.  Patients need to be 
on Repatha 420 mg for at least 30 days ±3 days during the lipid stabilization period 
before conducting Visit S3. 
10.2.3. 
PCSK9i Run-in Month -2 Screening/Prerandomization (Visit S3) 
One month (30 days) from S2, patients will have their LDL-C evaluation (local or central) prior 
to randomization.Prior to scheduling Visit S3, review the screening clinical results to evaluate 
whether the patient continues to meet eligibility criteria. 
• If the patient meets eligibility criteria, then schedule the Visit S3 and proceed with the 
Visit S3 procedures 
The patient will undergo the following assessments and procedures at (Visit S3) 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs (starting from signing of the informed consent document) 
• Obtain Vital signs 
• Basic fasting lipids (TC, calculated LDL-C, 
, non-HDL C, 
, and 
) 


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• PCSK9i monthly injection must be given at the end of procedures 
Note:  Central lab LDL-C results may take up to 3 days to obtain, so please plan 
accordingly if using the central lab.  
10.2.4 
PCSK9i Run-in Month -1 (Visit S4)  
One month (30 ± 3 days) from S3, patients will have their LDL-C evaluated a second time via 
central lab only prior to randomization on Day 1. 
The patient will undergo the following assessments and procedures at (Visit S4) 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs (starting from signing of the informed consent document) 
• Vital signs 
• Basic fasting lipids (TC, calculated LDL-C, 
, non-HDL-C, 
, and 
) 
− Schedule next visit Day 1 (Day 1 should occur immediately 30 ±3 days after 
S4, once LDL-C eligibility [≥70 mg/dL] is established) 
• PCSK9i monthly injection  must be given at the end of procedures 
10.2.4.10.2.5. Treatment Week 0 (Visit T1; Day 1) 
Prior to scheduling Visit T1, review S1, S2, S3, and S34 clinical results to evaluate whether the 
patient continues to meet eligibility criteria. 
• If the patient meets eligibility criteria, then schedule the Visit T1 and proceed with 
the Visit T1 procedures 
If the patient has met all inclusion criteria, none of the exclusion criteria, and has been on 
Repatha 420 mg for 30 ±3 days during each month of the PCSK9i run-in period, the patient 
may be randomized into the double-blind treatment period.  Patients who fail to meet any entry 
criterion prior to randomization are considered to be screen failures, will not be randomized into 
a treatment group, and are not required to return for additional visits.  Patients are considered 
randomized once all eligibility criteria are confirmed and a randomization number is obtained by 
the IWRS on the day of first dose.  
The patient will undergo the following assessments and procedures at (Visit T1) 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs (starting from signing of the informed consent document) 
• Weight 
• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Note:  Urine pregnancy test (for females of childbearing potential) 
− Basic fasting lipids (TC, calculated LDL-C, 
, non-HDL-C, 
, and 
) 


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− ApoB and hs-CRP 
− HbA1C  
• Predose PCSK9i and PK 
• Review inclusion/exclusion criteria to establish patient eligibility.  Patient must have 
an LDL-C ≥70 mg/dL on S3 at S4 before they can be randomized on Day 1. 
• Conduct diet and exercise counseling 
• IWRS contact to obtain the patient randomization number and MED ID number for 
double-blind study drug 
• Dispense IMP and provide dosing instructions (two 35-day supply bottles) 
− Subject should be randomized and receive IMP within 30 ± 3 days of S4S3, 
as soon as the final LDL-C entry criterion is met 
• PCSK9i injection and IMP must be given at the end of procedures 
• Schedule next visit 
10.2.510.2.6. Treatment Month 1 (Visit T2 ±3 days) 
If the patient is withdrawing early from the study at this visit, proceed to Section 10.3.2 for the 
list of the required assessments. 
If the patient is withdrawing from IMP treatment at this visit, proceed to Section 10.3.2 for the 
list of the required assessments.  
Patients will undergo the following assessments and procedures at Month 1 (Visit T2): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs since last visit (ongoing) 
• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, 
, non-HDL-C, 
, and 
) 
− ApoB and hs-CRP 
• Predose PCSK9 and PK.  Should be taken ideally within 4 hours of the patient’s 
normal time of dosing 
• Conduct diet and exercise counseling 
• Return of IMP; assessment and recording of IMP compliance 
• Re-dispense Dispense IMP container from Visit T1 to patient for continued dosing 
and provide dosing instructions (35-day supply bottles) 
• PCSK9i injection and IMP must be given at the end of procedures 
• Schedule next visit 


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Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
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Page 103 of 114 
10.2.610.2.7 Treatment Month 2 (Visit T3 ±3 days)/EOS 
If the patient is withdrawing early from the study at this visit, proceed to Section 10.3.2 for the 
list of the required assessments. 
 
CHANGE15 
ASSESSMENT OF SAFETY REVISION 
Location: 
Section 11.1, Safety Parameters 
Original Text: 
At all clinic visits, investigators will review all safety information including vital signs, AEs, 
concomitant medications, and electrocardiogram (ECG) reports and will ensure that the collected 
data are recorded into the appropriate eCRF.  Additionally, clinical laboratory samples will be 
collected and sent for analysis and the investigator will review the results to ensure continued 
patient safety while participating in the study.  
New Text: 
At all clinic visits, investigators will review all safety information including vital signs, AEs, and 
concomitant medications, and electrocardiogram (ECG) reports and will ensure that the collected 
data are recorded into the appropriate eCRF.  Additionally, clinical laboratory samples will be 
collected and sent for analysis and the investigator will review the results to ensure continued 
patient safety while participating in the study.  
 
CHANGE 16 
REPORTING ADVERSE EVENTS REVISIONS 
Location: 
Section 12.1.3, Reporting for Adverse Events  
Original Text: 
Clinically significant abnormal laboratory or other examination findings that are detected during 
the study or are present at baseline and significantly worsen during the study should be reported 
as AEs.  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.  
Significant abnormal laboratory values occurring during the clinical study will be followed until 
repeat tests return to normal, stabilize, or are no longer clinically significant.  Any abnormal test 
that is determined to be an error does not require reporting as an AE. 
New Text: 
Clinically significant abnormal laboratory or other examination findings that are detected during 
the study or are present at baseline 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.  Significant abnormal laboratory values occurring during the clinical study 
will be followed until repeat tests return to normal, stabilize, or are no longer clinically 


Bempedoic Acid 
 
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Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 104 of 114 
significant.  Any abnormal test that is determined to be an error does not require reporting as an 
AE. 
An abnormal laboratory value that is not already associated with an AE is to be recorded as an 
AE only if any one of the following criteria is met: 
• an action on the study drug is made as a result of the abnormality 
• intervention for management of the abnormality is required 
• at the discretion of the investigator should the abnormality be deemed clinically 
significant 
 
CHANGE 17 
ELEVATED CK MONITORING REVISION 
Location: 
Section 11.1.5.4.3, Monitoring and Management of Elevated Creatinine Kinase 
Original Text: 
If at any time after randomization a patient experiences a marked CK elevation >5 × ULN, the 
patient will undergo repeat confirmatory assessment as soon as is reasonably possible, preferably 
within 3 to 7 days of the laboratory result becoming available.  
Repeat CK assessment will include query for related symptoms.  
• If the repeat CK assessment confirms an unexplained (ie, not associated with recent 
trauma or physically strenuous activity) CK abnormality >5 × ULN, if asymptomatic the 
investigator with input from the Sponsor may consider continuing study medication with 
continued CK assessments every 1-2 weeks.  
New Text: 
If at any time after randomization a patient experiences a marked CK elevation >5 × ULN, the 
patient will undergo repeat confirmatory assessment as soon as is reasonably possible, preferably 
within 3 to 7 days of the laboratory result becoming available.  
Repeat CK assessment will include query for related symptoms.  
• If the repeat CK assessment confirms an unexplained (ie, not associated with recent 
trauma or physically strenuous activity) CK abnormality >5 × ULN, if asymptomatic, 
the patient should receive further assessment and investigation into the cause, assess 
whether there is renal injury, and measure CK approximately weekly or more 
frequently if clinically indicated until resolution.  If CK levels continue to rise; IMP 
should be discontinued the investigator with input from the Sponsor may consider 
continuing study medication with continued CK assessments every 1-2 weeks.  
 


