Clinical trial NCT02991118
Conditions: Hypercholesterolemia Atherosclerotic Cardiovascular Disease
Keywords: hyperlipidemia cholesterol familial hypercholesterolemia atherosclerotic cardiovascular disease ASCVD HeFH LDL
Sponsor: Esperion Therapeutics, Inc.
Start date: 2016-11-18; Completion date: 2018-08-22
Enrollment: 779 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to see if bemedoic acid (ETC-1002) is effective versus placebo in patients with high cardiovascular risk and elevated LDL cholesterol not adequately controlled by their current therapy.

Detailed description:

Arms: arm 1: bempedoic acid 180 mg/day arm 2: Placebo control
Interventions: intervention 1: bempedoic acid intervention 2: placebo
Intervention descriptions: intervention 1: bempedoic acid 180 mg tablet taken orally, once daily. Patients remain on ongoing lipid-modifying therapy (not study provided) intervention 2: Matching placebo tablet taken orally, once daily. Patients remain on ongoing lipid-modifying therapy (not study provided)

Protocol documents:
Prot_000.pdf: 
NCT number: NCT02991118
This NCT number has been applied to the document 
for purposes of  posting on clinicaltrials.gov


Bempedoic Acid 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
Amendment 3, 09 May 2017 
Confidential 
Page 2 of 184 
2.
SYNOPSIS
Name of Sponsor: Esperion Therapeutics, Inc. 
Name of Investigational Product: Bempedoic Acid (ETC-1002) 
 tablets 
Name of Active Ingredient: Bempedoic acid (ETC-1002) 
Title of Study: 
A Long-term, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy 
of Bempedoic Acid (ETC-1002) in Patients with Hyperlipidemia at High Cardiovascular Risk Not 
Adequately Controlled by Their Lipid-Modifying Therapy  
Study Number: 1002-047 
Phase of Development: 3 
Clinical Sites: Approximately 125 sites located in North America and Europe 
Objectives: 
Primary: 
•
To assess the 12-week efficacy of bempedoic acid (ETC-1002) 180 mg/day versus placebo in
decreasing low-density lipoprotein cholesterol (LDL-C) in high cardiovascular (CV) risk patients
with hyperlipidemia (with underlying heterozygous familial hypercholesterolemia [HeFH] and/or
atherosclerotic cardiovascular diseases [ASCVD]) who are not adequately controlled with their
maximally tolerated lipid-modifying therapy.
Secondary: 
•
To evaluate the effect of 24-week treatment with bempedoic acid 180 mg/day versus placebo on
LDL-C.
•
To evaluate the effect of bempedoic acid 180 mg/day versus placebo on non-high-density
lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), high-sensitivity C-reactive protein
(hs-CRP), and apolipoprotein B (apoB) after 12 weeks of treatment.
Tertiary: 
•
To evaluate the effect of long-term (52-week) treatment with bempedoic acid 180 mg/day versus
placebo on LDL-C, non-HDL-C, TC, high-density lipoprotein cholesterol (HDL-C), triglycerides
(TG), hs-CRP, and apoB.
•
To evaluate the long-term (52-week) safety and tolerability of bempedoic acid 180 mg/day
compared to placebo.


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Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 4 of 184 
 
High Intensity Statinsa 
Moderate Intensity Statins 
Low Intensity Statinsb 
Atorvastatin 40-80 mg 
Atorvastatin 10-20 mg 
Simvastatin 10 mg 
Rosuvastatin 20-40 mg 
Rosuvastatin 5-10 mg 
Pravastatin 10-20 mg 
 
Simvastatin 20 mg 
Lovastatin 20 mg 
 
Pravastatin 40-80 mg 
Fluvastatin 20-40 mg 
 
Lovastatin 40 mg 
Pitavastatin 1 mg 
 
Fluvastatin XL 80 mg 
 
 
Fluvastatin 40 mg BID 
 
 
Pitavastatin 2-4 mg 
 
a Simvastatin doses ≥40 mg/day are not allowed.  
b Low intensity statins also include those patients taking low-dose statins using an alternate regimen 
(ie, every other day, or for a specified number of times per week) and those unable to tolerate a statin 
at any dose 
Thus, the randomization stratum for this study are: 
 
HeFH (with or without ASCVD) 
ASCVD (without HeFH) 
HeFH + Low Intensity Statinsa 
ASCVD + Low Intensity Statinsa 
HeFH + Moderate Intensity Statins 
ASCVD + Moderate Intensity Statins 
HeFH + High Intensity Statins 
ASCVD + High Intensity Statins 
ASCVD = Atherosclerotic cardiovascular diseases; HeFH = Heterozygous familial 
hypercholesterolemia. 
a Low intensity statins also include those patients taking low-dose statins using an alternate regimen 
(ie, every other day, or for a specified number of times per week) and those unable to tolerate a statin 
at any dose  
 
Approximately 750 eligible patients will be randomized 2:1 on Day 1 (Visit T1) to receive either 
bempedoic acid 180 mg (n = 500), or placebo (n = 250) once daily for 52 weeks.  Randomized patients 
will return for clinic visits at Week 4 (Visit T2), Week 12 (Visit T4), Week 24 (Visit T5), and Week 52 
(T7).  A phone visit will occur at Week 8 (Visit T3) and Week 36 (T6).  Patients who withdraw from 
investigational medicinal product (IMP) treatment will be asked to continue to be followed for safety 
using the protocol-specified visit schedule and procedures.  For details of study assessments, see the 
Schedule of Events in Appendix 1. 
An independent expert Data Monitoring Committee (DMC) will formally review accumulating unblinded 
safety and efficacy data from this and other ongoing studies of bempedoic acid.  A blinded independent 
expert Clinical Events Committee (CEC) will adjudicate designated clinical endpoints, including all 
major adverse cardiac events (MACE) and non-MACE endpoints defined as:  CV death (MACE), non-
CV death (non-MACE), nonfatal myocardial infarction [MI] (MACE), nonfatal stroke (MACE), 
hospitalization for unstable angina (MACE), coronary revascularization (MACE), non-coronary arterial 
revascularization (non-MACE), and hospitalization for heart failure (non-MACE) using standardized 
definitions. Any clinical endpoints that meet serious adverse event (SAE) criteria will be reported as 
SAEs. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 5 of 184 
Primary Endpoint 
The primary efficacy endpoint for this study is the percent change from baseline to Week 12 in LDL-C 
Secondary Endpoints 
1. Percent change from baseline to Week 24 in LDL-C 
2. Percent change from baseline to Week 12 in non-HDL-C, TC, apoB, and hs-CRP 
3. Absolute change from baseline to Weeks 12 and 24 in LDL-C 
 
Tertiary Endpoints 
1. Absolute change and percent change from baseline to Week 52 in LDL-C 
2. Percent change from baseline to Weeks 24 and 52 in non-HDL-C, TC, apoB, and hs-CRP  
3. Percent change from baseline to Weeks 12, 24, and 52 in TG and HDL-C 
 
Safety Endpoints 
1. Patient incidence to treatment-emergent adverse events (TEAE) 
2. Safety laboratory values and vital signs 
3. Cardiovascular event rates  
Number of patients (planned): Approximately 750 adult male and female patients 
Duration of treatment: All patients will be treated for 52 weeks 
End of Study: The study will end when the last randomized patient completes the Week 52 visit.  The 
estimated overall duration of the study (first patient first visit [FPFV] to last patient last visit [LPLV]) is 
approximately 21 months. 
Diagnosis and criteria for patient eligibility:  
The study will enroll adult male and female patients with hyperlipidemia  
Each patient must meet the following criteria to be eligible for this study:  
Inclusion Criteria 
1. Provision of written informed consent prior to any study-specific procedure 
2. Age ≥18 years or legal age of majority depending on regional law, whichever is greater at Week -5 
(Visit S1) 
3. Men and nonpregnant, nonlactating women.  
4. Women must be either:  
• 
Naturally postmenopausal (as reported by the patient, defined as greater than 55 years and 
≥1 year without menses, <55 years and ≥1 year without menses with follicle-stimulating hormone 
(FSH) ≥40.0 IU/L), or surgically sterile including hysterectomy, bilateral oophorectomy, or tubal 
ligation or;  
• 
Women of childbearing potential must be willing to use 2 acceptable methods of birth control 
(unless they have agreed to follow the definition of true abstinence).  The minimal requirement 
for adequate contraception should be started on Day 1, continuing during the study period, and 
for at least 30 days after the last dose of study drug.  Acceptable methods of birth control include: 
oral, implantable, injectable, or topical birth control medications; placement of an intrauterine 
device (IUD) 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; or 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 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 6 of 184 
of abstinence for the duration of the 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. 
5. Fasting LDL-C (minimum of 10 hours) value at Week -5 (Visit S1) ≥100 mg/dL (2.6 mmol/L) and 
fasting LDL-C value at Week -1 (Visit S3) ≥70 mg/dL (1.8 mmol/L) 
6. Have high CV risk that is defined as either: 
• 
Diagnosis of HeFH.  Diagnosis must be made by either genotyping or by clinical assessment 
using either the World Health Organization (WHO) criteria/Dutch Lipid Clinical Network 
Criteria with a score that is >8 points (see Appendix 4) or the Simon Broome Register Diagnostic 
Criteria with an assessment of ‘Definite HeFH’ (see Appendix 5).  Patients with a diagnosis of 
HeFH may or may not have established coronary heart disease (CHD) or CHD risk equivalents. 
OR 
• 
Have ASCVD (with established CHD or CHD risk equivalents) 
Documented history of CHD (includes 1 or more of the following): 
o Acute MI 
o Silent MI 
o Unstable angina 
o Coronary revascularization procedure (eg, percutaneous coronary intervention [PCI] or 
coronary artery bypass graft [CABG] surgery) 
o Clinically significant CHD diagnosed by invasive or non-invasive testing (such as coronary 
angiography, stress test using treadmill, stress echocardiography, or nuclear imaging) 
Documented CHD risk equivalents (includes 1 or more of the following criteria): 
o Symptomatic peripheral arterial disease (PAD) defined as  
- peripheral vascular disease with symptoms of claudication or resting limb ischemia with 
either ankle brachial index <0.9 performed by a vascular lab or 
- angiogram (including computed tomographic angiography [CTA]) showing ≥50% 
stenosis or 
- peripheral arterial revascularization (surgical or percutaneous) occurring greater than 
90 days prior to Visit S1 or 
- abdominal aortic aneurysm confirmed by imaging or aortic aneurysm repair occurring 
greater than 90 days prior to Visit S1 or 
- lower extremity amputation due to peripheral vascular disease occurring greater than 
90 days prior to Visit S1 
o Cerebrovascular atherosclerotic disease defined by: 
- ischemic stroke occurring greater than 90 days prior to Visit S1 or 
- Carotid endarterectomy, carotid stenting, or more than 70% stenosis in a carotid artery 
determined by carotid ultrasound or angiogram occurring greater than 90 days prior to 
Visit S1.   
Note:  Patients with T2DM are allowed in this study; however, for this study T2DM is not 
considered a CHD risk equivalent 
7. Be on maximally tolerated lipid-modifying therapy, including a maximally tolerated statin either 
alone or in combination with other lipid-modifying therapies, at stable doses and regimens for at least 
4 weeks prior to screening (6 weeks for fibrates; however, gemfibrozil is not allowed as per co-
administration instructions defined in the statin label).  Maximally tolerated statin includes statin 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 7 of 184 
regimens other than daily dosing, including no to very low doses, but reasons for not using high-
intensity statin dosing must be documented.  
A patient’s maximally tolerated lipid-modifying therapy will be determined by the investigator using 
their medical judgment and available sources, including the patient’s self-reported history of lipid-
modifying therapy.  
Note:  Patients can be on any available lipid-modifying therapy with the exception of the exclusions 
listed below as long as they have been stable for 4 weeks prior to Screening Visit S1 and are taken at 
a consistent time each day.  In the case of PCSK9 inhibitor use, the patient must have received 
3 stable doses.  It is important that lipid values are measured at PCSK9i trough levels.  Therefore, 
study visits should be scheduled in accordance with the patient’s PCSK9i injection regimen so that 
measurement of lipid values for all visits occurs before the PCSK9i injection but not greater than 
48 hours before the next scheduled PCSK9i injection.  Patients who have discontinued investigational 
or commercial PCSK9 inhibitor must have had their last dose at least 4 months prior to Screening 
Visit S1. 
Exclusion Criteria: 
1. Total fasting (minimum of 10 hours) TG ≥500 mg/dL (5.6 mmol/L) at Week -5 (Visit S1) 
Note: TG may be repeated 1 time between Visits S1 and S2.  For those patients who have a repeat 
TG, the repeat value will be used to determine eligibility. 
2. Renal dysfunction or nephritic syndrome or a history of nephritis, 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 Week -5 (Visit S1) (Levey 2006).   
Note:  At the discretion of the investigator, the screening period may be extended up to 4 weeks for a 
single repeat eGFR.  For those patients who have a repeat eGFR, the repeat value should be obtained 
between Visits S1 and S2 and will be used to determine eligibility. 
3. Body mass index (BMI) ≥50 kg/m2 
4. Recent (within 3 months prior to the screening visit [Week -5 (Visit S1)] or between screening and 
randomization visits) MI, unstable angina leading to hospitalization, uncontrolled, symptomatic 
cardiac arrhythmia (or medication for an arrhythmia that was started or dose changed within 3 months 
of screening), CABG, PCI, carotid surgery or stenting, cerebrovascular accident, transient ischemic 
attack (TIA), endovascular procedure or surgical intervention for peripheral vascular disease or plans 
to undergo a major surgical or interventional procedure (eg, PCI, CABG, carotid or peripheral 
revascularization).  Patients with implantable pacemakers or automatic implantable cardioverter 
defibrillators may be considered if deemed by the Investigator to be stable for the previous 3 months. 
5. Uncontrolled hypertension, defined as sitting systolic blood pressure (SBP) ≥160 mmHg and diastolic 
blood pressure (DBP) ≥100 mmHg after sitting quietly for 5 minutes.   
Note: If the initial blood pressure (BP) values meet or exceed the specified level, an additional BP 
assessment may be completed.  If the systolic or the diastolic values continue to meet or exceed the 
threshold, the patient may not continue screening.  However, at the discretion of the Investigator, the 
screening period (between Visits S1 and S2) may be extended up to 4 weeks to allow for a repeat 
qualifying BP assessment following adjustment of BP medication(s), provided that the patient has 
been on a stable dose of the BP medication for a minimum of 2 weeks prior to randomization and the 
repeat BP measurements do not meet the exclusion criteria. 
6. Hemoglobin A1C (HbA1C) ≥10% at Week -5 (Visit S1) 
7. Uncontrolled hypothyroidism, including thyroid-stimulating hormone (TSH) >1.5 × the upper limit of 
normal (ULN) at Week -5 (Visit S1). Patients stabilized on thyroid replacement therapy for at least 
6 weeks prior to randomization are allowed. 
8. Liver disease or dysfunction, including:  


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 8 of 184 
• 
Positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies 
(HCV-AB) at Week -5 (Visit S1); or 
• 
Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≥2 × ULN, and/or total 
bilirubin (TB) ≥2 × ULN at Week -5 (Visit S1).  If TB ≥1.2 × ULN, a reflex indirect 
(unconjugated) bilirubin will be obtained and if consistent with Gilbert’s disease or if the patient 
has a history of 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 
prior to randomization.  For those patients who have a repeat ALT and/or AST, the repeat value 
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. Hematologic or coagulation disorders or a hemoglobin (Hgb) level <10.0 g/dL (100 g/L) at Week -5 
(Visit S1) 
11. Active malignancy, including those requiring surgery, chemotherapy, and/or radiation in the past 
5 years.  Nonmetastatic basal or squamous cell carcinoma of the skin and cervical carcinoma in situ 
are allowed 
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 with amphetamine derivatives prescribed by and under the care of a health care practitioner 
can be enrolled after evaluation by the Investigator. 
14. Blood donation, blood transfusion, participation in a clinical study with multiple blood draws, major 
trauma, or surgery with or without blood loss within 30 days prior to randomization 
15. Use of any experimental or investigational drugs within 30 days prior to screening.   
16. Previous enrollment in a bempedoic acid clinical study.   
17. Use of any of the following drugs or a plan to use these drugs during the study:  
• 
New or planned dose changes of systemic corticosteroids.  Stable doses (≥4 weeks before 
Visit S1) and topical corticosteroids allowed.  
• 
CETP inhibitors within the last 2 years prior to screening (Week -5, Visit S1) except for 
evaceptrapib within the last 3 months prior to screening (Week -5, Visit S1) 
• 
Mipomersen (6 months prior to screening, Week -5, Visit S1) 
• 
Lomitapide (3 months prior to screening, Week -5, Visit S1) 
• 
Apheresis (3 months prior to screening, Week -5, Visit S1) 
• 
Simvastatin ≥40 mg/day (4 weeks prior to screening, Week -5, Visit S1) 
• 
Red yeast rice extract -containing products are not allowed (2 weeks prior to screening,  
Week -5, Visit S1) 
18. Planned initiation of the following drugs during the clinical trial or changes prior to randomization 
(Day 1, Visit T1): 
• 
Hormone replacement (6 weeks prior to randomization) 
• 
Thyroid replacement (6 weeks prior to randomization) 
• 
Diabetes medications (4 weeks prior to randomization) 
• 
Obesity medication (4 weeks prior to randomization) 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 9 of 184 
19. Lack of adherence (ie, less than 80% of planned doses) with IMP (single-blind placebo) during the 
Run-in Period.  
20. Lack of tolerance with IMP (single-blind placebo) during the Run-in Period. 
21. 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. 
22. An employee or contractor of the facility conducting the study, or a family member of the Principal 
Investigator, Co-Investigator, or Sponsor. 
23. Pregnant, breastfeeding, or intending to become pregnant within 30 days after last dose of study drug. 
24. Patients who have enrolled in a study of an experimental siRNA inhibitor of PCSK9 are excluded.  
IMP, dosage and mode of administration:  
• 
Bempedoic acid 180-mg tablets.  
• 
Matching placebo tablets 
• 
All IMP will be ingested once daily with or without food. 
Non-investigational medicinal product(s) (NIMP), dosage and mode of administration: 
• 
Background lipid-lowering therapy including maximally tolerated statins 
• 
All background lipid-lowering therapy will be ingested as prescribed by a physician 
Criteria for evaluation: 
Lipid Assessments: 
• 
Calculated LDL-C, HDL-C, non-HDL-C, TC, apoB, and TG.  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. 
Safety Assessments: 
• 
Adverse events and SAEs will be collected and reported.  Clinical endpoints will be collected and 
adjudicated by an independent CEC.  Clinical endpoints will also be reported as SAEs as 
appropriate.  Other safety assessments will include clinical safety laboratories (including 
hematology, blood chemistry, coagulation, HbA1C, fasting glucose, and urinalysis), physical 
examination (PE) findings, vital signs, electrocardiogram (ECG) readings, 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 
• 
Coagulation:  Prothrombin time (PT), International Normalized Ratio (INR) 
• 
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: 
• 
HBsAg, hepatitis C virus (HCV), serum pregnancy test (only for females who are of childbearing 
potential), FSH (only for females who are <55 years old and >1 year without menses), urine 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 10 of 184 
pregnancy test (for females of childbearing potential) on Day 1 prior to randomization, TSH 
PK and other Biomarkers:  
• 
hs-CRP 
• 
Plasma PK concentrations will be collected prior to dose at Weeks 24 and 52, for use in further 
developing the population pharmacokinetic (PK) model. 
Safety and Monitoring: 
Monitoring and Management Plans for Lipid Elevations: 
Elevated LDL-C—Adjunctive Therapy: 
An adjunctive therapy plan is in place for those patients whose LDL-C values meet the protocol-defined 
LDL-C threshold criteria. Post-randomization, LDL-C results will be masked to investigators in order to 
maintain the blind; however, the following thresholds have been set to notify investigators and provide an 
opportunity to adjust the patient’s standard of care regimen.  
• 
Beginning at Week 24 (Visit T5) visit and for the duration of the study, the central laboratory will 
notify the investigator when the patient’s LDL-C value is >170 mg/dL (4.4 mmol/L) and ≥25% 
from the patient’s baseline value at Week 0 (Visit T1) 
• 
Upon receiving notification from the central laboratory that the patient has met or exceeded the 
threshold criteria for LDL-C, the investigator will initiate the following adjunctive therapy plan: 
- Patients will be scheduled to return to the clinic within 1 week for a repeat fasting blood 
lipid sample to confirm that the LDL-C value meets the threshold criteria  
- After confirming that the LDL-C value meets or exceeds the threshold criteria, the 
investigator will adjust the patient’s lipid-lowering treatment regimen per standard-of-
care and local practice, with the exception of simvastatin at doses ≥40 mg/day and the 
fibrate gemfibrozil. The patient’s LDL-C will be re-evaluated at the next scheduled clinic 
visit as defined in the Schedule of Visits (Appendix 1). 
- The initiation of any new or dose changes of any lipid-lowering treatment will be 
documented on the electronic case report form (eCRF) as a concomitant medication with 
the associated start date 
- Patients who have their lipid-lowering treatments modified, including new medications or 
dosage changes to existing medications, should return to the clinic in 4 weeks after the 
modification to their lipid-lowering treatment for a routine safety laboratory assessment. 
Additional safety laboratory assessments may be conducted at the investigator’s 
discretion. 
- Adjunctive therapy medications will not be provided by the sponsor 
- Patients continuing to exceed the LDL-C threshold after maximizing the standard-of-care 
LDL-C-lowering therapy and, in the opinion of the investigator, require therapies that are 
prohibited by the protocol will be discontinued from IMP treatment and will be asked to 
continue to be followed for safety using the protocol-specified visit schedule. 
Monitoring and Management Plans for Triglyceride Elevations: 
Elevated Triglycerides: 
Patients may continue to use stable doses of TG-lowering medications during the study.  An adjunctive 
therapy plan is in place for those patients whose TG values meet the protocol-defined threshold criteria.  
Post-randomization, TG results will be masked to investigators in order to maintain the blind; however, a 
threshold has been set to notify investigators and provide an opportunity to adjust the patient’s standard of 
care regimen.  Beginning at Week 4 (Visit T2), if the TG level exceeds 1000 mg/dL (11.3 mmol/L) while 
on treatment, the investigator will receive notification from the central laboratory that the patient has met 
or exceeded the protocol-defined threshold criteria for TG.  The investigator will initiate the following 
plan: 


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• 
Any patient with TG >1000 mg/dL (11.3 mmol/L) will be reminded to fast for at least 10 hours 
and will return to clinic within 1 week for a repeat, fasting TG sample to confirm the TG value 
meets the threshold criteria  
• 
Any patient with a confirmed TG >1000 mg/dL (11.3 mmol/L) may initiate standard-of-care 
therapy (however, gemfibrozil may not be added) to lower TG using a patient-specific 
prescription.  The initiation of this medication will be documented on the case report form as a 
concomitant medication with the associated start date.  These medications will not be provided by 
the sponsor. 
• 
Patients continuing to exceed the TG threshold after maximizing the standard-of-care triglyceride-
lowering therapy will be discontinued from IMP treatment and will be asked to continue to be 
followed for safety using the protocol-specified visit schedule. 
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.  Patients will be educated on the signs and symptoms of hypoglycemia and asked 
to report the experienced signs and symptoms to the investigator.  Investigator confirmed occurrences 
of hypoglycemia will be reported as AEs.  Potential cases of reversible hypoglycemia and metabolic 
acidosis will be identified by routine safety monitoring of AEs and clinical safety laboratories. 
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.  
Diabetes and Hyperglycemia: 
Cases of new onset of diabetes will be recorded as AEs.  Clinical laboratories, including HbA1C and 
glucose will also be evaluated across treatment groups during this study and all ongoing studies to 
identify potential cases of new onset of diabetes  
Neurocognitive Events: 
Neurocognitive events will be identified and evaluated by routine safety monitoring of PE findings 
and AEs. 
Clinical Endpoints: 
Clinical endpoints will be monitored and adjudicated by an independent expert CEC for this study and 
other ongoing studies in the bempedoic acid program. 
Routine cardiovascular monitoring will include review of cardiovascular AEs, SAEs, (both as 
adjudicated by the CEC), standard vital signs, and ECGs. 
Additional details regarding safety monitoring are included in Section 11.1.6.3.1 through 
Section 11.1.6.4.  
Further details on occurrence and monitoring are available in the Investigator’s Brochure (IB). 
Statistical methods: 
Sample Size 
The primary efficacy endpoint for this study is the percent change from baseline to Week 12 in LDL-C.   
The sample size of 500 randomized patients in the bempedoic acid 180 mg group and 250 randomized 
patients in the placebo group is expected to provide more than 95% power to detect a difference of 15% 
in the percent change from baseline to Week 12 in LDL-C between the bempedoic acid treatment group 
and the placebo group.  This calculation is based on a 2-sided t-test at the 5% level of significance 
(α = 0.05) and a common standard deviation of 15%.  The sample size of 500 randomized patients in the 
bempedoic acid 180 mg group and 250 randomized patients in the placebo group gives a total study 


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sample size of 750.  
Analysis Populations 
The Full Analysis Set (FAS), used for all of the efficacy summaries and analyses, is defined as all 
randomized patients.  The FAS is also known as the intention-to-treat (ITT) set of patients.  Patients in the 
FAS will be included in their randomized treatment group, regardless of their actual treatment.  
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.  
Disposition and Baseline Characteristics 
Disposition, including reason for withdrawal from the 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. 
Primary Endpoint  
The primary efficacy endpoint is the percent change from baseline to Week 12 in LDL-C.  The primary 
efficacy endpoint will be analyzed using analysis of covariance (ANCOVA), with treatment group, CV 
risk (ASCVD only; HeFH with or without ASCVD) and baseline statin intensity (high intensity, moderate 
intensity, low intensity) as factors and baseline LDL-C as a covariate.  Baseline LDL-C is defined as the 
mean of the LDL-C values from Week -1 (Visit S3) and predose Day 1/Week 0 (Visit T1).  The 
ANCOVA will be performed using the FAS, with patients included in their randomized treatment group 
regardless of the treatment they actually received.  Two methods for data handling will be used:  the first 
is observed case data only, while the second will involve specification of the missing data mechanism 
using a pattern mixture model (PMM).  The primary analysis will be that from the PMM, while the 
observed case analysis will be used as confirmatory.  The PMM will be used to specify different 
imputation strategies depending on whether the patient is still on study treatment.  Imputed datasets will 
be analyzed using ANCOVA with treatment group, CV risk (ASCVD only; HeFH with or without 
ASCVD) and baseline statin intensity (high intensity, moderate intensity, low intensity) as factors and 
baseline LDL-C as a covariate.  Approximately 200 imputed datasets will be created, with results from 
the analysis of each imputed dataset combined using Rubin’s method.  For each type of ANCOVA 
(observed case; imputation via PMM), 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 Tertiary Efficacy Endpoints 
Secondary efficacy endpoints are also of interest for this study, in terms of controlling the overall Type I 
error rate.  A gatekeeping or stepdown approach will be used to test the primary efficacy endpoint and 
then specific secondary efficacy endpoints sequentially in order to preserve the study-wise Type I error 
rate.  The sequence for the stepdown procedure in this study is as follows: 
1. Test the primary efficacy endpoint: percent change from baseline to Week 12 in LDL-C  
2. Test the percent change from baseline to Week 24 in LDL-C 
3. Test the percent change from baseline to Week 12 in non-HDL-C 
4. Test the percent change from baseline to Week 12 in TC 
5. Test the percent change from baseline to Week 12 in apoB 
6. Test the percent change from baseline to Week 12 in hs-CRP   
In this hierarchical testing structure, each hypothesis is tested at a significance level of 0.05, two-sided. 
Statistical significance at each step is required in order to test the next hypothesis.  If the primary endpoint 
meets the criteria for statistical significance, then the percent change from baseline to Week 24 in LDL-C 
will be tested; and so forth.  
Percent change from baseline to Week 24 in LDL-C; absolute change from baseline to Weeks 12, 24, 


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and 52 in LDL-C; percent change from baseline to Weeks 12, 24, and 52 in HDL-C, non-HDL-C, TG, 
TC, apoB, and hs-CRP will each be analyzed using ANCOVA with treatment group, CV risk (ASCVD 
only; HeFH with or without ASCVD) and baseline statin intensity (high intensity, moderate intensity, low 
intensity) as factors and the relevant baseline as a covariate.  Baseline for HDL-C, non-HDL-C, TG, and 
TC will be defined as the mean of the lipid values from Week -1 (Visit S3) and predose Day 1/Week 0 
(Visit T1).  If a repeat lipid measurement is performed at Week -1 (Visit S3), then baseline will be the 
mean of the lipid values from the second Week -1 assessment and predose Day 1/Week 0 (Visit T1).  
Baseline for apoB and hs-CRP will be defined as the predose Day 1/Week 0 (Visit T1) value.  Each 
ANCOVA will be performed using the FAS, with patients included in their randomized treatment group 
regardless of the treatment they actually received.  For each lipid 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. 
For all continuous efficacy endpoints (percent change from baseline in LDL-C, HDL-C, non-HDL-C, TC, 
TG, apoB, and hs-CRP; change from baseline in LDL-C; to Weeks 12, 24, and 52, as appropriate), the 
ANCOVA assumption of normality will be assessed.  If non-normality of the data is found at any time 
point for any parameter, either the data will be transformed so that it is normally distributed or a 
nonparametric test will be used instead of the planned ANCOVA. 
In addition, a summary of percent change from baseline to Week 12 LDL-C using the FAS, excluding 
patients who received additional lipid-lowering therapy by that time point (by Week 12 for the Week 12 
time point), will be provided. Percent change from baseline to Weeks 24 and 52 on LDL-C will be 
analyzed similarly, with patients in the FAS who did not receive additional LDL or triglyceride-lowering 
therapy by that time point (by Week 24 for the Week 24 analysis by Week 52 for the Week 52 analysis) 
included in the analyses.  Output from each time point will include the LSM and SE for each treatment 
group, as well as the placebo-correct LSM, 95% CI, and p-value. 
Additional post-randomization adjunctive lipid-modifying therapy 
The number and percent of patients in each treatment group requiring additional (post-randomization) 
adjunctive lipid-modifying therapy will be summarized. Medications and the reasons for their additional 
treatment (hyperlipidemia vs. hypertriglyceridemia) will be summarized separately. 
Safety Analyses 
The summarization of AEs will include TEAEs, defined as AEs with an onset date on or after initiation of 
study treatment.  TEAEs and SAEs will be summarized by system organ class (SOC), severity, and 
relationship to study drug for each treatment group.  These AE summaries will include cumulative 
incidence (percent of patients experiencing the AE) and patient-year adjusted incidence rates.  If 
appropriate, absolute and relative risk differences will be calculated using both cumulative incidence and 
incidence rates.  Deaths, withdrawal from study treatment due to AEs, and withdrawal from the study due 
to AEs will each be summarized by treatment group. 
Clinical safety laboratories, including hematology, blood chemistry, coagulation, HbA1C, glucose, and 
urinalysis; PE findings; vital signs; ECG readings; 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 
Liver-associated enzymes and TB will be summarized by the value and change from baseline in the value, 
by treatment group and visit. In addition, the number and percent of patients with abnormal values for 
ALT, AST, and TB will be summarized.  These summaries of patients with abnormal values will be 
performed overall; by normal baseline; and by abnormal baseline for each of ALT, AST, and TB.  Hy’s 
law criteria (≥3 × ULN for either ALT or AST, with accompanying TB >2 × ULN or patient’s baseline) 
will also be applied to the data; any potential Hy’s law cases will be listed separately.  In the case of 
patients with Gilbert’s disease, TB will be fractionated and the determination of 2 × ULN based upon 
direct (conjugated) bilirubin.  
Musculoskeletal Safety 


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AEs of muscle-related symptoms will be summarized by treatment group.  CK levels will be summarized 
by the value and change from baseline in the value, by treatment group and visit.  In addition, the number 
and percent of patients with abnormal CK values will be summarized.  These summaries of patients with 
abnormal CK will be performed overall; by normal baseline CK; and by abnormal baseline CK.  
Diabetes and 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.  Glucose and HbA1C will be monitored at baseline and at Weeks 12 and 24and be summarized. 
Renal Safety 
Baseline eGFR will be summarized by treatment group for actual value and for baseline eGFR categories.  
Shift tables of eGFR category from baseline over the study, will be provided by treatment group.  Shift 
tables of urine protein (negative/positive) from baseline over the study, will be provided by treatment 
group.  Values of CK over the study will be summarized by treatment group and by baseline eGFR 
category.  Finally, muscle-related AEs will be summarized by treatment group and by baseline eGFR 
category. 
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 SOC, severity, and relationship to study 
drug for each treatment group. 
Clinical Endpoints 
Clinical endpoints using standardized definitions will be adjudicated by an independent blinded expert 
CEC for all ongoing Phase 3 studies in the bempedoic acid program.  Investigator-reported clinical 
endpoints and adjudicated clinical endpoints will be summarized by event type and treatment group.  
Additional details regarding the clinical endpoints and their definitions will be included in CEC Charter.   
PK and Other biomarkers 
PK plasma concentrations of ETC-1002 and its metabolite ESP15228 will be summarized prior to dose at 
Weeks 24 and 52.  
 


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TABLE OF CONTENTS 
1. 
TITLE PAGE ................................................................................................................1 
2. 
SYNOPSIS ...................................................................................................................2 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................21 
4. 
INTRODUCTION ......................................................................................................25 
4.1. 
Lipid-Regulating Drugs and Cardiovascular Disease .................................................25 
4.2. 
Background on Bempedoic Acid ................................................................................27 
4.2.1. 
Mechanism of Action .................................................................................................27 
4.2.2. 
Nonclinical Experience ...............................................................................................27 
4.2.3. 
Previous Human Experience .......................................................................................28 
4.2.4. 
Dose Selection ............................................................................................................29 
4.2.5. 
Background Therapy ..................................................................................................29 
4.2.6. 
Risk Benefit Summary ................................................................................................29 
5. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................30 
5.1. 
Study Objectives .........................................................................................................30 
5.1.1. 
Primary Objective .......................................................................................................30 
5.1.2. 
Secondary Objectives .................................................................................................30 
5.1.3. 
Tertiary Objectives .....................................................................................................30 
5.2. 
Study Endpoints ..........................................................................................................30 
5.2.1. 
Primary Endpoint ........................................................................................................30 
5.2.2. 
Secondary Endpoints ..................................................................................................30 
5.2.3. 
Tertiary Endpoints ......................................................................................................30 
5.2.4. 
Safety Endpoints .........................................................................................................31 
6. 
INVESTIGATIONAL PLAN .....................................................................................32 
6.1. 
Overall Study Design ..................................................................................................32 
6.2. 
Study Hypothesis ........................................................................................................34 
6.3. 
Study Duration and Period ..........................................................................................34 


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6.4. 
End of Study ...............................................................................................................34 
6.5. 
Number of Patients .....................................................................................................35 
6.6. 
Patient Identification Numbers ...................................................................................35 
6.6.1. 
Randomization and Treatment Period ........................................................................35 
7. 
SELECTION AND WITHDRAWAL OF PATIENTS ..............................................36 
7.1. 
Subject Inclusion Criteria ...........................................................................................36 
7.2. 
Subject Exclusion Criteria ..........................................................................................38 
7.3. 
Patient Lifestyle and Dietary Guidelines ....................................................................40 
7.4. 
Investigator/Sponsor Suspension or Termination of Patient Enrollment ...................41 
8. 
TREATMENT OF PATIENTS ..................................................................................42 
8.1. 
Description of IMP .....................................................................................................42 
8.2. 
Concomitant Medications ...........................................................................................42 
8.2.1. 
Lipid-Regulating Medications and Supplements........................................................42 
8.2.2. 
Prohibited Medications ...............................................................................................43 
8.2.3. 
Allowable Medications ...............................................................................................44 
8.3. 
Treatment Compliance ................................................................................................44 
8.4. 
Blinding ......................................................................................................................45 
8.5. 
Overdose .....................................................................................................................46 
9. 
INVESTIGATIONAL MEDICINAL PRODUCT .....................................................47 
9.1. 
Investigational Medicinal Product Supply and Control ..............................................47 
9.2. 
Administration of Investigational Medicinal Product ................................................47 
9.3. 
Investigational Medicinal Product Accountability .....................................................48 
9.4. 
Investigational Medicinal Product Handling and Disposal ........................................48 
10. 
STUDY PROCEDURES ............................................................................................49 
10.1. 
Informed Consent .......................................................................................................49 
10.2. 
Procedures and Schedule of Assessments ..................................................................49 
10.2.1. 
Screening Week -5 (Visit S1; Day -35 ± 7 days) .......................................................49 
10.2.2. 
Placebo Run-in Week -4 (Visit S2; Day -28± 3 days) ................................................50 


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10.2.3. 
Placebo Run-in Week -1 (Visit S3; Day -7± 3 days) ..................................................51 
10.2.4. 
Treatment Week 0 (Visit T1; Day 1) ..........................................................................51 
10.2.5. 
Treatment Week 4 (Visit T2; 29 ±3 days) ..................................................................52 
10.2.6. 
Treatment Week 8 / Telephone Visit (Visit T3; 57 ±3 days) .....................................53 
10.2.7. 
Treatment Week 12 (Visit T4; 85 ±3 days) ................................................................53 
10.2.8. 
Treatment Week 24 (Visit T5; 168 ±7 days) ..............................................................54 
10.2.9. 
Treatment Week 36 / Telephone Visit (Visit T6; 252 ±3 days) .................................55 
10.2.10. 
Treatment Week 52/EOS (Visit T7; 365 ±7days) ......................................................55 
10.3. 
Subject Withdrawal Criteria .......................................................................................56 
10.3.1. 
Early Withdrawal from the Study ...............................................................................56 
10.3.2. 
Procedures for Early Withdrawal ...............................................................................57 
11. 
ASSESSMENT OF SAFETY .....................................................................................58 
11.1. 
Safety Parameters .......................................................................................................58 
11.1.1. 
Demographic/Medical History ...................................................................................58 
11.1.2. 
Vital Signs ..................................................................................................................58 
11.1.3. 
Weight, Height, and Body Mass Index .......................................................................58 
11.1.4. 
Physical Examination .................................................................................................59 
11.1.5. 
Electrocardiogram .......................................................................................................59 
11.1.5.1. 
Monitoring and Management of Abnormal Electrocardiograms ................................59 
11.1.6. 
Clinical Laboratory Tests ...........................................................................................60 
11.1.6.1. 
Laboratory Parameters (Safety) ..................................................................................60 
11.1.6.2. 
Sample Collection, Storage, and Shipping .................................................................61 
11.1.6.3. 
General Monitoring and Management of Abnormal Clinical Labs ............................61 
11.1.6.4. 
Monitoring and Management of Potential Hypoglycemia and Metabolic 
Acidosis ......................................................................................................................65 
11.1.6.5. 
Pharmacokinetic Assessments ....................................................................................66 
11.1.6.6. 
Collection and Assessment of Pharmacokinetic Samples ..........................................67 
11.1.6.7. 
Shipment of Pharmacokinetic Samples ......................................................................67 


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11.1.6.8. 
Total Blood Volume of Clinical Laboratory and Pharmacokinetic Samples .............67 
11.2. 
Adverse and Serious Adverse Events .........................................................................67 
11.2.1. 
Definition of Adverse Events .....................................................................................67 
11.2.2. 
Adverse Drug Reaction ...............................................................................................67 
11.2.3. 
Reporting ....................................................................................................................68 
11.2.4. 
Severity .......................................................................................................................69 
11.2.5. 
Relationship ................................................................................................................69 
11.2.6. 
Monitoring and Follow-up of Adverse Events ...........................................................70 
11.2.7. 
Treatment-Emergent Adverse Events .........................................................................70 
11.2.7.1. 
Definition of Serious Adverse Event ..........................................................................70 
11.2.7.2. 
Events not Qualifying as Serious Adverse Events .....................................................71 
11.2.7.3. 
Clinical Laboratory Assessments as Adverse Events and Serious Adverse 
Events .........................................................................................................................71 
11.3. 
Reporting Serious Adverse Events .............................................................................71 
11.3.1. 
Reporting of Serious Adverse Events to Regulatory Authorities ...............................72 
11.3.2. 
Reporting of Patient Death .........................................................................................72 
11.3.3. 
Reports of Pregnancy ..................................................................................................72 
11.4. 
Adverse Events of Special Interest .............................................................................73 
11.5. 
Data Monitoring Committee .......................................................................................75 
11.6. 
Clinical Event Committee (CEC) ...............................................................................75 
11.7. 
Assessment of Lipid Endpoints ..................................................................................76 
11.7.1. 
Lipid Parameters .........................................................................................................76 
11.7.2. 
Clinical Laboratory Tests (Lipids) ..............................................................................76 
12. 
STATISTICS ..............................................................................................................77 
12.1. 
General Considerations ...............................................................................................77 
12.2. 
Determination of Sample Size ....................................................................................77 
12.3. 
Analysis Populations ..................................................................................................77 
12.4. 
Disposition, Demographics, and Baseline Characteristics .........................................77 


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12.5. 
Primary Endpoint ........................................................................................................77 
12.6. 
Secondary and Tertiary Efficacy Endpoints ...............................................................78 
12.7. 
Additional Post-randomization Adjunctive LDL-lowering or Triglyceride-
Modifying Therapy .....................................................................................................79 
12.8. 
Safety Endpoints .........................................................................................................79 
12.9. 
Pharmacokinetics ........................................................................................................81 
13. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.........................................82 
13.1. 
Study Monitoring ........................................................................................................82 
13.2. 
Audits and Inspections ................................................................................................82 
14. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................84 
15. 
ETHICS ......................................................................................................................85 
15.1. 
Institutional Review Board/Independent Ethics Committee Approval ......................85 
15.2. 
Ethical Conduct of the Study ......................................................................................85 
15.3. 
Written Informed Consent ..........................................................................................86 
15.4. 
Patient Confidentiality ................................................................................................86 
16. 
DATA HANDLING AND RECORDKEEPING .......................................................87 
16.1. 
Inspection of Records .................................................................................................87 
16.2. 
Retention of Records ..................................................................................................87 
16.3. 
Case Report Forms and Study Records ......................................................................87 
17. 
ADMINISTRATIVE CONSIDERATIONS ..............................................................89 
17.1. 
Investigators ................................................................................................................89 
17.2. 
Study Administrative Structure ..................................................................................90 
17.3. 
Amendments ...............................................................................................................90 
17.4. 
Financial Disclosure ...................................................................................................91 
18. 
PUBLICATION AND DISCLOSURE POLICY .......................................................92 
19. 
LIST OF REFERENCES ............................................................................................93 
20. 
APPENDICES ............................................................................................................95 
APPENDIX 1. SCHEDULE OF EVENTS (SUBJECT VISIT SCHEDULE) ...........................96 


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APPENDIX 2. SPONSOR’S SIGNATURE ...............................................................................98 
APPENDIX 3. INVESTIGATOR’S SIGNATURE..................................................................102 
APPENDIX 4. DUTCH LIPID CLINIC NETWORK CRITERIA FOR FAMILIAL 
HYPERCHOLESTEROLEMIA...............................................................................103 
APPENDIX 5. SIMON BROOME REGISTER DIAGNOSTIC CRITERIA FOR 
HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA .........................105 
APPENDIX 6. SUMMARY OF CHANGES AMENDMENT 1 .............................................107 
APPENDIX 7. SUMMARY OF CHANGES AMENDMENT 2 .............................................111 
APPENDIX 8. SUMMARY OF CHANGES AMENDMENT 3 .............................................163 
 
LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................21 
Table 2: 
Baseline Statin Dose Categories .................................................................................33 
Table 3: 
Randomization Strata ..................................................................................................33 
Table 4: 
Investigational Medicinal Products ............................................................................42 
Table 5: 
Clinical Laboratory Parameters (Safety) ....................................................................60 
Table 6: 
Clinical Laboratory Parameters (Lipids) and Cardiometabolic Biomarkers ..............76 
 
LIST OF FIGURES 
Figure 1. 
Study 1002-047 Study Design ....................................................................................34 
 
 


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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 
ACS 
Acyl-CoA synthetase 
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 
CABG 
Coronary artery bypass graft 
CEC 
Clinical Event Committee 
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 
CMV 
Cytomegalovirus 
CNS 
Central nervous system 
CoA 
Acetyl-coenzyme A 


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Abbreviation or Specialist Term 
Explanation 
CO2 
Carbon dioxide 
CRO 
Contract research organization 
CT 
Computed tomography 
CTA 
Computed tomographic angiography 
CV 
Cardiovascular 
CYP 
Cytochrome P450 
DBP 
Diastolic blood pressure 
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
eGFR 
Estimated glomerular filtration rate 
EMA 
European Medicines Agency 
EOS 
End of Study 
ETC-1002 
Bempedoic acid 
EU 
European Union 
FAS 
Full analysis set 
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 
HDL-C 
High-density lipoprotein cholesterol 
HeFH 
Heterozygous familial hypercholesterolemia 
Hgb 
Hemoglobin 
HMG-CoA 
3-hydroxy-3-methylglutaryl-coenzyme A 
hs-CRP 
High-sensitivity C-reactive protein 
IB 
Investigator’s Brochure 
ICD 
Informed Consent Document 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 


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Abbreviation or Specialist Term 
Explanation 
IMP 
Investigational medicinal product 
IND 
Investigational New Drug Application 
INR 
International normalized ratio 
IRB 
Institutional Review Board 
ITT 
Intention-to-treat 
IUD 
Intrauterine device 
IWRS 
Interactive web response system 
K 
Potassium 
LDH 
Lactate dehydrogenase 
LDL-C 
Low-density lipoprotein cholesterol 
LDLR 
LDL receptor 
LFT 
Liver function test 
LPLV 
Last patient last visit 
LS 
Least square 
LSM 
Least square mean 
MACE 
Major adverse cardiac event 
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 
MI 
Myocardial infarction 
MRI 
Magnetic resonance imaging 
Na 
Sodium 
NA 
Not applicable 
NIMP 
Non-investigational medicinal product(s) 
NLA 
National Lipid Association 
NOAEL 
No-observed-adverse-effect level 
non-HDL-C 
Non-high-density lipoprotein cholesterol 
PAD 
Peripheral arterial disease 
PCI 
Percutaneous coronary intervention 
PCSK9 
Proprotein convertase subtilisin/kexin type 9 
PE 
Physical exam 
PK 
Pharmacokinetic(s) 
PMM 
Pattern mixed model 


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Abbreviation or Specialist Term 
Explanation 
PT 
Prothrombin time 
RBC 
Red blood cell 
RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SBP 
Systolic blood pressure 
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 
TIA 
Transient ischemic attack 
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. 
Lipid-Regulating Drugs and Cardiovascular Disease  
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. 
Hyperlipidemic patients at high CV risk due to either heterozygous familial 
hypercholesterolemia (HeFH) and/or established atherosclerotic cardiovascular disease 
(ASCVD) unable to meet their LDL-C treatment goals with currently available therapies are the 
target patient populations for this study.  
Elevated LDL-C is a major modifiable risk factor for the development of atherosclerosis and 
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).  
Patients with documented ASCVD are at very high risk for events and require intensive 
pharmacologic intervention (Stone 2014).  For a variety of reasons, many with ASCVD are 
unable to attain aggressive LDL-C treatment goals despite the addition of lipid-lowering agents 
to maximally tolerated statin therapy (Jacobson 2014).  
Familial hypercholesterolemia refers to individuals with extremely elevated LDL-C due to 
underlying genetic mutations of the LDL receptor (LDLR), apolipoprotein B (apoB), and 
proprotein convertase subtilisin/kexin type 9 (PCSK9) (FH Foundation 2015).  In adult HeFH 
patients, LDL-C usually exceeds 190 mg/dL (4.9 mmol/L) and can be as high as 400 mg/dL 
(10.4 mmol/L).  HeFH is the most common form of the disease with a prevalence of 
approximately 1 in 300 to 500 persons worldwide and as high as 1 in 100 persons in some 
populations (NORD 2015).  Patients with HeFH inherit a genetic mutation from 1 parent.  
Inheritance is generally via an autosomal-dominant mechanism (Robinson 2013).  HeFH 
increases the risk of atherosclerosis leading to CV events.  The mean age for the onset of CV 


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disease is relatively young, at 42 to 46 years in men and 51 to 52 years in women (Robinson 
2013).  The cumulative risk of experiencing a coronary event by the age of 60 years without 
effective treatment is at least 50% in men and approximately 30% in women with a marked 
increase in postmenopausal women.  Before effective treatment with statins became available, 
mortality from coronary disease was increased by nearly 100-fold in young adults 20 to 39 years 
of age, and approximately 4-fold for patients aged 40 to 59 years (Neil 2008).  The National 
Lipid Association (NLA) recommends achievement of ≥50% reduction in LDL-C in adult 
patients using statins.  HeFH patients at even higher risk for CV disease (such as those with 
established ASCVD, diabetes, smoking, family history, and other risk factors) have a treatment 
goal of ≤70 mg/dL (1.8 mmol/L).  Those unable to achieve these treatment goals with maximally 
tolerated statin therapy require additional lipid-lowering therapy and still may be unable to reach 
LDL-C treatment goals.  
Lowering LDL-C is the primary therapeutic lipid target in ASCVD and HeFH patients 
(Goldberg 2011).  LDL-C is largely accepted as a valid surrogate endpoint of CV events by 
clinicians and regulatory authorities (Stone 2014).  Long-term elevations in LDL-C lead to 
progressive accumulation of atherosclerotic lesions in the walls of arteries that require long-term 
management.  While lifestyle changes are the primary intervention, these measures rarely reduce 
plasma LDL-C by >15%.  Particularly in ASCVD and HeFH patients, pharmacologic treatments 
are required to adequately treat hyperlipidemia (Pollex 2008).  Evidence supporting LDL-C as a 
therapeutic target and surrogate for CV outcomes comes from interventional studies with 
LDL-C-lowering therapies, epidemiological studies, genetic variants (both gain of function and 
loss of function). Large randomized clinical studies aimed at lowering LDL-C show a consistent, 
log-linear relationship between LDL-C reduction and CV risk reduction, independent of the way 
LDL-C lowering was achieved based on mechanism of action (Kathiresan 2008; Baigent 2010; 
Robinson 2005; Stamler 1986).  A published patient-level meta-analysis including 26 trials and 
more than 160,000 participants, showed a consistent relationship between LDL-C reduction and 
CV outcomes (Baigent 2010).  This analysis showed that with a 1 mmol/L reduction in LDL-C 
associated with a 22% reduction in the 5-year incidence of major coronary events, 
revascularizations, and ischemic strokes.  Intensive statin therapy relative to low/moderate 
intensity statin treatment produces greater benefit in patients at high CV risk (Cannon 2004).  
Unfortunately, some patients are unable to take high intensity statins due to dosing limits based 
on co-morbidities, contraindications, and/or tolerance (Jacobson 2014).  Nonstatin therapies may 
provide additional lowering of CV risk as demonstrated in the IMPROVE-IT trial which added 
ezetimibe to statin therapy (Cannon 2015).  
Patients with ASCVD and HeFH on maximally tolerated lipid-lowering therapy including 
maximally tolerated doses of statins who require additional lipid-lowering therapy have an unmet 
medical need.  ETC-1002 may offer a once daily option for these patients.  The oral route of 
administration may be preferable to injectable biologic therapy for some patients.  Bempedoic 
acid has been well tolerated to date and Phase 2 data demonstrate significant LDL-C lowering, 
prompting further evaluation in Phase 3 clinical studies.  


