A Randomized, Double-blind, Placebo-controlled, Multicenter Long-term Safety and Tolerability Study of ETC-1002 in Patients With Hyperlipidemia at High Cardiovascular Risk Who Are Not Adequately Controlled by Their Lipid-Modifying Therapy
Phase: PHASE3
Conditions: Hypercholesterolemia, Atherosclerotic Cardiovascular Diseases
Sponsor: Esperion Therapeutics, Inc.

ETC-1002 
1002-040 
A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 
MULTICENTER LONG-TERM SAFETY AND TOLERABILITY STUDY 
OF ETC-1002 IN PATIENTS WITH HYPERLIPIDEMIA AT IDGH 
CARDIOVASCULAR RISK WHO ARE NOT ADEQUATELY 
CONTROLLED BY THEIR LIPID-MODIFYING THERAPY 
Study Phase: 
3 
IND Number: 
106 ,654 
EudraCT Number: 
2015-004136-36 
Indication: 
Treatment of hyperlipidemia 
Investigators: 
Approximately 125 sites located in the United States, Canada, 
Ge1many, Netherlands, Poland, United Kingdom 
Sponsor: 
Esperion Therapeutics, Inc. 
3891 Ranchero Drive, Suite 150 
Ann Arbor, MI 48108 
Sponsor Contact: 
Medical Monitor: 
Version 
Original Protocol: 
Amendment 1 
Amendment2 
Amendment3 
Amendment4 
Amendments 
Date 
02 October 2015 
28 Janua1y 2016 
23 Febmaiy 2016 
28 July2016 
14 October 2016 
10 May2017 
Confidentiality Statement 
THIS CONF1DENTIAL INFORMATION IS ABOUT AN INVESTIGA TIONAL DRUG PROVIDED FOR THE EXCLUSIVE USE OF INVESTIGATORS OF 
THIS DRUG AND IS SUBJECT TO RECALL AT ANY TIME. 1HE INFORMATION IN THIS DOCUMENT MAY NOT BE DISCLOSED UNLESS SUCH 
DISCLOSURE IS REQUIRED BY FEDERAL OR STATE LAW OR REGULATIONS. SUBJECT TO THE FOREGOING, THIS INFORMATION MAY BE 
DISCLOSED ONLY TO THOSE PERSONS INVOLVED IN THE STUDY WHO HA VE NEED TO KNOW, WITH THE OBLIGATION NOT TO FURTHER 
DISSEMINATE THIS INFORMATION. 1HEsE RESTRICTIONS ON DISCLOSURE WILL APPLY EQUALLY TO ALL FUTURE ORAL OR WRITTEN 
INFORMATION, SUPPLIED TO YOU BY ESPERION 1HERAPEUTICS, INC., WHICH IS DESIGNATED AS "PRIVILEGED" OR "CONFIDENTIAL." 
Confidential 
Page 1 of287 
NCT number: NCT02666664
This NCT number has been applied to the document
for purposes of  posting on clinicaltrials.gov

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 2 of 287 
2. 
SYNOPSIS 
Name of Sponsor: Esperion Therapeutics, Inc. 
Name of Investigational Product: ETC-1002 film-coated tablets 
Name of Active Ingredient: ETC-1002 (bempedoic acid) 
Title of Study:  
A Randomized, Double-blind, Placebo-controlled, Multicenter Long-term Safety and Tolerability Study 
of ETC-1002 in Patients with Hyperlipidemia at High Cardiovascular Risk Who are not Adequately 
Controlled by Their Lipid-Modifying Therapy  
Study Number: 1002-040 
Phase of Development: 3 
Clinical Sites: Approximately 125 sites located in the United States, Canada, Germany, Netherlands, 
Poland, United Kingdom 
Objectives:  
Primary Safety: 
• 
To evaluate the long-term safety and tolerability of ETC-1002 versus placebo 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 Efficacy: 
• 
To assess percent change from baseline to Week 12 in low-density lipoprotein cholesterol 
(LDL-C) 
Tertiary Efficacy: 
• 
To assess percent change from baseline to Week 24 and to Week 52 in LDL-C in patients who do 
not receive adjunctive lipid-lowering therapy 
• 
To assess high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC), 
and triglycerides (TG) values at Week 12, 24, and 52  
• 
To assess apolipoprotein B (apoB) and high-sensitivity C-reactive protein (hs-CRP) values at 
Week 12, 24, and 52  
Study Hypothesis:  
The primary clinical hypothesis is that long-term exposure of ETC-1002 will be safe and well tolerated 
in high CV risk patients with hyperlipidemia (patients with underlying HeFH and/or ASCVD) who are 
not adequately controlled with their maximally tolerated lipid-modifying therapy, including a maximally 
tolerated statin.  
The study will characterize the long-term safety and tolerability of ETC-1002 versus placebo in addition 
to maximally tolerated lipid-lowering therapy, including a maximally tolerated statin, in patients with 
hyperlipidemia. The randomized, double-blind, placebo controlled add-on to maximally tolerated lipid-
lowering therapy design will ensure that long-term safety data are meaningful and interpretable. The 
extended treatment duration (52 weeks) and large patient number (n = 1950) will provide robust long-
term safety in high CV risk patients who have an unmet medical need for additional lipid-lowering 
therapy, such as ETC-1002 once daily, orally bioavailable option.  

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 3 of 287 
Methodology:  
1002-040 STUDY DESIGN 
Study Design: 
This is a Phase 3, randomized, double-blind, placebo-controlled, parallel group, study evaluating the 
long-term safety and tolerability of ETC-1002 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-lowering therapy includes a maximally tolerated 
statin alone or in combination with other lipid-lowering therapies (eg, ezetimibe, fibrates [except 
gemfibrozil]). 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. However, patients who are currently taking simvastatin at average 
daily doses that are greater than 40 mg per day or who are currently taking a proprotein convertase 
subtilisin/kexin type 9 (PCSK9) inhibitor (alirocumab or evolocumab), or have taken a PCSK9 inhibitor 
within the past 4 weeks of Week -2 (Visit S1) will be excluded from enrolling in this study. PCSK9 
inhibitors may be initiated as adjunctive therapy at Week 24 if the LDL-C threshold criteria have been 
met as described in Section 11.1.6.3.5. 
Screening (Visit S1) will occur approximately 2 weeks prior to Day 1 (Visit T1). Patients on maximally 
tolerated lipid-lowering therapy, as determined by the investigator, will be stratified based on the 
patient’s CV risk and baseline statin dose. There will be no cap placed on randomization into any 
particular stratum. Approximately 1950 eligible patients will be randomized 2:1 on Day 1 (Visit T1) to 
receive either ETC-1002 180 mg (n = 1300), or placebo (n = 650) once daily for 52 weeks. Randomized 
patients will continue in the study until they have completed Week 52 (Visit T7). Randomized patients 
will return for clinic visits at Week 4 (Visit T2), Week 8 (Visit T3), Week 12 (Visit T4), Week 24 
(Visit T5), Week 36 (Visit T6), and Week 52 (Visit T7). 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 ETC-1002. A blinded 
independent expert Clinical Events Committee (CEC) will adjudicate designated clinical endpoints, 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 4 of 287 
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. 
Number of patients (planned): Approximately 1950 adult male and female patients 
Duration of treatment: Fifty-two weeks 
End of Study: The study will end when the last randomized patient completes their last study visit. The 
estimated overall duration of the study (first patient first visit [FPFV] to last patient last visit [LPLV]) is 
approximately 28 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 
• 
Provision of written informed consent prior to any study-specific procedure 
• 
Age ≥18 years or legal age of majority depending on regional law, whichever is greater at 
Week -2 (Visit S1) 
• 
Men and nonpregnant, nonlactating women. Women must be either:  
- Naturally postmenopausal (as reported by the patient, defined as greater than 55 years 
and ≥1 year without menses, less than 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 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). 
- There are no protocol-specific birth control requirements for men with partners who are 
able to become pregnant. 
• 
Fasting LDL-C value at Week -2 (Visit S1) ≥70 mg/dL (1.8 mmol/L) 
Note: LDL-C may be repeated 1 time with the screening period extended up to 2 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. 
• 
Have high cardiovascular 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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 5 of 287 
- 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 
• 
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). 
Regimens other than daily dosing, including those at very low doses, are acceptable. 
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.  
Patients currently taking an average daily dose of simvastatin that is greater than 40 mg will be 
excluded from this study. 
Patients who are currently taking a PCSK9 inhibitor (Praluent® [alirocumab] or Repatha® 
[evolocumab]) or have taken a PCSK9 inhibitor within the past 4 weeks of Week -2 (Visit S1) 
will be excluded from this study. 
Exclusion Criteria: 
• 
Total fasting triglyceride ≥500 mg/dL (5.6 mmol/L) at Week -2 (Visit S1) 
Note: TG may be repeated 1 time with the screening period extended up to 2 weeks. For those 
patients who have a repeat TG, the mean of the first value and the repeat value will be used to 
determine eligibility. 
• 
Renal dysfunction or nephritic syndrome or a history of nephritis, including eGFR (using 
central laboratory determined Modification of Diet in Renal Disease [MDRD] formula) 
<30 mL/min/1.73 m2 at Week -2 (Visit S1) [1].  
Note: At the discretion of the investigator, the screening period may be extended up to 2 weeks 
for a single repeat eGFR. For those patients who have a repeat eGFR, the repeat value will be 
used to determine eligibility. 
Note: Also excluded are renally impaired patients receiving an average daily dose of 
simvastatin 40 mg with eGFR below <45 mL/min/1.73 m2. 
• 
Body mass index (BMI) ≥50 kg/m.2 
• 
Concomitant use of simvastatin at average daily doses greater than 40 mg.  
• 
Concomitant use of a PCSK9 inhibitor (Praluent® [alirocumab] or Repatha® [evolocumab]) at 
Week -2 (Visit S1) or prior use of a PCSK9 inhibitor within the past 4 weeks of Week -2 
(Visit S1) will be excluded from this study. 
Note: Patients are allowed to initiate a PCSK9 inhibitor as adjunctive therapy at Week 24 if the 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 6 of 287 
LDL-C threshold criteria have been met as described in Section 11.1.6.3.5. 
• 
Recent (within 3 months prior to the screening visit [Week -2 (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. 
• 
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 2 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 
• 
Hemoglobin A1C (HbA1C) ≥10% at Week -2 (Visit S1) 
• 
Uncontrolled hypothyroidism, including thyroid-stimulating hormone (TSH) >1.5 × the upper 
limit of normal (ULN) at Week -2 (Visit S1). Patients stabilized on thyroid replacement therapy 
for at least 6 weeks prior to randomization are allowed. 
• 
Liver disease or dysfunction, including:  
- Positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies 
(HCV-AB) at Week -2 (Visit S1); or 
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≥2 × ULN, and/or 
total bilirubin (TB) ≥1.2 × ULN at Week -2 (Visit S1).  
Note: If HCV-AB is positive, a reflex HCV RNA will be performed to rule out active 
disease. Patients without active disease may be enrolled in the study. 
Note: At the discretion of the investigator, the screening period may be extended up to 
2 weeks for a single repeat of ALT, AST, and/or TB. For those patients who have a 
repeat ALT, AST, and/or TB, the repeat value will be used to determine eligibility. 
If TB ≥1.2 × ULN, a reflex indirect (unconjugated) bilirubin will be obtained and if the 
results are consistent with Gilbert’s disease, the patient may be enrolled in the study. 
• 
Gastrointestinal conditions or procedures (including weight loss surgery; eg, Lap-Band® or 
gastric bypass) that may affect drug absorption 
• 
Hematologic or coagulation disorders or a hemoglobin (Hgb) level <10.0 g/dL (100 g/L) at 
Week -2 (Visit S1) 
• 
Active malignancy, including those requiring surgery, chemotherapy, and/or radiation in the 
past 5 years. Patients with a history of nonmetastatic basal or squamous cell carcinoma of the 
skin and cervical carcinoma in situ are allowed. 
• 
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.  
• 
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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 7 of 287 
practitioner can be enrolled after evaluation by the Investigator. 
• 
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 
• 
Use of any experimental or investigational drugs within 30 days prior to screening or 5 half-
lives, whichever is longer 
• 
Prior participation in a previous ETC-1002 clinical study. Prior participation in a clinical study 
with ETC-1002 is defined as having been enrolled in an ETC-1002 study. 
• 
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  
• 
Requirement for 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) 
• 
An employee or contractor of the facility conducting the study, or a family member of the 
Principal Investigator, Co-Investigator, or Sponsor. 
IMP, dosage and mode of administration:  
• 
ETC-1002 180-mg tablets.  
• 
Matching placebo tablets 
• 
All IMP will be ingested once daily (once every 24 hours, at approximately the same time each 
day) 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: 
Safety Assessments: 
Adverse events (AEs) 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. Other safety 
assessments will include clinical safety laboratories (including hematology, blood chemistry, 
coagulation, HbA1C, 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),  

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 8 of 287 
• 
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: 
• 
Hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) (if HCV is positive, a reflex HCV 
RNA will be performed to rule out active disease), 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 pregnancy test Day 1 prior to randomization (only for females who are 
of childbearing potential), TSH 
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. 
Other Biomarkers:  
• 
hs-CRP 
• 
Reserve 10 mL blood samples for potential future measurement of ETC-1002 biomarkers. 
Based upon Sponsor assessment and decision, reserve sample collection will be discontinued 
after a sufficient number of samples have been collected. 
Other Assessments: 
• 
Trough plasma concentrations of ETC-1002 and its metabolite ESP15228 will be collected at 
Weeks 12, 24, and 52. 
• 
All patients will be invited to provide a blood sample for potential future genetic testing, but 
participation in this portion of the study is optional and where approved by the Institutional 
Review Board (IRB)/Independent Ethics Committee (IEC) and by local law. 
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 of ≥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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 9 of 287 
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. Patients receiving an average daily dose of simvastatin 40 mg 
based on lipid-lowering treatment modification, should adhere to the additional safety 
visits as described in Sections 10.2.5 and 10.2.6. 
- 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. 
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. 
Monitoring and Management of Potential AEs and Adverse Events of Special Interest (AESI) 
Adverse Events Associated with Experience with ETC-1002 to Date: 
Small group mean increases in uric acid and homocysteine, and decreases in hemoglobin have been 
observed, but in general, these shifts have not been associated with clinical symptoms. Clinical labs and 
hematology will be monitored throughout the study. 
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 instructed to report 
the signs and symptoms they experienced 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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 10 of 287 
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. 
Clinical Endpoints: 
Clinical endpoints will be monitored and adjudicated by an independent expert CEC for this study and 
other ongoing studies in the ETC-1002 program. 
Routine cardiovascular monitoring will include review of cardiovascular AEs, SAEs, (both as 
adjudicated by the CEC), standard vital signs, and ECGs 
Neurocognitive Events: 
Neurocognitive events will be identified and evaluated by routine safety monitoring of PE findings and 
AEs. 
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 
A total of 1950 patients will be enrolled in this study with 1300 patients randomized to ETC-1002 and 
650 patients randomized to placebo. Using an anticipated overall dropout rate of 7.5% at 6 months and 
10.0% at 12 months in each treatment group, the expected number of patients exposed to treatment 
during the study is as follows: 
 
Patients ≥6 Months 
Patients ≥12 Months 
ETC-1002 
1,202 
1,170 
Placebo 
601 
585 
 
Absolute risk will be addressed by 1300 patients randomized to ETC-1002 and will provide at least 95% 
power to detect AEs that occur at rates similar to those seen in the placebo group for the AEs of interest 
in the recently completed long-term safety study entitled Efficacy and Safety of Alirocumab in Reducing 
Lipids and Cardiovascular Events [2]. In this study, adverse event rates ranged from 0.5% to 13.6%. 
Additional assumptions include a two-sided test with significance level at 0.05. 
When AEs occur at a range of rates similar to those seen in the placebo group in the above referenced 
alirocumab study (0.5% to 13.6%), the sample size of 1300 patients randomized to ETC-1002 and 
650 patients randomized to placebo will allow for detection of relative risks of 1.0 and of 2.0 
(ETC-1002:placebo) with the following approximate 95% confidence limits:  
% Placebo Patients 
Experiencing AE 
% ETC-1002 Patients 
Experiencing AE 
Relative Risk 
Approximate 95% 
Confidence Interval 
0.5% 
0.5% 
1.0 
(0.3, 3.8) 
0.5% 
1.0% 
2.0 
(0.6, 6.7) 
13.6% 
13.6% 
1.0 
(0.8, 1.3) 
13.6% 
27.2% 
2.0 
(1.6, 2.5) 
 
 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 11 of 287 
Analysis Populations 
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.  
The Full Analysis Set (FAS), used for the LDL-C analyses and the lipid and cardiometabolic summaries, 
is defined as all randomized patients and is also known as the intention-to-treat (ITT) set of patients.  
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 Safety Endpoint  
The primary endpoint for this study is general safety, which includes AEs, clinical safety laboratories, 
PEs, vital signs, and ECGs. 
The summarization of AEs will include only treatment-emergent AEs (TEAEs), defined as AEs that 
begin or worsen after randomization and ingestion of the first dose of study drug. TEAEs and SAEs will 
be summarized by system organ class (SOC), severity, and relationship to study drug for each treatment 
group. 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 post-baseline 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) 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 will be based upon direct 
(conjugated) bilirubin. 
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 Glycemia 
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 estimated glomerular filtration rate (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. 
 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 12 of 287 
Clinical Endpoints 
Clinical endpoints will be monitored and adjudicated by an independent blinded expert CEC for ongoing 
studies the ETC-1002 program. Adjudicated clinical endpoints will be summarized by event type and 
treatment group. Additional details regarding clinical endpoints and clinical endpoint definitions will be 
included in CEC charter. 
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 
Key Efficacy Endpoints 
Percent change from baseline to Week 12 or Week 24 in LDL-C, non-HDL-C, TC, apoB, and hs-CRP 
will be analyzed using analysis of covariance (ANCOVA), with treatment and randomization strata 
(patient’s CV risk and baseline statin dose) as factors and respective baseline value as a covariate. The 
FAS will be used. Missing data for these endpoints will be imputed using multiple imputation taking 
account for treatment adherence.  
Other Efficacy Endpoints 
LDL-C, HDL-C, TG, TC, non-HDL-C, hs-CRP, and apoB values at other time points will be summarized 
and analyzed similarly to the key lipid endpoints. In addition, a summary using the FAS, excluding 
patients who received additional lipid-lowering therapy by that time point (by Week 24 for the Week 24 
time point; by Week 52 for the Week 52 time point), will be provided. For both summaries, only 
observed case data will be used (no imputation for missing data).  
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. 
PK and Other biomarkers 
Trough plasma concentrations will be collected at Weeks 12, 24, and 52 from patients randomized into 
the study prior to the implementation of Protocol Amendment 3 for use in further developing the 
population pharmacokinetic (PK) model. Trough plasma concentrations will not be collected from 
patients randomized into the study after the implementation of Protocol Amendment 3. 
 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 13 of 287 
TABLE OF CONTENTS 
1. 
TITLE PAGE ................................................................................................................1 
2. 
SYNOPSIS ...................................................................................................................2 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................19 
4. 
INTRODUCTION ......................................................................................................23 
4.1. 
Lipid-Regulating Drugs and Cardiovascular Disease .................................................23 
4.2. 
Background on ETC-1002 ..........................................................................................24 
4.2.1. 
Mechanism of Action .................................................................................................24 
4.2.2. 
Nonclinical Experience ...............................................................................................25 
4.2.3. 
Previous Human Experience .......................................................................................25 
4.2.4. 
Dose Selection ............................................................................................................27 
4.2.5. 
Background Therapy ..................................................................................................27 
4.2.6. 
Risk Benefit Summary ................................................................................................27 
5. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................28 
5.1. 
Primary Safety Objective ............................................................................................28 
5.2. 
Secondary Efficacy Objectives ...................................................................................28 
5.3. 
Tertiary Efficacy Objectives .......................................................................................28 
6. 
INVESTIGATIONAL PLAN .....................................................................................29 
6.1. 
Overall Study Design ..................................................................................................29 
6.2. 
Study Hypothesis ........................................................................................................31 
6.3. 
Study Duration and Period ..........................................................................................31 
6.4. 
End of Study ...............................................................................................................32 
6.5. 
Number of Patients .....................................................................................................32 
6.6. 
Patient Identification Numbers ...................................................................................32 
6.6.1. 
Screening ....................................................................................................................32 
6.6.2. 
Randomization and Treatment Period ........................................................................32 
7. 
SELECTION AND WITHDRAWAL OF PATIENTS ..............................................33 
7.1. 
Subject Inclusion Criteria ...........................................................................................33 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 14 of 287 
7.2. 
Subject Exclusion Criteria ..........................................................................................34 
7.3. 
Patient Lifestyle and Dietary Guidelines ....................................................................37 
7.4. 
Investigator/Sponsor Suspension or Termination of Patient Enrollment ...................37 
8. 
TREATMENT OF PATIENTS ..................................................................................39 
8.1. 
Description of IMP .....................................................................................................39 
8.2. 
Concomitant Medications ...........................................................................................39 
8.2.1. 
Lipid-Regulating Medications and Supplements........................................................40 
8.2.2. 
Prohibited Medications ...............................................................................................41 
8.2.3. 
Allowable Medications ...............................................................................................41 
8.3. 
Treatment Compliance ................................................................................................42 
8.4. 
Blinding ......................................................................................................................42 
8.5. 
Overdose .....................................................................................................................43 
9. 
INVESTIGATIONAL MEDICINAL PRODUCT .....................................................44 
9.1. 
Investigational Medicinal Product Supply and Control ..............................................44 
9.2. 
Administration of Investigational Medicinal Product ................................................44 
9.3. 
Investigational Medicinal Product Accountability .....................................................44 
9.4. 
Investigational Medicinal Product Handling and Disposal ........................................45 
10. 
STUDY PROCEDURES ............................................................................................46 
10.1. 
Informed Consent .......................................................................................................46 
10.2. 
Procedures and Schedule of Assessments ..................................................................46 
10.2.1. 
Screening Week -2 (Visit S1; Days -16 to -4) ............................................................46 
10.2.2. 
Treatment Week 0 (Visit T1; Day 1) ..........................................................................47 
10.2.3. 
Treatment Week 4 (Visit T2; ± 3 days) ......................................................................48 
10.2.4. 
Treatment Week 8 (Visit T3; ± 3 days) ......................................................................49 
10.2.5. 
Treatment Week 12 (Visit T4; ± 3 days) ....................................................................50 
10.2.5.1. 
Treatment Week 16 (Visit T4.1; ±3 days) ...................................................................51 
10.2.5.2. 
Treatment Week 20 (Visit T4.2; ±3 days) ..................................................................52 
10.2.6. 
Treatment Week 24 (Visit T5; ± 7 days) ....................................................................52 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 15 of 287 
10.2.6.1. 
Treatment Week 28 (Visit T5.1; ±7 days) ...................................................................53 
10.2.6.2. 
Treatment Week 32 (Visit T5.2; ±7 days) ...................................................................53 
10.2.7. 
Treatment Week 36 (Visit T6; ± 7 days) ....................................................................53 
10.2.8. 
Treatment Week 52 (Visit T7; ± 7 days) ....................................................................54 
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 .................................................................................................58 
11.1.5. 
Electrocardiogram .......................................................................................................59 
11.1.5.1. 
Monitoring and Management of Abnormal Electrocardiograms ................................59 
11.1.6. 
Clinical Laboratory Tests ...........................................................................................59 
11.1.6.1. 
Laboratory Parameters (Safety) ..................................................................................59 
11.1.6.2. 
Sample Collection, Storage, and Shipping .................................................................61 
11.1.6.3. 
General Monitoring and Management of Abnormal Clinical Labs ............................62 
11.1.6.4. 
Monitoring and Management of Potential Hypoglycemia and Metabolic 
Acidosis ......................................................................................................................66 
11.1.6.5. 
Pharmacokinetic Assessments ....................................................................................67 
11.1.6.6. 
Collection and Assessment of Pharmacokinetic Samples ..........................................67 
11.1.6.7. 
Exploratory Biomarker Measurement ........................................................................67 
11.1.6.8. 
Shipment of Pharmacokinetic Samples ......................................................................67 
11.1.6.9. 
Genetic Testing ...........................................................................................................67 
11.1.6.10. Total Blood Volume of Clinical Laboratory and Pharmacokinetic Samples .............67 
11.2. 
Adverse and Serious Adverse Events .........................................................................68 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 16 of 287 
11.2.1. 
Definition of Adverse Events .....................................................................................68 
11.2.2. 
Adverse Drug Reaction ...............................................................................................68 
11.2.3. 
Reporting ....................................................................................................................68 
11.2.4. 
Severity .......................................................................................................................69 
11.2.5. 
Relationship ................................................................................................................70 
11.2.6. 
Monitoring and Follow-up of Adverse Events ...........................................................70 
11.2.7. 
Treatment-Emergent Adverse Events .........................................................................71 
11.2.7.1. 
Definition of Serious Adverse Event ..........................................................................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 .........................................................................................73 
11.3.3. 
Reports of Pregnancy ..................................................................................................73 
11.4. 
Adverse Events of Special Interest .............................................................................73 
11.5. 
Data Monitoring Committee .......................................................................................76 
11.6. 
Clinical Event Committee (CEC) ...............................................................................76 
11.7. 
Assessment of Lipid Endpoints ..................................................................................76 
11.7.1. 
Lipid Parameters .........................................................................................................76 
11.7.2. 
Clinical Laboratory Tests (Lipids) ..............................................................................76 
12. 
STATISTICS ..............................................................................................................78 
12.1. 
General Considerations ...............................................................................................78 
12.2. 
Determination of Sample Size ....................................................................................78 
12.3. 
Analysis Populations ..................................................................................................79 
12.4. 
Disposition, Demographics, and Baseline Characteristics .........................................79 
12.5. 
Primary Safety Endpoint .............................................................................................79 
12.6. 
Efficacy Endpoints ......................................................................................................80 
12.6.1. 
Key Efficacy Endpoints ...............................................................................................80 
12.6.2. 
Other Efficacy Endpoints ............................................................................................81 
12.7. 
PK and Other Biomarkers ...........................................................................................81 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 17 of 287 
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 ...............................................................................................................91 
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 
APPENDIX 2. SPONSOR’S SIGNATURE ...............................................................................99 
APPENDIX 3. INVESTIGATOR’S SIGNATURE..................................................................103 
APPENDIX 4. DUTCH LIPID CLINIC NETWORK CRITERIA FOR FAMILIAL 
HYPERCHOLESTEROLEMIA...............................................................................104 
APPENDIX 5. SIMON BROOM REGISTER DIAGNOSTIC CRITERIA FOR 
HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA .........................107 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 18 of 287 
APPENDIX 6. SUMMARY OF CHANGES IN AMENDMENT 1 ........................................109 
APPENDIX 7. SUMMARY OF CHANGES IN AMENDMENT 2 ........................................192 
APPENDIX 8. SUMMARY OF CHANGES IN AMENDMENT 3 ........................................195 
APPENDIX 9. SUMMARY OF CHANGES IN AMENDMENT 4 ........................................247 
APPENDIX 10. SUMMARY OF CHANGES IN AMENDMENT 5 ......................................258 
 
LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................19 
Table 2: 
Baseline Statin Dose Categories .................................................................................29 
Table 3: 
Randomization Strata ..................................................................................................30 
Table 4: 
Investigational Medicinal Products ............................................................................39 
Table 5: 
Clinical Laboratory Parameters (Safety) ....................................................................60 
Table 6: 
Clinical Laboratory Parameters (Lipids) and Cardiometabolic Biomarkers .............77 
 
LIST OF FIGURES 
Figure 1. 
Study 1002-040 Study Design ....................................................................................31 
 
 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 19 of 287 
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 
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 
CO2 
Carbon dioxide 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 20 of 287 
Abbreviation or Specialist Term 
Explanation 
CPK 
creatine phosphokinase 
CT 
Computed tomography 
CV 
Cardiovascular 
CYP 
Cytochrome P450 
DBP 
Diastolic blood pressure 
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EMA 
European Medicines Agency 
eGFR 
Estimated glomerular filtration rate 
EOS 
End of Study 
EU 
European Union 
FAS 
Full analysis set 
FDA 
U.S. 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 
IMP 
Investigational medicinal product 
IND 
Investigational New Drug Application 
INR 
International normalized ratio 
IRB 
Institutional Review Board 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 21 of 287 
Abbreviation or Specialist Term 
Explanation 
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 
NIMP 
Non-investigational medicinal product(s) 
NLA 
National Lipid Association 
NOAEL 
No-observed-adverse-effect level 
non-HDL-C 
Non-high-density lipoprotein cholesterol 
PCI 
Percutaneous coronary intervention 
PCSK9 
Proprotein convertase subtilisin/kexin type 9 
PE 
Physical exam 
PK 
Pharmacokinetic(s) 
PMM 
Pattern mixed model 
PT 
Prothrombin time 
RBC 
Red blood cell 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SBP 
Systolic blood pressure 
SE 
Standard error 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 22 of 287 
Abbreviation or Specialist Term 
Explanation 
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 
WBC 
White blood cell 
WHO 
World Health Organization 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 23 of 287 
4. 
INTRODUCTION 
4.1. 
Lipid-Regulating Drugs and Cardiovascular Disease  
ETC-1002 (bempedoic acid) 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 risk unable to meet their treatment goals with currently 
available lipid-lowering therapies. 
Hyperlipidemic patients at high cardiovascular 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 [3]. Despite aggressive interventional and pharmacologic therapies, cardiovascular 
disease is the number 1 cause of death globally [4]. An estimated 17.5 million people died from 
cardiovascular diseases in 2012, representing 31% of all global deaths. Of these deaths, an 
estimated 7.4 million were due to coronary heart disease and 6.7 million were due to stroke [4]. 
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 (15 616.1 million deaths) were caused by cardiovascular disease in 2010, more than 
all communicable, maternal, neonatal and nutritional disorders combined, and double the number 
of deaths caused by cancers [5]. In the United States, based on 2011 death rate data, more than 
2150 Americans die from cardiovascular diseases daily, an average of 1 death every 40 seconds. 
Approximately 155, 000 Americans dying from cardiovascular disease are less than 65 years of 
age. In 2011, 34% of deaths due to cardiovascular disease occurred prior to the age of 75 years, 
less than the current 78.7-year average life expectancy [6].  
Patients with documented ASCVD are at very high risk for events and require intensive 
pharmacologic intervention [7]. 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 [8].  
Familial hypercholesterolemia refers to individuals with extremely elevated LDL-C due to 
underlying genetic mutations of the LDL receptor, apolipoprotein B (apoB), and proprotein 
convertase subtilisin/kexin type 9 (PCSK9) [9]. 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 [10]. Patients with HeFH inherit 
a genetic mutation from 1 parent. Inheritance is generally via an autosomal-dominant 
mechanism [11]. HeFH increases the risk of atherosclerosis leading to cardiovascular events. The 
mean age for the onset of cardiovascular disease is relatively young, at 42 to 46 years in men and 
51 to 52 years in women [11]. The cumulative risk of experiencing a coronary event by the age 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 24 of 287 
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 [12]. 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 cardiovascular 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 [13]. 
LDL-C is largely accepted as a valid surrogate endpoint of cardiovascular events by clinicians 
and regulatory authorities [7]. 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 [14]. Evidence supporting LDL-C as a therapeutic target and 
surrogate for cardiovascular 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 cardiovascular risk reduction, independent of the way 
LDL-C lowering was achieved based on mechanism of action [15,16,17,18]. A published 
patient-level meta-analysis including 26 trials and more than 160,000 participants, showed a 
consistent relationship between LDL-C reduction and cardiovascular outcomes [16]. 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 cardiovascular risk [19]. Unfortunately, some patients are unable to 
take high intensity statins due to dosing limits based on co-morbidities, contraindications, and/or 
tolerance [8]. Nonstatin therapies may provide additional lowering of cardiovascular risk as 
demonstrated in the IMPROVE-IT trial which added ezetimibe to statin therapy [20].  
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. ETC-1002 has 
been well tolerated to date and Phase 2 data demonstrate significant LDL-C lowering, prompting 
further evaluation in Phase 3 clinical studies.  
4.2. 
Background on ETC-1002  
4.2.1. 
Mechanism of Action 
ETC-1002 is a first-in-class small molecule inhibitor of ACL, an enzyme upstream of 
HMG-CoA in the cholesterol biosynthesis pathway. ETC-1002 is a prodrug that requires 
activation in liver to ETC-1002-coenzyme A (ETC-1002-CoA) which mediates competitive 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Amendment 5, 10 May 2017 
inhibition of ACL. Inhibition of ACL by ETC-1002-CoA decreases cholesterol synthesis in liver 
leading to increased LDL receptor (LDLR) expression and LDL pa1iicle 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 impo1i ant differentiating feature of ETC-1002 is that it does not inhibit cholesterol synthesis 
in skeletal muscle. In addition to preliminary data suggesting that only minor amounts of 
ETC-1002 enter skeletal muscle ( <5% of systeinic exposure), skeletal muscle does not express 
the enzyme required to activate ETC-1002 to ETC-1002-CoA and inhibit ACL. Therefore, 
ETC-1002 is not anticipated to mediate the adverse effects associated with inhibition of 
biological inte1mediates within the cholesterol biosynthesis pathway in skeletal muscle. 
4.2.2. 
Nonclinical Experience 
4.2.3. 
Previous Human Experience 
Confidential 
Page 25 of 287 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Amendment 5, 10 May 2017 
Confidential 
Page 26 of 287 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Amendment 5, 10 May 2017 
4.2.4. 
Dose Selection 
4.2.5. 
Background Therapy 
ETC-1002 in this study is cunently being evaluated as an add-on to statin therapy in high-risk 
patients (ie, those with HeFH and/or ASCVD) who have not achieved their LDL-C goal despite 
maximally tolerated statin therapy. 
4.2.6. 
Risk Benefit Summary 
To date, the nonclinical and clinical data indicate that ETC-1002 has a favorable risk-benefit 
profile. The ability of ETC-1002 to achieve clinically meaningful LDL-C-lowering responses 
while demonstrating a favorable tolerability profile in a variety of patient populations suppo1is 
continued development of ETC-1002, an oral ACL inhibitor, in Phase 3 studies. 
Please refer to the most recent 1B for additional infonnation regarding previous human 
expenence. 
Confidential 
Page 27 of 287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 28 of 287 
5. 
TRIAL OBJECTIVES AND PURPOSE 
5.1. 
Primary Safety Objective 
The primary objective is to evaluate the long-term safety and tolerability of ETC-1002 versus 
placebo in high cardiovascular (CV) risk patients with hyperlipidemia (with underlying HeFH 
and/or ASCVD) who are not adequately controlled with their maximally tolerated lipid-
modifying therapy. 
5.2. 
Secondary Efficacy Objectives 
• To assess percent change from baseline to Week 12 in LDL-C 
5.3. 
Tertiary Efficacy Objectives 
• To assess percent change from baseline to Week 24 and to Week 52 in LDL-C in 
patients who do not receive adjunctive lipid-lowering therapy  
• To assess high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total 
cholesterol (TC), and TG at Weeks 12, 24, and 52  
• To assess apoB and high-sensitivity C-reactive protein (hs-CRP) at Weeks 12, 24, 
and 52 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Amendment 5, 10 May 2017 
6. 
INVESTIGATIONAL PLAN 
6.1. 
Overall Study Design 
This is a Phase 3, randomized, double-blind, placebo-contrnlled, parallel group, study evaluating 
the long-te1m safety and tolerability of ETC-1002 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-lowering therapy 
includes a maximally tolerated statin alone or in combination with other lipid-lowering therapies 
(eg, ezetimibe, fibrates [except gemfibrozil]). A patient's maximally tolerated lipid-modifying 
therapy will be dete1mined by the investigator using their medical judgment and available 
sources, includin the atient' s self-re 01ied histo1 of li id-modif · n th era 
The study will be conducted at approximately 125 clinical sites in United States, Canada, 
Ge1many, Netherlands, Poland, and United Kingdom. 
Screening (Visit Sl) will occur approximately 2 weeks prior to Day 1 (Visit Tl). Patients on 
maximally tolerated lipid-lowering therapy, as dete1mined by the investigator, will be stratified 
based on CV risk (HeFH and ASCVD diagnosis) and baseline statin dose category (see Table 2). 
Patients will be randomized into 1 of the 6 strata (see Table 3). 
Statin dose categories, based on average daily dose, and randomization strata are defined in the 
Table 2 and Table 3 below, respectively: 
Table 2: 
Baseline Statin Dose Categories 
High Intensity Statins 
Moderate Intensity Statins 
Low Intensity Statinsa 
Atorvastatin 40-80 mg 
Atorvastatin 10-20 mg 
Simvastatin 10 mg 
Rosuvastatin 20-40 mg 
Rosuvastatin 5-10 mg 
Pravastatin 10-20 mg 
Simvastatin 20-40b 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 
• Low intensity statins also include those patients taking low-dose st.atins using an alternate regimen 
(ie, eve1y other day, or for a specified number of times per week) 
I 
Confidential 
Page 29 of 287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 30 of 287 
 
Table 3: 
Randomization Strata 
HeFH (with or without ASCVD) 
ASCVD (without HeFH) 
HeFH+ Low Intensity Statins 
ASCVD + Low Intensity Statins 
HeFH+ Moderate Intensity Statins 
ASCVD + Moderate Intensity Statins 
HeFH+ High Intensity Statinsa 
ASCVD + High Intensity Statinsa 
ASCVD = Atherosclerotic cardiovascular diseases; HeFH = Heterozygous familial hypercholesterolemia. 
a Simvastatin with doses ≥40 mg/day are not allowed in this study. 
There will be no cap placed on randomization into any particular stratum. Randomized patients 
will return for clinic visits at Week 4 (Visit T2), Week 8 (Visit T3), Week 12 (Visit T4), 
Week 24 (Visit T5), Week 36 (Visit T6), and Week 52 (Visit T7). 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 ETC-1002. All clinical 
endpoints, including all major 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), will be adjudicated by an independent blinded 
expert Clinical Events Committee (CEC), using standardized definitions. Any clinical endpoints 
that meet SAE criteria will be reported as SAEs 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 31 of 287 
Figure 1. 
Study 1002-040 Study Design 
 