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Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
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CHANGE 18 
ADVERSE EVENT MONITORING REVISION 
Location: 
Section 12.1.3, Reporting for Adverse Events 
Original Text: 
Clinically significant abnormal laboratory or other examination findings that are detected during 
the study or are present at baseline and significantly worsen during the study should be reported 
as AEs.  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.  
Significant abnormal laboratory values occurring during the clinical study will be followed until 
repeat tests return to normal, stabilize, or are no longer clinically significant.  Any abnormal test 
that is determined to be an error does not require reporting as an AE. 
New Text: 
Clinically significant abnormal laboratory or other examination findings that are detected during 
the study or are present at baseline 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.  Significant abnormal laboratory values occurring during the clinical study 
will be followed until repeat tests return to normal, stabilize, or are no longer clinically 
significant.  Any abnormal test that is determined to be an error does not require reporting as an 
AE. 
An abnormal laboratory value that is not already associated with an AE is to be recorded as an 
AE only if any one of the following criteria is met: 
• an action on the study drug is made as a result of the abnormality 
• intervention for management of the abnormality is required 
• at the discretion of the investigator should the abnormality be deemed clinically 
significant 
Location: 
Section 12.6.1, Monitoring and Follow-up of Adverse Events 
Original Text: 
Patients with AEs related to IMP that are ongoing at study discontinuation or completion must be 
followed until resolution or for 30 days after study completion, whichever comes first, with the 
exception of patients reporting SAEs (see Section 12.2.2). 
New Text: 
Patients with AEs related to IMP that are ongoing at study discontinuation or completion must be 
followed until resolution, until deemed stable/chronic, or for 30 days after study completion, 
whichever comes first, with the exception of patients reporting SAEs (see Section 12.2.2). 
 


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Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 106 of 114 
CHANGE 19 
SERIOUS ADVERSE EVENT DEFINITION ADDITION 
Location: 
Section 12.2.1., Definition of Serious Adverse Event 
Original Text: 
Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, they 
may jeopardize the patient and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition.  Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room, blood dyscrasias, 
convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
New Text: 
Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, they 
may jeopardize the patient and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition.  Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room, blood dyscrasias, 
convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
Events or Outcomes Not Qualifying as Serious Adverse Events 
The following are not considered SAEs and therefore do not need to be reported as such: 
• Preplanned or elective hospitalization including social and/or convenience 
situations (eg, due to inclement weather) 
• Overdose of either Esperion study drug or concomitant medication unless the event 
meets SAE criteria (eg, hospitalization).  However, the event should still be 
captured as a nonserious AE on the appropriate eCRF page 
Location: 
Section 12.2.2, Reporting Serious Adverse Events 
Original Text: 
To report the SAE, the SAE form in EDC should be completed within 24 hours of becoming 
aware of the event.  If you have questions, please call the designated Safety contact for 
assistance. 
Within 24 hours of receipt of follow-up information, the investigator must update the SAE form 
and submit any supporting documentation (eg, patient discharge summary or autopsy reports) to 
designated Safety contact. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 107 of 114 
New text: 
To report the SAE, the SAE form in EDC should be completedinformation should be entered on 
to the AE eCRF in the EDC database within 24 hours of becoming aware of the event.  If you 
have questions, please call the designated Safety contact for assistance. 
Within 24 hours of receipt of follow-up information, the investigator must update the SAE form 
information on the AE eCRF and submit any supporting documentation (eg, patient discharge 
summary or autopsy reports) to designated Safety contact. 
Location: 
Section 12.2.3, Reporting of Patient Death 
Original Text: 
The death of any patient during the study or within 30 days after the last dose of bempedoic acid 
must be reported as an SAE. 
New Text: 
The death of any patient during the study or within 30 days after the last dose of bempedoic acid 
study treatment must be reported as an SAE. 
 
CHANGE 20 
PREGNANCY REPORTING REVISION 
Location: 
Section 12.2.4, Reports of Pregnancy and Lactation 
Original Text: 
Although not considered an SAE (unless an event occurs with a serious outcome), pregnancy 
will be collected by the designated Safety contact.  If a female patient should become pregnant 
during the course of the study, the Principal Investigator or designee must contact the designated 
Safety contact within 24 hours of knowledge of the pregnancy.  In addition, a Pregnancy report 
form must be completed and submitted to the Safety contact. 
Patients who become pregnant must discontinue study medication immediately and will continue 
to be followed until the pregnancy is completed.  Once the outcome of the pregnancy is known, 
the Pregnancy Outcome report form must be completed and submitted to the Safety contact.  
Patients who lactate during the study may be required to discontinue study medication. 
New Text: 
Although not considered an SAE (unless an event occurs with a serious outcome), any event of 
pregnancy will be collected by the designated Safety contact.  If a female patient should become 
pregnant during the course of the study or within 30 days after last dose of study treatment, the 
Principal Investigator or designee must contact the designated Safety contact within 24 hours of 
knowledge of the pregnancy.  In addition, a paper Pregnancy Rreport Fform must be completed 
and submitted to the Safety contact. 
Patients who become pregnant must discontinue study medication immediately and will continue 
to be followed until the pregnancy is completed.  Once the outcome of the pregnancy is known, 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 108 of 114 
the paper Pregnancy Outcome Rreport Fform must be completed and submitted to the Safety 
contact.  Patients who are breastfeeding are excluded from this lactate during the study may be 
required to and should discontinue study medication. 
 
CHANGE 21 
STATISTIC REVISION 
Location: 
Section 13.9, PCSK91 
Original Text: 
13.9 
PCSK91 
PCSK9 concentrations will be collected and summarized from patients at S1, S2, T1, T2, and T3. 
New Text: 
13.9 
PCSK91 
PCSK9 concentrations will be collected and summarized from patients at S1, S2, T1, T2, and T3. 
 
CHANGE 22 
CASE REPORT FORMS AND STUDY RECORDS REVISION 
Location: 
Section 17.3, Case Report Forms and Study Recrods 
Original Text: 
It is essential that all dates appearing on the Sponsor’s patient data collection forms for 
laboratory tests, cultures, etc, be the dates on which the specimens were obtained or the 
procedures performed.  The eCRFs will be electronically signed by the Investigator and dated as 
verification of the accuracy of the recorded data.  All data collection forms should be completed 
within 48 hours following the evaluation. 
New Text: 
It is essential that all dates appearing on the Sponsor’s patient data collection forms for 
laboratory tests, cultures, etc, be the dates on which the specimens were obtained or the 
procedures performed.  The eCRFs will be electronically signed by the Investigator and dated as 
verification of the accuracy of the recorded data.  All data collection forms should be completed 
within 48 hours a timely manner according to the eCRF completion guidelines following the 
evaluation. 
 
CHANGE 23 
SCHEDULE OF EVENTS REVISION 
Location: 
Appendix 1, Schedule of Events 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 109 of 114 
Original Text: 
Schedule of Events 
Visit 
S11,2 
S2 
S3 
T1 
T2 
T3/EOS)3 
Week 
Month 
-2.5 
Month 
-1 
Pre- 
randomization 
Week 
0 
Month 
1 
Month 
2 
Day 
Procedure 
Day 
-75 
Day 
-30±3 
30 days 
post-S2 
Day 
1* 
Day 
31±3 
Day 
61±3 
Informed Consent 
X 
 
 
 
 
 
Enrollment Criteria 
X 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
Adverse Event Recording 
 
X 
X 
X 
X 
X 
Physical Exam 
 
X 
 
 
 
X 
Weight4 
X 
 
 
X 
 
X 
Height 
X 
 
 
 
 
 
Vital Signs6 
X 
X 
 
X 
X 
X 
Serology7 
X 
 
 
 
 
 
Serum Pregnancy/FSH8  
X 
 
 
 
 
 
Urine pregnancy test for 
women of childbearing 
potential only 
 
 
 
X 
 
 
TSH 
X 
 
 
 
 
 
Clinical Safety Labs9 
X 
 
 
X 
X 
X 
Basic Fasting Lipids10 
X 
X** 
X*** 
X 
X 
X 
ApoB and hs-CRP 
 
X 
 
X 
 
X 
HbA1C 
X 
 
 
X 
 
X 
PCSK9  
X 
X 
 
X 
X 
X 
PK – predose trough 
 
 
 
X 
X 
X 
Diet and exercise 
counseling11 
X 
X 
 
X 
X 
X 
Establish Patient Eligibility 
 
 
 