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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 
inhibition of ACL.  Inhibition of ACL by ETC-1002-CoA decreases cholesterol synthesis in liver 
leading to increased 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, unlike statins, it does not inhibit 
cholesterol synthesis in skeletal muscle.  The enzyme required to convert bempedoic acid to 
ETC-1002-CoA is not present in skeletal muscle.  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; however, the safety of bempedoic acid and 
its metabolites regarding human skeletal muscle is not yet established. 
4.2.2. 
Nonclinical Experience 
The primary pharmacology of bempedoic acid was evaluated in several well-characterized and 
predictive rodent models of dyslipidemia.  In these studies, bempedoic acid lowered LDL-C and 
triglycerides (TGs) and increased high-density lipoprotein cholesterol (HDL-C).  In a study of 
cholesterol-fed LDLR-deficient mice, bempedoic acid substantially slowed the progression of 
atherosclerosis in a dose-related manner. 
Results of the safety pharmacology studies did not identify any significant risks for subjects over 
the range of exposures intended for clinical studies. 
In toxicology studies, evaluations of bempedoic acid in mice, rats, and monkeys in oral studies 
up to 52 weeks in duration have been completed.  No significant central nervous system (CNS), 
respiratory, or CV liabilities were identified.  Target organs identified in repeat-dose studies 
were liver in rats and liver and kidney in monkeys, and changes were reversible following 
cessation of treatment.  Changes in clinical laboratory parameters indicative of hepatic and renal 
function were observed in animals at doses lower than those associated with frank toxicity.  
Routine clinical laboratory parameters will continue to be monitored carefully in clinical trials. 
Bempedoic acid is nonmutagenic and nonclastogenic in both in vitro and in vivo genetic 
toxicology assays.  
In the pivotal 26-week rat study, the no-observed-adverse-effect level (NOAEL) dose was 
30 mg/kg/day in rats and the corresponding area under the curve during 24 hours (AUC0-24) 
values of the sum of ETC-1002 and ESP15228 were up to 528 µg⋅hr/mL.  In the pivotal 52-week 
monkey study, the NOAEL dose was 60 mg/kg/day and the corresponding AUC0-24 values of the 
sum of ETC-1002 and ESP15228 were up to 4760 µg⋅hr/mL. 
In vitro studies indicated that bempedoic acid is neither an inhibitor nor inducer of major 
cytochrome P450 (CYP) enzymes at clinically relevant plasma concentrations.  In addition, 
ETC-1002 bempedoic acid does not appear to inhibit major drug transporters. 


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Please refer to the most recent Investigator’s Brochure (IB) for additional information regarding 
pharmacology, pharmacokinetics (PK), and nonclinical safety studies. 
4.2.3. 
Previous Human Experience 
Bempedoic acid has been evaluated in 15 completed clinical studies (nine Phase 1 and six 
Phase 2), with over 700 subjects receiving bempedoic acid doses from 2.5 mg/day up to 
240 mg/day (multiple doses) for up to 12 weeks.  All multiple-dose studies have demonstrated 
consistent, clinically meaningful LDL-C lowering with bempedoic acid treatment and have 
shown a positive safety profile.  This efficacy was observed across a range of patient 
populations, including those with primary hyperlipidemia and mixed dyslipidemia, some of 
whom also reported type 2 diabetes mellitus (T2DM), CHD, and/or statin intolerance.  In 
addition, a positive benefit/risk profile is shown across a range of low and moderate dose statins 
and ezetimibe. 
In both single- and multiple-dose studies, bempedoic acid is well absorbed (with a time to peak 
maximum concentration [Cmax] of approximately <4 hours).  The Cmax of ETC-1002 and 
ESP15228 increased in proportion to increasing dose; and the area under the concentration-time 
curve (AUC) showed slightly more than dose-proportional increases for ETC-1002 with 
increasing dose, but proportional increases in AUC were observed with ESP15228.  The terminal 
elimination half-life (t½) ranged from 15 to 27 hours for ETC-1002 and 20 to 33 hours for 
ESP15228. 
A study to assess the effect of a high-fat, high-calorie meal on the bioavailability of ETC-1002 
following administration of 180-mg tablet relative to the fasted state, the bioavailability of 
180-mg capsules relative to one 180-mg tablet in the fasted state, and the bioavailability of three 
60-mg tablets relative to one 180-mg tablet has completed (1002-016).  A high-fat meal has no 
effect on the PK of ETC-1002 180-mg tablet; ETC-1002 PK are equivalent whether taken in the 
fasting or fed state.  The evaluation of the tablet formulation that will be used in Phase 3 
demonstrates similar PK characteristics to the capsule formulation utilized in Phases 1 and 2.  
The PK following three 60-mg tablets was similar to one 180-mg tablet.  Only the 180-mg tablet 
is planned for use in Phase 3.  
Two studies evaluated clinical drug-drug interaction using bempedoic acid 240 mg and showed 
less than a 2-fold increase in the exposure of atorvastatin 10 mg, simvastatin 20 mg, pravastatin 
40 mg, and rosuvastatin 10 mg (Studies 1002-007 and 1002-012).  Likewise, when bempedoic 
acid 180 mg was dosed in combination with high-dose statins (atorvastatin 80 mg, pravastatin 
80 mg, rosuvastatin 40 mg, and simvastatin 40 mg), mean exposure of these statins increased 
between approximately 1.4- and 2-fold (1002-037).  
No drug interaction occurred between daily ETC-1002 180 mg and metformin in patients with 
T2DM.  A Phase 2 study showed no effect of ezetimibe 10 mg on steady-state trough ETC-1002 
plasma concentrations in 40 patients with hypercholesterolemia randomized to receive 
ETC-1002 plus ezetimibe (Study 1002-008).  Results of a drug interaction study in 19 patients 
(16 evaluable for PK) with the oral contraceptive Ortho-Novum 1/35 in healthy women 
demonstrate no effect of daily ETC-1002 180 mg on ethinyl estradiol or norethindrone exposure 
(Study 1002-017). 


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The results of the thorough QT/QTc (TQT) study (1002-022) showed no significant change in 
QTc.  Following daily bempedoic acid 240 mg for 9 days, bempedoic acid does not prolong QT 
interval duration and has no clinically significant effect on heart rate and PR and QRS intervals. 
Occurrences of treatment-emergent adverse events (TEAEs), withdrawals due to adverse events 
(AEs), and treatment-related AEs were similar across groups receiving bempedoic acid, placebo 
or an active comparator, ezetimibe.  Across the 15 clinical studies, the most frequently reported 
TEAEs included musculoskeletal and connective tissue disorders (back pain, pain in extremity, 
myalgia, arthralgia, muscle spasms), nervous system disorders (headache), gastrointestinal (GI) 
disorders (nausea, diarrhea), and infections and infestations.  Overall, AEs were generally 
reported with similar incidence between treatment groups; however, the incidence of headache 
was higher with bempedoic acid than placebo.  AEs were typically characterized as mild or 
moderate.  Treatment-emergent serious adverse events (SAEs) were reported for 11 subjects.  
There has been 1 death: an event of sudden death (cause unknown) in a bempedoic acid-treated 
subject in Clinical Study 1002-008. The event was assessed by the investigator as severe and as 
possibly related to study treatment.  The rationale for the investigator assessment was that a 
relationship to bempedoic acid could not be ruled out given the temporal nature of the event.  A 
full narrative for this event is presented in the IB. 
In general, laboratory results showed no clinically significant trends.  
4.2.4. 
Dose Selection 
Doses of bempedoic acid ranging from 40 to 240 mg/day have been evaluated in the Phase 2 
program.  Based on data from the integrated analysis of safety and efficacy, observed values and 
percent change from baseline in the primary efficacy endpoint, LDL-C together with a positive 
safety profile, support the choice of the 180-mg dose for the Phase 3 studies.  An integrated 
analysis of six Phase 2 studies resulted in placebo-adjusted least square (LS) means for percent 
change from baseline of approximately 32% with bempedoic acid 180 mg monotherapy, 50% 
with bempedoic acid 180 mg + ezetimibe 10 mg, and 22% for 180 mg on top of stable statin 
therapy.  The 180-mg dose was noted to have an excellent safety profile.  Overall, balancing 
efficacy and safety the 180-mg dose was chosen for the Phase 3 program. 
4.2.5. 
Background Therapy 
Bempedoic acid in this study is currently being evaluated as an add-on to lipid-modifying 
therapy in high-risk patients (ie, those with HeFH and/or ASCVD) who have not achieved their 
LDL-C goal despite maximally tolerated lipid-modifying 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 12-week efficacy of bempedoic acid 180 mg/day versus placebo in 
decreasing LDL-C in high CV risk patients with hyperlipidemia (with underlying 
HeFH and/or ASCVD) who are not adequately controlled with their maximally 
tolerated lipid-modifying therapy. 
5.1.2. 
Secondary Objectives 
• To evaluate the effect of 24-week treatment with bempedoic acid 180 mg/day versus 
placebo on LDL-C. 
• To evaluate the effect of bempedoic acid 180 mg/day versus placebo on non-high-
density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), high-sensitivity 
C-reactive protein (hs-CRP), and apoB after 12 weeks of treatment. 
5.1.3. 
Tertiary Objectives 
• To evaluate the effect of long-term treatment (52 weeks) with bempedoic acid 
180 mg/day versus placebo on LDL-C, non-HDL-C, TC, HDL-C, TG, hs-CRP, and 
apoB. 
• To evaluate the long-term (52 weeks) safety and tolerability of bempedoic acid 
180 mg/day compared to placebo. 
5.2. 
Study Endpoints 
5.2.1. 
Primary Endpoint 
The primary efficacy endpoint for this study is the percent change from baseline to Week 12 in 
LDL-C 
5.2.2. 
Secondary Endpoints 
1. Percent change from baseline to Week 24 in LDL-C 
2. Percent change from baseline to Week 12 in non-HDL-C, TC, apoB, and hs-CRP  
3. Absolute change from baseline to Weeks 12 and 24 in LDL-C 
5.2.3. 
Tertiary Endpoints 
Tertiary efficacy endpoints are of interest: 
1. Absolute change and percent change from baseline to Week 52 in LDL-C 


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2. Percent change from baseline to Weeks 24 and 52 in non-HDL-C, TC, apoB, and hs-CRP 
3. Percent change from baseline to Weeks 12, 24, and 52, in TG and HDL-C 
5.2.4. 
Safety Endpoints 
1. Patient incidence to TEAE 
2. Safety laboratory values and vital signs 
3. Cardiovascular event rates  
 


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6. 
INVESTIGATIONAL PLAN 
6.1. 
Overall Study Design 
This is a Phase 3, long-term randomized, double-blind, placebo-controlled, parallel group, study 
evaluating the efficacy of bempedoic acid in high CV risk patients with hyperlipidemia (patients 
with underlying HeFH and/or ASCVD) who are not adequately treated with their maximally 
tolerated lipid-modifying therapy.  Maximally tolerated lipid-modifying therapy includes a 
maximally tolerated statin alone or in combination with other lipid-modifying therapies (eg, 
ezetimibe, fibrates [except gemfibrozil, as per co-administration instructions defined in the statin 
label] and PCSK9 inhibitors).  A patient’s maximally tolerated lipid-modifying therapy will be 
determined by the investigator using their medical judgment and available sources, including the 
patient’s self-reported history of lipid-modifying therapy.   
The study will be conducted at approximately 125 clinical sites in the North America and 
Europe. 
Screening Week -5 (Visit S1) will be approximately 5 weeks prior to randomization, but can be 
extended for an additional 4 weeks if needed to adjust background medical therapy or for other 
reasons as specified in the protocol.  Eligible patients will return to the clinical site at Week -4 
(Visit S2) to initiate administration of single-blind (patient only) placebo.  Eligible patients will 
return at Week -1 (Visit S3) for lipid and safety laboratories and an assessment of tolerability and 
study drug adherence.  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. 
Patients on maximally tolerated lipid-modifying therapy, as determined by the investigator, will 
be stratified based on the patient’s CV risk (ASCVD alone; HeFH with or without ASCVD) and 
baseline statin intensity (high intensity statin, moderate intensity statin, low intensity statin) for a 
total of 6 strata.  Statin intensity categories and randomization strata are defined in Table 2 and 
Table 3 below, respectively. Intensity category is based on average daily dose.  


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Table 2: 
Baseline Statin Dose Categories 
High Intensity Statinsa 
Moderate Intensity Statins 
Low Intensity Statinsb 
Atorvastatin 40-80 mg 
Atorvastatin 10-20 mg 
Simvastatin 10 mg 
Rosuvastatin 20-40 mg 
Rosuvastatin 5-10 mg 
Pravastatin 10-20 mg 
 
Simvastatin 20 mg 
Lovastatin 20 mg 
 
Pravastatin 40-80 mg 
Fluvastatin 20-40 mg 
 
Lovastatin 40 mg 
Pitavastatin 1 mg 
 
Fluvastatin XL 80 mg 
 
 
Fluvastatin 40 mg BID 
 
 
Pitavastatin 2-4 mg 
 
a Simvastatin doses ≥40 mg/day are not allowed. 
b Low intensity statins also include those patients taking low-dose statins using an alternate regimen (ie, every other 
day, or for a specified number of times per week) and those unable to tolerate a statin at any dose. 
 
Table 3: 
Randomization Strata 
HeFH (with or without ASCVD) 
ASCVD (without HeFH) 
HeFH + Low Intensity Statinsa 
ASCVD + Low Intensity Statinsa 
HeFH + Moderate Intensity Statins 
ASCVD + Moderate Intensity Statins 
HeFH + High Intensity Statins 
ASCVD + High Intensity Statins 
ASCVD = Atherosclerotic cardiovascular diseases; HeFH = Heterozygous familial hypercholesterolemia. 
a Low intensity statins also include those patients taking low-dose statins using an alternate regimen (ie, every other 
day, or for a specified number of times per week) and those unable to tolerate a statin at any dose. 
Approximately 750 eligible patients will be randomized 2:1 on Day 1 (Visit T1) to receive either 
bempedoic acid 180 mg (n = 500), or placebo (n = 250) once daily for 52 weeks.  Randomized 
patients will return for clinic visits at Week 4 (Visit T2), Week 12 (Visit T4), Week 24 
(Visit T5), and Week 52 (Visit T7).  A phone visit will occur at Week 8 (Visit T3) and Week 36 
(Visit T6).   
Patients who withdraw from investigational medicinal product (IMP) treatment will be asked to 
continue to be followed for safety using the protocol-specified visit schedule.  For details of 
study assessments, see the Schedule of Events in Appendix 1. 
An independent expert Data Monitoring Committee (DMC) will formally review accumulating 
unblinded safety and efficacy data from this and other ongoing studies of bempedoic acid.  A 
blinded independent expert Clinical Events Committee (CEC) will adjudicate designated clinical 
endpoints, including all major adverse cardiac events (MACE) and non-MACE endpoints 
defined as:  CV death (MACE), non-CV death (non-MACE), nonfatal myocardial infarction 
[MI] (MACE), nonfatal stroke (MACE), hospitalization for unstable angina (MACE), coronary 
revascularization (MACE), non-coronary arterial revascularization (non-MACE), and 


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Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 35 of 184 
6.5. 
Number of Patients 
The study will enroll approximately 750 adult male and female HeFH and/or ASCVD patients 
with hyperlipidemia from approximately 125 clinical sites.  
6.6. 
Patient Identification Numbers 
A unique patient identification number will be assigned to each patient to identify each patient 
throughout the study and will be entered on all documentation.  If a patient is not eligible to 
receive treatment, or if a patient discontinues from the study, their patient identification number 
cannot be assigned to another patient.  
Patient identification numbers will be assigned sequentially by interactive web response system 
(IWRS) at the time of informed consent during the screening module transaction.  Screening and 
Placebo Run-in Period  
Screening will occur approximately 5 weeks prior to Day 1 (Visit T1) where the patient’s 
eligibility will be evaluated.  Eligible patients who are taking allowed concomitant medications 
must be on stable regimens as defined in Section 8.2.  At the investigator’s discretion, screening 
(time between visits S1 and S2) may be extended for an additional 4 weeks if needed to adjust 
background medical therapy or for other reasons as specified in the protocol.  Eligible patients 
will return to the clinical site at Week -4 (Visit S2) to initiate administration of single-blind 
(patient only) placebo.  Eligible patients will return at Week -1 (Visit S3) for lipid and safety 
laboratories and an assessment of tolerability and study drug adherence (see Section 7.1 and 
Section 7.2 for eligibility criteria).  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. 
6.6.1. 
Randomization and Treatment Period 
For patients who satisfy all entry criteria and complete the 1-week screening period and 4-week 
run-in period, randomization will occur and their randomization number will be assigned via 
IWRS at Week 0 (Visit T1).  Patients will be stratified on CV risk (HeFH and ASCVD 
diagnosis) and baseline statin intensity (high intensity statin, moderate intensity statin, low 
intensity statin), and randomized in a ratio of 2:1 to receive 1 of the 2 following treatments in a 
double-blind fashion: 
• Bempedoic acid 180-mg tablet 
• Matching placebo tablet 
For details regarding the randomization strata see Table 3. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 36 of 184 
7. 
SELECTION AND WITHDRAWAL OF PATIENTS 
7.1. 
Subject Inclusion Criteria 
Each patient with hyperlipidemia must meet the following criteria to be randomized in this study: 
1. Provision of written informed consent prior to any study-specific procedure 
2. Age ≥18 years or legal age of majority based on regional law, whichever is greater at 
Week -5 (Visit S1) 
3. Men and nonpregnant, nonlactating women.   
4. Women must be either: 
• Naturally postmenopausal (as reported by the patient, defined as greater than 55 years 
and ≥1 year without menses, <55 years and ≥1 year without menses with follicle-
stimulating hormone (FSH) ≥40.0 IU/L), or surgically sterile including hysterectomy, 
bilateral oophorectomy, or tubal ligation or;  
• Women of childbearing potential must be willing to use 2 acceptable methods of birth 
control (unless they have agreed to follow the definition of true abstinence).  The 
minimal requirement for adequate contraception it is that it should be started on 
Day 1, continuing during the study period, and for at least 30 days after the last dose 
of study drug.  Acceptable methods of birth control include: oral, implantable, 
injectable or topical birth control medications; placement of an intrauterine device 
(IUD) 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; or 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 
the 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. 
5. Fasting LDL-C (minimum of 10 hours) value at Week -5 (Visit S1) ≥100 mg/dL 
(2.6 mmol/L) and fasting LDL-C value at Week -1 (Visit S3) ≥70 mg/dL (1.8 mmol/L).  
6. Have high CV risk that is defined as either: 
• Diagnosis of HeFH.  Diagnosis must be made by either genotyping or by clinical 
assessment using either the World Health Organization (WHO) criteria/Dutch Lipid 
Clinical Network Criteria with a score that is >8 points (see Appendix 4) or the 
Simon Broome Register Diagnostic Criteria with an assessment of ‘Definite HeFH’ 
(see Appendix 5).  Patients with a diagnosis of HeFH may or may not have 
established CHD or CHD risk equivalents. 
OR 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 37 of 184 
• Have ASCVD (with established CHD or CHD risk equivalents) 
Documented history of CHD (includes 1 or more of the following): 
− Acute MI 
− Silent MI 
− Unstable angina 
− Coronary revascularization procedure (eg, percutaneous coronary intervention 
[PCI] or coronary artery bypass graft [CABG] surgery) 
− Clinically significant CHD diagnosed by invasive or non-invasive testing (such as 
coronary angiography, stress test using treadmill, stress echocardiography or 
nuclear imaging) 
Documented CHD risk equivalents (includes 1 or more of the following criteria): 
− Symptomatic peripheral arterial disease (PAD) defined as 
○ Peripheral vascular disease with symptoms of claudication or resting limb 
ischemia with either ankle brachial index <0.9 performed by a vascular lab or 
○ Angiogram (including computed tomographic angiography [CTA]) showing 
≥50% stenosis or 
○ Peripheral arterial revascularization (surgical or percutaneous) occurring 
greater than 90 days prior to Visit S1 or 
○ Lower extremity amputation due to peripheral vascular disease occurring 
greater than 90 days prior to Visit S1 
− Cerebrovascular atherosclerotic disease defined by: 
○ ischemic stroke occurring greater than 90 days prior to Visit S1 or 
○ Carotid endarterectomy, carotid stenting, or more than 70% stenosis in a 
carotid artery determined by carotid ultrasound or angiogram occurring 
greater than 90 days prior to Visit S1. 
Note:  Patients with T2DM are allowed in this study; however, for this study 
T2DM is not considered a CHD risk equivalent 
7. Be on maximally tolerated lipid-modifying therapy, including a maximally tolerated 
statin either alone or in combination with other lipid-lowering therapies, at stable doses 
and regimens for at least 4 weeks prior to screening (6 weeks for fibrates; however, 
gemfibrozil is not allowed as per co-administration instructions defined in the statin 
label).  Maximally tolerated statin includes statin regimens other than daily dosing, 
including no to very low doses, but reasons for not using high-intensity statin dosing 
must be documented.  
A patient’s maximally tolerated lipid-modifying therapy will be determined by the 
investigator using their medical judgment and available sources, including the patient’s 
self-reported history of lipid-modifying therapy.  


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 38 of 184 
Note:  Patients can be on any available lipid-modifying therapy with the exception of the 
exclusions listed below as long as they have been stable for 4 weeks prior to Screening 
Visit S1 and are taken at a consistent time each day. In the case of PCSK9 inhibitor use, 
the patient must have received 3 stable doses.  It is important that lipid values are 
measured at PCSK9i trough levels.  Therefore, study visits should be scheduled in 
accordance with the patient’s PCSK9i injection regimen so that measurement of lipid 
values for all visits occurs before the PCSK9i injection but not greater than 48 hours 
before the next scheduled PCSK9 injection.  Patients who have discontinued 
investigational or commercial PCSK9 inhibitor must have had their last dose at least 
4 months prior to Screening Visit S1. 
7.2. 
Subject Exclusion Criteria 
Patients who meet any of the following criteria will not be randomized: 
1. Total fasting (minimum of 10 hours) triglyceride ≥500 mg/dL (5.6 mmol/L) at Week -5 
(Visit S1) 
Note:  TG may be repeated 1 time between Visits S1 and S2.  For those patients who 
have a repeat TG, the repeat value will be used to determine eligibility. 
2. Renal dysfunction or nephritic syndrome or a history of nephritis, including estimated 
glomerular filtration rate (eGFR) (using central laboratory determined Modification of 
Diet in Renal Disease [MDRD] formula) <30 mL/min/1.73m2 at Week -5 (Visit S1) 
(Levey 2006).   
Note: At the discretion of the investigator, the screening period may be extended up to 
4 weeks for a single repeat eGFR.  For those patients who have a repeat eGFR, the repeat 
value should be obtained between visits S1 and S2 and will be used to determine 
eligibility. 
3. Body mass index (BMI) ≥50 kg/m2 
4. Recent (within 3 months prior to the screening visit [Week -5 (Visit S1)] or between 
screening and randomization visits) MI, unstable angina leading to hospitalization, 
uncontrolled, symptomatic cardiac arrhythmia (or medication for an arrhythmia that was 
started or dose changed within 3 months of screening), CABG, PCI, carotid surgery or 
stenting, cerebrovascular accident, transient ischemic attack (TIA), endovascular 
procedure or surgical intervention for peripheral vascular disease or plans to undergo a 
major surgical or interventional procedure (eg, PCI, CABG, carotid or peripheral 
revascularization).  Patients with implantable pacemakers or automatic implantable 
cardioverter defibrillators may be considered if deemed by the Investigator to be stable 
for the previous 3 months. 
5. Uncontrolled hypertension, defined as sitting systolic blood pressure (SBP) ≥160 mmHg 
and diastolic blood pressure (DBP) ≥100 mmHg after sitting quietly for 5 minutes 
Note:  If the initial blood pressure (BP) values meet or exceed the specified level, an 
additional BP assessment may be completed.  If the systolic or the diastolic values 
continue to meet or exceed the threshold, the patient may not continue screening.  
However, at the discretion of the Investigator, the screening period (between Visits S1 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 39 of 184 
and S2) may be extended up to 4 weeks to allow for a repeat qualifying BP assessment 
following adjustment of BP medication(s), provided that the patient has been on a stable 
dose of the BP medication for a minimum of 2 weeks prior to randomization and the 
repeat BP measurements do not meet the exclusion criteria. 
6. Hemoglobin A1C (HbA1C) ≥10% at Week -5 (Visit S1) 
7. Uncontrolled hypothyroidism, including thyroid-stimulating hormone (TSH) >1.5 × the 
upper limit of normal (ULN) at Week -5 (Visit S1).  Patients stabilized on thyroid 
replacement therapy for at least 6 weeks prior to randomization are allowed. 
8. Liver disease or dysfunction, including:  
• Positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C 
antibodies (HCV-AB) at Week -5 (Visit S1); or 
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≥2 × ULN, 
and/or total bilirubin (TB) ≥1.2 × ULN at Week -5 (Visit S1).  If TB ≥1.2 × ULN, a 
reflex indirect (unconjugated) bilirubin will be obtained and if consistent with 
Gilbert’s disease or if the patient has a history of 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 prior to randomization.  For those patients who have a repeat ALT and/or 
AST, the repeat value 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. Hematologic or coagulation disorders or a hemoglobin (Hgb) level <10.0 g/dL (100 g/L) 
at Week -5 (Visit S1) 
11. Active malignancy, including those requiring surgery, chemotherapy, and/or radiation in 
the past 5 years.  Nonmetastatic basal or squamous cell carcinoma of the skin and 
cervical carcinoma in situ are allowed. 
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 with amphetamine derivatives prescribed by and under the care of a 
health care practitioner can be enrolled after evaluation by the Investigator. 
14. Blood donation, blood transfusion for any reason, participation in a clinical study with 
multiple blood draws, major trauma, or surgery with or without blood loss within 30 days 
prior to randomization 
15. Use of any experimental or investigational drugs within 30 days prior to screening.  
16. Previous enrollment in a bempedoic acid clinical study.   


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 40 of 184 
17. Use of any of the following drugs or a plan to use these drugs during the study;  
• New or planned dose changes of systemic corticosteroids.  Stable doses (≥4 weeks 
before Visit S1) and topical steroids allowed. 
• CETP inhibitors within the last 2 years prior to screening (Week -5, Visit S1) except 
for evaceptrapib within the last 3 months prior to screening (Week -5, Visit S1) 
• Mipomersen (6 months prior to screening, Week -5, Visit S1) 
• Lomitapide (3 months prior to screening, Week -5, Visit S1) 
• Apheresis (3 months prior to screening, Week -5, Visit S1) 
• Simvastatin ≥40 mg/day (4 weeks prior to screening, Week -5, Visit S1) 
• Red yeast rice extract-containing products are not allowed (2 weeks prior to 
screening, Week -5, Visit S1) 
18. Planned initiation of the following drugs during the clinical trial or changes prior to 
randomization (Day 1, Visit T1): 
• Hormone replacement (6 weeks prior to randomization) 
• Thyroid replacement (6 weeks prior to randomization) 
• Diabetes medications (4 weeks prior to randomization) 
• Obesity medication (44 weeks prior to randomization) 
19. Lack of adherence (ie, less than 80% of planned doses) with IMP (single-blind placebo) 
during the Run-in Period. 
20. Lack of tolerance with IMP (single-blind placebo) during the Run-in Period. 
21. 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. 
22. An employee or contractor of the facility conducting the study, or a family member of the 
Principal Investigator, Co-Investigator, or Sponsor. 
23. Pregnant, breastfeeding, or intending to become pregnant within 30 days after last dose of 
study drug. 
24. Patients who have enrolled in a study of an experimental siRNA inhibitor of PCSK9 are 
excluded. 
7.3. 
Patient Lifestyle and Dietary Guidelines 
Patients will be counseled to follow a lipid-lowering diet as per local or regional guidelines and 
should be encouraged (as able) to participate in a regular exercise program throughout the study.  


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 41 of 184 
7.4. 
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. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 42 of 184 
8. 
TREATMENT OF PATIENTS 
8.1. 
Description of IMP 
Table 4: 
Investigational Medicinal Products 
 
Investigational Medicinal Product 
Product Name: 
Bempedoic acid 
Placebo 
Dosage Form: 
 tablets 
 tablets 
Unit Dose: 
180 mg 
Not applicable 
Container/Closurea 
100-count bottle (depending 
upon visit) with screw on, 
childproof cap 
35- and/or 100-count bottle with 
screw on, childproof cap 
Route of Administration: 
Oral, daily, with or without food 
Oral, daily, with or without food 
Physical Description: 
 
 
a A 100-day supply of IMP will be included in the 100-count bottle and a 35-day supply of single blind placebo 
lead-in will be included in the 35-count bottle. 
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.  
8.2.1. 
Lipid-Regulating Medications and Supplements 
Patients will be required to be on stable lipid-modifying therapy(s), including a maximally 
tolerated statin for at least 4 weeks prior to screening.  Maximally tolerated statin includes statin 
regimens other than daily dosing, including no to very low doses, but reasons for not using high-
intensity statin dosing must be documented.  Use of fibrates must be stable at least 6 weeks prior 
to screening.  Gemfibrozil, a fibrate, is prohibited as per co-administration instructions defined in 
the statin label.  Stable lipid-modifying therapy(s) includes, but is not limited to, monotherapies 
or combination therapies containing the compounds below: 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 43 of 184 
Statins 
• Atorvastatin (Lipitor®, Sortis®) 
• Fluvastatin (Lescol®) 
• Lovastatin (Mevacor®, Altoprev™) 
• Pravastatin (Pravachol®) 
• Pitavastatin (Livalo®, Lipostat®) 
• Rosuvastatin (Crestor®) 
• Simvastatin (Zocor®) (doses ≥40 mg/day are exclusionary) 
Selective cholesterol and/or bile acid absorption inhibitors 
• Cholestyramine/Colestyramine (Questran®, Questran Light®, Prevalite®, Locholest®, 
Locholest® Light) 
• Colestipol (Colestid®) 
• Colesevelam hydrochloride (Welchol®, Cholestagel®) 
• Ezetimibe (Zetia®, Ezetrol®) 
Fibrates 
• Fenofibrate (Antara®, Lofibra®, Tricor®, Triglide™, Lipantil®, Supralip®)  
• Bezafibrate (Bezalip®) 
• Ciprofibrate (Modalim®) 
PCSK9 inhibitors  
• Alirocumab (Praluent®) 
• Evolocumab (Repatha®) 
Other 
• Ezetimibe/simvastatin where simvastatin is less than 40 mg/day (Vytorin® 10/10 and 
10/20 Inegy® 10 mg/20 mg are allowed)  
• Atorvastatin/ezetimibe (Atozet®) 
8.2.2. 
Prohibited Medications 
Patients will not have used medications (monotherapies or combination therapies) listed below 
within the allotted time period prior to screening or use these drugs during the study: 
• New or planned dose changes of systemic corticosteroids.  Stable doses of systemic 
corticosteroids at screening are allowed (≥4 weeks).  Short-term intermittent use 
(<14 days) of pulse steroids are allowed.  Topical steroids are allowed. 
• Gemfibrozil (Lopid®) (as per co-administration instructions defined in the statin 
label) ≥6 weeks prior to screening (Visit S1) 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 44 of 184 
• Cholestin (red yeast rice extract, also known as monascus purpureus extract) 
(≥2 weeks prior to screening) 
• CETP inhibitors within the last 2 years prior to screening (Visit S1) except for 
evaceptrapib within the last 3 months prior to screening (Visit S1) 
• Mipomersen within 6 months prior to screening (Visit S1) 
• Lomitapide within 3 months prior to screening (Visit S1) 
• Apheresis within 3 months prior to screening (Visit S1) 
• Simvastatin ≥40 mg/day 
• Ezetimibe/simvastatin where simvastatin doses are ≥40 mg/day (Vytorin® 10/40 and 
10/80 and Inegy® 10 mg/40 mg and 10 mg/80 mg are exclusionary) 
8.2.3. 
Allowable Medications 
Other concomitant medications must be stable, if possible, not be adjusted during the study 
except for reasons of safety.  
The following must be stable for a minimum of 6 weeks prior to randomization: 
• Postmenopausal hormone therapy 
• Thyroid hormone supplements 
The following must be stable for a minimum of 4 weeks prior to randomization: 
• Diabetes medications 
• Antiobesity medications 
8.3. 
Treatment Compliance 
Screening Compliance 
No study medication treatment will be given during the Screening period; therefore, compliance 
will not be assessed.  
Placebo Run-in and Treatment Period Adherence 
At Week -1 (S3) visit in the placebo run-in period and at each of the subsequent patient visits, 
designated clinical site staff will assess patient for placebo and/or IMP adherence by counting the 
number of tablets that are returned as unused and by querying the patient with regards to daily 
intake.  If the patient has not taken all doses of study drug as instructed, the patient will be 
queried for a reason, findings will be documented, and the patient will be counseled on the 
importance of carefully following all dosing instructions.  Factors contributing to poor adherence 
will be determined and, if possible, remedied.  Patients demonstrating poor adherence will 
continue to be counseled on the importance of carefully following all dosing instructions, but 
will not be removed from the study.  However, patients with ≤80% adherence over the entire 
Run-in Period and/or who experienced a study drug-related AE, will not go onto randomization.  


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 45 of 184 
8.4. 
Blinding 
Patients who satisfy all entry criteria during the screening and complete single-blind placebo 
run-in period and meet the lipid, safety, tolerability, and drug adherence measures will be 
randomized to a treatment group at Week 0 (Visit T1).  Patients on maximally tolerated lipid-
modifying therapy, as determined by the investigator, will be stratified based on the patient’s CV 
risk (ASCVD alone; HeFH with or without ASCVD) and baseline statin intensity (high intensity 
statin, moderate intensity statin, low intensity statin) for a total of 6 strata.  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 based on their HeFH status and baseline statin 
use and dose and assign a randomization number and the appropriate study drug container via 
medication identification numbers (MED ID).   
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.  
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, TG, TC, HDL-C, 
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. 


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An independent blinded expert CEC will adjudicate all clinical endpoints, including death, using 
standardized definitions.  Clinical endpoints will also be reported as SAEs.  Additional details 
and definitions will be provided in a CEC Charter. 
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 ICON programmer and statistician.  Additional details will be provided in a DMC 
Charter. 
8.5. 
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, as per medical judgment. 


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9. 
INVESTIGATIONAL MEDICINAL PRODUCT  
9.1. 
Investigational Medicinal Product Supply and Control 
The Sponsor will supply the IMP for this study.  The IMP for this study includes bempedoic acid 
(180-mg 
 tablets) and matching placebo (
 tablets).  IMP will be distributed 
and released in accordance with regional and local requirements during the conduct of the study. 
The MED ID number (an identifier on the study drug packaging) will be obtained via IWRS and 
used to select placebo for the single-blind placebo run-in period and double-blind IMP for the 
treatment period from available clinical supplies at the clinical site.  
A 35-day supply of single-blind placebo drug will be dispensed one time at Week -4 (Visit S2) 
for the 4-week placebo run-in period of the study.  Double-blind IMP will be dispensed in 100-
day supply increments to patients by appropriate clinical site personnel. Patients will receive one 
100-day supply bottle at Week 0 (Visit T1), Week 12 (Visit T4), and two 100-day supply bottles 
at Week 24 (Visit T5).  At Week 12, patients will return their first bottle and tablets will be 
counted by study personnel who will then dispense a second bottle.  At Week 24, tablets from 
the second bottle will be counted and the final 2 bottles dispensed.  At Week 52, tablets will be 
counted by study personnel from the 2 bottles dispensed at Week 24.  
Please see Pharmacy Manual for detailed storage requirements and management instructions. 
9.2. 
Administration of Investigational Medicinal Product 
Patients will be instructed to ingest, placebo starting at Visit S2 for the duration the placebo run-
in period and the 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 T4 or T5 
or T7 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. 