6.2. 
Study Hypothesis 
The primary clinical hypothesis is that long-term exposure of ETC-1002 will be safe and well 
tolerated in high CV risk patients with hyperlipidemia (patients with underlying HeFH and/or 
ASCVD) who are not adequately controlled with their maximally tolerated lipid-modifying 
therapy, including a maximally tolerated statin.  
The study will characterize the long-term safety and tolerability of ETC-1002 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 long-term safety data are meaningful and interpretable. The 
extended treatment duration (52 weeks) and large patient number (n = 1950) will provide robust 
long-term safety in high CV risk patients who have an unmet medical need for additional lipid-
lowering therapy, such as ETC-1002 once daily, orally bioavailable option. 
6.3. 
Study Duration and Period 
The expected total duration of study participation for each randomized patient is approximately 
54 weeks. This duration includes a 2-week screening period and a 52-week treatment period. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 32 of 287 
6.4. 
End of Study 
The study will end when the last randomized patient completes their last study visit (last patient 
last visit [LPLV] for last randomized patient). The estimated overall duration of the study (first 
patient first visit [FPFV] to LPLV) is approximately 28 months. 
6.5. 
Number of Patients 
The study will enroll approximately 1950 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. The patient 
numbers will be an 8-digit patient unique number that is comprised of protocol, site, and 
patient-specific numbers (ie, 40-001-001 identifies Protocol 40, Site 001, Patient 001).  
6.6.1. 
Screening 
Screening will occur approximately 2 weeks prior to Day 1 (Visit T1) where the patient’s 
eligibility will be evaluated. Eligible patients who are taking concomitant medications must be 
on stable regimens as defined in Section 8.2. At the investigator’s discretion, screening may be 
extended by 2 weeks to allow for re-evaluation of LDL-C, TG, blood pressure, liver enzymes, 
and estimated glomerular filtration rate (eGFR) eligibility criteria (see Section 7.1 and 
Section 7.2). 
6.6.2. 
Randomization and Treatment Period 
For patients who satisfy all entry criteria and complete the 2-week screening 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 dose and randomized in a ratio of 2:1 to receive 1 of the 2 following treatments in a 
double-blind fashion: 
• ETC-1002 180-mg tablet 
• Matching placebo tablet 
• For details regarding the randomization strata see Table 3. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 33 of 287 
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. Age ≥18 years or legal age of majority based on regional law, whichever is greater at 
Week -2 (Visit S1) 
2. Men and nonpregnant, nonlactating women. Women must be either: 
• Naturally postmenopausal (as reported by the patient, defined as greater than 55 years 
and ≥1 year without menses, less than 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). 
• There are no protocol-specific birth control requirements for men with partners who 
are able to become pregnant. 
3. Fasting LDL-C value at Week -2 (Visit S1) ≥70 mg/dL (1.8 mmol/L).  
Note: LDL-C may be repeated 1 time with the screening period extended up to 2 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. 
4. Have high cardiovascular 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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 34 of 287 
• 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 
5. 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 
for at least 4 weeks prior to screening (6 weeks for fibrates; however, gemfibrozil is not 
allowed). Regimens other than daily dosing, including those at very low doses, are 
acceptable. 
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.  
7.2. 
Subject Exclusion Criteria 
Patients who meet any of the following criteria will not be randomized: 
1. Total fasting triglyceride ≥500 mg/dL (5.6 mmol/L) at Week -2 (Visit S1) 
Note: TG may be repeated 1 time with the screening period extended up to 2 weeks. For 
those patients who have a repeat TG, the mean of the first value and the repeat value will 
be used to determine eligibility. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 35 of 287 
2. Renal dysfunction or nephritic syndrome or a history of nephritis, including eGFR (using 
central laboratory determined Modification of Diet in Renal Disease [MDRD] formula) 
<30 mL/min/1.73 m2 at Week -2 (Visit S1) [1].  
Note: At the discretion of the investigator, the screening period may be extended up to 
2 weeks for a single repeat eGFR. For those patients who have a repeat eGFR, the repeat 
value will be used to determine eligibility. 
Note: Also excluded are renally impaired patients receiving an average daily dose of 
simvastatin 40 mg with eGFR below <45 mL/min/1.73 m2. 
3. Body mass index (BMI) ≥50 kg/m2 
4. Concomitant use of simvastatin at average daily doses greater than 40 mg.  
5. Concomitant use of a PCSK inhibitor (Praluent® [alirocumab] or Repatha® 
[evolocumab]) at Week -2 (Visit S1) or prior use of a PCSK9 inhibitor within the past 
4 weeks of Week -2 (Visit S1) will be excluded from this study. 
Note: Patients are allowed to initiate a PCSK9 inhibitor as adjunctive therapy at 
Week 24 if the LDL-C threshold criteria have been met as described in 
Section 11.1.6.3.5. 
6. Recent (within 3 months prior to the screening visit [Week -2 (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. 
7. 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 2 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 
8. Hemoglobin A1C (HbA1C) ≥10% at Week -2 (Visit S1) 
9. Uncontrolled hypothyroidism, including thyroid-stimulating hormone (TSH) >1.5 × the 
upper limit of normal (ULN) at Week -2 (Visit S1). Patients stabilized on thyroid 
replacement therapy for at least 6 weeks prior to randomization are allowed. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 36 of 287 
10. Liver disease or dysfunction, including:  
• Positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C 
antibodies (HCV-AB) at Week -2 (Visit S1); or 
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≥2 × ULN, 
and/or total bilirubin (TB) ≥1.2 × ULN at Week -2 (Visit S1).  
Note: If HCV-AB is positive, a reflex HCV RNA will be performed to rule out active 
disease. Patients without active disease may be enrolled the study. 
Note: At the discretion of the investigator, the screening period may be extended up to 
2 weeks for a single repeat of ALT, AST, and/or TB. For those patients who have a 
repeat ALT, AST, and/or TB, the repeat value will be used to determine eligibility. 
If TB ≥1.2 × ULN, a reflex indirect (unconjugated) bilirubin will be obtained and if 
consistent with Gilbert’s disease, the patient may be enrolled in the study. 
11. Gastrointestinal conditions or procedures (including weight loss surgery; eg, Lap-Band® 
or gastric bypass) that may affect drug absorption 
12. Hematologic or coagulation disorders or a hemoglobin (Hgb) level <10.0 g/dL (100 g/L) 
at Week -2 (Visit S1) 
13. Active malignancy, including those requiring surgery, chemotherapy, and/or radiation in 
the past 5 years. Patients with a history of nonmetastatic basal or squamous cell 
carcinoma of the skin and cervical carcinoma in situ are allowed) 
14. 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.  
15. 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. 
16. 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 
17. Use of any experimental or investigational drugs within 30 days prior to screening or 
5 half-lives, whichever is longer 
18. Prior participation in a previous ETC-1002 clinical study. Prior participation in a clinical 
study with ETC-1002 is defined as having been enrolled in an ETC-1002 study. 
19. 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  
• Requirement for mipomersen or lomitapide or apheresis therapy 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 37 of 287 
20. 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) 
21. An employee or contractor of the facility conducting the study, or a family member of the 
Principal Investigator, Co-Investigator, or Sponsor. 
7.3. 
Patient Lifestyle and Dietary Guidelines 
Each dose of study drug is comprised of 1 tablet from 1 bottle that will be dispensed at each 
scheduled clinic visit. Study drug should be taken once a day (once every 24 hours) at 
approximately the same time every day and may be taken with or without food. If a patient 
forgets to take study drug in the morning, it may be taken up to 12 hours later the same day. If 
study drug has not been ingested by that time, the patient should not take study drug that day and 
should resume ingestion of study drug the following morning.  
Patients will fast for a minimum of 10 hours prior to collection of all laboratory samples.  
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.  
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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 38 of 287 
If any serious or nonserious AEs have occurred at such a clinical site, all documentation relating 
to the event(s) must be obtained. 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Amendment 5, 10 May 2017 
8. 
TREATMENT OF PATIENTS 
8.1. 
Description of IMP 
Table 4: 
Investigational Medicinal Products 
Investigational Medicinal Product 
Product Name: 
Dosage Form: 
Unit Dose: 
Container/Closure
0 
Route of Administration: 
Physical Description: 
Manufacturer (Fill/Finish): 
ETC-1002 
Film-coated tablets 
180mg 
35- and/or 100-count bottle 
( depending upon visit) with 
screw on, non-child proof cap 
Oral, daily in the morning, with 
or without food 
Placebo 
Film-coated tablets 
Not applicable 
35- and/or 100-count bottle 
( depending upon visit) with 
screw on, non-child proof cap 
Oral, daily in the morning, with 
or without food 
0 A 100-day supply of IMP will be included in the 100-count bottle and a 35-day supply of IMP will be included in 
the 35-count bottle. 
Please see Phaimacy 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 inte1mittently during the study must be recorded 
with indication, total daily dose, and sta1t and stop dates of adrninisti·ation. 
The Pri01-/Concornitant electi·onic case repo1t fo1m ( 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. 
Confidential 
Page 39 of287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 40 of 287 
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. Use of fibrates must be stable at least 
6 weeks prior to screening. Gemfibrozil, a fibrate, is prohibited. Patients may not currently be 
taking or have taken a PCSK9 inhibitor within 4 weeks prior to Screening (Week -2, Visit S1); 
however, they may be allowed to initiate a PCSK9 inhibitor as adjunctive therapy at Week 24 if 
the LDL-C threshold criteria have been met as described in Section 11.1.6.3.5. Stable lipid-
modifying therapy(s) includes, but is not limited to, monotherapies or combination therapies 
containing the compounds below: 
Statins 
• Atorvastatin (Lipitor®, Sortis®) 
• Fluvastatin (Lescol®) 
• Lovastatin (Mevacor®, Altoprev™) 
• Pravastatin (Pravachol®) 
• Pitavastatin (Livalo®, Lipostat®) 
• Rosuvastatin (Crestor®) 
• Simvastatin (Zocor®), with daily doses less than 40 mg 
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 (allowed as adjunctive therapy beginning at Week 24 [Visit T5]; see 
Section 11.1.6.3.5) 
• Alirocumab (Praluent®) 
• Evolocumab (Repatha®) 
Other 
• Ezetimibe/simvastatin where simvastatin is less than 40 mg/day (Vytorin® 
10 mg/10 mg and 10 mg/20 mg, Inegy® 10 mg/20 mg are allowed) 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 41 of 287 
• Atorvastatin/ezetimibe (Atozet®) 
8.2.2. 
Prohibited Medications 
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. 
• Gemfibrozil (Lopid®)  
• Cholestin (red yeast rice, also known as monascus purpureus extract) 
• Simvastatin (Zocor®), greater than or equal to 40 mg/day 
• Ezetimibe/simvastatin where simvastatin doses are greater than or equal to 
40 mg/day (Vytorin® 10 mg/40 mg and 10 mg/80 mg per day and Inegy® 10 mg/40 mg 
and 10 mg/80 mg per day are prohibited) 
Patients will not have used the medications listed below within 4 weeks prior to screening: 
• Alirocumab (Praluent®) 
• Evolocumab (Repatha®) 
• Note: Patients may be allowed to initiate a PCSK9 inhibitor as adjunctive therapy at 
Week 24 if the LDL-C threshold has been met as described in Section 11.1.6.3.5. 
8.2.3. 
Allowable Medications 
Other concomitant medication must be stable for 2 weeks 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 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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 42 of 287 
The following may not be taken within 4 weeks of Screening (Week -2, Visit S1), but may be 
initiated beginning at Week 24 if LDL-C threshold criteria have been met and it is needed as 
adjunctive LDL-C-lowering therapy. 
• Alirocumab (Praluent®) 
• Evolocumab (Repatha®) 
8.3. 
Treatment Compliance 
Screening Compliance 
No study medication treatment will be given during the Screening period; therefore, compliance 
will not be assessed.  
Treatment Period Compliance 
At each patient visit during the treatment period, designated clinical site staff will assess patient 
IMP intake compliance 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 compliance will be determined and, if possible, remedied. Patients 
demonstrating poor compliance will continue to be counseled on the importance of carefully 
following all dosing instructions, but will not be removed from the study.  
8.4. 
Blinding 
At Week 0 (Visit T1), patients who satisfy all entry criteria during the screening period will be 
randomized to a treatment group. 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 dose and assign a randomization 
number and the appropriate study drug container via medication identification numbers 
(MED ID). A patient is considered to be randomized when they have been assigned a 
randomization number by IWRS. 
After patients have been randomized, study drug, which is assigned by the IWRS, will be 
administered in a double-blind fashion. The Sponsor, all clinical site personnel (Investigator, 
pharmacist, etc), and other vendor personnel will be blinded to the treatment group for each 
patient. Patients will also be blinded to the treatment they receive. Unblinded User(s) will be 
designated for each clinical site and at the sponsor (or designee) as needed. 
 will provide 
these unblinded individuals with 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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 43 of 287 
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,
.  
Postrandomization values for individual laboratory measures for LDL-C, TG, TC, HDL-C, non-
HDL, apoB, and hs-CRP, including any plasma concentration of ETC-1002 and its metabolite, 
that may inadvertently suggest treatment assignment will not be available to personnel from the 
clinical site, the patient, the Sponsor, 
 
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 
 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. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 44 of 287 
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 ETC-1002 
(180-mg film-coated tablets) and matching placebo (film-coated tablets). IMP will be distributed 
and released in accordance with regional and local requirements during the conduct of the study. 
The MED ID number (an identifier on the study drug packaging) will be obtained via IWRS and 
used to select double-blind IMP from available clinical supplies at the clinical site.  
Double-blind IMP will be dispensed in 100 day supply increments (one 100-day supply bottle) to 
patients by appropriate clinical site personnel at Week 0 (Visit T1), Week 12 (Visit T4), and 
Week 24 (Visit T5). Double-blind IMP will be dispensed in 35-day supply increments (2 bottles; 
one 100-day supply bottle and one 35-day supply bottle) to patients at Week 36 (Visit T6). 
Please see Pharmacy Manual for detailed storage requirements and management instructions. 
9.2. 
Administration of Investigational Medicinal Product 
Patients will be instructed to ingest IMP 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 arrive at clinic on Visits T4, 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 in the morning 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 morning. 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. 
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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 45 of 287 
• 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. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 46 of 287 
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. 
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. 
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 2 distinct periods: screening 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 -2 (Visit S1; Days -16 to -4) 
The screening period will begin with a screening visit that will occur 2 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) 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 47 of 287 
• Serology (including HBsAg, HCV)  
• Review of all inclusion/exclusion criteria that can be assessed at this time 
• Conduct diet and exercise counseling 
• Contact IWRS to register the patient  
Patients who meet all enrollment criteria that can be assessed 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 entry criterion. If this optional visit is completed, the mean of lipid values 
from both visits will be used to determine eligibility. 
• An optional visit between Visits S1 and T1 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 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, they have been on stable doses of blood 
pressure medications for at least 2 weeks, and the repeat blood pressure values (DBP 
and/or SBP) no longer meet exclusionary values. 
• An optional visit between Visits 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. 
• 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. 
Treatment Week 0 (Visit T1; Day 1) 
Prior to scheduling Visit T1, 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 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.  

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 48 of 287 
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) 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− apoB 
− HbA1C  
− hs-CRP 
− Reserve sample 
− Genetic sample (if the patient has consented to provide a genetic sample) 
• 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 
• Schedule next visit 
10.2.3. 
Treatment Week 4 (Visit T2; ± 3 days) 
If the patient is withdrawing early from the study at this visit, proceed to Section 10.2.8 for the 
list of the required assessments. 
If the patient is withdrawing from IMP treatment at this visit, proceed to Section 10.2.8 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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 49 of 287 
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, including muscle-related AEs (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 
• Return 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. 
10.2.4. 
Treatment Week 8 (Visit T3; ± 3 days) 
If the patient is withdrawing early from the study at this visit, proceed to Section 10.2.8 for the 
list of the required assessments. 
If the patient is withdrawing from IMP treatment at this visit, proceed to Section 10.2.8 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.  

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 50 of 287 
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 8 (Visit T3): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (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 
• Return 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 
medications, and current health status. 
10.2.5. 
Treatment Week 12 (Visit T4; ± 3 days) 
If the patient is withdrawing early from the study at this visit, proceed to Section 10.2.8 for the 
list of the required assessments. 
If the patient is withdrawing from IMP treatment at this visit, proceed to Section 10.2.8 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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 51 of 287 
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, including muscle-related AEs (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 (patients randomized after Protocol Amendment 3 and subsequent 
amendments are excluded from PK sampling) 
− Reserve 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  
• 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, reserve 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. 
10.2.5.1. Treatment Week 16 (Visit T4.1; ±3 days) 
Patients on simvastatin 40 mg/day will be scheduled for the additional Visit T4.1 for clinical 
safety laboratory evaluations specifically to monitor changes in creatine phosphokinase (CPK) 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 52 of 287 
and liver function tests (LFTs). Should changes be noted, the procedures described in 
Section 11.1.6.3.1 will apply. 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (ongoing) 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
• Conduct diet and exercise counseling 
10.2.5.2. Treatment Week 20 (Visit T4.2; ±3 days) 
Patients on simvastatin 40 mg/day will be contacted by telephone for the additional Visit T4.2  
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (ongoing) 
10.2.6. 
Treatment Week 24 (Visit T5; ± 7 days) 
If the patient is withdrawing early from the study at this visit, proceed to Section 10.2.8 for the 
list of the required assessments. 
If the patient is withdrawing from IMP treatment at this visit, proceed to Section 10.2.8 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, including muscle-related AEs (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 
− hs-CRP 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 53 of 287 
− PK sample (patients randomized after Protocol Amendment 3 and subsequent 
amendments are excluded from PK sampling) 
− Reserve 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  
• 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, reserve samples, and IMP (IMP dispensing, IMP compliance, IMP 
accountability) management 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. 
10.2.6.1. Treatment Week 28 (Visit T5.1; ±7 days) 
Patients on simvastatin 40 mg/day will be scheduled for the additional Visit T5.1 for clinical 
safety laboratory evaluations specifically to monitor changes in CPK and LFTs. Should changes 
be noted, the procedures described in Section 11.1.6.3.1 will apply. 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (ongoing) 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
• Conduct diet and exercise counseling 
10.2.6.2. Treatment Week 32 (Visit T5.2; ±7 days) 
Patients on simvastatin 40 mg/day will be contacted by telephone for the additional Visit T5.2  
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (ongoing) 
10.2.7. 
Treatment Week 36 (Visit T6; ± 7 days) 
If the patient is withdrawing early from the study at this visit, proceed to Section 10.2.8 for the 
list of the required assessments. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 54 of 287 
If the patient is withdrawing from IMP treatment at this visit, proceed to Section 10.2.8 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 36 (Visit T6): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (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 
• IWRS contact to obtain the MED ID number for IMP 
• Dispense IMP  
• 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 
medications, and current health status. 
10.2.8. 
Treatment Week 52 (Visit T7; ± 7 days) 
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: 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 55 of 287 
Patients will undergo the following assessments and procedures at Week 52 (Visit T7): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (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 (patients randomized after Protocol Amendment 3 and subsequent 
amendments are excluded from PK sampling) 
− Reserve sample 
• Return of IMP; assessment and recording of IMP compliance 
• Complete study status in IWRS (ie, early withdrawal or completed study) 
• Review and offer the open-label extension study (Study 1002-050) to the patient 
Note: For patients who withdraw from IMP treatment: 
− Capture the reason for withdrawing from IMP treatment and record on the eCRF 
− Determine whether the patient will or will not consent for follow-up visits through 
study completion 
− If the patient provides consent to continue to be followed for safety assessments 
per the protocol visit schedule, schedule follow-up visits as they would have 
occurred if the patient were continuing in the study and complete the visit 
required procedures listed in the appropriate visit specific section within 
Section 10 and Appendix 1. No further IMP will be dispensed for patients who 
withdraw from IMP treatment. 
− If the patient does not provide consent to be followed for safety assessments per 
the protocol (either by returning to clinic or by phone), this visit (Visit T7) will be 
considered the EOS/Early Withdrawal from study visit and no further visits will 
be scheduled. 
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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 56 of 287 
IMP treatment, all assessments except for those procedures pertaining to apoB, hs-CRP, 
PK samples, reserve samples, and IMP (IMP dispensing, IMP compliance, IMP 
accountability) management 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. 
10.3. 
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). 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).  
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 do not provide consent 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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 57 of 287 
• Illness, condition, or procedural complication (including AEs) affecting the patient’s 
ability to participate or requiring prohibited medication 
• The Sponsor or Investigator terminates the study  
• In the Investigator’s judgment, it is deemed in the best interest of the patient to 
discontinue his/her participation in the study 
• Any other reason 
If a patient is lost to follow-up, every reasonable effort must be made by the clinical site 
personnel to contact the patient and determine the reason for discontinuation/withdrawal. The 
measures taken to follow-up must be documented. 
10.3.2. 
Procedures for Early Withdrawal 
If a patient withdraws or is removed from the study for any reason, all early withdrawal 
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 10.2.8 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) 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 58 of 287 
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 diastolic and systolic blood pressure 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, blood pressure 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 in the morning while fasted and after voiding. 
Body weight will be measured in the morning 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 
11.1.4. 
Physical Examination 
PEs will include an assessment of the following: 
• General appearance 
• Skin 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 59 of 287 
• 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 all time points, 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. 
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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 60 of 287 
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 
Blood Chemistry (serum, fasting) 
• 
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 %) 
• 
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 
• 
Nitrate 
• 
Occult blood 
• 
pH 
• 
Protein 
• 
Specific gravity 
• 
Urobilinogen 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 61 of 287 
Table 5: 
Clinical Laboratory Parameters (Safety) (Continued) 
Clinical Laboratory Test 
Clinical Laboratory Test 
Urinalysis (Microscopic)-only if urine dipstick 
abnormal 
Coagulation—In all patients at screening, then only 
in patients receiving anticoagulant therapy that in 
the investigator’s judgment require monitoring at 
Visit T1 and 3 to 5 days post Visit T1 
• 
Bacteria 
• 
Casts 
• 
Crystals 
• 
Epithelial cells 
• 
Red blood cell (RBC) 
• 
WBC 
• 
Prothrombin time (PT) 
• 
International normalized ration (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 females of 
childbearing potential) 
• 
Thyroid-stimulating hormone (TSH) 
• 
Hemoglobin A1C (HbA1C) 
• 
Reserve blood samples for potential 
future measurement of ETC-1002 safety 
or pharmacodynamic biomarkers 
• 
PK sample (patients randomized after 
Protocol Amendment 3 and subsequent 
amendments are excluded from PK 
sampling) 
• 
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. 
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 11.1.6.4 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 ETC-1002 safety and efficacy biomarkers. A reserve genetic blood 
sample (optional) will also be stored frozen for potential future ETC-1002 genetic analyses.  
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) 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 62 of 287 
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 
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. 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 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 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). 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 63 of 287 
• If repeat LFT assessment confirms ALT and/or AST >3 × ULN in addition to any of 
the following, the patient should be given no further IMP treatment, but will be asked 
to continue to be followed for safety using the protocol-specified visit schedule (see 
Appendix 1): 
− TB >2 × ULN 
Note: In the case of patients with Gilbert’s disease, TB will be fractionated and 
the determination of 2 × ULN will be based upon direct (conjugated) bilirubin. 
− INR >1.5 × ULN (unless the patient is on stable dose of anticoagulation 
medication) 
− Appearance or worsening of right upper abdominal discomfort, anorexia, fatigue, 
nausea, vomiting, fever, rash, or eosinophilia 
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). 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 64 of 287 
At any time, the investigator may choose to consult with a specialist to further evaluate the cause 
of the alteration in hemoglobin. 
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). 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 65 of 287 
11.1.6.3.5. 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 
safety laboratory assessment. Additional safety laboratory assessments may be 
conducted at the investigator’s discretion. Patients receiving an average daily 
dose of simvastatin 40 mg based on lipid-lowering treatment modification, should 
adhere to the additional safety visits as described in Sections 10.2.5 and 10.2.6. 
− 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. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 66 of 287 
11.1.6.3.6. 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. 
11.1.6.4. 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.  

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 67 of 287 
11.1.6.5. Pharmacokinetic Assessments 
Plasma concentrations of ETC-1002 and its metabolite ESP15228 will be determined from 6 mL 
whole blood samples collected from patients at Weeks 12, 24, and 52. At the time of sample 
collection, the date and time of blood draw and the last 2 doses of study medication will be 
collected.  
11.1.6.6. Collection and Assessment of Pharmacokinetic Samples 
Pharmacokinetic samples will be collected from patients who were randomized into the study 
prior to the implementation of Protocol Amendment 3. 
Pharmacokinetic samples will not be collected for patients randomized into the study after 
initiation of Protocol Amendment 3. 
Plasma concentrations of ETC-1002 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 reserve 
samples. Based upon Sponsor assessment and decision, reserve sample collection will be 
discontinued after a sufficient number of samples have been collected. Study centers will be 
notified in writing informing them that sufficient samples have been collected and that further 
collection may be discontinued. 
11.1.6.8. Shipment of Pharmacokinetic Samples 
Plasma PK samples will be shipped frozen on dry ice according to instructions provided in the 
laboratory manual. 
11.1.6.9. 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. 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. 
11.1.6.10. 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. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 68 of 287 
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 (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 adverse drug reaction (ADR). “Responses” to a medicinal product means that a 
causal relationship between a medicinal product and an AE is at least a reasonable possibility 
(ie, the relationship cannot be ruled out). 
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) 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 -2), Investigators 
should make an assessment for AEs at each visit and record the event on the appropriate AE 
eCRF.  
Wherever possible, a specific disease or syndrome rather than individual associated signs and 
symptoms should be identified by the Investigator and recorded on the eCRF. However, if an 
observed or reported sign or symptom is not considered a component of a specific disease or 
syndrome by the Investigator, it should be recorded as a separate AE on the eCRF. Additionally, 
the condition that led to a medical or surgical procedure (eg, surgery, endoscopy, tooth 
extraction, transfusion) should be recorded as an AE, not the procedure.  

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 69 of 287 
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 
• 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.  

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 70 of 287 
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. 
• 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). 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 71 of 287 
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: Any hospital admission with at least 1 overnight stay will be considered an inpatient 
hospitalization. An emergency room visit without hospital admission 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.  
Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, they 
may jeopardize the patient and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition. Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room, blood dyscrasias, 
convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
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. 
11.3. 
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 
 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.  

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Amendment 5, 10 May 2017 
To repo1i the SAE, complete the provided SAE fonn and fax it to-
Medical and Safety 
Services within 24 hours of becoming aware of the occunence. Regional fax numbers will be 
listed on the bottom the provided SAE fo1m. If you are unable to fax the SAE fo1m or if you 
have questions, please call- Medical and Safety Services for assistance. -
Safety 
personnel are available for SAE repo1iing on a 24-hour basis. Incoming repo1is are reviewed 
during nonnal business hours. 
Safety Contact Info1mation: 
Medical and Safety Services 
24-Hour SAE hotline: 
Detailed instructions and contact info1m ation for the Global and Regional Medical Monitor(s) 
will be provided by-
in the SAE Completion Guidelines. 
The Investigator is required to subinit SAE repo1is to the IRB/IEC in accordance with local 
requirements. All Investigators involved in studies using the same investigational product will 
receive any safety ale1i notifications for onward subinission 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 drng 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 impaiiment), or the 
patient dies. 
Within 24 hours of receipt of follow-up infonnation, the Investigator must update the SAE fonn 
and subinit any suppo1i ing documentation (eg, patient discharge sUilllllary or autopsy reports) to 
-
Medical and Safety Services personnel via fax. 
11.3.1. 
Reporting of Serious Adverse Events to Regulatory Authorities 
The Sponsor (and/or designee) is responsible for subinitting expedited repo1is of suspected and 
unexpected serious adverse reactions (SUSARS) to the appropriate regulato1y authorities. All 
Investigators participating in ongoing clinical studies with the study drng 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 repo1i ed in accordance with local 
laws and regulations. Investigators should provide written documentation of IRB/IEC 
notification for each repo1i 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 
regulat01y 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 
Confidential 
Page 72 of 287 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Amendment 5, 10 May 2017 
• 
Corona,y 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 to -
Medical and Safety 
Services as detailed in Section 11.3. 
11.3.3. 
Reports of Pregnancy 
Although not considered an SAE (unless an event occurs with a serious outcome), pregnancy 
infonnation on female patients will be collected by-
Medical and Safety Services. If a 
female patient should be~
regnant during the course of the study, the Principal Investigator 
or designee must contact-
Medical and Safety Se1vices within 24 hours of the Principal 
Investigator or designee first becoming aware of the pregnancy. -
Medical and Clinical 
Safety Se1vices will then fo1ward the Exposure In Utero fo1m to the Investigator for completion. 
Patients who become pregnant will discontinue study medication immediately and complete the 
Early Withdrawal evaluations. 
11.4. 
Adverse Events of Special Interest 
The protocol procedures included in the ETC-1002 clinical studies are paii of standard clinical 
care for patients with prima1y hyperlipidemia and mixed dyslipideinia and also address the 
potential and theoretic risks of ETC-1002. 
All ETC-1002 studies will include standai·d phaimacovigilance including evaluation of AEs, PE 
findings, vital signs, and laborato1y assessments. Cardiovasculai· events will be adjudicated by an 
independent CEC in accordance with a pre-specified chaiier. 
Confidential 
Page 73 of 287 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Amendment 5, 10 May 2017 
I 
I 
Confidential 
Page 74 of287 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Amendment 5, 10 May 2017 
Confidential 
Page 75 of 287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 76 of 287 
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 ETC-1002 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. 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 ETC-1002 Phase 3 development program will be aggregated to allow for a 
safety assessment across the entire development program. 
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 
approximately every 12-16 weeks through 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 ETC-1002 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.  

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 77 of 287 
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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 78 of 287 
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), 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. 
12.2. 
Determination of Sample Size 
A total of 1950 patients will be enrolled in this study with 1300 patients randomized to 
ETC-1002 and 650 patients randomized to placebo. Using an anticipated overall dropout rate of 
7.5% at 6 months and 10.0% at 12 months in each treatment group, the expected number of 
patients exposed to treatment during the study is as follows: 
 
Patients ≥6 Months 
Patients ≥12 Months 
ETC-1002 
1,202 
1,170 
Placebo 
601 
585 
Absolute risk will be addressed by 1300 patients randomized to ETC-1002 and will provide at 
least 95% power to detect AEs that occur at rates similar to those seen in the placebo group for 
the AEs of interest in the recently completed long-term safety study entitled Efficacy and Safety 
of Alirocumab in Reducing Lipids and Cardiovascular Events[2]. In this study adverse event 
rates ranged from 0.5% to 13.6%. Additional assumptions include a two-sided test with 
significance level at 0.05. 
When AEs occur at a range of rates similar to those seen in the placebo group in the above 
referenced alirocumab study (0.5% to 13.6%), the sample size of 1300 patients randomized to 
ETC-1002 and 650 patients randomized to placebo will allow for detection of relative risks of 
1.0 and of 2.0 (ETC-1002:placebo) with the following approximate 95% confidence limits:  
% Placebo Patients 
Experiencing AE 
% ETC-1002 Patients 
Experiencing AE 
Relative Risk 
Approximate 95% 
Confidence Interval 
0.5% 
0.5% 
1.0 
(0.3, 3.8) 
0.5% 
1.0% 
2.0 
(0.6, 6.7) 
13.6% 
13.6% 
1.0 
(0.8, 1.3) 
13.6% 
27.2% 
2.0 
(1.6, 2.5) 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Amendment 5, 10 May 2017 
12.3. 
Analysis Populations 
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 ti-eatment group that they actually received, regardless of their randomized ti-eatment. 
The Full Analysis Set (FAS), used for the LDL ana~yses and the lipid and cardiometabolic 
summaries, is defined as all randomized patients and is also known as the intention-to-treat (ITT) 
set of patients. 
12.4. 
Disposition, Demographics, and Baseline Characteristics 
Disposition, including reason for withdrawal from the study, will be summarized by treatment 
group. Demographic infonnation 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 Safety Endpoint 
The primary endpoint for this study is general safety, which includes AEs, clinical safety 
laboratories, PEs, vital signs, and ECGs. 
The summarization of AEs will include only TEAEs, defined as AEs that begin or worsen after 
randomization and ingestion of the first dose of study diug. TEAEs and SAEs will be 
summarized by SOC, severity, and relationship to study diug for each treatment group. These AE 
summaries will be provided overall and for subgroups such as gender, age, and HeFH status. If 
appropriate, absolute and relative risk differences will be calculated using both cumulative 
incidence and incidence rates. Deaths, withdi·awal from study treatment due to AEs, and 
withdi·awal from the study due to AEs will each be summarized by treatment group. Potential 
AEs based on findings in non-clinical models include reversible hypoglycemia and metabolic 
acidosis. Fmther details on occmTence and monitoring are available in Section 11.1.6.4 and the 
IB. AESI will be summarized as follows: 
Confidential 
Page 79 of 287 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Amendment 5, 10 May 2017 
12.6. 
Efficacy Endpoints 
12.6.1. 
Key Eficacy Endpoints 
Selected efficacy endpoints will be included in a step-down testing procedure to control overall 
type I error. Below endpoints will be tested sequentially at alpha level of 0.05. Each endpoint 
will be tested only if the previous endpoint achieved statistical significance. 
1. percent change from baseline to Week 12 in LDL-C 
2. percent change from baseline to Week 24 in LDL-C 
3. percent change from baseline to Week 12 in non-HDL-C 
4. percent change from baseline to Week 12 in TC 
5. percent change from baseline to Week 12 in apoB 
6. percent change from baseline to Week 12 in hs-CRP 
Percent change in lipid parameters will be analyzed using analysis of covariance (ANCOVA), 
with treatment and randomization strata (patient's CV risk and baseline statin dose) as factors 
and respective baseline value as a covariate. Baseline value is defined as the average of the last 
Confidential 
Page 80 of 287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 81 of 287 
screening and the predose Day 1/Week 0 value. When only one assessment or value is available, 
that single assessment/value will be used as baseline. 
The FAS will be used for efficacy endpoints, with patients included in their randomized group, 
regardless of the treatment they actually received. Missing data for key lipid endpoints 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. The ANCOVA output will include the least squares 
mean (LSM) and standard error (SE) for each treatment group, along with the placebo-correct 
LSM and it’s 95% confidence interval (CI) and p-value. Specific details on how the PMM will be 
implemented will be included in the SAP.  
Additional sensitivity analyses based on subsets of the FAS or alternative missing data handling 
will be performed and the details will be provided in the SAP. 
12.6.2. 
Other Efficacy Endpoints 
Percent change or change in LDL-C, HDL-C, TG, TC, non-HDL-C, hs-CRP, and apoB values at 
other protocol-scheduled time points will be analyzed similarly using the ANCOVA model. The 
FAS will be used, with patients included in their randomized group, regardless of the treatment 
they actually received. No imputation for missing data will be performed. 
For each parameter at each time point, the value of the parameter and the percent change from 
baseline in the parameter will be summarized by treatment group.  
In addition, percent change from baseline to Week 24 and to Week 52 LDL-C will be analyzed 
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. 
PK and Other Biomarkers 
The FAS will be used, with patients included in their randomized treatment group, regardless of 
the treatment they actually received. Only observed case data will be used (no imputation for 
missing data).  
Trough plasma concentrations of ETC-1002 and ESP15228 will be collected from patients 
randomized before the implementation of Protocol Amendment 3 at Weeks 12, 24, and 52 for use 
in further developing the population PK model. Trough plasma concentrations will not be 
collected from patients randomized after the implementation of Protocol Amendment 3. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 82 of 287 
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.  

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 83 of 287 
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. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 84 of 287 
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. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 85 of 287 
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 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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 86 of 287 
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. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 87 of 287 
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.  

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 88 of 287 
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 hand-written 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 48 hours following the evaluation. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 89 of 287 
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 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Amendment 5, 10 May 2017 
• 
Guidance for Industiy - E6 Good Clinical Practice: Consolidated Guidance: 
http://www.fda.gov/cder/guidance/959fnl.pdf 
17 .2. 
Study Administrative Structure 
Fill/Finish Manufacturing: 
II 
Secondary Packaging/Depot for Clinical Site Dmg Shipments: 
Cent:I'al Laboratory: 
Confidential 
Page 90 of 287 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Amendment 5, 10 May 2017 
Randomization, IWRS, Statistical Analysis, Study Management and Monitoring, Data 
Management, Medical and Safety Services including Medical Monitoring (see Medical and 
Safety Se1vices below), Programming, and Medical Writing: 
Medical and Safety Se1v ices: 
17.3. 
Amendments 
Changes to the research covered by this protocol must be implemented by fo1mal protocol 
amendment. All amendments to the protocol must be initiated by the Sponsor and signed and 
dated by the Investigator. Protocol amendments must not be implemented without prior IRB or 
IEC approval. Documentation of amendment approval by the Investigator and IRB or IEC must 
be provided to the Sponsor or its authorized representative. When the change(s) involve only 
logistic or administrative aspects of the study, the IRB or IEC only needs to be notified. 
During the course of the study, in situations where a departure from the protocol is unavoidable, 
the Investigator will contact the Medical Monitor. Except in emergency situations, this contact 
should be made before implementing any departure from the protocol. In all cases, contact with 
the Medical Monitor must be made as soon as possible to discuss the situation and agree on an 
appropriate course of action. The data recorded on the eCRF and source documents will reflect 
any departure from the protocol and the source documents will describe the departure and the 
circumstances requiring it. 
17.4. 
Financial Disclosure 
Prior to the staii of the study, Investigators will release sufficient and accurate financial 
info1mation that pe1mits the Sponsor to demonstrate that an Investigator and all study relevant 
assigned personnel have no personal or professional financial incentive regai·ding the future 
approval or disapproval of the study dmg such that his or her research might be biased by such 
incentive. 
Confidential 
Page 91 of 287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 92 of 287 
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. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 93 of 287 
19. 
LIST OF REFERENCES 
1. 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. 
2. Robinson JG, Farnier M, Krempf M, Bergero J, Luc G, Averna M, et al. Efficacy and 
Safety of Alirocumab in Reducing Lipids and Cardiovascular Events. N Engl J Med. 
2015;372:1489-99. 
3. 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. 
4. World Health Organization (WHO) Fact Sheet No 317 Updated January 2015. 
5. Nichols M, Townsend N, Scarborough P, Rayner M. Cardiovascular disease in Europe 
2014: epidemiological update. Eur Heart J. 2014; 35:2950-9. 
6. 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. 
7. Stone NJ, Robinson J, Lichtenstein AH, et al. for the Heart Association Task Force on 
Practice Guidelines Cardiovascular Risk in Adults. 2013 ACC/AHA Guideline on the 
Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in 
Adults. Circ, DOI: 10.1161/01.cir.0000437738.63853.7a 
8. Jacobson TA for the NLA Task Force on Statin Safety - 2014 update. J Clin Lipidol. 
2014;8:S1-4.  
9. http://thefhfoundation.org/about-fh/what-is-fh/ accessed August 2015. 
10. https://rarediseases.org/rare-diseases/familial-
hypercholesterolemia/https://rarediseases.org/rare-diseases/familial-
hypercholesterolemia/accessed August 2015. 
11. 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. 
12. 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. 
13. Goldberg AC, Hopkins PN, Toth PP, Ballantyne CM, Rader DJ, Robinson JG, et al. 
Familial hypercholesterolemia: screening, diagnosis and management of pediatric and 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Amendment 5, 10 May 2017 
adult patients: clinical guidance from the National Lipid Association Expe1i Panel on 
Familial Hypercholesteroleinia. J Clin Lipidol. 2011;5 (3 Suppl):Sl-S8. 
14. Pollex RL, Joy TR, Hegele RA. Emerging antidyslipideinic diugs. Expert Opin Emerg 
Dmgs. 2008; 13(2):363-81. 
15. Kathiresan S, Melander 0 , Anevski D, Guiducci C, Bmi t NP, Roos C, et al. 
Polymorphisms associated with cholesterol and risk of cardiovascular events. New Engl 
J Med. 2008:358;12:1240-9. 
16. Baigent C, Blackwell L, Emberson J, et al. Cholesterol Treatment Trialists' (CTT) 
Collaboration. Efficacy and safety of more intensive lowering ofLDL cholesterol: a 
meta-analysis of data from 170 000 pa1iicipants in 26 randoinised trials. Lancet. 
2010;376:1670-81. 
17. 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. 
18. Stamler J, Wentworth D, Neaton J. Is relationship between semm cholesterol and risk for 
premature death from coronary heart disease continuous and graded? JAMA. Nov 28 
1986;256(20):2823-8. 
19. 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 corona1y syndi·omes. New Engl J Med. 2004;350:1495-504. 
20. Cannon CP, Blazing MA, Guiglian RP, McCagg A, White JA, Theroux P, et al, for the 
IMPROVE-IT Investigators. Ezetiinibe added to statin therapy after acute coronaiy. New 
Engl J Med. 2015;372(25):2387-97. 
Confidential 
Page 94 of 287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 95 of 287 
20. 
APPENDICES 
Appendix 1: Schedule of Assessments 
Appendix 2: Sponsor’s Signature 
Appendix 3: Investigator’s Signature 
Appendix 4: Dutch Lipid Clinic Network Criteria for Familial Hypercholesterolemia 
Appendix 5: Simon Broome Diagnostic Criteria for Familial Hypercholesterolemia 
Appendix 6: Summary of Changes in Amendment 1 
Appendix 7: Summary of Changes in Amendment 2 
Appendix 8: Summary of Changes in Amendment 3 
Appendix 9: Summary of Changes in Amendment 4 
Appendix 10: Summary of Changes in Amendment 5 
 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Amendment 5, 10 May 2017 
APPENDIX 1. SCHEDULE OF EVENTS (SUBJECT VISIT SCHEDULE) 
Sc1·een 
Tl'eatment 
Visit 
s11.z 
Tl 
T2 
T3 
T4 
T4.I 
T4.2 
TS 
TS.I 
TS.2 
T6 
T7 EOS3 
p hone 
p hone 
Week 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
-2 
0 
4 
8 
12 
16 
20 
24 
28 
32 
36 
52 
Prncedul'e 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
-16 to -4 
1 
29±3 
57±3 
85±3 
112±3 140±3 169±7 196±7 224±7 253±7 
365±7 
Info1med Consent 
X 
Enrollment Criteria 
X 
Demographics 
X 
Medical Histo1y 
X 
HeFH Status 
X 
Dete1mination 
Concomitant 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medications 
Adverse Event 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Recording 
Physical Exam 
X 
X 
Weight4 
X 
X 
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 
Senun Pregnancy 
X 
and/or FSif 
Urine Pregnancy Tesl 
X 
TSH 
X 
Clinical Safety Labs9 
X 
X 
X 
X 
X 
X 
X 
X 
Additional Clinical 
X 
X 
Safety Labs10 
Basic Fasting Lipids11 
X 
X 
X 
X 
X 
X 
X 
X 
HbA1c 
X 
X 
X 
X 
10 mL reserve 
X 
X 
X 
X 
sample12 
Genetic sample 
X 
apoB 
X 
X 
X 
X 
hs-CRP 
X 
X 
X 
X 
Diet and exercise 
X 
X 
X 
X 
X 
X 
X 
X 
X 
counseling13 
Plasma PK14 
X 
X 
X 
Establish Patient 
X 
Eligibility 
Randomization 
X 
Confidential 
Page 96 of 287 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Amendment 5, 10 May 2017 
Sc1·een 
Tl'eatment 
Visit 
s11.z 
Tl 
T2 
T3 
T4 
T4.I 
T4.2 
TS 
TS.I 
TS.2 
T6 
T7 EOS3 
p hone 
p hone 
Week 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
-2 
0 
4 
8 
12 
16 
20 
24 
28 
32 
36 
52 
Prncedul'e 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
-16 to -4 
1 
29±3 
57±3 
85±3 
112±3 140±3 169±7 196±7 224±7 253±7 
365±7 
IWRS Contact 
X 
X 
X 
X 
X 
xis 
Double-blind Dmg 
X 
X 
X 
X 
Dispensing16 
Dmg 
X 
X 
X 
X 
X 
X 
Retmn/Compliance 
Offer Study 1002-050 
x-7 
Schedule next visit 
X 
X 
X 
X 
X 
X 
X 
x-8 
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 w-ith infomiation regarding ctm·ent health status and to collect infomiation on AEs (eg, recent procedm·es, 
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 retmning to clinic or by phone), Visit T7 ,vill be considered the EOS/Early Withdrawal 
from study and no further visits will be scheduled. 
1 An optional visit approxiniately 1 week later MAY be completed if patient fails to meet a lipid entiy criterion. If this optional 
visit is completed, the mean of lipid values from both visits will be used to detenuine eligibility. 
2 An optional visit between Visits Sl and Tl niay be completed if the patient's DBP and/or SBP meet the exclusion criteria 
levels. Patients may randomize after blood pressm·e medications have been adjusted, the patients have been on stable doses of 
blood pressure medications for at least 2 weeks, and the repeat blood pressm·e values (DBP and/or SBP) do not meet 
exclusionary values. An optional visit between Visit S 1 and Tl may be completed to detemwe 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 
detemlllle 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 in the morning while fasting, using consistent scales, after voiding, and without shoes and 
oute1wear (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. Urine pregnancy test is completed in premenopausal women 
who are able to become pregnant. FSH test is completed in women <55 years old and> 1 year without menses 
9 Clinical safety labs include hematology, blood chemistiy, and m-inalysis at all visits. These will also be conducted 4 weeks after 
any changes in the patient's lipid-modifying treatment. Coagulation is included at Screening (Visit Sl)for all patients, and then 
only in patients receiving anticoagulant ther=
at in the investigator's judgement requires monitoring at Baseline (Visit Tl} 
and 3 to 5 days post Visit Tl. Please refer to-
laborato1y manual for detailed schedule of tests. 
11 Basic fasting lipids include total cholesterol, calculated LDL-C, HDL-C, non-HDL-C, and triglycerides. Repeat within 1 week if 
exceed protocol-specified criteria. 
12 Based upon Sponsor assessment and decision, reserve sample collection will be discontinued after a sufficient number of 
samples have been collected. 
13Diet and exercise counseling per local and/or regional guidelines for the management ofhyperlipidemia. 
14 Patients randomized after Protocol Amendment 3 and subsequent amendments are excluded from PK sampling. 
15 IWRS contact at either an early withdrawal or an EOS visit to register study discontinuation visit date. 
Confidential 
Page 97 of 287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 98 of 287 
16 Depending upon the length of time between visits, 1 or 2 bottles of study medication will be dispensed as instructed by IWRS. 
The bottle dispensed at Visit T1 will be returned to clinic at Visits T2 and T3 for evaluation of compliance and returned for 
continued use. 
17 Review and offer the open-label extension study (Study 1002-050) to the patient. If the patient was not offered Study 1002-050, 
record the reason why in the eCRF 
18 If patient is discontinuing treatment, 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 
 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Amendment 5, 10 May 2017 
APPENDIX 2. 
Study Title: 
Study Number: 
Final Date: 
SPONSOR'S SIGNATURE 
A Randomized, Double-blind, Placebo-controlled, Multicenter Long-term 
Safety and Tolerability Study ofETC-1002 in Patients with 
Hyperlipidemia at High Cardiovascular rusk Who are not Adequately 
Controlled by Their Lipid-Modifying Therapy 
1002-040 
10 May 2017 
This clinical study protocol was subject to critical review and has been approved by the Sponsor. 
The following personnel contributed to writing and/or approving this protocol: 
Signed: 
Date: 
Confidential 
Page 99 of 287 

ETC-1002 
Esperion Therapeutics. Inc. 
Clinical Study Protoc-01 J 002-040 
Amendment 5.101'1ey 2017 
Study Title: 
St«dy ·umber: 
Final Dare: 
A Randomized. Double-blind, Placebo-controlled .. Multjcenle:r Long-term. 
Safety Wld Tolt:mbility Study af ETC-1002 irr Patients with 
Oyperlipidemia at ffigb Cardiovascular Risk Who arc not Adequately 
Controlled by fbdr Lipid-Modifying Therapy 
I002-(J40 
to Ma} 2017 
1 his clinical study protocol was subject to critical review and lias been approved by the Sponsor. 
The foHo,,ing pe-rnonnel contributed to ,,ii ting and/or approving this pmtocol: 
Signed: 
Date:~ 't.. Jon: 
Confidential 
Page lOO of287 

ETC-1002
Esperion Therapeutics, Inc.
Clinical Study Protocol 1002-040
Amendment 5, 10 May 2017
Confidential
Page 101 of 287
Study Title:
A Randomized, Double-blind, Placebo-controlled, Multicenter Long-term 
Safety and Tolerability Study of ETC-1002 in Patients with 
Hyperlipidemia at High Cardiovascular Risk Who are not Adequately 
Controlled by Their Lipid-Modifying Therapy
Study Number:
1002-040
Final Date:
10 May 2017
This clinical study protocol was subject to critical review and has been approved by the Sponsor.
The following personnel contributed to writing and/or approving this protocol:
Signed:
Date:

• 
• 
I 
• • • 
ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Amendment 5, 10 May 2017 
Study Title: 
Study Number: 
Final Date: 
A Randomized, Double-blind, Placebo-controlled, Multicenter Long-term 
Safety and Tolerability Study of ETC-1002 in Patients with 
Hyperlipidemia at High Cardiovascular Risk Who are not Adequately 
Controlled by Their Lipid-Modifying Therapy 
1002-040 
10 May2017 
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: Lklfak[~ 
Confidential 
Page 102 of 287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 103 of 287 
APPENDIX 3. INVESTIGATOR’S SIGNATURE 
Study Title: 
A Randomized, Double-blind, Placebo-controlled, Multicenter Long-term 
Safety and Tolerability Study of ETC-1002 in Patients with 
Hyperlipidemia at High Cardiovascular Risk Who are not Adequately 
Controlled by Their Lipid-Modifying Therapy 
Study Number: 
1002-040 
Final Date: 
10 May 2017 
 
I have read the protocol described above. I agree to comply with all applicable regulations and to 
conduct the study as described in the protocol.  
 