X 
 
 
Randomization 
 
 
 
X 
 
 
IWRS Contact12 
X 
 
 
X 
X 
X 
PCSK9i administered at 
site 
 
X 
 
X 
X 
 
Double-blind Drug 
Dispensing 
 
 
 
X 
X 
 


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Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 110 of 114 
Schedule of Events 
Visit 
S11,2 
S2 
S3 
T1 
T2 
T3/EOS)3 
Week 
Month 
-2.5 
Month 
-1 
Pre- 
randomization 
Week 
0 
Month 
1 
Month 
2 
Day 
Procedure 
Day 
-75 
Day 
-30±3 
30 days 
post-S2 
Day 
1* 
Day 
31±3 
Day 
61±3 
IMP Return/Compliance 
 
 
 
 
X 
X 
PCSK9i 
Return/Accountability 
 
X 
 
X 
X 
 
NOTE: For patients who withdraw from study drug treatment, but consent to be followed for safety assessments and return to 
clinic for these visit, the visits will occur according to the protocol schedule.  Safety assessments should include clinical safety 
and basic lipid laboratories, adverse events (AEs), physical examination (PE), vital signs, and electrocardiograms (ECGs).  For 
patients who withdraw from study drug treatment, but consent to be followed for safety assessments by phone, the telephone 
contacts will occur according the protocol schedule with information regarding current health status and to collect information 
on AEs (eg, recent procedures, hospitalizations, and if the patient has died, the cause of death).  If a patient does not provide 
consent to be followed for safety assessments per the protocol (either by returning to clinic or by phone), Visit T4 will be 
considered the End of Study (EOS)/Early Withdrawal from study and no further visits will be scheduled. 
1 An optional basic fasting lipid MAY be completed prior to S2, but must occur just prior to the next witnessed PCSK9i dose if 
patient fails to meet lipid entry criterion at Visit S1.  If this optional basic fasting lipid is completed, the average of the 2 lipid 
values will be used to determine eligibility. 
2 A recheck of blood pressure may be completed prior to T1 if the patient’s diastolic blood pressure (DBP) and/or systolic blood 
pressure (SBP) meet the exclusion criteria levels.  Patients may randomize after blood pressure medications have been 
adjusted, the patients have been on stable doses of blood pressure medications for at least 2 weeks, and the repeat blood 
pressure values (DBP and/or SBP) do not meet exclusionary values.  Repeat labs may be completed prior to T1 to determine 
eligibility if the patient’s estimated glomerular filtration rate (eGFR), alanine aminotransferase (ALT), aspartate 
aminotransferase (AST) or other labs meet exclusion criteria levels.  If this optional lab is completed, the repeated value will 
be used to determine eligibility. 
3 All procedures will be completed for all patients at either EOS if completing the study or early withdrawal. 
4 Body weight will be measured in the morning while fasting, using consistent scales, after voiding, and without shoes and 
outerwear (eg, coats).   
6 Vital signs will include DBP, SBP, heart rate (HR) and will be collected prior to any blood sample collection.  Patient will rest 
for 5 minutes prior to assessments 
7 Serology for HBsAg, HCV-ABVivi 
8 Pregnancy test completed in women of child-bearing age only. FSH in naturally postmenopausal women ≥1 year without 
menses and <55 years; 
9 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits.  Please refer to laboratory manual for 
detailed schedule of tests. 
10 Basic fasting lipids include total cholesterol (TC), calculated low-density lipoprotein cholesterol (LDL-C),
 non-HDL-C,), and
).   
11 Diet and exercise counseling per local and/or regional guidelines for the management of hyperlipidemia. 
12 Interactive web response system (IWRS) contact at either an early withdrawal or an EOS visit to register study discontinuation 
visit date. 
* Patients must be on PCSK9 for at least 30 days before initiating Day 1.  Day 1 should occur immediately (ideally within 
3 days) after S3, once LDL-C eligibility is established 
** LDL-C must be ≥160 mg/dL and TG <500 mg/dL before initiating PCSK9i.  A local lab may be used to assess LDL-C and 
TG.  
*** LDL-C must be ≥70 mg/dL to qualify for randomization.  A local lab may be used to assess entry LDL-C. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 111 of 114 
New Text: 
 
Schedule of Events 
Visit 
S11,2 
S2 
S3 
S3 
T1 
T2 
T3/EOS)3 
Week Month Month -24.5 
Month -13 
Pre-
randomization 
Month -2 
Month -1 
Week 0 
Month 1 
Month 2 
Day 
Procedure 
Day -7135 
Day-390 ±3 
Day 1*-60 ±3 Day 31-30 ±3 
Day 
61±31* 
Day31 ±3 
Day61 ±3 
Informed Consent 
X 
 
 
 
 
 
 
Enrollment Criteria 
X 
X 
X 
X 
 
 
 
Demographics 
X 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
Adverse Event Recording 
 
X 
X 
X 
X 
X 
X 
Physical Exam 
 
X 
 
 
 
X 
X 
Weight4 
X 
 
 
 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
Vital Signs6 
X 
X 
X 
X 
X 
X 
X 
Serology7 
X 
 
 
 
 
 
 
Serum Pregnancy/FSH8  
X 
 
 
 
 
 
 
Urine pregnancy test for 
women of childbearing 
potential only 
 
 
 
 
X 
 
 
TSH 
X 
 
 
 
 
 
 
Clinical Safety Labs9 
X 
 
 
 
X 
X 
X 
Basic Fasting Lipids10 
X 
X** 
X*** 
X*** 
X 
X 
X 
ApoB and hs-CRP 
 
X 
 
 
X 
X 
X 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 112 of 114 
 
Schedule of Events 
Visit 
S11,2 
S2 
S3 
S3 
T1 
T2 
T3/EOS)3 
Week Month Month -24.5 
Month -13 
Pre-
randomization 
Month -2 
Month -1 
Week 0 
Month 1 
Month 2 
Day 
Procedure 
Day -7135 
Day-390 ±3 
Day 1*-60 ±3 Day 31-30 ±3 
Day 
61±31* 
Day31 ±3 
Day61 ±3 
HbA1C 
X 
 
 
 
X 
 
X 
PCSK9 
X 
X 
X 
 
X 
X 
X 
PK – predose trough 
 
 
 
 
X 
X 
X 
Diet and exercise counseling11 
X 
X 
 
 
X 
X 
X 
Establish Patient Eligibility 
 
 
 
 
X 
 
 
Randomization 
 
 
 
 
X 
 
 
IWRS Contact12 
X 
 
 
 
X 
X 
X 
PCSK9i administered at site 
 
X 
X 
X 
X 
X 
 
Double-blind Drug Dispensing 
 
 
 
 
X 
X 
 
IMP Return/Compliance 
 
 
 
 
 