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9.3. 
Investigational Medicinal Product Accountability 
Accurate records of the receipt of all IMP shipped by the Sponsor (or designee) and the 
disposition of that IMP 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 inventory (including 
entry/movement/disposition) 
• Date and amount of IMP dispensed to each patient, including unique patient 
identifiers 
• Date that IMP 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, single-blind placebo 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 Week -5 (Visit S1; Day -35 ± 7 days) 
The screening period will begin with a screening visit that will occur approximately 5 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, including assessment of HeFH status and ASCVD  
• Concomitant and prohibited medication review 
• Height (cm), weight (kg), BMI  
• Vital signs  
• Clinical laboratory evaluations:  
− Hematology, blood chemistry, coagulation, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− 
HbA1C 
− TSH  
− FSH (in appropriate female patients) 
− Serum pregnancy test (on appropriate female patients) 
• Serology (including HBsAg, 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 at Visit S1 will be instructed to 
continue their therapy(s) for lipid regulation 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). 
Note: 
• An optional visit approximately 1 week later MAY be completed if patient fails TG 
entry criterion.  If this optional visit is completed, the repeat lipid values will be used 
to determine eligibility. 
• An optional visit between Visits S1 and S2 may be scheduled to collect screening 
fasting labs in the event that the patient arrives at Visit S1 in a nonfasted state. 
• An optional visit between Visits S1 and S2 may be completed if the patient’s DBP 
and/or SBP meet the exclusion criteria levels.  Patients may randomize after BP 
medications have been adjusted, they have been on stable doses of BP medications 
for at least 2 weeks, and the repeat BP values (DBP and/or SBP) no longer meet 
exclusionary values. 
• An optional visit between Visits S1 and S2 may be completed to determine eligibility 
if the patient’s eGFR, ALT, AST, and/or TB meet exclusion criteria levels.  If this 
optional visit is completed, the repeated value will be used to determine eligibility. 
• Patients who are considered to be screen failures due to not meeting stability 
requirements for a condition or concurrent medication may be considered for 
rescreening after consultation with the Sponsor (or designee).  These patients must be 
re-consented, re-registered in the IWRS, and will have a new patient ID number 
assigned. 
10.2.2. 
Placebo Run-in Week -4 (Visit S2; Day -28± 3 days) 
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, SAEs, and potential clinical endpoints (starting from signing of the 
informed consent document) 
• Vital signs 


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• Conduct diet and exercise counseling 
• IWRS contact to obtain the and MED ID number for single-blind placebo  
• Dispense placebo and provide dosing instructions (one 35-day supply bottle) 
• Schedule next visit 
10.2.3. 
Placebo Run-in Week -1 (Visit S3; Day -7± 3 days) 
The patient will undergo the following assessments and procedures at (Visit S3) 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints (starting from signing of the 
informed consent document) 
• Vital signs 
• Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG); LDL-C 
must be ≥70 mg/dL (1.8 mmol/L) to be eligible 
• Conduct diet and exercise counseling 
• Re-dispense placebo container from Visit S2 to patient for continued dosing and 
provide dosing instruction 
• Assessment and recording of drug compliance 
• Schedule next visit 
10.2.4. 
Treatment Week 0 (Visit T1; Day 1) 
Prior to scheduling Visit T1, review the information collected at Visits S1, S2, and S3 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 and none of the exclusion criteria, 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, SAEs, and potential clinical endpoints  
• Physical examination (PE) 
• Weight 
• 12-Lead electrocardiogram (ECG) 


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• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
Note:  Urine pregnancy test (for females of childbearing potential) 
- Coagulation in patients on vitamin K antagonists only (and repeat 3-5 days later) 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− apoB 
− HbA1C  
− hs-CRP 
• Review inclusion/exclusion criteria to establish patient eligibility 
• 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 (one 100-day supply bottle) 
• Return of placebo tablets, record compliance and ensure patient meets eligibility 
criteria  
• Schedule next visit 
10.2.5. 
Treatment Week 4 (Visit T2; 29 ±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.  The patient will be asked to continue to be followed for safety 
using the protocol-specified visit schedule.   
Patients refusing to continue to return to the clinic for protocol assessments after withdrawing 
from IMP treatment will be asked to participate in phone calls from the site at protocol-specified 
visits, or at a minimum at 52 weeks, to inquire about the patient’s current health status and 
collect information on AEs (eg, recent procedures, hospitalizations, and if the patient has died, 
the cause of death).  If the patient consents for telephone contacts, schedule the next protocol-
specified visit. 
Patients will undergo the following assessments and procedures at Week 4 (Visit T2): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints since last visit (ongoing) 
• Weight 
• Vital signs 


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• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
• 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 
• Schedule next visit 
10.2.6. 
Treatment Week 8 / Telephone Visit (Visit T3; 57 ±3 days) 
Patients will undergo the following assessments via telephone at Week 8 (Visit T3): 
• Concomitant medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints 
• Diet and exercise counseling 
• Assessment of study drug dosing adherence 
Note:  If the patient discontinues at or between study visits, please proceed to Section 10.3.2 for 
detailed instructions. 
10.2.7. 
Treatment Week 12 (Visit T4; 85 ±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 10.2.10 for the 
list of the required assessments.  The patient will be asked to continue to be followed for safety 
using the protocol-specified visit schedule.  If the patient consents for follow-up, schedule the 
next protocol-specified visit.  
Patients who do not provide consent to continue to return to the clinic for safety assessments 
after withdrawing from IMP treatment will be asked to participate in phone calls from the site at 
protocol-specified visits, or at a minimum at 52 weeks, to inquire about the patient’s current 
health status and collect information on AEs (eg, recent procedures, hospitalizations, and if the 
patient has died, the cause of death).  If the patient consents for telephone contacts, schedule the 
next protocol-specified visit. 
Patients will undergo the following assessments and procedures at Week 12 (Visit T4): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints since last visit (ongoing) 
• Weight 
• Vital signs 


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• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− apoB 
− HbA1C 
− hs-CRP 
• Conduct diet and exercise counseling 
• Return of IMP; assessment and recording of IMP compliance 
• IWRS contact to obtain the MED ID number for IMP 
• Dispense IMP and provide dosing instructions (one 100-day supply bottle)  
• Schedule next visit 
10.2.8. 
Treatment Week 24 (Visit T5; 168 ±7 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 10.2.10 for the 
list of the required assessments.  The patient will be asked to continue to be followed for safety 
using the protocol-specified visit schedule.  If the patient consents for follow-up, schedule the 
next protocol-specified visit.  
Patients who do not provide consent to continue to return to the clinic for safety assessments 
after withdrawing from IMP treatment will be asked to participate in phone calls from the site at 
protocol-specified visits, or at a minimum at 52 weeks, to inquire about the patient’s current 
health status and collect information on AEs (eg, recent procedures, hospitalizations, and if the 
patient has died, the cause of death).  If the patient consents for telephone contacts, schedule the 
next protocol-specified visit. 
Patients will undergo the following assessments and procedures at Week 24 (Visit T5): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints since last visit (ongoing) 
• Weight 
• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− apoB 
− HbA1C 


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− hs-CRP 
• PK sample before dose 
• Conduct diet and exercise counseling 
• Return of IMP; assessment and recording of IMP compliance 
• IWRS contact to obtain the MED ID number for IMP 
• Dispense IMP and provide dosing instructions (two 100 day supply bottles)  
• Schedule next visit 
10.2.9. 
 Treatment Week 36 / Telephone Visit (Visit T6; 252 ±3 days) 
Patients will undergo the following assessments via telephone at Week 36 (Visit T6): 
• Concomitant medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints 
• Diet and exercise counseling 
• Assessment of study drug dosing adherence 
Note:  If the patient discontinues at or between study visits, please proceed to Section 10.3.2 for 
detailed instructions. 
10.2.10. 
Treatment Week 52/EOS (Visit T7; 365 ±7days) 
Patients will undergo the following assessments and procedures at Week 52 (Visit T7), when 
completing an End of Study (EOS) visit, withdrawing from study (early withdrawal), or 
withdrawing from IMP treatment: 
Patients will undergo the following assessments and procedures at Week 52 (Visit T7): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints since last visit (ongoing) 
• PE 
• Weight 
• 12-Lead ECG 
• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL C, HDL C, non-HDL C, and TG) 
− apoB 
− HbA1C 


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− hs-CRP 
− PK sample before dose 
• Return of IMP; assessment and recording of IMP compliance 
• Complete study status in IWRS (ie, early withdrawal or completed study). 
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 Week 52 (Visit T7) to be 
considered as having completed participation in the study.  
Patients who withdraw from IMP prior to Week 52 (Visit T7) for any reason will be asked to 
continue to be followed for safety assessments, including basic fasting lipids, at clinic visit 
following the protocol-specified visit schedule (see Appendix 1). 
Patients who temporarily withdraw from IMP prior to Week 52 (Visit T7) 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 4 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. 
Patients who refuse to continue to return to the clinic for safety assessments will be asked to 
participate in phone calls from the site at protocol-specified visits (see Appendix 1), or at a 
minimum at 52 weeks, to collect information on AEs, concomitant medications, and current 
health status.  The patient must provide consent to be contacted by phone by site personnel for 
the purposes of assessing current AEs and current health status. 
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  


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• 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. 
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 10.2.10 will be performed upon 
the discontinuation of the study. 
Patients choosing to withdraw from the study early should be encouraged to return for all study 
scheduled clinic visit even if they are no longer taking IMP.  Patients who withdraw from all 
aspects of the study will be asked to consent to clinical visits or phone calls for safety 
assessments, including AEs, concomitant medication, and current health status through Week 52 
(Visit T7). 


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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, 
concomitant medications, and 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.  
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 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 start of study drug will be recorded on the Medical 
History/Current Medical Conditions page of the eCRF.  Only changes from baseline physical 
examination 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 11.2.3. 
11.1.5. 
Electrocardiogram 
ECG collection will be preceded by a 10-minute rest time during which the patient will remain in 
the supine position.  At each time point, ECGs will be collected prior to blood collection.  ECGs 
will be assessed using machine readings and physician review. 
11.1.5.1. Monitoring and Management of Abnormal Electrocardiograms 
If a clinically significant ECG abnormality not present at baseline (screening) is determined by 
the Investigator to be related to study drug, the abnormality will be discussed with the Sponsor 
personnel or the authorized Medical Monitor, and followed and evaluated with additional tests (if 
necessary) until the underlying cause is determined or the event is brought to an acceptable 
resolution.  Additional clinical and laboratory information will be collected and carefully 
documented in order to better characterize the ECG abnormality and rule out alternative causes. 
ECG findings determined to be a clinically significant change from baseline should be reported 
as an AE regardless of causality. 
Unscheduled ECG assessments will be completed at the discretion of the Investigator. 


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11.1.6. 
Clinical Laboratory Tests 
11.1.6.1. 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 5.  Collection schedule, schedule of laboratory 
parameters by visit, and instructions are in the Clinical Laboratory Manual provided by Central 
Laboratory. 
Table 5: 
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 
Urinalysis (Dipstick) 
• 
Clarity 
• 
Bilirubin 
• 
Color 
• 
Glucose 
• 
Ketones 
• 
Leukocyte esterase 
• 
Nitrite 
• 
Occult blood 
• 
pH 
• 
Protein 
• 
Specific gravity 
• 
Urobilinogen 


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Table 5: 
Clinical Laboratory Parameters (Safety) (Continued) 
Clinical Laboratory Test 
Clinical Laboratory Test 
Urinalysis (Microscopic)-only if urine dipstick 
abnormal 
• 
Bacteria 
• 
Casts 
• 
Crystals 
• 
Epithelial cells 
• 
Red blood cell (RBC) 
• 
WBC 
Coagulation (screening for all patients, T1 and 
3-5 days after T1 in patients receiving 
anticoagulation therapy, only) 
• 
Prothrombin time (PT) 
• 
International normalized ratio (INR) 
Other Screening Labs 
Additional samples 
• 
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) 
• 
Hemoglobin A1C (HbA1C) 
• 
PK sample  
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. 
11.1.6.2. 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.  For 
collection and processing of PK samples, please see Section 11.1.6.5 and Section 11.1.6.6.  
Samples will be processed by the Central Laboratory.  
Blood draws for lipids, TG, 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, TG, 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) 
11.1.6.3. 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 


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significant change from baseline for the individual patient, with baseline defined as the last value 
or observation before the first dose of study drug.  The Investigator may repeat the laboratory 
test or request additional tests to verify the results of the original laboratory test. 
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.   
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 
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. 
11.1.6.3.1. 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 anti-cytomegalovirus/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) or more frequently 
if deemed by the investigator. 
• 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 


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to continue to be followed for safety using the protocol-specified visit schedule (see 
Appendix 1) or more frequently if deemed by the investigator: 
− 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 
11.1.6.3.2. 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) 
11.1.6.3.3. Monitoring and Management of Hemoglobin Change 
If at any time after randomization a patient experiences a decrease >2.0 g/dL (20 g/L) from 
baseline (Week 0 [Visit T1]), the patient will undergo repeat confirmatory hematology testing as 
soon as is reasonably possible, preferably within 3 to 7 days of the laboratory result becoming 
available.  
Repeat hematology assessment will include: 1) measurement of Hgb, hematocrit (Hct), mean 
corpuscular hemoglobin, mean corpuscular hemoglobin concentration, mean corpuscular 
volume, platelet count, reticulocyte count (percent and absolute), red blood cell count (RBC), 
and white blood cell count (WBC) with differential (absolute values only); 2) history of 
concomitant medication use; and 3) query for related symptoms.  Additionally, further testing 
may be warranted to rule out additional pathology depending on clinical presentation, and should 
be discussed with Esperion Therapeutics personnel or the authorized Medical Monitor.  
• If repeat Hgb assessment confirms a decrease >2.0 g/dL (20 g/L) from baseline, the 
patient should be monitored carefully during the study and return at 2-week intervals 
after study completion for additional Hgb measurement until the level returns to 
baseline or reaches a stable level.  
• If repeat Hgb assessment confirms Hgb <8 g/dL (80 g/L), the patient should be 
withdrawn from IMP treatment. The patient will return at 1-week intervals after 
withdrawing from IMP treatment for additional Hgb measurement until the level 
returns to baseline or reaches a satisfactory conclusion. 
• 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). 
At any time, the investigator may choose to consult with a specialist to further evaluate the cause 
of the alteration in Hgb. 


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11.1.6.3.4. 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. 
• 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). 


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11.1.6.4. 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.  
11.1.6.4.1. Monitoring and Management of Elevated LDL-C  
An adjunctive therapy plan is in place for those patients whose LDL-C values meet the protocol-
defined LDL-C threshold criteria. Post-randomization, LDL-C results will be masked to 
investigators in order to maintain the blind; however, the following thresholds have been set to 
notify investigators and provide an opportunity to adjust the patient’s standard of care regimen.  
• Beginning at Week 24 (Visit T5) visit and for the duration of the study, the central 
laboratory will notify the investigator when the patient’s LDL-C value is >170 mg/dL 
(4.4 mmol/L) and ≥25% from the patient’s baseline value at Week 0, (Visit T1)  
• Upon receiving notification from the central laboratory that the patient has met or 
exceeded the threshold criteria for LDL-C, the investigator will initiate the following 
adjunctive therapy plan: 
− Patients will be scheduled to return to the clinic within 1 week for a repeat fasting 
blood lipid sample to confirm that the LDL-C value meets the threshold criteria  
− After confirming that the LDL-C value meets or exceeds the threshold criteria, the 
investigator will adjust the patient’s lipid-lowering treatment regimen per 
standard-of-care and local practice, with the exception of simvastatin at doses 
≥40 mg/day and the fibrate, gemfibrozil. The patient’s LDL-C will be re-
evaluated at the next scheduled clinic visit as defined in the Schedule of Visits 
(Appendix 1). 
− The initiation of any new or dose changes of any existing lipid-lowering treatment 
will be documented on the eCRF as a concomitant medication with the associated 
start date 
− Patients who have their lipid-lowering medications modified, including new 
medications or dosage changes to existing medications, should return to the clinic 
in 4 weeks after the modification to their lipid-lowering treatment for a routine 


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safety laboratory assessment.  Additional safety laboratory assessments may be 
conducted at the investigator’s discretion. 
− Adjunctive therapy medications will not be provided by the sponsor 
− Patients continuing to exceed the LDL-C threshold after maximizing the standard-
of-care LCL-C-lowering therapy and, in the opinion of the investigator, require 
therapies that are prohibited by the protocol will be discontinued from IMP 
treatment and will be asked to continue to be followed for safety using the 
protocol-specified visit schedule (see Appendix 1). 
− Please see the Clinical Laboratory Manual and Section 11.7 for sample collection 
and instructions. 
11.1.6.4.2. Monitoring and Management of Elevated Triglycerides 
Patients may continue to use stable doses of TG-lowering medications during the study.  An 
adjunctive therapy plan is in place for those patients whose TG values meet the protocol-defined 
threshold criteria.  Post-randomization, TG results will be masked to investigators in order to 
maintain the blind; however, a threshold has been set to notify investigators and provide an 
opportunity to adjust the patient’s standard of care regimen.  Beginning at Week 4 (Visit T2), if 
the TG level exceeds 1000 mg/dL (11.3 mmol/L) while on treatment, the investigator will 
receive notification from the central laboratory that the patient has met or exceeded the protocol-
defined threshold criteria for TG.  The investigator will initiate the following plan: 
• Any patient with TG >1000 mg/dL (11.3 mmol/L), will be reminded to fast for at 
least 10 hours and will return to clinic within 1 week for a repeat, fasting TG sample 
to confirm the TG value meets the threshold criteria  
• Any patient with a confirmed TG >1000 mg/dL (11.3 mmol/L) may initiate standard-
of-care therapy (however, gemfibrozil may not be added) to lower TG using a patient-
specific prescription.  The initiation of this medication will be documented on the 
case report form as a concomitant medication with the associated start date.  These 
medications will not be provided by the sponsor. 
• Patients continuing to exceed the TG threshold after maximizing the standard-of-care 
triglyceride-lowering therapy will be discontinued from IMP treatment and will be 
asked to continue to be followed for safety using the protocol-specified visit schedule 
(see Appendix 1). 
• Please see the Clinical Laboratory Manual and Section 11.7 for sample collection and 
instructions. 
11.1.6.5. Pharmacokinetic Assessments 
Pharmacokinetic assessments to measure plasma concentrations of bempedoic acid and its 
metabolite ESP15228 will be conducted from 6 mL whole blood samples collected.  At the time 
of sample collection, the date and time of blood draw and the last 2 doses of study medication 
will be collected.  Pharmacokinetic sample analyses for bempedoic acid and ESP15228 will be 
conducted by the Bioanalytical Laboratory. 


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11.1.6.6. Collection and Assessment of Pharmacokinetic Samples 
Pharmacokinetic samples will be collected from patients at Weeks 24 and 52, for use in further 
developing the population PK model.  
Plasma concentrations of bempedoic acid and its metabolite (ESP15228) will be determined 
using validated methods.  Plasma PK samples will be labeled with preprinted information, 
including study number, patient identification number, study day, nominal time of sample 
collection, matrix, and a text identification (ie, “Plasma PK”).  See the study laboratory manual 
for further instructions. 
11.1.6.7. Shipment of Pharmacokinetic Samples 
Plasma PK samples will be shipped frozen on dry ice according to instructions provided in the 
laboratory manual. 
11.1.6.8. Total Blood Volume of Clinical Laboratory and Pharmacokinetic Samples 
The total number of venipunctures and total volume of whole blood collected during the study 
will be limited to that needed for safety monitoring, PK, efficacy, and biomarker assessment.  
Total whole blood volume collected over the study duration is not to exceed approximately 
250 mL for each patient. 
11.2. 
Adverse and Serious Adverse Events 
11.2.1. 
Definition of Adverse Events 
An AE is 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.  
An AE can be: 
• Any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, 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 
• Any deterioration in nonprotocol-required measurements of laboratory value or other 
clinical test (eg, ECG or x-ray) that results in symptoms, a change in treatment, or 
discontinuation from study drug 
• TEAEs are defined as AEs that begin or worsen after the first dose of study drug 
• Adverse drug reaction (ADR; see Section 11.2.2) 
11.2.2. 
Adverse Drug Reaction 
All noxious and unintended responses to a medicinal product related to any dose should be 
considered an ADR.  “Responses” to a medicinal product means that a causal relationship 


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between a 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). 
11.2.3. 
Reporting  
All AEs occurring during the course of the study (starting from signing informed consent to 
study completion or discontinuation) will be collected on the AE eCRF.  Patients should be 
instructed to report any AE that they experience to the Investigator through 30 days following 
the last dose of study drug.  Beginning with Visit S1 (Week -5), Investigators should make an 
assessment for AEs at each visit and record the event on the appropriate AE eCRF.  Any SAE 
that occurs from the time of ICF through 30 days following the last dose of study drug should be 
reported to the Sponsor per Section 11.3. 
Wherever possible, a specific disease or syndrome rather than individual associated signs and 
symptoms should be identified by the Investigator and recorded on the eCRF.  However, if an 
observed or reported sign or symptom is not considered a component of a specific disease or 
syndrome by the Investigator, it should be recorded as a separate AE on the eCRF.  Additionally, 
the condition that led to a medical or surgical procedure (eg, surgery, endoscopy, tooth 
extraction, transfusion) should be recorded as an AE, not the procedure.  
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 changes 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 (eg, ECG) 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. 
Each AE is to be evaluated for duration, severity, seriousness, and causal relationship to the 
investigational drug. 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 


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• Investigator’s assessment of relationship to study drug. 
A cluster of signs and symptoms that results from a single cause should be reported as a single 
AE (eg, fever, elevated WBC, cough, abnormal chest x-ray, etc, can all be reported as 
“pneumonia”). 
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 
the relationship of AEs to study drug administration should be determined by the Investigator or 
study physician after thorough consideration of all facts that are available. 
Additional information will be collected regarding muscle-related AEs that may include, but may 
not necessarily be limited to, a muscle-related questionnaire, with questions regarding type of 
muscle-related symptoms, location of the muscle-related AE, and potential cause of the muscle-
related AE.  
11.2.4. 
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. 
11.2.5. 
Relationship 
It is the Investigator’s responsibility to assess the relationship between the study drug and the 
AE.  The degree of “relatedness” of the AE to the study drug 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 for regulatory reporting purposes.  
• Possible: Temporal association, but other etiologies are likely the cause.  However, 
involvement of the study drug cannot be excluded. 
• Probable:  Temporal association, other etiologies are possible but unlikely.  The event 
may respond if the study drug is discontinued. 


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• Definite:  Established temporal association with administration of the study drug with 
no other more probable cause.  Typically, the event should resolve when the study 
drug is discontinued and recur on re-challenge. 
11.2.6. 
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. 
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, 
stabilization of the event(s), or until the patient is lost to follow-up or dies. 
Patients with AEs that are ongoing at study completion or study withdrawal must be followed 
until resolution or for 30 days after the last study visit, whichever comes first (see Section 11.3). 
11.2.7. 
Treatment-Emergent Adverse Events 
TEAE are defined as AEs that begin or worsen after the first dose of study drug. 
11.2.7.1. 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 in-patient 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:  Hospitalization is defined as a formal inpatient admission.  This will not include 
admissions under “23-hour Observational Status”, an Emergency Room visit without hospital 
admission or an Urgent Care visit and therefore, such events will not be recorded as an SAE 
under this criterion.  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 


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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. 
Any clinical endpoints that meet SAE criteria will be reported as SAEs.  The CEC will 
adjudicate clinical endpoints in a blinded fashion, but the DMC will review clinical endpoints 
and SAEs in an unblinded fashion. 
11.2.7.2. Events not Qualifying as Serious Adverse Events 
The following is not considered an SAE and therefore does not need to be reported as such: 
• 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 
11.2.7.3. Clinical Laboratory Assessments as Adverse Events and Serious Adverse Events 
It is the responsibility of the investigator to assess the clinical significance of all abnormal values 
as defined by the list of reference ranges from the central (or local where appropriate) laboratory.  
In some cases, significant changes in lab values within the normal range will require similar 
judgment.  For criteria of reporting abnormal lab values as AE, see Section 11.1.6.3. 
11.3. 
Reporting Serious Adverse Events 
All SAEs, regardless of relationship to study drug, occurring from the time of informed consent 
until 30 days following the last dose of IMP, must be reported by the Principal Investigator or 
designee to the authorized Medical and Safety Services within 24 hours of the Principal 
Investigator or the clinical site becoming aware of the occurrence.  For most patients this will be 
30 days following their Week 52 (Visit T7) visit. All SAEs that the Investigator considers related 
to study drug that occur after the 30-day follow-up of the study period must be reported to the 
Sponsor.  
To report the SAE, complete the SAE information in the clinical electronic data capture (EDC) 
database within 24 hours of becoming aware of the occurrence.  Additional information, such as 
diagnostic test results or hospital discharge summary can be sent via email 
 or via fax (
).  
The Investigator is required to submit SAE reports to the 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 study drug 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. 


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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 
the safety contact information provided on the SAE report form.  
11.3.1. 
Reporting of Serious Adverse Events to Regulatory Authorities 
The Sponsor (and/or designee) is responsible for submitting expedited reports of suspected and 
unexpected serious adverse reactions (SUSARS) to the appropriate regulatory authorities.  All 
Investigators participating in ongoing clinical studies with the study drug will be notified by the 
Sponsor (or designee) of SUSARs.  SUSARS must be communicated as soon as possible to the 
appropriate IRB/IEC by the investigator, as applicable and/or reported in accordance with local 
laws and regulations.  Investigators should provide written documentation of IRB/IEC 
notification for each report to the Sponsor. 
SAEs that are anticipated to occur in this patient population will be collected and reported by the 
Investigator as described in Section 11.3.  However, these events will not be submitted to the 
regulatory authorities as expedited reports unless they meet SUSAR criteria.  These events that 
are considered to be exempt from expedited reporting include the following clinical endpoints: 
• CV death 
• Nonfatal MI 
• Nonfatal stroke 
• Unstable angina requiring hospitalization 
• Coronary revascularization 
• Heart failure requiring hospitalization 
• Noncoronary arterial revascularization 
11.3.2. 
Reporting of Patient Death 
The death of any patient during the study, or within the 30-day follow-up period after they have 
completed the study (regardless of the cause), must be reported as detailed in Section 11.3. 
11.3.3. 
Reports of Pregnancy 
If a female patient becomes pregnant during the study or within 30 days after the last dose of 
study drug, the investigator is to stop dosing with study drug(s) immediately.  A pregnancy is not 
considered to be an AE or an SAE; however, it must be reported to the Sponsor / SAE designee 
using the paper Pregnancy Report Form within the same timelines as an SAE. A pregnancy 
should be followed through to outcome, whenever possible. Once the outcome of the pregnancy 
is known, the paper Pregnancy Outcome Report Form should be completed and reported to the 
Sponsor. Adverse events or SAEs that occur during pregnancy will be assessed and processed 
according to the AE or SAE processes using the appropriate AE CRF.  Patients who become 
pregnant will discontinue IMP immediately and complete the End of Study evaluations. 


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11.4. 
Adverse Events of Special Interest 
Adverse events of special interest (AESI) include metabolic acidosis (clinical laboratories), 
hepatic, muscular (AE and CK evaluation), new onset diabetes/hyperglycemia, renal, 
cardiovascular, and neurocognitive/neurologic events.  Based on previous experience with 
ETC-1002, uric acid and hemoglobin will be closely monitored.  Safety monitoring guidelines 
for hemoglobin is detailed in Section 11.1.6.3.3.  Specific monitoring guidelines are provided in 
the case of AEs uncovered through laboratory evaluations.  Patients are to be queried at each 
study visit regarding changes in cognition and or signs/symptoms of hypoglycemia. 
The protocol procedures included in the bempedoic acid clinical studies are part of standard 
clinical care for patients with primary hyperlipidemia and mixed dyslipidemia and also address 
the potential and theoretic risks of bempedoic acid.  
All bempedoic acid studies will include standard pharmacovigilance including evaluation of 
AEs, PE findings, vital signs, and laboratory assessments.  Cardiovascular events will be 
adjudicated by an independent CEC in accordance with a prespecified charter.  AESI monitoring 
will also include the following:  
• AEs associated with the experiences with bempedoic acid to date: 
Across clinical studies to date, the most frequently reported TEAEs included 
musculoskeletal and connective tissue disorders (back pain, pain in extremity, 
myalgia, arthralgia, and muscle spasms), nervous system disorders (headache), GI 
disorders (nausea and diarrhea), and infections and infestations.  Overall, AEs were 
generally reported with similar incidence between those patients treated with 
bempedoic acid in combination with ezetimibe or statin therapy, ezetimibe, statins, or 
placebo; however, the incidence of headache was higher with bempedoic acid than 
placebo. 
In general, laboratory results showed no clinically significant trends at the data cut-
off for End-of Phase 2.  A total of 7 patients receiving bempedoic acid monotherapy 
or in combination with a statin or ezetimibe experienced repeated and confirmed ALT 
and/or AST >3 × the ULN; in 1 of these patients receiving bempedoic acid 80 mg the 
elevation was assessed by Investigator as not related to study drug because the patient 
tested positive for acute cytomegalovirus (CMV) infection.  One patient receiving 
ezetimibe monotherapy experienced repeated and confirmed ALT and/or AST >3 × 
ULN.  All LFT abnormalities were considered mild to moderate and improved upon 
removal of the study drug.  Clinical chemistries, hematology, vitals, physical 
examinations, and ECGs will be routinely monitored in the bempedoic acid clinical 
program.  
• Potential AEs based on findings in nonclinical models: 
Hypoglycemia and metabolic acidosis led to monkey deaths in preclinical studies.  
Exposures in these studies were >17 times higher than those associated with the 
bempedoic acid 180-mg dose which will be evaluated in this study.  Subsequent 
monkey studies proved that hypoglycemia was reversible with discontinuation of 
study drug and nutritional support.  No cases of either hypoglycemia or metabolic 
acidosis have been identified in Phase 1 or 2 clinical trials to date.  Patients in all 


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clinical trials will be provided with information (in the ICF) regarding the signs and 
symptoms of hypoglycemia including lightheadedness, shakiness, shaking of the 
hands, sweating, tingling, blurred visions, nausea or vomiting, mental confusion, 
difficulty concentrating and drowsiness.  Patients who experience any of these 
symptoms will be instructed to report them to their study doctor.  Diabetes/glycemic 
monitoring plans are Section 11.1.6.4.  Occurrence of metabolic acidosis will be 
monitored by clinical safety laboratory chemistries. 
• AEs that are currently monitored for all experimental lipid-lowering therapies and 
have been associated with previous lipid-lowering therapies:  
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 (see Section 11.1.6.3.1).  
Muscle:  Muscle events have been associated with statins (Thompson 2003) and other 
lipid-lowering therapies and are mentioned in the product information for those 
products.  The exact mechanism in the development of muscle events is unclear.  
Bempedoic acid is a prodrug which needs to be converted by an acyl-CoA synthetase 
(ACS) to a coenzyme A (CoA) ester (ETC-1002-CoA).  The specific ACS known to 
convert bempedoic acid into its active form is not present in skeletal muscle.  This 
suggests that bempedoic acid may not lead to an increase in muscular side effects 
when given in conjunction with statins.  Nonetheless, muscle symptoms through AE 
review, CK elevations, and symptoms of potential myopathy will be closely 
monitored.  More detailed investigation will occur if results exceed 5 x ULN (see 
Section 11.1.6.3.2).  
Diabetes and Hyperglycemia:  New onset diabetes has been associated with the use of 
statins and is dose related.  The product information for statins mentions 
hyperglycemia increased HbA1C and increases in fasting glucose as potential adverse 
reactions.  Hyperglycemia occurred in 10.8% (n = 10) of the placebo treated patients 
vs none of the bempedoic acid 180 mg treated patients in the Phase 2 program.  
Regardless, new onset diabetes through AE monitoring will be captured and 
summarized for this study and across all of the bempedoic acid studies.  Clinical 
safety laboratories will also be evaluated during the studies including HbA1C, and 
fasting glucose.  
Renal:  Nonclinical studies have demonstrated nephrotoxic effects on tubular cells of 
some lipid-modifying agents.  In the Phase 2 program, creatinine elevations >25% 
over baseline occurred in 1 subject in the bempedoic acid 80 mg, 2 in the 180 mg, 
1 in the 180 mg + ezetimibe, 1 in the 240 mg, and 3 in the 240 mg + baseline statin.  
In most cases, this elevation occurred at the end of the study and the values were not 
repeated and the events were not considered related.  In 1 case, repeat values were 
obtained and the subject’s creatinine was returning to baseline by Week 12.  None 
exceeded a serum creatinine >1.8 mg/dL.  No subjects withdrew due an AE of 
increased creatinine.  In the Phase 3 program, repeat evaluation of creatinine will 
occur and patients exceeding protocol-specified values will be withdrawn from study 
medication (see Section 11.1.6.3.2).  Patients will be monitored beyond the 


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conclusion of the study if necessary to follow abnormal renal laboratory values until 
resolution or stabilization.  
Cardiovascular Events:  The occurrence of clinical endpoints will be monitored and 
adjudicated by an independent blinded CEC throughout the bempedoic acid program.  
The details of the monitoring program can be found in the charter of the CEC.  
Standard monitoring will include occurrence of CV AEs, SAEs, both as adjudicated 
by the CEC, standard vital signs, and ECGs.  
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 reports of cognitive impairment (eg, memory loss) associated with 
the use of statin drugs (FDA 2012).  The human brain has a significant requirement 
for cholesterol (Dietschy 2001; Dietschy 2004) and dysregulation of brain cholesterol 
homeostasis has been linked to chronic neurodegenerative disorders, including 
Alzheimer’s disease, Huntington’s disease, Parkinson’s disease, Niemann–Pick 
type C disease and Smith-Lemli-Opitz syndrome (Goedeke 2014).  In the Phase 2 
program, the only disorder in this system organ class (SOC) that occurred more 
commonly in the bempedoic acid treated group was headache. For the ongoing 
program, neurocognitive events will be evaluated by standard PE and adverse 
monitoring. Summarization of events will occur using prespecified Medical 
Dictionary for Regulatory Activities (MedDRA) terms. 
11.5. 
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. 
11.6. 
Clinical Event Committee (CEC) 
A blinded independent expert CEC will adjudicate clinical endpoints including all MACE and 
non-MACE endpoints defined as:  CV death (MACE), non-CV death (non-MACE), nonfatal MI 
(MACE), nonfatal stroke (MACE), hospitalization for unstable angina (MACE), coronary 
revascularization (MACE), non-coronary arterial revascularization (non-MACE), and 
hospitalization for heart failure (non-MACE) using standardized definitions.  Any clinical 
endpoints that meet SAE criteria will be reported as SAEs.  Additional details regarding clinical 
endpoints and clinical endpoint definitions are outlined below and will be included in the CEC 
charter.  The charter will also outline the committee’s composition, meeting timelines, and 
members’ roles and responsibilities.  Clinical endpoints from this study and other studies within 
the bempedoic acid Phase 3 development program will be aggregated to allow for a safety 
assessment across the entire development program. 


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11.7. 
Assessment of Lipid Endpoints 
11.7.1. 
Lipid Parameters 
After randomization, patients will return to clinic every 4 weeks for the first 12 weeks, then 
again 12 weeks later at Week 24 (Visit T5) and at Week 52 (Visit T7).  Clinical laboratory 
samples will be collected and analyzed for calculated LDL-C and lipid and cardiometabolic 
biomarkers including non-HDL-C, HDL-C, TC, apoB, and TG at baseline and all clinic visits for 
evaluation of bempedoic acid effects on lipids and cardiometabolic parameters.  
11.7.2. 
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 6.  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 11.1.6. 
When ECG, vital signs, and laboratory samples are to be collected at the same time point, ECG 
and vital sign measurements will precede laboratory sample collection.  
Table 6: 
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-density lipoprotein cholesterol (HDL-C) 
• 
Triglycerides (TG) 
• 
High-sensitivity C-reactive protein (hs-CRP) 
• 
apoB 


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12. 
STATISTICS 
12.1. 
General Considerations 
The statistical analyses described in this section will be performed as further outlined in a 
separate Statistical Analysis Plan (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. 
12.2. 
Determination of Sample Size 
The primary efficacy endpoint for this study is the percent change from baseline to Week 12 in 
LDL-C.   
The sample size of 500 randomized patients in the bempedoic acid 180 mg group and 
250 randomized patients in the placebo group is expected to provide more than 95% power to 
detect a difference of 15% in the percent change from baseline to Week 12 in LDL-C between 
the bempedoic acid treatment group and the placebo group.  This calculation is based on a 
2-sided t-test at the 5% level of significance (α = 0.05) and a common standard deviation of 15%.  
The sample size of 500 randomized patients in the bempedoic acid 180 mg group and 
250 randomized patients in the placebo group gives a total study sample size of 750.   
12.3. 
Analysis Populations  
The Full Analysis Set (FAS), used for all of the efficacy summaries and analyses, is defined as 
all randomized patients.  The FAS is also known as the intention-to-treat (ITT) set of patients.  
Patients in the FAS will be included in their randomized treatment group, regardless of their 
actual treatment.  
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.  
12.4. 
Disposition, Demographics, and Baseline Characteristics 
Disposition, including reason for withdrawal from the 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. 
12.5. 
Primary Endpoint 
The primary efficacy endpoint is the percent change from baseline to Week 12 in LDL-C.  The 
primary efficacy endpoint will be analyzed using analysis of covariance (ANCOVA), with 
treatment group, CV risk (ASCVD only; HeFH with or without ASCVD) and baseline statin 
intensity (high intensity, moderate intensity, low intensity) as factors and baseline LDL-C as a 


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covariate.  Baseline LDL-C is defined as the mean of the LDL-C values from Week -1 (Visit S3) 
and predose Day 1/Week 0 (Visit T1).  If a repeat lipid measurement is performed at Week -1 
(Visit S3), then baseline will be the mean of the LDL-C values from the second Week -1 
assessment and predose Day 1/Week 0 (Visit T1).  If only one value is available, then that single 
value will be used for baseline.  The ANCOVA will be performed using the FAS, with patients 
included in their randomized treatment group regardless of the treatment they actually received.  
The details of the ANCOVA model and options to correct for unequal variances and group size 
will be described in the SAP. 
Missing data for the primary endpoint will be imputed using a multiple imputation method that 
accounts for treatment adherence. A pattern mixture model (PMM) will be used to specify 
different imputation strategies depending on whether the patient is still on study treatment.  
Imputed datasets will be analyzed using ANCOVA with treatment group, CV risk (ASCVD 
only; HeFH with or without ASCVD) and baseline statin intensity (high intensity, moderate 
intensity, low intensity) as factors and baseline LDL-C as a covariate.  Approximately 
200 imputed datasets will be created, with results from the analysis of each imputed dataset 
combined using Rubin’s method.  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.  A confirmatory analysis using observed data only will also 
be performed for the primary endpoint. Details for PMM and multiple imputation will be 
descried in the SAP. 
12.6. 
Secondary and Tertiary Efficacy Endpoints 
Key secondary efficacy endpoints are also of interest for this study, in terms of controlling the 
overall Type I error rate.  A gatekeeping or stepdown approach will be used to test the primary 
efficacy endpoint and then specific secondary efficacy endpoints sequentially in order to 
preserve the study-wise Type I error rate.  The sequence for the stepdown procedure in this study 
is as follows: 
1. Test the primary efficacy endpoint: percent change from baseline to Week 12 in LDL-C  
2. Test the percent change from baseline to Week 24 in LDL-C 
3. Test the percent change from baseline to Week 12 in non-HDL-C 
4. Test the percent change from baseline to Week 12 in TC 
5. Test the percent change from baseline to Week 12 in apoB 
6. Test the percent change from baseline to Week 12 in hs-CRP   
In this hierarchical testing structure, each hypothesis is tested at a significance level of 0.05, two-
sided.  Statistical significance at each step is required in order to test the next hypothesis.  If the 
primary endpoint meets the criteria for statistical significance, then the percent change from 
baseline to Week 24 in LDL-C will be tested; and so forth. 
In general, change or percent change in lipid parameters at a given time point will be analyzed 
using similar ANCOVA model for the primary endpoint with treatment group, CV risk (ASCVD 
only; HeFH with or without ASCVD) and baseline statin intensity (high intensity, moderate 
intensity, low intensity) as factors and the relevant baseline as a covariate.   


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Baseline for HDL-C, non-HDL-C, TG, and TC will be defined as the mean of the lipid values 
from Week -1 (Visit S3) and predose Day 1/Week 0 (Visit T1).  If a repeat lipid measurement is 
performed at Week -1 (Visit S3), then baseline will be the mean of the lipid values from the 
second Week -1 assessment and predose Day 1/Week 0 (Visit T1).  Baseline for apoB and 
hs-CRP will be defined as the predose Day 1/Week 0 (Visit T1) value.   
Each ANCOVA will be performed using the FAS, with patients included in their randomized 
treatment group regardless of the treatment they actually received.  Same imputation method 
described for the primary endpoint will be used for those secondary endpoints included in the 
step-down procedure, while only observed data analysis will be used for other secondary and 
tertiary endpoints.  For each lipid 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. 
The ANCOVA assumption of normality will be assessed.  If non-normality of the data is found 
at any time point for any parameter, either the data will be transformed so that it is normally 
distributed or a nonparametric test will be considered instead of the planned ANCOVA. 
Percent change from baseline to Week 24 and to Week 52 LDL-C will be analyzed similarly 
with patients in the FAS who did not receive additional lipid-lowering therapy by that time point 
(by Week 24 for the Week 24 analysis; by Week 52 for the Week 52 analysis) included in the 
analyses. Only observed case data will be used (no imputation for missing data). Output from 
each time point will include the LSM and SE for each treatment group, as well as the placebo-
correct LSM, 95% CI, and p-value. 
12.7. 
Additional Post-randomization Adjunctive LDL-lowering or 
Triglyceride-Modifying Therapy 
The number and percent of patients in each treatment group requiring additional (post-
randomization) adjunctive LDL-C or triglyceride-modifying therapy will be summarized.  
Medications and the reasons for their additional treatment (hyperlipidemia vs. 
hypertriglyceridemia) will be summarized separately. 
12.8. 
Safety Endpoints 
The summarization of AEs will include TEAEs.  TEAEs and SAEs will be summarized by SOC, 
severity, and relationship to study drug for each treatment group.  These AE summaries will 
include cumulative incidence (percent of patients experiencing the AE) and patient-year adjusted 
incidence rates.  If appropriate, absolute and relative risk differences will be calculated using 
both cumulative incidence and incidence rates.  Deaths, withdrawal from study treatment due to 
AEs, and withdrawal from the study due to AEs will each be summarized by treatment group. 
Clinical safety laboratories, including hematology, blood chemistry, coagulation, HbA1C, 
glucose, and urinalysis; PE findings; vital signs; ECG readings; and weight will be summarized 
by the value and by change from baseline in the value (where appropriate) at each postbaseline 
time point. 


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Hepatic Safety 
Liver-associated enzymes and TB will be summarized by the value and change from baseline in 
the value, by treatment group and visit.  In addition, the number and percent of patients with 
abnormal values for ALT, AST, and TB will be summarized.  These summaries of patients with 
abnormal values will be performed overall; by normal baseline; and by abnormal baseline for 
each of ALT, AST, and TB. Hy’s law criteria (≥3 × ULN for either ALT or AST, with 
accompanying TB >2 × ULN or patient’s baseline) will also be applied to the data; any potential 
Hy’s law cases will be listed separately.  In the case of patients with Gilbert’s disease, TB will be 
fractionated and the determination of 2 × ULN based upon direct (conjugated) bilirubin.  For 
patients with Gilbert’s Disease 2 × the conjugated bilirubin will be used as the criterion. 
Musculoskeletal Safety 
AEs of muscle-related symptoms will be summarized by treatment group.  CK levels will be 
summarized by the value and change from baseline in the value, by treatment group and visit.  In 
addition, the number and percent of patients with abnormal CK values will be summarized.  
These summaries of patients with abnormal CK will be performed overall; by normal baseline 
CK; and by abnormal baseline CK.  
Diabetes and 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.  Glucose and HbA1C will be monitored at baseline and at Weeks 12, 
24, and 52, and be summarized. 
Renal Safety 
Baseline eGFR will be summarized by treatment group for actual value and for baseline eGFR 
categories.  Shift tables of eGFR category from baseline over the study, will be provided by 
treatment group.  Shift tables of urine protein (negative/positive) from baseline over the study, 
will be provided by treatment group.  Values of CK over the study will be summarized by 
treatment group and by baseline eGFR category.  Finally, muscle-related AEs will be 
summarized by treatment group and by baseline eGFR category. 
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 SOC, severity, and relationship to study drug for each 
treatment group. 
Clinical Endpoints 
Clinical endpoints using standardized definitions will be adjudicated by an independent blinded 
expert CEC for all ongoing Phase 3 studies in the bempedoic acid program.  Investigator-
reported clinical endpoints and adjudicated clinical endpoints will be summarized by event type 
and treatment group.  Additional details regarding the clinical endpoints and their definitions will 
be included in CEC Charter.   


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12.9. 
Pharmacokinetics 
Trough plasma concentrations of bempedoic acid and ESP15228 will be collected and 
summarized from patients prior to dose at Weeks 24 and 52 for use in further developing the 
population PK model. 


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13. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
13.1. 
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 Good Clinical Practice (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, ECGs) required to confirm information 
contained in the eCRFs. 
The monitoring strategy for the study foresees a risk-based monitoring approach, in line with the 
relevant Food and Drug Administration (FDA) and European Medicines Agency (EMA) 
recommendations, and will be described in details by the study-specific risk-based-monitoring 
plan. 
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. 
13.2. 
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.  


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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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14. 
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 13.2 for more details 
regarding the audit process. 


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15. 
ETHICS 
15.1. 
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. 
15.2. 
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. 
15.3. 
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. 
A separate informed consent will be obtained for collecting the genetic blood sample. 
The Principal Investigator(s) must maintain the original, signed ICD.  A copy of the signed ICD 
must be given to the patient. 
15.4. 
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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Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
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16. 
DATA HANDLING AND RECORDKEEPING 
16.1. 
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. 
16.2. 
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. 
16.3. 
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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Amendment 3, 09 May 2017 
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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, x-rays, and 
ECGs).  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 CRF completion guidelines. 


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Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
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17. 
ADMINISTRATIVE CONSIDERATIONS 
17.1. 
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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Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
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Page 90 of 184 
• Guidance for Industry – E6 Good Clinical Practice: Consolidated Guidance: 
http://www.fda.gov/cder/guidance/959fnl.pdf 
17.2. 
Study Administrative Structure 
Investigational medicinal product (IMP) supply chain details can be found in the pharmacy 
manual. 
Bioanalytical Laboratory: 
 
 
Central Laboratory: 
 
 
 
Randomization, IWRS, Statistical Analysis, Study Management and Monitoring, Data 
Management, Medical and Safety Services including Medical Monitoring (see Medical and 
Safety Services below), Programming, and Medical Writing: 
 
 
 
 
 
17.3. 
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 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 91 of 184 
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. 
17.4. 
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. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 92 of 184 
18. 
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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Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
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19. 
LIST OF REFERENCES 
Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, et al. Cholesterol Treatment 
Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL 
cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet. 
2010;376:1670-81. 
Cannon CP, Blazing MA, Guiglian RP, McCagg A, White JA, Theroux P, et al, for the 
IMPROVE-IT Investigators. Ezetimibe added to statin therapy after acute coronary. N Engl J 
Med. 2015;372(25):2387-97. 
Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, et al, for the 
Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial 
Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute 
coronary syndromes. New Engl J Med. 2004;350:1495-504. 
Dietschy JM, Turley SD. Cholesterol metabolism in the brain. Curr Opin Lipidol. 
2001(12):105-12. 
Dietschy JM, Turley SD. Cholesterol metabolism in the central nervous system during early 
development and in the mature animal. J Lipid Res. 2004(45):1375-97. 
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  
Goedeke L, Fernandez-Hernando C. microRNAs: A connection between cholesterol metabolism 
and neurodegeneration. Neurobiol Dis. 2014(72):48-53. 
Goldberg AC, Hopkins PN, Toth PP, Ballantyne CM, Rader DJ, Robinson JG, et al. Familial 
hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: 
clinical guidance from the National Lipid Association Expert Panel on Familial 
Hypercholesterolemia. J Clin Lipidol. 2011;5 (3 Suppl):S1-S8. 
https://rarediseases.org/rare-diseases/familial-hypercholesterolemia/ accessed August 2015. 
http://thefhfoundation.org/about-fh/what-is-fh/ accessed August 2015. 
Jacobson TA for the NLA Task Force on Statin Safety - 2014 update. J Clin Lipidol. 
2014;8:S1-4.  
Kathiresan S, Melander O, Anevski D, Guiducci C, Burtt NP, Roos C, et al. Polymorphisms 
associated with cholesterol and risk of cardiovascular events. New Engl J Med. 
2008:358;12:1240-9. 
Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, et al. Chronic Kidney 
Disease Epidemiology Collaboration. Using standardized serum creatinine values in the 
modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann 
Intern Med. 2006 Aug 15;145:247-54. 


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Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
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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. 
Neil A, Cooper H, Betteridge J, Capps N, McDowell I, Durrington P, et al. Reduction in all-
cause, cancer, and coronary mortality in statin-treated patients with heterozygous familial 
hypercholesterolaemia: a prospective registry study. Eur Heart J. 2008;29:2625-38. 
Nichols M, Townsend N, Scarborough P, Rayner M. Cardiovascular disease in Europe 2014: 
epidemiological update. Eur Heart J. 2014; 35:2950-9. 
Pollex RL, Joy TR, Hegele RA. Emerging antidyslipidemic drugs. Expert Opin Emerg Drugs. 
2008;13(2):363-81. 
Robinson JG. Management of Familial Hypercholesterolemia: A Review of the 
recommendations from the National Lipid Association Expert Panel on Familial 
Hypercholesterolemia. J Managed Care Pharm. 2013;19(2):139-49. 
Robinson JG, Smith B, Maheshwari N, Schrott H. Pleiotropic effects of statins: benefit beyond 
cholesterol reduction: A meta-regression analysis. J Am Coll Cardiol. 2005 Nov 15;46(10):1855-
62. Epub 2005 Oct 24. 
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. 
Stamler J, Wentworth D, Neaton J. Is relationship between serum cholesterol and risk for 
premature death from coronary heart disease continuous and graded? JAMA. Nov 28 
1986;256(20):2823-8. 
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. 
 