 
Signed:  
Date:  
 
Name and Credentials:  
Title:  
Affiliation:  
Address:  
Phone Number:  
 
 
 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 104 of 287 
APPENDIX 4. DUTCH LIPID CLINIC NETWORK CRITERIA FOR 
FAMILIAL HYPERCHOLESTEROLEMIA 
 
 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 105 of 287 
Dutch Lipid Clinic Network Diagnostic Criteria for Familial Hypercholesterolemia 1,2,3 
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 
 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 106 of 287 
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. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 107 of 287 
APPENDIX 5. SIMON BROOM REGISTER DIAGNOSTIC CRITERIA 
FOR HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Amendment 5, 10 May 2017 
Confidential 
Page 108 of 287 
Simon Broome Diagnostic Criteria for Familial Hypercholesterolemia 1  
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 
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. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 109 of 287 
APPENDIX 6. SUMMARY OF CHANGES IN AMENDMENT 1 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 110 of 287 
SUMMARY OF CHANGES 
CLINICAL STUDY PROTOCOL  
 
Study Number: 
1002-040 
Study Title: 
A Randomized, Double-blind, Placebo-controlled, 
Multicenter Long-term Safety and Tolerability Study of 
ETC-1002 in Patients with Hyperlipidemia at High 
Cardiovascular Risk Who are not Adequately Controlled 
by Their Lipid-Modifying Therapy 
Protocol Version Incorporating 
Current Summary of Changes: 
Amendment 1: Amended Protocol 28 January 2016 
Preceding Protocol Version: 
Original Protocol: 02 October 2015 
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 italicized. 
5. In the “New Text”, text deleted from the protocol is indicated in strikethrough font. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 111 of 287 
Summary and Justification of Changes 
The protocol was amended for the following: 
• Addition of secondary and tertiary study objectives to evaluate lipid and 
cardiometabolic parameters at specific time points throughout the study 
• Addition of protocol requirements to address the recent marketing of PCSK9 
inhibitors resulting in the addition of exclusion criteria, prohibited medications 
instructions, and allowable medication instructions to reflect the protocol 
requirements 
• Defined clinical endpoints to provide clarity regarding the events that will be 
adjudicated by the CEC 
• Clarified the definition for duration of treatment and end of study 
• Revised the reporting requirements for clinical endpoints  
• Revised inclusion/exclusion criteria by aligning the medical history and concurrent 
conditions of the study population with those commonly observed in patients with 
hyperlipidemia and high cardiovascular risk 
• Clarified that the IMP would be provided in 100-count or 35-counts bottles with 
either 100 or 35 pills included in each respective container 
• Updated clinical laboratory parameters (safety, lipid, and/cardiometabolic biomarker), 
the laboratory sample collection schedule, and laboratory result reporting to ensure 
consistency across sections within this protocol. 
− Removal of insulin and aPTT from list of clinical laboratory samples 
− Clarified that glucose will be a fasting value evaluated from collected serum 
− Clarified that FSH will be tested in the appropriate female patients 
− Clarified that WBC with differential will be reported in both absolute and percent 
values 
− Updated to include all lipid values will not be available to investigators and site 
staff, sponsor, 
 
• Updated the Study Procedures and the Schedule of Events (Appendix 1) to reflect the 
procedures and instructions required for each visit 
• Addition of instructions for subject withdrawal criteria and restarting IMP for patients 
who have had a temporary withdrawal from IMP 
• Revised safety monitoring and management instructions to ensure patient safety for 
the following: 
− Elevated serum creatinine 
− Hemoglobin 
− Elevated creatine kinase 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 112 of 287 
− LDL-C threshold criteria for the addition of adjunctive therapy beginning at 
Week 24 (Visit T5) 
− Hypoglycemia 
• Clarified the reporting requirements for AEs, SAEs, and pregnancies 
• Updated the lipid endpoint assessments for consistency with study objectives 
• Revised the statistical section to include: 
− Updated sample size justification 
− Clarification of the analysis population 
− Updated analysis and summarization description for primary endpoints 
− Addition of analysis and summarization description for secondary and tertiary 
endpoints 
− Updated analysis and summarization description for PK and biomarkers 
• Typographical errors and formatting were corrected or revised to improve clarity and 
consistency. These included, but were not limited to: 
− Updating the synopsis to include a complete list of inclusion and exclusion 
criteria 
− Consistently clarifying that a maximally tolerated statin is either alone or in 
combination with other lipid-lowering therapies 
− Updating the list of abbreviations and definition of terms 
− Revising the reference list and in text reference numbers to accommodate the 
addition of a reference 
This amendment represents cumulative changes to the original protocol. 
CHANGE 1 ADDITION OF SECONDARY AND TERTIARY STUDY OBJECTIVES 
Location: 
Synopsis; Secondary Objectives 
Original Text: 
Secondary: 
• 
To assess lipid values (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein 
cholesterol [HDL-C], non-HDL-C, total cholesterol [TC], and triglycerides [TG]) at 12, 24, and 
52 weeks  
• 
To assess apolipoprotein B (apoB) and high-sensitivity C-reactive protein (hs-CRP) at 12, 24, and 
52 weeks 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 113 of 287 
New Text: 
Secondary: 
• 
To assess percent change from baseline to Week 12 in low-density lipoprotein cholesterol 
(LDL-C) 
• 
To assess lipid values (low density lipoprotein cholesterol [LDL C], high density lipoprotein 
cholesterol [HDL C], non HDL C, total cholesterol [TC], and triglycerides [TG]) at 12, 24, and 
52 weeks  
• 
To assess apolipoprotein B (apoB) and high sensitivity C reactive protein (hs CRP) at 12, 24, and 
52 weeks 
CHANGE 2 ADDITION OF SECONDARY AND TERTIARY STUDY OBJECTIVES 
Location:  
• 
Synopsis; Tertiary Objectives 
Original Text:  
Original protocol did not have tertiary objectives; therefore, there is no original text to be 
displayed. 
New Text: 
Tertiary: 
• 
To assess percent change from baseline to Week 24 and to Week 52 in LDL-C in patients who do 
not receive adjunctive lipid-lowering therapy 
• 
To assess high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC), and 
triglycerides (TG) values at Week 12, 24, and 52  
• 
To assess apolipoprotein B (apoB) and high-sensitivity C-reactive protein (hs-CRP) values at 
Week 12, 24, and 52 
CHANGE 3 ADDITION OF PROTOCOL REQUIREMENTS TO ADDRESS THE 
AVAILABILITY OF PCSK9 INHIBITORS 
Location: 
Synopsis; Study Design 
Original Text 
Maximally tolerated lipid-lowering therapy includes a maximally tolerated statin alone or in combination 
with other lipid-lowering therapies (eg, ezetimibe, fibrates [except gemfibrozil], evolocumab, and 
alirocumab). 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. However, patients currently taking high-dose statins, defined as 
rosuvastatin 40 mg, atorvastatin 80 mg, or simvastatin 40 or 80 mg per day will be excluded from this 
study. 
New Text 
Maximally tolerated lipid-lowering therapy includes a maximally tolerated statin alone or in combination 
with other lipid-lowering therapies (eg, ezetimibe, fibrates [except gemfibrozil], evolocumab, and 
alirocumab). A patient’s maximally tolerated lipid-modifying therapy will be determined by the 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 114 of 287 
investigator using their medical judgment and available sources, including the patient’s self-reported 
history of lipid-modifying therapy. However, patients currently taking high-dose statins, defined as 
rosuvastatin 40 mg, atorvastatin 80 mg, or simvastatin 40 or 80 mg per day, or who are currently taking a 
proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (alirocumab or evolocumab), or have 
taken a PCSK9 inhibitor within the past 4 weeks will be excluded from enrolling in this study. PCSK9 
inhibitors may be initiated as adjunctive therapy at Week 24 if the LDL-C threshold criteria have been 
met as described in Section 11.1.6.3.5. 
CHANGE 4 TYPOGRAPHICAL AND FORMATTING 
Location: 
Synopsis; Study Design 
Original Text: 
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. 
New Text: 
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. 
CHANGE 5 DEFINITION OF CLINICAL ENDPOINTS 
Location:  
Synopsis; Study Design 
Original Text: 
An independent expert Data Monitoring Committee (DMC) will formally review accumulating unblinded 
safety data from this and other ongoing studies of ETC-1002. All CV events, including death, will be 
adjudicated by an independent blinded expert Clinical Events Committee (CEC), using standardized 
definitions. Until the CEC has been established, CV events will be reported as both serious adverse events 
(SAEs) and major adverse cardiovascular events and mortality (MACE). 
New Text: 
An independent expert Data Monitoring Committee (DMC) will formally review accumulating unblinded 
safety and efficacy data from this and other ongoing studies of ETC-1002. All CV events, including 
death, will be adjudicated by an independent blinded expert Clinical Events Committee (CEC), using 
standardized definitions.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 Until the CEC has been established, CV events 
will be reported as both serious adverse events (SAEs) and major adverse cardiovascular events and 
mortality (MACE).Any clinical endpoints that meet serious adverse event (SAE) criteria will be reported 
as SAEs. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 115 of 287 
CHANGE 6 CLARIFICATION OF DURATION OF TREATMENT AND END OF 
STUDY 
Location: 
Synopsis; Duration of treatment 
Original Text:  
Fifty-two weeks for all randomized patients who complete the study 
New Text: 
Fifty-two weeks for all randomized patients who complete the study 
CHANGE 7 CLARIFICATION OF DURATION OF TREATMENT AND END OF 
STUDY 
Location: 
Synopsis; End of Study 
Original Text: 
The study will end when the last randomized patient completes 52 weeks of treatment. The estimated 
overall duration of the study (first patient first visit [FPFV] to last patient last visit [LPLV]) is 
approximately 22 months. 
New Text: 
The study will end when the last randomized patient completes their last study visit 52 weeks of 
treatment. The estimated overall duration of the study (first patient first visit [FPFV] to last patient last 
visit [LPLV]) is approximately 22 months. 
CHANGE 8 TYPOGRAPHICAL AND FORMATTING 
Location: 
Synopsis; Diagnosis and criteria for patient eligibility 
Original Text: 
Diagnosis and key criteria for patient eligibility:  
The study will enroll adult male and female patients with hyperlipidemia  
Key eligibility criteria include the following:  
• 
Provision of written informed consent prior to any study-specific procedure 
• 
Men and nonpregnant, nonlactating women  
• 
Age ≥18 years or legal age of majority depending on regional law, whichever is greater at 
Week -2 (Visit S1) 
• 
Qualifying fasting LDL-C value at Week -2 (Visit S1) ≥70 mg/dL (1.8 mmol/L) 
• 
Qualifying fasting TG value at Week -2 (Visit S1) ≤400 mg/dL (4.5 mmol/L) 
• 
Body mass index (BMI) <50 kg/m2 
• 
Have high cardiovascular 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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 116 of 287 
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): 
 
Acute myocardial infarction (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 
• 
Be on maximally tolerated lipid-modifying therapy, including a statin, at a stable dose and 
regimen for at least 4 weeks prior to screening (6 weeks for fibrates). Regimens other than daily 
dosing, including those at very low doses, are acceptable. 
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.  
Patients currently taking high-dose statins, defined as rosuvastatin 40 mg, atorvastatin 80 mg, or 
simvastatin 40 or 80 mg per day will be excluded from this study. 
For the complete list of inclusion and exclusion criteria, please refer to Section 7 of the protocol. 
New Text: 
Diagnosis and key criteria for patient eligibility:  
The study will enroll adult male and female patients with hyperlipidemia  
Key Each patient must meet the following eligibility criteria include the followingto be eligible for this 
study:  
Inclusion Criteria 
• 
Provision of written informed consent prior to any study-specific procedure 
• 
Age ≥18 years or legal age of majority depending on regional law, whichever is greater at 
Week -2 (Visit S1) 
• 
Men and nonpregnant, nonlactating women. Women must be either:  
- Naturally postmenopausal (as reported by the patient, defined as greater than 55 years 
and ≥1 year without menses, less than 55 years and ≥1 year without menses with follicle-
stimulating hormone (FSH) ≥40.0 IU/L), or surgically sterile (including hysterectomy 
and/or bilateral oophorectomy, but not tubal ligation alone) or;  

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 117 of 287 
- Women of childbearing potential must be willing to use 1 acceptable method of birth 
control. 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). 
- There are no protocol-specific birth control requirements for men with partners who are 
able to become pregnant. 
• 
Age ≥18 years or legal age of majority depending on regional law, whichever is greater at 
Week 2 (Visit S1)Qualifying fFasting LDL-C value at Week -2 (Visit S1) ≥70 mg/dL 
(1.8 mmol/L) 
Note: LDL-C may be repeated 1 time with the screening period extended up to 2 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. 
• 
Qualifying fasting TG value at Week 2 (Visit S1) ≤400 mg/dL (4.5 mmol/L) 
• 
Body mass index (BMI) <50 kg/m2 
• 
Have high cardiovascular 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): 
 
Acute myocardial infarction (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 
• 
Be on maximally tolerated lipid-modifying therapy, including a maximally tolerated statin either 
alone or in combination with other lipid-lowering therapies, at astable doses and regimens for at 
least 4 weeks prior to screening (6 weeks for fibrates; however, gemfibrozil is not allowed). 
Regimens other than daily dosing, including those at very low doses, are acceptable. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 118 of 287 
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.  
Patients currently taking high-dose statins, defined as rosuvastatin 40 mg, atorvastatin 80 mg, or 
simvastatin 40 or 80 mg per day will be excluded from this study. 
Patients who are currently taking a PCSK9 inhibitor (Praluent® [alirocumab] or Repatha® 
[evolocumab]) or have taken a PCSK9 inhibitor within the past 4 weeks of Week -2 (Visit S1) will 
be excluded from this study. 
Exclusion Criteria: 
• 
Total fasting triglyceride >400 mg/dL (4.5 mmol/L) at Week -2 (Visit S1) 
Note: TG may be repeated 1 time with the screening period extended up to 2 weeks. For those 
patients who have a repeat TG, the mean of the first value and the repeat value will be used to 
determine eligibility. 
• 
Renal dysfunction or nephritic syndrome or a history of nephritis, including eGFR (using central 
laboratory determined Modification of Diet in Renal Disease [MDRD] formula) 
<45 mL/min/1.73 m2 at Week -2 (Visit S1) [1].  
Note: At the discretion of the investigator, the screening period may be extended up to 2 weeks for 
a single repeat eGFR. For those patients who have a repeat eGFR, the repeat value will be used 
to determine eligibility. 
• 
Body mass index (BMI) ≥50 kg/m2 
• 
Concomitant use of high-dose statins, defined as rosuvastatin 40 mg, atorvastatin 80 mg, or 
simvastatin 40 or 80 mg daily.  
• 
Concomitant use of a PCSK9 inhibitor (Praluent® [alirocumab] or Repatha® [evolocumab]) at 
Week -2 (Visit S1) or prior use of a PCSK9 inhibitor within the past 4 weeks of Week -2 (Visit S1) 
will be excluded from this study. 
Note: Patients are allowed to initiate a PCSK9 inhibitor as adjunctive therapy at Week 24 if the 
LDL-C threshold criteria have been met as described in Section 11.1.6.3.5. 
• 
Recent (within 3 months prior to the screening visit [Week -2 (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. 
• 
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 2 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 
• 
Hemoglobin A1C (HbA1C) ≥10% at Week -2 (Visit S1) 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 119 of 287 
• 
Uncontrolled hypothyroidism, including thyroid-stimulating hormone (TSH) >1.5 × the upper 
limit of normal (ULN) at Week -2 (Visit S1). Patients stabilized on thyroid replacement therapy 
for at least 6 weeks prior to randomization are allowed. 
• 
Liver disease or dysfunction, including:  
• 
Positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies 
(HCV-AB) at Week -2 (Visit S1); or 
• 
Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≥1.5 × ULN, and/or total 
bilirubin (TB) ≥1.2 × ULN at Week -2 (Visit S1).  
Note: At the discretion of the investigator, the screening period may be extended up to 2 weeks for 
a single repeat of ALT, AST, and/or TB. For those patients who have a repeat ALT, AST, and/or 
TB, the repeat value will be used to determine eligibility. 
• 
Gastrointestinal conditions or procedures (including weight loss surgery; eg, Lap-Band® or 
gastric bypass) that may affect drug absorption 
• 
Hematologic or coagulation disorders or a hemoglobin (Hgb) level <10.0 g/dL (100 g/L) at 
Week -2 (Visit S1) 
• 
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) 
• 
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.  
• 
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. 
• 
Blood donation, participation in a clinical study with multiple blood draws, major trauma, or 
surgery with or without blood loss within 30 days prior to randomization 
• 
Blood transfusion for any reason within 90 days prior to randomization 
• 
Use of any experimental or investigational drugs within 30 days prior to screening or 5 half-
lives, whichever is longer 
• 
Prior participation in a previous ETC-1002 clinical study. Prior participation in a clinical study 
with ETC-1002 is defined as having been enrolled in an ETC-1002 study. 
• 
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  
• 
Requirement for 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 (6 months prior to randomization 
• 
An employee or contractor of the facility conducting the study, or a family member of the 
Principal Investigator, Co-Investigator, or Sponsor. 
For the complete list of inclusion and exclusion criteria, please refer to Section 7 of the protocol. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 120 of 287 
CHANGE 9 DEFINITION OF CLINICAL ENDPOINTS 
Location: 
Synopsis; Criteria for evaluation 
Original Text: 
Safety Assessments: 
Adverse events (AEs) and SAEs will be collected and reported. MACE will be collected and adjudicated 
by an independent CEC. Until the CEC has been established, MACE that also meets the definition of an 
SAE will be reported both as MACE and as SAEs. 
New Text: 
Safety Assessments: 
Adverse events (AEs) and SAEs will be collected and reported. MACE Clinical endpoints will be 
collected and adjudicated by an independent CEC. Until the CEC has been established, MACE that also 
meets the definition of an SAE will be reported both as MACE and as SAEsClinical endpoints will also 
be reported as SAEs. 
CHANGE 10 UPDATE CLINICAL LABORATORY PARAMETERS 
Location: 
Synopsis; Criteria for evaluation 
Original Text: 
Safety Assessments: 
Other safety assessments will include clinical safety laboratories (including hematology, blood chemistry, 
coagulation, glycosylated hemoglobin type A1C [HbA1C], fasting glucose, and urinalysis), physical 
examination (PE) findings, vital signs, electrocardiogram [ECG] readings, and weight. 
New Text: 
Safety Assessments: 
Other safety assessments will include clinical safety laboratories (including hematology, blood chemistry, 
coagulation, glycosylated hemoglobin type A1C [HbA1C], fasting glucose, and urinalysis), physical 
examination (PE) findings, vital signs, electrocardiogram [ECG] readings, and weight. 
CHANGE 11 UPDATE CLINICAL LABORATORY PARAMETERS 
Location: 
Synopsis; Criteria for evaluation 
Original Text: 
Clinical Laboratory Assessments: 
• 
Coagulation: Prothrombin time (PT), activated partial thromboplastin time (PTT) 
New Text: 
Clinical Laboratory Assessments: 
• 
Coagulation: Prothrombin time (PT), activated partial thromboplastin time (PTT) 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 121 of 287 
CHANGE 12 UPDATE CLINICAL LABORATORY PARAMETERS 
Location: 
Synopsis; Criteria for evaluation 
Original Text: 
Clinical Laboratory Assessments: 
• 
Insulin 
New Text: 
Clinical Laboratory Assessments: 
• 
Insulin 
CHANGE 13 UPDATE CLINICAL LABORATORY PARAMETERS 
Location: 
Synopsis; Criteria for evaluation 
Original Text: 
Other Screening Laboratories: 
• 
Hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV), serum pregnancy test (only for 
females who are of childbearing potential), thyroid-stimulating hormone (TSH) 
New Text: 
Other Screening Laboratories: 
• 
Hepatitis B surface antigen (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), thyroid stimulating hormone (TSH) 
CHANGE 14 REVISE SAFETY MONITORING AND MANAGEMENT 
INSTRUCTIONS 
Location: 
Synopsis; Safety and Monitoring: 
Original Text: 
Monitoring and Management Plans for Lipid Elevations: 
• 
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: 
• 
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) 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 122 of 287 
CHANGE 15 REVISE SAFETY MONITORING AND MANAGEMENT 
INSTRUCTIONS 
Location: 
Synopsis; Safety and Monitoring: 
Original Text: 
Monitoring and Management of Potential AEs and Adverse Events of Special Interest (AESI) 
Potential AEs: 
Based on findings in nonclinical models, potential AEs include reversible hypoglycemia and metabolic 
acidosis. Potential cases of reversible hypoglycemia and metabolic acidosis will be identified by routine 
safety monitoring of AEs and clinical safety laboratories. Potential cases of reversible hypoglycemia and 
metabolic acidosis will be identified by routine safety monitoring of AEs and clinical safety laboratories. 
New Text: 
Monitoring and Management of Potential AEs and Adverse Events of Special Interest (AESI) 
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 provided with a 
wallet card that gives instructions for treatment and for reporting 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. 
CHANGE 16 REVISE SAFETY MONITORING AND MANAGEMENT 
INSTRUCTIONS 
Location: 
Synopsis; Safety and Monitoring: 
Original Text:  
Diabetes and Glycemia: 
Cases of new onset of diabetes will be recorded as AEs. Clinical laboratories, including HbA1c, glucose, 
and insulin will also be evaluated across treatment groups during this study and all ongoing studies to 
identify potential cases of new onset of diabetes. 
New Text: 
Diabetes and GlycemiaHyperglycemia: 
Cases of new onset of diabetes will be recorded as AEs. Clinical laboratories, including HbA1c, and 
glucose, and insulin will also be evaluated across treatment groups during this study and all ongoing 
studies to identify potential cases of new onset of diabetes. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 123 of 287 
CHANGE 17 REVISE SAFETY MONITORING AND MANAGEMENT 
INSTRUCTIONS 
Location: 
Synopsis; Safety and Monitoring: 
Original Text: 
Cardiovascular Events (MACE): 
MACE will be monitored and adjudicated by an independent expert CEC for this study and other ongoing 
studies in the ETC-1002 program. 
New Text: 
Cardiovascular Events (MACE)Clinical Endpoints: 
MACE Clinical endpoints will be monitored and adjudicated by an independent expert CEC for this study 
and other ongoing studies in the ETC-1002 program. 
CHANGE 18 REVISED STATISTICS 
Location: 
Synopsis; Statistical Methods: 
Original Text: 
Sample Size 
The sample size of 600 patients randomized to ETC-1002 and 300 patients randomized to placebo will 
provide 900 total patients. This sample size was selected to provide a robust long-term safety profile in 
patients considered to have an unmet need for additional lipid lowering in a chronic setting. 
New Text: 
Sample Size 
A total of 900 patients will be enrolled in this study with 600 patients randomized to ETC-1002 and 
300 patients randomized to placebo. Using an anticipated overall dropout rate of 7.5% at 6 months and 
10.0% at 12 months in each treatment group, the expected number of patients exposed to treatment 
during the study is as follows: 
 
Patients ≥6 Months 
Patients ≥12 Months 
ETC-1002 
555 
540 
Placebo 
278 
270 
Absolute risk will be addressed by 600 patients randomized to ETC-1002 and will provide at least 95% 
power to detect Adverse Events (AEs) that occur at rates similar to those seen in the placebo group for 
the AEs of interest in the recently completed long-term safety study entitled Efficacy and Safety of 
Alirocumab in Reducing Lipids and Cardiovascular Events [2]. In this study adverse event rates ranged 
from 0.5% to 13.6%. Additional assumptions include a two-sided test with significance level at 0.05. 
When AEs occur at a range of rates similar to those seen in the placebo group in the above referenced 
alirocumab study (0.5% to 13.6%), the sample size of 600 patients randomized to ETC-1002 and 
300 patients randomized to placebo will allow for detection of relative risks of 1.0 and of 2.0 
(ETC-1002:placebo) with the following approximate 95% confidence limits):  

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 124 of 287 
% Placebo Patients 
Experiencing AE 
% ETC-1002 Patients 
Experiencing AE 
Relative Risk 
Approximate 95% 
Confidence Interval 
0.5% 
0.5% 
1.0 
(0.1, 7.0) 
0.5% 
1.0% 
2.0 
(0.3, 11.9) 
13.6% 
13.6% 
1.0 
(0.7, 1.4) 
13.6% 
27.2% 
2.0 
(0.5, 2.3) 
The sample size of 600 patients randomized to ETC 1002 and 300 patients randomized to placebo will 
provide 900 total patients. This sample size was selected to provide a robust long term safety profile in 
patients considered to have an unmet need for additional lipid lowering in a chronic setting. 
CHANGE 19 REVISED STATISTICS 
Location: 
Synopsis; Statistical Methods: 
Original Text: 
Analysis Populations 
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.  
The Full Analysis Set (FAS), used for all of the lipid and cardiometabolic summaries, is defined as all 
randomized patients and is also known as the intention-to-treat (ITT) set of patients. 
New Text: 
Analysis Populations 
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.  
The Full Analysis Set (FAS), used for the LDL-C analyses and the all of the lipid and cardiometabolic 
summaries, is defined as all randomized patients and is also known as the intention-to-treat (ITT) set of 
patients. 
CHANGE 20 REVISED STATISTICS 
Location: 
Synopsis; Statistical Methods: 
Original Text: 
Primary Endpoint  
The primary endpoint for this study is general safety, which includes AEs, clinical safety laboratories, 
PEs, vital signs, and ECGs. 
No statistical analyses will be performed on any of the safety data in this study. The summarization of 
AEs will include only treatment-emergent AEs (TEAEs), defined as AEs that begin or worsen after 
randomization and ingestion of the first dose of study drug. TEAEs and SAEs will be summarized by 
system organ class (SOC), severity, and relationship to study drug for each treatment group. AE 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 125 of 287 
summaries will be provided overall and for subgroups such as gender, age, and HeFH status. 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, insulin, 
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 post-baseline time point. 
New Text: 
Primary Endpoint  
The primary endpoint for this study is general safety, which includes AEs, clinical safety laboratories, 
PEs, vital signs, and ECGs. 
No statistical analyses will be performed on any of the safety data in this study. The summarization of 
AEs will include only treatment-emergent AEs (TEAEs), defined as AEs that begin or worsen after 
randomization and ingestion of the first dose of study drug. TEAEs and SAEs will be summarized by 
system organ class (SOC), severity, and relationship to study drug for each treatment group. AE 
summaries will include cumulative incidence (percent of patients experiencing the AE) and patient-year 
adjusted incidence rates. These AE summaries will be provided overall and for subgroups such as gender, 
age, and HeFH status. 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, insulin, 
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 post-baseline time point. 
CHANGE 21 REVISED STATISTICS 
Location: 
Synopsis; Statistical Methods: 
Original Text: 
Diabetes and Glycemia 
Cases of new onset of diabetes will be recorded as AEs. Clinical laboratories, including HbA1c, glucose, 
and insulin will also be evaluated across treatment groups during this study and all ongoing studies to 
identify potential cases of new onset of diabetes. 
New Text 
Diabetes and Glycemia 
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. insulin, Glucose and HbA1C will be monitored at baseline and at Weeks 12, 24, and 52, and be 
summarized. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 126 of 287 
CHANGE 22 REVISED STATISTICS 
Location: 
Synopsis; Statistical Methods: 
Original Text: 
Renal Safety 
Baseline estimated glomerular filtration rate (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. If needed, post-baseline eGFR categories will be modified to include the 
possibility of patients with eGFR values <45 mL/min/1. 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. 
New Text: 
Renal Safety 
Baseline estimated glomerular filtration rate (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. If needed, post baseline eGFR categories will be modified to include the 
possibility of patients with eGFR values <45 mL/min/1. 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. 
CHANGE 23 REVISED STATISTICS 
Location: 
Synopsis; Statistical Methods: 
Original Text: 
Cardiovascular Events (MACE) 
MACE will be monitored and adjudicated by an independent blinded expert CEC for ongoing studies the 
ETC-1002 program. Adjudicated MACE will be summarized by event type and treatment group. 
Additional details regarding MACE and MACE definitions will be included in CEC charter. 
New Text: 
Cardiovascular Events (MACE)Clinical Endpoints 
MACE Clinical endpoints will be monitored and adjudicated by an independent blinded expert CEC for 
ongoing studies the ETC-1002 program. Adjudicated MACE clinical endpoints will be summarized by 
event type and treatment group. Additional details regarding MACE clinical endpoints and MACE 
clinical endpoint definitions will be included in CEC charter. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 127 of 287 
CHANGE 24 REVISED STATISTICS 
Location: 
Synopsis; Statistical Methods: 
Original Text: 
Lipids 
LDL-C, HDL-C, TG, TC, non-HDL-C, and apoB values at Weeks 12, 24, and 52 will be summarized. For 
each parameter at each time point, the value of the parameter and the percent change from baseline in the 
parameter will be summarized by treatment group. Missing values for any of the lipid parameters will not 
be imputed; that is, only observed case data will be used. 
New Text: 
Secondary Endpoint Lipids 
Percent change from baseline to Week 12 in LDL-C will be analyzed using analysis of covariance 
(ANCOVA), with treatment and randomization strata (patient’s CV risk and baseline statin dose) as 
factors and baseline LDL-C as a covariate. The FAS will be used, with patients included in their 
randomized 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). For each ANCOVA (observed case; imputation 
via PMM), output will include the least squares mean (LSM) and standard error (SE) for each treatment 
group, along with the placebo-correct LSM and it’s 95% confidence interval (CI) and p-value.  
Tertiary Endpoint Lipids 
LDL-C, HDL-C, TG, TC, non-HDL-C, and apoB values at Weeks 12, 24, and 52 will be summarized. For 
each parameter at each time point, the value of the parameter and the percent change from baseline in 
the parameter will be summarized by treatment group. The FAS will be used, with patients included in 
their randomized group, regardless of the treatment they actually received. In addition, a summary using 
the FAS, excluding patients who received additional lipid-lowering therapy by that timepoint (by Week 24 
for the Week 24 timepoint; by Week 52 for the Week 52 timepoint), will be provided. For both summaries, 
only observed case data will be used (no imputation for missing data).  
Percent change from baseline to Week 24 and to Week 52 on LDL-C will be analyzed similarly, with 
patients in the FAS who did not receive additional lipid-lowering therapy by that timepoint (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. 
LDL C, HDL C, TG, TC, non HDL C, and apoB values at Weeks 12, 24, and 52 will be summarized. For 
each parameter at each time point, the value of the parameter and the percent change from baseline in the 
parameter will be summarized by treatment group. Missing values for any of the lipid parameters will not 
be imputed; that is, only observed case data will be used. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 128 of 287 
CHANGE 25 REVISED STATISTICS 
Location: 
Synopsis; Statistical Methods: 
Original Text: 
PK and Other biomarkers 
hs-CRP values and percent change from baseline in values will be summarized by treatment group at 
Weeks 12, 24, and 52. Missing values for hs-CRP will not be imputed; only observed case data will be 
used. 
In addition, trough plasma concentrations will be collected at Weeks 12, 24, and 52 for use in further 
developing the population pharmacokinetic (PK) model. 
New Text: 
PK and Other biomarkers 
hs-CRP values and percent change from baseline in values will be summarized by treatment group at 
Weeks 12, 24, and 52. The FAS will be used, with patients included in their randomized treatment group, 
regardless of the treatment they actually received. Only observed case data will be used (no imputation 
for missing data).Missing values for hs CRP will not be imputed; only observed case data will be used. 
In addition, trough plasma concentrations will be collected at Weeks 12, 24, and 52 for use in further 
developing the population pharmacokinetic (PK) model. 
CHANGE 26 TYPOGRAPHICAL AND FORMATTING 
Location: 
Table 1: Abbreviations and Specialist Terms 
Original Text: 
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 
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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 129 of 287 
Abbreviation or Specialist Term 
Explanation 
BMI 
Body mass index 
BP 
Blood pressure 
BUN 
Blood urea nitrogen 
Ca 
Calcium 
CABG 
Coronary artery bypass graft 
CEC 
Clinical Event Committee 
CFR 
Code of Federal Regulations 
CHD 
Coronary heart disease 
CK 
Creatine kinase 
Cl 
Chloride 
Cmax 
Time to peak maximum concentrations 
CMV 
Cytomegalovirus 
CNS 
Central nervous system 
CoA 
Acetyl-coenzyme A 
CO2 
Carbon dioxide 
CrCL 
Creatinine clearance 
CT 
Computed tomography 
CV 
Cardiovascular 
CYP 
Cytochrome P450 
DBP 
Diastolic blood pressure 
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EMA 
European Medicines Agency 
eGFR 
Estimated glomerular filtration rate 
EU 
European Union 
FAS 
Full analysis set 
FDA 
U.S. 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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 130 of 287 
Abbreviation or Specialist Term 
Explanation 
HCV 
Hepatitis C virus 
HCV-AB 
Hepatitis C antibodies 
HDL-C 
High-density lipoprotein cholesterol 
HeFH 
Heterozygous familial hypercholesterolemia 
Hgb 
Hemoglobin 
HIV 
Human immunodeficiency virus 
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 
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 
MACE 
Major adverse cardiovascular events and mortality 
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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 131 of 287 
Abbreviation or Specialist Term 
Explanation 
Na 
Sodium 
NIMP 
Non-investigational medicinal product(s) 
NLA 
National Lipid Association 
NOAEL 
No-observed-adverse-effect level 
non-HDL-C 
Non-high-density lipoprotein cholesterol 
NYHA 
New York Heart Association 
PCI 
Percutaneous coronary intervention 
PCSK9 
Proprotein convertase subtilisin/kexin type 9 
PE 
Physical exam 
PK 
Pharmacokinetic(s) 
PT 
Prothrombin time 
PTT 
Partial thromboplastin time 
RBC 
Red blood cell 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SBP 
Systolic blood pressure 
SGOT 
Serum glutamic oxaloacetic transaminase 
SGPT 
Serum glutamic pyruvic transaminase 
SOC 
System organ class 
SOP 
Standard operating procedures 
SP 
Safety population 
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 
WBC 
White blood cell 
WHO 
World Health Organization 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 132 of 287 
New Text: 
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 
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 
CO2 
Carbon dioxide 
CrCL 
Creatinine clearance 
CT 
Computed tomography 
CV 
Cardiovascular 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 133 of 287 
Abbreviation or Specialist Term 
Explanation 
CYP 
Cytochrome P450 
DBP 
Diastolic blood pressure 
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EMA 
European Medicines Agency 
eGFR 
Estimated glomerular filtration rate 
EOS 
End of Study 
EU 
European Union 
FAS 
Full analysis set 
FDA 
U.S. 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 
HIV 
Human immunodeficiency virus 
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 
IMP 
Investigational medicinal product 
IND 
Investigational New Drug Application 
INR 
International normalized ratio 
IRB 
Institutional Review Board 
ITT 
Intention-to-treat 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 134 of 287 
Abbreviation or Specialist Term 
Explanation 
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 cardiovascular cardiac event and mortality 
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 
NIMP 
Non-investigational medicinal product(s) 
NLA 
National Lipid Association 
NOAEL 
No-observed-adverse-effect level 
non-HDL-C 
Non-high-density lipoprotein cholesterol 
NYHA 
New York Heart Association 
PCI 
Percutaneous coronary intervention 
PCSK9 
Proprotein convertase subtilisin/kexin type 9 
PE 
Physical exam 
PK 
Pharmacokinetic(s) 
PMM 
Pattern mixed model 
PT 
Prothrombin time 
PTT 
Partial thromboplastin time 
RBC 
Red blood cell 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 135 of 287 
Abbreviation or Specialist Term 
Explanation 
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 
WBC 
White blood cell 
WHO 
World Health Organization 
CHANGE 27 TYPOGRAPHICAL AND FORMATTING 
Location: 
4.1 
Lipid-Regulating Drugs and Cardiovascular Disease 
7.2 
Subject Exclusion Criteria 
11.4 
Adverse Events of Special Interest 
Note: 
References were updated to include an additional reference in the amendment and renumbered 
accordingly. The new reference numbers within the text are not highlighted as edited text. 
CHANGE 28 TYPOGRAPHICAL AND FORMATTING 
Location: 
4.1 
Lipid-Regulating Drugs and Cardiovascular Disease 
Original Text: 
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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 136 of 287 
patients aged 40 to 59 years [12]. The National Lipid Association (NLA) adult recommendations 
achievement of ≥50% reduction in LDL-C using statins. 
New Text: 
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 [12]. The National Lipid Association (NLA) adult recommendations 
recommends achievement of ≥50% reduction in LDL-C in adult patients using statins. 
CHANGE 29 ADDITION OF SECONDARY AND TERTIARY STUDY OBJECTIVES 
Location: 
5 
TRIAL OBJECTIVES AND PURPOSE 
Original Text: 
5. 
TRIAL OBJECTIVES AND PURPOSE 
5.1 
Primary Objective 
The primary objective is to evaluate the long-term safety and tolerability of ETC-1002 versus 
placebo in high cardiovascular (CV) risk patients with hyperlipidemia (with underlying HeFH 
and/or ASCVD) who are not adequately controlled with their maximally tolerated lipid-
modifying therapy. 
5.2 
Secondary Objectives 
• To assess lipid values LDL-C, high-density lipoprotein cholesterol [HDL-C], 
non-HDL-C, total cholesterol [TC], and TG) at 12, 24, and 52 weeks 
• To assess apoB and high-sensitivity C-reactive protein (hs-CRP) at 12, 24, and 
52 weeks 
New Text: 
5. 
TRIAL OBJECTIVES AND PURPOSE 
5.1 
Primary Objective 
The primary objective is to evaluate the long-term safety and tolerability of ETC-1002 versus 
placebo in high cardiovascular (CV) risk patients with hyperlipidemia (with underlying HeFH 
and/or ASCVD) who are not adequately controlled with their maximally tolerated lipid-
modifying therapy. 
5.2 
Secondary Objectives 
• To assess percent change from baseline to Week 12 in LDL-C 
• To assess lipid values LDL C, high density lipoprotein cholesterol [HDL C], 
non HDL C, total cholesterol [TC], and TG) at 12, 24, and 52 weeks 
• To assess apoB and high sensitivity C reactive protein (hs CRP) at 12, 24, and 
52 weeks 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 137 of 287 
5.3 
Tertiary Objectives 
• To assess percent change from baseline to Week 24 and to Week 52 in LDL-C in 
patients who do not receive adjunctive lipid-lowering therapy  
• To assess high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total 
cholesterol (TC), and TG at Weeks 12, 24, and 52  
• To assess apoB and high-sensitivity C-reactive protein (hs-CRP) at Weeks 12, 24, 
and 52 
CHANGE 30 ADDITION OF PROTOCOL REQUIREMENTS TO ADDRESS THE 
AVAILABILITY OF PCSK9 INHIBITORS 
Location: 
6.1 
Overall Study Design 
Original Text: 
This is a Phase 3, randomized, double-blind, placebo-controlled, parallel group, study evaluating 
the long-term safety and tolerability of ETC-1002 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-lowering therapy 
includes a maximally tolerated statin alone or in combination with other lipid-lowering therapies 
(eg, ezetimibe, fibrates [except gemfibrozil], evolocumab, and alirocumab). 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. However, patients currently taking high-dose statins, defined as rosuvastatin 
40 mg, atorvastatin 80 mg, or simvastatin 40 or 80 mg per day will be excluded from this study. 
New Text: 
This is a Phase 3, randomized, double-blind, placebo-controlled, parallel group, study evaluating 
the long-term safety and tolerability of ETC-1002 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-lowering therapy 
includes a maximally tolerated statin alone or in combination with other lipid-lowering therapies 
(eg, ezetimibe, fibrates [except gemfibrozil], evolocumab, and alirocumab). 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. However, patients currently taking high-dose statins, defined as rosuvastatin 
40 mg, atorvastatin 80 mg, or simvastatin 80 mg per day, or who are currently taking a PCSK9 
inhibitor (alirocumab or evolocumab), or have taken a PCSK9 inhibitor within the past 4 weeks 
of Week -2 (Visit S1) will be excluded from enrolling in this study. PCSK9 inhibitors may be 
initiated as adjunctive therapy at Week 24 if the LDL-C threshold criteria have been met as 
described in Section 11.1.6.3.5.  