X 
X 
PCSK9i Return/Accountability 
 
X 
X 
X 
X 
X 
 
NOTE: For patients who withdraw from study drug treatment, but consent to be followed for safety assessments and return to clinic for these visit, the visits will occur according 
to the protocol schedule.  Safety assessments should include clinical safety and basic lipid laboratories, adverse events (AEs), physical examination (PE), and vital signs, and 
electrocardiograms (ECGs).  For patients who withdraw from study drug treatment, but consent to be followed for safety assessments by phone, the telephone contacts will occur 
according the protocol schedule with information regarding current health status and to collect information on AEs (eg, recent procedures, hospitalizations, and if the patient has 
died, the cause of death).  If a patient does not provide consent to be followed for safety assessments per the protocol (either by returning to clinic or by phone), Visit T4 will be 
considered the End of Study (EOS)/Early Withdrawal from study and no further visits will be scheduled. 
1 An optional basic fasting lipid MAY be completed prior to S2, but must occur just prior to the next witnessed PCSK9i dose if patient fails to meet lipid entry criterion at 
Visit S1.  If this optional basic fasting lipid is completed, the average of the 2 lipid values will be used to determine eligibility. 
2 A recheck of blood pressure may be completed prior to T1 if the patient’s diastolic blood pressure (DBP) and/or systolic blood pressure (SBP) meet the exclusion criteria levels.  
Patients may randomize after blood pressure medications have been adjusted, the patients have been on stable doses of blood pressure medications for at least 2 weeks, and the 
repeat blood pressure values (DBP and/or SBP) do not meet exclusionary values.  Repeat labs may be completed prior to T1 to determine eligibility if the patient’s estimated 
glomerular filtration rate (eGFR), alanine aminotransferase (ALT), aspartate aminotransferase (AST) or other labs meet exclusion criteria levels.  If this optional lab is 
completed, the repeated value will be used to determine eligibility. 
3 All procedures will be completed for all patients at either T3/EOS if completing the study or early withdrawal. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 113 of 114 
4 Body weight will be measured in the morning while fasting, using consistent scales, after voiding, and without shoes and outerwear (eg, coats).   
6 Vital signs will include DBP, SBP, heart rate (HR) and will be collected prior to any blood sample collection.  Patient will rest for 5 minutes prior to assessments 
7 Serology for HBsAg, HCV-ABVivi 
8 Pregnancy test completed in women of child-bearing age only. FSH in naturally postmenopausal women ≥1 year without menses and <55 years; 
9 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits.  Please refer to laboratory manual for detailed schedule of tests. 
10 Basic fasting lipids include total cholesterol (TC), calculated low-density lipoprotein cholesterol (LDL-C), 
, non-HDL-C,), and 
).   
11 Diet and exercise counseling per local and/or regional guidelines for the management of hyperlipidemia. 
12 Interactive web response system (IWRS) contact at either an early withdrawal or an EOS visit to register study discontinuation visit date. 
* Patients must be on PCSK9 for at least 30 ± 3 days during each month of the PCSK9 run-in period before initiating Day 1.  Day 1 should occur immediately (ideally within 
3 days) after S3, once LDL-C eligibility is established 
** LDL-C must be ≥160 mg/dL and TG <500 mg/dL before initiating PCSK9i.  A local lab may be used to assess LDL-C and TG for eligibility prior to initiating Repatha, but a 
central lab must also be conducted at this visit.  
*** LDL-C must be ≥70 mg/dL to qualify for randomization.  A local Only a central lab may be used to assess entry LDL-C. 


Bempedoic Acid 
 
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Clinical Study Protocol 1002-039 
 
Amendment 1, 05 March 2017 
Confidential 
Page 114 of 114 
CHANGE 24 
SPONSOR’S SIGNATURE PAGE REVISIONS 
Location: 
Appendix 2, Sponsor’s Signature 
Original Text: 
Study Title: 
A Randomized, Double-Blind, Parallel Group, Multicenter Study to 
Evaluate the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180 mg 
QD when added to PCSK9-Inhibitor Therapy 
Study Number: 
1002-039 
Final Date: 
22 November 2016 
 
This clinical study protocol was subject to critical review and has been approved by the Sponsor.  
The following personnel contributed to writing and/or approving this protocol: 
 
 
Signed:  
Date:  
 
 
 
New Text: 
Study Title: 
A Randomized, Double-Blind, Parallel Group, Multicenter Study to 
Evaluate the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180 mg 
QD when added to PCSK9-Inhibitor Therapy 
Study Number: 
1002-039 
Final Date: 
05 March 201722 November 2016 
 
This clinical study protocol was subject to critical review and has been approved by the Sponsor.  
The following personnel contributed to writing and/or approving this protocol: 
 
 
Signed:  
Date:  
 
 
 
 

SAP_001.pdf: 
Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
Title: 
Protocol: 
Clinical Phase: 
Product: 
Version (Date): 
Status: 
Prepared by: 
Statistical Analysis Plan 
A Randomized, Double-Blind, Parallel Group, Multicenter Study to 
Evaluate the Efficacy and Safety ofBempedoic Acid (ETC-1002) 180 mg 
QD when Added to Proprotein Convertase Subtilisin/Kexin Type 9 
(PCSK9}Inhibitor Therapy 
ETC-1002-039 
2 
ETC-1002 
Statistical Analysis Plan - Final Version 1.1 (Jan. 25, 2018) 
Final 
On behalf of: 
Esperion Therapeutics 
Confidentiality statement: 
• 
The information provided in this document is strictly confidential. 
• 
The recipients of the SAP must not disclose the confidential information contained within this 
document or any related information to other persons without the permission of the sponsor. 
• 
In addition, the recipients of the SAP must keep this confidential document in a controlled 
environment which prevents unauthorized access to the document. 
Confidential 
Page 1 of25 
NCT number: NCT03193047
This NCT number has been applied to the document
for purposes of posting on clinicaltrials.gov


Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
Prepared at 
 by: 
 
26 Jan 2018 02:05:003+0000 
REASON: I approve this document 
e320d079-81e7-4489-a492-2479a385701a 
Reviewed at 
 by: 
 
26 Jan 2018 02:06:045+0000 
REASON: I approve this document 
Se9eb6ba-ac95-46d 1-aa92-422b0263855d 
Approved at 
 by: 
 
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REASON: I approve this document 
261a023d-a1f4-4503-9229-8584164bb8c3 
 
26 Jan 2018 15:37:029+0000 
REASON: I approve this document 
82d408a9-910c-4aa3-91e6-f0193e13e048 
Confidential 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
Date 
Date 
Date 
Date 
Page 2 of25 
DocUUID: 2c822907-a925-499o-9be8~c54c2cf6db8 


Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
REVISION IDSTORY 
Item Version 
Description of change 
No. 
Affected 
1 
1.0, 1.1 
Changed analysis set/definition from FAS to m.ITT. 
2 
1.1 
Repatha treatment duration calculation and compliance were written 
in detail. 
3 
1.1 
A non-parametric approach for hs-CRP and TG analysis were 
included. 
Confidential 
Page 3 of25 


Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
Table of Contents 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
1 
List of Abbreviations ................................................................................................ 5 
2 
Introduction ............................................................................................................... 7 
3 
Study Objectives and Endpoints ............................................................................. 7 
3.1 
Objectives ............................................................................................................. 7 
3.2 
Endpoints .............................................................................................................. 7 
3.2.l 
Primary Endpoint .......................................................................................... 8 
3 .2.2 
Secondary Endpoints .................................................................................... 8 
3.2.3 
Exploratory Endpoints .................................................................................. 8 
4 
Study Design. .............................................................................................................. 8 
4.1 
Study Design ........................................................................................................ 8 
4.2 
Randomization ..................................................................................................... 9 
4.3 
Sam.pie Size Justification ..................................................................................... 9 
5 
Sta tis ti cal and .Analytical Plans ............................................................................. 10 
5 .1 
General Statistical Considerations ..................................................................... 10 
5 .2 
Statistical Analysis Plans ................................................................................... 11 
5 .2. L 
Analysis Sets ............................................................................................... 11 
5 .2.2 
Baseline Definition ..................................................................................... 11 
5.2.3 
Protocol Violations and Deviations ............................................................ 12 
5.2.4 
Patient Disposition ...................................................................................... 12 
5 .2 .5 
Demographic and Baseline Characteristics ................................................ 12 
5.2.6 
Medical ffistory .......................................................................................... 12 
5.2.7 
Prior Medications and Concomitant Medications/Procedures .................... 12 
5.2.8 
Study Drug (ETC-1002 or placebo) Exposure and Compliance ................ 13 
5.2.9 
Repatha Exposure and Compliance ............................................................ 13 
5.3 
Efficacy Endpoints and Analyses ....................................................................... 14 
5.3. l 
For all efficacy endpoints and analyses, the Modified Intent to Treat (mIT1) 
analysis set will be used. Primary Endpoint Analysis .............................................. 14 
5.3.2 
Secondary Efficacy Endpoint Analyses and Exploratory Endpoint Analyses 
14 
5. 3. 3 
Phannacokinetics ........................................................................................ 15 
5.4 
Safety Endpoints and Analyses .......................................................................... 15 
5.4.l 
Adverse Events (AEs) ................................................................................. 16 
5.4.2 
Adverse Events of Special Interest ............................................................. 17 
5. 4. 3 
Laboratory Evaluations ............................................................................... 18 
5.4.4 
Physical Examinations (PEs) ...................................................................... 20 
5.4.5 
Vital Signs ................................................................................................... 20 
6 
Changes in Statistical .Analysis Plan Based on the Study-Specific Protocol ••••• 21 
7 
Reference ....................................................................................................................................................... 22 
8 
Appendices ................................................................................................................ 23 
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Page 4 of25 


Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
1 List of Abbreviations 
Abbreviation or Specialist Term 
AE 
AESI 
ALB 
ALK-P 
ALT 
ANCOVA 
ApoB 
AST 
BMI 
BUN 
CI 
CK 
C02 
CPK 
DBP 
DMC 
eCRF 
eGFR 
EOS 
ETC-1002 
FSH 
GI 
HbA1c 
HBsAg 
Hct 
HCV 
Hgb 
hs-CRP 
ICH 
IMP 
INR 
mITT 
IWRS 
LDL-C 
LDH 
LOCF 
LSM 
Confidential 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
Explanation 
Adverse event 
Adverse events of special interest 
Albumin 
Alkaline phosphatase 
Alanine aminotransferase 
Analysis of covariance 
Apolipoprotein B 
Aspartate aminotransferase 
Body mass index 
Blood urea nitrogen 
Confidence interval 
Creatine kinase 
Carbon dioxide 
Creatine phosphokinase 
Diastolic blood pressure 
Data Monitoring Committee 
Electronic case report form 
Estimated glomerular filtration rate 
End of Study 
Bempedoic acid 
Follicle-stimulating hormone 
Gastrointestinal 
Glycosylated hemoglobin, Type Al C 
Hepatitis B surface antigen 
Hematocrit 
Hepatitis C virus 
Hemoglobin 
Hiltlt-sensitivity C-reactive protein 
International Conference on Harmonisation 
Investigational medicinal product 
International normalized ratio 
Modified Intention-to-treat 
Interactive web response system 
Low-density lipoorotein cholesterol 
Lactate dehydrogenase 
last observation carried forward 
Least square mean 
Page 5 of25 


Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
Abbreviation or Specialist Term 
MACE 
MCH 
MCHC 
MCV 
MedDRA 
mITT 
non-HDL-C 
PCSK9 
PCSK9i 
PE 
PMM 
PT 
RBC 
SAE 
SAP 
SBP 
SE 
SOOT 
SOPT 
soc 
SP 
TB 
TC 
TEAE 
TO 
TSH 
ULN 
WBC 
WHO 
Confidential 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
Explanation 
Maior adverse cardiac event 
Mean corpuscular hemoglobin 
Mean corpuscular hemoglobin concentration 
Mean corouscular volume 
Medical Dictionary for Regulatory Activities 
Modified Intent to Treat analysis set 
N on-hilili-density lipoprotein cholesterol 
Proprotein convertase subtilisin/kexin type 9 
PCSK9 inhibitor 
Physical exam 
Pattern mixture model 
Preferred term 
Red blood cell 
Serious adverse event 
Statistical Analysis Plan 
Systolic blood pressure 
Standard error 
Serum glutamic oxaloacetic transaminase 
Serum glutamic pyruvic transaminase 
System organ class 
Safety population 
Total bilirubin 
Total cholesterol 
Treatment-emergent adverse event 
Triglycerides 
Thyroid-stimulating hormone 
Upper limit of normal 
White blood cell 
World Health Organization 
Page 6 of25 


Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
2 Introduction 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
The purpose of this document is to describe the statistical methods, data derivations and 
data swnmaries to be employed in ETC-1002-039. The preparation of this statistical 
analysis plan (SAP) has been based on International Conference on Harmonisation (ICH) 
E3 and E9 Guidelines and in reference to Protocol 1002-039 (Protocol Amendment 1, 
March 05, 2017). 
The SAP will supersede the protocol in the event of any differences between the two 
documents in the plans for data analysis, and the protocol will be amended if appropriate. 
The SAP will be included as an appendix in the clinical study report for this protocol. 
3 Study Objectives and Endpoints 
3.1 Objectives 
The primary objective for this study is to assess the 2-month efficacy of bempedoic acid 
180 mg/day versus placebo in the reduction of low-density lipoprotein cholesterol (LDL-
C) in patients on proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK91) therapy. 
The secondary objectives are: 
• To assess the 1-month efficacy of bempedoic acid 180 mg/day versus placebo in the 
reduction of LDL-C in patients on PCSK9i therapy 
• To evaluate the effect of bempedoic acid 180 mg/day versus placebo on apolipoprotein 
B (ApoB), non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), 
and high-sensitivity C-reactive protein (hs-CRP) after 1 and 2 months in patients on 
PCSK9i therapy 
• To evaluate the safety and tolerability of bempedoic acid 180 mg/day compared to 
placebo in patients on PCSK9i therapy 
The exploratory objectives are: 
3.2 Endpoints 
The following endpoints will be used to evaluate the objectives of the study. 
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Page 7 of25 


Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
3.2.1 Primary Endpoint 
• Percent change from baseline to Month 2 in LDL-C 
3.2.2 Secondary Endpoints 
• Percent change from baseline to Month I in LDL-C 
• Change from baseline to Months I and 2 in LDL-C 
Version I.I, 25Jan20I8 
Statistical Analysis Plan 
•Percent change from baseline to Months I and 2 in ApoB, non-HDL-C, TC, and hs-CRP 
• Safety and tolerability of bempedoic acid in this patient population over 2 months, as 
assessed by AEs and clinical laboratory values 
3.2.3 Exploratory Endpoints 
4 Study Design 
4.1 Study Design 
This is a Phase 2, randomized, double-blind, placebo-controlled, parallel group multicenter 
study that will be conducted at approximately 20 clinical sites in North America. Screening 
Month -4.5 (Visit SI) will occur approximately 18 weeks prior to randomization. After 
providing informed consent at Visit SI, patients will stop all background lipid-lowering 
therapy and lipid-modifying nutritional supplements, if applicable. All patients will return 
to the clinic on Month-3 (Visit 82). During this visit, patients with an LDL-C value ?:.160 
mg/dL (via central or local lab) and triglycerides <500 mg/dL (via central or local lab) will 
initiate PCSK9 background therapy (Repatha 420 mg once monthly [QM]). Sites that do 
not use a local lab may need to bring patients back for another visit to administer PCSK.9 
background therapy, as a qualifying LDL value is required prior to initiating the 3-month 
PCSK.9i run-in period. No other background lipid-modifying therapy except study 
provided PCSK9i will be permitted during the trial. After 1 month (at least 30 ± 3 days), 
patients will return to the clinic for Month -2 (Visit S3) followed by Month -I (Visit S4) 
30 ± 3 days later. During these visits, Repatha will be administered, labs will be collected, 
and safety assessed. At Visit S4, LDL-C will be checked a second time prior to 
randomization. Patients with an LDL-C ?:.70 mg/dL (via central lab only) at this visit will 
qualify for randomization. Patients with LDL-C <70 mg/dL at Visit S4 will be screen failed 
and no further PCSK9i therapy will be administered. Day 1 should occur 3 0 days ± 3 days 
after Visit S4, once LDL-C eligibility is established. On Day I, qualified patients will be 
randomized I:I to bempedoic acid 180 mg/day (n = 26) or matching placebo (n = 26). 
Randomized patients will return for clinic visits at Month 1 (Visit T2) and Month 2 (Visit 
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Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
Version 1.1, 2SJan2018 
Statistical Analysis Plan 
T3). Both study drug and PCSK.9i doses will be administered on site during clinic visits 
after all procedures have been completed. 
Figure 1. Stucly10~039 Study Design 
Bempedolc Ret<l lllOm~ (n=26) 
Placebo (n =26) 
Study Supplied Repalha 420mg QM 
Study 
Screen/ 
3 month PCSK9 
Phase 
Washout 
Run-In 
Efficacy Evaluation 
Month 
-M4.5 
-M3 
-M2 
-M1 
Day 1 
M1 
M2 
Visit 
S1 
S2 
S3 
S4 
T1 
T2 
T3 
LDL..C: 
LDL-C: 
~160 mgfdl 
~70mg/d l 
4.2 Randomization 
Patients who satisfy all entry criteria, complete the 1.5-month screening period and 3-
month PCSK9i run-in period and have an LDL-C ~70 mg/dL at Visit S4 will be 
randomized. Rando:miz.ation numbers will be assigned via IWRS on Day 1 (Visit Tl). 
Patients will be randomized in a ratio of 1: 1 to receive 1 of the following 2 treatments in a 
double-blind fashion in addition to monthly PCSK.9i background therapy: 
• Bempedoic acid 180-mg tablet 
• Matching placebo tablet 
4.3 Sample Size Justification 
The planned total sample size for this study is 52 with 26 patients in the bempedoic acid 
180 mg group and 26 in the placebo group. This sample size is expected to 
 