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Amendment 3, 09 May 2017 
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20. 
APPENDICES 
Appendix 1: 
Schedule of Events (Subject Visit Schedule) 
Appendix 2: 
Sponsor’s Signature 
Appendix 3: 
Investigator’s Signature 
Appendix 4: 
Dutch Lipid Clinic Network Criteria for Familial Hypercholesterolemia 
Appendix 5: 
Simon Broome Register Diagnostic Criteria Heterozygous Familial 
Hypercholesterolemia 
Appendix 6: 
Summary of Changes Amendment 1 
Appendix 7: 
Summary of Changes Amendment 2 
Appendix 8: 
Summary of Changes Amendment 3 
 


Bempedoic Acid 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
Amendment 3, 09 May 2017 
APPENDIX 1. SCHEDULE OF EVENTS (SUBJECT VISIT SCHEDULE) 
Screen 
Run-in 
Treatment 
Visit 
Sl l.Z 
82 
83 
Tl 
T2 
T3/phone 
T4 
TS 
T6/phone T7/EOS3 
Week 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
-5 
-4 
-1 
0 
4 
8 
12 
24 
36 
52 
Procedure 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 365 
--35± 7 
-28±3 
-7±3 
1 
29±3 
57±3 
85±3 
168±7 
252±7 
±7 
Informed Consent 
x 
Enrolhnent Criteria 
x 
Demographics 
x 
Medical Histo1y 
x 
HeFH Status Detennination 
x 
Concomitant Medications 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Adverse Event Recording 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Physical Exam 
x 
x 
Weight4 
x 
x 
x 
x 
x 
x 
Height/BM! 
x 
12-Lead ECG5 
x 
x 
Vital Signs6 
x 
x 
x 
x 
x 
x 
x 
x 
7 
Serology 
x 
Serum Pregnancy and/or FSH8 
x 
Urine Pregnancy Test8 
x 
TSH 
x 
Clinical Safety Labs9 
x 
x 
x 
x 
x 
x 
Basic Fasting Lipids10 
x 
x 
x 
x 
x 
x 
x 
HbA1c 
x 
x 
x 
x 
x 
apoB 
x 
x 
x 
x 
hs-CRP 
x 
x 
x 
x 
Diet and exercise counseling11 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Plasma PK 
x 
x 
Establish Patient Eligibility 
x 
Randomization 
x 
IWRS Contact 
x 
x 
x 
x 
x 
x'2 
Single-Blind Drug Dispensing 
x 
Double-blind Drug Dispensing13 
x 
x 
x 
Drug Return/Compliance 
x 
x 
x 
x 
x 
x 
Schedule next visit 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Confidential 
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Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
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NOTE: For patients who withdraw from IMP treatment, they will continue to have visits according to the protocol schedule. Safety 
assessments should include clinical safety and basic lipid laboratories (except for apoB and hs-CRP), adverse events, PE, vital signs, 
and ECGs. For patients who withdraw from IMP treatment, but refuse to come to the clinic for assessments, assessments will take 
place 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). 
1 An optional visit between Visits S1 and S2 may be completed if patient fails to meet TG entry criterion. If this optional basic fasting 
(minimum of 10 hours) lipid value visit is completed, the repeat lipid value will be used to determine eligibility. 
2 An optional visit between Visits S1 and S2 may be completed if the patient’s DBP and/or 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. An optional 
visit between Visit S1 and S2 may be completed to determine eligibility if the patient’s eGFR, ALT, AST, and/or TB meet exclusion 
criteria levels. If this optional visit is completed, the repeated value will be used to determine eligibility. 
3 All procedures will be completed for all patients at either End of Study (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).  
5 Single 12-lead ECG will be collected prior to any blood sample collection. 
6 Vital signs will include DBP, SBP, and 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  
8 Serum pregnancy test completed in premenopausal women only.  FSH test is completed in women <55 years old and >1 year without 
menses. Urine pregnancy test in women of childbearing potential just prior to randomization.  
9 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits. Coagulation is included at Screening (Visit S1) 
for all patients, Baseline (Visit T1) and 3-5 days after Visit T1 only if on anticoagulants).  Please refer to laboratory manual for 
detailed schedule of tests.  A local laboratory may be used for assessment at 3-5 days after Visit T1. 
10 Basic fasting (minimum of 10 hours) lipids include total cholesterol, calculated LDL-C, HDL-C, non-HDL-C, and triglycerides.  
11 Diet and exercise counseling per local and/or regional guidelines for the management of hyperlipidemia. 
12 IWRS contact at either an early withdrawal or an EOS visit to register study discontinuation visit date.  
13 Depending upon the length of time between visits, 1 or 2 bottles of study medication will be dispensed as instructed by IWRS. 
14 If patient is discontinuing treatment and completing the EOS visit, but will be continuing in the study either by returning to clinic or 
by phone, continue to schedule study visits for the patient according to the protocol Schedule of Events 
 


Bempedoic Add 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
Amendment 3, 09 May 2017 
APPENDIX 2. SPONSOR'S SIGNATURE 
Study Title: 
A Long-term, Randomized, Double-blind, Placebo-controlled, Multicenter 
Study to Evaluate the Efficacy of Bempedoic Acid (ETC-1002) in Patients 
with Hyperlipidemia at High Cardiovascular Risk Not Adequately 
Controlled by Their Lipid-Modifying Therapy 
Study Number: 
1002-047 
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: 
\ O- ~ 0-'} 
Z..ol~ 
Confidential 
Page 98 of 184 


Bempedoic Acid 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
Amendment 3, 09 May 2017 
Study Title: 
Study Number: 
A Long-term, Randomized, Double-blind, Placebo-controlled, Multicenter 
Study to Evaluate the Efficacy of Bempedoic Acid (ETC- I 002) in Patients 
with Hyperlipidemia at High Cardiovascular Risk Not Adequately 
Controlled by Their Lipid-Modifying Therapy 
1002-047 
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: tJt/ 1141:J ZOI± 
Confidential 
Page 99 of 184 


Bempedoic Acid
Esperion Therapeutics, Inc.
Clinical Study Protocol 1002-047
Amendment 3, 09 May 2017
Confidential
Page 100 of 184
Study Title:
A Long-term, Randomized, Double-blind, Placebo-controlled, Multicenter 
Study to Evaluate the Efficacy of Bempedoic Acid (ETC-1002) in Patients 
with Hyperlipidemia at High Cardiovascular Risk Not Adequately 
Controlled by Their Lipid-Modifying Therapy
Study Number:
1002-047
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:


Bempedoic Acid 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-04 7 
Amendment 3, 09 May 2017 
Study Title: 
Study Number: 
A Long-term, Randomized, Double-blind, Placebo-controlled, Multicenter 
Study to Evaluate the Efficacy of Bempedoic Acid (ETC-1002) in Patients 
with Hyperlipidemia at High Cardiovascular Risk Not Adequately 
Controlled by Their Lipid-Modifying Therapy 
1002-047 
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: 5-9-1+ 
Confidential 
Page 101 of 184 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 102 of 184 
APPENDIX 3. INVESTIGATOR’S SIGNATURE 
Study Title: 
A Long-term, Randomized, Double-blind, Placebo-controlled, Multicenter 
Study to Evaluate the Efficacy of Bempedoic Acid (ETC-1002) in Patients 
with Hyperlipidemia at High Cardiovascular Risk Not Adequately 
Controlled by Their Lipid-Modifying Therapy 
Study Number: 
1002-047 
 
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 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 103 of 184 
APPENDIX 4. DUTCH LIPID CLINIC NETWORK CRITERIA FOR 
FAMILIAL HYPERCHOLESTEROLEMIA 
Dutch Lipid Clinic Network Diagnostic Criteria for Familial Hypercholesterolemia1,2,3 
Diagnostic Scoring for Familial Hypercholesterolemia 
 
CRITERIA 
POINTS 
POSSIBLE 
Family History 
First-degree relative with known prematurea coronary and vascular disease, OR 
First-degree relative with known LDL-C above the 95th percentile 
1 
First-degree relative with tendinous xanthomata and/or arcus cornealis, OR 
Children aged less than 18 years with LDL-C level above the 95th percentile 
2 
Clinical History 
Patient with prematurea coronary artery disease 
2 
Patient with prematurea cerebral or peripheral artery disease 
1 
Physical Examination 
Tendinous xanthomata 
6 
Arcus cornealis prior to age 45 years 
4 
Cholesterol Levels mg/dL (mmol/L) 
LDL-C ≥330 mg/dL (≥8.5 mmol/L) 
8 
LDL-C 250-329 mg/dL (6.5-8.4 mmol/L) 
5 
LDL-C 190-249 mg/dL (5.0-6.4 mmol/L) 
3 
LDL-C 155-189 mg/dL (4.0-4.9 mmol/L) 
1 
DNA Analysis 
Functional mutation in the LDLR, apoB, or PCSK9 gene 
8 
apoB = apolipoprotein B; LDL-C = low-density lipoprotein cholesterol; LDLR = low-density lipoprotein 
receptor; FH = familial hypercholesterolemia; PCSK9 = Proprotein convertase subtilisin/kexin type 9. 
a Premature ≤55 years in men; ≤60 years in women 
Scoring: 
Diagnosis (Diagnosis Based Upon Total Score Obtained) 
Definite Familial Hypercholesterolemia 
>8 
Probable Familial Hypercholesterolemia 
6-8 
Possible Familial Hypercholesterolemia 
3-5 
Unlikely Familial Hypercholesterolemia 
<3 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 104 of 184 
References: 
1. Austin MA, Hutter CM, Zimmern RL, Humphries SE. Genetic causes of monogenic 
heterozygous familial hypercholesterolemia: a HuGE prevalence review. Am J 
Epidemiol. 2004;160:407-20. 
2. Haase A, Goldberg AC. Identification of people with heterozygous familial 
hypercholesterolemia. Curr Opin Lipidol. 2012;23:282-9. 
3. Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia is 
underdiagnosed and undertreated in the general population: guidance for clinicians to 
prevent coronary heart disease: consensus statement of the European Atherosclerosis 
Society. Eur Heart J. 2013;34:2478-3490a. 
 


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Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 105 of 184 
APPENDIX 5. SIMON BROOME REGISTER DIAGNOSTIC CRITERIA 
FOR HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA 
Simon Broome Diagnostic Criteria for Familial Hypercholesterolemia1  
Definite Familial Hypercholesterolemia: 
• Required laboratory = high cholesterol levels: 
− Adult = Total cholesterol levels >290 mg/dL (7.5 mmol/L) or LDL-C 
>190 mg/dL (4.9 mmol/L) 
− Child less than 16 years of age = Total cholesterol levels >260 mg/dL 
(6.7 mmol/L) or LDL-C >155 mg/dL (4.0 mmol/L) 
• Plus at least one of the two: 
− Plus physical finding = tend xanthomas, or tendon xanthomas in first or second 
degree relative 
OR 
− DNA-based evidence of an LDL-receptor mutation, familial defective apoB-100, 
or PCSK9 mutation 
Possible Familial Hypercholesterolemia: 
• Required laboratory = high cholesterol levels: 
− Adult = Total cholesterol levels >290 mg/dL (7.5 mmol/L) or LDL-C 
>190 mg/dL (4.9 mmol/L) 
− Child less than 16 years of age = Total cholesterol levels >260 mg/dL 
(6.7 mmol/L) or LDL-C >155 mg/dL (4.0 mmol/L) 
• Plus at least one of the two: 
− Family history of myocardial infarction at: 
▪ 
Age 60 years or younger in first degree relative 
▪ 
Age 50 years or younger in second degree relative 
OR 
− Family history of elevated total cholesterol 
▪ 
Greater than 290 mg/dL (7.5 mmol/L) in adult first or second degree relative 
▪ 
Greater than 260 mg/dL (6.7 mmol/L) in child, brother or sister aged younger 
than 16 years 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 106 of 184 
References: 
1. Austin MA, Hutter CM, Zimmern RL, Humphries SE. Genetic causes of monogenic 
heterozygous familial hypercholesterolemia: a HuGE prevalence review. Am J 
Epidemiol. 2004;160:407-20. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 107 of 184 
APPENDIX 6. SUMMARY OF CHANGES AMENDMENT 1 
 
SUMMARY OF CHANGES 
CLINICAL STUDY PROTOCOL 
Study Number: 
1002-047 
Study Title: 
A Long-term Randomized, Double-blind, Placebo-
controlled, Multicenter Study to Evaluate the Efficacy of 
Bempedoic Acid (ETC-1002) in Patients with 
Hyperlipidemia at High Cardiovascular Risk Not 
Adequately Controlled by Their Lipid-Modifying Therapy 
Protocol Version Incorporating 
Current Summary of Changes: 
Amendment 1:  18 January 2017 
Preceding Protocol Version: 
Original Protocol:  22 September 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 
The protocol was amended for the following: 
• Added a line for Amendment 1 version and date to reflect amendment version details. 
• Under Inclusion Criteria, revised the definition of true abstinence to reflect guidance 
from the Heads of Medicines Agency. 
• Removed date within the body of the text on all pages within Appendix 2 as the date 
is included in the header 
• Changed names and titles of Sponsor representatives providing signage on the 
protocol amendment 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 108 of 184 
CHANGE 1 REVISION OF SPONSOR CONTACT AND PROTOCOL VERSION 
INFORMATION 
Location: 
Title Page; Sponsor Contact and Version 
Original Text: 
Sponsor Contact: 
 
 
New text: 
Sponsor Contact: 
 
 
Original Text: 
 
Version 
Date 
 
 
Original Protocol: 
22 September 2016 
 
New Text: 
 
Version 
Date 
 
 
Amendment 1: 
18 January 2017 
 
 
CHANGE 2 REVISION OF INCLUSION CRITERIA  
Location: 
Synopsis, Diagnosis and criteria for patient eligibility, Inclusion Criteria, and  
Section 7.1, Subject Inclusion Criteria 
Original Text: 
4. Women must be either: 
• Naturally postmenopausal (as reported by the patient, defined as greater than 55 years 
and ≥1 year without menses, <55 years and ≥1 year without menses with follicle-
stimulating hormone (FSH) ≥40.0 IU/L), or surgically sterile including hysterectomy, 
bilateral oophorectomy, or tubal ligation or;  
• Women of childbearing potential must be willing to use 1 acceptable method of birth 
control.  The minimal requirement for adequate contraception it is that it should be 
started on Day 1, continuing during the study period, and for at least 30 days after the 
last dose of study drug.  Acceptable methods of birth control include: oral birth 
control medications; placement of an intrauterine device (IUD) 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; or true abstinence (not including periodic abstinence such as calendar, 
ovulation, symptothermal, postovulation methods, or withdrawal). 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 109 of 184 
There are no protocol-specific birth control requirements for men with partners who are 
able to become pregnant. 
New Text: 
4. Women must be either: 
• Naturally postmenopausal (as reported by the patient, defined as greater than 55 years 
and ≥1 year without menses, <55 years and ≥1 year without menses with follicle-
stimulating hormone (FSH) ≥40.0 IU/L), or surgically sterile including hysterectomy, 
bilateral oophorectomy, or tubal ligation or;  
• Women of childbearing potential must be willing to use 1 acceptable method of birth 
control.  The minimal requirement for adequate contraception should be started on 
Day 1, continuing during the study period, and for at least 30 days after the last dose 
of study drug.  Acceptable methods of birth control include: oral birth control 
medications; placement of an intrauterine device (IUD) 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; 
or true abstinence when this is in line with the preferred and usual lifestyle of the 
subject (not including periodic abstinence [eg, such as calendar, ovulation, 
symptothermal, postovulation methods, or withdrawal)], declaration of abstinence 
for the duration of the 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. 
 
CHANGE 3 REMOVED FINAL DATE 
Location:  
Appendix 2:  Final Date, all pages within Appendix 2 
Original text: 
Final Date: 
22 September 2016 
New text: 
Final Date: 
22 September 2016 
 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 110 of 184 
CHANGE 4 CHANGE IN SPONSOR REPRESENTATIVES PROVIDING PROTOCOL 
SIGNAGE 
Location:  
Appendix 2:  Sponsor Signatures 
Original text: 
Signed:  
Date:  
 
 
 
 
New text: 
Signed:  
Date:  
 
 
 
 
 
Original text: 
Signed:  
Date:  
 
 
 
 
New text: 
Signed:  
Date:  
 
 
 
 
 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 111 of 184 
APPENDIX 7. SUMMARY OF CHANGES AMENDMENT 2 
 
SUMMARY OF CHANGES 
CLINICAL STUDY PROTOCOL 
Study Number: 
1002-047 
Study Title: 
A Long-term, Randomized, Double-blind, Placebo-
controlled, Multicenter Study to Evaluate the Efficacy of 
Bempedoic Acid (ETC-1002) in Patients with 
Hyperlipidemia at High Cardiovascular Risk Not 
Adequately Controlled by Their Lipid-Modifying Therapy 
Protocol Version Incorporating 
Current Summary of Changes: 
Amendment 2:  22 March 2017 
Preceding Protocol Version: 
Amendment 1:  18 January 2017 
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 
The protocol was amended for the following: 
• Added a line for Amendment 2 version and date to reflect amendment version details. 
• Updated text pertaining to bempedoic acid mechanism of action based on new 
information. 
• Reduced planned patient enrollment from 750 to 525 with 350 randomized to 
bempedoic acid 180 mg and 175 randomized to matching placebo.  Reducing sample 
size has no impact on the statistical power with respect to the efficacy endpoints as 
this study was originally over-sized to provide a higher number for the exposure 
dataset.  The sample size of 350 randomized patients in the bempedoic acid 180 mg 
group and 175 randomized patients in the placebo group is expected to provide more 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 112 of 184 
than 95% power to detect a difference of 15% in the percent change from baseline to 
Week 12 in LDL-C between the bempedoic acid treatment group and the placebo 
group.  This calculation is based on a 2-sided t-test at the 5% level of significance 
(α = 0.05) and a common standard deviation of 15%.  Text and figures where patient 
numbers are presented were updated accordingly. 
• Removed the requirement that strata (statin dose and patient status) could not be 
capped in order to ensure adequate numbers of patient characteristics if imbalance 
occurs. 
• Revised secondary and tertiary endpoints as well as added safety endpoints to more 
accurately describe statistical testing and analysis. 
• Added additional clinical and telephone visits for patients taking simvastatin 40 mg 
based on a request from the Food and Drug Administration (FDA). 
• Added implantable, injectable, or topical method as allowable forms of hormonal 
contraception.  
• Added requirement that women use 2 rather than 1 form of acceptable contraception 
based on a request from the European Heads of Medicines Agency’s Voluntary 
Harmonization Procedure review of another Esperion sponsored protocol.  This 
amendment is to maintain consistency across protocols and is not based on any new 
data with bempedoic acid. 
• Added additional fasting LDL-C assessment (Week -1 (Visit S3) ≥70 mg/dL 
(1.8 mmol/L) after the Run-in period to inclusion criteria.  Removed the allowance of 
repeating a screening LDL-C measurement after Visit S1. 
• Clarified the timing of the collection of lipid values with reference to PCSK9 
inhibitor injections in order to ensure lipid values are obtained at trough levels of 
PCSK9. 
• Further defined inclusion criteria around peripheral arterial disease and 
cerebrovascular atherosclerotic disease. 
• Based on a request from the FDA, added eGFR <45 mL/min/1.73m2 in patients 
taking simvastatin as exclusionary. 
• Based on the extremely long half-live of experimental siRNA inhibitor, Inclisiran, 
excluded patients who have enrolled in a study of an experimental siRNA inhibitor of 
PCSK9. 
• Clarified time period during which subjects should not intend to become pregnant. 
• Altered the 3-month time period for not using the following drugs prior to screening 
based on the half-life of these medications:  expanded mipomersen to 6 months and 
reduced simvastatin to 4 weeks as well as reduced the time period for use of obesity 
medications from 3 months to 4 weeks prior to randomization. 
• Removed collection of optional genetic sampling. 
• Removed collection of reserve samples. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 113 of 184 
• Removed collection of pharmacokinetic (PK) sample collection on Day 1 and 
clarified that collection needs to be prior to dosing at visits where PK samples are 
collected. 
• Added windows (eg, ± 3 or ± 7 days) to all visits.   
• Removed manufacturing contact details from the protocol and indicated the details 
will be described in the pharmacy manual. 
• Based on a request from the FDA, the monitoring and management of CK values for 
asymptomatic patients was modified.    
• Revised statistical sections to clarify level of significance, standard deviation, and 
methods for imputation of missing data. 
• Added details to clarify the time period and reporting process for collection of AEs 
throughout the protocol as required.   
• Added the following sections to the protocol: 
− Definition of Serious Adverse Event Events or Outcomes not Qualifying as 
Serious Adverse Events 
− Clinical Laboratory Assessments as Adverse Events and Serious Adverse 
Events 
• Made administrative changes throughout the protocol where required to correct 
inconsistencies, add clarification, or correct errors. 
 


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Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 116 of 184 
5.2.3 
Tertiary Endpoints 
Tertiary efficacy endpoints are of interest: 
1. Absolute cChange and percent change from baseline to Week 52 in LDL-C 
2. Percent change from baseline to Weeks 24 and 52 in non-HDL-C, TC, apoB, and hs-CRP 
3. Percent change from baseline to Weeks 12, 24, and 52, in TG and HDL-C 
5.2.4 
Safety Endpoints 
1. Patient incidence to TEAE 
2. Safety laboratory values and vital signs 
3. Cardiovascular event rates  
 
CHANGE 4 
SUBJECT INCLUSION CRITERIA REVISIONS 
Location: 
Section 2, Synopsis; Section 7.1, Subject Inclusion Criteria 
Original Text: 
1. Provision of written informed consent prior to any study-specific procedure 
2. Age ≥18 years or legal age of majority based on regional law, whichever is greater at 
Week -5 (Visit S1) 
3. Men and nonpregnant, nonlactating women.   
4. Women must be either: 
• Naturally postmenopausal (as reported by the patient, defined as greater than 55 years 
and ≥1 year without menses, <55 years and ≥1 year without menses with follicle-
stimulating hormone (FSH) ≥40.0 IU/L), or surgically sterile including hysterectomy, 
bilateral oophorectomy, or tubal ligation or;  
• Women of childbearing potential must be willing to use 1  2 acceptable methods of 
birth control.  The minimal requirement for adequate contraception it is that it should 
be started on Day 1, continuing during the study period, and for at least 30 days after 
the last dose of study drug.  Acceptable methods of birth control include: oral birth 
control medications; placement of an intrauterine device (IUD) 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; or 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 the 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 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 117 of 184 
5. Fasting LDL-C (minimum of 10 hours) value at Week -5 (Visit S1) ≥100 mg/dL 
(2.6 mmol/L)  
Note:  LDL-C may be repeated 1 time with the screening period extended up to 4 weeks.  
For those patients who have a repeat LDL-C, the mean of the first value and the repeat 
value will be used to determine eligibility. 
6. Have high CV risk that is defined as either: 
• Diagnosis of HeFH.  Diagnosis must be made by either genotyping or by clinical 
assessment using either the World Health Organization (WHO) criteria/Dutch Lipid 
Clinical Network Criteria with a score that is >8 points (see Appendix 4) or the 
Simon Broome Register Diagnostic Criteria with an assessment of ‘Definite HeFH’ 
(see Appendix 5).  Patients with a diagnosis of HeFH may or may not have 
established CHD or CHD risk equivalents. 
OR 
• Have ASCVD (with established CHD or CHD risk equivalents) 
Documented history of CHD (includes 1 or more of the following): 
− Acute MI 
− Silent MI 
− Unstable angina 
− Coronary revascularization procedure (eg, percutaneous coronary intervention 
[PCI] or coronary artery bypass graft [CABG] surgery) 
− Clinically significant CHD diagnosed by invasive or non-invasive testing (such as 
coronary angiography, stress test using treadmill, stress echocardiography or 
nuclear imaging) 
Documented CHD risk equivalents (includes 1 or more of the following criteria):   
− Peripheral arterial disease  
− Previous ischemic stroke with a focal ischemic neurological deficit that persisted 
more than 24 hours, considered as being of atherothrombotic origin.  Computed 
tomography (CT) or magnetic resonance imaging (MRI) must have been 
performed to rule out hemorrhage and non-ischemic neurological disease 
Note:  Patients with T2DM are allowed in this study; however, for this study 
T2DM is not considered a CHD risk equivalent 
7. Be on maximally tolerated lipid-modifying therapy, including a maximally tolerated 
statin either alone or in combination with other lipid-lowering therapies, at stable doses 
and regimens for at least 4 weeks prior to screening (6 weeks for fibrates; however, 
gemfibrozil is not allowed as per co-administration instructions defined in the statin 
label).  Maximally tolerated statin includes statin regimens other than daily dosing, 
including no to very low doses, but reasons for not using high-intensity statin dosing 
must be documented.  


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 118 of 184 
A patient’s maximally tolerated lipid-modifying therapy will be determined by the 
investigator using their medical judgment and available sources, including the patient’s 
self-reported history of lipid-modifying therapy.  
Note:  Patients can be on any available lipid-modifying therapy with the exception of the 
exclusions listed below as long as they have been stable for 4 weeks prior to Screening 
Visit S1 and are taken at a consistent time each day. In the case of PCSK9 inhibitor use, 
the patient must have received 3 stable doses and all lipid values obtained 1-2 days prior 
to their next dose.  Patients must have not discontinued investigational or commercial 
PCSK9 inhibitor within 4 months prior to Screening Visit S1. 
New Text: 
1. Provision of written informed consent prior to any study-specific procedure 
2. Age ≥18 years or legal age of majority based on regional law, whichever is greater at 
Week -5 (Visit S1) 
3. Men and nonpregnant, nonlactating women.   
4. Women must be either: 
• Naturally postmenopausal (as reported by the patient, defined as greater than 55 years 
and ≥1 year without menses, <55 years and ≥1 year without menses with follicle-
stimulating hormone (FSH) ≥40.0 IU/L), or surgically sterile including hysterectomy, 
bilateral oophorectomy, or tubal ligation or;  
• Women of childbearing potential must be willing to use 1  2 acceptable methods of 
birth control (unless they have agreed to follow the definition of true abstinence).  
The minimal requirement for adequate contraception it is that it should be started on 
Day 1, continuing during the study period, and for at least 30 days after the last dose 
of study drug.  Acceptable methods of birth control include: oral, implantable, 
injectable, or topical birth control medications; placement of an intrauterine device 
(IUD) 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; or 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 
the 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. 
5. Fasting LDL-C (minimum of 10 hours) value at Week -5 (Visit S1) ≥100 mg/dL 
(2.6 mmol/L) and fasting LDL-C value at Week -1 (Visit S3) ≥70 mg/dL (1.8 mmol/L) 
Note:  LDL C may be repeated 1 time with the screening period extended up to 4 weeks.  
For those patients who have a repeat LDL C, the mean of the first value and the repeat 
value will be used to determine eligibility. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 119 of 184 
6. Have high CV risk that is defined as either: 
• Diagnosis of HeFH.  Diagnosis must be made by either genotyping or by clinical 
assessment using either the World Health Organization (WHO) criteria/Dutch Lipid 
Clinical Network Criteria with a score that is >8 points (see Appendix 4) or the 
Simon Broome Register Diagnostic Criteria with an assessment of ‘Definite HeFH’ 
(see Appendix 5).  Patients with a diagnosis of HeFH may or may not have 
established CHD or CHD risk equivalents. 
OR 
• Have ASCVD (with established CHD or CHD risk equivalents) 
Documented history of CHD (includes 1 or more of the following): 
− Acute MI 
− Silent MI 
− Unstable angina 
− Coronary revascularization procedure (eg, percutaneous coronary intervention 
[PCI] or coronary artery bypass graft [CABG] surgery) 
− Clinically significant CHD diagnosed by invasive or non-invasive testing (such as 
coronary angiography, stress test using treadmill, stress echocardiography or 
nuclear imaging) 
Documented CHD risk equivalents (includes 1 or more of the following criteria): 
− Symptomatic peripheral arterial disease (PAD) defined as  
○ peripheral vascular disease with symptoms of claudication or resting limb 
ischemia with either ankle brachial index <0.9 performed by a vascular lab 
or 
○ angiogram (including computed tomographic angiography [CTA]) showing 
≥50% stenosis or 
○ peripheral arterial revascularization (surgical or percutaneous) occurring 
greater than 90 days prior to Visit S1 or 
○ abdominal aortic aneurysm confirmed by imaging or aortic aneurysm repair 
occurring greater than 90 days prior to Visit S1 or 
○ lower extremity amputation due to peripheral vascular disease occurring 
greater than 90 days prior to Visit S1 
− Cerebrovascular atherosclerotic disease defined by: 
○ Previous iIschemic stroke occurring greater than 90 days prior to Visit S1 or 
○ Carotid endarterectomy, carotid stenting, or more than 70% stenosis in a 
carotid artery determined by carotid ultrasound or angiogram occurring 
greater than 90 days prior to Visit S1.  with a focal ischemic neurological 
deficit that persisted more than 24 hours, considered as being of 


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atherothrombotic origin. Computed tomography (CT) or magnetic resonance 
imaging (MRI) must have been performed to rule out hemorrhage and non
ischemic neurological disease 
Note:  Patients with T2DM are allowed in this study; however, for this study 
T2DM is not considered a CHD risk equivalent 
7. Be on maximally tolerated lipid-modifying therapy, including a maximally tolerated 
statin either alone or in combination with other lipid-lowering therapies, at stable doses 
and regimens for at least 4 weeks prior to screening (6 weeks for fibrates; however, 
gemfibrozil is not allowed as per co-administration instructions defined in the statin 
label).  Maximally tolerated statin includes statin regimens other than daily dosing, 
including no to very low doses, but reasons for not using high-intensity statin dosing 
must be documented.  
A patient’s maximally tolerated lipid-modifying therapy will be determined by the 
investigator using their medical judgment and available sources, including the patient’s 
self-reported history of lipid-modifying therapy.  
Note:  Patients can be on any available lipid-modifying therapy with the exception of the 
exclusions listed below as long as they have been stable for 4 weeks prior to Screening 
Visit S1 and are taken at a consistent time each day. In the case of PCSK9 inhibitor use, 
the patient must have received 3 stable doses. It is important that lipid values are 
measured at PCSK9i trough levels.  Therefore, study visits should be scheduled in 
accordance with the patient’s PCSK9i injection regimen so that measurement of lipid 
values for all visits occurs before the PCSK9i injection but not greater than 48 hours 
before the next scheduled PCSK9i injection. and all lipid values obtained 1 2 days prior 
to their next dose.  Patients must have not who have discontinued investigational or 
commercial PCSK9 inhibitor must have had their last dose at least within 4 months 
prior to Screening Visit S1. 
 
CHANGE 5 
SUBJECT EXCLUSION CRITERIA REVISIONS 
Location:  
Section 2, Synopsis; Section 7.2, Subject Exclusion Criteria 
Original Text: 
1. Total fasting (minimum of 10 hours) triglyceride ≥500 mg/dL (5.6 mmol/L) at Week -5 
(Visit S1) 
Note:  TG may be repeated 1 time with the screening period extended up to 4 weeks.  For 
those patients who have a repeat TG, the repeat value will be used to determine 
eligibility. 


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2. Renal dysfunction or nephritic syndrome or a history of nephritis, including estimated 
glomerular filtration rate (eGFR) (using central laboratory determined Modification of 
Diet in Renal Disease [MDRD] formula) <30 mL/min/1.73m2 at Week -5 (Visit S1) 
(Levey 2006).  
Note: At the discretion of the investigator, the screening period may be extended up to 
4 weeks for a single repeat eGFR.  For those patients who have a repeat eGFR, the repeat 
value will be used to determine eligibility. 
New Text: 
1. Total fasting (minimum of 10 hours) triglyceride ≥500 mg/dL (5.6 mmol/L) at Week -5 
(Visit S1) 
Note:  TG may be repeated 1 time with the screening period extended up to 4 weeks 
between Visits S1 and S2.  For those patients who have a repeat TG, the repeat value will 
be used to determine eligibility. 
2. Renal dysfunction or nephritic syndrome or a history of nephritis, including estimated 
glomerular filtration rate (eGFR) (using central laboratory determined Modification of 
Diet in Renal Disease [MDRD] formula) <30 mL/min/1.73m2 at Week -5 (Visit S1) 
(Levey 2006).  In patients taking simvastatin 40 mg, eGFR <45 mL/min/1.73 m2 is 
exclusionary. 
Note: At the discretion of the investigator, the screening period may be extended up to 
4 weeks for a single repeat eGFR.  For those patients who have a repeat eGFR, the repeat 
value should be obtained between Visits S1 and S2 and will be used to determine 
eligibility. 
Original Text: 
5. Uncontrolled hypertension, defined as sitting systolic blood pressure (SBP) ≥160 mmHg 
and diastolic blood pressure (DBP) ≥100 mmHg after sitting quietly for 5 minutes.   
Note: If the initial blood pressure (BP) values meet or exceed the specified level, an 
additional BP assessment may be completed.  If the systolic or the diastolic values 
continue to meet or exceed the threshold, the patient may not continue screening.  
However, at the discretion of the Investigator, the screening period may be extended up 
to 4 weeks to allow for a repeat qualifying BP assessment following adjustment of BP 
medication(s), provided that the patient has been on a stable dose of the BP medication 
for a minimum of 2 weeks prior to randomization and the repeat BP measurements do not 
meet the exclusion criteria. 
New Text 
5. Uncontrolled hypertension, defined as sitting systolic blood pressure (SBP) ≥160 mmHg 
and diastolic blood pressure (DBP) ≥100 mmHg after sitting quietly for 5 minutes.   
Note: If the initial blood pressure (BP) values meet or exceed the specified level, an 
additional BP assessment may be completed.  If the systolic or the diastolic values 
continue to meet or exceed the threshold, the patient may not continue screening.  
However, at the discretion of the Investigator, the screening period (between Visits S1 
and S2) may be extended up to 4 weeks to allow for a repeat qualifying BP assessment 


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following adjustment of BP medication(s), provided that the patient has been on a stable 
dose of the BP medication for a minimum of 2 weeks prior to randomization and the 
repeat BP measurements do not meet the exclusion criteria. 
Original Text: 
14. Blood donation, blood transfusion for any reason, participation in a clinical study with 
multiple blood draws, major trauma, or surgery with or without blood loss within 30 days 
prior to randomization 
15. Use of any experimental or investigational drugs within 30 days prior to screening. 
16. Previous enrollment in a bempedoic acid clinical study.   
17. Use of any of the following drugs within 3 months prior to screening or a plan to use 
these drugs during the study:  
• New or planned dose changes of systemic corticosteroids.  Stable doses and topical 
steroids allowed. 
• Requirement for simvastatin >40 mg, mipomersen or lomitapide or apheresis therapy 
• Planned initiation of the following drugs during the clinical trial or changes to the 
following drugs prior to randomization: 
− Hormone replacement (6 weeks prior to randomization) 
− Thyroid replacement (6 weeks prior to randomization) 
− Diabetes medications (4 weeks prior to randomization) 
− Obesity medication (3 months prior to randomization) 
− Red yeast rice extract-containing products are not allowed (2 weeks prior to 
screening) 
18. Lack of adherence (ie, less than 80% of planned doses) with IMP (single-blind placebo) 
during the Run-in Period. 
19. Lack of tolerance with IMP (single-blind placebo) during the Run-in Period. 
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. An employee or contractor of the facility conducting the study, or a family member of the 
Principal Investigator, Co-Investigator, or Sponsor. 
22. Pregnant, breastfeeding, or intending to become pregnant. 
New Text:  
14. Blood donation, blood transfusion for any reason, participation in a clinical study with 
multiple blood draws, major trauma, or surgery with or without blood loss within 30 days 
prior to randomization 
15. Use of any experimental or investigational drugs within 30 days prior to screening.  
16. Previous enrollment in a bempedoic acid clinical study.   


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17. Use of any of the following drugs within 3 months prior to screening or a plan to use 
these drugs during the study:  
• New or planned dose changes of systemic corticosteroids.  Stable doses (>4 weeks 
before Visit S1) and topical steroids allowed. 
• Requirement for simvastatin >40 mg, mipomersen or lomitapide or apheresis therapy 
• Planned initiation of the following drugs during the clinical trial or changes to the 
following drugs prior to randomization: 
• CETP inhibitors within the last 2 years prior to screening (Week -5, Visit S1) except 
for evaceptrapib within the last 3 months prior to screening (Week -5, Visit S1) 
• Mipomersen (6 months prior to screening, Week -5, Visit S1) 
• Lomitapide (3 months prior to screening, Week -5, Visit S1) 
• Apheresis (3 months prior to screening, Week -5, Visit S1) 
• Simvastatin >40 mg (4 weeks prior to screening, Week -5, Visit S1) 
• Red yeast rice extract -containing products are not allowed (2 weeks prior to 
screening, Week -5, Visit S1) 
18. Planned initiation of the following drugs during the clinical trial or changes prior to 
randomization (Day 1, Visit T1): 
• Hormone replacement (6 weeks prior to randomization) 
• Thyroid replacement (6 weeks prior to randomization) 
• Diabetes medications (4 weeks prior to randomization) 
• Obesity medication (3 months 4 weeks prior to randomization) 
Red yeast rice extract containing products are not allowed (2 weeks prior to 
screening) 
19. Lack of adherence (ie, less than 80% of planned doses) with IMP (single-blind placebo) 
during the Run-in Period. 
20. Lack of tolerance with IMP (single-blind placebo) during the Run-in Period. 
21. 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. 
22. An employee or contractor of the facility conducting the study, or a family member of the 
Principal Investigator, Co-Investigator, or Sponsor. 
23. Pregnant, breastfeeding, or intending to become pregnant within 30 days after last dose 
of study drug. 
24. Patients who have enrolled in a study of an experimental siRNA of PCSK9 are 
excluded. 
 


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CHANGE 6 
SAFETY AND MONITORING REVISIONS  
Location:  
Section 2, Synopsis  
Original Text: 
Monitoring and Management Plans for Lipid Elevations: 
Elevated LDL-C—Adjunctive Therapy: 
An adjunctive therapy plan is in place for those patients whose LDL-C values meet the protocol-
defined LDL-C threshold criteria. Post-randomization, LDL-C results will be masked to 
investigators in order to maintain the blind; however, the following thresholds have been set to 
notify investigators and provide an opportunity to adjust the patient’s standard of care regimen.  
• Beginning at Week 24 (Visit T5) visit and for the duration of the study, the central 
laboratory will notify the investigator when the patient’s LDL-C value is ≥25% from 
the patient’s baseline value at Week 0 (Visit T1) 
New Text: 
Monitoring and Management Plans for Lipid Elevations: 
Elevated LDL-C—Adjunctive Therapy: 
An adjunctive therapy plan is in place for those patients whose LDL-C values meet the protocol-
defined LDL-C threshold criteria. Post-randomization, LDL-C results will be masked to 
investigators in order to maintain the blind; however, the following thresholds have been set to 
notify investigators and provide an opportunity to adjust the patient’s standard of care regimen.  
• Beginning at Week 24 (Visit T5) visit and for the duration of the study, the central 
laboratory will notify the investigator when the patient’s LDL-C value is >170 mg/dL 
(4.4 mmol/L) and ≥25% from the patient’s baseline value at Week 0 (Visit T1) 
 
CHANGE 7 
STATISTICAL METHODS REVISIONS 
Location:  
Section 2, Synopsis; Section 12.6, Secondary and Tertiary Efficacy Endpoints 
Original Text: 
In this hierarchical testing structure, each hypothesis is tested at a significance level of 0.05, two-
sided. Statistical significance at each step is required in order to test the next hypothesis.  If the 
primary endpoint meets the criteria for statistical significance, then the percent change from 
baseline to Week 24 in LDL-C will be tested; and so forth.  
Percent change from baseline to Week 24 in LDL-C; change from baseline to Weeks 12, 24, 
and 52 in LDL-C; percent change from baseline to Weeks 12, 24, and 52 in HDL-C, non-
HDL-C, TG, TC, apoB, and hs-CRP will each be analyzed using ANCOVA with treatment 
group, CV risk (ASCVD only; HeFH with or without ASCVD) and baseline statin intensity 
(high intensity, moderate intensity, low intensity) as factors and the relevant baseline as a 
covariate.   


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New Text: 
In this hierarchical testing structure, each hypothesis is tested at a significance level of 0.05, two-
sided. Statistical significance at each step is required in order to test the next hypothesis.  If the 
primary endpoint meets the criteria for statistical significance, then the percent change from 
baseline to Week 24 in LDL-C will be tested; and so forth.  
Percent change from baseline to Week 24 in LDL-C; absolute change from baseline to 
Weeks 12, 24, and 52 in LDL-C; percent change from baseline to Weeks 12, 24, and 52 in 
HDL-C, non-HDL-C, TG, TC, apoB, and hs-CRP will each be analyzed using ANCOVA with 
treatment group, CV risk (ASCVD only; HeFH with or without ASCVD) and baseline statin 
intensity (high intensity, moderate intensity, low intensity) as factors and the relevant baseline as 
a covariate.   
Location: 
Synopsis, Safety Analyses 
Original Text: 
No statistical analyses will be performed on any of the safety data in this study.   
The summarization of AEs will include treatment-emergent AEs (TEAEs), defined as AEs with 
an onset date on or after initiation of study treatment.  TEAEs and SAEs will be summarized by 
system organ class (SOC), severity, and relationship to study drug for each treatment group.   
New Text: 
No statistical analyses will be performed on any of the safety data in this study.   
The summarization of AEs will include treatment-emergent AEs (TEAEs), defined as AEs with 
an onset date on or after initiation of study treatment.  TEAEs and SAEs will be summarized by 
system organ class (SOC), severity, and relationship to study drug for each treatment group.   
Location: 
Synopsis, PK and Other biomarkers 
Original Text: 
PK plasma concentrations will be summarized at predose (T1) Weeks 24 and 52. 
New Text: 
PK plasma concentrations of ETC-1002 and its metabolite ESP15228 will be summarized at 
predose (T1) Weeks 24 and 52. 
 
CHANGE 8 
MECHANISM OF ACTION REVISIONS 
Location:  
Section 4.2.1, Mechanism of Action 


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Original Text: 
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. 
New Text: 
An important differentiating feature of bempedoic acid is that, unlike statins, it does not inhibit 
cholesterol synthesis in skeletal muscle.  The enzyme required to convert bempedoic acid to 
ETC-1002-CoA is not present 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; however, the safety of bempedoic acid and its metabolites 
regarding human skeletal muscle is not yet established. 
 
CHANGE 9 
STUDY DESIGN REVISIONS 
Location:  
Section 2, Synopsis; Section 6.1, Overall Study Design 
Original Text: 
There will be no cap placed on randomization into any particular stratum.  Approximately 
750 eligible patients will be randomized 2:1 on Day 1 (Visit T1) to receive either bempedoic acid 
180 mg (n = 500), or placebo (n = 250) once daily for 52 weeks.  Randomized patients will 
return for clinic visits at Week 4 (Visit T2), Week 12 (Visit T4), Week 24 (Visit T5), and 
Week 52 (Visit T7).  A phone visit will occur at Week 8 (Visit T3) and Week 36 (Visit T6). 
New Text: 
There will be no cap placed on randomization into any particular stratum.  Approximately 525 
eligible patients will be randomized 2:1 on Day 1 (Visit T1) to receive either bempedoic acid 180 
mg (n = 500350), or placebo (n = 250175) once daily for 52 weeks.  Randomized patients will 
return for clinic visits at Week 4 (Visit T2), Week 12 (Visit T4), Week 24 (Visit T5), and Week 
52 (Visit T7).  A phone visit will occur at Week 8 (Visit T3) and Week 36 (Visit T6).  For 
patients taking simvastatin 40 mg, there will be additional clinic visits to assess safety at 
Weeks 16 and 28 as well as telephone visits at Weeks 20 and 32. 
 