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 138 of 287 
CHANGE 31 TYPOGRAPHICAL AND FORMATTING 
Location: 
6.1 
Overall Study Design 
Table 2, footnotes 
Original Text: 
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) 
b Atorvastatin 80 mg is not allowed in this study 
c Rosuvastatin 40 mg is not allowed in this study 
d Simvastatin 40 mg is not allowed in this study 
New Text: 
Note: The highest dose statins are allowed if given on less than a daily basis. 
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) 
b Atorvastatin 80 mg daily is not allowed in this study.  
c Rosuvastatin 40 mg daily is not allowed in this study 
d Simvastatin 40-80 mg daily is not allowed in this study 
CHANGE 32 TYPOGRAPHICAL AND FORMATTING 
Location: 
6.1 
Overall Study Design 
Table 3, footnotes 
Original Text: 
ASCVD = Atherosclerotic cardiovascular diseases; HeFH = Heterozygous familial hypercholesterolemia. 
a Atorvastatin 80 mg, rosuvastatin 40 mg, and simvastatin 40 mg are not allowed in this study. 
New Text: 
ASCVD = Atherosclerotic cardiovascular diseases; HeFH = Heterozygous familial hypercholesterolemia. 
a Atorvastatin 80 mg, rosuvastatin 40 mg, and simvastatin 40-80 mg daily are not allowed in this study. 
CHANGE 33 DEFINITIION OF CLINICAL ENDPOINTS 
Location: 
6.1 
Overall Study Design 
Original Text: 
An independent expert Data Monitoring Committee (DMC) will formally review accumulating 
unblinded safety data from this and other ongoing studies of ETC-1002. All CV events, 
including death, will be adjudicated by an independent blinded expert Clinical Events Committee 
(CEC), using standardized definitions. Until the CEC has been established, CV events will be 
reported as both SAE and major adverse cardiovascular events and mortality (MACE). 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 139 of 287 
New Text: 
An independent expert Data Monitoring Committee (DMC) will formally review accumulating 
unblinded safety and efficacy data from this and other ongoing studies of ETC-1002. All CV 
events clinical endpoints, including all major 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), will be adjudicated by an independent blinded 
expert Clinical Events Committee (CEC), using standardized definitions. Until the CEC has been 
established, CV Any clinical endpoints that meet SAE criteria will be reported as bothSAEs and 
major adverse cardiovascular events and mortality (MACE). 
CHANGE 34 TYPOGRAPHICAL AND FORMATTING 
Location: 
6.2 
Study Hypothesis 
Original Text: 
The study will characterize the long-term safety and tolerability of ETC-1002 versus placebo in 
addition to maximally tolerated lipid-lowering therapy, including a maximally tolerated statin, in 
patients with hyperlipidemia. The randomized, double-blind, placebo controlled add-on to 
maximally tolerated lipid-lowering therapy design will ensure that long-term safety data are 
meaningful and interpretable. The extended treatment duration (52 weeks) and large patient 
number (n = 900) will provide robust long-term safety in high CV risk patients who have an 
unmet medical need for additional lipid-lowering therapy, such as ETC-1002 once daily, orally 
bioavailable option. 
New Text: 
The study will characterize the long-term safety and tolerability of ETC-1002 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 long-term safety data are meaningful and interpretable. The 
extended treatment duration (52 weeks) and large patient number (n = 900) will provide robust 
long-term safety in high CV risk patients who have an unmet medical need for additional lipid-
lowering therapy, such as ETC-1002 once daily, orally bioavailable option. 
CHANGE 35 CLARIFICATION OF DURATION OF TREATMENT AND END OF 
STUDY 
Location: 
6.3 
End of Study 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 140 of 287 
Original Text: 
The study will end when the last randomized patient completes 52 weeks of treatment (last 
patient last visit [LPLV] for last randomized patient). The estimated overall duration of the study 
(first patient first visit [FPFV] to LPLV) is approximately 22 months. 
New Text: 
The study will end when the last randomized patient completes 52 weeks of their last study visit 
treatment (last patient last visit [LPLV] for last randomized patient). The estimated overall 
duration of the study (first patient first visit [FPFV] to LPLV) is approximately 22 months. 
CHANGE 36 REVISED INCLUSION/EXCLUSION CRITERIA 
Location: 
7.1 
Subject Inclusion Criteria 
Original Text: 
5. Be on maximally tolerated lipid-modifying therapy, including a maximally tolerated 
statin, at a stable dose for at least 4 weeks prior to screening (6 weeks for fibrates; 
however, gemfibrozil is not allowed). Regimens other than daily dosing, including those 
at very low doses, are acceptable. 
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. 
New Text: 
5. Be on maximally tolerated lipid-modifying therapy, including a maximally tolerated 
statin either alone or in combination with other lipid-lowering therapies, at a stable doses 
for at least 4 weeks prior to screening (6 weeks for fibrates; however, gemfibrozil is not 
allowed). Regimens other than daily dosing, including those at very low doses, are 
acceptable. 
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. 
CHANGE 37 REVISED INCLUSION/EXCLUSION CRITERIA 
Location: 
7.2 
Subject Exclusion Criteria 
Original Text: 
4. Concomitant use of high-dose statins, defined as rosuvastatin 40 mg, atorvastatin 80 mg, 
or simvastatin 40 or 80 mg 
5. Recent (within 3 months prior to the screening visit [Week -2 (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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 141 of 287 
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. 
6. Current clinically significant cardiovascular disease, including but not limited to: 
• New York Heart Association (NYHA) Functional Classification Class III or IV heart 
failure 
• 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 2 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, or 
7. Hemoglobin A1C (HbA1C) ≥10% at Week -2 (Visit S1) 
8. History of chronic, unstable musculoskeletal symptoms that may require changes in 
background medications or, in the opinion of the Investigator, may confound an 
evaluation of AEs associated with muscle symptoms. Patients with stable 
musculoskeletal diseases on stable therapy may enroll at the discretion of the 
Investigator. 
9. Uncontrolled hypothyroidism, including thyroid-stimulating hormone (TSH) >1.5 × the 
upper limit of normal (ULN) at Week -2 (Visit S1). Patients stabilized on thyroid 
replacement therapy for at least 6 weeks prior to randomization are allowed. 
10. Liver disease or dysfunction, including:  
• Positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C 
antibodies (HCV-AB) at Week -2 (Visit S1); or 
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≥1.5 × ULN, 
and/or total bilirubin (TB) ≥1.2 × ULN at Week -2 (Visit S1).  
Note: At the discretion of the investigator, the screening period may be extended up 
to 2 weeks for a single repeat of ALT, AST, and/or TB. For those patients who have a 
repeat ALT, AST, and/or TB, the repeat value will be used to determine eligibility. 
11. Gastrointestinal conditions or procedures (including weight loss surgery; eg, Lap-Band® 
or gastric bypass) that may affect drug absorption 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 142 of 287 
12. Hematologic or coagulation disorders or a hemoglobin (Hgb) level <12.0 g/dL (120 g/L) 
at Week -2 (Visit S1) 
13. History of Acquired Immunodeficiency Syndrome or a positive test for human 
immunodeficiency virus (HIV) 
14. 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) 
15. 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.  
16. 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. 
17. Blood donation, participation in a clinical study with multiple blood draws, major trauma, 
or surgery with or without blood loss within 30 days prior to randomization 
18. Blood transfusion for any reason within 90 days prior to randomization 
19. Use of any experimental or investigational drugs within 30 days prior to screening or 
5 half-lives, whichever is longer 
20. Prior participation in a previous ETC-1002 clinical study. Prior participation in a clinical 
study with ETC-1002 is defined as having been enrolled in an ETC-1002 study. 
21. 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  
• Requirement for mipomersen or lomitapide or apheresis therapy 
22. 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 (6 months prior to randomization 
23. Any current condition, laboratory finding, family history, or electrocardiogram (ECG) 
finding that in either the Investigator’s, Sponsor’s, or authorized Medical Monitor’s 
opinion may compromise patient safety or ability to complete the study or interfere with 
study data interpretation 
24. An employee or contractor of the facility conducting the study, or a family member of the 
Principal Investigator, Co-Investigator, or Sponsor. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 143 of 287 
New Text: 
4. Concomitant use of high-dose statins, defined as rosuvastatin 40 mg, atorvastatin 80 mg, 
or simvastatin 40 or 80 mg daily 
5. Concomitant use of a PCSK9 inhibitor (Praluent® [alirocumab] or Repatha® 
[evolocumab]) at Week -2 (Visit S1) or prior use of a PCSK9 inhibitor within the past 
4 weeks of Week -2 (Visit S1) will be excluded from this study. 
Note: Patients are allowed to initiate a PCSK9 inhibitor as adjunctive therapy at 
Week 24 if the LDL-C threshold criteria have been met as described in 
Section 11.1.6.3.5. 
56. Recent (within 3 months prior to the screening visit [Week -2 (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. 
• Current clinically significant cardiovascular disease, including but not limited to:New 
York Heart Association (NYHA) Functional Classification Class III or IV heart 
failure 
•7. 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 2 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, or 
8. Hemoglobin A1C (HbA1C) ≥10% at Week -2 (Visit S1) 
9. History of chronic, unstable musculoskeletal symptoms that may require changes in 
background medications or, in the opinion of the Investigator, may confound an 
evaluation of AEs associated with muscle symptoms. Patients with stable 
musculoskeletal diseases on stable therapy may enroll at the discretion of the 
Investigator. 
9. Uncontrolled hypothyroidism, including thyroid-stimulating hormone (TSH) >1.5 × the 
upper limit of normal (ULN) at Week -2 (Visit S1). Patients stabilized on thyroid 
replacement therapy for at least 6 weeks prior to randomization are allowed. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 144 of 287 
10. Liver disease or dysfunction, including:  
• Positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C 
antibodies (HCV-AB) at Week -2 (Visit S1); or 
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≥1.5 × ULN, 
and/or total bilirubin (TB) ≥1.2 × ULN at Week -2 (Visit S1).  
Note: At the discretion of the investigator, the screening period may be extended up to 
2 weeks for a single repeat of ALT, AST, and/or TB. For those patients who have a 
repeat ALT, AST, and/or TB, the repeat value will be used to determine eligibility. 
11. Gastrointestinal conditions or procedures (including weight loss surgery; eg, Lap-Band® 
or gastric bypass) that may affect drug absorption 
12. Hematologic or coagulation disorders or a hemoglobin (Hgb) level <1210.0 g/dL 
(120100 g/L) at Week -2 (Visit S1) 
13. History of Acquired Immunodeficiency Syndrome or a positive test for human 
immunodeficiency virus (HIV) 
13. 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) 
14. 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.  
15. 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. 
16. Blood donation, participation in a clinical study with multiple blood draws, major trauma, 
or surgery with or without blood loss within 30 days prior to randomization 
17. Blood transfusion for any reason within 90 days prior to randomization 
18. Use of any experimental or investigational drugs within 30 days prior to screening or 
5 half-lives, whichever is longer 
19. Prior participation in a previous ETC-1002 clinical study. Prior participation in a clinical 
study with ETC-1002 is defined as having been enrolled in an ETC-1002 study. 
20. 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  
• Requirement for mipomersen or lomitapide or apheresis therapy 
21. 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) 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Summaiy of Changes Amendment 1 
Amendment 5, 10 May 2017 
• 
Thyroid replacement ( 6 weeks prior to randomization) 
• 
Diabetes medications ( 4 weeks prior to randomization) 
• 
Obesity medication ( 6 months prior to randomization 
22. ,'\By eat'reftt eeBat.tiea, la.eent-tery fH'laiBg, Family B-istery, er eleetreearat.egntIB (BCGJ 
fiBatBg that is eitlier tlie mvestigater's, £J3easer's, er a.t1tlierizea Meaieel Meaiter's 
eJ3iB-ieB Hifr)' eeHifJremise J3atieBt sa.fety er e:eihty te eeHifJlete tfte stt-Iay er iBtet-fere witli 
stl-lay SM8: iflte1']3retatieB 
22. An employee or contractor of the facility conducting the study, or a fainily member of the 
Principal Investigator, Co-Investigator, or Sponsor. 
CHANGE 38 CLARIFICATION OF IMP 
Location: 
8.1 
Description of IMP 
Table 4 
Original T ex.t: 
Investigational Medicinal Product 
Product Name: 
Dosage Form: 
Unit Dose: 
Container/Closure 
Route of Administration: 
Physical Description: 
Manufacturer (Fill/Finish): 
Confidential 
ETC-1002 
Film-coated tablets 
180mg 
35 and/or 100 count bottle 
( depending upon visit) with 
screw on, non-child proof cap 
Oral, daily in the morning, with 
or without food 
Oval, white to off-while film-
coated tablet debossed with 
"ABC" on one face and debossed 
with "000" on the opposite face 
Page 145 of287 
Placebo 
Film-coated tablets 
Not applicable 
35 and/or 100 count bottle 
( depending upon visit) with 
screw on, non-child proof cap 
Oral, daily in the morning, with 
or without food 
Oval, white to off-while film-
coated tablet debossed with 
"ABC" on one face and debossed 
with "000" on the opposite face 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Summaiy of Changes Amendment 1 
Amendment 5, 10 May 2017 
New Text: 
Investigational Medicinal Product 
Product Name: 
Dosage Form: 
Unit Dose: 
Container/Closure
0 
Route of Administration: 
Physical Description: 
Manufacturer (Fill/Finish): 
ETC-1002 
Film-coated tablets 
180mg 
35- and/or 100-coWlt bottle 
( depending upon visit) with 
screw on, non-child proof cap 
Oral, daily in the morning, with 
or without food 
Oval, white to off-while film-
coated tablet debossed with 
"ABC" on one face and debossed 
with "000" on the opposite face 
Placebo 
Film-coated tablets 
Not applicable 
35- and/or 100-coWlt bottle 
( depending upon visit) with 
screw on, non-child proof cap 
Oral, daily in the morning, with 
or without food 
Oval, white to off-while film-
coated tablet debossed with 
"ABC" on one face and debossed 
with "000" on the opposite face 
0 A 100-day supply of IMP will be included in the 100-count bottle and a 35-day supply of IMP will be included in 
the 35-count bottle. 
CHANGE 39 ADDITION OF PROTOCOL REQUIREMENTS TO ADDRESS THE 
AVAILABILITY OF PCSK9 INHIBITORS 
Location: 
8.2.1 
Lipid-Regulating Medications and Supplements 
Original Text: 
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. Use of fibrates must be stable at least 
6 weeks prior to screening. Gemfibrozil, a fibrate, is prohibited. Stable lipid-modifying 
therapy(s) includes, but is not limited to, monotherapies or combination therapies containing the 
compounds below: 
Confidential 
Page 146 of 287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 147 of 287 
Statins 
• Atorvastatin (Lipitor®, Sortis®), with doses <80 mg 
• Fluvastatin (Lescol®) 
• Lovastatin (Mevacor®, Altoprev™) 
• Pravastatin (Pravachol®) 
• Pitavastatin (Livalo®, Lipostat®) 
• Rosuvastatin (Crestor®), with doses <40 mg 
• Simvastatin (Zocor®), with doses <40 mg 
Selective cholesterol and/or bile acid absorption inhibitors 
• Cholestyramine/Colestryamine (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®) 
Other 
• Simvastatin/ezetimibe (Vytorin®, Inegy®) with dose of simvastatin <40 mg 
• Lovastatin/niacin (Advicor®) 
• Simvastatin/niacin (Simcor®) with dose of simvastatin<40 mg 
• Atorvastatin/ezetimibe (Liptruset®, Atozet®) with dose of atorvastatin <80 mg 
New Text: 
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. Use of fibrates must be stable at least 
6 weeks prior to screening. Gemfibrozil, a fibrate, is prohibited. Patients may not currently be 
taking or have taken a PCSK9 inhibitor within 4 weeks prior to Screening (Week -2, Visit S1); 
however, they may be allowed to initiate a PCSK9 inhibitor as adjunctive therapy at Week 24 if 
the LDL-C threshold criteria have been met as described in Section 11.1.6.3.5. Stable lipid-
modifying therapy(s) includes, but is not limited to, monotherapies or combination therapies 
containing the compounds below: 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 148 of 287 
Statins 
• Atorvastatin (Lipitor®, Sortis®), with doses <80 mg 
• Fluvastatin (Lescol®) 
• Lovastatin (Mevacor®, Altoprev™) 
• Pravastatin (Pravachol®) 
• Pitavastatin (Livalo®, Lipostat®) 
• Rosuvastatin (Crestor®), with doses <40 mg 
• Simvastatin (Zocor®), with doses <40 mg 
Selective cholesterol and/or bile acid absorption inhibitors 
• Cholestyramine/Colestryaminery (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 (allowed as adjunctive therapy beginning at Week 24 [Visit T5]; see 
Section 11.1.6.3.5) 
• Alirocumab (Praluent®) 
• Evolocumab (Repatha®) 
Other 
• Simvastatin/ezetimibe (Vytorin®, Inegy®) with dose of simvastatin <40 mg 
• Lovastatin/niacin (Advicor®) 
• Simvastatin/niacin (Simcor®) with dose of simvastatin<40 mg 
• Atorvastatin/ezetimibe (Liptruset®, Atozet®) with dose of atorvastatin <80 mg 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 149 of 287 
CHANGE 40 ADDITION OF PROTOCOL REQUIREMENTS TO ADDRESS THE 
AVAILABILITY OF PCSK9 INHIBITORS 
Location: 
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. 
• Gemfibrozil (Lopid®)  
• Cholestin (red yeast rice, also known as monascus purpureus extract) 
• Atorvastatin (Lipitor®, Sortis®) 80 mg, Simvastatin (Zocor®) 40-80 mg, and 
Rosuvastatin (Crestor®) 40 mg alone or in fixed-dose combinations (eg, Liptruzet®, 
Vytorin®/Inegy®, Simcor®) 
New 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. 
• Gemfibrozil (Lopid®)  
• Cholestin (red yeast rice, also known as monascus purpureus extract) 
• Atorvastatin (Lipitor®, Sortis®) 80 mg, Simvastatin (Zocor®) 40-80 mg, and 
Rosuvastatin (Crestor®) 40 mg alone or in fixed-dose combinations (eg, Liptruzet®, 
Vytorin®/Inegy®, Simcor®) 
Patients will not have used the medications listed below within 4 weeks prior to screening: 
• Alirocumab (Praluent®) 
• Evolocumab (Repatha®) 
• Note: Patients may be allowed to initiate a PCSK9 inhibitor as adjunctive therapy at 
Week 24 if the LDL-C threshold has been met as described in Section 11.1.6.3.5. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 150 of 287 
CHANGE 41 ADDITION OF PROTOCOL REQUIREMENTS TO ADDRESS THE 
AVAILABILITY OF PCSK9 INHIBITORS 
Location: 
8.2.3 
Allowable Medications 
Original Text: 
Other concomitant medication must be stable for 2 weeks 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 used for 
the purposes of lipid lowering  
• Diabetes medications 
The following must be stable for a minimum of 6 months prior to screening and, if possible not 
be adjusted during the study except for reasons of safety: 
• Antiobesity medications 
New Text: 
Other concomitant medication must be stable for 2 weeks 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 used for 
the purposes of lipid lowering  
• Diabetes medications 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 151 of 287 
The following must be stable for a minimum of 6 months prior to screening and, if possible not 
be adjusted during the study except for reasons of safety: 
• Antiobesity medications 
The following may not be taken within 4 weeks of Screening (Week -2, Visit S1), but may be 
initiated beginning at Week 24 if LDL-C threshold criteria have been met and it is needed as 
adjunctive LDL-C-lowering therapy. 
• Alirocumab (Praluent®) 
• Evolocumab (Repatha®) 
CHANGE 42 UPDATE CLINICAL LABORATORY PARAMETERS 
Location: 
8.4 
Blinding 
Original Text: 
Postrandomization values for individual laboratory measures for LDL-C, TG, apoB, and hs-CRP, 
including any plasma concentration of ETC-1002 and its metabolite, that may inadvertently 
suggest treatment assignment will not be available to personnel from the clinical site, the patient, 
the Sponsor, 
 
New Text: 
Postrandomization values for individual laboratory measures for LDL-C, TG, TC, HDL-C, non-
HDL, apoB, and hs-CRP, including any plasma concentration of ETC-1002 and its metabolite, 
that may inadvertently suggest treatment assignment will not be available to personnel from the 
clinical site, the patient, the Sponsor, and 
 
CHANGE 43 DEFINITION OF CLINICAL ENDPOINTS 
Location: 
8.4 
Blinding 
Original Text: 
An independent blinded expert CEC will adjudicate all CV events, including death, using 
standardized definitions. Until the CEC has been established, CV events will be reported as both 
SAE and MACE. Additional details and definitions will be provided in a CEC Charter. 
An independent DMC will monitor unblinded accumulating patient safety 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 information 
from ongoing studies will be provided to the DMC by an independent, unblinded 
 
programmer and statistician. Additional details will be provided in a DMC Charter. 
New Text: 
An independent blinded expert CEC will adjudicate all CV eventsclinical endpoints, including 
death, using standardized definitions. Clinical endpoints will also be reported as SAEs.Until the 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 152 of 287 
CEC has been established,CV events will be reported as both SAE and MACE. 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 
 programmer and statistician. Additional details will be provided in a DMC 
Charter. 
CHANGE 44 CLARIFICATION OF IMP 
Location: 
8.4 
Blinding 
Original Text: 
Double-blind IMP will be dispensed in 90 day supply increments (one 90-day supply bottle) to 
patients by appropriate clinical site personnel at Week 0 (Visit T1), Week 12 (Visit T4), and 
Week 24 (Visit T5). Double-blind IMP will be dispensed in 125-day supply increments 
(2 bottles; one 90-day supply bottle and one 35-day supply bottle) to patients at Week 36 
(Visit T6). 
New Text: 
Double-blind IMP will be dispensed in 90100 day supply increments (one 90100-day supply 
bottle) to patients by appropriate clinical site personnel at Week 0 (Visit T1), Week 12 
(Visit T4), and Week 24 (Visit T5). Double-blind IMP will be dispensed in 125135-day supply 
increments (2 bottles; one 90100-day supply bottle and one 35-day supply bottle) to patients at 
Week 36 (Visit T6). 
CHANGE 45 UPDATED STUDY PROCEDURES AND SCHEDULE OF EVENTS 
Location: 
10.2.1 
Screening Week -2 (Visit S1; Days -16 to -4) 
Original Text: 
The screening period will begin with a screening visit that will occur 2 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), waist circumference (cm), BMI  
• Vital signs  

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 153 of 287 
• 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  
− Serum pregnancy test (on appropriate female patients) 
• Serology (including HBsAg, HCV)  
• Review of all inclusion/exclusion criteria that can be assessed at this time 
• Conduct diet and exercise counseling 
• Contact IWRS to register the patient  
Patients who meet all enrollment criteria that can be assessed 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 entry criterion. If this optional visit is completed, the mean of lipid values 
from both visits will be used to determine eligibility. 
• 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, they have been on stable doses of blood 
pressure medications for at least 2 weeks, and the repeat blood pressure values (DBP 
and/or SBP) no longer meet exclusionary values. 
• An optional visit between Visits 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. 
• 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. 
New Text: 
The screening period will begin with a screening visit that will occur 2 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: 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 154 of 287 
• Demographics 
• Clinically relevant medical history, including assessment of HeFH status and ASCVD  
• Concomitant and prohibited medication review 
• Height (cm), weight (kg), waist circumference (cm),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)  
• 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 to 
meet a lipid entry criterion. If this optional visit is completed, the mean of lipid values 
from both visits will be used to determine eligibility. 
• An optional visit between Visits S1 and T1 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 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, they have been on stable doses of blood 
pressure medications for at least 2 weeks, and the repeat blood pressure values (DBP 
and/or SBP) no longer meet exclusionary values. 
• An optional visit between Visits 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. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 155 of 287 
• 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. 
CHANGE 46 UPDATED STUDY PROCEDURES AND SCHEDULE OF EVENTS 
Location: 
10.2.2 
Treatment Week 0 (Visit T1; Days 1) 
Original Text: 
The patient will undergo the following assessments and procedures at (Visit T1) 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs (starting from signing the informed consent document) 
• Physical examination (PE) 
• Weight 
• 12-Lead ECG 
• 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) 
- apoB 
- HbA1C  
- Insulin 
- hs-CRP 
- Reserve sample 
• 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 
• Schedule next visit 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 156 of 287 
New Text: 
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 ECG 
• 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) 
- apoB 
- HbA1C  
- Insulin 
- hs-CRP 
- Reserve sample 
• 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 
• Schedule next visit 
CHANGE 47 UPDATED STUDY PROCEDURES AND SCHEDULE OF EVENTS 
Location: 
10.2.3 
Treatment Week 4 (Visit T2; ± 3 days) 
Original Text: 
Patients will undergo the following assessments and procedures at Week 4 (Visit T2): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (ongoing) 
• Weight 
• Vital signs 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 157 of 287 
• 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 
• Return IMP container from Visit T1 to patient for continued dosing and provide 
dosing instruction 
• Schedule next visit 
New Text: 
Patients will undergo the following assessments and procedures at Week 4 (Visit T2): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (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 
• Return 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. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 158 of 287 
CHANGE 48 UPDATED STUDY PROCEDURES AND SCHEDULE OF EVENTS 
Location: 
10.2.4 
Treatment Week 8 (Visit T3; ± 3 days) 
Original Text: 
Note: If this visit is being conducted at the site for patients who have consented to be followed 
for safety assessments 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 and current health status. 
New Text: 
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 medications, and current 
health status. 
CHANGE 49 UPDATED STUDY PROCEDURES AND SCHEDULE OF EVENTS 
Location: 
10.2.5 
Treatment Week 12 (Visit T4; ± 3 days) 
Original Text: 
Patients will undergo the following assessments and procedures at Week 12 (Visit T4): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (ongoing) 
• Weight 
• 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) 
− apoB 
− HbA1C 
− Insulin 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 159 of 287 
− hs-CRP 
− PK sample 
− Reserve 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  
• Schedule next visit 
Note: If this visit is being conducted at the site for patients who have consented to be 
followed for safety assessments after withdrawing from IMP treatment, all assessments 
except for those procedures pertaining to apoB, hs-CRP, PK samples, reserve 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 and current health 
status. 
New Text: 
Patients will undergo the following assessments and procedures at Week 12 (Visit T4): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (ongoing) 
• Weight 
• 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) 
− apoB 
− HbA1C 
− Insulin 
− hs-CRP 
− PK sample 
− Reserve sample  
• Conduct diet and exercise counseling 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 160 of 287 
• Return of IMP; assessment and recording of IMP compliance 
• IWRS contact to obtain the MED ID number for IMP 
• Dispense IMP  
• 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, reserve 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. 
CHANGE 50 UPDATED STUDY PROCEDURES AND SCHEDULE OF EVENTS 
Location: 
10.2.6 
Treatment Week 24 (Visit T5; ± 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, including muscle-related AEs (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 
− Insulin 
− hs-CRP 
− PK sample 
− Reserve 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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 161 of 287 
• Dispense IMP  
• Schedule next visit 
Note: If this visit is being conducted at the site for patients who have consented to be 
followed for safety assessments after withdrawing from IMP treatment, all assessments 
except for those procedures pertaining to apoB, hs-CRP, PK samples, reserve samples, 
and IMP (IMP dispensing, IMP compliance, IMP accountability) management 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 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, including muscle-related AEs (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 
− Insulin 
− hs-CRP 
− PK sample 
− Reserve 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  
• 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, 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 162 of 287 
PK samples, reserve samples, and IMP (IMP dispensing, IMP compliance, IMP 
accountability) management 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. 
CHANGE 51 UPDATED STUDY PROCEDURES AND SCHEDULE OF EVENTS 
Location: 
10.2.7 
Treatment Week 36 (Visit T6; ± 3 days) 
Original Text: 
Note: If this visit is being conducted at the site for patients who have consented to be 
followed for safety assessments 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 and current health 
status. 
New Text: 
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 
medications, and current health status. 
CHANGE 52 UPDATED STUDY PROCEDURES 
Location: 
10.2.8 
Treatment Week 52 (Visit T7; ± 7 days) 
Original Text: 
Patients will undergo the following assessments and procedures at Week 52 (Visit T7): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (ongoing) 
• PE 
• Weight 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 163 of 287 
• 12-Lead ECG 
• 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) 
− apoB 
− HbA1C 
− Insulin 
− 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) 
Note: For patients who withdraw from IMP treatment: 
− Determine whether the patient will or will not consent for follow-up visits through 
study completion 
− If the patient provides consent to continue to be followed for safety assessments 
per the protocol visit schedule, schedule follow-up visits as they would have 
occurred if the patient were continuing in the study and complete the visit 
required procedures listed in the appropriate visit specific section within 
Section 10 and Appendix 1. No further IMP will be dispensed for patients who 
withdraw from IMP treatment. 
− If the patient does not provide consent to be followed for safety assessments per 
the protocol (either by returning to clinic or by phone), this visit (Visit T7) will be 
considered the EOS/Early Withdrawal from study visit and no further visits will 
be scheduled. 
Note: If this visit is being conducted at the site for patients who have consented to be 
followed for safety assessments after withdrawing from IMP treatment, all assessments 
except for those procedures pertaining to apoB, hs-CRP, PK samples, reserve samples, 
and IMP (IMP dispensing, IMP compliance, IMP accountability) management 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 and current health 
status. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 164 of 287 
New Text: 
Patients will undergo the following assessments and procedures at Week 52 (Visit T7): 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (ongoing) 
• PE 
• Weight 
• 12-Lead ECG 
• 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) 
− apoB 
− HbA1C 
− Insulin 
− 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) 
Note: For patients who withdraw from IMP treatment: 
− Capture the reason for withdrawing from IMP treatment and record on the eCRF 
− Determine whether the patient will or will not consent for follow-up visits through 
study completion 
− If the patient provides consent to continue to be followed for safety assessments 
per the protocol visit schedule, schedule follow-up visits as they would have 
occurred if the patient were continuing in the study and complete the visit 
required procedures listed in the appropriate visit specific section within 
Section 10 and Appendix 1. No further IMP will be dispensed for patients who 
withdraw from IMP treatment. 
− If the patient does not provide consent to be followed for safety assessments per 
the protocol (either by returning to clinic or by phone), this visit (Visit T7) will be 
considered the EOS/Early Withdrawal from study visit and no further visits will 
be scheduled. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 165 of 287 
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, reserve samples, and IMP (IMP dispensing, IMP compliance, IMP 
accountability) management 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. 
CHANGE 53 ADDED INSTRUCTIONS FOR SUBJECT WITHDRAWAL AND 
RESTARTING IMP 
Location: 
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 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).  
Patients who do not provide consent 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 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. 
New Text: 
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).  
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. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 166 of 287 
Patients who do not provide consent 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. 
CHANGE 54 ADDED INSTRUCTION FOR SUBJECT WITHDRAWAL AND 
RESTARTING IMP 
Location: 
10.3.2 
Procedures for Early Withdrawal 
Original Text:  
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 through Week 52 (Visit T7). 
New Text: 
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). 
CHANGE 55 UPDATED STUDY PROCEDURES AND SCHEDULE OF EVENTS 
Location: 
11.1.3 
Weight, Height, and Body Mass Index 
Original Text: 
11.1.3 
Weight, Height, Waist Circumference, and Body Mass Index 
Weight will be measured on a calibrated scale in the morning while fasted and after voiding. 
Body weight will be measured in the morning while fasting, using consistent scales, after 
voiding, and without shoes and outerwear (eg, coats).  
Waist circumference will be measured around the bare abdomen just above the hipbone. Tape 
should be snug (but not compress skin) and parallel to the floor. The patient should be asked to 
relax and exhale prior to measurement. 
New Text: 
11.1.3 
Weight, Height, Waist Circumference, and Body Mass Index 
Weight will be measured on a calibrated scale in the morning while fasted and after voiding. 
Body weight will be measured in the morning while fasting, using consistent scales, after 
voiding, and without shoes and outerwear (eg, coats).  

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 167 of 287 
Waist circumference will be measured around the bare abdomen just above the hipbone. Tape 
should be snug (but not compress skin) and parallel to the floor. The patient should be asked to 
relax and exhale prior to measurement. 
CHANGE 56 UPDATE CLINICAL LABORATORY PARAMETERS 
Location: 
11.1.6.1 
Laboratory Parameters (Safety) 
Table 5 
Original Text: 
Clinical Laboratory Test 
Clinical Laboratory Test 
• 
Hematology 
Blood Chemistry (serum, fasting) 
• 
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 values only 
• 
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 
• 
Insulin 
• 
Lactate dehydrogenase (LDH) 
• 
Phosphorus 
• 
Potassium (K) 
• 
Sodium (Na) 
• 
Total and direct bilirubin (TB) 
• 
Total protein 
• 
Uric acid 
Urinalysis (Dipstick) 
• 
Clarity 
• 
Bilirubin 
• 
Color 
• 
Glucose 
• 
Ketones 
• 
Leukocyte esterase 
• 
Nitrate 
• 
Occult blood 
• 
pH 
• 
Protein 
• 
Specific gravity 
• 
Urobilinogen 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 168 of 287 
Clinical Laboratory Test 
Clinical Laboratory Test 
Urinalysis (Microscopic)-only if urine dipstick 
abnormal 
Coagulation  
• 
Bacteria 
• 
Casts 
• 
Crystals 
• 
Epithelial cells 
• 
Red blood cell (RBC) 
• 
WBC 
• 
Prothrombin time (PT) 
• 
Activated partial thromoboplastin time 
(aPTT) 
• 
International normalized ration (INR) 
Other Screening Labs 
Additional samples 
• 
Hepatitis B surface antigen (HBsAg), 
hepatitis C virus (HCV), Serum 
pregnancy test (only for females of 
childbearing potential) 
• 
Thyroid-stimulating hormone (TSH) 
• 
Hemoglobin A1C (HbA1C) 
• 
Reserve blood samples for potential 
future measurement of ETC-1002 safety 
or pharmacodynamic biomarkers 
• 
PK sample  
• 
Reserve genetic blood sample (optional) 
New Text: 
Clinical Laboratory Test 
Clinical Laboratory Test 
• 
Hematology 
Blood Chemistry (serum, fasting) 
• 
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 values onlyand %) 
• 
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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 169 of 287 
Clinical Laboratory Test 
Clinical Laboratory Test 
Urinalysis (Dipstick) 
• 
Clarity 
• 
Bilirubin 
• 
Color 
• 
Glucose 
• 
Ketones 
• 
Leukocyte esterase 
• 
Nitrate 
• 
Occult blood 
• 
pH 
• 
Protein 
• 
Specific gravity 
• 
Urobilinogen 
 
Clinical Laboratory Test 
Clinical Laboratory Test 
Urinalysis (Microscopic)-only if urine dipstick 
abnormal 
Coagulation  
• 
Bacteria 
• 
Casts 
• 
Crystals 
• 
Epithelial cells 
• 
Red blood cell (RBC) 
• 
WBC 
• 
Prothrombin time (PT) 
• 
Activated partial thromoboplastin time 
(aPTT) 
• 
International normalized ration (INR) 
Other Screening Labs 
Additional samples 
• 
Hepatitis B surface antigen (HBsAg), 
hepatitis C virus (HCV) 
• 
Serum pregnancy test (only for females 
of childbearing potential) 
• 
Follicle-stimulating hormone (FSH; 
Females <55 years and >1 year without 
menses) 
• 
Thyroid-stimulating hormone (TSH) 
• 
Hemoglobin A1C (HbA1C) 
• 
Reserve blood samples for potential 
future measurement of ETC-1002 safety 
or pharmacodynamic biomarkers 
• 
PK sample  
• 
Reserve genetic blood sample (optional) 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 170 of 287 
CHANGE 57 REVISED SAFETY MONITORING AND MANAGEMENT 
INSTRUCTIONS 
Location: 
11.1.6.3 
General Monitoring and Management of Abnormal Clinical Labs 
Original Text: 
It is the Investigator’s responsibility to review the results of all laboratory tests as they become 
available and to sign and date the review. For each laboratory test outside of the laboratory 
normal range, the Investigator needs to ascertain if this is a clinically significant change from 
baseline for the individual patient, 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. 
New Text: 
It is the Investigator’s responsibility to review the results of all laboratory tests as they become 
available and to sign and date the report to document their review. For each laboratory test 
outside of the laboratory normal range, the Investigator needs to ascertain if this is a clinically 
significant change from baseline for the individual patient, 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. 
CHANGE 58 REVISED SAFETY MONITORING AND MANAGEMENT 
INSTRUCTIONS 
Location: 
11.1.6.3.2 Monitoring and Management of Elevated Serum Creatinine 
Original Text: 
If at any time after randomization a patient experiences a marked creatinine elevation 
>1.0 mg/dL (44 µmol/L) above 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.  
If repeat creatinine assessment confirms serum creatinine >1.0 mg/dL (44 µmol/L) above ULN 
or MDRD creatinine clearance (CrCL) <30 mL/min), 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) 
New Text: 
If at any time after randomization a patient experiences a marked creatinine elevation 
>1.0 mg/dL (44 µmol/L) above 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.  
If at any time after randomization, a patient experiences a decrease in repeat creatinine 
assessment confirms serum creatinine >1.0 mg/dL (44 µmol/L) above ULN or MDRD creatinine 
clearance (CrCLeGFR to the level of) <30 15 mL/min/1.73 m2) or if the patient experiences 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 171 of 287 
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) 
CHANGE 59 REVISED SAFETY MONITORING AND MANAGEMENT 
INSTRUCTIONS 
Location: 
11.1.6.3.3 Monitoring and Management of Hemoglobin Change 
Original Text: 
If at any time after randomization a patient experiences Hgb <10 g/dL (100 g/L) and/or 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 Hgb <10 g/dL (100 g/L) and/or 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. 
New Text: 
If at any time after randomization a patient experiences Hgb <10 g/dL (100 g/L) and/or 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 Hgb <10 g/dL (100 g/L) and/or 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. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 172 of 287 
CHANGE 60 REVISED SAFETY MONITORING AND MANAGEMENT 
INSTRUCTIONS 
Location: 
11.1.6.3.4 Monitoring and Management of Elevated Creatine Kinase 
Original Text: 
If at any time after randomization a patient experiences a marked CK elevation >5 × ULN, the 
patient will undergo repeat confirmatory assessment as soon as is reasonably possible, preferably 
within 3 to 7 days of the laboratory result becoming available.  
Repeat CK assessment will include query for related symptoms.  
• If the repeat CK assessment confirms an unexplained (ie, not associated with recent 
trauma or physically strenuous activity) CK abnormality >5 × ULN, if asymptomatic 
the investigator with input from the Sponsor may consider continuing study 
medication with continued CK assessments every 1-2 weeks. If symptomatic, 
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:  
− >5 × ULN that is associated with symptoms of muscle pain, muscle weakness, or 
dark urine; or  
− >10 × ULN, even in the absence of symptoms.  
• 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). 
New Text: 
If at any time after randomization a patient experiences a marked CK elevation >5 × ULN, the 
patient will undergo repeat confirmatory assessment as soon as is reasonably possible, preferably 
within 3 to 7 days of the laboratory result becoming available.  
Repeat CK assessment will include query for related symptoms.  
• If the repeat CK assessment confirms an unexplained (ie, not associated with recent 
trauma or physically strenuous activity) CK abnormality >5 × ULN, if asymptomatic 
the investigator with input from the Sponsor may consider continuing study 
medication with continued CK assessments every 1-2 weeks.  
• 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)  