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Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
5 Statistical and Analytical Plans 
5.1 General Statistical Considerations 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
Summary statistics for continuous variables will include the number of patients, mean, 
median, standard deviation or standard error, minimum, and maximum. Minimum and 
maximum will be presented same number of decimal places as reported/collected, one 
additional decimal place for mean and median, and two additional decimal places for SD. 
For categorical variables, the frequency and percentage will be given. Percentage will be 
presented with one decimal place. All categories will be presented (even if no patients are 
counted in the category). Counts of zero in any category will be presented without 
percentage. 
Data will be presented on listings in order of patient, assessment date and assessment (in 
order collected on CRF, unless specified otherwise). Dates will be presented in format 
DDMMMYYYY. 
The visit schedules and window are shown below. 
Visit 
Sl 
S2 
S3 
S4 
Tl 
T2 
T3,EOS 
Slotted 
Month 
Month 
Month 
Month 
Week 
Month 
Month 
Study 
-4.5 
-3 
-2 
-1 
0 
1 
2 
Month 
Target 
NA 
Day of first 
Day of 
Day of 
Day 1 
Day31 
Day61 
Study 
420mg 
420mg 
420mg 
Day 
PCSK.9i 
PCSK9i 
PCSK9i 
injection 
injection injection 
during S3 during S4 
Analysis 
NA 
within21 
420mg 
420mg 
PCSK9i 
Tl injection 
T2 injection 
Visit 
days prior to 
PCSK9i 
PCSK9i 
injection 
ofPCSK.9i 
ofPCSK9i 
Windows 
420mg 
injection injection 
(regardless 
(regardless 
(regardless 
PCSK.9i 
during 83 during S4 dose) during 
dose)+ 30 
dose)+ 30 
injection 
visit± 3 
visit± 3 
Tl visit± 3 
± 3 days 
± 3 days 
days 
days 
davs 
Protocol 
-135 
-90±3 
-60±3 
-30±3 
1 
31±3 
61±3 
Defined 
Visit 
Window 
The details of visit window derivations will be described on the programming 
specifications. 
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Page 10 of25 


Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
5.2 Statistical Analysis Plans 
5.2.1 Analysis Sets 
5.2.1.1 Safety Population (SP) 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
The Safety Population (SP), used for all of the safety summaries, is defined as all 
randomized patients who received at least 1 dose of double-blind study medication. 
Patients in the SP will be included in the treatment group that they actually received, 
regardless of their randomized treatment. 
5.2.1.2 Modified Intent to Treat (mITT) Analysis Set 
The Modified Intent to Treat (mITT) Analysis Set, used for all of the efficacy analyses, is 
defined as all randomized patients with a baseline lipid value, at least 1 post-baseline lipid 
value, and having taken 1) their study drug within 2 days prior to the lipid measurement and 2) 
Repatha 420 mg within 30 days +/- 3 days prior to the lipid measurement. Patients in the mITT 
analysis set will be included in their randomized treatment group, regardless of the treatment 
they actually received. 
5.2.1.3 Treatment Completer Set 
The treatment completer set includes patients who were in mITT analysis set, and received 
all planned PCSK9i dosing as well as the double-blinded treatment, as indicated on the end 
of treatment CRF. Sensitivity analysis for primary and secondary efficacy endpoints will 
be performed using the treatment completer set. 
5.2.1.4 Pharmacokinetic Analysis Set (PK) 
The PK Analysis Set will include all subjects in the safety analysis set who have at least 
one PK assessment. These patients will be evaluated for PK concentration summaries 
unless significant protocol deviations have affected the data or if key dosing or sampling 
information is missing. 
5.2.2 Baseline Defmition 
Baseline LDL-C, TC, non-HDL-C,
is defined as the average oflast two 
non-missing values within Visit S4 and Day 1 (including unscheduled assessments), if only 1 
value is available, then that single value will be used as baseline. 
Baseline value for ApoB and hs-CRP will be the Day 1 value. 
If missing value presented at Visit S4 or Day 1, then the last non-missing value prior to the 
first dose of double-blind study medication (including unscheduled assessments) within Visit 
S4 and Day 1 will be used to compute the baseline for lipid measurements. 
Baseline of the laboratory evaluations, vital signs and physical examination is def med as 
the last non-missing value prior to the first dose of study medication, except baseline of 
blood pressure is defined as average of measures at same visit. 
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Page 11 of25 


Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
5.2.3 Protocol Violations and Deviations 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
A full list of protocol violations and deviations will be compiled and reviewed by the 
clinical team to identify major versus minor violations/deviations before fmal database 
lock. For violations at study entry, patients will be assessed against the inclusion and 
exclusion criteria of the protocol. For on-study deviations, compliance with the protocol 
will be examined using blinded review of the database with regard to prohibited therapies, 
and timing and availability of planned assessments. The determination of major versus 
minor protocol deviations will be conducted prior to the database lock. Any major protocol 
deviation will be summarized by treatment group, and all protocol deviation will be listed. 
5.2.4 Patient Disposition 
Disposition, including reason for withdrawal from the study drug and study, will be 
summarized by treatment group. In addition, the number of patients who withdraw from 
the study and withdraw from study drug will be summarized by discontinuation reason. 
5.2.S Demographic and Baseline Characteristics 
Demographic information and important patient baseline characteristics including, but not 
limited to, gender, race, age, baseline vital sign, and baseline lipid parameter values will 
also be summarized by treatment group. 
The following demographic and baseline characteristics will be summarized by treatment 
group, as well as overall, for safety population and for mITT: age (years), gender, race, 
ethnicity, height (cm), weight (kg), body mass index (kg/m2), systolic and diastolic blood 
pressure (mmHg), heart rate (bpm), fasting lipid parameters (TC [mg/dL], calculated LDL-
C [mg/dL],
 non-HDL-C [mg/dL] and
, ApoB (mg/dL), and 
hs-CRP (mg/dL). Data will be summarized using descriptive statistics for continuous 
variables and using counts and percentages for categorical variables by treatment group 
and overall. Age will be summarized as a continuous variable and by age group (18-40, 
41-64, 65-74, and >=75). 
5.2.6 Medical History 
General medical history will be summarized by treatment group, as well as overall, for 
safety population and mITT population and presented in a by-patient listing. Where 
appropriate, terms will be coded using the latest version of Medical Dictionary for 
Regulatory Activities (MedDRA). 
5.2. 7 Prior Medications and Concomitant Medications/Procedures 
Prior medications are defined as medications that ended prior to the initiation of double-
blind study drug. Concomitant medications are defined as medications that were ongoing 
at the time of double-blind study drug initiation or new medications that started post 
double-blind study drug initiation and within 30 days following the date of the last dose of 
study drug. 
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Page 12 of25 


Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
Medications, including prior statin medications, will be coded using WHO Drug (Sept 
2016, or later). The frequency of use of prior medications and use of concomitant 
medications will be summarized by treatment group, as well as overall, for the safety 
population according to Anatomical Therapeutic Chemical {ATC) class and preferred term. 
Prior medications, concomitant medications, and concomitant procedures will be listed for 
each patient. 
5.2.8 Study Drug (ETC-1002 or placebo) Exposure and Compliance 
The length of exposure to study drug {ETC-1002 or placebo) will be calculated as the 
number of days from the first dose of double-blind study drug to the last dose of double-
blind study drug, regardless if the patient missed one or more doses of study drug. Length 
of exposure to study drug during the double-blinded period will be summarized by 
treatment group using descriptive statistics for the safety population. 
The number and percentage of patients who were compliant with taking study drug will be 
summarized by treatment group and post-baseline time point for the safety population for 
the following categories <80%; >= 80%. Compliance for study drug will be assessed by 
counting the number of tablets that are returned as unused study drug and querying the 
patient regarding daily intake and calculated using the formula: 100* (Number Dispensed-
Number Returned) I (Duration in days between study drug dispensed and study drug 
returned). Overall compliance during the study will be calculated by programmer. 
Administration and compliance data of the study drug, including reasons for poor 
compliance, will be listed for each patient. 
5.2.9 Repatha Exposure and Compliance 
The length of exposure to Repatha for run-in and double-blinded period will be calculated 
as the number of days from the first dose of Repatha to the last dose of Repatha + 3 0 days 
within run-in and double-blinded period, respectively, regardless if the patient missed one 
or more doses of study drug. The exposure to Repatha (in total doses) will be summarized 
during the run-in period in an overall group, as well as within the treatment group during 
the double-blind period. Length of exposure to Repatha (in total doses) for overall group 
during run-in and by treatment group during double-blinded period will be summarized 
using descriptive statistics for the safety population. 
The number and percentage of patients who were compliant with taking Repatha will be 
summarized by treatment group for the safety population for the following categories 
<80%; >= 80%. For Repatha Compliance, it will be calculated using the formula: 100 * 
{Total number ofRepatha administration with 420 mg/number of planned injections). The 
number of planned injections are 3 and 2 for run-in and double-blinded period, 
respectively. 
Administration and compliance data of Repatha, including reasons for poor compliance, 
will be listed for each patient. 
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Page 13 of25 