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CHANGE 10 
CONCOMITANT MEDICATIONS REVISIONS 
Location:  
Section 8.2.1, Lipid-Regulating Medications and Supplements 
Original Text: 
Statins 
• Atorvastatin (Lipitor®, Sortis®) 
• Fluvastatin (Lescol®) 
• Lovastatin (Mevacor®, Altoprev™) 
• Pravastatin (Pravachol®) 
• Pitavastatin (Livalo®, Lipostat®) 
• Rosuvastatin (Crestor®) 
• Simvastatin (Zocor®)  
New Text: 
Statins 
• Atorvastatin (Lipitor®, Sortis®) 
• Fluvastatin (Lescol®) 
• Lovastatin (Mevacor®, Altoprev™) 
• Pravastatin (Pravachol®) 
• Pitavastatin (Livalo®, Lipostat®) 
• Rosuvastatin (Crestor®) 
• Simvastatin (Zocor®) (doses ≥ 40 mg are exclusionary) 
 
CHANGE 11 
PROHIBITED MEDICATIONS REVISIONS 
Location:  
Section 8.2.2, Prohibited Medications 
Original Text: 
Patients will not have used medications (monotherapies or combination therapies) listed below 
within 4 weeks prior to screening or use these drugs during the study: 
• New or planned dose changes of systemic corticosteroids.  Stable doses of systemic 
corticosteroids at screening are allowed (≥4 weeks).  Short-term intermittent use 
(<14 days) of pulse steroids are allowed.  Topical steroids are allowed. 
• Gemfibrozil (Lopid®) (as per co-administration instructions defined in the statin 
label) 


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• Cholestin (red yeast rice extract, also known as monascus purpureus extract) (2 weeks 
prior to screening) 
New Text: 
Patients will not have used medications (monotherapies or combination therapies) listed below 
within the allotted time period 4 weeks prior to screening or use these drugs during the study: 
• New or planned dose changes of systemic corticosteroids.  Stable doses of systemic 
corticosteroids at screening are allowed (≥4 weeks).  Short-term intermittent use 
(<14 days) of pulse steroids are allowed.  Topical steroids are allowed. 
• Gemfibrozil (Lopid®) (as per co-administration instructions defined in the statin 
label) ≥6 weeks prior to screening (Visit S1) 
• Cholestin (red yeast rice extract, also known as monascus purpureus extract) 
(≥2 weeks prior to screening) 
• CETP inhibitors within the last 2 years prior to screening (Visit S1) except for 
evaceptrapib within the last 3 months prior to screening (Visit S1) 
• Mipomersen within 6 months prior to screening (Visit S1) 
• Lomitapide within 3 months prior to screening (Visit S1) 
• Apheresis within 3 months prior to screening (Visit S1) 
• Simvastatin >40 mg 
 
CHANGE 12 
ALLOWABLE MEDICATIONS REVISIONS 
Location:  
Section 8.2.3, Allowable Medications 
Original Text: 
Other concomitant medication must be stable prior to screening and, if possible, not be adjusted 
during the study except for reasons of safety.  
The following must be stable for a minimum of 6 weeks prior to randomization: 
• Postmenopausal hormone therapy 
• Thyroid hormone supplements 
• Fibrates (excluding gemfibrozil) 
The following must be stable for a minimum of 4 weeks prior to screening: 
• Hypertriglyceridemia therapy  
• Lipid-lowering therapy, including dietary supplements and herbal remedies (except 
red yeast rice extract-containing products, which are exclusionary used for the 
purposes of lipid lowering). 
• Diabetes medications 


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The following must be stable for a minimum of 3 months prior to screening and, if possible not 
be adjusted during the study except for reasons of safety: 
• Antiobesity medications 
New Text: 
Other concomitant medications must be stable prior to screening and, if possible, not be adjusted 
during the study except for reasons of safety.  
The following must be stable for a minimum of 6 weeks prior to randomization: 
• Postmenopausal hormone therapy 
• Thyroid hormone supplements 
• Fibrates (excluding gemfibrozil) 
The following must be stable for a minimum of 4 weeks prior to screeningrandomization: 
• Hypertriglyceridemia therapy  
• Lipid lowering therapy, including dietary supplements and herbal remedies (except 
red yeast rice extract containing products, which are exclusionary used for the 
purposes of lipid lowering). 
• Diabetes medications 
The following must be stable for a minimum of 3 months prior to screening and, if possible not 
be adjusted during the study except for reasons of safety: 
• Antiobesity medications 
 
CHANGE 13 
INVESTIGATIONAL MEDICINAL PRODUCT SUPPLY AND 
CONTROL REVISION 
Location:  
Section 9.1, Investigational Medicinal Product Supply and Control 
Original Text: 
A 35-day supply of single-blind placebo drug will be dispensed one time at Week -4 (Visit S2) 
for the 4-week placebo run-in period of the study.  Double-blind IMP will be dispensed in 
100 day supply increments to patients by appropriate clinical site personnel. Patients will receive 
one 100-day supply bottle at Week 0 (Visit T1), Week 12 (Visit T4), and two 100-day supply 
bottles at Week 24 (Visit T5).   
New Text: 
A 35-day supply of single-blind placebo drug will be dispensed one time at Week -4 (Visit S2) 
for the 4-week placebo run-in period of the study.  Double-blind IMP will be dispensed in 
100 day supply increments to patients by appropriate clinical site personnel. Patients will receive 
one 100-day supply bottle at Week 0 (Visit T1), Week 12 (Visit T4), and two 100-day supply 
bottles at Week 24 (Visit T5).  At Week 12, patients will return their first bottle and tablets will 


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be counted by study personnel who will then dispense a second bottle.  At Week 24, tablets 
from the second bottle will be counted and the final 2 bottles dispensed.  At Week 52, tablets 
will be counted by study personnel from the 2 bottles dispensed at Week 24.  
 
CHANGE 14 
STUDY PROCEDURES REVISION 
Location: 
Section 10.1, Informed Consent 
Original Text: 
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.  
Participation in banking of samples for genetic analysis is optional for all patients, and consent 
for this must be documented in the patient’s written informed consent. 
New Text: 
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.  
Participation in banking of samples for genetic analysis is optional for all patients, and consent 
for this must be documented in the patient’s written informed consent. 
 
CHANGE 15 
PROCEDURES AND SCHEDULE OF ASSESSMENTS REVISIONS 
Location: 
Section 10.2.1, Screening Week -5 (Visit S1; Day -35 ± 7 days) 
Original Text: 
10.2.1 
Screening Week -5 (Visit S1; Day -35) 
New Text: 
10.2.1 
Screening Week -5 (Visit S1; Day -35 ± 7 days) 
Original Text: 
Patients who meet all enrollment criteria that can be assessed at Visit S1 will be instructed to 
continue their therapy(s) for lipid regulation 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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Note: 
• An optional visit approximately 1 week later MAY be completed if patient fails to 
meet a lipid entry criterion.  If this optional visit is completed, the repeat lipid values 
will be used to determine eligibility. 
• An optional visit between Visits S1 and TI may be scheduled to collect screening 
fasting labs in the event that the patient arrives at Visit S1 in a nonfasted state. 
• An optional visit between Visits S1 and TI may be completed if the patient’s DBP 
and/or SBP meet the exclusion criteria levels.  Patients may randomize after BP 
medications have been adjusted, they have been on stable doses of BP medications 
for at least 2 weeks, and the repeat BP values (DBP and/or SBP) no longer meet 
exclusionary values. 
• An optional visit between Visits S1 and TI may be completed to determine eligibility 
if the patient’s eGFR, ALT, AST, and/or TB meet exclusion criteria levels.  If this 
optional visit is completed, the repeated value will be used to determine eligibility. 
New Text: 
Patients who meet all enrollment criteria that can be assessed at Visit S1 will be instructed to 
continue their therapy(s) for lipid regulation 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). 
Note: 
• An optional visit approximately 1 week later MAY be completed if patient fails to 
meet a lipid TG entry criterion.  If this optional visit is completed, the repeat lipid 
values will be used to determine eligibility. 
• An optional visit between Visits S1 and TI S2 may be scheduled to collect screening 
fasting labs in the event that the patient arrives at Visit S1 in a nonfasted state. 
• An optional visit between Visits S1 and TI S2 may be completed if the patient’s DBP 
and/or SBP meet the exclusion criteria levels.  Patients may randomize after BP 
medications have been adjusted, they have been on stable doses of BP medications 
for at least 2 weeks, and the repeat BP values (DBP and/or SBP) no longer meet 
exclusionary values. 
• An optional visit between Visits S1 and TI S2 may be completed to determine 
eligibility if the patient’s eGFR, ALT, AST, and/or TB meet exclusion criteria levels.  
If this optional visit is completed, the repeated value will be used to determine 
eligibility. 
Original Text: 
10.2.2 
Placebo Run-in Week -4 (Visit S2; Day -28) 


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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) 
• Vital signs 
New Text: 
10.2.2 
Placebo Run-in Week -4 (Visit S2; Day -28 ±3 days) 
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, SAEs and potential clinical endpoints (starting from signing of the 
informed consent document) 
• Vital signs 
Original Text: 
10.2.3 
Placebo Run-in Week -1 (Visit S3; Day -7) 
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, HDL-C, non-HDL-C, and TG) 
• Conduct diet and exercise counseling 
New Text: 
10.2.3 
Placebo Run-in Week -1 (Visit S3; Day -7 ±3 days) 
The patient will undergo the following assessments and procedures at (Visit S3) 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, SAEs and potential clinical endpoints (starting from signing of the 
informed consent document) 


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• Vital signs 
• Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG); LDL-C 
must be ≥70 mg/dL (1.8 mmol/L) to be eligible 
• Conduct diet and exercise counseling 
Original Text: 
10.2.4 
Treatment Week 0 (Visit T1; Day 1) 
Prior to scheduling Visit T1, review the screening and placebo run-in 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 and none of the exclusion criteria, 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) 
• Physical examination (PE) 
• Weight 
• 12-Lead electrocardiogram (ECG) 
• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Note:  Urine pregnancy test (for females of childbearing potential) 
− Coagulation  in patients on vitamin K antagonists only (and repeat 3-5 days later) 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− apoB 
− HbA1C  
− hs-CRP 
− Reserve sample 
− Genetic sample (optional) 
• Review inclusion/exclusion criteria to establish patient eligibility 


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• Plasma PK 
• 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 (one 100-day supply bottle) 
• Return of placebo assessment and recording of drug compliance 
• Schedule next visit 
New Text: 
10.2.4 
Treatment Week 0 (Visit T1; Day 1) 
Prior to scheduling Visit T1, review the information collected at Visits S1, S2, and S3 to 
evaluate whether the patient continues to meet eligibility criteria.  screening and placebo run in 
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 and none of the exclusion criteria, 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, SAEs, and potential clinical endpoints (starting from signing of the 
informed consent document) 
• Physical examination (PE) 
• Weight 
• 12-Lead electrocardiogram (ECG) 
• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Note:  Urine pregnancy test (for females of childbearing potential) 
− Coagulation  in patients on vitamin K antagonists only (and repeat 3-5 days later) 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− apoB 
− HbA1C  


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Clinical Study Protocol 1002-047 
 
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− hs-CRP 
− Reserve sample 
 Genetic sample (optional) 
• Review inclusion/exclusion criteria to establish patient eligibility 
• Plasma PK 
• 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 (one 100-day supply bottle) 
• Return of placebo assessment tablets, record compliance and ensure patient meets 
eligibility criteria and recording of drug compliance 
• Schedule next visit 
Original Text: 
10.2.5 
Treatment Week 4 (Visit T2; 29 ±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.  The patient will be asked to continue to be followed for safety 
using the protocol-specified visit schedule.  If the patient consents for follow-up, schedule the 
next protocol-specified visit.  
Patients who do not provide consent to continue to return to the clinic for safety assessments 
after withdrawing from IMP treatment will be asked to participate in phone calls from the site at 
protocol-specified visits, or at a minimum at 52 weeks, to inquire about the patient’s current 
health status and collect information on AEs (eg, recent procedures, hospitalizations, and if the 
patient has died, the cause of death).  If the patient consents for telephone contacts, schedule the 
next protocol-specified visit. 
Patients will undergo the following assessments and procedures at Week 4 (Visit T2): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs since last visit (ongoing) 
• Weight 
• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
• Conduct diet and exercise counseling 


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• 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 
• Schedule next visit 
Note:  If this visit is being conducted at the site for patients who have consented to be 
followed for safety assessments, including basic fasting lipids, after withdrawing from 
IMP treatment, all assessments except for those procedures pertaining to IMP 
management (IMP dispensing, IMP compliance, IMP accountability) should be 
completed. 
Note:  If this visit is being conducted by telephone contact for patients who have 
consented to be followed by phone for safety assessments after withdrawing from IMP 
treatment, collect information as reported by the patient regarding AEs, concomitant 
medication, and current health status. 
New Text: 
10.2.5 
Treatment Week 4 (Visit T2; 29 ±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.  The patient will be asked to continue to be followed for safety 
using the protocol-specified visit schedule.  If the patient consents for follow up, schedule the 
next protocol specified visit.  
Patients who do not provide consent refusing to continue to return to the clinic for safety 
protocol assessments after withdrawing from IMP treatment will be asked to participate in phone 
calls from the site at protocol-specified visits, or at a minimum at 52 weeks, to inquire about the 
patient’s current health status and collect information on AEs (eg, recent procedures, 
hospitalizations, and if the patient has died, the cause of death).  If the patient consents for 
telephone contacts, schedule the next protocol-specified visit. 
Patients will undergo the following assessments and procedures at Week 4 (Visit T2): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints since last visit (ongoing) 
• Weight 
• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
• Conduct diet and exercise counseling 
• Return of IMP; assessment and recording of IMP compliance 


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Clinical Study Protocol 1002-047 
 
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• Re-dispense IMP container from Visit T1 to patient for continued dosing and provide 
dosing instruction 
• Schedule next visit 
Note:  If this visit is being conducted at the site for patients who have consented to be 
followed for safety assessments, including basic fasting lipids, after withdrawing from 
IMP treatment, all assessments except for those procedures pertaining to IMP 
management (IMP dispensing, IMP compliance, IMP accountability) should be 
completed. 
Note:  If this visit is being conducted by telephone contact for patients who have 
consented to be followed by phone for safety assessments after withdrawing from IMP 
treatment, collect information as reported by the patient regarding AEs, concomitant 
medication, and current health status. 
Original Text: 
10.2.7 
Treatment Week 12 (Visit T4; 85 ±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.  The patient will be asked to continue to be followed for safety 
using the protocol-specified visit schedule.   
Patients refusing to continue to return to the clinic for protocol assessments after withdrawing 
from IMP treatment will be asked to participate in phone calls from the site at protocol-specified 
visits, or at a minimum at 52 weeks, to inquire about the patient’s current health status and 
collect information on AEs (eg, recent procedures, hospitalizations, and if the patient has died, 
the cause of death).  If the patient consents for telephone contacts, schedule the next protocol-
specified visit. 
Patients will undergo the following assessments and procedures at Week 12 (Visit T4): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs since last visit (ongoing) 
• Weight 
• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− apoB 
− HbA1C 
− hs-CRP 
• Conduct diet and exercise counseling 


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Amendment 3, 09 May 2017 
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• Return of IMP; assessment and recording of IMP compliance 
• IWRS contact to obtain the MED ID number for IMP 
• Dispense IMP and provide dosing instructions (one 100-day supply bottle)  
• Schedule next visit 
Note:  If this visit is being conducted at the site for patients who have consented to be 
followed for safety assessments, including basic fasting lipids, after withdrawing from 
IMP treatment, all assessments except for those procedures pertaining to apoB, hs-CRP, 
PK samples, and IMP management (IMP dispensing, IMP compliance, IMP 
accountability) should be completed. 
Note:  If this visit is being conducted by telephone contact for patients who have 
consented to be followed by phone for safety assessments after withdrawing from IMP 
treatment, collect information as reported by the patient regarding AEs, concomitant 
medications, and current health status. 
New Text: 
10.2.7 
Treatment Week 12 (Visit T4; 85 ±3 days) 
Patients will undergo the following assessments and procedures at Week 12 (Visit T4): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs SAEs, and potential clinical endpoints since last visit (ongoing) 
• Weight 
• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− apoB 
− HbA1C 
− hs-CRP 
• Conduct diet and exercise counseling 
• Return of IMP; assessment and recording of IMP compliance 
• IWRS contact to obtain the MED ID number for IMP 
• Dispense IMP and provide dosing instructions (one 100-day supply bottle)  
• Schedule next visit 
Note:  If this visit is being conducted at the site for patients who have consented to be 
followed for safety assessments, including basic fasting lipids, after withdrawing from 
IMP treatment, all assessments except for those procedures pertaining to apoB, hs CRP, 


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Amendment 3, 09 May 2017 
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PK samples, and IMP management (IMP dispensing, IMP compliance, IMP 
accountability) should be completed. 
Note:  If this visit is being conducted by telephone contact for patients who have 
consented to be followed by phone for safety assessments after withdrawing from IMP 
treatment, collect information as reported by the patient regarding AEs, concomitant 
medications, and current health status. 
10.2.8 
Treatment Week 16 (Visit T4.1; 112 ± 3 days) Only for Patients Taking Simvastatin 
40 mg 
Patients taking an average daily dose of simvastatin 40 mg will be scheduled for an additional 
visit, Visit T4.1 for clinical safety laboratory evaluations specifically to monitor changes in 
CPK and LFTs as well as additional assessments as described below.  Should changes be 
noted, the procedures described in Sections 11.1.6.3.1 and 11.1.6.3.4 will apply.   
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints since last visit (ongoing) 
• Clinical laboratory evaluations 
− Hematology, blood chemistry, and urinalysis 
10.2.9 
Treatment Week 20/Telephone Visit (Visit T4.2; 140 ± 3 days) Only for Patients 
Taking Simvastatin 40 mg 
Patients taking an average daily dose of simvastatin 40 mg will be contacted by telephone for 
additional Visit T4.2 to collect the following information: 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints since last visit (ongoing) 
Original Text: 
10.2.8 
Treatment Week 24 (Visit T5; 168 ±3 days) 
New Text: 
10.2.10 
Treatment Week 24 (Visit T5; 168 ±3 days) 
Original Text: 
Patients will undergo the following assessments and procedures at Week 24 (Visit T5): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs since last visit (ongoing) 
• Weight 
• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 


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Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
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− apoB 
− HbA1C 
− hs-CRP 
• PK sample  
• Conduct diet and exercise counseling 
• Return of IMP; assessment and recording of IMP compliance 
• IWRS contact to obtain the MED ID number for IMP 
• Dispense IMP and provide dosing instructions (two 100 day supply bottles)  
• Schedule next visit 
Note:  If this visit is being conducted at the site for patients who have consented to be 
followed for safety assessments, including basic fasting lipids, after withdrawing from 
IMP treatment, all assessments except for those procedures pertaining to apoB, hs-CRP, 
PK samples, and IMP management (IMP dispensing, IMP compliance, IMP 
accountability) should be completed. 
Note:  If this visit is being conducted by telephone contact for patients who have 
consented to be followed by phone for safety assessments after withdrawing from IMP 
treatment, collect information as reported by the patient regarding AEs, concomitant 
medications, and current health status. 
New Text: 
Patients will undergo the following assessments and procedures at Week 24 (Visit T5): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints since last visit (ongoing) 
• Weight 
• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− apoB 
− HbA1C 
− hs-CRP 
• PK sample before dose 
• Conduct diet and exercise counseling 
• Return of IMP; assessment and recording of IMP compliance 
• IWRS contact to obtain the MED ID number for IMP 


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Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
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• Dispense IMP and provide dosing instructions (two 100 day supply bottles)  
• Schedule next visit 
Note:  If this visit is being conducted at the site for patients who have consented to be 
followed for safety assessments, including basic fasting lipids, after withdrawing from 
IMP treatment, all assessments except for those procedures pertaining to apoB, hs CRP, 
PK samples, and IMP management (IMP dispensing, IMP compliance, IMP 
accountability) should be completed. 
Note:  If this visit is being conducted by telephone contact for patients who have 
consented to be followed by phone for safety assessments after withdrawing from IMP 
treatment, collect information as reported by the patient regarding AEs, concomitant 
medications, and current health status. 
10.2.11 
Treatment Week 28 (Visit T5.2; 196 ± 7 days) Only for Patients Taking Simvastatin 
40 mg 
Patients taking an average daily dose of simvastatin 40 mg will be scheduled for an additional 
visit, Visit T5.2 for clinical safety laboratory evaluations specifically to monitor changes in 
CPK and LFTs as well as additional assessments as described below.  Should changes be 
noted, the procedures described in Sections 11.1.6.3.1 and 11.1.6.3.4 will apply.   
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints since last visit (ongoing) 
• Clinical laboratory evaluations 
− Hematology, blood chemistry, and urinalysis 
10.2.12 
Treatment Week 32/Telephone Visit (Visit 5.2; 224 ± 7 days) Only for Patients 
Taking Simvastatin 40 mg 
Patients taking an average daily dose of simvastatin 40 mg will be contacted by telephone for 
additional Visit T4.2 to collect the following information: 
• Concomitant ad prohibited medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints since last visit (ongoing) 
Original Text: 
10.2.14 
Treatment Week 52/EOS (Visit T7; 365 ±7days) 
Patients will undergo the following assessments and procedures at Week 52 (Visit T7), when 
completing an End of Study (EOS) visit, withdrawing from study (early withdrawal), or 
withdrawing from IMP treatment: 
Patients will undergo the following assessments and procedures at Week 52 (Visit T7): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs since last visit (ongoing) 
• PE 


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• Weight 
• 12-Lead ECG 
• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL C, HDL C, non-HDL C, and TG) 
− apoB 
− HbA1C 
− hs-CRP 
• PK sample  
• Reserve sample  
• Return of IMP; assessment and recording of IMP compliance 
• Complete study status in IWRS (ie, early withdrawal or completed study). 
New Text: 
10.2.14 
Treatment Week 52/EOS (Visit T7; 365 ±7days) 
Patients will undergo the following assessments and procedures at Week 52 (Visit T7), when 
completing an End of Study (EOS) visit, withdrawing from study (early withdrawal), or 
withdrawing from IMP treatment: 
Patients will undergo the following assessments and procedures at Week 52 (Visit T7): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs SAEs, and potential clinical endpoint since last visit (ongoing) 
• PE 
• Weight 
• 12-Lead ECG 
• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL C, HDL C, non-HDL C, and TG) 
− apoB 
− HbA1C 
− hs-CRP 
• PK sample before dose 


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Amendment 3, 09 May 2017 
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• Reserve sample  
• Return of IMP; assessment and recording of IMP compliance 
• Complete study status in IWRS (ie, early withdrawal or completed study). 
 
CHANGE 16 
SUBJECT WITHDRWAL CRITERIA REVISION 
Location: 
Section 10.3.1, Early Withdrawal from the Study 
Original Text: 
Patients must remain in the study until the last scheduled visit at Week 52 (Visit T7) to be 
considered as having completed participation in the study.  
Patients who withdraw from IMP prior to Week 52 (Visit T7) for any reason will be asked to 
continue to be followed for safety assessments, including basic fasting lipids, at clinic visit 
following the protocol-specified visit schedule (see Appendix 1). The patient must provide 
consent to be followed in the study after withdrawing from IMP treatment.  Protocol procedures 
to be completed for patients who consent will include those specified at each visit as noted in 
Schedule of Events (see Appendix 1).  
New Text: 
Patients must remain in the study until the last scheduled visit at Week 52 (Visit T7) to be 
considered as having completed participation in the study.  
Patients who withdraw from IMP prior to Week 52 (Visit T7) for any reason will be asked to 
continue to be followed for safety assessments, including basic fasting lipids, at clinic visit 
following the protocol-specified visit schedule (see Appendix 1). The patient must provide 
consent to be followed in the study after withdrawing from IMP treatment.  Protocol procedures 
to be completed for patients who consent will include those specified at each visit as noted in 
Schedule of Events (see Appendix 1).  
 


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CHANGE 17 
ADDITIONAL SAMPLES REVISIONS 
Location: 
Section 11.1.6.1, Laboratory Parameters (Safety) 
Original Text: 
Table 5: 
Clinical Laboratory Parameters (Safety) (Continued) 
Clinical Laboratory Test 
Clinical Laboratory Test 
Urinalysis (Microscopic)-only if urine dipstick 
abnormal 
• Bacteria 
• Casts 
• Crystals 
• Epithelial cells 
• Red blood cell (RBC) 
• WBC 
Coagulation (screening for all patients, T1 and 
3-5 days after T1 in patients receiving 
anticoagulation therapy, only) 
• Prothrombin time (PT) 
• International normalized ratio (INR) 
Other Screening Labs 
Additional samples 
• 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) 
• Hemoglobin A1C (HbA1C) 
• Reserve blood samples for potential 
future measurement of bempedoic 
acid safety or pharmacodynamic 
biomarkers 
• PK sample  
• Reserve genetic blood sample 
(optional) 
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. 
 


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Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
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New Text: 
Table 5: 
Clinical Laboratory Parameters (Safety) (Continued) 
Clinical Laboratory Test 
Clinical Laboratory Test 
Urinalysis (Microscopic)-only if urine dipstick 
abnormal 
• Bacteria 
• Casts 
• Crystals 
• Epithelial cells 
• Red blood cell (RBC) 
• WBC 
Coagulation (screening for all patients, T1 and 
3-5 days after T1 in patients receiving 
anticoagulation therapy, only) 
• Prothrombin time (PT) 
• International normalized ratio (INR) 
Other Screening Labs 
Additional samples 
• 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) 
• Hemoglobin A1C (HbA1C) 
• Reserve blood samples for potential 
future measurement of bempedoic 
acid safety or pharmacodynamic 
biomarkers 
• PK sample  
• Reserve genetic blood sample 
(optional) 
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. 
 
CHANGE 18 
SAMPLE COLLECTION REVISIONS 
Location: 
Section 16.1.6.2, Sample Collection, Storage, and Shipping 
Original Text: 
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.  For 
collection and processing of PK samples, please see Section 11.1.6.5 and Section 11.1.6.6.  
Samples will be processed by the Central Laboratory, and PK samples will be forwarded to the 
Bioanalytical Laboratory for analysis.  Reserve samples will be stored frozen for potential future 
measurement of additional bempedoic acid safety and efficacy biomarkers.  A reserve genetic 
blood sample (optional) will also be stored frozen for potential future bempedoic acid genetic 
analyses.  


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Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
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New Text: 
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.  For 
collection and processing of PK samples, please see Section 11.1.6.5 and Section 11.1.1.6.  
Samples will be processed by the Central Laboratory. and PK samples will be forwarded to the 
Bioanalytical Laboratory for analysis.  Reserve samples will be stored frozen for potential future 
measurement of additional bempedoic acid safety and efficacy biomarkers.  A reserve genetic 
blood sample (optional) will also be stored frozen for potential future bempedoic acid genetic 
analyses.  
 
CHANGE 19 
MONITORING ABNORMAL LABS REVISIONS 
Location: 
Section 11.1.6.3, General Monitoring and Management of Abnormal Clinical Labs 
Original Text: 
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. 
New Text: 
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.   
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 
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. 
 


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CHANGE 20 
MONITORING ELEVATED LIVER FUNCTION TESTS 
Location: 
Section 11.1.6.3.1, Monitoring and Management of Elevated Liver Function Tests 
Original Text: 
• 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): 
New Text: 
• 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) or more 
frequently if deemed by the investigator. 
• 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) or more frequently if deemed by the investigator. 
 
CHANGE 21 
MONITORING ELEVATED CREATINE KINASE 
Location: 
Section 11.1.6.3.4, Monitoring and Management of Elevated Creatine Kinase 
Original Text: 
11.1.6.3.4 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 investigator with input from the Sponsor may consider continuing study 
medication with continued CK assessments every 1-2 weeks.  


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New Text: 
11.1.6.3.4 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. investigator with input from the Sponsor may consider 
continuing study medication with continued CK assessments every 1 2 weeks. 
 
CHANGE 22 
SAMPLE COLLECTION, BIOMARKER, AND GENETIC TESTING 
REVISIONS 
Location: 
Sections 11.1.6.6 through 11.1.6.10 
Original Text: 
11.1.6.6 
Collection and Assessment of Pharmacokinetic Samples 
Pharmacokinetic samples will be collected from patients prior to the first dose (T1), Weeks 24 
and 52, for use in further developing the population PK model.  
Plasma concentrations of bempedoic acid and its metabolite (ESP15228) will be determined 
using validated methods.  Plasma PK samples will be labeled with preprinted information, 
including study number, patient identification number, study day, nominal time of sample 
collection, matrix, and a text identification (ie, “Plasma PK”).  See the study laboratory manual 
for further instructions. 
11.1.7. 
Exploratory Biomarker Measurement 
Additional exploratory safety, efficacy, PK, or potential biomarkers may be assayed from 10 mL 
blood samples reserved for potential future measurement of potential biomarkers.  
11.1.8. 
Shipment of Pharmacokinetic Samples 
Plasma PK samples will be shipped frozen on dry ice according to instructions provided in the 
laboratory manual. 
11.1.9 
Genetic Testing 
As part of this study, all patients will be invited to provide a blood sample to be banked for 
potential future genetic analyses, but participation in this portion of the study is optional and 
where is approved by the IRB/IEC and by local law.  Those who choose not to provide a sample 
for genetic analysis may still participate in the main portion of the study.  Samples will be 


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Confidential 
Page 149 of 184 
anonymized before testing to assure that the results cannot be traced back to an individual 
patient.  Signing a separate informed consent document is required to obtain this sample. 
11.1.10 
Total Blood Volume of Clinical Laboratory and Pharmacokinetic Samples 
The total number of venipunctures and total volume of whole blood collected during the study 
will be limited to that needed for safety monitoring, PK, efficacy, biomarker assessment, and 
genetic analysis.  Total whole blood volume collected over the study duration is not to exceed 
approximately 250 mL for each patient. 
New Text: 
11.1.6.6 
Collection and Assessment of Pharmacokinetic Samples 
Pharmacokinetic samples will be collected from patients prior to the first dose (T1), at Weeks 24 
and 52, for use in further developing the population PK model.  
Plasma concentrations of bempedoic acid and its metabolite (ESP15228) will be determined 
using validated methods.  Plasma PK samples will be labeled with preprinted information, 
including study number, patient identification number, study day, nominal time of sample 
collection, matrix, and a text identification (ie, “Plasma PK”).  See the study laboratory manual 
for further instructions. 
11.1.6.7. Exploratory Biomarker Measurement 
Additional exploratory safety, efficacy, PK, or potential biomarkers may be assayed from 10 mL 
blood samples reserved for potential future measurement of potential biomarkers.  
11.1.6.78. Shipment of Pharmacokinetic Samples 
Plasma PK samples will be shipped frozen on dry ice according to instructions provided in the 
laboratory manual. 
11.1.9 
Genetic Testing 
As part of this study, all patients will be invited to provide a blood sample to be banked for 
potential future genetic analyses, but participation in this portion of the study is optional and 
where is approved by the IRB/IEC and by local law.  Those who choose not to provide a sample 
for genetic analysis may still participate in the main portion of the study.  Samples will be 
anonymized before testing to assure that the results cannot be traced back to an individual 
patient.  Signing a separate informed consent document is required to obtain this sample. 
11.1.6.810 Total Blood Volume of Clinical Laboratory and Pharmacokinetic Samples 
The total number of venipunctures and total volume of whole blood collected during the study 
will be limited to that needed for safety monitoring, PK, efficacy, and biomarker assessment and 
genetic analysis.  Total whole blood volume collected over the study duration is not to exceed 
approximately 250 mL for each patient. 
 
CHANGE 23 
ADVERSE EVENT REPORTING REVISIONS 
Location: 
11.2.3 Reporting 


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Original Text: 
11.2.3 Reporting 
All AEs occurring during the course of the study (starting from signing informed consent to 
study completion) will be collected on the AE eCRF.  Patients should be instructed to report any 
AE that they experience to the Investigator. Beginning with Visit S1 (Week -5), Investigators 
should make an assessment for AEs at each visit and record the event on the appropriate AE 
eCRF.  
New Text: 
11.2.3 Reporting 
All AEs occurring during the course of the study (starting from signing informed consent to 
study completion or discontinuation) will be collected on the AE eCRF.  Patients should be 
instructed to report any AE that they experience to the Investigator through 30 days following 
the last dose of study drug.  Beginning with Visit S1 (Week -5), Investigators should make an 
assessment for AEs at each visit and record the event on the appropriate AE eCRF. Any SAE 
that occurs from the time of ICF through 30 days following the last dose of study drug should 
be reported to the Sponsor per Section 11.3. 
 
CHANGE 24 
SAE REPORTING REVISIONS 
Location: 
Section 11.2.7.1, Definition of Serious Adverse Event  
Original Text: 
Any clinical endpoints that meet SAE criteria will be reported as SAEs.  The CEC will 
adjudicate clinical endpoints in a blinded fashion, but the DMC will review clinical endpoints 
and SAEs in an unblinded fashion. 
New Text: 
Any clinical endpoints that meet SAE criteria will be reported as SAEs.  The CEC will 
adjudicate clinical endpoints in a blinded fashion, but the DMC will review clinical endpoints 
and SAEs in an unblinded fashion. 
11.2.7.2 
Definition of Serious Adverse Event 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 non-serious AE on the appropriate eCRF page 


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11.2.7.3 
Clinical Laboratory Assessments as Adverse Events and Serious Adverse Events 
It is the responsibility of the investigator to assess the clinical significance of all abnormal 
values as defined by the list of reference ranges from the central (or local where appropriate) 
laboratory.  In some cases, significant changes in lab values within the normal range will 
require similar judgment.  For criteria of reporting abnormal lab values as AE, see 
Section 11.1.6.3 
 
CHANGE 25 
SAE REPORTING REVISIONS 
Location: 
Section 11.3, Reporting Serious Adverse Events 
Original Text: 
11.3 
Reporting Serious Adverse Events 
All SAEs, regardless of relationship to study drug, occurring from the time of informed consent 
until 30 days following study completion or study discontinuation, must be reported by the 
Principal Investigator or designee to the authorized Medical and Safety Services within 24 hours 
of the Principal Investigator or the clinical site becoming aware of the occurrence.  For most 
patients this will be 30 days following their Week 52 (Visit T7) visit. All SAEs that the 
Investigator considers related to study drug that occur after the 30-day follow-up of the study 
period must be reported to the Sponsor.  
To report the SAE, complete the provided SAE form and email or fax it to the contact 
information provided on the SAE form within 24 hours of becoming aware of the occurrence. 
New Text: 
All SAEs, regardless of relationship to study drug, occurring from the time of informed consent 
until 30 days following study completion or study discontinuation, the last dose of IMP must be 
reported by the Principal Investigator or designee to the authorized Medical and Safety Services 
within 24 hours of the Principal Investigator or the clinical site becoming aware of the 
occurrence.  For most patients this will be 30 days following their Week 52 (Visit T7) visit. All 
SAEs that the Investigator considers related to study drug that occur after the 30-day follow-up 
of the study period must be reported to the Sponsor.  
To report the SAE, complete the provided SAE form information in the clinical electronic data 
capture (EDC) database and email or fax it to the contact information provided on the SAE form 
within 24 hours of becoming aware of the occurrence.  Additional information, such as 
diagnostic test results or hospital discharge summary can be sent via email 
 or via fax (
).  
 
CHANGE 26 
PREGNANCY REPORTING REVISIONS 
Location: 
Section 11.3.3, Reports of Pregnancy 


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Clinical Study Protocol 1002-047 
 
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Confidential 
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Original Text: 
11.3.3 
Reports of Pregnancy 
If a female patient becomes pregnant during the study the investigator is to stop dosing with 
study drug(s) immediately. A pregnancy is not considered to be an AE or an SAE; however, it 
must be reported to the Sponsor / SAE designee using the Pregnancy Report Form within the 
same timelines as an SAE. A pregnancy should be followed through to outcome, whenever 
possible. Once the outcome of the pregnancy is known, the Pregnancy Outcome Report Form 
should be completed and reported to the Sponsor. Adverse events or SAEs that occur during 
pregnancy will be assessed and processed according to the AE or SAE processes using the 
appropriate AE or SAE forms. Patients who become pregnant will discontinue IMP immediately 
and complete the End of Study evaluations. 
New Text: 
If a female patient becomes pregnant during the study or within 30 days after the last dose of 
study drug, the investigator is to stop dosing with study drug(s) immediately. A pregnancy is not 
considered to be an AE or an SAE; however, it must be reported to the Sponsor / SAE designee 
using the paper Pregnancy Report Form within the same timelines as an SAE. A pregnancy 
should be followed through to outcome, whenever possible. Once the outcome of the pregnancy 
is known, the paper Pregnancy Outcome Report Form should be completed and reported to the 
Sponsor. Adverse events or SAEs that occur during pregnancy will be assessed and processed 
according to the AE or SAE processes using the appropriate AE CRFor SAE forms. Patients 
who become pregnant will discontinue IMP immediately and complete the End of Study 
evaluations. 
 
CHANGE 27 
STATISTICAL METHODS REVISIONS 
Location: 
Sections 12.1, General Considerations; 12.5, Primary Endpoint; 12.6, Secondary and Tertiary 
Endpoints 
Original Text: 
12.1 
General Considerations 
The statistical analyses described in this section will be performed as further outlined in a 
separate Statistical Analysis Plan (SAP), which will be finalized prior to the first DMC 
assessment of safety.  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. 
New Text: 
12.1 
General Considerations 
The statistical analyses described in this section will be performed as further outlined in a 
separate Statistical Analysis Plan (SAP), which will be finalized prior to the first DMC 
assessment of safety.  The SAP will supersede the protocol in the event of any differences 


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Clinical Study Protocol 1002-047 
 
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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. 
Original Text: 
12.5 
Primary Endpoint; 
The primary efficacy endpoint is the percent change from baseline to Week 12 in LDL-C.  The 
primary efficacy endpoint will be analyzed using analysis of covariance (ANCOVA), with 
treatment group, CV risk (ASCVD only; HeFH with or without ASCVD) and baseline statin 
intensity (high intensity, moderate intensity, low intensity) as factors and baseline LDL-C as a 
covariate.  Baseline LDL-C is defined as the mean of the LDL-C values from Week -1 (Visit S3) 
and predose Day 1/Week 0 (Visit T1).  If a repeat lipid measurement is performed at Week -1 
(Visit S3), then baseline will be the mean of the LDL-C values from the second Week -1 
assessment and predose Day 1/Week 0 (Visit T1).  The ANCOVA will be performed using the 
FAS, with patients included in their randomized treatment group regardless of the treatment they 
actually received.  Two methods for data handling will be used: the first is observed case data 
only, while the second will involve specification of the missing data mechanism using a pattern 
mixture model (PMM).  The primary analysis will be that from the PMM, while the observed 
case analysis will be used as confirmatory.  The PMM will be used to specify different 
imputation strategies depending on whether the patient is still on study treatment.  The PMM will 
be used to specify different imputation strategies depending on whether the patient is still on 
study treatment.  Patients with missing LDL-C data at Week 12 who are no longer taking study 
treatment can be assumed to no longer be benefitting from study medication, and their missing 
value(s) can be assumed to be returning toward their baseline value.  In this instance, it is 
reasonable to impute LDL-C values based on the patients’ baseline value.  Patients with missing 
LDL-C data at Week 12 who are still taking study treatment can be assumed to continue to 
benefit from study medication, and their missing value(s) can be assumed to be similar to those 
who remain on study treatment and have data.  In this instance, it is reasonable to impute LDL-C 
values based on the observed values in their randomized treatment group at Week 12.  To 
account for uncertainty, missing values will be imputed using multiple imputation. 
Imputed datasets will be analyzed using ANCOVA with treatment group, CV risk (ASCVD 
only; HeFH with or without ASCVD) and baseline statin intensity (high intensity, moderate 
intensity, low intensity) as factors and baseline LDL-C as a covariate.  Approximately 
100 imputed datasets will be created, with results from the analysis of each imputed dataset 
combined using Rubin’s method.  For each type of ANCOVA (observed case; imputation via 
PMM), the least squares mean (LSM) and standard error (SE) will be provided for both treatment 
groups, along with the placebo-corrected LSM, its 95% CI and associated p-value.   
12.6 
Secondary and Tertiary Efficacy Endpoints 
Secondary efficacy endpoints are also of interest for this study, in terms of controlling the overall 
Type I error rate.  A gatekeeping or stepdown approach will be used to test the primary efficacy 
endpoint and then specific secondary efficacy endpoints sequentially in order to preserve the 
study-wise Type I error rate.  The sequence for the stepdown procedure in this study is as 
follows: 
1. Test the primary efficacy endpoint: percent change from baseline to Week 12 in LDL-C  


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Clinical Study Protocol 1002-047 
 
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2. Test the percent change from baseline to Week 24 in LDL-C 
3. Test the percent change from baseline to Week 12 in non-HDL-C 
4. Test the percent change from baseline to Week 12 in TC 
5. Test the percent change from baseline to Week 12 in apoB 
6. Test the percent change from baseline to Week 12 in hs-CRP   
In this hierarchical testing structure, each hypothesis is tested at a significance level of 0.05, two-
sided.  Statistical significance at each step is required in order to test the next hypothesis.  If the 
primary endpoint meets the criteria for statistical significance, then the percent change from 
baseline to Week 24 in LDL-C will be tested; and so forth. 
Percent change from baseline to Weeks 24 and 52 in LDL-C; change from baseline to Weeks 12, 
24, and 52 in LDL-C; percent change from baseline to Weeks 12, 24, and 52, in HDL-C, non-
HDL-C, TG, TC, apoB, and hs-CRP will each be analyzed using ANCOVA with treatment 
group, CV risk (ASCVD only; HeFH with or without ASCVD) and baseline statin intensity 
(high intensity, moderate intensity, low intensity) as factors and the relevant baseline as a 
covariate.  Baseline for HDL-C, non-HDL-C, TG, and TC will be defined as the mean of the 
lipid values from Week -1 (Visit S3) and predose Day 1/Week 0 (Visit T1).  If a repeat lipid 
measurement is performed at Week -1 (Visit S3), then baseline will be the mean of the lipid 
values from the second Week -1 assessment and predose Day 1/Week 0 (Visit T1).  Baseline for 
apoB and hs-CRP will be defined as the predose Day 1/Week 0 (Visit T1) value.  Each 
ANCOVA will be performed using the FAS, with patients included in their randomized 
treatment group regardless of the treatment they actually received.  Only observed case data will 
be included in each analysis (no imputation will be performed for missing data).  For each lipid 
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. 
For all continuous efficacy endpoints (percent change from baseline in LDL-C, HDL-C, non-
HDL-C, TC, TG, apoB, and hs-CRP; change from baseline in LDL-C; to Weeks 12, 24, and 52 
as appropriate), the ANCOVA assumption of normality will be assessed.  If non-normality of the 
data is found at any time point for any parameter, either the data will be transformed so that it is 
normally distributed or a nonparametric test will be used instead of the planned ANCOVA. 
Percent change from baseline to Week 24 and to Week 52 LDL-C will be analyzed similarly 
with patients in the FAS who did not receive additional lipid-lowering therapy by that time point 
(by Week 24 for the Week 24 analysis; by Week 52 for the Week 52 analysis) included in the 
analyses. Only observed case data will be used (no imputation for missing data). Output from 
each time point will include the LSM and SE for each treatment group, as well as the placebo-
correct LSM, 95% CI, and p-value. 
New Text: 
12.5  Primary Endpoint; 
The primary efficacy endpoint is the percent change from baseline to Week 12 in LDL-C.  The 
primary efficacy endpoint will be analyzed using analysis of covariance (ANCOVA), with 
treatment group, CV risk (ASCVD only; HeFH with or without ASCVD) and baseline statin 
intensity (high intensity, moderate intensity, low intensity) as factors and baseline LDL-C as a 


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Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
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Page 155 of 184 
covariate.  Baseline LDL-C is defined as the mean of the LDL-C values from Week -1 (Visit S3) 
and predose Day 1/Week 0 (Visit T1).  If a repeat lipid measurement is performed at Week -1 
(Visit S3), then baseline will be the mean of the LDL-C values from the second Week -1 
assessment and predose Day 1/Week 0 (Visit T1). If only one value is available, then that single 
value will be used for baseline.  The details of the ANCOVA model and options to correct for 
unequal variances and group size will be described in the SAP. 
Missing data for the primary endpoint will be imputed using a multiple imputation method 
that accounts for treatment adherence.  A pattern mixture model (PMM) will be used to 
specify different imputation strategies depending on whether the patient is still on study 
treatment.  Imputed datasets will be analyzed using ANCOVA with treatment group, CV risk 
(ASCVD only; HeFH with or without ASCVD) and baseline statin intensity (high intensity, 
moderate intensity, low intensity) as factors as factors and baseline LDL-C as a covariate.  
Approximately 200 imputed datasets will be created, with results from the analysis of each 
imputed dataset combined using Rubin’s method.  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.  A confirmatory 
analysis using observed data only will also be performed for the primary endpoint. Details for 
PMM and multiple imputation will be descried in the SAP. To account for uncertainty, missing 
values will be imputed using multiple imputation. 
The ANCOVA will be performed using the FAS, with patients included in their randomized 
treatment group regardless of the treatment they actually received.  Two methods for data 
handling will be used: the first is observed case data only, while the second will involve 
specification of the missing data mechanism using a pattern mixture model (PMM).  The primary 
analysis will be that from the PMM, while the observed case analysis will be used as 
confirmatory.  The PMM will be used to specify different imputation strategies depending on 
whether the patient is still on study treatment.  The PMM will be used to specify different 
imputation strategies depending on whether the patient is still on study treatment.  Patients with 
missing LDL C data at Week 12 who are no longer taking study treatment can be assumed to no 
longer be benefitting from study medication, and their missing value(s) can be assumed to be 
returning toward their baseline value.  In this instance, it is reasonable to impute LDL C values 
based on the patients’ baseline value.  Patients with missing LDL C data at Week 12 who are 
still taking study treatment can be assumed to continue to benefit from study medication, and 
their missing value(s) can be assumed to be similar to those who remain on study treatment and 
have data.  In this instance, it is reasonable to impute LDL C values based on the observed 
values in their randomized treatment group at Week 12.  To account for uncertainty, missing 
values will be imputed using multiple imputation. 
Imputed datasets will be analyzed using ANCOVA with treatment group, CV risk (ASCVD 
only; HeFH with or without ASCVD) and baseline statin intensity (high intensity, moderate 
intensity, low intensity) as factors and baseline LDL C as a covariate.  Approximately 
100 imputed datasets will be created, with results from the analysis of each imputed dataset 
combined using Rubin’s method.  For each type of ANCOVA (observed case; imputation via 
PMM), the least squares mean (LSM) and standard error (SE) will be provided for both treatment 
groups, along with the placebo corrected LSM, its 95% CI and associated p value.   
12.6 
Secondary and Tertiary Efficacy Endpoints 


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Key secondary efficacy endpoints are also of interest for this study, in terms of controlling the 
overall Type I error rate.  A gatekeeping or stepdown approach will be used to test the primary 
efficacy endpoint and then specific secondary efficacy endpoints sequentially in order to 
preserve the study-wise Type I error rate.  The sequence for the stepdown procedure in this study 
is as follows: 
1. Test the primary efficacy endpoint: percent change from baseline to Week 12 in LDL-C  
2. Test the percent change from baseline to Week 24 in LDL-C 
3. Test the percent change from baseline to Week 12 in non-HDL-C 
4. Test the percent change from baseline to Week 12 in TC 
5. Test the percent change from baseline to Week 12 in apoB 
6. Test the percent change from baseline to Week 12 in hs-CRP   
In this hierarchical testing structure, each hypothesis is tested at a significance level of 0.05, two-
sided.  Statistical significance at each step is required in order to test the next hypothesis.  If the 
primary endpoint meets the criteria for statistical significance, then the percent change from 
baseline to Week 24 in LDL-C will be tested; and so forth. 
In general, change or percent change in lipid parameters at a given time point will be analyzed 
using similar ANCOVA model for the primary endpoint Percent change from baseline to 
Weeks 24 and 52 in LDL C; change from baseline to Weeks 12, 24, and 52 in LDL C; percent 
change from baseline to Weeks 12, 24, and 52, in HDL C, non HDL C, TG, TC, apoB, and 
hs CRP will each be analyzed using ANCOVA with treatment group, CV risk (ASCVD only; 
HeFH with or without ASCVD) and baseline statin intensity (high intensity, moderate intensity, 
low intensity) as factors and the relevant baseline as a covariate.   
Baseline for HDL-C, non-HDL-C, TG, and TC will be defined as the mean of the lipid values 
from Week -1 (Visit S3) and predose Day 1/Week 0 (Visit T1).  If a repeat lipid measurement is 
performed at Week -1 (Visit S3), then baseline will be the mean of the lipid values from the 
second Week -1 assessment and predose Day 1/Week 0 (Visit T1).  Baseline for apoB and 
hs-CRP will be defined as the predose Day 1/Week 0 (Visit T1) value.   
Each ANCOVA will be performed using the FAS, with patients included in their randomized 
treatment group regardless of the treatment they actually received.  Same imputation method 
described for the primary endpoint will be used for those secondary endpoints included in the 
step-down procedure, while only observed data analysis will be used for other secondary and 
tertiary endpoints. Only observed case data will be included in each analysis (no imputation will 
be performed for missing data).  For each lipid 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. 
For all continuous efficacy endpoints (percent change from baseline in LDL C, HDL C, non
HDL C, TC, TG, apoB, and hs CRP; change from baseline in LDL C; to Weeks 12, 24, and 52 
as appropriate), 
Tthe ANCOVA assumption of normality will be assessed.  If non-normality of the data is found 
at any time point for any parameter, either the data will be transformed so that it is normally 
distributed or a nonparametric test will be used considered instead of the planned ANCOVA. 