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 173 of 287 
− 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:  
− >5 × ULN that is associated with symptoms of muscle pain, muscle weakness, or 
dark urine; or  
− >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) 
CHANGE 61 REVISED SAFETY MONITORING AND MANAGEMENT 
INSTRUCTIONS 
Location: 
11.1.6.3.5 Monitoring and Management of Elevated LDL-C 
Original Text: 
• 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: 
• 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) 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Summaiy of Changes Amendment 1 
Amendment 5, 10 May 2017 
CHANGE 62 REVISED SAFETY MONITORING AND MANAGEMENT 
INSTRUCTIONS 
Location: 
11.1.6.4 
Monitoring and Management of Potential Hypoglycemia and Metabolic Acidosis 
-
Confidential 
Page 174 of 287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 175 of 287 
CHANGE 63 CLARIFIED REPORTING REQUIREMENTS FOR AES, SAES, AND 
PREGNANCIES 
Location: 
11.2.4 
Severity 
Original Text: 
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. 
New Text: 
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, life-threatening, or 
fatal 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 
• Life-threatening: Events that are life-threatening with urgent intervention indicated 
• Fatal: Death related to AE 
CHANGE 64 CLARIFIED REPORTING REQUIREMENTS FOR AES, SAES, AND 
PREGNANCIES 
Location: 
11.2.6 
Monitoring and Follow-up of Adverse Events 
Original Text: 
For all AEs that require the patient to be discontinued from the study, relevant clinical 
assessments and laboratory tests must be repeated at appropriate intervals until final resolution or 
stabilization of the event(s). 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Summaiy of Changes Amendment 1 
Amendment 5, 10 May 2017 
Patients with AEs related to study dmg that ai·e ongoing at study completion or study withdrawal 
must be followed until resolution or for 30 days after the last dose of study diug, whichever 
comes first, with the exception of patients repo1ting SAEs (see Section 11.3). 
New Text: 
For all AEs that require the patient to be discontinued from the study, relevant clinical 
assessments and laborato1y tests must be repeated at appropriate intervals until final resolution, 
ef stabilization of the event(s ), or until the patient is lost to follow-up or dies. 
Patients with AEs rela:-tea ta smEl-y amg that ai·e ongoing at study completion or study withdi·awal 
must be followed until resolution or for 30 days after the last ease af study ~isit, whichever 
comes first, v,i.t,a the eneetiti.aft afJ3a:-ti.eftts retiati:i.Bg £ABs (see Section 11.3). 
CHANGE 65 CLARIFIED REPORTING REQUIREMENTS FOR AES, SAES, AND 
PREGNANCIES 
Location: 
11.2.7.1 
Definition of Serious Adverse Event 
Original Text: 
Until the CEC has been established, MACE events that also meet the definition of an SAE will 
be repo1ted as both MACE and SAEs. The CEC will adjudicate MACE in a blinded fashion, but 
the DMC will review MACE and SAEs in an unblinded fashion. 
New Text: 
Uftti.l the C:BC has eeeft esta:ehshea, MACB tWefttsAny clinical endpoints that meet SAE criteria 
t,aa.t alsa meet the aefiH-iti.aft af aft £AB will be repo1ted as eath MACB afta SAEs. The CEC will 
adjudicate MACB clinical endpoints in a blinded fashion, but the DMC will review MACB 
clinical endpoints and SAEs in an unblinded fashion. 
CHANGE 66 CLARIFIED REPORTING REQUIREMENTS FOR AES, SAES, AND 
PREGNANCIES 
Location: 
11.3 
Reporting Serious Adverse Events 
Confidential 
Page 176 of 287 

ETC-1002 
Clinical Study Protocol 1002-040 
-
Confidential 
Page 177 of 287 
Esperion Therapeutics, Inc. 
Summaiy of Changes Amendment 1 
Amendment 5, 10 May 2017 

ETC-1002 
Clinical Study Protocol 1002-040 
Esperion Therapeutics, Inc. 
Summaiy of Changes Amendment 1 
Amendment 5, 10 May 2017 
CHANGE 67 CLARIFIED REPORTING REQUIREMENTS FOR AES, SAES, AND 
PREGNANCIES 
Location: 
11.3.1 
Reporting of Serious Adverse Events to Regulatory Authorities 
Original Text: 
The Sponsor (and/or designee) is responsible for submitting expedited repo1ts of suspected 
serious and unexpected adverse reactions to the appropriate regulatory authorities. All 
Investigators responsible for ongoing clinical studies with the study drng will be notified by the 
Sponsor ( or designee) of all SAEs that require prompt submission to their IRB/IEC. Repo1ts of 
all SAEs must be communicated as soon as possible to the appropriate IRB/IEC and/or reported 
in accordance with local laws and regulations. Investigators should provide written 
documentation of IRB/IEC notification for each repo1t to the Sponsor. 
New Text: 
The Sponsor (and/or designee) is responsible for submitting expedited repo1ts of suspected 
seriet1s and unexpected serious adverse reactions (SUSARS) to the appropriate regulatory 
authorities. All Investigators resf)ee:siele fer participating in ongoing clinical studies with the 
study drng will be notified by the Sponsor ( or designee) of all £ABs tlia-t reEtMire flt'0ffif)t 
s:-teJ:Rissiee: te tftetr JRB/IBCSUSARs. Ref)e1is ef all £A.BsSUSARS must be communicated as 
soon as possible to the appropriate IRB/IEC by the investigator, as applicable and/or repo1ted in 
Confidential 
Page 178 of 287 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Summaiy of Changes Amendment 1 
Amendment 5, 10 May 2017 
accordance with local laws and regulations. Investigators should provide written documentation 
of IRB/IEC notification for each repo1t 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 
regulat01y 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 
• 
Corona,y revascularization 
• 
Heart failure requiring hospitalization 
• 
Noncoronary arterial revascularization 
CHANGE 68 CLARIFIED REPORTING REQUIREMENTS FOR AES, SAES, AND 
PREGNANCIES 
Location: 
11.3.2 
Reporting of Patient Death 
Original Text: 
The death of any patient durin~tudy or within 30 days after study completion (regai·dless of 
the cause, must be reported to-
Medical and Safety Se1vices as detailed in Section 11.3. 
New Text: 
The death of any patient during the study, or within the 30~ay follow-up period after they 
have completed the studyemEl;r esm13letiss (regai·dless of the cause), must be reported to_ 
Medical and Safety Se1v ices as detailed in Section 11. 3. 
CHANGE 69 CLARIFIED REPORTING REQUIREMENTS FOR AES, SAES, AND 
PREGNANCIES 
Location: 
11.4 
Adverse Events of Special Interest 
Confidential 
Page 179 of 287 

ETC-1002 
Clinical Study Protocol 1002-040 
-
Esperion Therapeutics, Inc. 
Summaiy of Changes Amendment 1 
Amendment 5, 10 May 2017 
CHANGE 70 CLARIFIED REPORTING REQUIREMENTS FOR AES, SAES, AND 
PREGNANCIES 
Location: 
11.4 
Adverse Events of Special Interest 
-
CHANGE 71 CLARIFIED REPORTING REQUIREMENTS FOR AES, SAES, AND 
PREGNANCIES 
Location: 
11.5 
Data Monitoring Committee 
Original T ex.t: 
An independent DMC will monitor unblinded acclllllulating patient safety data until the last 
patient has completed study treatment. In addition, data on SAEs and deaths, including MACE, 
will be monitored by the DMC dming this period. At each DMC review, relevant unblinded 
safety infonnation fror~ing studies of ETC-1002 will be provided to the DMC by an 
independent unblinded- statistician and prograinmer. Additional details will be provided in 
a DMC Chaiter. 
Confidential 
Page 180 of 287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 181 of 287 
New Text: 
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 
MACEclinical endpoints, will be monitored by the DMC during this period. At each DMC 
review, relevant unblinded safety and efficacy information from ongoing studies of ETC-1002 
will be provided to the DMC by an independent unblinded 
 statistician and programmer. 
Additional details will be provided in a DMC Charter. 
CHANGE 72 CLARIFIED REPORTING REQUIREMENTS FOR AES, SAES, AND 
PREGNANCIES 
Location: 
11.6 
Clinical Event Committee (CEC) 
Original Text: 
A blinded independent expert CEC will adjudicate MACE. Additional details regarding MACE 
and MACE 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. MACE from this study and other studies within the ETC-1002 Phase 3 
development program will be aggregated to allow for a safety assessment across the entire 
development program. 
New Text: 
A blinded independent expert CEC will adjudicate MACEclinical endpoints. Additional details 
regarding MACE clinical endpoints and MACEclinical 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. MACEClinical 
endpoints from this study and other studies within the ETC-1002 Phase 3 development program 
will be aggregated to allow for a safety assessment across the entire development program. 
CHANGE 73 UPDATED THE LIPID ENDPOINT ASSESSMENTS 
Location: 
11.7.1 
Lipid Parameters 
Original Text: 
After randomization, patients will return to clinic every 4 weeks for the first 12 weeks, then 
approximately every 12-16 weeks through 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 will be collected at baseline and all clinic 
visits and analyzed at Weeks 12, 24, and 52.  
New Text: 
After randomization, patients will return to clinic every 4 weeks for the first 12 weeks, then 
approximately every 12-16 weeks through 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 will be collected at baseline and all clinic 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 182 of 287 
visits and analyzed atfor evaluation of ETC-1002 effects on lipids and cardiometabolic 
parametersWeeks 12, 24, and 52. 
CHANGE 74 UPDATE CLINICAL LABORATORY PARAMETERS 
Location: 
11.7.2 
Clinical Laboratory Tests (Lipids) 
Original Text: 
Clinical laboratory samples will be collected at all clinic visits and analyzed at Weeks 12, 24, 
and 52.  
Blood draws for lipids (and glucose [not safety]) 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. 
New Text: 
Clinical laboratory samples will be collected at all clinic visitsand analyzed at Weeks 12, 24, and 
52.  
Blood draws for lipids (and glucose[not safety]) 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. 
CHANGE 75 TYPOGRAPHICAL AND FORMATTING 
Location: 
11.7.2 
Clinical Laboratory Tests (Lipids) 
Original Text: 
Table 6: 
Clinical Laboratory Parameters (Lipids) 
Clinical Laboratory Test  
Clinical Laboratory Test 
Basic Lipid Parameters 
Other Parameters 
• 
Total cholesterol (TC) 
• 
High-sensitivity C-reactive protein (hs-CRP) 
• 
Calculated low-density lipoprotein 
cholesterol (LDL-C) and non-HDL-C 
• 
apoB 
• 
High-density lipoprotein cholesterol 
(HDL-C) 
 
• 
Triglycerides (TG) 
 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 183 of 287 
New Text: 
Table 6: Clinical Laboratory Parameters (Lipids) and Cardiometabolic Biomarkers 
Clinical Laboratory Test  
Clinical Laboratory Test 
Basic Lipid Parameters 
Other Parameters 
• 
Total cholesterol (TC) 
• 
Calculated 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 
CHANGE 76 REVISED STATISTICS 
Location: 
12.2 
Determination of Sample Size 
Original Text: 
The sample size of 600 patients randomized to ETC-1002 and 300 patients randomized to 
placebo will provide 900 total patients. This sample size was selected to provide a robust long-
term safety profile in patients considered to have an unmet need for additional lipid lowering in a 
chronic setting. 
New Text: 
A total of 900 patients will be enrolled in this study with 600 patients randomized to ETC-1002 
and 300 patients randomized to placebo. Using an anticipated overall dropout rate of 7.5% at 
6 months and 10.0% at 12 months in each treatment group, the expected number of patients 
exposed to treatment during the study is as follows: 
 
Patients ≥6 Months 
Patients ≥12 Months 
ETC-1002 
555 
540 
Placebo 
278 
270 
Absolute risk will be addressed by 600 patients randomized to ETC-1002 and will provide at 
least 95% power to detect AEs that occur at rates similar to those seen in the placebo group for 
the AEs of interest in the recently completed long-term safety study entitled Efficacy and Safety 
of Alirocumab in Reducing Lipids and Cardiovascular Events [2]. In this study adverse event 
rates ranged from 0.5% to 13.6%. Additional assumptions include a two-sided test with 
significance level at 0.05. 
When AEs occur at a range of rates similar to those seen in the placebo group in the above 
referenced alirocumab study (0.5% to 13.6%), the sample size of 600 patients randomized to 
ETC-1002 and 300 patients randomized to placebo will allow for detection of relative risks of 
1.0 and of 2.0 (ETC-1002:placebo) with the following approximate 95% confidence limits):  

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 184 of 287 
% Placebo Patients 
Experiencing AE 
% ETC-1002 Patients 
Experiencing AE 
Relative Risk 
Approximate 95% 
Confidence Interval 
0.5% 
0.5% 
1.0 
(0.1, 7.0) 
0.5% 
1.0% 
2.0 
(0.3, 11.9) 
13.6% 
13.6% 
1.0 
(0.7, 1.4) 
13.6% 
27.2% 
2.0 
(0.5, 2.3) 
CHANGE 77 REVISED STATISTICS 
Location: 
12.3 
Analysis Population 
Original Text: 
The Full Analysis Set (FAS), used for all of the lipid and cardiometabolic summaries, is defined 
as all randomized patients and is also known as the intention-to-treat (ITT) set of patients. 
New Text:  
The Full Analysis Set (FAS), used for the LDL analyses and the all of the lipid and 
cardiometabolic summaries, is defined as all randomized patients and is also known as the 
intention-to-treat (ITT) set of patients. 
CHANGE 78 REVISED STATISTICS 
Location: 
12.5 
Primary Endpoint 
Original Text: 
No statistical analyses will be performed on any of the safety data in this study. The 
summarization of AEs will include only TEAEs, defined as AEs that begin or worsen after 
randomization and ingestion of the first dose of study drug. TEAEs and SAEs will be 
summarized by SOC, severity, and relationship to study drug for each treatment group. AE 
summaries will be provided overall and for subgroups such as gender, age, and HeFH status. 
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 only TEAEs, defined as AEs that begin or worsen after 
randomization and ingestion of the first dose of study drug. TEAEs and SAEs will be 
summarized by SOC, severity, and relationship to study drug for each treatment group. AE 
summaries will include cumulative incidence (percent of patients experiencing the AE) and 
patient-year adjusted incidence rates. These AE summaries will be provided overall and for 
subgroups such as gender, age, and HeFH status. 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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 185 of 287 
each be summarized by treatment group. Cumulative incidence (percent of patients experiencing 
the AE) and patient year adjusted incidence rates will be presented. If appropriate, absolute and 
relative risk differences will be calculated using both cumulative incidence and incidence rates. 
CHANGE 79 REVISED STATISTICS 
Location: 
12.5 
Primary Endpoint 
Original Text: 
Diabetes and Glycemia 
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. Fasting insulin, glucose, and HbA1C will be monitored at baseline and 
at Weeks 12, 24, and 52, and be summarized. 
New Text: 
Diabetes and GlycemiaHyperglycemia 
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. Fasting insulin, gGlucose, and HbA1C will be monitored at baseline 
and at Weeks 12, 24, and 52, and be summarized. 
CHANGE 80 REVISED STATISTICS 
Location: 
12.5 
Primary Endpoint 
Original Text: 
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. If needed, postbaseline eGFR categories will be modified to include the 
possibility of patients with eGFR values <45 mL/min/1. 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. 
New Text: 
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. If needed, postbaseline eGFR categories will be modified to include the 
possibility of patients with eGFR values <45 mL/min/1. Shift tables of urine protein 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 186 of 287 
(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. 
CHANGE 81 REVISED STATISTICS 
Location: 
12.5 
Primary Endpoint 
Original Text: 
Cardiovascular Events (MACE) 
MACE will be monitored and adjudicated by an independent blinded expert CEC for this study 
and other ongoing studies the ETC-1002 program. Adjudicated MACE will be summarized by 
event type and treatment group. Additional details regarding MACE and MACE definitions will 
be included in CEC charter. 
New Text: 
Cardiovascular Events (MACEClinical Cardiovascular Endpoints) 
Clinical cardiovascular endpoints will be monitored and adjudicated by an independent blinded 
expert CEC for this study and other ongoing studies the ETC-1002 program. Adjudicated 
MACEclinical endpoints will be summarized by event type and treatment group. Additional 
details regarding MACEclinical endpoints and MACEclinical endpoint definitions will be 
included in CEC charter. 
CHANGE 82 REVISED STATISTICS 
Location: 
12.6 
Secondary and Tertiary Lipids 
Original Text: 
12.6 
Lipids  
LDL-C, HDL-C, TG, TC, non-HDL-C, and apoB values at Weeks 12, 24, and 52 will be 
summarized. For each parameter at each time point, the value of the parameter and the percent 
change from baseline in the parameter will be summarized by treatment group. Missing values 
for any of the lipid parameters will not be imputed; that is, only observed case data will be used. 
New Text: 
12.6 
Secondary and Tertiary Lipids 
12.6.1 
Secondary Lipids 
Percent change from baseline to Week 12 in LDL-C will be analyzed using analysis of 
covariance (ANCOVA), with treatment and randomization strata (patient’s CV risk and baseline 
statin dose) as factors and baseline LDL-C as a covariate. Baseline LDL-C is defined as the 
predose Day 1/Week 0 value. The FAS will be used, with patients included in their randomized 
group, regardless of the treatment they actually received. Two methods for data handling will be 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 187 of 287 
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). For each ANCOVA (observed 
case; imputation via PMM), output will include the least squares mean (LSM) and standard 
error (SE) for each treatment group, along with the placebo-correct LSM and it’s 95% 
confidence interval (CI) and p-value. Specific details on how the PMM will be implemented will 
be included in the SAP.  
12.6.2 
Tertiary Lipids 
LDL-C, HDL-C, TG, TC, non-HDL-C, and apoB values at Weeks 12, 24, and 52 will be 
summarized. For each parameter at each time point, the value of the parameter and the percent 
change from baseline in the parameter will be summarized by treatment group. Baseline for each 
lipid is defined as the predose Day 1/Week 0 value. The FAS will be used, with patients included 
in their randomized group, regardless of the treatment they actually received. In addition, a 
summary using the FAS, excluding patients who received additional lipid-lowering therapy by 
that timepoint (by Week 24 for the Week 24 timepoint; by Week 52 for the Week 52 timepoint), 
will be provided. For both summaries, only observed case data will be used (no imputation for 
missing data).  
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 timepoint (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 timepoint will include the LSM and SE for each treatment group, as well as the placebo-
correct LSM, 95% CI and p-value. 
CHANGE 83 REVISED STATISTICS 
Location: 
12.7 
PK and Other Biomarkers 
Original Text: 
hs-CRP values and percent change from baseline in values will be summarized by treatment 
group at Weeks 12, 24, and 52. Missing values for hs-CRP will not be imputed; only observed 
case data will be used 
New Text: 
hs-CRP values and percent change from baseline in values will be summarized by treatment 
group at Weeks 12, 24, and 52. Baseline for hs-CRP is defined as the predose Day 1/Week 0 
value. The FAS will be used, with patients included in their randomized treatment group, 
regardless of the treatment they actually received. Only observed case data will be used (no 
imputation for missing data). Missing values for hs CRP will not be imputed; only observed case 
data will be used. 

ETC-1002 
Clinical Study Protocol 1002-040 
CHANGE 84 REVISED STATISTICS 
Location: 
12. 7 
PK and Other Bio markers 
Original Text: 
Esperion Therapeutics, Inc. 
Summaiy of Changes Amendment 1 
Amendment 5, 10 May 2017 
hs-CRP values and percent change from baseline in values will be summai·ized by treatment 
group at Weeks 12, 24, and 52. Missing values for hs-CRP will not be imputed; only observed 
case data will be used 
New Text: 
hs-CRP values and percent change from baseline in values will be summai·ized by treatment 
group at Weeks 12, 24, and 52. Baseline f or hs-CRP is defined as the predose Day I/Week 0 
value. The FAS will be used, with patients included in their randomized treatment group, 
regardless of the treatment they actually received. Only observed case data will be used (no 
imputation for missing data). Missing ·rallies :fer as CRP will aet ae iffif)litea; ealy 00se1vea ease 
aata ·will ae liSea. 
CHANGE 85UPDATED STUDYPROCEDURES 
Location: 
Appendix 1 
Screen 
Treatment 
Visit 
S11,2 
Tl 
T2 
T3 
T4 
T5 
T6 
T7 EOS3 
Week 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
-2 
0 
4 
8 
12 
24 
36 
52 
Procedure 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
-16 to -4 
1 
29±3 
57±3 
85±3 
169±7 
253±7 
365±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 
Adverse Event Recording 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
X 
X 
Weight
4 
X 
X 
X 
X 
X 
X 
X 
X 
Height/BM! 
X 
Waist Circmnference 
X 
12-Lead ECG5 
X 
X 
Vital Signs6 
X 
X 
X 
X 
X 
X 
X 
X 
Serology
7 
X 
Sermn Pregnancy8 
X 
TSH 
X 
Confidential 
Page 188 of 287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 189 of 287 
Clinical Safety Labs9 
X 
X 
X 
X 
X 
X 
X 
X 
Basic Fasting Lipids10 
X 
X 
X 
X 
X 
X 
X 
X 
HbA1C 
X 
X 
 
 
X 
 
 
X 
Insulin 
 
X 
 
 
X 
X 
 
X 
10 mL reserve sample 
 
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 
 
Plasma PK 
 
 
 
 
X 
X 
 
X 
Establish Patient Eligibility 
 
X 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
IWRS Contact 
X 
X 
 
 
X 
X 
X 
X12 
Double-blind Drug Dispensing13 
 
X 
 
 
X 
X 
X 
 
Drug Return/Compliance 
 
 
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 
visit is completed, the mean of lipid values from both visits 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 in the morning 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, 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-AB  
8 Pregnancy test completed in premenopausal women only 
9 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits. Coagulation is included at Screening 
(Visit S1), Baseline (Visit T1), Week 12 (Visit T4), and at EOS (Visit T7). Please refer to 
 laboratory manual for 
detailed schedule of tests. 
10 Basic fasting 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. The bottle dispensed at Visit T1 will be returned to clinic at Visits T2 and T3 for evaluation of compliance and 
returned for continued use. 

ETC-1002 
Clinical Study Protocol 1002-040 
New Text: 
Screen 
Visit 
S11,2 
Tl 
T2 
T3 
Week 
Wk 
Wk 
Wk 
Wk 
-2 
0 
4 
8 
Procedure 
Day 
Day 
Day 
Day 
-16 to -4 
1 
29±3 
57±3 
Informed Consent 
X 
Enrolhnent Criteria 
X 
Demographics 
X 
Medical Histo1y 
X 
HeFH Status Detennination 
X 
Concomitant Medications 
X 
X 
X 
X 
Adverse Event Recording 
X 
X 
X 
Physical Exam 
X 
Weight
4 
X 
X 
X 
X 
Height/BM! 
X 
lJtaisi ~Y:-~
:F@ae@ 
12-Lead ECG5 
X 
Vital Signs6 
X 
X 
X 
X 
Serology
7 
X 
Serum Pregnancy and/or FSFr 
X 
TSH 
X 
Clinical Safety Labs9 
X 
X 
X 
X 
Basic Fasting Lipids10 
X 
X 
X 
X 
HbA1c 
X 
X 
~ 
~ 
IO mL rese1ve sample 
X 
apoB 
X 
hs-CRP 
X 
Diet and exercise counseling11 
X 
X 
X 
X 
Plasma PK 
Establish Patient Eligibility 
X 
Randomization 
X 
IWRS Contact 
X 
X 
Double-blind Drug Dispensing13 
X 
Drug Return/Compliance 
X 
X 
Schedule next visit 
X 
X 
X 
X 
Confidential 
Page 190 of 287 
Esperion Therapeutics, Inc. 
Summaiy of Changes Amendment 1 
Amendment 5, 10 May 2017 
Treatment 
T4 
T5 
T6 
T7 EOS3 
Wk 
Wk 
Wk 
Wk 
12 
24 
36 
52 
Day 
Day 
Day 
Day 
85±3 
169±7 
253±7 
365±7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
~ 
~ 
~ 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
x'2 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
x' 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 1 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 191 of 287 
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 
visit is completed, the mean of lipid values from both visits 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 in the morning 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, HCVAB  
8 Pregnancy test completed in premenopausal women only. FSH test is completed in women < 55 years old and > 1 year 
without menses 
9 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits. Coagulation is included at Screening 
(Visit S1), Baseline (Visit T1), Week 12 (Visit T4), and at EOS (Visit T7). Please refer to 
 laboratory manual for 
detailed schedule of tests. 
10 Basic fasting 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. The bottle dispensed at Visit T1 will be returned to clinic at Visits T2 and T3 for evaluation of compliance and 
returned for continued use. 
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 
 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 2 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 192 of 287 
APPENDIX 7. SUMMARY OF CHANGES IN AMENDMENT 2 
 
 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 2 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 193 of 287 
SUMMARY OF CHANGES 
CLINICAL STUDY PROTOCOL 
 
Study Number: 
1002-040 
Study Title: 
A Randomized, Double-blind, Placebo-controlled, 
Multicenter Long-term Safety and Tolerability Study of 
ETC-1002 in Patients with Hyperlipidemia at High 
Cardiovascular Risk Who are not Adequately Controlled 
by Their Lipid-Modifying Therapy 
Protocol Version Incorporating 
Current Summary of Changes: 
Amendment 2: Amended Protocol 23 February 2016 
Preceding Protocol Version: 
Amendment 1: Amended Protocol 28 January 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 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: 
• For program consistency, revision of severity categories for adverse events to the 3 
categories of severity. 
• Typographical errors and formatting were corrected or revised to improve clarity and 
consistency 
• This amendment represents cumulative changes to the original protocol. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 2 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 194 of 287 
CHANGE 1 REVISION OF ADVERSE EVENT SEVERITY 
Location: 
Section 11.2.4, Severity 
Original Text: 
The severity of the AE will be characterized as mild, moderate, or severe, life-threatening, or 
fatal 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 
• Life-threatening: Events that are life-threatening with urgent intervention indicated 
• Fatal: Death related to AE 
New Text: 
The severity of the AE will be characterized as mild, moderate, or or severe, life threatening, or 
fatal 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 
• Life threatening: Events that are life threatening with urgent intervention indicated 
• Fatal: Death related to AE 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 195 of 287 
APPENDIX 8. SUMMARY OF CHANGES IN AMENDMENT 3 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 196 of 287 
SUMMARY OF CHANGES 
CLINICAL STUDY PROTOCOL 
 
Study Number: 
1002-040 
Study Title: 
A Randomized, Double-blind, Placebo-controlled, 
Multicenter Long-term Safety and Tolerability Study of 
ETC-1002 in Patients with Hyperlipidemia at High 
Cardiovascular Risk Who are not Adequately Controlled 
by Their Lipid-Modifying Therapy 
Protocol Version Incorporating 
Current Summary of Changes: 
Amendment 3: Amended Protocol 28 July 2016 
Preceding Protocol Version: 
Amendment 2: Amended Protocol 23 February 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 italicized. 
5. In the “New Text”, text deleted from the protocol is indicated in strikethrough font.

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Summaiy of Changes Amendment 3 
Amendment 5, 10 May 2017 
Summary and Justification of Changes 
The protocol was amended for the following: 
• 
Increased sample size from 900 randomized patients to 1950 randomized patients to 
support the assessment of safety for the bempedoic acid (ETC-1002) program. 
• 
Applicable statistical sections were updated to align with other revisions in this 
amendment. 
• 
Revised the high-dose statin exclusion to allow patients on high-dose statins with the 
exception of atients on simvastatin takin avera e dail doses that are ·eater than 
40 m . 
• 
Increased overall study duration to account for additional recrnitment time required to 
randomize additional patients 
• 
Revised inclusion criteria to be consistent with cunent safety data and to comply with 
Health Canada requests 
Revised to include tubal ligation in the study definition for 'surgically sterile' 
Revised to include the bi1t h control requirement as requested by Health Canada. 
This revision only applies to Canadian sites. 
• 
Revised exclusion criteria to be consistent with cmTent safety data. This includes: 
Increasing the total fasting triglyceride level from >400 mg/dL (4.5 mmol/L) to 
>500 mg/dL (5.6 mmol/L) 
Decreasing the eGFR level from <45 mL/min/1.73 m2 to <30 mL/min/1.73 m2 
Allowing patients with positive HCV-AB results to have a reflex HCV RNA 
peifonned so that those patients without active disease may be considered for 
emollment 
Allowing patients whose total bilirnbin levels exceeding ~1.2 x ULN to have a 
reflex indirect (unconjugated) bilirnbin test so that those patients with results that 
are consistent with Gilbe1t's disease may be considered for emollment 
Shorten the duration from when a patient may have had, for any reason, a blood 
transfosion from 90 days to 30 days 
Decrease the amount of time patients should be stable on obesity medications 
from 6 months to 3 month. 
• 
Revised references to clinical safety laboratories, other screening laboratories, and 
lipid assessments (Study Procedures, Assessment of Safety, Schedule of Study 
Events) for consistency with new or revised assessments and procedures 
Confidential 
Page 197 of 287 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Summaiy of Changes Amendment 3 
Amendment 5, 10 May 2017 
• 
Revised to include a section in the protocol to address overdose 
• 
Revised administrntion instructions for IMP for consistency across the development 
prograin 
• 
Revised testing requirement for coagulation for consistency across the development 
prograin 
• 
Revised the Monitoring and Management of Elevated Liver Function Tests to include 
additional clai·ity and testing for patients with Gilbe1t's disease 
• 
Revised the Monitoring and Management of Elevated LDL-C to allow for the use of 
high-dose statins, excluding average daily doses of simvastatin that ai·e greater than 
40 mg. Additionally, 4 weeks after patients have their lipid-lowering medications 
modified should return to the clinic for a safety laborato1y assessment. 
• 
Revised the Monitoring and Management of Elevated Triglycerides for consistency 
across the development prograin 
• 
• 
Removed the collection of blood samples for phannacokinetic assessment for those 
patients who randomize into the study after the implementation of Protocol 
Amendment3 
• 
For consistency across the development prograin, revised the adverse event 
relationship to study drng scale to include 'Unlikely' 
• 
Typographical eITors and fonnatting were coITected or revised to improve clai·ity and 
consistency. Only substantive changes are included in the Summaiy of Changes 
document. 
• 
This amendment represents cumulative changes to the original protocol. 
Confidential 
Page 198 of 287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 199 of 287 
CHANGE 1 INCREASE IN SAMPLE SIZE 
Location: 
Synopsis, Study Hypothesis 
Original Text: 
The study will characterize the long-term safety and tolerability of ETC-1002 versus placebo in 
addition to maximally tolerated lipid-lowering therapy, including a maximally tolerated statin, in 
patients with hyperlipidemia. The randomized, double-blind, placebo controlled add-on to 
maximally tolerated lipid-lowering therapy design will ensure that long-term safety data are 
meaningful and interpretable. The extended treatment duration (52 weeks) and large patient 
number (n = 900) will provide robust long-term safety in high CV risk patients who have an 
unmet medical need for additional lipid-lowering therapy, such as ETC-1002 once daily, orally 
bioavailable option. 
New Text: 
The study will characterize the long-term safety and tolerability of ETC-1002 versus placebo in 
addition to maximally tolerated lipid-lowering therapy, including a maximally tolerated statin, in 
patients with hyperlipidemia. The randomized, double-blind, placebo controlled add-on to 
maximally tolerated lipid-lowering therapy design will ensure that long-term safety data are 
meaningful and interpretable. The extended treatment duration (52 weeks) and large patient 
number (n = 9001950) will provide robust long-term safety in high CV risk patients who have an 
unmet medical need for additional lipid-lowering therapy, such as ETC-1002 once daily, orally 
bioavailable option. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 200 of 287 
CHANGE 2 INCREASED SAMPLE SIZE 
Location:  
Synopsis, Methodology 
Section 6.1., Overall Study Design, Figure 1  
Original Text:  
 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 201 of 287 
New Text: 
 
CHANGE 3 REVISED HIGH-DOSE STATIN EXCLUSION 
Location: 
Synopsis, Study Design 
Original Text: 
This is a Phase 3, randomized, double-blind, placebo-controlled, parallel group, study evaluating 
the long-term safety and tolerability of ETC-1002 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-lowering therapy 
includes a maximally tolerated statin alone or in combination with other lipid-lowering therapies 
(eg, ezetimibe, fibrates [except gemfibrozil]). 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. However, 
patients currently taking high-dose statins, defined as rosuvastatin 40 mg, atorvastatin 80 mg, or 
simvastatin 40 or 80 mg per day, or who are currently taking a PCSK9 inhibitor (alirocumab or 
evolocumab), or have taken a PCSK9 inhibitor within the past 4 weeks of Week -2 (Visit S1) will 
be excluded from enrolling in this study. PCSK9 inhibitors may be initiated as adjunctive 
therapy at Week 24 if the LDL-C threshold criteria have been met as described in 
Section 11.1.6.3.5. 
New Text: 
This is a Phase 3, randomized, double-blind, placebo-controlled, parallel group, study evaluating 
the long-term safety and tolerability of ETC-1002 in high CV risk patients with hyperlipidemia 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 202 of 287 
(patients with underlying HeFH and/or ASCVD) who are not adequately treated with their 
maximally tolerated lipid-modifying therapy. Maximally tolerated lipid-lowering therapy 
includes a maximally tolerated statin alone or in combination with other lipid-lowering therapies 
(eg, ezetimibe, fibrates [except gemfibrozil]). 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. However, 
patients who are currently taking high dose statins, defined as rosuvastatin 40 mg, atorvastatin 
80 mg, or simvastatin at average daily doses that are greater than 40or 80 mg per day or who 
are currently taking a PCSK9 inhibitor (alirocumab or evolocumab), or have taken a PCSK9 
inhibitor within the past 4 weeks of Week -2 (Visit S1) will be excluded from enrolling in this 
study. PCSK9 inhibitors may be initiated as adjunctive therapy at Week 24 if the LDL-C 
threshold criteria have been met as described in Section 11.1.6.3.5.  
CHANGE 4 INCREASED SAMPLE SIZE 
Location: 
Synopsis, Study Design 
Original Text: 
Screening (Visit S1) will occur approximately 2 weeks prior to Day 1 (Visit T1). Patients on 
maximally tolerated lipid-lowering therapy, as determined by the investigator, will be stratified 
based on the patient’s CV risk and baseline statin dose. There will be no cap placed on 
randomization into any particular stratum. Approximately 1950 eligible patients will be 
randomized 2:1 on Day 1 (Visit T1) to receive either ETC-1002 180 mg (n = 1300), or placebo 
(n = 650) once daily for 52 weeks. Randomized patients will continue in the study until they 
have completed Week 52 (Visit T7). Randomized patients will return for clinic visits at Week 4 
(Visit T2), Week 8 (Visit T3), Week 12 (Visit T4), Week 24 (Visit T5), Week 36 (Visit T6), and 
Week 52 (Visit T7). 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: 
Screening (Visit S1) will occur approximately 2 weeks prior to Day 1 (Visit T1). Patients on 
maximally tolerated lipid-lowering therapy, as determined by the investigator, will be stratified 
based on the patient’s CV risk and baseline statin dose. There will be no cap placed on 
randomization into any particular stratum. Approximately 9001950 eligible patients will be 
randomized 2:1 on Day 1 (Visit T1) to receive either ETC-1002 180 mg (n = 6001300), or 
placebo (n = 300650) once daily for 52 weeks. Randomized patients will continue in the study 
until they have completed Week 52 (Visit T7). Randomized patients will return for clinic visits at 
Week 4 (Visit T2), Week 8 (Visit T3), Week 12 (Visit T4), Week 24 (Visit T5), Week 36 
(Visit T6), and Week 52 (Visit T7). 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. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 203 of 287 
CHANGE 5 INCREASED SAMPLE SIZE 
Location:  
Synopsis, Number of patients planned 
Original Text: 
Approximately 900 adult male and female patients 
New Text: 
Approximately 9001950 adult male and female patients 
CHANGE 6 INCREASED STUDY DURATION 
Location: 
Synopsis, End of Study 
Original Text:  
The study will end when the last randomized patient completes their last study visit. The 
estimated overall duration of the study (first patient first visit [FPFV] to last patient last visit 
[LPLV]) is approximately 22 months 
New Text: 
The study will end when the last randomized patient completes their last study visit. The 
estimated overall duration of the study (first patient first visit [FPFV] to last patient last visit 
[LPLV]) is approximately 2228 months 
CHANGE 7 REVISED INCLUSION CRITERIA 
Location: 
Synopsis, Diagnosis and criteria for patient eligibility, Inclusion Criteria 
Original Text: 
• 
Men and nonpregnant, nonlactating women. Women must be either:  
- Naturally postmenopausal (as reported by the patient, defined as greater than 
55 years and ≥1 year without menses, less than 55 years and ≥1 year without 
menses with follicle-stimulating hormone (FSH) ≥40.0 IU/L), or surgically sterile 
(including hysterectomy and/or bilateral oophorectomy, but not tubal ligation 
alone) or;  
- Women of childbearing potential must be willing to use 1 acceptable method of 
birth control. 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). 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 204 of 287 
New Text: 
• 
Men and nonpregnant, nonlactating women. Women must be either:  
- Naturally postmenopausal (as reported by the patient, defined as greater than 
55 years and ≥1 year without menses, less than 55 years and ≥1 year without 
menses with follicle-stimulating hormone (FSH) ≥40.0 IU/L), or surgically sterile 
(including hysterectomy, and/or bilateral oophorectomy, but notor tubal 
ligationalone) or;  
- Women of childbearing potential must be willing to use 1 acceptable method of 
birth control. The minimal requirement for adequate contraception 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). 
Original Text: 
• 
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). Regimens other than daily dosing, including those at very 
low doses, are acceptable. 
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.  
Patients currently taking high-dose statins, defined as rosuvastatin 40 mg, atorvastatin 
80 mg, or simvastatin 40 or 80 mg per day will be excluded from this study. 
Patients who are currently taking a PCSK9 inhibitor (Praluent® [alirocumab] or 
Repatha® [evolocumab]) or have taken a PCSK9 inhibitor within the past 4 weeks of 
Week -2 (Visit S1) will be excluded from this study. 
New Text: 
• 
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). Regimens other than daily dosing, including those at very 
low doses, are acceptable. 
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.  