PROC MIXED DATA=adxx method=reml;  
  
class usubjid armcd; 
 
model pchg = blres armcd  / solution ddfm=kenwardroger; 
 
repeated/group=armcd; 
 
lsmeans armcd / diff  cl; 


Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
applicable. For each parameter and analysis time point, the LSM and SE will be provided 
for both treatment groups, along with the placebo-corrected LSM, its 95% CI and 
associated p value. 
All efficacy endpoints will be analyzed at a significance level of 0.05, no multiplicity 
adjustment will be implemented. We will analyze observed data and LOCF data separately. 
The same analysis will be performed as sensitivity analysis on treatment completer set for 
secondary efficacy endpoints. 
The mean ( ± SE) will be plotted for secondary efficacy endpoints by visit. 
Exploratory endpoints 
 will be summarized by descriptive 
statistics. 
5.3.3 Pharmacokinetics 
Plasma concentrations ofbempedoic acid and ESP15228 will be expressed in ng/mL. All 
concentrations below the limit of quantification or missing data will be labeled as such in 
the concentration data listings. Concentrations below the lower limit of quantification will 
be treated as zero in summary statistics. 
PK observations with missing concentration, missing dose, missing elapsed time will be 
flagged as such in the concentration data listings and excluded from PK statistical 
summary. 
PK concentration with elapsed time less than 18 or more than 30 hours post-dose (most 
recent dose) will be flagged as "out of sampling window" in the concentration data listings 
and excluded from descriptive statistics. 
Three trough plasma concentrations of bempedoic acid and ESPl 5228 will be summarized 
from patients at pre-dose (Tl), T2, and T3 using descriptive statistics, including subject 
numbers, mean, standard deviation, CV, median and range. 
Population PK analysis may be performed if needed. The result will be reported separately 
from the clinical study report (CSR). 
5.4 Safety Endpoints and Analyses 
For all safety endpoints, the safety population (SP) will be used. Descriptive summaries 
will be provided for safety endpoints. 
The summarization of AEs will include TEAEs defined as AEs that begin or worsen after 
the first dose of double-blind study drug administration and ingestion of the first dose of 
study drug until 3 0 days after last dose of study drug. The AEs reported during the Repatha 
run-in period will be summarized separately by overall group. All TEAEs, SAEs, related 
AEs (to IMP or to Repatha), AEs leading to withdrawal of the study drug or Repatha and 
study, fatal AEs and AEs of special interest will be summarized by MedDRA System 
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Page 15 of25 


Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
Organ Class (SOC) and Preferred Term (PT) in descending order of frequency by treatment 
group. 
Clinical safety laboratories, including hematology, blood chemistry, HbAlC, glucose, and 
urinalysis; PE findings; vital signs; and weight will be summarized by the value and by 
change from baseline in the value (where appropriate) at each post-baseline time point. 
5.4.1 Adverse Events (AEs) 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
Version 19.l or later and will be categorized by MedDRA SOC and preferred term (PT). 
Patients with AEs that are ongoing at study completion or study withdrawal must be 
followed until resolution, until stable/chronic, or for 30 days after the last study visit, 
whichever comes first. Summary tables will focus on TEAEs; however, listings will 
include all AEs (with non-TEAEs flagged). 
In summary tables, TEAEs will be counted as "Not Related" if relationship to IMP was 
assessed as 'Not Related' or "Unlikely". Events will be counted as "Related" if relationship 
to IMP was assessed as 'Possible', 'Probable', 'Definite', or if relationship to IMP is 
missing. TEAEs related to the Repatha will be summarized in the similar fashion. 
The severity of the AE will be characterized as mild, moderate, or severe, to the following 
definitions: 
• 
Mild: Events are usually transient and do not interfere with the patient's daily 
activities 
• 
Moderate: Events introduce a low level of inconvenience or concern to the patient 
and may interfere with daily activities 
• 
Severe: Events interrupt the patient's usual daily activity, are incapacitating with 
inability to do usual activities, or significantly affect clinical status and warrant 
intervention and/or close follow-up 
The run-un period will be defined as the period subjects receive Repatha prior to Visit Tl. 
It's 3 months prior to Visit Tl. 
Overviews of TEAEs will be presented by treatment group containing the following counts 
and percentages for: 
• 
Patients with AE during the run-in period 
• 
patients with TEAEs 
• 
patients with TEAEs by SOC and PT 
• 
patients with AEs during run-in period by SOC and PT 
• 
patients with TEAEs by maximum severity 
• 
patients with treatment-related TEAEs by IMP or by Repatha 
• 
patients with SAE during the run-in period 
• 
patients with treatment-emergent serious adverse events (TE SAEs) 
• 
patients with TE SAEs by SOC and PT 
• 
patients with SAEs during the run-in period by SOC and PT 
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Page 16 of 25 


Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
• 
patients with TE SAEs by maximum severity 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
• 
patients with treatment-related TE SAEs by IMP or by Repatha 
• 
withdrawal from study drug due to TEAEs 
• 
patients with TEAE by PT 
• 
patients with TE SAEs by PT 
• 
patients with study drug-related TEAEs by PT 
The AE overview summaries will count a patient at most once in each AE category (at the 
"highest/most extreme" designation of each category regardless of preferred term) and 
percentages will be based on the total number of patients in the safety population. 
In addition to a comprehensive listing of all AEs (with non-TEAEs flagged), separate 
listings will be generated for SAEs, AEs resulting in withdrawal of study drug, and AEs 
with a fatal outcome. 
5.4.2 Adverse Events of Special Interest 
Across clinical studies to date, the most :frequently reported TEAEs associated with the 
experiences with ETC-1002 included musculoskeletal and connective tissue disorders 
(pain in extremity, myalgia, arthralgia, and muscle spasms), nervous system disorders 
(headache), and gastrointestinal disorders (nausea and diarrhea). 
As with other lipid lowering medications, adverse events of special interest (AESI) include 
hepatic disorders (including changes in hepatic aminotransferases), musculoskeletal events 
(AE and CK evaluation), new onset diabetes/hyperglycemia, renal events, and 
neurocognitive/neurologic events. These events will be evaluated from the AE database by 
SOC and PT, and will be identified as safety monitoring endpoints. 
• 
AEs of muscle-related symptoms will be summarized by treatment group. In 
addition, the number and percent of patients with abnormal CK values will be 
summarized. 
• 
New onset diabetes/hyperglycemia will be recorded as AEs and will be summarized 
using the appropriate SOC. The events will be summarized by severity and 
relationship to study drug for each treatment group. 
• 
Baseline eGFR and values of CK will be summarized by treatment group and by 
baseline eGFR categories. Shift tables of eGFR category from baseline over the 
study, will be provided by treatment group. 
• 
Neurocognitive events will be identified and evaluated by routine monitoring of PE 
findings and AEs. Summarization of neurocognitive events will occur using pre-
specified MedDRA terms and will be performed by treatment group. 
• 
Hypoglycemia/Metabolic acidosis occurrences will be summarized based on AE 
evaluations. 
AESI will be presented in a listing and summarized by SOC, PT and treatment group. 
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Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
5.4.3 Laboratory Evaluations 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
Continuous laboratory parameters (serum chemistry, hematology), urinalysis, urinalysis 
[microscopic]) listed in Table 4; glucose, and HbAl c will be summarized using descriptive 
statistics for the observed value and the change from baseline for all post-baseline study 
visits. Missing values for any of the laboratory evaluations will not be imputed; that is, 
only observed case data will be used. Categorical urinalysis data will be listed, but will not 
be summarized. 
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Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
Table 4: 
Clinical Laboratory Parameters (Safety) 
Hematology 
• 
Hematology 
• 
Hematocrit (Hct) 
• 
Hemoglobin (Hgb) 
• 
Mean corpuscular hemoglobin 
(MCH) 
• 
Mean corpuscular hemoglobin 
concentration (MCHC) 
• 
Mean corpuscular volume (MCV) 
• 
Platelet count 
• 
Red blood (RBC) cell count 
• 
White blood (WBC) cell count 
with differential (absolute and % ) 
Urinalysis (Dipstick) 
• 
Clarity 
• 
Bilirubin 
• 
Color 
• 
Glucose 
• 
Ketones 
• 
Leukocyte esterase 
• 
Nitrate 
• 
Occult blood 
• 
pH 
• 
Protein 
• 
Specific gravity 
• 
Urobilinogen 
Urinalysis (Microscopic)-only if urine 
dipstick abnormal 
• 
Bacteria 
• 
Casts 
• 
Crystals 
• 
Epithelial cells 
• 
Red blood cell (RBC) 
• 
WBC 
Blood Chemistry (serum, fasting) 
• 
Albumin (Alb) 
• 
Alkaline phosphatase (Alk-P) 
• 
Alanine aminotransferase 
(ALT; SGPT) 
• 
Aspartate aminotransferase 
(AST; SGOT) 
• 
Blood urea nitrogen (BUN) 
• 
Calcium (Ca) 
• 
Carbon dioxide (C02) 
• 
Chloride (Cl) 
• 
Creatinine 
• 
Creatine kinase (CK) 
• 
Glucose 
• 
Lactate dehydrogenase (LDH) 
• 
Phosphorus 
• 
Potassium (K) 
• 
Sodium (Na) 
• 
Total and direct bilirubin (TB) 
• 
Total protein 
• 
Uric acid 
Coagulation (only in patients receiving 
anticoagulant therapy that in the 
investigator's judgment require 
monitoring at Visit Tl and 3 to 5 
days post Visit T 1) 
• 
Prothrombin time (PT) 
• 
International normalized ration 
(INR) 
Additional samples 
• 
Hemoglobin AlC (HbAlC) 
• 
PK 
The number and percentage of patients with laboratory abnormalities (i.e., laboratory 
values outside the stated laboratory normal range) will be summarized at each time point 
(i.e., including baseline and post-baseline time points) for each laboratory parameter. The 
determination of laboratory abnormalities will take into account any unscheduled 
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Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
laboratory assessments. Additional lab-related summaries will be provided as follows for 
hepatic safety, musculoskeletal safety, diabetes and hyperglycemia, and renal safety. 
5.4.3.1 Hepatic Safety 
For liver-associated enzymes and total bilirubin (TB), the number and percent of patients 
with abnormal values for ALT(> 3 x ULN, > 5 x ULN), AST(> 3 x ULN, > 5 x ULN), 
and TB(> 2xULN) will be summarized by treatment group and overall, normal baseline 
ALT/AST/TB and abnormal baseline ALT/AST/TB. 
Potential Hy's law criteria (> 3 x upper limit of normal [ULN] for either ALT or AST, with 
accompanying TB > 2 x ULN, with no other known cause) will also be applied to the data; 
any potential Hy's law cases will be listed separately. 
5.4.3.2 Renal Safety 
Baseline eGFR and values of CK will be summarized by treatment group and by baseline 
eGFR categories. Shift tables of eGFR category from baseline over the study, will be 
provided by treatment group. 
5.4.4 Physical Examinations (PEs) 
Listings of PE data will include only those records where the body system at the baseline 
PE was normal, but the body system at a post-baseline PE was marked as 'Change from 
previous exam, clinically significant.' Only changes from baseline physical examination 
findings that meet the definition of an AE will be recorded on the AE page of the eCRF 
and will be summarized with other AE outcomes. 
5.4.5 '\Tital Signs 
Actual values and changes from baseline in vital signs (heart rate, systolic blood pressure, 
diastolic blood pressure, weight, height [baseline only], and BMI) will be summarized 
using descriptive statistics by treatment group and post-baseline time point on the observed 
values. Baseline is defined as the last value prior to the first dose of study medication. 
Vital signs data will be listed for each patient, with increases from baseline of> 15 mmHg 
in systolic or diastolic blood pressure flagged. 
For vital signs, observed values and changes from baseline will be summarized for all post-
baseline study visits. 
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Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
6 Changes in Statistical Analysis Plan Based on the Study-
Specific Protocol 
1. To be consistent with other Esperion studies, the LDL-M will be used as primary 
endpoint where triglycerides (TG) > 400 mg/dL or LDL-C < 50 mg/dL for primary efficacy 
endpoint analysis. 
2. The treatment completer set will be used for sensitivity analyses of primary and 
secondary efficacy endpoints. 
3. AEs during run-in period will be summarized. 
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Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
7 Reference 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
1. Sharrett AR, Ballantyne CM, Coady SA, Heiss G, Sorlie PD, Catellier D, et al. 
Atherosclerosis Risk in Communities Study Group. Coronary Heart Disease 
Prediction from Lipoprotein Cholesterol Levels, Triglycerides, Lipoprotein(A), 
Apolipoproteins A-I and B, and HDL Density Subfractions. The Atherosclerosis 
Risk in Communities (ARIC) Study. Circulation. 2001;104:1108-13. 
2. World Health Organization (WHO) Fact Sheet No 317 Updated January 2015. 
3. Glynn RJ, Laird NM, and Rubin DB. (1986). Selection modelling versus mixture 
modelling with nonignorable nonresponse. In H. Wainer (ed.), Drawing 
Inferences from Self-Selected Samples, pp. 115-142. New York: Springer. 
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Page 22 of25 


Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
8 Appendices 
Appendix 1: Schedule of Events (Subject Visit Schedule) 
Visit 
s11,2 
S2 
Month 
Month-4.5 
Month-3 
Day 
Day-135 
Day-90±3 
Procedure 
Informed Consent 
x 
Enrollment Criteria 
x 
x 
Demographics 
x 
Medical History 
x 
Concomitant Medications 
x 
x 
Adverse Event Recording 
x 
Physical Exam 
x 
Weight4 
x 
Height 
x 
Vital Signs6 
x 
x 
Serology' 
x 
Serum Pregnancy/FSH8 
x 
Urine pregnancy test for 
women of childbearing 
potential only 
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Schedule of Events 
S3 
S4 
Month-2 
Month-1 
Day-60±3 
Day-30±3 
x 
x 
x 
x 
x 
x 
x 
x 
Tl 
WeekO 
Day 
1* 
x 
x 
x 
x 
x 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
Tl 
T3/EOS3 
Month 1 
Month2 
Day31±3 
Day61±3 
x 
x 
x 
x 
x 
x 
x 
x 
Page 23 of25 
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Esperion Therapeutics, Inc. 
Protocol: ETC-1002-039 
Visit 
Month 
Day 
Procedure 
TSH 
Clinical Safety Labs9 
Basic Fasting Lipids 10 
ApoB and hs-CRP 
HbA1c 
PK - predose trough 
Diet and exercise counseling11 
Establish Patient Eligibility 
Randomization 
IWRS Contact
12 
PCSK9i administered at site 
Double-blind Drug Dispensing 
IMP Return/Compliance 
PCSK9i Return/ Accountability 
s11,2 
S2 
Month-4.5 
Month-3 
Day-135 
Day-90±3 
x 
x 
x 
x•• 
x 
x 
x 
x 
x 
x 
x 
Schedule of Events 
S3 
S4 
Month-2 
Month-1 
Day-60±3 
Day-30±3 
x 
x••• 
x 
x 
x 
x 
Tl 
WeekO 
Day 
1* 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Version 1.1, 25Jan2018 
Statistical Analysis Plan 
Tl 
T3/EOS3 
Month 1 
Month2 
Day31±3 
Day61±3 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
NOTE: For patients who withdraw from study drug treatment, but consent to be followed for safety assessments and return to clinic for these visit, the visits will occur according to the 
protocol schedule. Safety assessments should include clinical safety and basic lipid laboratories, adverse events (AEs ), physical examination (PE), vital signs. For patients who withdraw 
from study drug treatment, but consent to be followed for safety assessments by phone, the telephone contacts will occur according the protocol schedule with information regarding cmrent 
health status and t.o collect infonnation on AEs ( eg, recent procedures, hospitalizations, and if the patient has died, the cause of death). If a patient does not provide consent t.o be followed for 
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