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Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 157 of 184 
Percent change from baseline to Week 24 and to Week 52 LDL-C will be analyzed similarly 
with patients in the FAS who did not receive additional lipid-lowering therapy by that time point 
(by Week 24 for the Week 24 analysis; by Week 52 for the Week 52 analysis) included in the 
analyses. Only observed case data will be used (no imputation for missing data). Output from 
each time point will include the LSM and SE for each treatment group, as well as the placebo-
correct LSM, 95% CI, and p-value. 
 
CHANGE 28 
SAFETY ENDPOINTS TEXT CLARIFICATION 
Location: 
Section 12.8, Safety Endpoints 
Original Text: 
12.8 
Safety Endpoints 
No statistical analyses will be performed on any of the safety data in this study.   
The summarization of AEs will include TEAEs.  TEAEs and SAEs will be summarized by SOC, 
severity, and relationship to study drug for each treatment group.  These AE summaries will 
include cumulative incidence (percent of patients experiencing the AE) and patient-year adjusted 
incidence rates.  If appropriate, absolute and relative risk differences will be calculated using 
both cumulative incidence and incidence rates.  Deaths, withdrawal from study treatment due to 
AEs, and withdrawal from the study due to AEs will each be summarized by treatment group. 
New Text: 
No statistical analyses will be performed on any of the safety data in this study.   
The summarization of AEs will include TEAEs.  TEAEs and SAEs will be summarized by SOC, 
severity, and relationship to study drug for each treatment group.  These AE summaries will 
include cumulative incidence (percent of patients experiencing the AE) and patient-year adjusted 
incidence rates.  If appropriate, absolute and relative risk differences will be calculated using 
both cumulative incidence and incidence rates.  Deaths, withdrawal from study treatment due to 
AEs, and withdrawal from the study due to AEs will each be summarized by treatment group. 
 
CHANGE 29 
PHARMACOKINETICS REVISION 
Location: 
Section 2, Synopsis; Section 12.9, Pharmacokinetics 
Original Text: 
12.9 
Pharmacokinetics 
Trough plasma concentrations of bempedoic acid and ESP15228 will be collected and 
summarized from patients at predose (T1), Weeks 24 and 52 for use in further developing the 
population PK model. 


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Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 158 of 184 
New Text: 
Trough plasma concentrations of bempedoic acid and ESP15228 will be collected and 
summarized from patients prior to dose at predose (T1), Weeks 24 and 52 for use in further 
developing the population PK model. 
 
CHANGE 30 
MOVED TEXT TO PHARMACY MANUAL 
Location: 
Table 4, Investigational Medicinal Products; Section 17.2, Study Administrative Structure 
Original Text: 
Fill/Finish Manufacturing: 
 
 
 
 
 
 
 
 
 
 
Secondary Packaging/Depot for Clinical Site Drug Shipments:  
 
 
 
 
 
 
 
 
 
 
New Text: 
Investigational medicinal product (IMP) supply chain details can be found in the pharmacy 
manual. 
Fill/Finish Manufacturing: 
 
 


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Secondary Packaging/Depot for Clinical Site Drug Shipments:  
 
 
 
 
 
 
 
 
 
 
 
CHANGE 31 
SCHEDULE OF EVENTS REVISIONS 
Location: 
Appendix 1, Schedule of Events (Subject Visit Schedule) 
Original Text: 
APPENDIX 1. 
SCHEDULE OF EVENTS (SUBJECT VISIT SCHEDULE) 
 
 
Screen Run-in 
Treatment 
 
 
Visit 
S11,2 
S2 
S3 
T1 
T2 
T3/phone 
T4 
T5 
T6/phone T7/EOS3 
Week 
Wk 
-5 
Wk 
-4 
Wk 
-1 
Wk 
0 
Wk 
4 
Wk 
8 
Wk 
12 
Wk 
24 
Wk 
36 
Wk 
52 
Procedure 
Day 
--35 
Day 
-28 
Day 
-7 
Day 
1 
Day 
29±3 
Day 
57±3 
Day 
85±3 
Day 
169±7 
Day 
252±7 
Day 365 
±7 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
Enrollment Criteria 
X 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
HeFH Status Determination 
X 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Event Recording 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
 
 
 
X 
 
 
 
 
 
X 
Weight4 
X 
 
 
X 
X 
 
X 
X 
 
X 
Height/BMI 
X 
 
 
 
 
 
 
 
 
 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 160 of 184 
 
 
Screen Run-in 
Treatment 
 
 
Visit 
S11,2 
S2 
S3 
T1 
T2 
T3/phone 
T4 
T5 
T6/phone T7/EOS3 
Week 
Wk 
-5 
Wk 
-4 
Wk 
-1 
Wk 
0 
Wk 
4 
Wk 
8 
Wk 
12 
Wk 
24 
Wk 
36 
Wk 
52 
Procedure 
Day 
--35 
Day 
-28 
Day 
-7 
Day 
1 
Day 
29±3 
Day 
57±3 
Day 
85±3 
Day 
169±7 
Day 
252±7 
Day 365 
±7 
12-Lead ECG5 
 
 
 
X 
 
 
 
 
 
X 
Vital Signs6 
X 
X 
X 
X 
X 
 
X 
X 
 
X 
Serology7 
X 
 
 
 
 
 
 
 
 
 
Serum Pregnancy and/or FSH8  
X 
 
 
 
 
 
 
 
 
 
Urine Pregnancy Test8 
 
 
 
X 
 
 
 
 
 
 
TSH 
X 
 
 
 
 
 
 
 
 
 
Clinical Safety Labs9 
X 
 
 
X 
X 
 
X 
X 
 
X 
Basic Fasting Lipids10 
X 
 
X 
X 
X 
 
X 
X 
 
X 
HbA1C 
X 
 
 
X 
 
 
X 
X 
 
X 
10 mL reserve sample 
 
 
 
X 
 
 
 
 
 
X 
Genetic sample (optional) 
 
 
 
X 
 
 
 
 
 
 
apoB 
 
 
 
X 
 
 
X 
 
 
X 
hs-CRP 
 
 
 
X 
 
 
X 
 
 
X 
Diet and exercise counseling11 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Plasma PK 
 
 
 
X 
 
 
 
X 
 
X 
Establish Patient Eligibility 
 
 
 
X 
 
 
 
 
 
 
Randomization 
 
 
 
X 
 
 
 
 
 
 
IWRS Contact 
X 
X 
 
X 
 
 
X 
X 
 
X12 
Single-Blind Drug Dispensing 
 
X 
 
 
 
 
 
 
 
 
Double-blind Drug Dispensing13 
 
 
 
X 
 
 
X 
X 
 
 
Drug Return/Compliance 
 
 
X 
X 
X 
 
X 
X 
 
X 
Schedule next visit 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
NOTE: For patients who withdraw from IMP 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 (except for apoB and hs-CRP), adverse events, PE, vital signs, and ECGs. For patients who withdraw from IMP 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 T7 will be considered the EOS/Early Withdrawal from study and no further visits will be 
scheduled. 
1 An optional visit approximately 1 week later MAY be completed if patient fails to meet a lipid entry criterion. If this optional basic 
fasting (minimum of 10 hours) lipid value visit is completed, the mean of the first value and repeat lipid value will be used to 
determine eligibility. 
2 An optional visit between Visits S1 and T1 may be completed if the patient’s DBP and/or 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. An optional 
visit between Visit S1 and T1 may be completed to determine eligibility if the patient’s eGFR, ALT, AST, and/or TB meet exclusion 
criteria levels. If this optional visit is completed, the repeated value will be used to determine eligibility. 
3 All procedures will be completed for all patients at either End of Study (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).  
5 Single 12-lead ECG will be collected prior to any blood sample collection. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 161 of 184 
6 Vital signs will include DBP, SBP, and 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  
8 Serum pregnancy test completed in premenopausal women only.  FSH test is completed in women <55 years old and >1 year without 
menses. Urine pregnancy test in women of childbearing potential just prior to randomization.  
9 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits. Coagulation is included at Screening (Visit S1), 
Baseline (Visit T1) only if on anticoagulants).  Please refer to laboratory manual for detailed schedule of tests. 
10 Basic fasting (minimum of 10 hours) lipids include total cholesterol, calculated LDL-C, HDL-C, non-HDL-C, and triglycerides. 
Repeat within 1 week if exceed protocol-specified criteria. 
11 Diet and exercise counseling per local and/or regional guidelines for the management of hyperlipidemia. 
12 IWRS contact at either an early withdrawal or an EOS visit to register study discontinuation visit date.  
13 Depending upon the length of time between visits, 1 or 2 bottles of study medication will be dispensed as instructed by IWRS. 
14 If patient is discontinuing treatment and completing the EOS visit, but will be continuing in the study either by returning to clinic or 
by phone, continue to schedule study visits for the patient according to the protocol Schedule of Events 
 
New Text: 
APPENDIX 1. 
SCHEDULE OF EVENTS (SUBJECT VISIT SCHEDULE) 
 
 
Screen Run-in 
Treatment* 
 
 
Visit 
S11,2 
S2 
S3 
T1 
T2 
T3/phone 
T4 
T5 
T6/phone T7/EOS3 
Week 
Wk 
-5 
Wk 
-4 
Wk 
-1 
Wk 
0 
Wk 
4 
Wk 
8 
Wk 
12 
Wk 
24 
Wk 
36 
Wk 
52 
Procedure 
Day 
--35±7 
Day 
-28±3 
Day 
-7±3 
Day 
1 
Day 
29±3 
Day 
57±3 
Day 
85±3 
Day 
169±7 
Day 
252±7 
Day 365 
±7 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
Enrollment Criteria 
X 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
HeFH Status Determination 
X 
 
 
 
 
 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Event Recording 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
 
 
 
X 
 
 
 
 
 
X 
Weight4 
X 
 
 
X 
X 
 
X 
X 
 
X 
Height/BMI 
X 
 
 
 
 
 
 
 
 
 
12-Lead ECG5 
 
 
 
X 
 
 
 
 
 
X 
Vital Signs6 
X 
X 
X 
X 
X 
 
X 
X 
 
X 
Serology7 
X 
 
 
 
 
 
 
 
 
 
Serum Pregnancy and/or FSH8  
X 
 
 
 
 
 
 
 
 
 
Urine Pregnancy Test8 
 
 
 
X 
 
 
 
 
 
 
TSH 
X 
 
 
 
 
 
 
 
 
 
Clinical Safety Labs9 
X 
 
 
X 
X 
 
X 
X 
 
X 
Basic Fasting Lipids10 
X 
 
X 
X 
X 
 
X 
X 
 
X 
HbA1C 
X 
 
 
X 
 
 
X 
X 
 
X 
10 mL reserve sample 
 
 
 
X 
 
 
 
 
 
X 
Genetic sample (optional) 
 
 
 
X 
 
 
 
 
 
 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 162 of 184 
apoB 
 
 
 
X 
 
 
X 
X 
 
X 
hs-CRP 
 
 
 
X 
 
 
X 
X 
 
X 
Diet and exercise counseling11 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Plasma PK 
 
 
 
X 
 
 
 
X 
 
X 
Establish Patient Eligibility 
 
 
 
X 
 
 
 
 
 
 
Randomization 
 
 
 
X 
 
 
 
 
 
 
IWRS Contact 
X 
X 
 
X 
 
 
X 
X 
 
X12 
Single-Blind Drug Dispensing 
 
X 
 
 
 
 
 
 
 
 
Double-blind Drug Dispensing13 
 
 
 
X 
 
 
X 
X 
 
 
Drug Return/Compliance 
 
 
X 
X 
X 
 
X 
X 
 
X 
Schedule next visit 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
NOTE: For patients who withdraw from IMP treatment, but consent to be followed for safety assessments and return to clinic for these 
visit, the they will continue to have visits will occur according to the protocol schedule. Safety assessments should include clinical 
safety and basic lipid laboratories (except for apoB and hs-CRP), adverse events, PE, vital signs, and ECGs. For patients who 
withdraw from IMP treatment, but refuse to come to the clinic for assessments consent to be followed for safety assessments will take 
place 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 T7 will be considered the EOS/Early Withdrawal from study and no further visits will be scheduled. 
* Patients receiving simvastatin 40 mg will have clinic visits performed at Weeks 16 and 28 and telephone visits at Weeks 20 and 32.  
At clinic visits at Weeks 16 and 28, perform clinical safety labs as defined in Footnote 9, assess adverse events and review changes 
in concomitant medications.  At telephone visits performed at Weeks 20 and 32, assess adverse events and review changes in 
concomitant medications.   
1 An optional visit approximately 1 week later MAY between Visits S1 and S2 may completed if patient fails to meet a lipid entry TG 
criterion. If this optional basic fasting (minimum of 10 hours) lipid value visit is completed, the mean of the first value and repeat lipid 
value will be used to determine eligibility. 
2 An optional visit between Visits S1 and S2 T1 may be completed if the patient’s DBP and/or 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. An optional 
visit between Visit S1 and S2 T1 may be completed to determine eligibility if the patient’s eGFR, ALT, AST, and/or TB meet 
exclusion criteria levels. If this optional visit is completed, the repeated value will be used to determine eligibility. 
3 All procedures will be completed for all patients at either End of Study (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).  
5 Single 12-lead ECG will be collected prior to any blood sample collection. 
6 Vital signs will include DBP, SBP, and 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  
8 Serum pregnancy test completed in premenopausal women only.  FSH test is completed in women <55 years old and >1 year without 
menses. Urine pregnancy test in women of childbearing potential just prior to randomization.  
9 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits. Coagulation is included at Screening (Visit S1) 
for all patients, Baseline (Visit T1) and 3-5 days after Visit T1 only if on anticoagulants).  Please refer to laboratory manual for 
detailed schedule of tests.  A local laboratory may be used for assessment at 3-5 days after Visit T1. 
.10Basic fasting (minimum of 10 hours) lipids include total cholesterol, calculated LDL-C, HDL-C, non-HDL-C, and triglycerides. 
Repeat within 1 week if exceed protocol-specified criteria. 
11 Diet and exercise counseling per local and/or regional guidelines for the management of hyperlipidemia. 
12 IWRS contact at either an early withdrawal or an EOS visit to register study discontinuation visit date.  
13 Depending upon the length of time between visits, 1 or 2 bottles of study medication will be dispensed as instructed by IWRS. 
14If patient is discontinuing treatment and completing the EOS visit, but will be continuing in the study either by returning to clinic or by 
phone, continue to schedule study visits for the patient according to the protocol Schedule of Events 
 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 163 of 184 
APPENDIX 8. SUMMARY OF CHANGES AMENDMENT 3 
 
SUMMARY OF CHANGES 
CLINICAL STUDY PROTOCOL 
Study Number: 
1002-047 
Study Title: 
A Long-term, Randomized, Double-blind, Placebo-
controlled, Multicenter Study to Evaluate the Efficacy of 
Bempedoic Acid (ETC-1002) in Patients with 
Hyperlipidemia at High Cardiovascular Risk Not 
Adequately Controlled by Their Lipid-Modifying Therapy 
Protocol Version Incorporating 
Current Summary of Changes: 
Amendment 3:  09 May 2017 
Preceding Protocol Version: 
Amendment 2:  22 March 2017 
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 
The protocol was amended for the following: 
• Added a line for Amendment 3 version and date to reflect amendment version details. 
• Prohibited use of simvastatin ≥40 mg/day 
 
 
 The protocol has been 
amended to exclude patients receiving simvastatin ≥40 mg and remove study visits at 
Weeks 16, 20, 28, and 32 that were only for patients taking simvastatin 40 mg/day.  A 
letter was provided to all investigators with instructions on how to proceed for 
enrolled patients receiving simvastatin 40 mg/day. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 164 of 184 
• Increased number of patients to be enrolled from approximately 525 to approximately 
750 with 500 randomized to bempedoic acid and 250 randomized to matching 
placebo as was included in the original protocol and Amendment 1.  The reason for 
the increase in patients is due to the recent decision to discontinue IMP in patients 
receiving simvastatin 40 mg/day across our program. Based on this decision, the 
safety database will be smaller than anticipated; therefore, we would like to increase 
the number of patients in this protocol to 750 as originally planned to ensure a robust 
safety database. 
• Clarified that the requirement to have ≥80% treatment compliance during the Run-in 
Period refers to the average treatment compliance over the entire Run-in Period 
(compliance measured at Visits S3 and T1). 
• Corrected the visit window for Week 24 within the protocol text and Appendix 1, 
Schedule of Events, to reflect 168 ± 7 days.  
• Updated the definition of SAEs to include hospitalizations for preplanned surgeries 
and/or elective surgeries. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 165 of 184 
CHANGE 1 
REVISION OF TITLE PAGE VERSION INFORMATION 
Location: 
Title Page  
Original Text: 
 
Version 
Date 
 
 
Amendment 1: 
18 January 2017 
 
 
Amendment 2: 
22 March 2017 
 
New Text: 
 
Version 
Date 
 
 
Amendment 1: 
18 January 2017 
 
 
Amendment 2: 
22 March 2017 
 
 
Amendment 3: 
09 May 2017 
 
 
CHANGE 2 
REVISION TO LOCATION OF SITES 
Location: 
Section 2, Synopsis 
Original Text: 
Clinical Sites: Approximately 125 sites located TBD 
New Text: 
Clinical Sites: Approximately 125 sites located TBDin North America and Europe 
 


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Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 167 of 184 
CHANGE 4 
SUBJECT EXCLUSION CRITERIA REVISIONS 
Location:  
Section 2, Synopsis; Section 7.2, Subject Exclusion Criteria 
Original Text: 
2. Renal dysfunction or nephritic syndrome or a history of nephritis, including estimated 
glomerular filtration rate (eGFR) (using central laboratory determined Modification of 
Diet in Renal Disease [MDRD] formula) <30 mL/min/1.73m2 at Week -5 (Visit S1) 
(Levey 2006).  In patients taking simvastatin 40 mg, eGFR <45 mL/min/1.73 m2 is 
exclusionary. 
Note: At the discretion of the investigator, the screening period may be extended up to 
4 weeks for a single repeat eGFR.  For those patients who have a repeat eGFR, the repeat 
value should be obtained between Visits S1 and S2 and will be used to determine 
eligibility. 
New Text: 
2. Renal dysfunction or nephritic syndrome or a history of nephritis, including estimated 
glomerular filtration rate (eGFR) (using central laboratory determined Modification of 
Diet in Renal Disease [MDRD] formula) <30 mL/min/1.73m2 at Week -5 (Visit S1) 
(Levey 2006).  In patients taking simvastatin 40 mg, eGFR <45 mL/min/1.73 m2 is 
exclusionary. 
Note: At the discretion of the investigator, the screening period may be extended up to 
4 weeks for a single repeat eGFR.  For those patients who have a repeat eGFR, the repeat 
value should be obtained between Visits S1 and S2 and will be used to determine 
eligibility. 
Original Text: 
17. Use of any of the following drugs or a plan to use these drugs during the study:  
• New or planned dose changes of systemic corticosteroids.  Stable doses (≥4 weeks 
before Visit S1) and topical corticosteroids allowed.  
• CETP inhibitors within the last 2 years prior to screening (Week -5, Visit S1) except 
for evaceptrapib within the last 3 months prior to screening (Week -5, Visit S1) 
• Mipomersen (6 months prior to screening, Week -5, Visit S1) 
• Lomitapide (3 months prior to screening, Week -5, Visit S1) 
• Apheresis (3 months prior to screening, Week -5, Visit S1) 
• Simvastatin >40 mg (4 weeks prior to screening, Week -5, Visit S1) 
• Red yeast rice extract -containing products are not allowed (2 weeks prior to 
screening, Week -5, Visit S1) 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 168 of 184 
New Text 
17. Use of any of the following drugs or a plan to use these drugs during the study:  
• New or planned dose changes of systemic corticosteroids.  Stable doses (≥4 weeks 
before Visit S1) and topical corticosteroids allowed.  
• CETP inhibitors within the last 2 years prior to screening (Week -5, Visit S1) except 
for evaceptrapib within the last 3 months prior to screening (Week -5, Visit S1) 
• Mipomersen (6 months prior to screening, Week -5, Visit S1) 
• Lomitapide (3 months prior to screening, Week -5, Visit S1) 
• Apheresis (3 months prior to screening, Week -5, Visit S1) 
• Simvastatin >≥40 mg/day (4 weeks prior to screening, Week -5, Visit S1) 
• Red yeast rice extract -containing products are not allowed (2 weeks prior to 
screening, Week -5, Visit S1) 
 
CHANGE 5 
INCREASE IN NUMBER OF PATIENTS TO BE ENROLLED 
Location: 
Section 2, Synopsis, Study Design 
Original Text: 
Approximately 525 eligible patients will be randomized 2:1 on Day 1 (Visit T1) to receive either 
bempedoic acid 180 mg (n = 350), or placebo (n = 175) once daily for 52 weeks.  Randomized 
patients will return for clinic visits at Week 4 (Visit T2), Week 12 (Visit T4), Week 24 
(Visit T5), and Week 52 (T7).  A phone visit will occur at Week 8 (Visit T3) and Week 36 (T6).  
Patients who withdraw from investigational medicinal product (IMP) treatment will be asked to 
continue to be followed for safety using the protocol-specified visit schedule and procedures.  
For details of study assessments, see the Schedule of Events in Appendix 1. 
New Text: 
Approximately 750525 eligible patients will be randomized 2:1 on Day 1 (Visit T1) to receive 
either bempedoic acid 180 mg (n = 500350), or placebo (n = 250175) once daily for 52 weeks.  
Randomized patients will return for clinic visits at Week 4 (Visit T2), Week 12 (Visit T4), 
Week 24 (Visit T5), and Week 52 (T7).  A phone visit will occur at Week 8 (Visit T3) and 
Week 36 (T6).  Patients who withdraw from investigational medicinal product (IMP) treatment 
will be asked to continue to be followed for safety using the protocol-specified visit schedule and 
procedures.  For details of study assessments, see the Schedule of Events in Appendix 1. 
Location: 
Section 2, Synopsis: Number of patients (planned) 
Original Text: 
Number of patients (planned): Approximately 525 adult male and female patients 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 169 of 184 
New Text: 
Number of patients (planned): Approximately 750525 adult male and female patients 
Location: 
Section 2, Synopsis: Statistical methods, Sample Size 
Original Text: 
The primary efficacy endpoint for this study is the percent change from baseline to Week 12 in 
LDL-C.   
The sample size of 350 randomized patients in the bempedoic acid 180 mg group and 
175 randomized patients in the placebo group is expected to provide more than 95% power to 
detect a difference of 15% in the percent change from baseline to Week 12 in LDL-C between 
the bempedoic acid treatment group and the placebo group.  This calculation is based on a 
2-sided t-test at the 5% level of significance (α = 0.05) and a common standard deviation of 15%.  
The sample size of 350 randomized patients in the bempedoic acid 180 mg group and 
175 randomized patients in the placebo group gives a total study sample size of 525.  
New Text: 
The primary efficacy endpoint for this study is the percent change from baseline to Week 12 in 
LDL-C.   
The sample size of 500350 randomized patients in the bempedoic acid 180 mg group and 
250175 randomized patients in the placebo group is expected to provide more than 95% power to 
detect a difference of 15% in the percent change from baseline to Week 12 in LDL-C between 
the bempedoic acid treatment group and the placebo group.  This calculation is based on a 
2-sided t-test at the 5% level of significance (α = 0.05) and a common standard deviation of 15%.  
The sample size of 500350 randomized patients in the bempedoic acid 180 mg group and 
250175 randomized patients in the placebo group gives a total study sample size of 750525.  
Location: 
Section 6.1, Overall Study Design 
Original Text: 
Approximately 525 eligible patients will be randomized 2:1 on Day 1 (Visit T1) to receive either 
bempedoic acid 180 mg (n = 350), or placebo (n = 175) once daily for 52 weeks.  Randomized 
patients will return for clinic visits at Week 4 (Visit T2), Week 12 (Visit T4), Week 24 
(Visit T5), and Week 52 (Visit T7).  A phone visit will occur at Week 8 (Visit T3) and Week 36 
(Visit T6).  For patients taking simvastatin 40 mg, there will be additional clinic visits to assess 
safety at Weeks 16 and 28 as well as telephone visits at Weeks 20 and 32. 
New Text: 
Approximately 750525 eligible patients will be randomized 2:1 on Day 1 (Visit T1) to receive 
either bempedoic acid 180 mg (n = 500350), or placebo (n = 250175) once daily for 52 weeks.  
Randomized patients will return for clinic visits at Week 4 (Visit T2), Week 12 (Visit T4), 
Week 24 (Visit T5), and Week 52 (Visit T7).  A phone visit will occur at Week 8 (Visit T3) and 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 170 of 184 
Week 36 (Visit T6).  For patients taking simvastatin 40 mg, there will be additional clinic visits 
to assess safety at Weeks 16 and 28 as well as telephone visits at Weeks 20 and 32. 
Location: 
Section 6.2, Study Hypothesis 
Original Text: 
The study will assess the 12-week efficacy of bempedoic acid in decreasing LDL-C versus 
placebo in addition to maximally tolerated lipid-lowering therapy, including a maximally 
tolerated statin alone or in combination with other lipid-lowering therapies, in patients with 
hyperlipidemia.  The randomized, double-blind, placebo-controlled add-on to maximally 
tolerated lipid-lowering therapy design will ensure that efficacy data are meaningful and 
interpretable.  The treatment duration (52 weeks) and large patient number (n = 525) will provide 
robust long-term data on lipid profile, safety, and tolerability in high CV risk patients who have 
an unmet medical need for additional lipid-lowering therapy, such as bempedoic acid once daily, 
orally bioavailable option. 
New Text: 
The study will assess the 12-week efficacy of bempedoic acid in decreasing LDL-C versus 
placebo in addition to maximally tolerated lipid-lowering therapy, including a maximally 
tolerated statin alone or in combination with other lipid-lowering therapies, in patients with 
hyperlipidemia.  The randomized, double-blind, placebo-controlled add-on to maximally 
tolerated lipid-lowering therapy design will ensure that efficacy data are meaningful and 
interpretable.  The treatment duration (52 weeks) and large patient number (n = 750525) will 
provide robust long-term data on lipid profile, safety, and tolerability in high CV risk patients 
who have an unmet medical need for additional lipid-lowering therapy, such as bempedoic acid 
once daily, orally bioavailable option. 
Location: 
Section 6.5, Number of Patients 
Original Text: 
The study will enroll approximately 525 adult male and female HeFH and/or ASCVD patients 
with hyperlipidemia from approximately 125 clinical sites.  
New Text: 
The study will enroll approximately 750525 adult male and female HeFH and/or ASCVD 
patients with hyperlipidemia from approximately 125 clinical sites.  
Location: 
Section 12.2, Determination of Sample Size 
Original Text: 
The primary efficacy endpoint for this study is the percent change from baseline to Week 12 in 
LDL-C.   
The sample size of 350 randomized patients in the bempedoic acid 180 mg group and 
175 randomized patients in the placebo group is expected to provide more than 95% power to 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 171 of 184 
detect a difference of 15% in the percent change from baseline to Week 12 in LDL-C between 
the bempedoic acid treatment group and the placebo group.  This calculation is based on a 
2-sided t-test at the 5% level of significance (α = 0.05) and a common standard deviation of 15%.  
The sample size of 350 randomized patients in the bempedoic acid 180 mg group and 
125 randomized patients in the placebo group gives a total study sample size of 525. 
New Text: 
The primary efficacy endpoint for this study is the percent change from baseline to Week 12 in 
LDL-C.   
The sample size of 500350 randomized patients in the bempedoic acid 180 mg group and 
250175 randomized patients in the placebo group is expected to provide more than 95% power to 
detect a difference of 15% in the percent change from baseline to Week 12 in LDL-C between 
the bempedoic acid treatment group and the placebo group.  This calculation is based on a 
2-sided t-test at the 5% level of significance (α = 0.05) and a common standard deviation of 15%.  
The sample size of 500350 randomized patients in the bempedoic acid 180 mg group and 
250175 randomized patients in the placebo group gives a total study sample size of 750525.   
 
CHANGE 6 
BASELINE STATIN DOSE CATEGORIES TABLE REVISIONS 
Location: 
Section 2, Synopsis; Section 6.1, Overall Study Design, Table 2 
Original Text: 
High Intensity Statinsa 
Moderate Intensity Statins 
Low Intensity Statinsb 
Atorvastatin 40-80 mg 
Atorvastatin 10-20 mg 
Simvastatin 10 mg 
Rosuvastatin 20-40 mg 
Rosuvastatin 5-10 mg 
Pravastatin 10-20 mg 
 
Simvastatin 20-40 mg 
Lovastatin 20 mg 
 
Pravastatin 40-80 mg 
Fluvastatin 20-40 mg 
 
Lovastatin 40 mg 
Pitavastatin 1 mg 
 
Fluvastatin XL 80 mg 
 
 
Fluvastatin 40 mg BID 
 
 
Pitavastatin 2-4 mg 
 
a Simvastatin doses >40 mg average daily dose not allowed  
b Low intensity statins also include those patients taking low-dose statins using an alternate regimen 
(ie, every other day, or for a specified number of times per week) and those unable to tolerate a statin 
at any dose 


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Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 172 of 184 
New Text:  
High Intensity Statinsa 
Moderate Intensity Statins 
Low Intensity Statinsb 
Atorvastatin 40-80 mg 
Atorvastatin 10-20 mg 
Simvastatin 10 mg 
Rosuvastatin 20-40 mg 
Rosuvastatin 5-10 mg 
Pravastatin 10-20 mg 
 
Simvastatin 20 mg20 40 mg 
Lovastatin 20 mg 
 
Pravastatin 40-80 mg 
Fluvastatin 20-40 mg 
 
Lovastatin 40 mg 
Pitavastatin 1 mg 
 
Fluvastatin XL 80 mg 
 
 
Fluvastatin 40 mg BID 
 
 
Pitavastatin 2-4 mg 
 
a Simvastatin doses >≥40 mg/day are average daily dose not allowed. 
b Low intensity statins also include those patients taking low-dose statins using an alternate regimen 
(ie, every other day, or for a specified number of times per week) and those unable to tolerate a statin 
at any dose 
 
CHANGE 7 
SAFETY AND MONITORING REVISIONS 
Location: 
Section 2, Synopsis: Monitoring and Management Plans for Lipid Elevations;  
Section 11.1.6.4.1, Monitoring and Management of Elevated LDL-C 
Original Text: 
An adjunctive therapy plan is in place for those patients whose LDL-C values meet the protocol-
defined LDL-C threshold criteria. Post-randomization, LDL-C results will be masked to 
investigators in order to maintain the blind; however, the following thresholds have been set to 
notify investigators and provide an opportunity to adjust the patient’s standard of care regimen.  
• Beginning at Week 24 (Visit T5) visit and for the duration of the study, the central 
laboratory will notify the investigator when the patient’s LDL-C value is >170 mg/dL 
(4.4 mmol/L) and ≥25% from the patient’s baseline value at Week 0 (Visit T1) 
• Upon receiving notification from the central laboratory that the patient has met or 
exceeded the threshold criteria for LDL-C, the investigator will initiate the following 
adjunctive therapy plan: 
− Patients will be scheduled to return to the clinic within 1 week for a repeat fasting 
blood lipid sample to confirm that the LDL-C value meets the threshold criteria  
− After confirming that the LDL-C value meets or exceeds the threshold criteria, the 
investigator will adjust the patient’s lipid-lowering treatment regimen per 
standard-of-care and local practice, with the exception of simvastatin at daily 
doses greater than 40 mg and the fibrate gemfibrozil. The patient’s LDL-C will be 
re-evaluated at the next scheduled clinic visit as defined in the Schedule of Visits 
(Appendix 1). 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 173 of 184 
New Text: 
An adjunctive therapy plan is in place for those patients whose LDL-C values meet the protocol-
defined LDL-C threshold criteria. Post-randomization, LDL-C results will be masked to 
investigators in order to maintain the blind; however, the following thresholds have been set to 
notify investigators and provide an opportunity to adjust the patient’s standard of care regimen.  
• Beginning at Week 24 (Visit T5) visit and for the duration of the study, the central 
laboratory will notify the investigator when the patient’s LDL-C value is >170 mg/dL 
(4.4 mmol/L) and ≥25% from the patient’s baseline value at Week 0 (Visit T1) 
• Upon receiving notification from the central laboratory that the patient has met or 
exceeded the threshold criteria for LDL-C, the investigator will initiate the following 
adjunctive therapy plan: 
− Patients will be scheduled to return to the clinic within 1 week for a repeat fasting 
blood lipid sample to confirm that the LDL-C value meets the threshold criteria  
− After confirming that the LDL-C value meets or exceeds the threshold criteria, the 
investigator will adjust the patient’s lipid-lowering treatment regimen per 
standard-of-care and local practice, with the exception of simvastatin at daily 
doses greater than ≥40 mg/day and the fibrate gemfibrozil. The patient’s LDL-C 
will be re-evaluated at the next scheduled clinic visit as defined in the Schedule of 
Visits (Appendix 1). 
 
CHANGE 8 
CONCOMITANT MEDICATIONS REVISIONS 
Location:  
Section 8.2.1, Lipid-Regulating Medications and Supplements 
Original Text: 
Statins 
• Atorvastatin (Lipitor®, Sortis®) 
• Fluvastatin (Lescol®) 
• Lovastatin (Mevacor®, Altoprev™) 
• Pravastatin (Pravachol®) 
• Pitavastatin (Livalo®, Lipostat®) 
• Rosuvastatin (Crestor®) 
• Simvastatin (Zocor®) (doses ≥40 mg are exclusionary) 
New Text: 
Statins 
• Atorvastatin (Lipitor®, Sortis®) 
• Fluvastatin (Lescol®) 


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Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 174 of 184 
• Lovastatin (Mevacor®, Altoprev™) 
• Pravastatin (Pravachol®) 
• Pitavastatin (Livalo®, Lipostat®) 
• Rosuvastatin (Crestor®) 
• Simvastatin (Zocor®) (doses ≥40 mg/day are exclusionary) 
Original Text: 
Other 
• Simvastatin/ezetimibe (Vytorin®, Inegy®)  
• Atorvastatin/ezetimibe (Atozet®) 
New Text: 
Other 
• Simvastatin/ezetimibeEzetimibe/simvastatin where simvastatin is less than 
40 mg/day (Vytorin® 10/10 and 10/20, Inegy® 10 mg/20 mg are allowed)  
• Atorvastatin/ezetimibe (Atozet®) 
 
CHANGE 9 
PROHIBITED MEDICATIONS REVISIONS 
Location:  
Section 8.2.2, Prohibited Medications 
Original Text: 
Patients will not have used medications (monotherapies or combination therapies) listed below 
within the allotted time period prior to screening or use these drugs during the study: 
• New or planned dose changes of systemic corticosteroids.  Stable doses of systemic 
corticosteroids at screening are allowed (≥4 weeks).  Short-term intermittent use 
(<14 days) of pulse steroids are allowed.  Topical steroids are allowed. 
• Gemfibrozil (Lopid®) (as per co-administration instructions defined in the statin 
label) ≥6 weeks prior to screening (Visit S1) 
• Cholestin (red yeast rice extract, also known as monascus purpureus extract) 
(≥2 weeks prior to screening) 
• CETP inhibitors within the last 2 years prior to screening (Visit S1) except for 
evaceptrapib within the last 3 months prior to screening (Visit S1) 
• Mipomersen within 6 months prior to screening (Visit S1) 
• Lomitapide within 3 months prior to screening (Visit S1) 
• Apheresis within 3 months prior to screening (Visit S1) 
• Simvastatin >40 mg 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 175 of 184 
New Text: 
Patients will not have used medications (monotherapies or combination therapies) listed below 
within the allotted time period prior to screening or use these drugs during the study: 
• New or planned dose changes of systemic corticosteroids.  Stable doses of systemic 
corticosteroids at screening are allowed (≥4 weeks).  Short-term intermittent use 
(<14 days) of pulse steroids are allowed.  Topical steroids are allowed. 
• Gemfibrozil (Lopid®) (as per co-administration instructions defined in the statin 
label) ≥6 weeks prior to screening (Visit S1) 
• Cholestin (red yeast rice extract, also known as monascus purpureus extract) 
(≥2 weeks prior to screening) 
• CETP inhibitors within the last 2 years prior to screening (Visit S1) except for 
evaceptrapib within the last 3 months prior to screening (Visit S1) 
• Mipomersen within 6 months prior to screening (Visit S1) 
• Lomitapide within 3 months prior to screening (Visit S1) 
• Apheresis within 3 months prior to screening (Visit S1) 
• Simvastatin >≥40 mg/day 
• Ezetimibe/simvastatin where simvastatin doses are ≥40 mg/day (Vytorin® 10/40 and 
10/80 and Inegy® 10 mg/40 mg and 10 mg/80 mg are exclusionary) 
 
CHANGE 10 
TREATMENT COMPLIANCE REVISIONS 
Location:  
Section 8.3, Treatment Compliance 
Original Text: 
Screening Compliance 
No study medication treatment will be given during the Screening period; therefore, compliance 
will not be assessed.  
Placebo Run-in and Treatment Period Adherence 
At Week -1 (S3) visit in the placebo run-in period and at each of the subsequent patient visits, 
designated clinical site staff will assess patient for placebo and/or IMP adherence by counting the 
number of tablets that are returned as unused and by querying the patient with regards to daily 
intake.  If the patient has not taken all doses of study drug as instructed, the patient will be 
queried for a reason, findings will be documented, and the patient will be counseled on the 
importance of carefully following all dosing instructions.  Factors contributing to poor adherence 
will be determined and, if possible, remedied.  Patients demonstrating poor adherence will 
continue to be counseled on the importance of carefully following all dosing instructions, but 
will not be removed from the study.  However, patients with ≤80% adherence and/ or who 
experienced a study drug-related AE, will not go onto randomization.  


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 176 of 184 
New Text: 
Screening Compliance 
No study medication treatment will be given during the Screening period; therefore, compliance 
will not be assessed.  
Placebo Run-in and Treatment Period Adherence 
At Week -1 (S3) visit in the placebo run-in period and at each of the subsequent patient visits, 
designated clinical site staff will assess patient for placebo and/or IMP adherence by counting the 
number of tablets that are returned as unused and by querying the patient with regards to daily 
intake.  If the patient has not taken all doses of study drug as instructed, the patient will be 
queried for a reason, findings will be documented, and the patient will be counseled on the 
importance of carefully following all dosing instructions.  Factors contributing to poor adherence 
will be determined and, if possible, remedied.  Patients demonstrating poor adherence will 
continue to be counseled on the importance of carefully following all dosing instructions, but 
will not be removed from the study.  However, patients with ≤80% adherence over the entire 
Run-in Period and/ or who experienced a study drug-related AE, will not go onto randomization.  
 
CHANGE 11 
PROCEDURES AND SCHEDULE OF ASSESSMENTS REVISIONS 
Location: 
Section 10.2.8, Treatment Week 16 (Visit T4.1; 112 ± 3 days) Only for Patients Taking 
Simvastatin 40 mg 
Original Text: 
10.2.8 
Treatment Week 16 (Visit T4.1; 112 ± 3 days) Only for Patients Taking 
Simvastatin 40 mg 
Patients taking an average daily dose of simvastatin 40 mg will be scheduled for an additional 
visit, Visit T4.1 for clinical safety laboratory evaluations specifically to monitor changes in CPK 
and LFTs as well as additional assessments as described below.  Should changes be noted, the 
procedures described in Sections 11.1.6.3.1 and 11.1.6.3.4 will apply.   
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints since last visit (ongoing) 
• Clinical laboratory evaluations 
− Hematology, blood chemistry, and urinalysis 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 177 of 184 
New Text 
10.2.8 
Treatment Week 16 (Visit T4.1; 112 ± 3 days) Only for Patients Taking 
Simvastatin 40 mg 
Patients taking an average daily dose of simvastatin 40 mg will be scheduled for an additional 
visit, Visit T4.1 for clinical safety laboratory evaluations specifically to monitor changes in CPK 
and LFTs as well as additional assessments as described below.  Should changes be noted, the 
procedures described in Sections 11.1.6.3.1 and 11.1.6.3.4 will apply.   
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints since last visit (ongoing) 
• Clinical laboratory evaluations 
 Hematology, blood chemistry, and urinalysis 
Original Text: 
10.2.9 
Treatment Week 20/Telephone Visit (Visit T4.2; 140 ± 3 days) Only for Patients 
Taking Simvastatin 40 mg 
Patients taking an average daily dose of simvastatin 40 mg will be contacted by telephone for 
additional Visit T4.2 to collect the following information: 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints since last visit (ongoing) 
New Text: 
10.2.9 
Treatment Week 20/Telephone Visit (Visit T4.2; 140 ± 3 days) Only for Patients 
Taking Simvastatin 40 mg 
Patients taking an average daily dose of simvastatin 40 mg will be contacted by telephone for 
additional Visit T4.2 to collect the following information: 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints since last visit (ongoing) 
Original Text: 
10.2.10 
Treatment Week 24 (Visit T5; 168 ±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 10.2.14 for the 
list of the required assessments.  The patient will be asked to continue to be followed for safety 
New Text: 
10.2.810.2.10 Treatment Week 24 (Visit T5; 168 ±7 days ± 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. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 178 of 184 
If the patient is withdrawing from IMP treatment at this visit, proceed to Section 10.2.1410.2.10 
for the list of the required assessments.  The patient will be asked to continue to be followed for 
safety 
Original Text: 
10.2.11 
Treatment Week 28 (Visit T5.2; 196 ± 7 days) Only for Patients Taking 
Simvastatin 40 mg 
Patients taking an average daily dose of simvastatin 40 mg will be scheduled for an additional 
visit, Visit T5.2 for clinical safety laboratory evaluations specifically to monitor changes in CPK 
and LFTs as well as additional assessments as described below.  Should changes be noted, the 
procedures described in Sections 11.1.6.3.1 and 11.1.6.3.4 will apply.   
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints since last visit (ongoing) 
• Clinical laboratory evaluations 
− Hematology, blood chemistry, and urinalysis 
New Text: 
10.2.11 
Treatment Week 28 (Visit T5.2; 196 ± 7 days) Only for Patients Taking 
Simvastatin 40 mg 
Patients taking an average daily dose of simvastatin 40 mg will be scheduled for an additional 
visit, Visit T5.2 for clinical safety laboratory evaluations specifically to monitor changes in CPK 
and LFTs as well as additional assessments as described below.  Should changes be noted, the 
procedures described in Sections 11.1.6.3.1 and 11.1.6.3.4 will apply.   
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints since last visit (ongoing) 
• Clinical laboratory evaluations 
− Hematology, blood chemistry, and urinalysis 
Original Text: 
10.2.12 
Treatment Week 32/Telephone Visit (Visit 5.2; 224 ± 7 days) Only for Patients 
Taking Simvastatin 40 mg 
Patients taking an average daily dose of simvastatin 40 mg will be contacted by telephone for 
additional Visit T4.2 to collect the following information: 
• Concomitant ad prohibited medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints since last visit (ongoing) 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 179 of 184 
New Text: 
10.2.12 
Treatment Week 32/Telephone Visit (Visit 5.2; 224 ± 7 days) Only for Patients 
Taking Simvastatin 40 mg 
Patients taking an average daily dose of simvastatin 40 mg will be contacted by telephone for 
additional Visit T4.2 to collect the following information: 
• Concomitant ad prohibited medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints since last visit (ongoing) 
 
CHANGE 12 
DEFINITION OF SAES AND OUTCOMES NOT QUALIFYING AS 
SERIOUS ADVERSE EVENT CHANGES 
Location: 
Section 11.2.7.1, Definition of Serious Adverse Event; Section 11.2.7.2, Definition of Outcomes 
not Qualifying as Serious Adverse Events 
Original Text: 
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 in-patient 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:  Hospitalization is defined as a formal inpatient admission.  This will not include 
admissions under “23-hour Observational Status”, an Emergency Room visit without hospital 
admission or an Urgent Care visit and therefore, such events will not be recorded as an SAE 
under this criterion, nor will 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.  