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 205 of 287 
Patients currently taking an average daily dose ofhigh dose statins, defined as 
rosuvastatin 40 mg, atorvastatin 80 mg, or simvastatin 40 or 80 that is greater than 40 mg 
per day will be excluded from this study. 
Patients who are currently taking a PCSK9 inhibitor (Praluent® [alirocumab] or 
Repatha® [evolocumab]) or have taken a PCSK9 inhibitor within the past 4 weeks of 
Week -2 (Visit S1) will be excluded from this study. 
CHANGE 8 REVISED EXCLUSION CRITERIA 
Location: 
Synopsis, Diagnosis and criteria for patient eligibility, Exclusion Criteria 
Original Text: 
• 
Total fasting triglyceride >400 mg/dL (4.5 mmol/L) at Week -2 (Visit S1) 
Note: TG may be repeated 1 time with the screening period extended up to 2 weeks. For 
those patients who have a repeat TG, the mean of the first value and the repeat value will 
be used to determine eligibility. 
• 
Renal dysfunction or nephritic syndrome or a history of nephritis, including eGFR (using 
central laboratory determined Modification of Diet in Renal Disease [MDRD] formula) 
<45 mL/min/1.73 m2 at Week -2 (Visit S1) [1].  
Note: At the discretion of the investigator, the screening period may be extended up to 
2 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: 
• 
Total fasting triglyceride >400500 mg/dL (4.55.6 mmol/L) at Week -2 (Visit S1) 
Note: TG may be repeated 1 time with the screening period extended up to 2 weeks. For 
those patients who have a repeat TG, the mean of the first value and the repeat value will 
be used to determine eligibility. 
• 
Renal dysfunction or nephritic syndrome or a history of nephritis, including eGFR (using 
central laboratory determined Modification of Diet in Renal Disease [MDRD] formula) 
<4530 mL/min/1.73 m2 at Week -2 (Visit S1) [1].  
Note: At the discretion of the investigator, the screening period may be extended up to 
2 weeks for a single repeat eGFR. For those patients who have a repeat eGFR, the repeat 
value will be used to determine eligibility. 
Original Text: 
• 
Concomitant use of high-dose statins, defined as rosuvastatin 40 mg, atorvastatin 80 mg, 
or simvastatin 40 or 80 mg daily. 
New Text: 
• 
Concomitant use of high dose statins, defined as rosuvastatin 40 mg, atorvastatin 80 mg, 
or simvastatin at40 or 80 mg average daily doses greater than 40 mg. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 206 of 287 
Original Text: 
• 
Liver disease or dysfunction, including:  
- Positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C 
antibodies (HCV-AB) at Week -2 (Visit S1); or 
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≥1.5 × ULN, 
and/or total bilirubin (TB) ≥1.2 × ULN at Week -2 (Visit S1).  
Note: At the discretion of the investigator, the screening period may be extended 
up to 2 weeks for a single repeat of ALT, AST, and/or TB. For those patients who 
have a repeat ALT, AST, and/or TB, the repeat value will be used to determine 
eligibility. 
New Text: 
• 
Liver disease or dysfunction, including:  
- Positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C 
antibodies (HCV-AB) at Week -2 (Visit S1); or 
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≥1.52 × 
ULN, and/or total bilirubin (TB) ≥1.2 × ULN at Week -2 (Visit S1).  
Note: If HCV-AB is positive, a reflex HCV RNA will be performed to rule out 
active disease. Patients without active disease may be enrolled in the study. 
Note: At the discretion of the investigator, the screening period may be extended 
up to 2 weeks for a single repeat of ALT, AST, and/or TB. For those patients who 
have a repeat ALT, AST, and/or TB, the repeat value will be used to determine 
eligibility. 
If TB ≥1.2 × ULN, a reflex indirect (unconjugated) bilirubin will be obtained and 
if the results are consistent with Gilbert’s disease, the patient may be enrolled in 
the study.  
Original Text: 
• 
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). 
New Text: 
• 
Active malignancy, including those requiring surgery, chemotherapy, and/or radiation in 
the past 5 years. Patients with a history of nNonmetastatic basal or squamous cell 
carcinoma of the skin and cervical carcinoma in situ are allowed). 
Original Text: 
• 
Blood donation, participation in a clinical study with multiple blood draws, major 
trauma, or surgery with or without blood loss within 30 days prior to randomization 
• 
Blood transfusion for any reason within 90 days prior to randomization 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 207 of 287 
New Text: 
• 
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 
• 
Blood transfusion for any reason within 90 days prior to randomization 
Original Text: 
• 
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 (6 months prior to randomization) 
New Text: 
• 
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 (6 3 months prior to randomization) 
CHANGE 9 REVISED ADMINISTRATION INSTRUCTIONS FOR IMP 
Location: 
Synopsis, IMP, dosage and mode of administration 
Original Text: 
• 
All IMP will be ingested once daily in the morning with or without food. 
New Text: 
• 
All IMP will be ingested once daily in the morning (once every 24 hours, at 
approximately the same time each day) with or without food. 
CHANGE 10 REVISED REFERENCES TO CLINICAL SAFETY LABORATORIES, 
OTHER SCREENING LABORATORIES, AND LIPID ASSESSMENTS 
Location: 
Synopsis, Criteria for evaluation 
Original Text: 
Other Screening Laboratories: 
• Hepatitis B surface antigen (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), TSH 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 208 of 287 
New Text: 
Other Screening Laboratories: 
• Hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) (if HCV is positive, a 
reflex HCV RNA will be performed to rule out active disease), 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 pregnancy test Day 1 prior to randomization 
(only in Canada, for females who are of childbearing potential), TSH 
CHANGE 11 REVISED THE MONITORING AND MANAGEMENT OF ELEVATED 
LDL-C 
Location: 
Synopsis, Safety and Monitoring 
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 >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 using high doses of 
statins excluded from the study (rosuvastatin 40 mg, atorvastatin 80 mg, and 
simvastatin 40 or 80 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). 
- The initiation and or dose change of these medications will be documented on the 
electronic case report form (eCRF) as a concomitant medication with the 
associated start date 
- 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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 209 of 287 
treatment and will be asked to continue to be followed for safety using the 
protocol-specified visit schedule. 
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) 
• 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 using high doses of 
statins excluded from the study (rosuvastatin 40 mg, atorvastatin 80 mg, and 
simvastatin at average daily doses greater than 40 mg40 or 80 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). 
- The initiation of any new andor dose changes of these medicationsany 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. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 210 of 287 
CHANGE 12 REVISED THE MONITORING AND MANAGEMENT OF ELEVATED 
TRIGLYCERIDES 
Location:  
Synopsis, Safety and Monitoring 
Original Text:  
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 500 mg/dL (5.6 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 >500 mg/dL (5.6 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 >500 mg/dL (5.6 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. 
New Text: 
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 5001000 mg/dL (5.611.3 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 >5001000 mg/dL (11.35.6 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 >5001000 mg/dL (5.611.3 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 

ETC-1002 
Clinical Study Protocol 1002-040 
Esperion Therapeutics, Inc. 
Summaiy of Changes Amendment 3 
Amendment 5, 10 May 2017 
case repo1i fo1m as a concomitant medication with the associated staii date. These 
medications will not be provided by the sponsor. 
• 
Patients continuing to exceed the TG threshold after maximizing the standai·d-of-cai·e 
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. 
-
-
Confidential 
Page 211 of287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 212 of 287 
CHANGE 14 INCREASED SAMPLE SIZE AND APPLICABLE STATISTICAL 
SECTIONS WERE UPDATED TO ALIGN WITH OTHER REVISIONS IN 
THIS AMENDMENT  
Location: 
Synopsis, Statistical methods 
Original Text: 
Sample Size 
A total of 900 patients will be enrolled in this study with 600 patients randomized to ETC-1002 
and 300 patients randomized to placebo. Using an anticipated overall dropout rate of 7.5% at 
6 months and 10.0% at 12 months in each treatment group, the expected number of patients 
exposed to treatment during the study is as follows: 
 
Patients ≥6 Months 
Patients ≥12 Months 
ETC-1002 
555 
540 
Placebo 
278 
270 
 
Absolute risk will be addressed by 600 patients randomized to ETC-1002 and will provide at 
least 95% power to detect AEs that occur at rates similar to those seen in the placebo group for 
the AEs of interest in the recently completed long-term safety study entitled Efficacy and Safety 
of Alirocumab in Reducing Lipids and Cardiovascular Events [2]. In this study, adverse event 
rates ranged from 0.5% to 13.6%. Additional assumptions include a two-sided test with 
significance level at 0.05. 
When AEs occur at a range of rates similar to those seen in the placebo group in the above 
referenced alirocumab study (0.5% to 13.6%), the sample size of 600 patients randomized to 
ETC-1002 and 300 patients randomized to placebo will allow for detection of relative risks of 
1.0 and of 2.0 (ETC-1002:placebo) with the following approximate 95% confidence limits:  
% Placebo Patients 
Experiencing AE 
% ETC-1002 
Patients 
Experiencing AE 
Relative Risk 
Approximate 95% 
Confidence Interval 
0.5% 
0.5% 
1.0 
(0.1, 7.0) 
0.5% 
1.0% 
2.0 
(0.3, 11.9) 
13.6% 
13.6% 
1.0 
(0.7, 1.4) 
13.6% 
27.2% 
2.0 
(0.5, 2.3) 
 
New Text: 
Sample Size 
A total of 9001950 patients will be enrolled in this study with 600 1300 patients randomized to 
ETC-1002 and 300 650 patients randomized to placebo. Using an anticipated overall dropout 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 213 of 287 
rate of 7.5% at 6 months and 10.0% at 12 months in each treatment group, the expected number 
of patients exposed to treatment during the study is as follows: 
 
Patients ≥6 Months 
Patients ≥12 Months 
ETC-1002 
5551,202 
5401,170 
Placebo 
278601 
270585 
 
Absolute risk will be addressed by 6001300 patients randomized to ETC-1002 and will provide 
at least 95% power to detect AEs that occur at rates similar to those seen in the placebo group 
for the AEs of interest in the recently completed long-term safety study entitled Efficacy and 
Safety of Alirocumab in Reducing Lipids and Cardiovascular Events [2]. In this study, adverse 
event rates ranged from 0.5% to 13.6%. Additional assumptions include a two-sided test with 
significance level at 0.05. 
When AEs occur at a range of rates similar to those seen in the placebo group in the above 
referenced alirocumab study (0.5% to 13.6%), the sample size of 6001300 patients randomized 
to ETC-1002 and 300650 patients randomized to placebo will allow for detection of relative 
risks of 1.0 and of 2.0 (ETC-1002:placebo) with the following approximate 95% confidence 
limits:  
% Placebo Patients 
Experiencing AE 
% ETC-1002 
Patients 
Experiencing AE 
Relative Risk 
Approximate 95% 
Confidence Interval 
0.5% 
0.5% 
1.0 
(0.1, 7.0)(0.3, 3.8) 
0.5% 
1.0% 
2.0 
(0.3, 11.9)(0.6, 6.7) 
13.6% 
13.6% 
1.0 
(0.7, 1.4)(0.8, 1.3) 
13.6% 
27.2% 
2.0 
(0.5, 2.3)(1.6, 2.5) 
CHANGE 15 APPLICABLE STATISTICAL SECTIONS WERE UPDATED TO ALIGN 
WITH OTHER REVISIONS IN THIS AMENDMENT 
Location:  
Synopsis, Statistical methods 
Original Text: 
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) will also be applied to the data; any potential Hy’s law cases will 
be listed separately. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 214 of 287 
New Text: 
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) 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 will be based upon direct (conjugated) bilirubin. 
CHANGE 16 REMOVED THE COLLECTION OF BLOOD SAMPLES FOR 
PHARMACOKINETIC ASSESSMENT 
Location: 
Synopsis, Statistical methods 
Original Text:  
PK and Other biomarkers 
hs-CRP values and percent change from baseline in values will be summarized by treatment 
group at Weeks 12, 24, and 52. The FAS will be used, with patients included in their randomized 
treatment group, regardless of the treatment they actually received. Only observed case data will 
be used (no imputation for missing data). 
In addition, trough plasma concentrations will be collected at Weeks 12, 24, and 52 for use in 
further developing the population pharmacokinetic (PK) model. 
New Text: 
PK and Other biomarkers 
hs-CRP values and percent change from baseline in values will be summarized by treatment 
group at Weeks 12, 24, and 52. The FAS will be used, with patients included in their randomized 
treatment group, regardless of the treatment they actually received. Only observed case data will 
be used (no imputation for missing data). 
In addition, trough plasma concentrations will be collected at Weeks 12, 24, and 52 from patients 
randomized into the study prior to the implementation of Protocol Amendment 3 for use in 
further developing the population pharmacokinetic (PK) model. Trough plasma concentrations 
will not be collected from patients randomized into the study after the implementation of 
Protocol Amendment 3. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 215 of 287 
CHANGE 17 TYPOGRAPHICAL ERRORS AND FORMATTING 
Location: 
Section 4.2.3., Previous Human Experience 
Original Text: 
In clinical drug-drug interaction studies, ETC-1002 240 mg showed less than a 2-fold transient 
increase in the exposure of atorvastatin 10 mg, simvastatin 20 mg, pravastatin 40 mg, and 
rosuvastatin 10 mg in 2 statin drug-drug interaction studies (Studies 1002-007 and 1002-012). 
New Text: 
InTwo clinical (Studies 1002-007 and 1002-012) drug drug interaction studies that evaluated 
drug-drug interactions of ETC-1002 240 mg with statins showed less than a 2-fold 
transientincrease in the exposure of atorvastatin 10 mg, simvastatin 20 mg, pravastatin 40 mg, 
and rosuvastatin 10 mg in 2 statin drug drug interaction studies(Studies 1002 007 
and 1002 012). Likewise, when ETC-1002 180 mg was dosed in combination with high-dose 
statins (atorvastatin 80 mg, pravastatin 80 mg, rosuvastatin 40 mg, and simvastatin 40 mg) 
exposure of these statins increased between approximately 1.4- and 2-fold (Study 1002-035).  
CHANGE 18 REVISED HIGH-DOSE STATIN EXCLUSION 
Location: 
Section 6.1., Overall Study Design 
Original Text: 
This is a Phase 3, randomized, double-blind, placebo-controlled, parallel group, study evaluating 
the long-term safety and tolerability of ETC-1002 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-lowering therapy 
includes a maximally tolerated statin alone or in combination with other lipid-lowering therapies 
(eg, ezetimibe, fibrates [except gemfibrozil]). 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. However, 
patients currently taking high-dose statins, defined as rosuvastatin 40 mg, atorvastatin 80 mg, or 
simvastatin 40 or 80 mg per day, or who are currently taking a PCSK9 inhibitor (alirocumab or 
evolocumab), or have taken a PCSK9 inhibitor within the past 4 weeks of Week -2 (Visit S1) will 
be excluded from enrolling in this study. PCSK9 inhibitors may be initiated as adjunctive 
therapy at Week 24 if the LDL-C threshold criteria have been met as described in 
Section 11.1.6.3.5. 
New Text: 
This is a Phase 3, randomized, double-blind, placebo-controlled, parallel group, study evaluating 
the long-term safety and tolerability of ETC-1002 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-lowering therapy 
includes a maximally tolerated statin alone or in combination with other lipid-lowering therapies 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 216 of 287 
(eg, ezetimibe, fibrates [except gemfibrozil]). 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. However, 
patients who are currently taking high dose statins, defined as rosuvastatin 40 mg, atorvastatin 
80 mg, or simvastatin at average daily doses that are greater than 40or 80 mg per day or who 
are currently taking a PCSK9 inhibitor (alirocumab or evolocumab), or have taken a PCSK9 
inhibitor within the past 4 weeks of Week -2 (Visit S1) will be excluded from enrolling in this 
study. PCSK9 inhibitors may be initiated as adjunctive therapy at Week 24 if the LDL-C 
threshold criteria have been met as described in Section 11.1.6.3.5. 
Original Text: 
Statin dose categories and randomization strata are defined in the Table 2 and Table 3 below, 
respectively: 
Table 2: 
Baseline Statin Dose Categories 
High Intensity Statins 
Moderate Intensity Statins 
Low Intensity Statinsa 
Atorvastatin 40-80b mg 
Atorvastatin 10-20 mg 
Simvastatin 10 mg 
Rosuvastatin 20-40c mg 
Rosuvastatin 5-10 mg 
Pravastatin 10-20 mg 
 
Simvastatin 20-40d 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 
 
Note: The highest dose statins are allowed if given on less than a daily basis. 
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) 
b Atorvastatin 80 mg daily is not allowed in this study.  
c Rosuvastatin 40 mg daily is not allowed in this study 
d Simvastatin 40-80 mg daily is not allowed in this study 
New Text: 
Statin dose categories, based on average daily dose, and randomization strata are defined in the 
Table 2 and Table 3 below, respectively: 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 217 of 287 
Table 2: 
Baseline Statin Dose Categories 
High Intensity Statins 
Moderate Intensity Statins 
Low Intensity Statinsa 
Atorvastatin 40-80b mg 
Atorvastatin 10-20 mg 
Simvastatin 10 mg 
Rosuvastatin 20-40c mg 
Rosuvastatin 5-10 mg 
Pravastatin 10-20 mg 
 
Simvastatin 20-40db 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 
 
Note: The highest dose statins are allowed if given on less than a daily basis. 
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) 
b Atorvastatin 80 mg daily is not allowed in this study.  
c Rosuvastatin 40 mg daily is not allowed in this study 
db Simvastatin average daily doses greater than 40 80 mg daily is are not allowed in this study 
Original Text: 
Table 3: 
Randomization Strata 
HeFH (with or without ASCVD) 
ASCVD (without HeFH) 
HeFH+ Low Intensity Statins 
ASCVD + Low Intensity Statins 
HeFH+ Moderate Intensity Statins 
ASCVD + Moderate Intensity Statins 
HeFH+ High Intensity Statinsa 
ASCVD + High Intensity Statinsa 
ASCVD = Atherosclerotic cardiovascular diseases; HeFH = Heterozygous familial hypercholesterolemia. 
a Atorvastatin 80 mg, rosuvastatin 40 mg, and simvastatin 40-80 mg daily are not allowed in this study. 
New Text: 
Table 3: 
Randomization Strata 
HeFH (with or without ASCVD) 
ASCVD (without HeFH) 
HeFH+ Low Intensity Statins 
ASCVD + Low Intensity Statins 
HeFH+ Moderate Intensity Statins 
ASCVD + Moderate Intensity Statins 
HeFH+ High Intensity Statinsa 
ASCVD + High Intensity Statinsa 
ASCVD = Atherosclerotic cardiovascular diseases; HeFH = Heterozygous familial hypercholesterolemia. 
a Atorvastatin 80 mg, rosuvastatin 40 mg, and sSimvastatin average daily doses greater than 40 80 mg daily are not 
allowed in this study 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 218 of 287 
CHANGE 19 INCREASED SAMPLE SIZE 
Location: 
Section 6.2., Study Hypothesis 
Original Text: 
The study will characterize the long-term safety and tolerability of ETC-1002 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 long-term safety data are meaningful and interpretable. The 
extended treatment duration (52 weeks) and large patient number (n = 900) will provide robust 
long-term safety in high CV risk patients who have an unmet medical need for additional lipid-
lowering therapy, such as ETC-1002 once daily, orally bioavailable option 
New Text: 
The study will characterize the long-term safety and tolerability of ETC-1002 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 long-term safety data are meaningful and interpretable. The 
extended treatment duration (52 weeks) and large patient number (n = 9001950) will provide 
robust long-term safety in high CV risk patients who have an unmet medical need for additional 
lipid-lowering therapy, such as ETC-1002 once daily, orally bioavailable option 
CHANGE 20 INCREASED STUDY DURATION 
Location: 
Section 6.4., End of Study 
Original Text: 
The study will end when the last randomized patient completes their last study visit (last patient 
last visit [LPLV] for last randomized patient). The estimated overall duration of the study (first 
patient first visit [FPFV] to LPLV) is approximately 22 months. 
New Text: 
The study will end when the last randomized patient completes their last study visit (last patient 
last visit [LPLV] for last randomized patient). The estimated overall duration of the study (first 
patient first visit [FPFV] to LPLV) is approximately 2228 months. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 219 of 287 
CHANGE 21 INCREASED SAMPLE SIZE 
Location: 
Section 6.5., Number of Patients 
Original Text: 
The study will enroll approximately 900 adult male and female HeFH and/or ASCVD patients 
with hyperlipidemia from approximately 125 clinical sites. 
New Text: 
• The study will enroll approximately 9001950 adult male and female HeFH and/or 
ASCVD patients with hyperlipidemia from approximately 125 clinical sites. 
CHANGE 22 REVISED INCLUSION CRITERIA 
Location: 
Section 7.1., Subject Inclusion Criteria 
Original Text: 
2. Men and nonpregnant, nonlactating women. Women must be either:  
• 
Naturally postmenopausal (as reported by the patient, defined as greater than 
55 years and ≥1 year without menses, less than 55 years and ≥1 year without 
menses with follicle-stimulating hormone (FSH) ≥40.0 IU/L), or surgically sterile 
(including hysterectomy and/or bilateral oophorectomy, but not tubal ligation 
alone) or;  
• Women of childbearing potential must be willing to use 1 acceptable method of 
birth control. 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). 
New Text: 
2. Men and nonpregnant, nonlactating women. Women must be either:  
• Naturally postmenopausal (as reported by the patient, defined as greater than 
55 years and ≥1 year without menses, less than 55 years and ≥1 year without 
menses with follicle-stimulating hormone (FSH) ≥40.0 IU/L), or surgically sterile 
(including hysterectomy, and/or bilateral oophorectomy, but notor tubal 
ligationalone) or;  
• Women of childbearing potential must be willing to use 1 acceptable method of 
birth control. The minimal requirement for adequate contraception 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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 220 of 287 
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). 
CHANGE 23 REVISED INCLUSION CRITERIA 
Location:  
Section 7.2., Subject Exclusion Criteria 
Original Text:  
1. Total fasting triglyceride >400 mg/dL (4.5 mmol/L) at Week -2 (Visit S1) 
Note: TG may be repeated 1 time with the screening period extended up to 2 weeks. For 
those patients who have a repeat TG, the mean of the first value and the repeat value will 
be used to determine eligibility. 
2. Renal dysfunction or nephritic syndrome or a history of nephritis, including eGFR (using 
central laboratory determined Modification of Diet in Renal Disease [MDRD] formula) 
<45 mL/min/1.73m2 at Week -2 (Visit S1) [1]. 
New Text: 
1. Total fasting triglyceride >400500 mg/dL (45.56 mmol/L) at Week -2 (Visit S1) 
Note: TG may be repeated 1 time with the screening period extended up to 2 weeks. For 
those patients who have a repeat TG, the mean of the first value and the repeat value will 
be used to determine eligibility. 
2. Renal dysfunction or nephritic syndrome or a history of nephritis, including eGFR (using 
central laboratory determined Modification of Diet in Renal Disease [MDRD] formula) 
<4530 mL/min/1.73 m2 at Week -2 (Visit S1) [1]. 
Original Text: 
4. Concomitant use of high dose statins, defined as rosuvastatin 40 mg, atorvastatin 80 mg, 
or simvastatin 40 or 80 mg daily.  
New Text: 
4. Concomitant use of high dose statins, defined as rosuvastatin 40 mg, atorvastatin 80 mg, 
or simvastatin 40 or 80 mg at average daily doses greater than 40 mg.  
Original Text: 
10. Liver disease or dysfunction, including:  
• Positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C 
antibodies (HCV-AB) at Week -2 (Visit S1); or 
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≥1.5 × ULN, 
and/or total bilirubin (TB) ≥1.2 × ULN at Week -2 (Visit S1).  

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 221 of 287 
Note: At the discretion of the investigator, the screening period may be extended up to 
2 weeks for a single repeat of ALT, AST, and/or TB. For those patients who have a 
repeat ALT, AST, and/or TB, the repeat value will be used to determine eligibility. 
New Text: 
10. Liver disease or dysfunction, including:  
• Positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C 
antibodies (HCV-AB) at Week -2 (Visit S1); or 
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≥1.52 × ULN, 
and/or total bilirubin (TB) ≥1.2 × ULN at Week -2 (Visit S1).  
Note: If HCV-AB is positive, a reflex HCV RNA will be performed to rule out active 
disease. Patients without active disease may be enrolled the study. 
Note: At the discretion of the investigator, the screening period may be extended up to 
2 weeks for a single repeat of ALT, AST, and/or TB. For those patients who have a 
repeat ALT, AST, and/or TB, the repeat value will be used to determine eligibility. 
If TB ≥1.2 × ULN, a reflex indirect (unconjugated) bilirubin will be obtained and if 
consistent with Gilbert’s disease, the patient may be enrolled in the study. 
Original Text: 
16. Blood donation, participation in a clinical study with multiple blood draws, major trauma, 
or surgery with or without blood loss within 30 days prior to randomization 
17. Blood transfusion for any reason within 90 days prior to randomization 
New Text: 
16. 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 
17. Blood transfusion for any reason within 90 days prior to randomization 
Original Text: 
21. 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 (6 months prior to randomization) 
New Text: 
20. Planned initiation of the following drugs during the clinical trial or changes to the 
following drugs prior to randomization: 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 222 of 287 
• Hormone replacement (6 weeks prior to randomization) 
• Thyroid replacement (6 weeks prior to randomization) 
• Diabetes medications (4 weeks prior to randomization) 
• Obesity medication (63 months prior to randomization) 
CHANGE 24 REVISED ADMINISTRATION INSTRUCTIONS FOR IMP 
Location: 
Section 7.3., Patient Lifestyle and Dietary Guidelines 
Original Text: 
Each dose of study drug is comprised of 1 tablet from 1 bottle that will be dispensed at each 
scheduled clinic visit. Study drug should be taken each morning and may be taken with or 
without food. 
New Text: 
Each dose of study drug is comprised of 1 tablet from 1 bottle that will be dispensed at each 
scheduled clinic visit. Study drug should be taken each morningonce a day (once every 24 hours) 
at approximately the same time every day and may be taken with or without food. 
CHANGE 25 REVISED HIGH-DOSE STATIN EXCLUSION 
Location: 
Section 8.2.1., Lipid-Regulating Medications and Supplements 
Original Text: 
Statins 
• Atorvastatin (Lipitor®, Sortis®), with doses <80 mg 
• Fluvastatin (Lescol®) 
• Lovastatin (Mevacor®, Altoprev™) 
• Pravastatin (Pravachol®) 
• Pitavastatin (Livalo®, Lipostat®) 
• Rosuvastatin (Crestor®), with doses <40 mg 
• Simvastatin (Zocor®), with doses <40 mg 
Selective cholesterol and/or bile acid absorption inhibitors 
• Cholestyramine/Colestryamine (Questran®, Questran Light®, Prevalite®, Locholest®, 
Locholest® Light) 
• Colestipol (Colestid®) 
• Colesevelam hydrochloride (Welchol®,Cholestagel®) 
• Ezetimibe (Zetia®, Ezetrol®) 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 223 of 287 
Fibrates 
• Fenofibrate (Antara®, Lofibra®, Tricor®, Triglide™, Lipantil®, Supralip®)  
• Bezafibrate (Bezalip®) 
• Ciprofibrate (Modalim®) 
PCSK9 inhibitors (allowed as adjunctive therapy beginning at Week 24 [Visit T5]; see 
Section 11.1.6.3.5) 
• Alirocumab (Praluent®) 
• Evolocumab (Repatha®) 
Other 
• Simvastatin/ezetimibe (Vytorin®, Inegy®) with dose of simvastatin <40 mg 
• Lovastatin/niacin (Advicor®) 
• Simvastatin/niacin (Simcor®) with dose of simvastatin<40 mg 
• Atorvastatin/ezetimibe (Liptruset®, Atozet®) with dose of atorvastatin <80 mg 
New Text: 
Statins 
• Atorvastatin (Lipitor®, Sortis®), with doses <80 mg 
• Fluvastatin (Lescol®) 
• Lovastatin (Mevacor®, Altoprev™) 
• Pravastatin (Pravachol®) 
• Pitavastatin (Livalo®, Lipostat®) 
• Rosuvastatin (Crestor®), with doses <40 mg 
• Simvastatin (Zocor®), with daily doses <40 mg 
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®) 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 224 of 287 
• Ciprofibrate (Modalim®) 
PCSK9 inhibitors (allowed as adjunctive therapy beginning at Week 24 [Visit T5]; see 
Section 11.1.6.3.5) 
• Alirocumab (Praluent®) 
• Evolocumab (Repatha®) 
Other 
• Simvastatin/ezetimibe (Vytorin®, Inegy®) with the average daily dose of simvastatin 
<≤40 mg 
• Lovastatin/niacin (Advicor®) 
• Simvastatin/niacin (Simcor®) with dose of simvastatin<40 mg 
• Atorvastatin/ezetimibe (Liptruset®, Atozet®) with dose of atorvastatin <80 mg 
CHANGE 26 REVISED HIGH-DOSE STATIN EXCLUSION 
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. 
• Gemfibrozil (Lopid®)  
• Cholestin (red yeast rice, also known as monascus purpureus extract) 
• Atorvastatin (Lipitor®, Sortis®) 80 mg, Simvastatin (Zocor®) 40-80 mg, and 
Rosuvastatin (Crestor®) 40 mg alone or in fixed-dose combinations (eg, Liptruzet®, 
Vytorin®/Inegy®, Simcor®) 
New 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. 
• Gemfibrozil (Lopid®)  
• Cholestin (red yeast rice, also known as monascus purpureus extract) 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 225 of 287 
• Atorvastatin (Lipitor®, Sortis®) 80 mg, Simvastatin (Zocor®), average daily doses 
greater than 40 80 mg,and Rosuvastatin (Crestor®) 40 mg alone or in fixed-dose 
combinations (eg, Liptruzet®, Vytorin®/Inegy®, Simcor®, with average daily doses 
greater than 40 mg/10 mg) 
CHANGE 27 DECREASE THE AMOUNT OF TIME PATIENTS SHOULD BE STABLE 
ON OBESITY MEDICATIONS 
Location: 
Section 8.2.3., Allowable Medications 
Original Text:  
The following must be stable for a minimum of 6 months prior to screening and, if possible not 
be adjusted during the study except for reasons of safety: 
• Antiobesity medications 
New Text: 
The following must be stable for a minimum of 63 months prior to screening and, if possible not 
be adjusted during the study except for reasons of safety: 
• Antiobesity medications 
CHANGE 28 INCLUDE A SECTION IN THE PROTOCOL TO ADDRESS OVERDOSE 
Location: 
Section 8.5 
Original Text: 
Note: No original text as it was not included in the previous versions of the protocol 
New Text: 
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. 
CHANGE 29 REVISED ADMINISTRATION INSTRUCTIONS FOR IMP 
Location: 
Section 9.2., Administration of Investigational Medicinal Product 
Original Text: 
Patients will be instructed to ingest IMP orally once daily in the morning with up to 16 ounces of 
water with or without food. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 226 of 287 
New Text: 
Patients will be instructed to ingest IMP orally once daily (once every 24 hours in the morningat 
approximately the same time each day with up to 16 ounces of water. IMP may be taken with or 
without food. 
CHANGE 30 REVISED REFERENCES TO CLINICAL SAFETY LABORATORIES, 
OTHER SCREENING LABORATORIES, AND LIPID ASSESSMENTS 
Location: 
Section 10.2.2., Treatment Week 0 (Visit T1; Day1) 
Original Text: 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, coagulation, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− apoB 
− HbA1C  
− hs-CRP 
− Reserve sample 
• Review inclusion/exclusion criteria to establish patient eligibility 
New Text: 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, coagulation, and urinalysis 
Note: Urine pregnancy test (only in Canada for appropriate female patients) 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− apoB 
− HbA1C  
− hs-CRP 
− Reserve sample  
− Genetic sample (if the patient has consented to provide a genetic sample) 
• Review inclusion/exclusion criteria to establish patient eligibility 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 227 of 287 
CHANGE 31 REVISED REFERENCES TO CLINICAL SAFETY LABORATORIES, 
OTHER SCREENING LABORATORIES, AND LIPID ASSESSMENTS 
Location: 
10.2.5., Treatment Week 12 (Visit T4; ± 3 days) 
Original Text: 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, coagulation, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− apoB 
− HbA1C 
− hs-CRP 
− PK sample 
− Reserve sample  
• Conduct diet and exercise counseling 
New Text: 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, coagulation, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− apoB 
− HbA1C 
− hs-CRP 
− PK sample (for patients who were randomized into the study prior to the 
implementation of Protocol Amendment 3) 
− Reserve sample  
• Conduct diet and exercise counseling 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 228 of 287 
CHANGE 32 REVISED REFERENCES TO CLINICAL SAFETY LABORATORIES, 
OTHER SCREENING LABORATORIES, AND LIPID ASSESSMENTS 
Location: 
10.2.6., Treatment Week 24 (Visit T5; ± 7 days) 
Original Text: 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− apoB 
− hs-CRP 
− PK sample 
− Reserve sample  
• Conduct diet and exercise counseling 
New Text: 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− apoB 
− hs-CRP 
− PK sample (for patients who were randomized into the study prior to the 
implementation of Protocol Amendment 3) 
− Reserve sample  
• Conduct diet and exercise counseling 
CHANGE 33 REVISED REFERENCES TO CLINICAL SAFETY LABORATORIES, 
OTHER SCREENING LABORATORIES, AND LIPID ASSESSMENTS 
Location: 
Section 10.2.8., Treatment Week 52 (Visit T7; ± 7 days) 
Original Text: 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, coagulation, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− apoB 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 229 of 287 
− HbA1C 
− hs-CRP 
− PK sample 
− Reserve sample 
New Text: 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, coagulation, and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− apoB 
− HbA1C 
− hs-CRP 
− PK sample (for patients who were randomized into the study prior to the 
implementation of Protocol Amendment 3) 
− Reserve sample 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 230 of 287 
CHANGE 34 REVISED REFERENCES TO CLINICAL SAFETY LABORATORIES, 
OTHER SCREENING LABORATORIES, AND LIPID ASSESSMENTS 
Location: 
Section 11.1.6.1., Laboratory Parameters, Table 5 
Original Text: 
Table 5: 
Clinical Laboratory Parameters (Safety) 
Clinical Laboratory Test 
Clinical Laboratory Test 
• 
Hematology 
Blood Chemistry (serum, fasting) 
• 
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 %) 
• 
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) 
• 
Total protein 
• 
Uric acid 
Urinalysis (Dipstick) 
• 
Clarity 
• 
Bilirubin 
• 
Color 
• 
Glucose 
• 
Ketones 
• 
Leukocyte esterase 
• 
Nitrate 
• 
Occult blood 
• 
pH 
• 
Protein 
• 
Specific gravity 
• 
Urobilinogen 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 231 of 287 
Table 5: 
Clinical Laboratory Parameters (Safety) (Continued) 
Clinical Laboratory Test 
Clinical Laboratory Test 
Urinalysis (Microscopic)-only if urine dipstick 
abnormal 
Coagulation  
• 
Bacteria 
• 
Casts 
• 
Crystals 
• 
Epithelial cells 
• 
Red blood cell (RBC) 
• 
WBC 
• 
Prothrombin time (PT) 
• 
International normalized ration (INR) 
Other Screening Labs 
Additional samples 
• 
Hepatitis B surface antigen (HBsAg), 
hepatitis C virus (HCV) 
• 
Serum pregnancy test (only for females 
of childbearing potential) 
• 
Follicle-stimulating hormone (FSH; 
Females <55 years and >1 year without 
menses) 
• 
Thyroid-stimulating hormone (TSH) 
• 
Hemoglobin A1C (HbA1C) 
• 
Reserve blood samples for potential 
future measurement of ETC-1002 safety 
or pharmacodynamic biomarkers 
• 
PK sample  
• 
Reserve genetic blood sample (optional) 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 232 of 287 
New Text: 
Table 5: 
Clinical Laboratory Parameters (Safety) 
Clinical Laboratory Test 
Clinical Laboratory Test 
• 
Hematology 
Blood Chemistry (serum, fasting) 
• 
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 %) 
• 
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 
• 
Nitrate 
• 
Occult blood 
• 
pH 
• 
Protein 
• 
Specific gravity 
• 
Urobilinogen 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 233 of 287 
Table 5: 
Clinical Laboratory Parameters (Safety) (Continued) 
Clinical Laboratory Test 
Clinical Laboratory Test 
Urinalysis (Microscopic)-only if urine dipstick 
abnormal 
Coagulation—In all patients at screening, then only 
in patients receiving anticoagulant therapy that in 
the investigator’s judgment require monitoring at 
Visit T1 and 3 to 5 days post Visit T1 
• 
Bacteria 
• 
Casts 
• 
Crystals 
• 
Epithelial cells 
• 
Red blood cell (RBC) 
• 
WBC 
• 
Prothrombin time (PT) 
• 
International normalized ration (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 (only in Canada for 
appropriate female patients) 
• 
Thyroid-stimulating hormone (TSH) 
• 
Hemoglobin A1C (HbA1C) 
• 
Reserve blood samples for potential 
future measurement of ETC-1002 safety 
or pharmacodynamic biomarkers 
• 
PK sample (for patients who were 
randomized into the study prior to the 
implementation of Protocol 
Amendment 3)  
• 
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 35 REVISED THE MONITORING AND MANAGEMENT OF ELEVATED 
LIVER FUNCTION TESTS 
Location: 
11.1.6.3.1., Monitoring and Management of Elevated Liver Function Tests 
Original Text: 
• If repeat LFT assessment confirms ALT and/or AST >3 × ULN in addition to any of 
the following, the patient should be given no further IMP treatment, but will be asked 
to continue to be followed for safety using the protocol-specified visit schedule (see 
Appendix 1): 
− TB >2 × ULN 
− INR >1.5 × ULN (unless the patient is on stable dose of anticoagulation 
medication) 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 234 of 287 
− Appearance or worsening of right upper abdominal discomfort, anorexia, fatigue, 
nausea, vomiting, fever, rash, or eosinophilia 
New Text: 
• If repeat LFT assessment confirms ALT and/or AST >3 × ULN in addition to any of 
the following, the patient should be given no further IMP treatment, but will be asked 
to continue to be followed for safety using the protocol-specified visit schedule (see 
Appendix 1): 
− TB >2 × ULN 
− Note: In the case of patients with Gilbert’s disease, TB will be fractionated and 
the determination of 2 × ULN will be based upon direct (conjugated) bilirubin. 
− INR >1.5 × ULN (unless the patient is on stable dose of anticoagulation 
medication) 
− Appearance or worsening of right upper abdominal discomfort, anorexia, fatigue, 
nausea, vomiting, fever, rash, or eosinophilia 
CHANGE 36 REVISED THE MONITORING AND MANAGEMENT OF ELEVATED 
LDL-C 
Location: 
Section 11.1.6.3.5., Monitoring and Management of Elevated LDL-C 
Original Text: 
− 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 using high doses of 
statins excluded from the study (rosuvastatin 40 mg, atorvastatin 80 mg, and 
simvastatin 40 or 80 mg daily) 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 and or dose change of these medications will be documented on the 
eCRF as a concomitant medication with the associated start date 
− Adjunctive therapy medications will not be provided by the sponsor 
New Text: 
− 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 using high doses of 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 235 of 287 
statins excluded from the study (rosuvastatin 40 mg, atorvastatin 80 mg, and 
simvastatin at average daily doses greater than 40 mg 40 or 80 mg daily) 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 and or dose changes of any existing lipid-lowering 
treatmentof these medications 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 
safety laboratory assessment that will include hematology, blood chemistry, and 
urinalysis. Additional safety laboratory assessments may be conducted at the 
investigator’s discretion.  
− Adjunctive therapy medications will not be provided by the sponsor 
CHANGE 37 REVISED THE MONITORING AND MANAGEMENT OF ELEVATED 
TRIGLYCERIDES 
Location: 
Section 11.1.6.3.6., Monitoring and Management of Elevated Triglycerides 
Original Text: 
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 500 mg/dL (5.6 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 >500 mg/dL (5.6 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 >500 mg/dL (5.6 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. 
New Text: 
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 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Summaiy of Changes Amendment 3 
Amendment 5, 10 May 2017 
opportunity to adjust the patient's standard of care regimen. Beginning at Week 4 (Visit T2), if 
the TG level exceeds JOO~ mg/dL (~11.3 mmol/L) while on ti·eatment, the investigator will 
receive notification from the centi·al laborato1y 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 confom 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 repo1i fo1m as a concomitant medication with the associated staii date. 
These medications will not be provided by the sponsor. 
-
-
Confidential 
Page 236 of 287 

ETC-1002 
Clinical Study Protocol 1002-040 
Esperion Therapeutics, Inc. 
Summaiy of Changes Amendment 3 
Amendment 5, 10 May 2017 
CHANGE 39 REMOVED THE COLLECTION OF BLOOD SAMPLES FOR 
PHARMACOKINETIC ASSESSMENT 
Location: 
Section 11.1.6.5., Phaimacokinetic Assessments 
Original Text: 
Phaimacokinetic assessments to measure plasma concentrations of ETC-1002 and its metabolite 
ESP 15228 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. Phaimacokinetic sample analyses for ETC-1002 and ESP15228 will be conducted by 
the Bioanalytical Laborato1y. 
New Text: 
Ph8ilfta.eekmetie a,ssessmeftts Plasma te measare t3lasma concentrations of ETC-1002 and its 
metabolite ESP15228 will be eeaaaetea determined from 6 mL whole blood samples collected 
from patients at Weeks 12, 24, and 52. At the time of sample collection, the date and time of 
blood draw and the last 2 doses of study medication will be collected. Ph8i·Hlaeekifletie S8:Hlf)le 
aaalyses fer BTC H)Q2 e.ae B£Pl5228 will ee eeae:ietee ey the Bie8:ftalytie8:l Laeera.tery. 
CHANGE 40 REMOVED THE COLLECTION OF BLOOD SAMPLES FOR 
PHARMACOKINETIC ASSESSMENT 
Location: 
Section 11.1.6.6., Collection and Assessment of Phaimacokinetic Samples 
Original Text: 
Plasma concentrations ofETC-1002 and its metabolite (ESP15228) will be detennined using 
validated methods. Plasma PK samples will be labeled with preprinted info1mation, 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 fmiher 
instructions 
New Text: 
Pharmacokinetic samples will be collected from patients who were randomized into the study 
prior to the implementation of Protocol Amendment 3. 
Confidential 
Page 237 of287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 238 of 287 
Pharmacokinetic samples will not be collected for patients randomized into the study after 
initiation of Protocol Amendment 3. 
• Plasma concentrations of ETC-1002 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 
CHANGE 41 REVISED THE ADVERSE EVENT RELATIONSHIP TO STUDY DRUG 
SCALE 
Location: 
Section 11.2.5., Relationship 
Original Text: 
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  
• 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. 
• 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. 
New Text: 
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. 

ETC-1002 
Clinical Study Protocol 1002-040 
Esperion Therapeutics, Inc. 
Summaiy of Changes Amendment 3 
Amendment 5, 10 May 2017 
• 
Definite: Established temporal association with administration of the study drng with 
no other more probable cause. Typically, the event should resolve when the study 
drng is discontinued and recur on re-challenge. 
-
- I 
Confidential 
Page 239 of287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 240 of 287 
CHANGE 43 INCREASED SAMPLE SIZE AND APPLICABLE STATISTICAL 
SECTIONS WERE UPDATED TO ALIGN WITH OTHER REVISIONS IN 
THIS AMENDMENT 
Location: 
Section 12.2., Determination of Sample Size 
Original Text: 
A total of 900 patients will be enrolled in this study with 600 patients randomized to ETC-1002 
and 300 patients randomized to placebo. Using an anticipated overall dropout rate of 7.5% at 
6 months and 10.0% at 12 months in each treatment group, the expected number of patients 
exposed to treatment during the study is as follows: 
 
Patients ≥6 Months 
Patients ≥12 Months 
ETC-1002 
555 
540 
Placebo 
278 
270 
Absolute risk will be addressed by 600 patients randomized to ETC-1002 and will provide at 
least 95% power to detect AEs that occur at rates similar to those seen in the placebo group for 
the AEs of interest in the recently completed long-term safety study entitled Efficacy and Safety 
of Alirocumab in Reducing Lipids and Cardiovascular Events[2]. In this study adverse event 
rates ranged from 0.5% to 13.6%. Additional assumptions include a two-sided test with 
significance level at 0.05. 
When AEs occur at a range of rates similar to those seen in the placebo group in the above 
referenced alirocumab study (0.5% to 13.6%), the sample size of 600 patients randomized to 
ETC-1002 and 300 patients randomized to placebo will allow for detection of relative risks of 
1.0 and of 2.0 (ETC-1002:placebo) with the following approximate 95% confidence limits:  
% Placebo Patients 
Experiencing AE 
% ETC-1002 Patients 
Experiencing AE 
Relative Risk 
Approximate 95% 
Confidence Interval 
0.5% 
0.5% 
1.0 
(0.1, 7.0) 
0.5% 
1.0% 
2.0 
(0.3, 11.9) 
13.6% 
13.6% 
1.0 
(0.7, 1.4) 
13.6% 
27.2% 
2.0 
(0.5, 2.3) 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 241 of 287 
New Text: 
A total of 9001950 patients will be enrolled in this study with 6001300 patients randomized to 
ETC-1002 and 300650 patients randomized to placebo. Using an anticipated overall dropout 
rate of 7.5% at 6 months and 10.0% at 12 months in each treatment group, the expected number 
of patients exposed to treatment during the study is as follows: 
 
Patients ≥6 Months 
Patients ≥12 Months 
ETC-1002 
5551,202 
540,170 
Placebo 
278601 
270585 
Absolute risk will be addressed by 6001300 patients randomized to ETC-1002 and will provide 
at least 95% power to detect AEs that occur at rates similar to those seen in the placebo group 
for the AEs of interest in the recently completed long-term safety study entitled Efficacy and 
Safety of Alirocumab in Reducing Lipids and Cardiovascular Events[2]. In this study adverse 
event rates ranged from 0.5% to 13.6%. Additional assumptions include a two-sided test with 
significance level at 0.05. 
When AEs occur at a range of rates similar to those seen in the placebo group in the above 
referenced alirocumab study (0.5% to 13.6%), the sample size of 6001300 patients randomized 
to ETC-1002 and 300650 patients randomized to placebo will allow for detection of relative 
risks of 1.0 and of 2.0 (ETC-1002:placebo) with the following approximate 95% confidence 
limits:  
% Placebo Patients 
Experiencing AE 
% ETC-1002 Patients 
Experiencing AE 
Relative Risk 
Approximate 95% 
Confidence Interval 
0.5% 
0.5% 
1.0 
(0.1, 7.0)(0.3, 3.8) 
0.5% 
1.0% 
2.0 
(0.3, 11.9)(0.6, 6.7) 
13.6% 
13.6% 
1.0 
(0.7, 1.4)(0.8, 1.3) 
13.6% 
27.2% 
2.0 
(0.5, 2.3) (1.6, 2.5) 
CHANGE 44 STATISTICAL SECTIONS WERE UPDATED TO ALIGN WITH OTHER 
REVISIONS IN THIS AMENDMENT 
Location: 
Section 12.5., Primary Endpoint 
Original Text: 
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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 242 of 287 
accompanying TB >2 × ULN) will also be applied to the data; any potential Hy’s law cases will 
be listed separately. 
New Text: 
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) will also be applied to the data; any potential Hy’s 
law cases will be listed separately. 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. 
CHANGE 45 STATISTICAL SECTIONS WERE UPDATED TO ALIGN WITH OTHER 
REVISIONS IN THIS AMENDMENT 
Location: 
Section 12.7., PK and Other Biomarkers 
Original Text: 
In addition, trough plasma concentrations of ETC-1002 and ESP15228 will be collected at 
Weeks 12, 24, and 52 for use in further developing the population PK model. 
New Text: 
In addition, trough plasma concentrations of ETC-1002 and ESP15228 will be collected from 
patients randomized before the implementation of Protocol Amendment 3 at Weeks 12, 24, 
and 52 for use in further developing the population PK model. Trough plasma concentrations 
will not be collected from patients randomized after the implementation of Protocol 
Amendment 3. 
CHANGE 46 REVISED REFERENCES TO CLINICAL SAFETY LABORATORIES, 
OTHER SCREENING LABORATORIES, AND LIPID ASSESSMENTS 
(STUDY PROCEDURES, ASSESSMENT OF SAFETY, SCHEDULE OF 
STUDY EVENTS) 
Location: 
Appendix 1., Schedule of Events (Subject Visit Schedule) 

ETC-1002 
Clinical Study Protocol 1002-040 
Original T ex.t: 
Esperion Therapeutics, Inc. 
Summaiy of Changes Amendment 3 
Amendment 5, 10 May 2017 
APPENDIX 1. 
SCHEDULE OF EVENTS (SUBJECT VISIT SCHEDULE) 
Screen 
Treatment 
Visit 
S11,2 
Tl 
T2 
T3 
T4 
T5 
T6 
T7 EOS3 
Week 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
-2 
0 
4 
8 
12 
24 
36 
52 
Procedure 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
-16 to -4 
1 
29±3 
57±3 
85±3 
169±7 
253±7 
365±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 
Adverse Event Recording 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
X 
X 
Weight
4 
X 
X 
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 FSFr 
X 
TSH 
X 
Clinical Safety Labs9 
X 
X 
X 
X 
X 
X 
X 
X 
Basic Fasting Lipids10 
X 
X 
X 
X 
X 
X 
X 
X 
HbA1c 
X 
X 
X 
X 
IO mL rese1ve sample 
X 
X 
X 
X 
apoB 
X 
X 
X 
X 
hs-CRP 
X 
X 
X 
X 
Diet and exercise counseiing11 
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 
Double-blind Drug Dispensing13 
X 
X 
X 
X 
Drug Return/Compliance 
X 
X 
X 
X 
X 
X 
Schedule next visit 
X 
X 
X 
X 
X 
X 
X 
x' 
Confidential 
Page 243 of 287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 244 of 287 
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 
visit is completed, the mean of lipid values from both visits 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 in the morning 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 Pregnancy test completed in premenopausal women only. FSH test is completed in women <55 years old and >1 year without 
menses 
9 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits. Coagulation is included at Screening 
(Visit S1), Baseline (Visit T1), Week 12 (Visit T4), and at EOS (Visit T7). Please refer to 
 laboratory manual for 
detailed schedule of tests. 
10 Basic fasting 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. The bottle dispensed at Visit T1 will be returned to clinic at Visits T2 and T3 for evaluation of compliance and 
returned for continued use. 
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 

ETC-1002 
Clinical Study Protocol 1002-040 
New Text: 
Esperion Therapeutics, Inc. 
Summaiy of Changes Amendment 3 
Amendment 5, 10 May 2017 
APPENDIX 1. 
SCHEDULE OF EVENTS (SUBJECT VISIT SCHEDULE) 
Screen 
Treatment 
Visit 
S11,2 
Tl 
T2 
T3 
T4 
T5 
T6 
T7 EOS3 
Week 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
-2 
0 
4 
8 
12 
24 
36 
52 
Procedure 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
-16 to -4 
1 
29±3 
57±3 
85±3 
169±7 
253±7 
365±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 
Adverse Event Recording 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
X 
X 
Weight
4 
X 
X 
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 FSFr 
X 
Urine Pregnancy Tes/ 
X 
TSH 
X 
Clinical Safety Labs
9 
X 
X 
X 
X 
X 
X 
X 
X 
Basic Fasting Lipids10 
X 
X 
X 
X 
X 
X 
X 
X 
HbA1c 
X 
X 
X 
X 
IO mL rese1ve sample 
X 
X 
X 
X 
Genetic sample 
X 
apoB 
X 
X 
X 
X 
hs-CRP 
X 
X 
X 
X 
D' 
d 
. 
lin 11 
1et an exercise counse 
g 
X 
X 
X 
X 
X 
X 
X 
Plasma PK12 
X 
X 
X 
Establish Patient Eligibility 
X 
Randomization 
X 
IWRS Contact 
X 
X 
X 
X 
X 
XJ.J+;! 
Double-blind Drug 
X 
X 
X 
X 
Dispensing1m 
Drug Return/Compliance 
X 
X 
X 
X 
X 
X 
Schedule next visit 
X 
X 
X 
X 
X 
X 
X 
x4x5 
Confidential 
Page 245 of 287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 3 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 246 of 287 
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 
visit is completed, the mean of lipid values from both visits 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 in the morning 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. Urine pregnancy test is completed in premenopausal women 
who are able to become pregnant in Canada only. FSH test is completed in women <55 years old and >1 year without 
menses 
9 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits. These will also be conducted 4 weeks 
after any changes in the patient’s lipid-modifying treatment. Coagulation is included at Screening (Visit S1) for all patients, 
and then only in patients receiving anticoagulant therapy that in the investigator’s judgement requires monitoring at Baseline 
(Visit T1) and 3 to 5 days post Visit T1. Please refer to 
laboratory manual for detailed schedule of tests. 
10 Basic fasting 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. 
1212 PK samples will be collected from patients who were randomized prior to the implementation of Protocol Amendment 3.  
13 IWRS contact at either an early withdrawal or an EOS visit to register study discontinuation visit date.  
14 Depending upon the length of time between visits, 1 or 2 bottles of study medication will be dispensed as instructed by 
IWRS. The bottle dispensed at Visit T1 will be returned to clinic at Visits T2 and T3 for evaluation of compliance and 
returned for continued use. 
1415 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 
 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 4 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 247 of 287 
APPENDIX 9. SUMMARY OF CHANGES IN AMENDMENT 4 
 
 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 4 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 248 of 287 
SUMMARY OF CHANGES 
CLINICAL STUDY PROTOCOL 
 
Study Number: 
1002-040 
Study Title: 
A Randomized, Double-blind, Placebo-controlled, 
Multicenter Long-term Safety and Tolerability Study of 
ETC-1002 in Patients with Hyperlipidemia at High 
Cardiovascular Risk Who are not Adequately Controlled 
by Their Lipid-Modifying Therapy 
Protocol Version Incorporating 
Current Summary of Changes: 
Amendment 4: Amended Protocol 14 October 2016 
Preceding Protocol Version: 
Amendment 3: Amended Protocol 28 July 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 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: 
• Revised exclusion criteria to be consistent with current safety data and comply with 
US Food and Drug Administration request. Excluded are renally impaired patients 
receiving an average daily dose of simvastatin 40 mg with eGFR below 
<45 mL/min/1.73 m2 g. 
• To comply with US Food and Drug Administration request, additional visits (2 in the 
clinic and 2 by telephone) were added for clinical safety laboratory evaluations and 
adverse event monitoring for patients receiving an average daily dose of simvastatin 
40 mg.  
• Specify urine pregnancy test (for females of childbearing potential) for all countries. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 4 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 249 of 287 
• Typographical errors and formatting were corrected or revised to improve clarity and 
consistency. Only substantive changes are included in the Summary of Changes 
document. 
 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 4 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 250 of 287 
CHANGE 1 EXCLUSION CRITERIA MODIFICATION 
Location:  
Synopsis Exclusion Criteria; Section 7.2 
Original Text: 
• Renal dysfunction or nephritic syndrome or a history of nephritis, including eGFR 
(using central laboratory determined Modification of Diet in Renal Disease [MDRD] 
formula) <30 mL/min/1.73 m2 at Week -2 (Visit S1) [1].  
Note: At the discretion of the investigator, the screening period may be extended up 
to 2 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: 
• Renal dysfunction or nephritic syndrome or a history of nephritis, including eGFR 
(using central laboratory determined Modification of Diet in Renal Disease [MDRD] 
formula) <30 mL/min/1.73 m2 at Week -2 (Visit S1) [1].  
Note: At the discretion of the investigator, the screening period may be extended up 
to 2 weeks for a single repeat eGFR. For those patients who have a repeat eGFR, the 
repeat value will be used to determine eligibility. 
Note: Also excluded are renally impaired patients receiving an average daily dose of 
simvastatin 40 mg with eGFR below <45 mL/min/1.73 m2. 
CHANGE 2 URINE PREGNANCY TEST RQUIREMENT 
Location:  
Synopsis 
Original Text: 
Other Screening Laboratories: 
• Hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) (if HCV is positive, a 
reflex HCV RNA will be performed to rule out active disease), 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 pregnancy test Day 1 prior to 
randomization (only in Canada for females who are of childbearing potential), TSH 
New Text: 
Other Screening Laboratories: 
• Hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) (if HCV is positive, a 
reflex HCV RNA will be performed to rule out active disease), 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 pregnancy test Day 1 prior to 
randomization (only in Canada for females who are of childbearing potential), TSH 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 4 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 251 of 287 
CHANGE 3 ADDITIONAL SAFETY VISITS FOR PATIENTS WITH LIPID-
LOWERING TREATMENT MODIFICATIONS 
Location:  
Synopsis; Section 11.1.6.3.5 
Original Text: 
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.  
New Text: 
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. 
Patients receiving an average daily dose of simvastatin 40 mg based on lipid-lowering treatment 
modification, should adhere to the additional safety visits as described in Sections 10.2.5 
and 10.2.6. 
CHANGE 4 CORRECTION OF SYMBOL 
Location:  
Section 8.2.1 
Original Text: 
Simvastatin (Zocor®), with daily doses <40 mg 
New Text: 
Simvastatin (Zocor®), with daily doses ≤40 mg 
CHANGE 5 URINE PREGNANCY TEST RQUIREMENT 
Location:  
Section 10.2.2; Table 5 
Original Text: 
− Hematology, blood chemistry, and urinalysis 
Note: Urine pregnancy test (only in Canada for appropriate female patients) 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 4 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 252 of 287 
New Text 
− Hematology, blood chemistry, and urinalysis 
Note: Urine pregnancy test (only in Canada for appropriate female patientsfor 
females of childbearing potential) 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
CHANGE 6 EXCLUSION OF PATIENTS FROM PK SAMPLING  
Location:  
Sections 10.2.5; 10.2.6; 10.2.8; Table 5 
Original Text: 
• 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 (for patients who were randomized into the study prior to the 
implementation of Protocol Amendment 3) 
New Text: 
• 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 (for patients who were randomized into the study prior to the 
implementation of after Protocol Amendment 3 and subsequent amendments are 
excluded from PK sampling) 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 4 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 253 of 287 
CHANGE 7 ADDITIONAL SAFETY VISITS FOR PATIENTS RECEIVING AN 
AVERAGE DAILY DOSE OF SIMVASTATIN 40 MG AFTER VISITS T4 
AND T5 (identical except for visit numbers) 
Location:  
Sections 10.2.5.1, 10.2.5.2, 10.2.6.1, 10.2.6.2; Appendix 1, Schedule of Events  
New Text: 
10.2.5.1 
Treatment Week 16 (Visit T4.1; ±3 days) 
Patients on an average daily dose of simvastatin 40 mg will be scheduled for the additional 
Visit T4.1 for clinical safety laboratory evaluations specifically to monitor changes in creatine 
phosphokinase (CPK) and liver function tests (LFTs). Should changes be noted, the procedures 
described in Section 11.1.6.3.1 will apply. 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (ongoing) 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
• Conduct diet and exercise counseling 
10.2.5.2 
Treatment Week 20 (Visit T4.2; ±3 days) 
Patients on an average daily dose of simvastatin 40 mg will be contacted by telephone for the 
additional Visit T4.2 to 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (ongoing) 
• Remind subjects to take IMP as scheduled 
New Text: 
10.2.6.1 
Treatment Week 28 (Visit T5.1; ±7 days) 
Patients on an average daily dose of simvastatin 40 mg will be scheduled for the additional 
Visit T5.1 for clinical safety laboratory evaluations specifically to monitor changes in CPK and 
LFTs. Should changes be noted, the procedures described in Section 11.1.6.3.1 will apply. 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (ongoing) 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
• Conduct diet and exercise counseling 

ETC-1002 
Clinical Study Protocol 1002-040 
10.2.6.2 
Treatment Week 32 (Visit T5.2; ±7 days) 
Esperion Therapeutics, Inc. 
Summaiy of Changes Amendment 4 
Amendment 5, 10 May 2017 
Patients on an average daily dose of simvastatin 40 mg will be contacted by telephone for the 
additional Visit T5.2 to 
• 
Concomitant and prohibited medication review (ongoing) 
• 
Assess AEs, including muscle-related AEs (ongoing) 
• 
Remind subjects to take IMP as scheduled 
Original T ex.t: 
Screen 
Treatment 
Visit 
S11,2 
Tl 
T2 
T3 
T4 
T5 
Week 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
-2 
0 
4 
8 
12 
24 
Procedure 
Day 
Day 
Day 
Day 
Day 
Day 
-16 to -4 
1 
29±3 
57±3 
85±3 
169±7 
Informed Consent 
X 
Enrolhnent Criteria 
X 
Demographics 
X 
Medical Histo1y 
X 
HeFH Status Detennination 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
Adverse Event Recording 
X 
X 
X 
X 
X 
Physical Exam 
X 
Weight
4 
X 
X 
X 
X 
X 
X 
Height/BM! 
X 
12-Lead ECG5 
X 
Vital Signs6 
X 
X 
X 
X 
X 
X 
Serology
7 
X 
Serum Pregnancy and/or FSFr 
X 
Urine Pregnancy Tes/ 
X 
TSH 
X 
Clinical Safety Labs
9 
X 
X 
X 
X 
X 
X 
Basic Fasting Lipids10 
X 
X 
X 
X 
X 
X 
HbA1c 
X 
X 
X 
IO mL rese1ve sample 
X 
X 
X 
Genetic sample 
X 
apoB 
X 
X 
X 
hs-CRP 
X 
X 
X 
D' 
d 
. 
lin 11 
1et an exercise counse 
g 
X 
X 
X 
X 
X 
X 
Plasma PK12 
X 
X 
Establish Patient Eligibility 
X 
Randomization 
X 
Confidential 
Page 254 of 287 
T6 
T7 EOS3 
Wk 
Wk 
36 
52 
Day 
Day 
253±7 
365±7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 4 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 255 of 287 
IWRS Contact 
X 
X 
 
 
X 
X 
X 
X13 
Double-blind Drug Dispensing14 
 
X 
 
 
X 
X 
X 
 
Drug Return/Compliance 
 
 
X 
X 
X 
X 
X 
X 
Schedule next visit 
X 
X 
X 
X 
X 
X 
X 
X15 
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 
visit is completed, the mean of lipid values from both visits 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 in the morning 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. Urine pregnancy test is completed in premenopausal women 
who are able to become pregnant in Canada only. FSH test is completed in women <55 years old and >1 year without 
menses 
9 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits. These will also be conducted 4 weeks 
after any changes in the patient’s lipid-modifying treatment. Coagulation is included at Screening (Visit S1) for all patients, 
and then only in patients receiving anticoagulant therapy that in the investigator’s judgement requires monitoring at Baseline 
(Visit T1) and 3 to 5 days post Visit T1. Please refer to 
 laboratory manual for detailed schedule of tests. 
10 Basic fasting 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 PK samples will be collected from patients who were randomized prior to the implementation of Protocol Amendment 3.  
13 IWRS contact at either an early withdrawal or an EOS visit to register study discontinuation visit date.  
14 Depending upon the length of time between visits, 1 or 2 bottles of study medication will be dispensed as instructed by 
IWRS. The bottle dispensed at Visit T1 will be returned to clinic at Visits T2 and T3 for evaluation of compliance and 
returned for continued use. 
15 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 

ETC-1002 
Clinical Study Protocol 1002-040 
New Text: 
Sc1·een 
Visit 
s11.z 
Tl 
T2 
Week 
Wk 
Wk 
Wk 
-2 
0 
4 
Prncedul'e 
Day 
Day 
Day 
-16 to -4 
1 
29±3 
Info1med Consent 
X 
Enrollment Criteria 
X 
Demographics 
X 
Medical Histo1y 
X 
HeFH Status 
X 
Dete1mination 
Concomitant 
X 
X 
X 
Medications 
Adverse Event 
X 
X 
Recording 
Physical Exam 
X 
Weight4 
X 
X 
X 
Height/BMI 
X 
12-Lead ECG5 
X 
Vital Signs6 
X 
X 
X 
Serology7 
X 
Senun Pregnancy 
X 
and/or FSif 
Urine Pregnancy Tesl 
X 
TSH 
X 
Clinical Safety Labs9 
X 
X 
X 
Additional Clinical 
Safety Labs10 
Basic Fasting Lipidsll 
X 
X 
X 
HbA1c 
X 
X 
10 mL reserve sample 
X 
Genetic sample 
X 
apoB 
X 
hs-CRP 
X 
Diet and exercise 
X 
X 
X 
counseling12 
Plasma PK13 
Establish Patient 
X 
Eligibility 
Randomization 
X 
IWRS Contact 
X 
X 
Confidential 
T3 
T4 
T4.I 
Wk 
Wk 
Wk 
8 
12 
16 
Day 
Day 
Day 
57±3 
85±3 
112±3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Page 256 of 287 
Esperion Therapeutics, Inc. 
Summaiy of Changes Amendment 4 
Amendment 5, 10 May 2017 
Tl'eatment 
T4.2 
TS 
TS.I 
TS.2 
T6 
T7 EOS3 
phone 
phone 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
20 
24 
28 
32 
36 
52 
Day 
Day 
Day 
Day 
Day 
Day 
140±3 169±7 196±7 224±7 253±7 
365±7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X/4 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Summaiy of Changes Amendment 4 
Amendment 5, 10 May 2017 
Sc1·een 
Tl'eatment 
Visit 
s11.z 
Tl 
T2 
T3 
T4 
T4.I 
T4.2 
TS 
TS.I 
TS.2 
T6 
T7 EOS3 
p hone 
p hone 
Week 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
-2 
0 
4 
8 
12 
16 
20 
24 
28 
32 
36 
52 
Prncedul'e 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
-16 to -4 
1 
29±3 
57±3 
85±3 
112±3 140±3 169±7 196±7 224±7 253±7 
365±7 
Double-blind Dmg 
X 
X 
X 
X 
Dispensing15 
Dmg 
X 
X 
X 
X 
X 
X 
Retmn/Compliance 
Schedule next visit 
X 
X 
X 
X 
X 
X 
X 
.x'-6 
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 w-ith infomiation regarding ctm·ent health status and to collect infomiation on AEs (eg, recent procedm·es, 
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 retmning to clinic or by phone), Visit T7 ,vill be considered the EOS/Early Withdrawal 
from study and no further visits will be scheduled. 
1 An optional visit approxiniately 1 week later MAY be completed if patient fails to meet a lipid entiy criterion. If this optional 
visit is completed, the mean of lipid values from both visits will be used to detenuine eligibility. 
2 An optional visit between Visits Sl and Tl niay be completed if the patient's DBP and/or SBP meet the exclusion criteria 
levels. Patients may randomize after blood pressm·e medications have been adjusted, the patients have been on stable doses of 
blood pressure medications for at least 2 weeks, and the repeat blood pressm·e values (DBP and/or SBP) do not meet 
exclusionary values. An optional visit between Visit S 1 and Tl may be completed to detemiine 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 in the morning while fasting, using consistent scales, after voiding, and without shoes and 
oute1wear (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 Sernm pregnancy test completed in premenopausal women only. Urine pregnancy test is completed in premenopausal women 
who are able to become pregnant. FSH test is completed in women <55 years old and > 1 year without menses 
9 Clinical safety labs include heniatology, blood chemistiy, and m-inalysis at all visits. These will also be conducted 4 weeks after 
any changes in the patient's lipid-modifying treatment. Coagulation is included at Screening (Visit Sl )for all patients, and then 
only in patients receiving anticoagulant ther-
that in the investigator's judgement requires monitoring at Baseline (Visit Tl} 
and 3 to 5 days post Visit Tl. Please refer to 
laborato1y manual for detailed schedule of tests. 
IO Patients on an average daily dose of simvastatin 40 mg will be scheduled for additional Visits T4. l and T5.l to monitor clinical 
laboratory assessments and AE and SAE occurrence. These patients will also be contacted by telephone at Visits T4.2 and T5.2 
to monitor AE and SAE occurrence. 
II Basic fasting lipids include total cholesterol, calculated LDL-C, HDL-C, non-HDL-C, and triglycerides. Repeat within 1 week if 
exceed protocol-specified criteria. 
12Diet and exercise counseling per local and/or regional guidelines for the management ofhyperlipidemia. 
13 Patients randomized after Protocol Amendment 3 and subsequent amendments are excluded from PK sampling. 
14IWRS contact at either an early withdrawal or an EOS visit to register study discontinuation visit date. 
15 Depending upon the length of time between visits, 1 or 2 bottles of study medication will be dispensed as instructed by IWRS. 
The bottle dispensed at Visit Tl will be returned to clinic at Visits T2 and T3 for evaluation of compliance and rettuned for 
continued use. 
16 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 
Confidential 
Page 257 of 287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 258 of 287 
APPENDIX 10. SUMMARY OF CHANGES IN AMENDMENT 5

ETC-1002 
Clinical Study Protocol 1002-040 
Esperion Therapeutics, Inc. 
Summaiy of Changes Amendment 5 
Amendment 5, 10 May 2017 
SUMMARY OF CHANGES 
CLINICAL STUDY PROTOCOL 
Study Number: 
Study Title: 
Protocol Version Incorporating 
Current Summary of Changes: 
Preceding Protocol Version: 
Investigational Product Name: 
1002-040 
A Randomized, Double-blind, Placebo-controlled, 
Multicenter Long-tenn Safety and Tolerability Study of 
ETC-1002 in Patients with Hyperlipidemia at High 
Cai·diovasculai· Risk Who ai·e not Adequately Contrnlled 
by Their Lipid-Modifying Therapy 
Amendment 5: Amended Protocol 10 May 2017 
Amendment 4: Amended Protocol 14 October 2016 
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 inc01p orates the items specified in this Summaiy 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 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: 
• 
• 
Revised the collection of reserve samples to allow Sponsor to discontinue collection 
after it has been detennined that a sufficient number of samples have been collected 
• 
Revised procedures for Visits T4.1, T4.2, T5.1, and T5.2 to indicate that patients who 
were on 40 mg or greater simvastatin that were discontinued from IMP and who have 
provided consent to be followed in the safety follow-up should be scheduled for these 
visits 
• 
Added a procedure to Visit T7 for patients who are completing the study while taking 
IMP to collect info1mation regai·ding whether: 1) the patient was offered the open-
Confidential 
Page 259 of 287 

ETC-1002 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
Summaiy of Changes Amendment 5 
Amendment 5, 10 May 2017 
label extension study (Study 1002-050) and 2) if not, the reason that the open-label 
extension study was not offered to the patient 
• 
To fmther ensure patient safety, the monitoring and management of Creatine Kinase 
(CK) has been revised to include additional instructions for the investigator in cases 
where the repeat CK is confinned to be greater than 5 x ULN and the patient is 
asymptomatic 
• 
The study objectives and statistical section has been revised to be consistent with the 
revised version of the Statistical Analysis Plan (SAP) 
• 
Appendix 1; Schedule of Events (Subject Visit Schedule) revised to reflect all 
necessary changes in the amendment 
• 
Administrative Change: 
-
Revised header fo1mat to align with new Esperion Therapeutics, INC. protocol 
template 
Note: These changes will not be reflected in italics in the final amended protocol 
• 
Typographical eITors and fonnatting were co1Tected or revised to improve clai·ity and 
consistency. 
• 
Only substantive changes ai·e included in the Summaiy of Changes document 
Confidential 
Page 260 of 287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 261 of 287 
CHANGE 1 REVISION OF STUDY OBJECTIVES AND STATISTICAL SECTION TO 
ALIGN WITH REVISED SAP 
Location: 
Synopsis; Objectives 
Original Text: 
Primary: 
• 
To evaluate the long-term safety and tolerability of ETC-1002 versus placebo 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 assess percent change from baseline to Week 12 in low-density lipoprotein cholesterol 
(LDL-C) 
Tertiary: 
• 
To assess percent change from baseline to Week 24 and to Week 52 in LDL-C in patients who do 
not receive adjunctive lipid-lowering therapy 
• 
To assess high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC), and 
triglycerides (TG) values at Week 12, 24, and 52  
• 
To assess apolipoprotein B (apoB) and high-sensitivity C-reactive protein (hs-CRP) values at 
Week 12, 24, and 52 
New Text: 
Primary Safety: 
• 
To evaluate the long-term safety and tolerability of ETC-1002 versus placebo 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 Efficacy: 
• 
To assess percent change from baseline to Week 12 in low-density lipoprotein cholesterol 
(LDL-C) 
Tertiary Efficacy: 
• 
To assess percent change from baseline to Week 24 and to Week 52 in LDL-C in patients who do 
not receive adjunctive lipid-lowering therapy 
• 
To assess high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC), and 
triglycerides (TG) values at Week 12, 24, and 52  
• 
To assess apolipoprotein B (apoB) and high-sensitivity C-reactive protein (hs-CRP) values at 
Week 12, 24, and 52 
 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 262 of 287 
CHANGE 2 REMOVAL OF RESERVE SAMPLE COLLECTION 
Location: 
Synopsis; Other Biomarkers 
Original Text: 
Other Biomarkers:  
• 
hs-CRP 
• 
Reserve 10 mL blood samples for potential future measurement of ETC-1002 biomarkers  
New Text: 
Other Biomarkers:  
• 
hs-CRP 
• 
Reserve 10 mL blood samples for potential future measurement of ETC-1002 biomarkers. Based 
upon Sponsor assessment and decision, reserve sample collection will be discontinued after a 
sufficient number of samples have been collected.  
 
CHANGE 3 ADDITION OF 40 MG SIMVASTATIN AS A PROHIBITED 
MEDICATION 
Location:  
Synopsis; Safety and Monitoring 
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 >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 average 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). 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 263 of 287 
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) 
• 
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 average 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 4 REVISION OF STUDY OBJECTIVES AND STATISTICAL SECTION TO 
ALIGN WITH REVISED SAP 
Location: 
Synopsis; Statistical Methods 
Original Text 
Primary Endpoint  
The primary endpoint for this study is general safety, which includes AEs, clinical safety laboratories, 
PEs, vital signs, and ECGs. 
No statistical analyses will be performed on any of the safety data in this study.  
The summarization of AEs will include only treatment-emergent AEs (TEAEs), defined as AEs that begin 
or worsen after randomization and ingestion of the first dose of study drug. TEAEs and SAEs will be 
summarized by system organ class (SOC), severity, and relationship to study drug for each treatment 
group. AE summaries will include cumulative incidence (percent of patients experiencing the AE) and 
patient-year adjusted incidence rates. These AE summaries will be provided overall and for subgroups 
such as gender, age, and HeFH status. 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 post-baseline time point. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 264 of 287 
New Text 
Primary Safety Endpoint  
The primary endpoint for this study is general safety, which includes AEs, clinical safety laboratories, 
PEs, vital signs, and ECGs. 
No statistical analyses will be performed on any of the safety data in this study.The summarization of AEs 
will include only treatment-emergent AEs (TEAEs), defined as AEs that begin or worsen after 
randomization and ingestion of the first dose of study drug. TEAEs and SAEs will be summarized by 
system organ class (SOC), severity, and relationship to study drug for each treatment group. AE 
summaries will include cumulative incidence (percent of patients experiencing the AE) and patient year 
adjusted incidence rates. These AE summaries will be provided overall and for subgroups such as gender, 
age, and HeFH status. 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.  
Original Text 
Secondary Endpoint Lipids 
Percent change from baseline to Week 12 in LDL-C will be analyzed using analysis of covariance 
(ANCOVA), with treatment and randomization strata (patient’s CV risk and baseline statin dose) as 
factors and baseline LDL-C as a covariate. The FAS will be used, with patients included in their 
randomized 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). For each ANCOVA (observed case; imputation 
via PMM), output will include the least squares mean (LSM) and standard error (SE) for each treatment 
group, along with the placebo-correct LSM and it’s 95% confidence interval (CI) and p-value.  
Tertiary Endpoint Lipids 
LDL-C, HDL-C, TG, TC, non-HDL-C, and apoB values at Weeks 12, 24, and 52 will be summarized. For 
each parameter at each time point, the value of the parameter and the percent change from baseline in 
the parameter will be summarized by treatment group. The FAS will be used, with patients included in 
their randomized group, regardless of the treatment they actually received. In addition, a summary using 
the FAS, excluding patients who received additional lipid-lowering therapy by that timepoint (by Week 24 
for the Week 24 timepoint; by Week 52 for the Week 52 timepoint), will be provided. For both summaries, 
only observed case data will be used (no imputation for missing data).  
Percent change from baseline to Week 24 and to Week 52 on LDL-C will be analyzed similarly, with 
patients in the FAS who did not receive additional lipid-lowering therapy by that timepoint (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 timepoint 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. 
PK and Other biomarkers 
hs-CRP values and percent change from baseline in values will be summarized by treatment group at 
Weeks 12, 24, and 52. The FAS will be used, with patients included in their randomized treatment group, 
regardless of the treatment they actually received. Only observed case data will be used (no imputation 
for missing data). 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 265 of 287 
In addition, trough plasma concentrations will be collected at Weeks 12, 24, and 52 from patients 
randomized into the study prior to the implementation of Protocol Amendment 3 for use in further 
developing the population pharmacokinetic (PK) model. Trough plasma concentrations will not be 
collected from patients randomized into the study after the implementation of Protocol Amendment 3 
New Text 
Secondary Key Efficacy Endpoints Lipids 
Percent change from baseline to Week 12 or Week 24 in LDL-C, non-HDL-C, TC, apoB, and hs-CRP will 
be analyzed using analysis of covariance (ANCOVA), with treatment and randomization strata (patient’s 
CV risk and baseline statin dose) as factors and respective baseline value LDL C as a covariate. The FAS 
will be used. Missing data for these endpoints will be imputed using multiple imputation taking account 
for treatment adherence. , with patients included in their randomized 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). For each ANCOVA (observed case; imputation via PMM), output will include the least squares 
mean (LSM) and standard error (SE) for each treatment group, along with the placebo correct LSM and 
it’s 95% confidence interval (CI) and p value. 
Other Efficacy Tertiary Endpoints Lipids 
LDL-C, HDL-C, TG, TC, non-HDL-C, hs-CRP, and apoB values at other time points Weeks 12, 24, and 
52 will be summarized and analyzed similarly to the key lipid endpoints. For each parameter at each time 
point, the value of the parameter and the percent change from baseline in the parameter will be 
summarized by treatment group. The FAS will be used, with patients included in their randomized group, 
regardless of the treatment they actually received. In addition, a summary using the FAS, excluding 
patients who received additional lipid-lowering therapy by that time point (by Week 24 for the Week 24 
time point; by Week 52 for the Week 52 time point), will be provided. For both summaries, only observed 
case data will be used (no imputation for missing data).  
Percent change from baseline to Week 24 and to Week 52 on LDL C will be analyzed similarly, with 
patients in the FAS who did not receive additional lipid lowering therapy by that timepoint (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 timepoint 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. 
PK and Other biomarkers 
hs CRP values and percent change from baseline in values will be summarized by treatment group at 
Weeks 12, 24, and 52. The FAS will be used, with patients included in their randomized treatment group, 
regardless of the treatment they actually received. Only observed case data will be used (no imputation 
for missing data). 
In addition, tTrough plasma concentrations will be collected at Weeks 12, 24, and 52 from patients 
randomized into the study prior to the implementation of Protocol Amendment 3 for use in further 
developing the population pharmacokinetic (PK) model. Trough plasma concentrations will not be 
collected from patients randomized into the study after the implementation of Protocol Amendment 3. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 266 of 287 
CHANGE 5 REVISION OF STUDY OBJECTIVES AND STATISTICAL SECTION TO 
ALIGN WITH REVISED SAP  
Location: 
Section 5 Trial Objectives and Purpose (including Sections 5.1; 5.2; 5.3) 
Original Text: 
5.1 
Primary Objective 
The primary objective is to evaluate the long-term safety and tolerability of ETC-1002 versus 
placebo in high cardiovascular (CV) risk patients with hyperlipidemia (with underlying HeFH 
and/or ASCVD) who are not adequately controlled with their maximally tolerated lipid-
modifying therapy. 
5.2 
Secondary Objectives 
• To assess percent change from baseline to Week 12 in LDL-C 
5.3 Tertiary Objectives 
• To assess percent change from baseline to Week 24 and to Week 52 in LDL-C in 
patients who do not receive adjunctive lipid-lowering therapy  
• To assess high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total 
cholesterol (TC), and TG at Weeks 12, 24, and 52  
• To assess apoB and high-sensitivity C-reactive protein (hs-CRP) at Weeks 12, 24, 
and 52 
New Text: 
5.1 
Primary Safety Objective 
The primary objective is to evaluate the long-term safety and tolerability of ETC-1002 versus 
placebo in high cardiovascular (CV) risk patients with hyperlipidemia (with underlying HeFH 
and/or ASCVD) who are not adequately controlled with their maximally tolerated lipid-
modifying therapy. 
5.2 
Secondary Efficacy Objectives 
• To assess percent change from baseline to Week 12 in LDL-C 
5.3 
Tertiary Efficacy Objectives 
• To assess percent change from baseline to Week 24 and to Week 52 in LDL-C in 
patients who do not receive adjunctive lipid-lowering therapy  
• To assess high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total 
cholesterol (TC), and TG at Weeks 12, 24, and 52  
• To assess apoB and high-sensitivity C-reactive protein (hs-CRP) at Weeks 12, 24, 
and 52 
 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 267 of 287 
CHANGE 6 ADDITION OF 40 MG SIMVASTATIN AS A PROHIBITED 
MEDICATION 
Location: 
Section 6.1; Tables 2 and 3 
Original Text: 
Table 2: 
Baseline Statin Dose Categories 
High Intensity Statins 
Moderate Intensity Statins 
Low Intensity Statinsa 
Atorvastatin 40-80 mg 
Atorvastatin 10-20 mg 
Simvastatin 10 mg 
Rosuvastatin 20-40 mg 
Rosuvastatin 5-10 mg 
Pravastatin 10-20 mg 
 
Simvastatin 20-40b 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 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) 
b Simvastatin average daily doses greater than 40 mg are not allowed in this study 
New Text: 
Table 2: 
Baseline Statin Dose Categories 
High Intensity Statins 
Moderate Intensity Statins 
Low Intensity Statinsa 
Atorvastatin 40-80 mg 
Atorvastatin 10-20 mg 
Simvastatin 10 mg 
Rosuvastatin 20-40 mg 
Rosuvastatin 5-10 mg 
Pravastatin 10-20 mg 
 
Simvastatin 20-40b 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 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) 
b Simvastatin average with daily doses greater than or equal to ≥40 mg/day are not allowed in this 
study. 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 268 of 287 
Original Text: 
Table 3: 
Randomization Strata 
HeFH (with or without ASCVD) 
ASCVD (without HeFH) 
HeFH+ Low Intensity Statins 
ASCVD + Low Intensity Statins 
HeFH+ Moderate Intensity Statins 
ASCVD + Moderate Intensity Statins 
HeFH+ High Intensity Statinsa 
ASCVD + High Intensity Statinsa 
ASCVD = Atherosclerotic cardiovascular diseases; HeFH = Heterozygous familial hypercholesterolemia. 
a Simvastatin average daily doses greater than 40 mg are not allowed in this study. 
New Text: 
Table 3: 
Randomization Strata 
HeFH (with or without ASCVD) 
ASCVD (without HeFH) 
HeFH+ Low Intensity Statins 
ASCVD + Low Intensity Statins 
HeFH+ Moderate Intensity Statins 
ASCVD + Moderate Intensity Statins 
HeFH+ High Intensity Statinsa 
ASCVD + High Intensity Statinsa 
ASCVD = Atherosclerotic cardiovascular diseases; HeFH = Heterozygous familial hypercholesterolemia. 
a Simvastatin average with daily doses greater than or equal to ≥40 mg/day are not allowed in this study. 
 