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 180 of 184 
New Text: 
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 in-patient 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:  Hospitalization is defined as a formal inpatient admission.  This will not include 
admissions under “23-hour Observational Status”, an Emergency Room visit without hospital 
admission or an Urgent Care visit and therefore, such events will not be recorded as an SAE 
under this criterion, nor will 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.  
Original Text: 
11.2.7.2 
Definition of Serious Adverse Event 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 
New Text: 
11.2.7.2 
Definition of Serious Adverse Event Events or Outcomes not Qualifying as 
Serious Adverse Events 
The following areis not considered an SAEs and therefore does 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 


Bempedoic Acid 
Clinical Study Protocol 1002-047 
CHANGE 13 
SCHEDULE OF EVENTS REVISIONS 
Location: 
Appendix 1, Schedule of Events (Subject Visit Schedule) 
Original Text: 
Esperion Therapeutics, Inc. 
Amendment 3, 09 May 2017 
APPENDIX 1. 
SCHEDULE OF EVENTS (SUBJECT VISIT SCHEDULE) 
Screen 
Run-in 
Treatment* 
Visit 
Sl l.Z 
S2 
S3 
Tl 
T2 
T3/phone 
T4 
TS 
T6/phone T7/EOS3 
Week 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
-5 
-4 
-1 
0 
4 
8 
12 
24 
36 
52 
Procedure 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 365 
--35± 7 
-28±3 
-7±3 
1 
29±3 
57±3 
85±3 
169±7 
252±7 
±7 
Informed Consent 
x 
Enrolhnent Criteria 
x 
Demographics 
x 
Medical Histo1y 
x 
HeFH Status Detennination 
x 
Concomitant Medications 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Adverse Event Recording 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Physical Exam 
x 
x 
Weight4 
x 
x 
x 
x 
x 
x 
Height/BM! 
x 
12-Lead ECG5 
x 
x 
Vital Signs6 
x 
x 
x 
x 
x 
x 
x 
x 
Serology
7 
x 
Serum Pregnancy and/or FSH8 
x 
Urine Pregnancy Test8 
x 
TSH 
x 
Clinical Safety Labs9 
x 
x 
x 
x 
x 
x 
Basic Fasting Lipids10 
x 
x 
x 
x 
x 
x 
x 
HbA1c 
x 
x 
x 
x 
x 
apoB 
x 
x 
x 
x 
hs-CRP 
x 
x 
x 
x 
Diet and exercise counseling11 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Plasma PK 
x 
x 
Establish Patient Eligibility 
x 
Randomization 
x 
IWRS Contact 
x 
x 
x 
x 
x 
x'2 
Single-Blind Drug Dispensing 
x 
Double-blind Drug Dispensing13 
x 
x 
x 
Drug Return/Compliance 
x 
x 
x 
x 
x 
x 
Schedule next visit 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Confidential 
Page 181 of 184 


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Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 182 of 184 
NOTE: For patients who withdraw from IMP treatment, they will continue to have visits according to the protocol schedule. Safety 
assessments should include clinical safety and basic lipid laboratories (except for apoB and hs-CRP), adverse events, PE, vital signs, 
and ECGs. For patients who withdraw from IMP treatment, but refuse to come to the clinic for assessments, assessments will take 
place 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). 
* Patients receiving simvastatin 40 mg will have clinic visits performed at weeks 16 and 28 and telephone visits at Weeks 20 and 32.  At 
clinic visits at Weeks 16 and 28, perform clinical safety labs as defined in Footnote 9, assess adverse events and review changes in 
concomitant medications.  At telephone visits performed at Weeks 20 and 32, assess adverse events and review changes in 
concomitant medications.   
1 An optional visit between Visits S1 and S2 may be completed if patient fails to meet TGTG entry criterion. If this optional basic 
fasting (minimum of 10 hours) lipid value visit is completed, the repeat lipid value will be used to determine eligibility. 
2 An optional visit between Visits S1 and S2 may be completed if the patient’s DBP and/or 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. An optional 
visit between Visit S1 and S2 may be completed to determine eligibility if the patient’s eGFR, ALT, AST, and/or TB meet exclusion 
criteria levels. If this optional visit is completed, the repeated value will be used to determine eligibility. 
3 All procedures will be completed for all patients at either End of Study (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).  
5 Single 12-lead ECG will be collected prior to any blood sample collection. 
6 Vital signs will include DBP, SBP, and 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  
8 Serum pregnancy test completed in premenopausal women only.  FSH test is completed in women <55 years old and >1 year without 
menses. Urine pregnancy test in women of childbearing potential just prior to randomization.  
9 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits. Coagulation is included at Screening (Visit S1) 
for all patients, Baseline (Visit T1) and 3-5 days after Visit T1 only if on anticoagulants).  Please refer to laboratory manual for 
detailed schedule of tests.  A local laboratory may be used for assessment at 3-5 days after Visit T1. 
10 Basic fasting (minimum of 10 hours) lipids include total cholesterol, calculated LDL-C, HDL-C, non-HDL-C, and triglycerides.  
11 Diet and exercise counseling per local and/or regional guidelines for the management of hyperlipidemia. 
12 IWRS contact at either an early withdrawal or an EOS visit to register study discontinuation visit date.  
13 Depending upon the length of time between visits, 1 or 2 bottles of study medication will be dispensed as instructed by IWRS. 
14 If patient is discontinuing treatment and completing the EOS visit, but will be continuing in the study either by returning to clinic or 
by phone, continue to schedule study visits for the patient according to the protocol Schedule of Events 
 


Bempedoic Acid 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
Amendment 3, 09 May 2017 
New Text: 
APPENDIX 1. 
SCHEDULE OF EVENTS (SUBJECT VISIT SCHEDULE) 
Screen 
Run-in 
Treatmentz 
Visit 
Sl l.Z 
S2 
S3 
Tl 
T2 
T3/phone 
T4 
TS 
T6/phone T7/EOS3 
Week 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
-5 
-4 
-1 
0 
4 
8 
12 
24 
36 
52 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 365 
Procedure 
--35± 7 
-28±3 
-7±3 
1 
29±3 
57±3 
85±3 168M9 
252±7 
±7 
±7 
Informed Consent 
x 
Enrolhnent Criteria 
x 
Demographics 
x 
Medical Histo1y 
x 
HeFH Status Detennination 
x 
Concomitant Medications 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Adverse Event Recording 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Physical Exam 
x 
x 
Weight4 
x 
x 
x 
x 
x 
x 
Height/BM! 
x 
12-Lead ECd 
x 
x 
Vital Signs6 
x 
x 
x 
x 
x 
x 
x 
x 
Serology
7 
x 
Serum Pregnancy and/or FSH8 
x 
Urine Pregnancy Test8 
x 
TSH 
x 
Clinical Safety Labs9 
x 
x 
x 
x 
x 
x 
Basic Fasting Lipids10 
x 
x 
x 
x 
x 
x 
x 
HbA1c 
x 
x 
x 
x 
x 
apoB 
x 
x 
x 
x 
hs-CRP 
x 
x 
x 
x 
Diet and exercise counseling11 
x 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Plasma PK 
x 
x 
Establish Patient Eligibility 
x 
Randomization 
x 
IWRS Contact 
x 
x 
x 
x 
x 
x 12 
Single-Blind Drug Dispensing 
x 
Double-blind Drug Dispensing13 
x 
x 
x 
Drug Return/Compliance 
x 
x 
x 
x 
x 
x 
Schedule next visit 
x 
x 
x 
x 
x 
x 
x 
x 
x 
Confidential 
Page 183 of 184 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-047 
 
Amendment 3, 09 May 2017 
Confidential 
Page 184 of 184 
NOTE: For patients who withdraw from IMP treatment, they will continue to have visits according to the protocol schedule. Safety 
assessments should include clinical safety and basic lipid laboratories (except for apoB and hs-CRP), adverse events, PE, vital signs, 
and ECGs. For patients who withdraw from IMP treatment, but refuse to come to the clinic for assessments, assessments will take 
place 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). 
* Patients receiving simvastatin 40 mg will have clinic visits performed at weeks 16 and 28 and telephone visits at Weeks 20 and 32.  At 
clinic visits at Weeks 16 and 28, perform clinical safety labs as defined in Footnote 9, assess adverse events and review changes in 
concomitant medications.  At telephone visits performed at Weeks 20 and 32, assess adverse events and review changes in 
concomitant medications.   
1 An optional visit between Visits S1 and S2 may be completed if patient fails to meet TGTG entry criterion. If this optional basic 
fasting (minimum of 10 hours) lipid value visit is completed, the repeat lipid value will be used to determine eligibility. 
2 An optional visit between Visits S1 and S2 may be completed if the patient’s DBP and/or 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. An optional 
visit between Visit S1 and S2 may be completed to determine eligibility if the patient’s eGFR, ALT, AST, and/or TB meet exclusion 
criteria levels. If this optional visit is completed, the repeated value will be used to determine eligibility. 
3 All procedures will be completed for all patients at either End of Study (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).  
5 Single 12-lead ECG will be collected prior to any blood sample collection. 
6 Vital signs will include DBP, SBP, and 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  
8 Serum pregnancy test completed in premenopausal women only.  FSH test is completed in women <55 years old and >1 year without 
menses. Urine pregnancy test in women of childbearing potential just prior to randomization.  
9 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits. Coagulation is included at Screening (Visit S1) 
for all patients, Baseline (Visit T1) and 3-5 days after Visit T1 only if on anticoagulants).  Please refer to laboratory manual for 
detailed schedule of tests.  A local laboratory may be used for assessment at 3-5 days after Visit T1. 
10 Basic fasting (minimum of 10 hours) lipids include total cholesterol, calculated LDL-C, HDL-C, non-HDL-C, and triglycerides.  
11 Diet and exercise counseling per local and/or regional guidelines for the management of hyperlipidemia. 
12 IWRS contact at either an early withdrawal or an EOS visit to register study discontinuation visit date.  
13 Depending upon the length of time between visits, 1 or 2 bottles of study medication will be dispensed as instructed by IWRS. 
14 If patient is discontinuing treatment and completing the EOS visit, but will be continuing in the study either by returning to clinic or 
by phone, continue to schedule study visits for the patient according to the protocol Schedule of Events 
 

SAP_001.pdf: 
Version Number: 
0.5 
Version Date: 
14Jun2018 
ESPERION THERAPEUTICS, INC. 
STATISTICAL ANALYSIS PLAN: PROTOCOL 1002‐047 
Page 1 of 48 
STATISTICAL ANALYSIS PLAN 
PROTOCOL 1002‐047 
 A LONG‐TERM, RANDOMIZED, DOUBLE‐BLIND, PLACEBO‐
CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY 
OF BEMPEDOIC ACID (ETC‐1002) IN PATIENTS WITH 
HYPERLIPIDEMIA AT HIGH CARDIOVASCULAR RISK NOT 
ADEQUATELY CONTROLLED BY THEIR LIPID‐MODIFYING 
THERAPY  
AUTHOR: 
VERSION NUMBER AND DATE: V0.5, 14JUNE2018 
NCT number: NCT02991118
This NCT number has been applied to the document 
for purposes of  posting on clinicaltrials.gov


~- IOVI A .. 
Statistical Analysis Plan 
ESPERION THERAPEUTICS, INC. 
STATISTICAL ANALYSIS PLAN: PROTOCOL 1002-047 
Page 2 of48 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE 
Statistical Analysis Plan V05(Dated14June2018) for Protocol 1002-047 amendment 3 dated 09 May 
2017. 
Name 
Signature 
Date 
Author: 
--
Position: 
Company: 
lml 
Upon review of this document, t he undersigned approves this version of the Statistical Analysis Plan, 
authorizing that the content i!> acceptable for the reporting of this study. 
Name 
Approved By: -
Position: 
Company: 
Approved By: -
Position: 
Company: -
Approved By: 
Position: 
Company: 
-
Signature 
• 
Date 
!'1 J.u1.<.o/3 
0.5 
14June2018 


Statistical Analysis Plan 
ESPERION THERAPEUTICS, INC. 
STATISTICAL ANALYSIS PLAN: PROTOCOL 1002‐047 
Page 3 of 48 
Version Number: 
0.5 
Version Date: 
           14June2018 
MODIFICATION HISTORY 
Unique 
Identifier 
for this 
Version 
Date of the 
Document 
Version 
Author 
Significant Changes from  
Previous Authorized Version 
0.1 
25APR2017 
Not Applicable – First Version 
0.2 
08JUN2017 
Addressed comments for draft 1 from 
Esperion 
0.3 
21May2018 
Addressed comments for draft 2 from 
Esperion and added changes based on 
046 and 048 
0.4  
05June208 
Accept Client Comments 
0.5 
14Jun2018 
Accept Client Comments 


 
Statistical Analysis Plan 
ESPERION THERAPEUTICS, INC. 
STATISTICAL ANALYSIS PLAN: PROTOCOL 1002‐047 
Page 4 of 48 
 
 
 
 
 
Version Number: 
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Version Date: 
                           14June2018 
 
 
 
 
 
TABLE OF CONTENTS 
 
1.  INTRODUCTION ............................................................................................................................. 10 
2.  STUDY OBJECTIVES ...................................................................................................................... 10 
2.1. 
Primary Objective ............................................................................................................................... 10 
2.2. 
Secondary Objectives ......................................................................................................................... 10 
2.3. 
Tertiary Objectives ............................................................................................................................. 10 
3.  STUDY DESIGN ............................................................................................................................... 11 
3.1. 
General Description ............................................................................................................................ 11 
3.2. 
Schedule of Events ............................................................................................................................. 11 
4.  PLANNED ANALYSIS ..................................................................................................................... 12 
4.1. 
Data Monitoring Committee (DMC) .................................................................................................... 12 
4.2. 
Final Analysis ...................................................................................................................................... 12 
5.  ANALYSIS SETS .............................................................................................................................. 12 
5.1. 
Safety Analysis Set [SAF] ..................................................................................................................... 12 
5.2. 
Full Analysis Set [FAS] ......................................................................................................................... 12 
5.3. 
PK Analysis Set [PKS] .......................................................................................................................... 13 
6.  GENERAL CONSIDERATIONS ..................................................................................................... 13 
6.1. 
Reference Start Date and Study Day ................................................................................................... 13 
6.2. 
Baseline ............................................................................................................................................. 13 
6.3. 
Retests, Unscheduled Visits and Early Termination Data ..................................................................... 14 
6.4. 
Visit Windowing ................................................................................................................................. 14 


 
Statistical Analysis Plan 
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6.5. 
Statistical Tests ................................................................................................................................... 14 
6.6. 
Common Calculations ......................................................................................................................... 15 
6.7. 
Software Version ................................................................................................................................ 15 
7.  STATISTICAL CONSIDERATIONS ............................................................................................. 15 
7.1. 
Sample Size ........................................................................................................................................ 15 
7.2. 
Adjustments for Covariates and Factors to be Included in Analysis ...................................................... 15 
7.3. 
Multicenter Studies ............................................................................................................................ 16 
7.4. 
Missing data ....................................................................................................................................... 16 
7.5. 
Multiple Comparisons/ Multiplicity .................................................................................................... 16 
8.  OUTPUT PRESENTATIONS ......................................................................................................... 16 
9.  DISPOSITION AND WITHDRAWALS ....................................................................................... 17 
10. PROTOCOL DEVIATIONS ............................................................................................................ 17 
11. DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS .......................................... 17 
11.1. 
Derivations ......................................................................................................................................... 18 
12. MEDICAL AND SURGICAL HISTORY ........................................................................................ 18 
13. CONCOMITANT ILLNESSES ........................................................................................................ 18 
14. CARDIOVASCULAR HISTORY/RISK FACTORS ..................................................................... 19 
15. MEDICATIONS ................................................................................................................................ 19 
15.1. 
Background Lipid Modifying Therapy .................................................................................................. 19 
15.2. 
Additional Post‐randomization Adjunctive Triglyceride‐lowering Therapy ........................................... 19 
15.3. 
Additional Post‐randomization lipid modifying therapy ...................................................................... 20 


 
Statistical Analysis Plan 
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16. STUDY MEDICATION COMPLIANCE AND EXPOSURE ........................................................ 20 
16.1. 
Derivations ......................................................................................................................................... 20 
17. EFFICACY OUTCOMES .................................................................................................................. 21 
17.1. 
Primary Efficacy .................................................................................................................................. 21 
17.1.1. 
Primary Efficacy Variable & Derivation .....................................................................................................21 
17.1.2. 
Primary Analysis of Primary Efficacy Variable ..........................................................................................21 
17.1.3. 
Missing Data Methods For Primary Efficacy Variable ...............................................................................22 
17.2. 
Secondary Efficacy .............................................................................................................................. 22 
17.2.1. 
Key Secondary Efficacy Endpoints ............................................................................................................22 
17.2.2. 
Other Secondary Efficacy Variables & derivations ...................................................................................23 
17.2.3. 
Sensitivity Analysis of Primary and Key Secondary Efficacy Variables ......................................................23 
17.2.3.1. 
Analysis Using Derived Stratification Factors ...................................................................................23 
17.2.3.2. 
Adjunctive Lipid‐modifying Therapy (LMT) Analysis .........................................................................23 
17.2.3.3. 
On‐treatment Analysis ......................................................................................................................24 
17.2.3.4. 
Observed Data Analysis ....................................................................................................................24 
17.2.4. 
Subgroup Analysis of Primary Efficacy Variable .......................................................................................24 
17.3. 
Tertiary Efficacy .................................................................................................................................. 25 
17.3.1. 
Tertiary Efficacy Variables & Derivations ..................................................................................................25 
17.3.2. 
Missing Data Methods for Tertiary Efficacy Variables ..............................................................................25 
17.3.3. 
Analysis of Tertiary Efficacy Variables ......................................................................................................25 
17.3.1. 
Additional analysis ....................................................................................................................................25 
18. SAFETY OUTCOMES ...................................................................................................................... 25 
18.1. 
Adverse Events ................................................................................................................................... 26 
18.1.1. 
All TEAEs ...................................................................................................................................................26 
18.1.2. 
Severity .....................................................................................................................................................26 
18.1.3. 
Relationship to Study Medication ............................................................................................................26 
18.1.4. 
TEAEs Leading to Discontinuation of Study Medication ...........................................................................26 
18.1.5. 
Serious Adverse Events .............................................................................................................................27 
18.1.6. 
Adverse Events Of Special Interest (AESI) .................................................................................................27 
18.2. 
Deaths ................................................................................................................................................ 27 
18.3. 
Clinical Endpoints ............................................................................................................................... 27 
18.4. 
Safety Laboratory Evaluations ............................................................................................................ 28 
18.4.1. 
Laboratory Reference Ranges and Markedly Abnormal Criteria ..............................................................29 
18.5. 
ECG Evaluations .................................................................................................................................. 29 


 
Statistical Analysis Plan 
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18.6. 
Vital Signs ........................................................................................................................................... 29 
18.7. 
Physical Examination .......................................................................................................................... 29 
18.8. 
Pharmacokinetics ............................................................................................................................... 30 
19. DATA NOT SUMMARIZED OR PRESENTED ........................................................................... 30 
20. REFERENCES ................................................................................................................................... 31 
APPENDIX 1. PROGRAMMING CONVENTIONS FOR OUTPUT ................................................. 32 
Quintiles Output Conventions ........................................................................................................................... 32 
Dates & Times ................................................................................................................................................... 37 
Presentation of Treatment Groups .................................................................................................................... 37 
Presentation of Visits ........................................................................................................................................ 37 
APPENDIX 2. PARTIAL DATE CONVENTIONS .............................................................................. 39 
APPENDIX 3. LIST OF DMC TABLES, LISTINGS, AND FIGURES ............................................... 42 
APPENDIX 4. DETAILS OF MULTIPLE IMPUTATION METHOD .............................................. 44 
APPENDIX 5. LIST OF ADVERSE EVENTS OF SPECIAL INTEREST .......................................... 46 
 
 


 
Statistical Analysis Plan 
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Version Date: 
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LIST OF ABBREVIATIONS   
 
Abbreviation or Specialist Term  
Explanation  
ACS  
acyl-CoA synthetase  
ADaM 
Analysis Data Model 
AE  
adverse event  
AESI  
adverse events of special interest  
ALT  
alanine aminotransferase  
ANCOVA  
analysis of covariance  
apoB  
apolipoprotein B  
ASCVD  
atherosclerotic cardiovascular diseases  
AST  
aspartate aminotransferase  
BMI  
body mass index  
BP  
blood pressure  
BUN  
blood urea nitrogen  
CEC  
Clinical Event Committee  
CHD  
coronary heart disease  
CI  
confidence interval  
CK  
creatine kinase  
CPK 
Creatine phosphokinase 
CV  
cardiovascular  
DBP  
diastolic blood pressure  
DMC  
Data Monitoring Committee  
ECG  
electrocardiogram  
eCRF  
electronic case report form  
EDC 
Electronic data capture 
eGFR  
estimated glomerular filtration rate  
EOS  
end of study  
ETC-1002  
Bempedoic acid 
EU  
European Union  
FAS  
full analysis set  
HbA1C 
glycosylated hemoglobin, Type A1C  
HeFH 
heterozygous familial hypercholesterolemia 
HDL-C  
high-density lipoprotein cholesterol  
Hgb  
hemoglobin  
hsCRP  
high-sensitivity C-reactive protein  
ICH  
International Conference on Harmonisation  
IMP  
investigational medicinal product  
ITT  
intention-to-treat 
LDL-C  
low-density lipoprotein cholesterol  
LFT  
liver function test  
LSM  
least square mean  
MACE  
major adverse cardiac event  
MedDRA  
Medical Dictionary for Regulatory Activities  
MI  
myocardial infarction  


 
Statistical Analysis Plan 
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non-HDL-C  
non-high-density lipoprotein cholesterol  
PCSK9  
proprotein convertase subtilisin/kexin type 9  
PE  
physical exam  
PK  
pharmacokinetic(s)  
PMM  
pattern mixed model  
PPS 
per-protocol set 
PT  
preferred term  
SAE  
serious adverse event  
SAF 
safety analysis set 
SAP  
statistical analysis plan 
SBP  
systolic blood pressure  
SE  
standard error  
SOC  
system organ class  
SDTM 
study data tabulation model 
T2DM  
type 2 diabetes mellitus  
TB  
total bilirubin  
TC  
total cholesterol  
TEAE  
treatment-emergent adverse event  
TG  
triglycerides  
ULN  
upper limit of normal  
US  
United States  
WBC  
white blood cell  
WHO  
World Health Organization 
 
 


 
Statistical Analysis Plan 
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1. INTRODUCTION 
This document describes the rules and conventions to be used in the presentation and analysis of 
efficacy and safety data for Protocol 1002‐047. It describes the data to be summarized and analyzed, 
including specifics of the statistical analysis to be performed.  
This statistical analysis plan (SAP) is based on the final protocol version dated September 22, 2016 and 
amendment 1 dated 18 January 2017, amendment 2 dated 22 March 2017, and amendment 3 dated 
09 May 2017. 
2. STUDY OBJECTIVES 
2.1. PRIMARY OBJECTIVE 
The primary objective is to assess the 12‐week efficacy of bempedoic acid 180 mg/day versus placebo 
in decreasing low‐density lipoprotein cholesterol (LDL‐C) in high cardiovascular (CV) risk patients with 
hyperlipidemia (with underlying heterozygous familial hypercholesterolemia [HeFH] and/or 
atherosclerotic cardiovascular diseases [ASCVD]) who are not adequately controlled with their 
maximally tolerated lipid‐modifying therapy.  
2.2. SECONDARY OBJECTIVES 
The secondary objectives are: 
 
To evaluate the effect of 24‐week treatment with bempedoic acid 180 mg/day versus placebo on 
LDL‐C.  
 
To evaluate the effect of bempedoic acid 180 mg/day versus placebo on non‐high‐density 
lipoprotein cholesterol (non‐HDL‐C), total cholesterol (TC), high‐sensitivity C‐reactive protein 
(hsCRP), and apolipoprotein B (apoB) after 12 weeks of treatment.  
2.3. TERTIARY OBJECTIVES 
The tertiary objectives are: 
 
To evaluate the long‐term treatment (52 weeks) with bempedoic acid 180 mg/day versus 
placebo on LDL‐C, non‐HDL‐C, TC, HDL‐C, TG, hsCRP, and apoB.  
 
To evaluate the 52‐week safety and tolerability of bempedoic acid 180 mg/day compared to 
placebo.  
 


IMS Health & O.uiin.tJles a<e "°'"""" 
Statistical Analysis Plan 
3. STUDY DESIGN 
3.1. GENERAL DESCRIPTION 
ESPERION THERAPEUTICS, INC. 
STATISTICAL ANALYSIS PLAN: PROTOCOL 1002-047 
Page 11of48 
This is a Phase 3, long-term randomized, double-blind, placebo-controlled, parallel group, study 
evaluating the efficacy of bempedoic acid in high CV risk patients with hyperlipidemia (patients with 
underlying HeFH and/or ASCVD) who are not adequately t reated with their maximally tolerated lipid-
modifying therapy. The study will be conducted at approximately 125 clinical sites in North America 
and Europe. Screening Week -5 (Visit Sl) will be approximately 5 weeks prior to randomization, but 
can be extended for an additional 4 weeks if needed to adjust background medical therapy or for other 
reasons as specified in the protocol. Eligible patients will return to the clinical site at Week -4 (Visit 52) 
to initiate administration of single-blind (patient only) placebo. Eligible patients will return at Week -1 
(Visit 53) for lipid and safety laboratories and an assessment of tolerability and study drug adherence. 
Approximately 750 eligible patients will be randomized 2:1 on Day 1 (Visit Tl) to receive either 
bempedoic acid 180 mg (n = 500), or placebo (n = 250) once daily for 52 weeks. Randomized patients 
will return for clinic visits at Week 4 (Visit T2}, Week 12 (Visit T4), Week 24 (Visit TS), and Week 52 
(Visit T7). A phone visit will occur at Week 8 (Visit T3) and Week 36 (Visit T6). 
Table A: 
1002-047 Study Design 
ETC-1002 180 mg (n=500) 
Placebo (n=250) 
Study 
Screen 
Placebo run-
52-Week Treatment Period 
Phase 
Period in, Stable LMT 
Week 
't 
i 
i 
-5 
-4 
-1 
0 
4 
8 
12 
24 
Study 
51 
S2 
S3 T1 
T2 
T3 
T4 
T5 
Visit 
(pnone) 
3.2. SCHEDULE OF EVENTS 
The schedule of events can be found in Appendix I of the protocol. 
--- -
Version Number: 
Version Date: 
36 
T6 
(phone) 
0.5 
14June2018 
52 
T7 


 
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4. PLANNED ANALYSIS 
The following analysis will be performed for this study: 
 
Analysis for Data Monitoring Committee (DMC) meetings 
 
Final Analysis  
4.1. DATA MONITORING COMMITTEE (DMC)  
The subset of outputs for the DMC is listed in Appendix 3.  Access to results will be provided by 
Quintiles in a separate unblinding plan. 
4.2. FINAL ANALYSIS  
All final, planned analysis identified in this SAP will be performed by IQVIA Biostatistics following 
Sponsor Authorization of this Statistical Analysis Plan, Database Lock, Sponsor Authorization of 
Analysis Sets and unblinding of Treatment. 
5. ANALYSIS SETS 
Agreement and authorization of subjects included/ excluded from each analysis set will be conducted 
prior to the unblinding of the study.  
5.1. SAFETY ANALYSIS SET [SAF] 
The Safety Analysis Set (SAF), 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 SAF will be 
included in the treatment group that they actually received, regardless of their randomized treatment. 
5.2. FULL ANALYSIS SET [FAS] 
The Full Analysis Set (FAS), used for all of the efficacy analysis, is defined as all randomized patients. 
The FAS is also known as the intention‐to‐treat (ITT) set of patients. Patients in the FAS will be included 
in their randomized treatment group, regardless of the treatment they actually received.  
 


 
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5.3. PK ANALYSIS SET [PKS] 
The PK Analysis Set will include all patients in the safety analysis set who have at least one non‐missing 
PK assessment. These patients will be summarized for PK concentrations unless major protocol 
deviations are identified during the protocol deviation review or if key dosing or sampling information 
is missing. 
6. GENERAL CONSIDERATIONS 
6.1. REFERENCE START DATE AND STUDY DAY 
Study Day will be calculated from the reference start date, and will be used to show start/ stop day of 
assessments and events.  
Reference start date is defined as the day of the first dose of double‐blind study medication (Day 1 is 
the day of the first dose of study medication. In case the first dose date is missing, the randomization 
date will be used instead. 
If the date of the event is on or after the reference date then:  
Study Day = (date of event – reference date) + 1. 
 
If the date of the event is prior to the reference date then:  
Study Day = (date of event – reference date). 
In the situation where the event date is partial or missing, the date will appear partial or missing in the 
listings, and Study Day, and any corresponding durations will be presented based on the imputations 
specified in Appendix 2; Partial Date Conventions. 
6.2. BASELINE 
Unless otherwise specified, baseline is defined as the last non‐missing measurement taken on or prior 
to reference start date (including unscheduled assessments). In the case where the last non‐missing 
measurement and the reference start date coincide, that measurement will be considered pre‐
baseline, but Adverse Events (AEs) and medications commencing on the reference start date will be 
considered post‐baseline. 
Baseline for calculated LDL‐C, HDL‐C, non‐HDL‐C, TG, and TC is defined as the mean of the values from 
Week ‐1 (Visit S3) and predose Day 1/Week 0 (Visit T1) (i.e., the last two non‐missing values on or prior 
to Day 1). If only one value is available then that single value will be used as baseline. 
Baseline for apoB and hsCRP is defined as the predose Day 1/Week 0 (Visit T1) value (i.e. the last non‐


 
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missing value on or prior to Day 1). If this is not available, then the last non‐missing value prior to the 
first dose of double‐blind study medication (including unscheduled assessments) will be used as 
baseline. 
6.3. RETESTS, UNSCHEDULED VISITS AND EARLY TERMINATION DATA 
In the event of a missing value at a scheduled visit, and if an unscheduled visit falls within the protocol‐
defined window of that visit (see table below), the value from the unscheduled visit will be used for 
that visit.  
In the case of a retest (same visit number assigned), the later available measurement for that visit will 
be used for by‐visit summaries.  
Listings will include scheduled, unscheduled, retest and early discontinuation data. 
6.4. VISIT WINDOWING 
Protocol‐defined assessments will be “slotted” to study weeks based on collection date and applying 
the rules summarized in the following table.  If there is more than one scheduled visit in a visit 
window, the visit closest to the target date will be used.  If there is a tie between the numbers of days 
from the target date, the visit after the target date will be used.  Unscheduled visits that fall within the 
protocol‐defined visit windows will be summarized in the by‐visit analyses if there is no scheduled visit 
available.  If there is more than one unscheduled visit within the protocol‐defined visit window and no 
scheduled visit available, the unscheduled visit closest to the scheduled visit date will be used.  If there 
is a tie between the numbers of days from the target date, the visit after the target date will be used.   
However, exposure data obtained from the drug accountability and administration CRF will be 
summarized and listed according to nominal visit information. 
Analysis Visit 
S1 
S2 
S3 
T1 
T2 
T3 
T4 
T5 
T6 
T7 
Study  
Week 
‐5 
‐4 
‐1 
week 
0 
4 
8 
12 
24 
36 
52/EOS 
Target Study  
Day 
‐35 
‐28 
‐7 
1 
29 
57 
85 
168 
252 
365 
Analysis Visit  
Windows 
[‐∞,‐32]  [‐31 ,‐18]  [‐17, ‐1]  [1,1]  [2,43]  [44,71]  [72,127]  [128, 
211] 
[212, 
309] 
[310,∞] 
 
6.5. STATISTICAL TESTS 
The default significance level will be (5%); confidence intervals will be 95% and all tests will be two‐


 
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sided, unless otherwise specified in the description of the analysis. 
6.6. COMMON CALCULATIONS 
For quantitative measurements, change from baseline will be calculated as: 
 
 
Test Value at Visit X – Baseline Value 
Percent change from baseline will be calculated as: 
 
 
[(Test Value at Visit X – Baseline Value)/Baseline Value] x 100 
6.7. SOFTWARE VERSION 
All analysis will be conducted using SAS version 9.4 or higher.  
7. STATISTICAL CONSIDERATIONS 
7.1. SAMPLE SIZE 
The primary efficacy endpoint for this study is the percent change from baseline to Week 12 in LDL‐C.  
The sample size of 500 randomized patients in the bempedoic acid 180 mg group and 250 randomized 
patients in the placebo group is expected to provide more than 95% power to detect a difference of 
15% in the percent change from baseline to Week 12 in LDL‐C between the bempedoic acid treatment 
group and the placebo group. This calculation is based on a 2‐sided t‐test at the 5% level of significance 
(α = 0.05) and a common standard deviation of 15%. The sample size of 500 randomized patients in 
the bempedoic acid 180 mg group and 250 randomized patients in the placebo group gives a total 
study sample size of 750. 
7.2. ADJUSTMENTS FOR COVARIATES AND FACTORS TO BE INCLUDED IN ANALYSIS 
The following covariates and factors are used in the analysis. For details of their inclusion in the 
models, see the specific analysis section. 
 
treatment group (bempedoic acid 180 mg/day; placebo) 
 
CV risk (ASCVD only; HeFH with or without ASCVD) 
 
baseline statin intensity (high intensity; moderate intensity; low intensity) 
 
baseline laboratory value of interest 


 
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 
treatment by subgroup interaction term for subgroup analyses of efficacy variables 
7.3. MULTICENTER STUDIES 
This study will be conducted by multiple investigators at multiple centers in North America and 
Europe.   
7.4. MISSING DATA 
Missing efficacy data will be handled as described in section 15.1.2 of this analysis plan.  
7.5. MULTIPLE COMPARISONS/ MULTIPLICITY 
In terms of controlling the overall Type I error rate, a gatekeeping or stepdown approach will be 
used to test the primary efficacy endpoint and then specific secondary efficacy endpoints 
sequentially in order to preserve the study‐wise Type I error rate. The sequence for the stepdown 
procedure in this study is as follows:  
  
 
Test the primary efficacy endpoint: percent change from baseline to Week 12 in LDL‐C  
 
Test the percent change from baseline to Week 24 in LDL‐C  
 
Test the percent change from baseline to Week 12 in non‐HDL‐C  
 
Test the percent change from baseline to Week 12 in TC  
 
Test the percent change from baseline to Week 12 in apoB  
 
Test the percent change from baseline to Week 12 in hsCRP 
In this hierarchical testing structure, each hypothesis is tested at a significance level of 0.05, two‐sided. 
Statistical significance at each step is required in order to test the next hypothesis. If the primary 
endpoint meets the criteria for statistical significance, then the percent change from baseline to Week 
24 in LDL‐C will be tested; and so forth. 
8. OUTPUT PRESENTATIONS 
Appendix 1 shows conventions for presentation of data in outputs.  
The templates provided with this SAP describe the presentations for this study and therefore the 


 
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format and content of the summary tables, figures and listings to be provided by IQVIA Biostatistics. 
Unless otherwise specified all outputs will be presented by randomized treatment group. 
9. DISPOSITION AND WITHDRAWALS 
All patients who were screened will be accounted for in this study. Reasons for screen failure will be 
summarized by pre‐defined categories per CRF. For screen fail due to inclusion or exclusion criteria 
violation, the criteria category will be presented.  Patient disposition and withdrawals (both from study 
treatment and the study) will be summarized for the FAS.  The number of patients in each analysis set 
and by visit will be presented for all randomized patients.  
10. PROTOCOL DEVIATIONS 
All protocol deviations will be provided in a listing with type and description. Major protocol deviations 
will be summarized by treatment group. The protocol deviations are recorded and tracked in the trial 
monitoring platform CTMS.  The final protocol deviations will be determined before treatment group is 
unblinded. 
11. DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
Demographic data and other baseline characteristics will be summarized by treatment group for the 
FAS. 
No statistical testing will be carried out for demographic or other baseline characteristics. 
The following demographic and other baseline characteristics will be reported for this study: 
 
Age (years) ‐ calculated relative to date of randomization 
 
Age category (<65 years vs. ≥65 years and < 75 years vs. ≥75 years) 
 
Gender 
 
Race  
 
Ethnicity 
 
Region (US vs. Canada vs. EU) 
 
Stratification factor 
 
CV risk (ASCVD only; HeFH (with or without ASCVD)) 
 
Baseline statin intensity (high intensity; moderate intensity; low intensity) 
 
Weight (kg) 


 
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 
Height (cm) 
 
BMI (kg/m2) 
 
BMI category (< 25 vs. 25 ‐ < 30 vs. ≥ 30 kg/ m2) 
 
Baseline Laboratory Results (Total Cholesterol, LDL‐C, HDL‐C, Triglycerides, Non‐HDL‐C, 
Apolipoprotein B, and hsCRP) 
 
Baseline LDL‐C category (<130 mg/dL, ≥130 and < 160 mg/dL, or ≥160 mg/dL) 
 
Baseline eGFR (normal: ≥90 mL/min/1.73m2; mild Renal Impairment: 60‐89 mL/min/1.73m2; 
moderate Renal Impairment: 30‐59 mL/min/1.73m2, and severe Renal Impairment (15‐29 
mL/min/1.73m2) 
 
History of diabetes (Yes vs. No) 
 
History of hypertension (Yes vs. No) 
 
Baseline Vital Signs (systolic blood pressure (SBP) and diastolic blood pressure (DBP) ) 
 
Alcohol consumption (Non‐Drinker, Former Drinker, or Current Drinker) 
 
Tobacco use (Never Used, Former User, or Current User) 
11.1. DERIVATIONS 
 
Age (years) = (date of randomization – date of birth)/365.25 
 
BMI (kg/ m2) = weight (kg)/ height (m)2 
12. MEDICAL AND SURGICAL HISTORY 
Medical and Surgical History information will be presented by MedDRA SOC (System Organ Class) and 
PT (Preferred Term) for the FAS.  Medical History conditions are defined as those conditions which 
started prior to signing the inform consent form (ICF) and stopped prior to or at screening.  Medical 
History will be coded using MedDRA Version 20.1.  
 
13. CONCOMITANT ILLNESSES 
Concomitant Illnesses will be presented by SOC (System Organ Class) and PT (Preferred Term) for the 
FAS.  Concomitant Illnesses are conditions (other than the indication being studied) which started prior 
to signing ICF and are ongoing at the date of randomization.   Concomitant Illnesses will be coded using 
MedDRA Version 20.1 


 
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14. CARDIOVASCULAR HISTORY/RISK FACTORS 
Cardiovascular history/risk factors collected at screening will be presented in a table by treatment 
group and data listing. 
15. MEDICATIONS 
Prior and concomitant medications will be presented for the SAF and coded using the September 2017 
version of the World Health Organization Drug Dictionary Enhanced (WHO‐DDE). 
Medications will be summarized by ATC classification and preferred term by treatment group.  Prior 
and concomitant lipid modifying therapy including statin, PCSK9i, ezetimibe and others will be 
tabulated and listed separately. 
See Appendix 2 for handling of partial dates for medications, in the case where it is not possible to 
define a medication as prior or concomitant to treatment, the medication will be classified by the 
worst case, i.e. concomitant.  
Prior medications are medications which started and stopped prior to the first dose of double‐blind 
study medication.  
Concomitant medications are medications which: started prior to, on or after the first dose of double‐
blind study medication and started no later than 30 days following end of study medication, AND 
ended on or after the date of first dose of study medication or were ongoing at the end of the study.  
15.1. BACKGROUND LIPID MODIFYING THERAPY 
Baseline background lipid modifying therapy is defined as any lipid modifying agents that are on‐going 
at the time of randomization. It will be presented by treatment group in separate table and listing by 
category , ATC class 4 and coded medication name. 
15.2. ADDITIONAL POST‐RANDOMIZATION ADJUNCTIVE TRIGLYCERIDE‐LOWERING 
THERAPY  
The number and percent of patients requiring additional (post‐randomization) TG‐lowering therapy 
(only when TG>1000) will be summarized by treatment group, ATC class 4 and medication name, as 
well as provided in a listing.  The TG lowering medication will be identified as post‐randomization 
concomitant medications with indication of ‘hypertriglyceridemia’. 


 
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15.3. ADDITIONAL POST‐RANDOMIZATION LIPID MODIFYING THERAPY 
The number and percent of patients in each treatment group requiring additional (post‐
randomization) lipid‐lowering therapy will be summarized by treatment group, ATC class 4 and 
medication name as well as provided in a listing. The lipid‐lowering therapy includes all post‐
randomization concomitant medications based on ATC class 2 = lipid‐modifying agent.  
16. STUDY MEDICATION COMPLIANCE AND EXPOSURE  
Compliance to study medication will be presented for the SAF.  At visit Week ‐1 (S3)  and each patient 
visit during the study, clinical site staff will count the number of tablets that are returned as unused 
and query the patient with regards to daily intake.  
16.1. DERIVATIONS 
Compliance with placebo‐run in (as an overall group) and double‐blind study medication by treatment 
group, based on the drug accountability data, will be calculated as the number of tablets taken (total 
dispensed – total returned) divided by the number of days on treatment within each of the 2 periods. 
During the run‐in period, the compliance will be summarized as a single overall group and during the 
double‐blind period, compliance will be summarized by treatment group (bempedoic acid and 
placebo).  
Compliance will not be computed by visit. 
 A 35‐day supply of single‐blind placebo drug will be dispensed one time at Week ‐4 (Visit S2) for the 4‐
week placebo run‐in period of the study. Double‐blind IMP will be dispensed in 100 day supply 
increments to patients by appropriate clinical site personnel. Patients will receive one 100‐day supply 
bottle at Week 0 (Visit T1), Week 12 (Visit T4), and two 100‐day supply bottles at Week 24 (Visit T5). 
The treatment is taken once daily and it is assumed that the patient takes medication on the visit day 
at which their medication is initially dispensed to the day of their last medication return date.  For 
example, if the initial dispense date is Day 1 and the last return date is Day 84, then the patient should 
have taken the first tablet at Day 1, once a day on Days 2 to 83 and 1 tablet on Day 84; hence, the total 
number of prescribed tablets would be 84. 
For subjects who did not return any bottle during the run‐in or double‐blind period, their compliance 
will be set to missing. 
Treatment exposure will be calculated in weeks as (date of last dose of study medication – first date of 
first dose of study medication +1)/7.  Descriptive statistics will be presented for exposure as well as 
categorization into time periods. (e.g., <12weeks, 12‐<24 weeks, 24‐<48 weeks and >=48 weeks, etc.). 
 


 
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17. EFFICACY OUTCOMES  
17.1. PRIMARY EFFICACY 
17.1.1. 
PRIMARY EFFICACY VARIABLE & DERIVATION 
The primary efficacy endpoint is the percent change from baseline to Week 12 in LDL‐C. Baseline LDL‐C is 
defined as the mean of the LDL‐C values from Week ‐1 (Visit S3) and predose Day 1/Week 0 (Visit T1) 
(last two non‐missing values on or prior to Day 1).  
 
In cases where triglycerides (TG) is >400 mg/dL or LDL‐C is ≤50 mg/dL, a measured LDL (LDL‐M) will be 
used instead of LDL‐C for the analysis of that time point.  If both values are available, the LDL‐M will be 
used. 
17.1.2. 
PRIMARY ANALYSIS OF PRIMARY EFFICACY VARIABLE 
The null hypothesis, H0, will be that there is no difference between bempedoic acid 180 mg/day and 
placebo in mean percent change from baseline to Week 12 in LDL‐C. The alternative hypothesis, H1, will 
be that bempedoic acid 180 mg/day is different from placebo: 
H0: p = b 
H1: p  b 
where p and b denote the mean percent change from baseline to Week 12 in LDL‐C on placebo and 
bempedoic acid 180 mg/day respectively. 
The primary efficacy endpoint will be analyzed using analysis of covariance (ANCOVA), with treatment 
group and randomization stratification factors (CV risk and baseline statin intensity) as factors and 
baseline LDL‐C as a covariate. In case the of number of subjects within a stratum is too small for a 
meaningful analysis, the strata may be combined to obtain larger cell size. The ANCOVA will be 
performed using the FAS, with patients included in their randomized treatment group regardless of the 
treatment they actually received. To account for the likelihood of unequal variances between the 
treatment groups, the ANCOVA model will be implemented within mixed model framework and the 
<repeated/group=> option will be used to allow estimating the residual variances separately between 
the groups. Assumptions for ANCOVA model will be assessed and if the assumptions are severely 
violated, a non‐parametric rank based method will be performed. 
 
In addition, descriptive statistics will be presented for LDL‐C at each visit and for change/percent 
change from baseline by treatment group for overall population and for each stratification factor. 


 
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17.1.3. 
MISSING DATA METHODS FOR PRIMARY EFFICACY VARIABLE 
For the primary endpoint of percent change from baseline to Week 12 in LDL‐C values, a pattern mixture 
model (PMM) will be used to specify different imputation strategies depending on whether the patient is 
still on study treatment. Patients with missing lipid data at Week 12 who are no longer taking study 
treatment (defined by date of last dose of study medication is < Week 12 visit date ‐7) can be assumed to 
no longer be benefitting from study medication, and their missing value(s) can be assumed to be similar 
to those in placebo group who remained on study and have data. To account for uncertainty, missing 
values will be imputed using multiple imputation via a regression based model including stratification 
and baseline data from placebo subjects only.  In this imputation model, treatment group will not be 
included as a factor. 
 
Patients with missing lipid data at Week 12 who are still taking study treatment (date of last dose of 
study medication is ≥ Week 12 visit date ‐7) can be assumed to continue to benefit from study 
medication, and their missing value(s) can be assumed to be similar to those who remain on study 
treatment and have data and as a result, lipid values will be imputed based on the observed values in 
their randomized treatment group at Week 12. To account for uncertainty, missing values will be 
imputed using multiple imputation via a regression based model including treatment, stratification and 
baseline data. 
 
Imputed datasets will be analyzed using an ANCOVA model with treatment, CV risk, baseline statin 
intensity as a factors and baseline LDL‐C as a covariate. Approximately 200 imputed datasets will be 
created, with results from the analysis of each imputed dataset combined using Rubin’s method. 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.  To account for 
possibility of unequal variances between the groups, the ANCOVA model will be implemented within 
mixed model framework where <repeated/group=> option will be used to allow separate estimation of 
residual variance between the groups. 
 
Further information on the multiple imputation method is presented in Appendix 4. 
17.2. SECONDARY EFFICACY 
The secondary efficacy analyses will be performed for the full analysis set (FAS). 
17.2.1. 
KEY SECONDARY EFFICACY ENDPOINTS 
The key secondary endpoints, which are included in the hierarchical analysis described in Section 7.5, 
are: 
 
percent change from baseline to Week 24 in LDL‐C  


 
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 
percent change from baseline to Week 12 in non‐HDL‐C  
 
percent change from baseline to Week 12 in TC  
 
percent change from baseline to Week 12 in apoB  
 
percent change from baseline to Week 12 in hsCRP  
Key secondary endpoints of LDL‐C, non‐HDL‐C, TC, and apoB will be analyzed using the same ANCOVA 
model described in 17.1.2.   
Similar to the primary endpoint, missing data will be imputed using multiple imputation method as 
described in 17.1.3.   
For hsCRP, a non‐parametric (Wilcoxon rank‐sum test) analysis with Hodges‐Lehmann estimates and 
confidence interval will be performed because based on historical knowledge, publication precedence 
(Brendan etc., 2006) and recent data available, hsCRP is known to be skewed by extreme values and 
have non‐normal distribution.  
Graphic presentations (mean+/‐SE) or median (IQR) for efficacy parameters will be provided.  
17.2.2. 
OTHER SECONDARY EFFICACY VARIABLES & DERIVATIONS 
 
change from baseline to Week 12 in LDL‐C  
 
change from baseline to Week 24 in LDL‐C  
Other secondary endpoints will be analyzed using descriptive statistics by treatment group using 
observed data as well as on‐treatment approach.  
17.2.3. 
SENSITIVITY ANALYSIS OF PRIMARY AND KEY SECONDARY EFFICACY VARIABLES 
17.2.3.1. 
Analysis Using Derived Stratification Factors 
In order to assess any potential impact to the efficacy result from mis‐stratification, the stratification 
factors of disease characters and statin intensity will be derived in cases there is a known stratification 
error.  The primary endpoint will be re‐analyzed using the same method as described in section 17.1.2 
using derived stratification factors. 
17.2.3.2. 
Adjunctive Lipid‐modifying Therapy (LMT) Analysis 
To explore the potential impact from adjunctive lipid‐modifying therapy use during the study, a 
sensitivity analysis will be performed for primary and key secondary endpoints using data prior to the 
change of the post‐baseline LMT only, i.e., lab test date <=change date of LMT.  There will be no 
imputation for missing data. 


 
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17.2.3.3. 
On‐treatment Analysis 
To explore the impact to efficacy from patient discontinue study medication, an on‐treatment analysis 
will also be conducted for primary and key secondary endpoints using data collected from the on‐
treatment period, i.e. lab test date <= of last dose of double‐blind IMP+7 days.   On‐treatment analysis 
will be based on FAS.  There will be no imputation for missing data. 
17.2.3.4. 
Observed Data Analysis 
The observed case data with no imputation for missing data will be used in sensitivity analyses for 
primary and key secondary endpoints to explore any difference between a observed analysis vs. 
missing data imputation using PMM method. 
 
 
17.2.4. 
SUBGROUP ANALYSIS OF PRIMARY EFFICACY VARIABLE 
The primary endpoint for LDL‐C will be analysed within subgroups below using the same analysis 
method previously described.   The treatment and subgroup interaction will be examined by including 
the interaction term in the ANCOVA model for the overall population first. No imputation will be 
performed on missing data for subgroup analyses.  In case the number of subjects within a subgroup is 
too small, e.g. less than 5% of the overall population, the analyses may not be performed or the 
subgroup levels may be combined.  Forest plots for the primary efficacy variable will also be 
presented.  
 
CV risk category (HeFH (with or without ASCVD) vs. ASCVD only) 
 
Baseline statin intensity (Low or Moderate, vs. High) 
 
Baseline LDL category (<130mg/dL, ≥130 mg/dL and < 160 mg/dL, ≥160mg/dL) 
(efficacy only) 
 
History of diabetes (yes vs.no) 
 
Age (< 65 yrs. vs. ≥65 yrs. and <75 yrs vs. ≥75 yrs) 
 
Race (White vs. other) 
 
Gender  (male vs. female) 
 
Region (North America vs. EU) 
 
BMI category (< 25 vs. 25 ‐ < 30 vs. ≥ 30 kg/ m2) 


 
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17.3. TERTIARY EFFICACY  
17.3.1. 
TERTIARY EFFICACY VARIABLES & DERIVATIONS 
The tertiary efficacy endpoints are: 
 
Absolute change and percent change from baseline to Week 52 in LDL‐C 
 
Percent change from baseline to Weeks 24 and 52 in non‐HDL‐C, TC, apoB, and hsCRP 
 
Percent change from baseline to Weeks 12, 24, and 52 in TG and HDL‐C 
17.3.2. 
MISSING DATA METHODS FOR TERTIARY EFFICACY VARIABLES 
No missing data imputation will be used for the tertiary analyses. 
17.3.3. 
ANALYSIS OF TERTIARY EFFICACY VARIABLES 
Tertiary efficacy endpoints of LDL‐C, non‐HDL‐C, TC and ApoB will be analyzed using the same ANCOVA 
model described in 17.1.2.  Each statistical comparison will be conducted at significant level of 0.05. 
hsCRP will be analysed using non‐parametric Wilcoxon rank sum test as described in 17.2.1. 
In addition, the LDL‐C endpoint at week 52 will be analyzed with patients in the FAS who did not 
receive additional lipid‐lowering therapy by that time point (by week 52). Only observed case data will 
be used (no imputation for missing data). 
For endpoint of HDL‐C and TG at week 12, 24, and 52 summary statistics will be provided for actual 
value, change and percent change at each visit by treatment group. 
17.3.1. 
ADDITIONAL ANALYSIS 
Proportion of patients achieve hsCRP <2 mg/L at Weeks 12, 24, and 52 for whom baseline hsCRP >2 
mg/L will be analysed by Cochran–Mantel–Haenszel (CMH) method adjusted by stratification factor. 
Summary statistics and treatment difference estimates are based on observed data with no imputation 
for the missing data. 
18. SAFETY OUTCOMES 
All outputs for safety outcomes will be based on the Safety Analysis Set.  
There will be no statistical comparisons between the treatment groups for safety data, unless 
otherwise specified with the relevant section.  


 
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18.1. ADVERSE EVENTS 
Adverse Events (AEs) will be coded using MedDRA, Version 20.1. 
Treatment emergent adverse events (TEAEs) are defined as AEs that started or worsened in severity  
after the first dose of double‐blind study medication and prior to the last date of study medication + 
30 days. AEs that occurred on day 1 will be only be determined as TEAE if the site indicated it occurred 
after first dose on the AE CRF. 
See Appendix 2 for handling of partial dates for AEs.  In the case where it is not possible to define an 
AE as treatment emergent or not, the AE will be classified by the worst case scenario, i.e. treatment 
emergent.  
An overall summary of number of patients within each of the categories described in the sub‐section 
below, will be provided as specified in the templates.  Listings will include TEAEs and Non‐TEAEs. 
18.1.1. 
ALL TEAES  
Incidence of TEAEs will be presented by System Organ Class (SOC) and Preferred Term (PT) and also 
broken down further by maximum severity and relationship to study medication. TEAEs will also be 
presented by PT in descending frequency.  Adverse events by the subgroups in Section 17.2.4 with the 
exception of baseline LDL subgroup will also be presented. 
18.1.2. 
SEVERITY 
Severity is classed as mild/ moderate/ severe (increasing severity). TEAEs starting after the first dose of 
double‐blind study medication with a missing severity will be classified according to worst case 
scenario, ie, as severe. If a subject reports a TEAE more than once within that SOC/ PT, the AE with the 
worst case severity will be used in the corresponding severity summaries. 
18.1.3. 
RELATIONSHIP TO STUDY MEDICATION 
Relationship, as indicated by the Investigator, is “not related” if the TEAE is “not related” or “unlikely 
related” A ”related” TEAE is defined as a TEAE with a relationship of ”possibly related”,  ”probably 
related”, or “definitely related” to study medication. TEAEs with a missing relationship to study 
medication will be regarded as ”related” to study medication. If a subject reports the same AE more 
than once within that SOC/ PT, the AE with the worst case relationship to study medication will be 
used in the corresponding relationship summaries.  
18.1.4. 
TEAES LEADING TO DISCONTINUATION OF STUDY MEDICATION 
TEAEs leading to permanent discontinuation of study medication will be identified by using the 


 
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response of ‘Drug Withdrawn/Permanently discontinued’ on the Action Taken With Study Drug Field 
on the AE eCRF page.  For TEAEs leading to discontinuation of study medication, summaries of 
incidence rates (frequencies and percentages) by SOC and PT will be prepared.  
18.1.5. 
SERIOUS ADVERSE EVENTS 
Serious adverse events (SAEs) are those events recorded as ”Serious” on the Adverse Events page of 
the (e)CRF. A summary of serious TEAEs by SOC and PT will be prepared. Serious TEAEs will also be 
presented by PT in descending frequency.  
18.1.6. 
ADVERSE EVENTS OF SPECIAL INTEREST (AESI) 
Adverse events of special interest will be identified by pre‐specified MedDRA preferred terms provided 
by Esperion Therapeutics Inc. (see Appendix 5).  These events will be summarized by AESI category, 
SOC and PT. All AESI will be summarized by severity and relationship to study medication.  In addition, 
AESI will be evaluated by monitoring safety labs as detailed in section 18.4. 
18.2. DEATHS 
If any patients die during the study, as recorded on the Death Event page of the eCRF , the information 
will be presented in a data listing.  Deaths will be categorized as cardiovascular (CV) death (MACE) or 
non‐CV death (non‐MACE). 
18.3. CLINICAL ENDPOINTS 
Clinical endpoints will be monitored and adjudicated by an independent blinded expert CEC for this 
study.  The following clinical endpoints will be tabulated: 
 
CV death (MACE) 
 
Non‐CV death (non‐MACE) 
 
Nonfatal myocardial infarction [MI] (MACE) 
 
Nonfatal stroke (MACE) 
 
Hospitalization for unstable angina (MACE) 
 
Coronary revascularization (MACE)  
 
Non‐coronary arterial revascularization (non‐MACE)  
 
Hospitalization for heart failure (non‐MACE) 
 


 
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Additional details regarding clinical endpoints and clinical endpoint definitions will be included in CEC 
charter.  The number of patients with at least one adjudicated event and incidences and percentage of 
patients with each event will be presented in a table. 
18.4. SAFETY LABORATORY EVALUATIONS 
Results from the central laboratory will be included in the reporting of this study for Hematology, 
Blood Chemistry, Lipids, Coagulation, HbA1C, hsCRP and Urinalysis. A list of laboratory assessments to 
be included in the outputs is included in Protocol, Section 11.1.6.1.  
Presentations will use SI Units and conventional units.  
Quantitative laboratory measurements reported as “< X”, i.e. below the lower limit of quantification 
(BLQ), or “> X”, i.e. above the upper limit of quantification (ULQ), will be converted to X for the 
purpose of quantitative summaries, but will be presented as recorded, i.e. as “< X” or “> X” in the 
listings. 
The formula to calculate eGFR is:  eGFR = 186 x (Creatinine / 88.4)‐1.154 x (Age)‐0.203 x (0.742 if 
female) x (1.210 if black), where creatinine is in mmol/L. 
Summaries for all lab results, including unscheduled visit values, will be included for below analyses: 
Observed and change/percent change from baseline by visit (for quantitative measurements). 
Shift from baseline by visit according to normal ranges. 
Shift from baseline according to normal ranges for HbA1c and glucose by history of diabetes and visit. 
eGFR and values of CK will be summarized by treatment group and by baseline eGFR categories (low, 
normal, high).    
Potential Hy’s law cases (>3 × ULN for either ALT or AST AND Total Bilirubin >2 × ULN in the setting of 
no known other cause) will be tabulated and listed. 
Laboratory abnormalities in parameters of interest 
ALT or AST (> 3x ULN , >5xULN)  
TB (>2x ULN)  
CK (> 5x ULN) and (>10x ULN)  
Fasting Blood Glucose (≤50 mg/dL, ≥126 mg/dL) by history of diabetes  
HbA1c (≥6.5%) by history of diabetes  
Creatinine (change from baseline for >1 mg/dL )  
eGFR (< 15 mL/min/1.73m2, 15 –< 30 mL/min/1.73m2)  
Hgb (decrease from baseline for ≥2 g/dL)  
Hgb (<8 g/dL) 


 
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18.4.1. 
LABORATORY REFERENCE RANGES AND MARKEDLY ABNORMAL CRITERIA 
Quantitative laboratory measurements will be compared with the relevant laboratory reference 
ranges in SI units and categorized as: 
Low: Below the lower limit of the laboratory reference range.  
Normal: Within the laboratory reference range (upper and lower limit included). 
High: Above the upper limit of the laboratory reference range. 
In addition to the high and low quantitative laboratory assignments, Hy’s law criteria (≥3 × ULN for 
either ALT or AST, with accompanying total bilirubin >2 × ULN in the absence of other known causes) 
will be used to identify potential Hy’s law cases. 
18.5. ECG EVALUATIONS 
The Investigator’s judgment of overall assessment of ECG (Normal, Abnormal, Not Clinically Significant 
(ANCS), and Abnormal, Clinically Significant (ACS)) will be recorded at baseline and end of study.  A 
summary of shift from baseline to end of study in overall assessment will be provided. 
18.6. VITAL SIGNS 
The following Vital Signs measurements will be reported for this study: 
 
Sitting Systolic Blood Pressure (mmHg) 
 
Sitting Diastolic Blood Pressure (mmHg) 
 
Sitting Heart Rate (bpm) 
 
Weight (kg) 
 
Height (cm) (at Screening only) 
 
BMI (kg/m2) (calculated automatically by the EDC system) 
The following summaries will be provided for vital signs data: 
 
Observed and change from baseline by visit 
18.7. PHYSICAL EXAMINATION 
Abnormalities in physical examinations will be presented in a listing. 


 
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18.8. PHARMACOKINETICS 
A PK blood sample will be collected prior to dosing at Weeks 24 and 52. Descriptive statistics for 
concentrations of bempedoic acid and its metabolite ESP15228 will be presented for each visit for the 
PK Analysis Set as defined in section 5.4.  All concentration data will also be presented in a listing.  
All concentrations below the limit of quantification or missing data will be labelled 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. 
19. DATA NOT SUMMARIZED OR PRESENTED 
The other variables and/or domains not summarized or presented are: 
• 
Comments 
• 
Variables used by the data entry system to direct user to proper page (e.g., patient visit status, 
patient health status) 
• 
Inclusion/Exclusion Criteria that are not violated 
• 
Normal Physical Examination Results 
These domains and/or variables will not be summarized or presented, but will be available in the 
clinical study database, SDTM and/or ADaM datasets. 


 
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20. REFERENCES  
Demets, David L., and K. K. Lan. "Interim analysis: the alpha spending function approach." Statistics in 
medicine 13.13‐14 (1994): 1341‐1352. 
ICH E9. E9 Statistical Principles for Clinical Trials. Federal Register. 1998; 63(179):49583‐49598. 
Liang, K., Zeger, S., Longitudinal Data Analysis for Continuous and Discrete Responses for Pre‐Post 
Designs.  Sankhyta:  The Indian Journal of Statistics.  2000.  62(B):  134‐148. 
Little, R. & Rubin,  D.(1987) Statistical Analysis with Missing Data, Wiley, New York.  
Ratitch, B. and O’Kelley, M., “Implementation of Pattern‐Mixture Models Using Standard SAS/STAT 
Procedures,” in Proceedings of PharmaSUG 2011 (Pharmaceutical Industry SAS Users Group), SP04, 
Nashville. 
O'Brien, Peter C., and Thomas R. Fleming. "A multiple testing procedure for clinical trials." Biometrics 
(1979): 549‐556. 
Brendan M.Everett, TobiasKurth, Julie E.Buring, Paul M.Ridker. “The Relative Strength of C‐Reactive 
Protein and Lipid Levels as Determinants of Ischemic Stroke Compared With Coronary Heart Disease in 
Women.” Journal of the American College of Cardiology (2006), Volume 48, Issue 11, 
 
 
 
 
 
 
 


 
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APPENDIX 1. PROGRAMMING CONVENTIONS FOR OUTPUT 
QUINTILES OUTPUT CONVENTIONS 
OUTPUT FILE NAMING CONVENTIONS 
 
File names should only consist of uppercase letters, lowercase letters, digits (0 to 9) and underscores. A 
period should only be used to indicate a separator between the file name and the extension. No spaces, 
other special characters or punctuation marks are permitted. 
 
As far as possible, output files should be in RTF format, although .DOC files are also permitted. 
 
The program, program log and output file name should reflect the type and number of the statistical 
output. If this is not possible, then the output name should be at least as descriptive as possible. A prefix 
can be used to distinguish between a Table, Listing and Figure document (‘T’ for table, ‘L’ for listing and 
‘F’ for figure). If there is only 1 digit in the number of the table, listing or figure in the place where 2 digits 
are possible, a leading zero should be added in the file name to make sorting consistent with the 
sequence (eg T14_3_01_1.RTF) 
 
PAPER SIZE, ORIENTATION AND MARGINS 
 
The size of paper will be Letter for the United States, otherwise A4. 
The page orientation should preferably be landscape, but portrait is also permitted. 
Margins should provide at least 1 inch (2.54 centimeters) of white space all around the page, regardless 
of the paper size. 
The number of columns per page (linesize) should be 145 for A4 and 134 for Letter. 
The number of rows per page (pagesize) should be 49 for A4 and 51 for Letter. 
 
 
 
 


 
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FONTS 
 
The font type ‘Courier New’ should be used as a default for tables and listings, with a font size of 8. The 
font color should be black. No bolding, underlining italics or subscripting should be permitted. Try to 
avoid using super‐scripts, unless absolutely necessary. Single spacing should be used for all text. 
Figures should have a default font of “Times Roman”, “Helvetica”, or “Courier New” . 
This can be achieved by using the following options in SAS: 
goptions 
gunit = pct 
cback = white 
colors = (black) 
hby = 2.4 
ftext = "TimesRoman" 
htext = 2.5 
device = cgmof97l 
gaccess = gsasfile; 
filename gsasfile "….cgm"; 
 
HEADER INFORMATION 
 
Headers should be defined as follows: 
• The header should be placed at the top of the page (same place on each page) regardless of the size or 
orientation of the table or listing 
• The customer name and protocol number should appear in row 1, left‐aligned 
• The output identification number should appear in row 2, centered 
• The output title should start in row 3, centered 
• The output population should appear in row 4, centered. The population should be spelled out in full, 
e.g. Intention‐to‐Treat in preference to ITT. 
• Row 5 should be a continuous row of underscores (‘_’) (the number of underscores should equal the 
linesize) 
• Row 6 should be a blank line 
• Mixed case should be used for titles 
• The output titles should be designed so that they are arranged consistently through all outputs. For 
example, content (eg Vital Signs) followed by metric (eg Change from Baseline) e.g. Vital Signs – 
Change from Baseline. 
• Titles should not contain quotation marks or footnote references 
• The column headings should be underlined with a row of underscores (‘_’) 
• Column headings spanning more than one column should be underlined and have underscores on 
either side of the title and should be centered 
• Column headings containing numbers should be centered 
• Column headings should be in sentence case 
• In general, the population count should appear in the column header in the form “(N=XXX)” 


 
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• “Statistic” should be the column header over n, Mean, SE, n (%) etc. 
• As a rule, all columns should have column headings. 
 
TABLE AND LISTING OUTPUT CONVENTIONS 
 
General: 
• The first row in the body of the table or listing should be blank 
• The left hand column should start in column 1. No indenting or centering of the output should occur. 
• Rounding should be done with the SAS function ROUND. 
• Numbers in tables should be rounded, not truncated. 
• Alphanumeric output should be left aligned. 
• Numbers should be decimal point aligned. 
• Whole numbers should be right aligned. 
• Text values should be left aligned. 
• The first letter of a text entry should be capitalized 
• Listings of adverse events, concomitant medications, medical histories etc. should be sorted in 
chronological order, with earliest adverse event, medication or history coming first. 
• The study drug should appear first in tables with treatments as columns 
• In general, only present totals (across treatment groups) at baseline/randomization, and do not 
present them post randomization, unless the customer specifically requests it. 
• If possible, include 100% frequencies in the table shell, so that it is clear what the denominator is for 
percentage calculations. 
• All listing outputs should be sorted (preferably by Treatment, Site Number and Subject Number). 
• Do not use superscripts and subscripts 
• Exponentiation will be expressed using a double asterisk, i.e., mm3 will be written as mm**3. 
• All variables that are output in the CRF (which have data present) should appear in the listings, along 
with all derived data appearing in the corresponding tables 
• The width of the entire output should match the linesize 
 
Univariate Statistics: 
• Statistics should be presented in the same order across tables (i.e., n, Mean, SD, Q1, Median, Q3, 
Minimum, Maximum) 
• Table statistics should line up under the N part of the (N=XXX) in the table header. All decimal points 
should line up. If the minimum and maximum are output on one line as Minimum, Maximum then the 
comma should line up with the decimal point. 
• If the original data has N decimal places, then the summary statistics should have the following decimal 
places: 
Minimum and maximum: N 
Mean, median and CV%: N + 1 
SD: N + 2 
 
 


 
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Frequencies and percentages (n and %): 
• Percent values should be reported inside parentheses, with one space between the count and the left 
parenthesis of the percentage. Parentheses should be justified to accept a maximum of 100.0 as a 
value and padded with blank space if the percent is less than 100.0. An example is given below: 
77 (100.0%) 
50 ( 64.9%) 
0 ( 0.0%) 
• Percentages will be reported to one decimal place, except percents <100.0% but >99.9% will be 
presented as ‘>99.9%’ (e.g., 99.99% is presented as >99.9%); and percents < 0.1% will be presented as 
‘<0.1%’ (e.g., 0.08% is presented as <0.1%). Rounding will be applied after the <0.1% and >99.9% rule. 
Eg ( <0.1%) 
( 6.8%) 
(>99.9%) 
Percentages may be reported to 0 decimal places as appropriate (for example, where the 
denominator is relatively small). 
• Where counts are zero, percentages of 0.0% should appear in the output. 
 
Confidence Intervals: 
• As a rule confidence intervals are output to one place more than the raw data, and standard deviations 
and standard errors to two places more than the raw data 
• Confidence intervals should be justified so that parentheses displayed on consecutive lines of a table 
“line up”. 
• Boundary values of confidence intervals should be separated by a comma. 
• Boundary values should be padded as necessary to accept negative values and to allow alignment of 
the decimal place. 
• An example is given below: 
(‐0.12, ‐0.10) 
( 9.54, 12.91) 
 
P‐values: 
• P‐values should be reported to three decimal places, except values <1.000 but >0.999 will be presented 
as ‘>0.999’ (e.g., 0.9998 is presented as >0.999); and values <0.001 will be presented as ‘<0.001’ (e.g., 
0.0009 is presented as <0.001). Rounding will be applied after the <0.001 and >0.999 rule 
 
Ratios: 
• Ratios should be reported to one more decimal place than the original data. 
 
Spacing: 
• There must be a minimum of 1 blank space between columns (preferably 2) 
 
 


 
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Denominators: 
• If a different count other than the population count is used for a denominator (within the table) to 
calculate percentages, there should be a row in the table that identifies that number “n”. 
• Alternatively, a footnote should be included in each table with percentages to indicate the 
denominator for percentages. 
 
Missing values 
• A “0” should be used to indicate a zero frequency. 
• A blank will be used to indicate missing data in an end‐of‐text table or subject listing. 
 
FIGURE OUTPUT CONVENTIONS 
 
• Figures should be provided in RTF files using the SAS Output Delivery System (ODS), as Computer 
Graphics Metafile (CGM) formatted graphical output generated by SAS. 
• The CGM file itself should contain the title or footer. 
• The image should be clear and of high quality when viewed in the Word document, and when printed. 
• In general, boxes around the figures should be used. 
 
FOOTNOTE INFORMATION 
 
Footers should be defined as follows: 
• A continuous line of underscores (‘_’) will follow the body of the table or listing prior to any footnotes 
at the bottom of the page 
• Table footnotes should be defined using compute statements in the proc report, and should appear 
directly after the body of the table 
• The program path and name and version number (if applicable) should appear as footnote 1 at the 
bottom of the page 
• The date/time stamp should appear as footnote 2 at the bottom of the page 
• Footnotes should be left‐aligned. 
• Footnotes should be in sentence case. 
• Only “typewriter” symbols are permitted – eg “*”, “$”, “#”, “@”, “&” and “+”. 
• The choice of footnote symbols should be consistent. E.g. if you have the footnote “# indicates last 
observation carried forward” for one table, the same symbol and footnote should indicate LOCF for 
all tables. 
• If text wraps across more than one line (for a note), the first letter for all lines of text after the first one 
will be indented to align beneath the first letter of the text in the first line. 
• The page identification in the format Page X of Y (where Y is the total number of pages for the output) 
should appear in the first footnote, right aligned 
 
Ordering of footnotes should be as follows: 
 
1.) Source data listing reference, if necessary 


 
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2.) Abbreviations and definitions 
3.) Formulae 
4.) P‐value significance footnote 
5.) Symbols 
6.) Specific notes 
• Common notes from table to table should appear in the same order. 
• The symbols should appear in the same order as what they are defined in the table or listing, from left 
to right. 
 
PROGRAMMING INSTRUCTIONS 
 
Programming instructions must appear in blue font at the end of each table or listing shell. Programming 
instructions, where necessary, should follow the table or listing shells in blue font, beginning with the 
words “Programming Note” followed by a colon. These include notes on the output, reminders of how to 
handle missing values, repeat shells for similar tables etc. 
 
DATES & TIMES 
Depending on data available, dates and times will take the form yyyy‐mm‐ddThh:mm:ss. 
PRESENTATION OF TREATMENT GROUPS 
For outputs, treatment groups will be represented as follows and in that order: 
Treatment Group 
For Tables and Graphs 
For Listings  
Placebo 
Placebo 
Placebo 
Bempedoic Acid 180 mg 
Bempedoic Acid 180 mg 
Bempedoic Acid 180 mg 
Not Randomized 
Not Randomized 
Not Randomized 
PRESENTATION OF VISITS 
For outputs, visits will be represented as follows and in that order: 
Long Name (default) 
Short Name  
Week ‐5 (Visit S1) 
W‐5 (VS1) 
Week ‐4 (Visit S2) 
W‐4 (VS2) 


 
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Long Name (default) 
Short Name  
Week ‐1 (Visit S3) 
W‐2 (VS3) 
Week 0 (Visit T1)/Baseline 
W0 (VT1) 
Week 4 (Visit T2) 
W4 (VT2) 
Week 8 (Visit T3) 
W8 (VT3) 
Week 12 (Visit T4) 
W12 (VT4) 
 
Week 16 (Visit T4.1) 
W16 (VT4.1) 
 
Week 20 (Visit T4.2) 
W20 (VT4.2) 
 
Week 24 (Visit T5) 
W24 (VT5) 
Week 28 (Visit T5.2) 
W28 (VT5.2) 
 
Week 32 (Visit T5.3) 
W32 (VT5.3) 
 
Week 36 (Visit T6) 
W36 (VT6) 
Week 52 (Visit T7) 
W52 (VT7) 
 
Listings 
All listings will be ordered by the following (unless otherwise indicated in the template): 
 
randomized treatment  
 
center‐subject ID,  
 
date (where applicable), 
 
For listings where non‐randomized patients are included, these will appear in a category after the 
randomized treatment groups labelled ‘Not Randomized’. 
 
 


IMS Healt.h & Quint-lies a...-e now 
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APPENDIX 2. PARTIAL DATE CONVENTIONS 
Imputed dates wi ll NOT be presented in the listings. 
Algorithm for Treatment Emergence of Adverse Events: 
START DATE 
STOP DATE 
Known 
Known 
Partial 
Missing 
Partial, but known 
Known 
components show t hat it 
cannot be on or after 
st udy med start date 
Partial 
Missing 
Partial, could be on or 
Known 
after st udy med start 
date 
Partial 
Missing 
Missing 
Known 
Partial 
--- -
ACTION 
If start date < st udy med start date, then not TEAE 
If start date >= study med start date and <=study med 
end date+ 30, t hen TEAE 
If start date < st udy med start date, then not TEAE 
If start date >= study med start date and <=study med 
end date+ 30, t hen TEAE 
If start date < st udy med start date, then not TEAE 
If start date >= study med start date and <=study med 
end date + 30 , t hen TEAE 
NotTEAE 
NotTEAE 
NotTEAE 
If stop date <study med start date, t hen not TEAE 
If stop date >= study med start date and <=study med 
end date + 30, t hen TEAE 
Impute stop date as latest possible date (i.e. last day 
of month if day unknown or 31st December if day and 
month are unknown), then: 
If stop date <study med start date, t hen not TEAE 
If stop date >= study med start date and <=study med 
end date+ 30, t hen TEAE 
Assumed TEAE 
If stop date <study med start date, t hen not TEAE 
If stop date >= study med start date and <=study med 
end date + 30, t hen TEAE 
Impute stop date as latest possible date (i.e. last day 
of month if day unknown or 31st December if day and 
month are unknown), then: 
If stop date < study med start date and <=study med 
end date+ 30, t hen not TEAE 
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IMS Healt.h & Quint-lies a...-e now 
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START DATE 
STOP DATE 
Missing 
ACTION 
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If stop date >= study med st art date and <=study med 
end date+ 30, t hen TEAE 
Assumed TEAE 
Algorithm for Prior / Concomitant Medications: 
START DATE 
STOP 
DATE 
Known 
Known 
Partial 
Missing 
Partial 
Known 
Partial 
--- -
ACTION 
If stop date< study med start date, assign as prior 
If stop date >= study med start date and start date <= end of treatment, 
assign as concomitant 
If stop date >= study med start date and start date > end of treatment, 
assign as post study 
Impute stop date as latest possible date (i.e. last day of month if day 
unknown or 31st December if day and month are unknown), then: 
If stop date< study med start date, assign as prior 
If stop date >= study med start date and start date <= end of treatment, 
assign as concomitant 
If stop date >= study med start date and start date >end of treatment, 
assign as post treatment 
If stop date is missing could never be assumed a prior medication 
If start date <= end of treatment, assign as concomitant 
If start date >end of treatment, assign as post treatment 
Impute start date as earliest possible date (i.e. first day of month if day 
unknown or 1st January if day and month are unknown), then: 
If stop date< study med start date, assign as prior 
If stop date >= study med start date and start date <= end of treatment, 
assign as concomitant 
If stop date >= study med start date and start date >end of treatment, 
assign as post treatment 
Impute start date as earliest possible date (i.e. first day of month if day 
unknown or 1st January if day and month are unknown) and impute stop 
date as latest possible date (i.e. last day of month if day unknown or 31st 
December if day and month are unknown), then: 
If stop date< study med start date, assign as prior 
If stop date >= study med start date and start date <= end of treatment, 
assign as concomitant 
If stop date >= study med start date and start date >end of treatment, 
assign as post treatment 
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IMS Healt.h & Quint-lies a...-e now 
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START DATE 
STOP 
DATE 
Missing 
Missing 
Known 
Partial 
Missing 
--- -
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Page 41 of 48 
ACTION 
Impute start date as earliest possible date (i.e. first day of month if day 
unknown or 1•t January if day and month are unknown), t hen: 
If stop date is missing could never be assumed a prior medication 
If start date<= e nd of treatment, assign as concomitant 
If start date >end of treatment, assign as post t reatment 
If stop date< study med start date, assign as prior 
If stop date >= study med start date, assign as concomita nt 
Cannot be assigned as 'post treatment' 
Impute stop date as latest possible date (i.e. last day of month if day 
unknown or 31st December if day a nd month a re unknown), then: 
If stop date< study med start date, assign as prior 
If stop date >= study med start date, assign as concomita nt 
Cannot be assigned as 'post treatment' 
Assign as concomitant 
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APPENDIX 3. LIST OF DMC TABLES, LISTINGS, AND FIGURES 
TABLES 
 
14.1.1.1 
Patient Disposition – All Patients 
14.1.2.1a 
Demographic and Other Baseline Characteristics – Full Analysis Set 
14.1.3.1 
Medical/Surgical History – Full Analysis Set 
14.1.3.3 
Targeted Cardiovascular History/Risk Factors – Full Analysis Set 
14.1.5.1 
Study Drug Compliance – Safety Analysis Set 
14.3.1.1 
Overview of Treatment‐Emergent Adverse Events – Safety Analysis Set 
14.3.1.2 
Treatment‐Emergent Adverse Events by Maximum Severity, System Organ Class and 
Preferred Term – Safety Analysis Set 
14.3.1.3 
Serious Treatment‐Emergent Adverse Events by Maximum Severity, System Organ Class 
and Preferred Term – Safety Analysis Set 
14.3.1.4 
Related Treatment‐Emergent Adverse Events by Maximum Severity, System Organ Class 
and Preferred Term – Safety Analysis Set 
14.3.1.5 
Related Serious Treatment‐Emergent Adverse Events by Maximum Severity, System 
Organ Class and Preferred Term – Safety Analysis Set 
14.3.1.6 
Treatment‐Emergent Adverse Events That Led to Discontinuation of Study Drug by 
Maximum Severity, System Organ Class and Preferred Term – Safety Analysis Set 
14.3.1.8 
Treatment‐Emergent AESIs by Maximum Severity, System Organ Class and Preferred 
Term – Safety Analysis Set 
14.3.1.15 
Investigator‐reported Major Cardiac Events (MACE) by Event Type – Safety Analysis Set 
14.3.1.16 
Adjudicated Major Cardiac Events (MACE) by Event Type – Safety Analysis Set 
14.3.2.8 
Laboratory Parameters of Interest:  Observed and Change from Baseline – Safety 
Analysis Set 
14.3.2.9 
Laboratory Parameters of Interest:  Laboratory Abnormalities – Safety Analysis Set 


 
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14.3.2.10 
Quantitative Clinical Laboratory Evaluations: Lipids – Safety Analysis Set (note that this 
table is produced for DMC only) 
FIGURES 
14.3.1   
Boxplots of Hematology Parameters 
14.3.2   
Boxplots of Chemistry Parameters 
The next 2 listings will created at the same time frame as DMC TLFs above. However, these 2 listings will 
be sent to Esperion Team only for monitoring thresholds for protocol deviations and for evaluable 
patients, but not sent to DMC members. 
Listing 16.2.3 
Patient Inclusion per Analysis Population – All Screened Patients 
Listing 16.2.4 
Screen Failures – All Screened Patients (note that this listing is produced for DMC only) 
 
 
 


 
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APPENDIX 4. DETAILS OF MULTIPLE IMPUTATION METHOD 
Missing Week 12 values will be imputed based on baseline values.  The following table details the possible cohorts 
and which cohorts will be used for imputation.  Missing Week 24 values will be imputed in the same way. 
 
 
Treatment 
Week 12 
Value 
On 
Treatment 
at Week 12 
 
 
 
 
Imputation Cohort(s) 
1 
Placebo 
Missing 
Yes 
Cohort 5: 
Placebo patients with non-missing 
Week 12 
2 
BA 
Missing 
Yes 
Cohorts 6 and 8 
BA patients with non-missing Week 12 
3 
placebo 
Missing 
No 
Cohort 5: 
Placebo patients with non-missing 
Week 12 
4 
BA 
Missing 
No 
Cohorts 5 and 7 
Placebo patients with non-missing Week 12 and not on 
treatment 
5 
placebo 
Non-missing 
Yes 
 
6 
BA 
Non-missing 
Yes 
 
7 
placebo 
Non-missing 
No 
 
8 
BA 
Non-missing 
No 
 
 
Imputation code for Cohorts 1‐3. 
proc mi; 
where cohort in(1,2,3,5,6,8); 
  class trt01pn strata; 
  monotone regression; 
  var trt01pn strata base aval; 
run; 
 
Imputation code for Cohort 4. 
proc mi; 
where cohort in(4,5,7);  
class strata; 
monotone regression; 
  var strata base aval; 
run; 
 


 
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Two hundred imputed datasets will be created, with results from the analysis of each imputed dataset 
(ANCOVA) combined using Rubin’s method. 
 


 
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APPENDIX 5. 
LIST OF ADVERSE EVENTS OF SPECIAL INTEREST 
Adverse Event Terms per Protocol 
Associated MedDRA Preferred Terms 
Creatine kinase elevations 
Blood creatine phosphokinase abnormal 
Creatine kinase elevations 
Blood creatine phosphokinase increased 
Creatine kinase elevations 
Blood creatine phosphokinase MM 
abnormal 
Creatine kinase elevations 
Blood creatine phosphokinase MM 
increased 
New onset or worsening diabetes mellitus 
Blood glucose abnormal 
New onset or worsening diabetes mellitus 
Blood glucose increased 
New onset or worsening diabetes mellitus 
Diabetes mellitus 
New onset or worsening diabetes mellitus 
Diabetes mellitus inadequate control 
New onset or worsening diabetes mellitus 
Diabetic ketoacidosis 
New onset or worsening diabetes mellitus 
Glucose tolerance impaired 
New onset or worsening diabetes mellitus 
Glucose urine present 
New onset or worsening diabetes mellitus 
Glycosuria 
New onset or worsening diabetes mellitus 
Glycosylated haemoglobin increased 
New onset or worsening diabetes mellitus 
Hyperglycaemia 
New onset or worsening diabetes mellitus 
Impaired fasting glucose 
New onset or worsening diabetes mellitus 
Ketoacidosis 
New onset or worsening diabetes mellitus 
Ketosuria 
New onset or worsening diabetes mellitus 
Ketosis 
New onset or worsening diabetes mellitus 
Type 2 diabetes mellitus 
New onset or worsening diabetes mellitus 
Urine ketone body present 
Hepatic disorders 
Alanine aminotransferase abnormal 
Hepatic disorders 
Alanine aminotransferase increased 
Hepatic disorders 
Aspartate aminotransferase abnormal 
Hepatic disorders 
Aspartate aminotransferase increased 
Hepatic disorders 
Blood bilirubin abnormal 
Hepatic disorders 
Blood bilirubin increased 
Hepatic disorders 
Hepatic enzyme abnormal 
Hepatic disorders 
Hepatic enzyme increased 
Hepatic disorders 
Hypertransaminaseaemia 
Hepatic disorders 
Liver function test abnormal 
Hepatic disorders 
Liver function test increased 
Hepatic disorders 
Transaminases abnormal 


 
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Adverse Event Terms per Protocol 
Associated MedDRA Preferred Terms 
Hepatic disorders 
Transaminases increased 
Hypoglycemia 
Blood glucose abnormal 
Hypoglycemia 
Blood glucose decreased 
Hypoglycemia 
Hypoglycaemia 
Hypoglycemia 
Hypoglycaemic coma 
Hypoglycemia 
Hypoglycaemic encephalopathy 
Hypoglycemia 
Hypoglycaemic seizure 
Hypoglycemia 
Shock hypoglycaemic  
Metabolic acidosis 
Metabolic acidosis 
Muscular disorders 
Muscular weakness 
Muscular disorders 
Muscle necrosis 
Muscular disorders 
Muscle spasms 
Muscular disorders 
Myalgia 
Muscular disorders 
Myoglobin blood increased 
Muscular disorders 
Myoglobin blood present 
Muscular disorders 
Myoglobin urine present 
Muscular disorders 
Myoglobinaemia 
Muscular disorders 
Myoglininuria 
Muscular disorders 
Myopathy 
Muscular disorders 
Myopathy toxic 
Muscular disorders 
Necrotizing myositis 
Muscular disorders 
Pain in extremity 
Muscular disorders 
Rhabdomyolysis 
Neurocognitive/Neurologic disorders 
Amnesia 
Neurocognitive/Neurologic disorders 
Cognitive disorder 
Neurocognitive/Neurologic disorders 
Confusional state 
Neurocognitive/Neurologic disorders 
Disorientation 
Neurocognitive/Neurologic disorders 
Memory impairment 
Neurocognitive/Neurologic disorders 
Mental status changes 
Renal disorders 
Acute kidney injury 
Renal disorders 
Acute prerenal failure 
Renal disorders 
Blood creatinine abnormal 
Renal disorders 
Blood creatinine increased 
Renal disorders 
Blood urea abnormal 
Renal disorders 
Blood urea increased 
Renal disorders 
Blood urea nitrogen/Creatinine ratio 


 
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Adverse Event Terms per Protocol 
Associated MedDRA Preferred Terms 
increased 
Renal disorders 
Creatinine renal clearance abnormal 
Renal disorders 
Creatinine renal clearance decreased 
Renal disorders 
Glomerular filtration rate abnormal 
Renal disorders 
Glomerular filtration rate decreased 
Renal disorders 
Oliguria 
Renal disorders 
Prerenal  failure 
Renal disorders 
Renal failure 
Renal disorders 
Renal function test abnormal 
Renal disorders 
Renal impairment 
Gout 
Gout 
 


 
Esperion Therapeutics, Inc. 
Dec 17, 2018 
Protocol: ETC-1002-047 
Addendum to Statistical Analysis Plan 
 
Confidential 
Page 1 of 2 
 
 
Addendum to Statistical Analysis Plan 
Title: 
A LONG-TERM, RANDOMIZED, DOUBLE-BLIND, PLACEBO-
CONTROLLED, MULTICENTER STUDY TO EVALUATE THE 
EFFICACY OF BEMPEDOIC ACID (ETC-1002) IN PATIENTS 
WITH HYPERLIPIDEMIA AT HIGH CARDIOVASCULAR RISK 
NOT 
ADEQUATELY 
CONTROLLED 
BY 
THEIR 
LIPID-
MODIFYING THERAPYE 
Protocol: 
ETC-1002-047 
Clinical Phase: 
3 
Product: 
ETC-1002 
Date: 
Dec 17, 2018  
 
 
 


 
Esperion Therapeutics, Inc. 
Dec 17, 2018 
Protocol: ETC-1002-047 
Addendum to Statistical Analysis Plan 
 
Confidential 
Page 2 of 2 
 
Addendum to the Statistical Analysis Plan for Study 1002-047 
Post-hoc Analyses 
 
Esperion completed the planned analysis as described in Study 1002-047 SAP for all data 
collected in the study. After unblinding, additional tables and figures were generated to 
address some issues of clinical interest. 
The tables and figures may be presented in the manuscript, presented in the top line results 
press release, reported in the CSR, and included the communications with the regulatory 
agencies for the NDA/MAA submissions. 
The listing of tables and figures for the post-hoc analyses is provided in the table below. 
Table 17.2.4.1a 
Efficacy Subgroup Analysis: Percent Change from Baseline to Week 12 in Low 
Density Lipoprotein Cholesterol (LDL-C) by Derived Baseline Statin Intensity / 
Full Analysis Set 
Table 17.2.4.1b 
Efficacy Subgroup Analysis: Percent Change from Baseline to Week 12 in Low 
Density Lipoprotein Cholesterol (LDL-C) by Baseline Lipid-modifying / 
Therapies (LMT) Medications Full Analysis Set 
Table 17.2.2.6a 
Key Secondary Efficacy Non-parameteric Analysis: Wilcoxon Rank Sum Test 
on Percent Change from Baseline to Week 12 and 52 in High-Sensitivity C-
reactive Protein (hsCRP) by Derived  Baseline Statin Intensity /Full Analysis Set 
Table 17.2.2.6b 
Key Secondary Efficacy Non-parameteric Analysis: Wilcoxon Rank Sum Test 
on Percent Change from Baseline to Week 12 and 52 in High-Sensitivity C-
reactive Protein (hsCRP) by Baseline Lipid-modifying Therapies (LMT) 
Medications / Full Analysis Set 
Table 17.2.2.6c  
Key Secondary Efficacy Non-parametric Analysis: Wilcoxon Rank Sum Test on 
Percent Change from Baseline to Week 24 and 52 in High-Sensitivity C-reactive 
Protein (hsCRP) On-Treatment Analysis / Full Analysis Set 
Table 17.3.1.1 
Incidence of Positively Adjudicated Treatment-Emergent Composite Clinical 
Endpoints / Safety Analysis Set 
Table 17.4.1.1 
Post-Randomization Abnormal Liver Function Summary / Safety Analysis Set 
Figure 19.1.1 
Waterfall Plot of Percent Change from Baseline to Week 12 in Low Density 
Lipoprotein Cholesterol (LDL-C) / Full Analysis Set