CHANGE 7 ADDITION OF 40 MG SIMVASTATIN AS A PROHIBITED 
MEDICATION 
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®), with daily doses ≤40 mg 
Selective cholesterol and/or bile acid absorption inhibitors 
• Cholestyramine/Colestyramine (Questran®, Questran Light®, Prevalite®, Locholest®, 
Locholest® Light) 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 269 of 287 
• Colestipol (Colestid®) 
• Colesevelam hydrochloride (Welchol®,Cholestagel®) 
• Ezetimibe (Zetia®, Ezetrol®) 
Fibrates 
• Fenofibrate (Antara®, Lofibra®, Tricor®, Triglide™, Lipantil®, Supralip®)  
• Bezafibrate (Bezalip®) 
• Ciprofibrate (Modalim®) 
PCSK9 inhibitors (allowed as adjunctive therapy beginning at Week 24 [Visit T5]; see 
Section 11.1.6.3.5) 
• Alirocumab (Praluent®) 
• Evolocumab (Repatha®) 
Other 
• Simvastatin/ezetimibe (Vytorin®, Inegy®) with the average daily dose of simvastatin 
≤40 mg 
• Atorvastatin/ezetimibe (Atozet®) 
New Text: 
Statins 
• Atorvastatin (Lipitor®, Sortis®) 
• Fluvastatin (Lescol®) 
• Lovastatin (Mevacor®, Altoprev™) 
• Pravastatin (Pravachol®) 
• Pitavastatin (Livalo®, Lipostat®) 
• Rosuvastatin (Crestor®) 
• Simvastatin (Zocor®), with daily doses less than 40 mg 
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®) 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 270 of 287 
Fibrates 
• Fenofibrate (Antara®, Lofibra®, Tricor®, Triglide™, Lipantil®, Supralip®)  
• Bezafibrate (Bezalip®) 
• Ciprofibrate (Modalim®) 
PCSK9 inhibitors (allowed as adjunctive therapy beginning at Week 24 [Visit T5]; see 
Section 11.1.6.3.5) 
• Alirocumab (Praluent®) 
• Evolocumab (Repatha®) 
Other 
• Ezetimibe/simvastatin/ezetimibe (Vytorin®, Inegy®) with the average daily dose of 
where simvastatin is less than 40 mg/day (Vytorin® 10 mg/10 mg and 10 mg/20 mg, 
Inegy®10 mg/20 mg are allowed) 
• Atorvastatin/ezetimibe (Atozet®) 
 
CHANGE 8 ADDITION OF 40 MG SIMVASTATIN AS A PROHIBITED 
MEDICATION 
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. 
• Gemfibrozil (Lopid®)  
• Cholestin (red yeast rice, also known as monascus purpureus extract) 
• Simvastatin (Zocor®), average daily doses greater than 40 mg alone or in fixed-dose 
combination (eg, Vytorin®, with average daily doses greater than 40 mg/10 mg) 
New 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. 
• Gemfibrozil (Lopid®)  

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 271 of 287 
• Cholestin (red yeast rice, also known as monascus purpureus extract) 
• Simvastatin (Zocor®), average daily doses greater than or equal to 40 mg/day alone 
or in fixed dose combination (eg, Vytorin®, with average daily doses greater than 
40 mg/10 mg) 
• Ezetimibe/simvastatin where simvastatin doses are greater than or equal to 
40 mg/day (Vytorin® 10 mg/40 mg and 10 mg/80 mg and Inegy® 10 mg/40 mg and 
10 mg/80 mg per day are prohibited) 
 
CHANGE 9 REVISED STUDY PROCEDURES 
Locations: 
Section 10.2.5.1 Treatment Week 16 (Visit T4.1; ±3 days) and Section 10.2.5.2 Treatment 
Week 20 (Visit T4.2; ±3 days) 
Original Text:  
Section 10.2.5.1 Treatment Week 16 (Visit T4.1; ±3 days) 
Patients on an average daily dose of simvastatin 40 mg will be scheduled for the additional 
Visit T4.1 for clinical safety laboratory evaluations specifically to monitor changes in creatine 
phosphokinase (CPK) and liver function tests (LFTs). Should changes be noted, the procedures 
described in Section 11.1.6.3.1 will apply. 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (ongoing) 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
• Conduct diet and exercise counseling 
Section 10.2.5.2 Treatment Week 20 (Visit T4.2; ±3 days) 
Patients on an average daily dose of simvastatin 40 mg will be contacted by telephone for the 
additional Visit T4.2 to 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (ongoing) 
• Remind subjects to take IMP as scheduled 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 272 of 287 
New Text: 
Section 10.2.5.1 Treatment Week 16 (Visit T4.1; ±3 days) 
Patients on an average daily dose of simvastatin 40 mg/day will be scheduled for the additional 
Visit T4.1 for clinical safety laboratory evaluations specifically to monitor changes in creatine 
phosphokinase (CPK) and liver function tests (LFTs). Should changes be noted, the procedures 
described in Section 11.1.6.3.1 will apply. 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (ongoing) 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
• Conduct diet and exercise counseling 
Section 10.2.5.2 Treatment Week 20 (Visit T4.2; ±3 days) 
Patients on an average daily dose of simvastatin 40 mg/day will be contacted by telephone for 
the additional Visit T4.2 to 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (ongoing) 
• Remind subjects to take IMP as scheduled 
 
CHANGE 10 REVISED STUDY PROCEDURES 
Locations: 
Section 10.2.6.1 Treatment Week 28 (Visit T5.1; ±7 days) and Section 10.2.6.2 Treatment 
Week 32 (Visit T5.2; ±7 days) 
Original Text:  
Section 10.2.6.1 Treatment Week 28 (Visit T5.1; ±7 days) 
Patients on an average daily dose of simvastatin 40 mg will be scheduled for the additional 
Visit T5.1 for clinical safety laboratory evaluations specifically to monitor changes in CPK and 
LFTs. Should changes be noted, the procedures described in Section 11.1.6.3.1 will apply. 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (ongoing) 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
• Conduct diet and exercise counseling 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 273 of 287 
Section 10.2.6.2 Treatment Week 32 (Visit T5.2; ±7 days) 
Patients on an average daily dose of simvastatin 40 mg will be contacted by telephone for the 
additional Visit T5.2 to  
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (ongoing) 
• Remind subjects to take IMP as scheduled 
New Text: 
Section 10.2.6.1 Treatment Week 28 (Visit T5.1; ±7 days) 
Patients on an average daily dose of simvastatin 40 mg/day will be scheduled for the additional 
Visit T5.1 for clinical safety laboratory evaluations specifically to monitor changes in CPK and 
LFTs. Should changes be noted, the procedures described in Section 11.1.6.3.1 will apply. 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (ongoing) 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
• Conduct diet and exercise counseling 
Section 10.2.6.2 Treatment Week 32 (Visit T5.2; ±7 days) 
Patients on an average daily dose of simvastatin 40 mg/day will be contacted by telephone for 
the additional Visit T5.2 to 
• Concomitant and prohibited medication review (ongoing) 
• Assess AEs, including muscle-related AEs (ongoing) 
• Remind subjects to take IMP as scheduled 
 
CHANGE 11 REVISED STUDY PROCEDURES 
Location: 
Section 10.2.8 Treatment Week 52 (Visit T7; ±7 days)  
Original Text:  
• Return of IMP; assessment and recording of IMP compliance 
• Complete study status in IWRS (ie, early withdrawal or completed study) 
Note: For patients who withdraw from IMP treatment: 
New Text: 
• Return of IMP; assessment and recording of IMP compliance 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 274 of 287 
• Complete study status in IWRS (ie, early withdrawal or completed study) 
• Review and offer the open-label extension study (Study 1002-050) to the patient 
Note: For patients who withdraw from IMP treatment: 
 
CHANGE 12 REVISED MONITORING AND MANAGEMENT OF ELEVATED CK 
Location: 
Section 11.1.6.3.4 Monitoring and Management of Elevated Creatine Kinase  
Original Text:  
If at any time after randomization a patient experiences a marked CK elevation >5 × ULN, the 
patient will undergo repeat confirmatory assessment as soon as is reasonably possible, preferably 
within 3 to 7 days of the laboratory result becoming available.  
Repeat CK assessment will include query for related symptoms.  
• If the repeat CK assessment confirms an unexplained (ie, not associated with recent 
trauma or physically strenuous activity) CK abnormality >5 × ULN, if asymptomatic 
the investigator with input from the Sponsor may consider continuing study 
medication with continued CK assessments every 1-2 weeks. 
New Text: 
If at any time after randomization a patient experiences a marked CK elevation >5 × ULN, the 
patient will undergo repeat confirmatory assessment as soon as is reasonably possible, preferably 
within 3 to 7 days of the laboratory result becoming available.  
Repeat CK assessment will include query for related symptoms.  
• If the repeat CK assessment confirms an unexplained (ie, not associated with recent 
trauma or physically strenuous activity) CK abnormality >5 × ULN, if asymptomatic 
the patient should receive further assessment and investigation into the cause, assess 
whether there is renal injury, and measure CK approximately weekly or more 
frequently if clinically indicated until resolution. If CK levels continue to rise; IMP 
should be discontinued.investigator with input from the Sponsor may consider 
continuing study medication with continued CK assessments every 1 2 weeks. 
 
CHANGE 13 ADDITION OF 40 MG SIMVASTATIN AS A PROHIBITED 
MEDICATION  
Location: 
Section 11.1.6.3.5 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 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 275 of 287 
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 average 
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). 
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 average 
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). 
 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 276 of 287 
CHANGE 14 REMOVAL OF RESERVE SAMPLE COLLECTION 
Location: 
Section 11.1.6.7 Exploratory Biomarker Measurement 
Original Text:  
Additional exploratory safety, efficacy, PK, or potential biomarkers may be assayed from reserve 
sample. 
New Text: 
Additional exploratory safety, efficacy, PK, or potential biomarkers may be assayed from reserve 
samples. Based upon Sponsor assessment and decision, reserve sample collection will be 
discontinued after a sufficient number of samples have been collected. Study centers will be 
notified in writing informing them that sufficient samples have been collected and that further 
collection may be discontinued. 
 
CHANGE 15 REVISION OF STUDY OBJECTIVES AND STATISTICAL SECTION TO 
ALIGN WITH REVISED SAP 
Location: 
Section 12.5 Primary Safety Endpoint 
Original Text:  
12.5 
Primary Endpoint 
The primary endpoint for this study is general safety, which includes AEs, clinical safety 
laboratories, PEs, vital signs, and ECGs. 
No statistical analyses will be performed on any of the safety data in this study. The 
summarization of AEs will include only TEAEs, defined as AEs that begin or worsen after 
randomization and ingestion of the first dose of study drug. TEAEs and SAEs will be 
summarized by SOC, severity, and relationship to study drug for each treatment group. AE 
summaries will include cumulative incidence (percent of patients experiencing the AE) and 
patient-year adjusted incidence rates. These AE summaries will be provided overall and for 
subgroups such as gender, age, and HeFH status. 
New Text: 
12.5 
Primary Safety Endpoint 
The primary endpoint for this study is general safety, which includes AEs, clinical safety 
laboratories, PEs, vital signs, and ECGs. 
No statistical analyses will be performed on any of the safety data in this study. The 
summarization of AEs will include only TEAEs, defined as AEs that begin or worsen after 
randomization and ingestion of the first dose of study drug. TEAEs and SAEs will be 
summarized by SOC, severity, and relationship to study drug for each treatment group. AE 
summaries will include cumulative incidence (percent of patients experiencing the AE) and 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 277 of 287 
patient year adjusted incidence rates. These AE summaries will be provided overall and for 
subgroups such as gender, age, and HeFH status. 
 
CHANGE 16 REVISION OF STUDY OBJECTIVES AND STATISTICAL SECTION TO 
ALIGN WITH REVISED SAP 
Location: 
Section 12.6 Efficacy Endpoints 
Original Text:  
12.6 
Secondary and Tertiary Lipids 
12.6.1 Secondary Lipids 
Percent change from baseline to Week 12 in LDL-C will be analyzed using analysis of 
covariance (ANCOVA), with treatment and randomization strata (patient’s CV risk and baseline 
statin dose) as factors and baseline LDL-C as a covariate. Baseline LDL-C is defined as the 
predose Day 1/Week 0 value. The FAS will be used, with patients included in their randomized 
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). For each ANCOVA (observed 
case; imputation via PMM), output will include the least squares mean (LSM) and standard 
error (SE) for each treatment group, along with the placebo-correct LSM and it’s 95% 
confidence interval (CI) and p-value. Specific details on how the PMM will be implemented will 
be included in the SAP.  
New Text: 
12.6 
Secondary and Tertiary Lipids Efficacy Endpoints 
12.6.1 Secondary Key Lipids Efficacy Endpoints 
Selected efficacy endpoints will be included in a step-down testing procedure to control overall 
type I error. Below endpoints will be tested sequentially at alpha level of 0.05. Each endpoint 
will be tested only if the previous endpoint achieved statistical significance. 
1. percent change from baseline to Week 12 in LDL-C  
2. percent change from baseline to Week 24 in LDL-C  
3. percent change from baseline to Week 12 in non-HDL-C  
4. percent change from baseline to Week 12 in TC  
5. percent change from baseline to Week 12 in apoB  
6. percent change from baseline to Week 12 in hs-CRP 
Percent change from baseline to Week 12 in LDL C willin lipid parameters will be analyzed 
using analysis of covariance (ANCOVA), with treatment and randomization strata (patient’s CV 
risk and baseline statin dose) as factors and respective baseline LDL Cvalue as a covariate. 
Baseline LDL Cvalue is defined as the average of the last screening and the predose 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 278 of 287 
Day 1/Week 0 value. When only one assessment or value is available, that single 
assessment/value will be used as baseline. 
The FAS will be used for efficacy endpoints, with patients included in their randomized 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 usingMissing data for key lipid endpoints will be imputed using a multiple 
imputation method that accounts for treatment adherence. aA pattern mixture model (PMM) will 
be used to specify different imputation strategies depending on whether the patient is still on 
study treatment. For eachThe ANCOVA (observed case; imputation via PMM), output will 
include the least squares mean (LSM) and standard error (SE) for each treatment group, along 
with the placebo-correct LSM and it’s 95% confidence interval (CI) and p-value. Specific details 
on how the PMM will be implemented will be included in the SAP.  
Additional sensitivity analyses based on subsets of the FAS or alternative missing data handling 
will be performed and the details will be provided in the SAP. 
Original Text:  
12.6.2 Tertiary Lipids 
LDL-C, HDL-C, TG, TC, non-HDL-C, and apoB values at Weeks 12, 24, and 52 will be 
summarized. For each parameter at each time point, the value of the parameter and the percent 
change from baseline in the parameter will be summarized by treatment group. Baseline for each 
lipid is defined as the predose Day 1/Week 0 value. The FAS will be used, with patients included 
in their randomized group, regardless of the treatment they actually received. In addition, a 
summary using the FAS, excluding patients who received additional lipid-lowering therapy by 
that time point (by Week 24 for the Week 24 time point; by Week 52 for the Week 52 time point), 
will be provided. For both summaries, only observed case data will be used (no imputation for 
missing data).  
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: 
12.6.2 Tertiary Other Lipids Efficacy Endpoints 
Percent change or change in LDL-C, HDL-C, TG, TC, non-HDL-C, hs-CRP, and apoB values at 
Weeks 12, 24, and 52 will be summarizedother protocol-scheduled time points will be analyzed 
similarly using the ANCOVA model. The FAS will be used, with patients included in their 
randomized group, regardless of the treatment they actually received. No imputation for missing 
data will be performed. 
For each parameter at each time point, the value of the parameter and the percent change from 
baseline in the parameter will be summarized by treatment group. Baseline for each lipid is 
defined as the predose Day 1/Week 0 value. The FAS will be used, with patients included in their 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 279 of 287 
randomized group, regardless of the treatment they actually received. In addition, a summary 
using the FAS, excluding patients who received additional lipid lowering therapy by that 
timepoint (by Week 24 for the Week 24 timepoint; by Week 52 for the Week 52 timepoint), will be 
provided. For both summaries, only observed case data will be used (no imputation for missing 
data).  
In addition, Ppercent 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 18 REVISION OF STUDY OBJECTIVES AND STATISTICAL SECTION TO 
ALIGN WITH REVISED SAP 
Location: 
Section 12.7 PK and Other Biomarkers 
Original Text:  
hs-CRP values and percent change from baseline in values will be summarized by treatment 
group at Weeks 12, 24, and 52. Baseline for hs-CRP is defined as the predose Day 1/Week 0 
value. The FAS will be used, with patients included in their randomized treatment group, 
regardless of the treatment they actually received. Only observed case data will be used (no 
imputation for missing data).  
In addition, trough plasma concentrations of ETC-1002 and ESP15228 will be collected from 
patients randomized before the implementation of Protocol Amendment 3 at Weeks 12, 24, 
and 52 for use in further developing the population PK model. Trough plasma concentrations 
will not be collected from patients randomized after the implementation of Protocol 
Amendment 3. 
New Text: 
hs CRP values and percent change from baseline in values will be summarized by treatment 
group at Weeks 12, 24, and 52. Baseline for hs CRP is defined as the predose Day 1/Week 0 
value. The FAS will be used, with patients included in their randomized treatment group, 
regardless of the treatment they actually received. Only observed case data will be used (no 
imputation for missing data).  
In addition, tTrough plasma concentrations of ETC-1002 and ESP15228 will be collected from 
patients randomized before the implementation of Protocol Amendment 3 at Weeks 12, 24, 
and 52 for use in further developing the population PK model. Trough plasma concentrations 
will not be collected from patients randomized after the implementation of Protocol 
Amendment 3. 

ETC-1002 
Clinical Study Protocol 1002-040 
Esperion Therapeutics, Inc. 
Summaiy of Changes Amendment 5 
Amendment 5, 10 May 2017 
CHANGE 19 REVISIONS TO SCHEDULE OF EVENTS 
Location: 
Appendix 1; Schedule of Events (Subject Visit Schedule) 
Original T ex.t: 
Sc1·een 
Visit 
s11.z 
Tl 
T2 
T3 
T4 
T4.I 
Week 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
-2 
0 
4 
8 
12 
16 
Prncedul'e 
Day 
Day 
Day 
Day 
Day 
Day 
-16 to -4 
1 
29±3 
57±3 
85±3 
112±3 
Info1med Consent 
X 
Enrollment Criteria 
X 
Demographics 
X 
Medical Histo1y 
X 
HeFH Status 
X 
Dete1mination 
Concomitant 
X 
X 
X 
X 
X 
X 
Medications 
Adverse Event 
X 
X 
X 
X 
X 
Recording 
Physical Exam 
X 
Weight4 
X 
X 
X 
X 
X 
Height/BMI 
X 
12-Lead ECG5 
X 
Vital Signs6 
X 
X 
X 
X 
X 
Serology7 
X 
Senun Pregnancy 
X 
and/or FSif 
Urine Pregnancy Tesl 
X 
TSH 
X 
Clinical Safety Labs9 
X 
X 
X 
X 
X 
Additional Clinical 
X 
Safety Labs10 
Basic Fasting Lipidsll 
X 
X 
X 
X 
X 
HbA1c 
X 
X 
X 
10 mL reserve sample 
X 
X 
Genetic sample 
X 
apoB 
X 
X 
hs-CRP 
X 
X 
Diet and exercise 
X 
X 
X 
X 
X 
X 
counseling12 
Plasma PK13 
X 
Confidential 
Page 280 of 287 
Tl'eatment 
T4.2 
TS 
TS.I 
TS.2 
T6 
T7 EOS3 
phone 
phone 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
20 
24 
28 
32 
36 
52 
Day 
Day 
Day 
Day 
Day 
Day 
140±3 169±7 196±7 224±7 253±7 
365±7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

ETC-1002 
Clinical Study Protocol 1002-040 
Sc1·een 
Visit 
s11.z 
Tl 
T2 
T3 
T4 
Week 
Wk 
Wk 
Wk 
Wk 
Wk 
-2 
0 
4 
8 
12 
Prncedul'e 
Day 
Day 
Day 
Day 
Day 
-16 to -4 
1 
29±3 
57±3 
85±3 
Establish Patient 
X 
Eligibility 
Randomization 
X 
IWRS Contact 
X 
X 
X 
Double-blind Dmg 
X 
X 
Dispensing15 
Dmg 
X 
X 
X 
Retmn/Compliance 
Schedule next visit 
X 
X 
X 
X 
X 
T4.I 
Wk 
16 
Day 
112±3 
Esperion Therapeutics, Inc. 
Summaiy of Changes Amendment 5 
Amendment 5, 10 May 2017 
Tl'eatment 
T4.2 
TS 
TS.I 
TS.2 
T6 
T7 EOS3 
p hone 
p hone 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
20 
24 
28 
32 
36 
52 
Day 
Day 
Day 
Day 
Day 
Day 
140±3 169±7 196±7 224±7 253±7 
365±7 
X 
X 
X/4 
X 
X 
X 
X 
X 
X 
X 
.xJ-6 
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 w-ith infomiation regarding ctm·ent health status and to collect infomiation on AEs (eg, recent procedm·es, 
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 retmning to clinic or by phone), Visit T7 ,viii be considered the EOS/Early Withdrawal 
from study and no further visits will be scheduled. 
1 An optional visit approxiniately 1 week later MAY be completed if patient fails to meet a lipid entry criterion. If this optional 
visit is completed, the mean of lipid values from both visits will be used to detenuine eligibility. 
2 An optional visit between Visits Sl and Tl niay 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 pressm·e medications for at least 2 weeks, and the repeat blood pressm·e values (DBP and/or SBP) do not meet 
exclusionary values. An optional visit between Visit S 1 and Tl may be completed to detemwe 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 
detemlllle eligibility. 
3 All procedm·es 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 in the morning while fasting, using consistent scales, after voiding, and without shoes and 
oute1wear (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 Sernm pregnancy test completed in premenopausal women only. Urine pregnancy test is completed in premenopausal women 
who are able to become pregnant. FSH test is completed in women <55 years old and > 1 year without menses 
9 Clinical safety labs include heniatology, blood chemistry, and m-inalysis at all visits. These will also be conducted 4 weeks after 
any changes in the patient's lipid-modifying treatment. Coagulation is included at Screening (Visit Sl )for all patients, and then 
only in patients receiving anticoagulant ther=
at in the investigator's judgement requires monitoring at Baseline (Visit Tl) 
and 3 to 5 days post Visit Tl. Please refer to-
laboratory manual for detailed schedule of tests. 
IO Patients on an average daily dose of simvastatin 40 mg will be scheduled for additional Visits T4. l and T5.l to monitor clinical 
laboratory assessments and AE and SAE occurrence. These patients will also be contacted by telephone at Visits T4.2 and T5.2 
to monitor AE and SAE occurrence. 
II Basic fasting lipids include total cholesterol, calculated LDL-C, HDL-C, non-HDL-C, and triglycerides. Repeat within 1 week if 
exceed protocol-specified criteria. 
12Diet and exercise counseling per local and/or regional guidelines for the management ofhyperlipidemia. 
13 Patients randomized after Protocol Amendment 3 and subsequent amendments are excluded from PK sampling. 
14 IWRS contact at either an early withdrawal or an EOS visit to register study discontinuation visit date. 
Confidential 
Page 281 of 287 

ETC-1002 
Clinical Study Protocol 1002-040 
Esperion Therapeutics, Inc. 
Summaiy of Changes Amendment 5 
Amendment 5, 10 May 2017 
15 Depending upon the length of time between visits, 1 or 2 bottles of study medication will be dispensed as instructed by IWRS. 
The bottle dispensed at Visit Tl will be returned to clinic at Visits T2 and T3 for evaluation of compliance and retumed for 
continued use. 
16If patient is discontinuing treatment and completing the EOS visit, but w-ill 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: 
Sc1·een 
Tl'eatment 
Visit 
s11.z 
Tl 
T2 
T3 
T4 
T4.I 
T4.2 
TS 
TS.I 
TS.2 
T6 
T7 EOS3 
phone 
phone 
Week 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
-2 
0 
4 
8 
12 
16 
20 
24 
28 
32 
36 
52 
Prncedul'e 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
Day 
-16 to -4 
1 
29±3 
57±3 
85±3 
112±3 140±3 169±7 196±7 224±7 253±7 
365±7 
Info1med Consent 
X 
Enrolhnent Criteria 
X 
Demographics 
X 
Medical Histo1y 
X 
HeFH Status 
X 
Dete1mination 
Concomitant 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medications 
Adverse Event 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Recording 
Physical Exam 
X 
X 
Weight4 
X 
X 
X 
X 
X 
X 
X 
X 
Height/BM! 
X 
12-Lead ECG5 
X 
X 
Vital Signs6 
X 
X 
X 
X 
X 
X 
X 
X 
Serology7 
X 
Serum Preg;I}ancy 
X 
andlorFSir 
Urine Pregnancy Tesl 
X 
TSH 
X 
Clinical Safety Labs9 
X 
X 
X 
X 
X 
X 
X 
X 
Additional Clinical 
X 
X 
Safety Labs10 
Basic Fasting LipidsJJ 
X 
X 
X 
X 
X 
X 
X 
X 
HbA1c 
X 
X 
X 
X 
10 mL reserve 
X 
X 
X 
X 
sample12 
Genetic sample 
X 
apoB 
X 
X 
X 
X 
hs-CRP 
X 
X 
X 
X 
Diet and exercise 
X 
X 
X 
X 
X 
X 
X 
X 
X 
counseling13,1 
Plasma PK1.u 
X 
X 
X 
Confidential 
Page 282 of 287 

ETC-1002 
Clinical Study Protocol 1002-040 
Sc1·een 
Visit 
s11.z 
Tl 
T2 
T3 
T4 
Week 
Wk 
Wk 
Wk 
Wk 
Wk 
-2 
0 
4 
8 
12 
Prncedul'e 
Day 
Day 
Day 
Day 
Day 
-16 to -4 
1 
29±3 
57±3 
85±3 
Establish Patient 
X 
Eligibility 
Randomization 
X 
IWRS Contact 
X 
X 
X 
Double-blind Dmg 
X 
X 
Dispensing16.l-
Dmg 
X 
X 
X 
Retmn/Compliance 
Offer Study 1002-050 
Schedule next visit 
X 
X 
X 
X 
X 
T4.I 
Wk 
16 
Day 
112±3 
Esperion Therapeutics, Inc. 
Summaiy of Changes Amendment 5 
Amendment 5, 10 May 2017 
Tl'eatment 
T4.2 
TS 
TS.I 
TS.2 
T6 
T7 EOS3 
p hone 
p hone 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
20 
24 
28 
32 
36 
52 
Day 
Day 
Day 
Day 
Day 
Day 
140±3 169±7 196±7 224±7 253±7 
365±7 
X 
X 
X/54 
X 
X 
X 
X 
X 
.x'-7~ 
X 
X 
.x'-8+ 
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 w-ith infomiation regarding Ctlffent health status and to collect infomiation 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 ,viii be considered the EOS/Eady Withdrawal 
from study and no further visits will be scheduled. 
1 An optional visit approxiniately 1 week later MAY be completed if patient fails to meet a lipid entry criterion. If this optional 
visit is completed, the mean of lipid values from both visits will be used to detenuine eligibility. 
2 An optional visit between Visits Sl and Tl niay 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 pressm·e values (DBP and/or SBP) do not meet 
exclusionary values. An optional visit between Visit S 1 and Tl may be completed to detemiine 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 procedm·es 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 in the morning while fasting, using consistent scales, after voiding, and without shoes and 
oute1wear (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. Urine pregnancy test is completed in premenopausal women 
who are able to become pregnant. FSH test is completed in women <55 years old and > 1 year without menses 
9 Clinical safety labs include heniatology, blood chemistry, and m-inalysis at all visits. These will also be conducted 4 weeks after 
any changes in the patient's lipid-modifying treatment. Coagulation is included at Screening (Visit Sl )for all patients, and then 
only in patients receiving anticoagulant ther=
at in the investigator's judgement requires monitoring at Baseline (Visit Tl) 
and 3 to 5 days post Visit Tl. Please refer to-
laboratory manual for detailed schedule of tests. 
IO Patients on s11 sverll,:B Mily &86e ef simvastatin 40 mg/day will be scheduled for additional Visits T4. l and T5.l to monitor 
clinical laboratory assessments and AE and SAE occurrence. These patients will also be contacted by telephone at Visits T4.2 
and T5.2 to monitor AE and SAE occurrence. 
II Basic fasting lipids include total cholesterol, calculated LDL-C, HDL-C, non-HDL-C, and triglycerides. Repeat within 1 week if 
exceed protocol-specified criteria. 
12 Based upon Sponsor assessment and decision, reserve sample collection will be discontinued after a sufficient number of 
samples have been collected. 
Confidential 
Page 283 of 287 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 284 of 287 
132 
Diet and exercise counseling per local and/or regional guidelines for the management of hyperlipidemia. 
143Patients randomized after Protocol Amendment 3 and subsequent amendments are excluded from PK sampling.  
154IWRS contact at either an early withdrawal or an EOS visit to register study discontinuation visit date.  
165Depending upon the length of time between visits, 1 or 2 bottles of study medication will be dispensed as instructed by IWRS. 
The bottle dispensed at Visit T1 will be returned to clinic at Visits T2 and T3 for evaluation of compliance and returned for 
continued use. 
176 Review and offer the open-label extension study (Study 1002-050) to the patient. If the patient was not offered 
Study 1002-050, record the reason why in the eCRF 
187 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 
 

ETC-1002 
Clinical Study Protocol 1002-040 
CHANGE18 ADMINSTRATIVE CHANGE 
Location: 
Appendix 2: Sponsor's Signature Page. 
Original T ex.t: 
Esperion Therapeutics, Inc. 
Summaiy of Changes Amendment 5 
Amendment 5, 10 May 2017 
Study Title: 
A Randomized, Double-blind, Placebo-controlled, Multicenter Long-te1m 
Safety and Tolerability Study of ETC-1002 in Patients with 
Hyperlipidemia at High Cardiovasculai· Risk Who are not Adequately 
Controlled by Their Lipid-Modifying Therapy 
Study Number: 
1002-040 
Final Date: 
14 October 2016 
This clinical study protocol was subject to critical review and has been approved by the Sponsor. 
The following personnel contributed to writing and/or approving this protocol: 
Date: 
Confidential 
Page 285 of 287 

ETC-1002 
Clinical Study Protocol 1002-040 
New Text: 
Esperion Therapeutics, Inc. 
Summaiy of Changes Amendment 5 
Amendment 5, 10 May 2017 
Study Title: 
A Randomized, Double-blind, Placebo-controlled, Multicenter Long-te1m 
Safety and Tolerability Study ofETC-1002 in Patients with 
Hyperlipidemia at High Cardiovasculai· Risk Who are not Adequately 
Controlled by Their Lipid-Modifying Therapy 
Study Number: 
1002-040 
Final Date: 
14 Oeteaer 2QleJO May 2017 
This clinical study protocol was subject to critical review and has been approved by the Sponsor. 
The following personnel contributed to writing and/or approving this protocol: 
CHANGE18 ADMINSTRATIVE CHANGE 
Location: 
Protocol Header: Synopsis, Protocol Body, Appendices 
Original Format: 
Synopsis, Protocol Body, Appendices 1 through 5 
Esperion Therapeutics, Inc. 
Final, DD Month YYYY 
Summai·y of Changes for Amendments, Appendices 6 throughl 0: 
Esperion Therapeutics, Inc. 
Summai·y of Changes Amendment Nlllllber 
Final, DD Month YYYY 
New Format: 
Synopsis, Protocol Body, Appendices 1 through 5: 
Esperion Therapeutics, Inc. 
Amendment 5, DD Month YYYY 
Confidential 
Page 286 of 287 
Date: 

ETC-1002 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-040 
 
Summary of Changes Amendment 5 
 
 
Amendment 5, 10 May 2017 
Confidential 
Page 287 of 287 
Summary of Changes for Amendments, Appendices 6 through10: 
Esperion Therapeutics, Inc. 
Summary of Changes Amendment Number (actual amendment number) 
Amendment Number (current amendment number), DD Month YYYY 
 

1002-040 Protocol Version: Amendment #2 
Administrative Change Letter: 
1002-040-Am2-CA-01-Admin 
Canadian Sites Only 
Date: 
12 April 2016 
To: 
1002-040 Canadian Investigators and Study Staff 
Re: 
I 002-040 Protocol Amendment #2, 
Administrative Change Letter 1002-040-Am2-CA-O 1-Admin 
Dear Investigators and Study Staff, 
This Jetter serves to communicate administrative changes to the 1002-040 Protocol titled "A 
Randomized, Double-blind, Placebo-controlled, Multicenter Long-term Safety and Tolerability 
Study ofETC-1002 in Patients with Hyperlipidemia at High Cardiovascular Risk Who are not 
Adequately Controlled by Their Lipid-Modl/ying Therapy, " (version: Protocol Amendment #2; 
dated 23 February 2016). Tbese administrative changes were requested by Health Canada and 
are highlighted in the attached Summary of Change Document. 
This Administrative Change Letter #1.CAN is important study documentation. Please retain this 
letter within your study file. 
Esperion Therapeutics, Inc. 
Confidential 
Final 12 April 2016 
3891 Ranchero Drive 
Suite 150 
Ann Arbor, MI 48108 
Page 1 of 16 

1002-040 Protocol Version:  Amendment #2   
Administrative Change Letter:  
1002-040-Am2-CA-01-Admin 
Canadian Sites Only 
 
3891 Ranchero Drive 
Suite 150 
Ann Arbor, MI 48108 
Confidential 
Final 12 April 2016 
Page 2 of 16 
TABLE OF CONTENTS 
SUMMARY OF CHANGE .............................................................................................................3 
1. 
SYNOPSIS ...................................................................................................................3 
2. 
SECTION 7.1 ...............................................................................................................4 
3. 
SECTION 8.5 ...............................................................................................................6 
4. 
SECTION 10.2.2 ..........................................................................................................6 
5. 
SECTION 11.1.6.1 .......................................................................................................8 
6. 
APPENDIX 1..............................................................................................................12 
 
 

1002-040 Protocol Version:  Amendment #2   
Administrative Change Letter:  
1002-040-Am2-CA-01-Admin 
Canadian Sites Only 
 
 
3891 Ranchero Drive 
Suite 150 
Ann Arbor, MI 48108 
Confidential 
Final 12 April 2016 
Page 3 of 16 
SUMMARY OF CHANGE 
The changes included in this Administrative Change Letter are: 
 Clarification of adequate birth control requirements for women of childbearing potential 
 The addition of a urine pregnancy test for women of childbearing potential prior to 
randomization 
 The addition of instructions for management of a bempedoic acid overdose 
The specific changes to protocol text with reference to location and rationale for change are 
provided below.  Changes to text or added text are italicized.  Deleted text will be indicated with 
strikethrough font. 
1. 
SYNOPSIS 
Previous Text [Diagnosis and criteria for patient eligibility] 
1. Men and nonpregnant, nonlactating women. Women must be either:  
- Naturally postmenopausal (as reported by the patient, defined as greater than 
55 years and ≥1 year without menses, less than 55 years and ≥1 year without 
menses with follicle-stimulating hormone (FSH) ≥40.0 IU/L), or surgically sterile 
(including hysterectomy and/or bilateral oophorectomy, but not tubal ligation 
alone) or;  
- Women of childbearing potential must be willing to use 1 acceptable method of 
birth control. 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). 
- There are no protocol-specific birth control requirements for men with partners 
who are able to become pregnant. 
New Text [Diagnosis and criteria for patient eligibility] 
2. Men and nonpregnant, nonlactating women. Women must be either:  
- Naturally postmenopausal (as reported by the patient, defined as greater than 
55 years and ≥1 year without menses, less than 55 years and ≥1 year without 
menses with follicle-stimulating hormone (FSH) ≥40.0 IU/L), or surgically sterile 
(including hysterectomy and/or bilateral oophorectomy, but not tubal ligation 
alone) or;  

1002-040 Protocol Version:  Amendment #2   
Administrative Change Letter:  
1002-040-Am2-CA-01-Admin 
Canadian Sites Only 
 
 
3891 Ranchero Drive 
Suite 150 
Ann Arbor, MI 48108 
Confidential 
Final 12 April 2016 
Page 4 of 16 
- 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 (not including periodic abstinence such 
as calendar, ovulation, symptothermal, postovulation methods, or withdrawal). 
- There are no protocol-specific birth control requirements for men with partners 
who are able to become pregnant. 
Rationale 
Additional clarification to the start and duration of acceptable methods of birth control were 
required by Health Canada. 
 
Previous Text [Criteria for evaluation)] 
Other Screening Laboratories: 
 Hepatitis B surface antigen (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), TSH 
New Text [Criteria for evaluation)] 
Other Screening Laboratories: 
 Hepatitis B surface antigen (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 pregnancy test Day 1 prior to 
randomization (only for females who are of childbearing potential),  TSH 
Rationale 
Additional confirmation of pregnancy status of women of childbearing prior to randomization 
was required by Health Canada. 
2. 
SECTION 7.1 
Previous Text [Subject Inclusion Criteria] 
2. Men and nonpregnant, nonlactating women. Women must be either:  

1002-040 Protocol Version:  Amendment #2   
Administrative Change Letter:  
1002-040-Am2-CA-01-Admin 
Canadian Sites Only 
 
 
3891 Ranchero Drive 
Suite 150 
Ann Arbor, MI 48108 
Confidential 
Final 12 April 2016 
Page 5 of 16 
a. Naturally postmenopausal (as reported by the patient, defined as greater than 
55 years and ≥1 year without menses, less than 55 years and ≥1 year without 
menses with follicle-stimulating hormone (FSH) ≥40.0 IU/L), or surgically sterile 
(including hysterectomy and/or bilateral oophorectomy, but not tubal ligation 
alone) or;  
b. Women of childbearing potential must be willing to use 1 acceptable method of 
birth control. 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). 
c. There are no protocol-specific birth control requirements for men with partners 
who are able to become pregnant. 
New Text [Subject Inclusion Criteria] 
2. Men and nonpregnant, nonlactating women. Women must be either:  
a. Naturally postmenopausal (as reported by the patient, defined as greater than 
55 years and ≥1 year without menses, less than 55 years and ≥1 year without 
menses with follicle-stimulating hormone (FSH) ≥40.0 IU/L), or surgically sterile 
(including hysterectomy and/or bilateral oophorectomy, but not tubal ligation 
alone) or;  
b. 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 (not including periodic abstinence such 
as calendar, ovulation, symptothermal, postovulation methods, or withdrawal). 
c. There are no protocol-specific birth control requirements for men with partners 
who are able to become pregnant. 
Rationale 
Additional clarification to the start and duration of acceptable methods of birth control were 
required by Health Canada. 

1002-040 Protocol Version:  Amendment #2   
Administrative Change Letter:  
1002-040-Am2-CA-01-Admin 
Canadian Sites Only 
 
 
3891 Ranchero Drive 
Suite 150 
Ann Arbor, MI 48108 
Confidential 
Final 12 April 2016 
Page 6 of 16 
3. 
SECTION 8.5 
New Text-New Section [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. 
Rationale 
Information regarding overdose of bempedoic acid was required by Health Canada. 
4. 
SECTION 10.2.2 
Previous Text [Treatment Week 0 (Visit T1; Day 1] 
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, coagulation, and urinalysis 
 Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
 apoB 
 HbA1C  
 hs-CRP 
 Reserve sample 
New Text [Treatment Week 0 (Visit T1; Day 1] 
The patient will undergo the following assessments and procedures at (Visit T1) 
 Concomitant and prohibited medication review (ongoing) 

1002-040 Protocol Version:  Amendment #2   
Administrative Change Letter:  
1002-040-Am2-CA-01-Admin 
Canadian Sites Only 
 
 
3891 Ranchero Drive 
Suite 150 
Ann Arbor, MI 48108 
Confidential 
Final 12 April 2016 
Page 7 of 16 
 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, coagulation, and urinalysis 
 Urine pregnancy test (only for females of childbearing potential) 
 Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
 apoB 
 HbA1C  
 hs-CRP 
 Reserve sample 
Rationale 
Additional confirmation of pregnancy status of women of childbearing prior to randomization 
was required by Health Canada. 

1002-040 Protocol Version:  Amendment #2   
Administrative Change Letter:  
1002-040-Am2-CA-01-Admin 
Canadian Sites Only 
 
 
3891 Ranchero Drive 
Suite 150 
Ann Arbor, MI 48108 
Confidential 
Final 12 April 2016 
Page 8 of 16 
5. 
SECTION 11.1.6.1 
Previous Text [Laboratory Parameters (Safety), Table 5] 
Table 1: 
Clinical Laboratory Parameters (Safety) 
Clinical Laboratory Test 
Clinical Laboratory Test 
 
Hematology 
Blood Chemistry (serum, fasting) 
 
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 %) 
 
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) 
 
Total protein 
 
Uric acid 
Urinalysis (Dipstick) 
 
Clarity 
 
Bilirubin 
 
Color 
 
Glucose 
 
Ketones 
 
Leukocyte esterase 
 
Nitrate 
 
Occult blood 
 
pH 
 
Protein 
 
Specific gravity 
 
Urobilinogen 

1002-040 Protocol Version:  Amendment #2   
Administrative Change Letter:  
1002-040-Am2-CA-01-Admin 
Canadian Sites Only 
 
 
3891 Ranchero Drive 
Suite 150 
Ann Arbor, MI 48108 
Confidential 
Final 12 April 2016 
Page 9 of 16 
Table 1: 
Clinical Laboratory Parameters (Safety) (Continued) 
Clinical Laboratory Test 
Clinical Laboratory Test 
Urinalysis (Microscopic)-only if urine dipstick 
abnormal 
Coagulation  
 
Bacteria 
 
Casts 
 
Crystals 
 
Epithelial cells 
 
Red blood cell (RBC) 
 
WBC 
 
Prothrombin time (PT) 
 
International normalized ration (INR) 
Other Screening Labs 
Additional samples 
 
Hepatitis B surface antigen (HBsAg), 
hepatitis C virus (HCV) 
 
Serum pregnancy test (only for females 
of childbearing potential) 
 
Follicle-stimulating hormone (FSH; 
Females <55 years and >1 year without 
menses) 
 
Thyroid-stimulating hormone (TSH) 
 
Hemoglobin A1C (HbA1C) 
 
Reserve blood samples for potential 
future measurement of ETC-1002 safety 
or pharmacodynamic biomarkers 
 
PK sample  
 
Reserve genetic blood sample (optional) 

1002-040 Protocol Version:  Amendment #2   
Administrative Change Letter:  
1002-040-Am2-CA-01-Admin 
Canadian Sites Only 
 
 
3891 Ranchero Drive 
Suite 150 
Ann Arbor, MI 48108 
Confidential 
Final 12 April 2016 
Page 10 of 16 
New Text [Laboratory Parameters (Safety), Table 5] 
Table 2: 
Clinical Laboratory Parameters (Safety) 
Clinical Laboratory Test 
Clinical Laboratory Test 
 
Hematology 
Blood Chemistry (serum, fasting) 
 
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 %) 
 
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) 
 
Total protein 
 
Uric acid 
Urinalysis (Dipstick) 
 
Clarity 
 
Bilirubin 
 
Color 
 
Glucose 
 
Ketones 
 
Leukocyte esterase 
 
Nitrate 
 
Occult blood 
 
pH 
 
Protein 
 
Specific gravity 
 
Urobilinogen 

1002-040 Protocol Version:  Amendment #2   
Administrative Change Letter:  
1002-040-Am2-CA-01-Admin 
Canadian Sites Only 
 
 
3891 Ranchero Drive 
Suite 150 
Ann Arbor, MI 48108 
Confidential 
Final 12 April 2016 
Page 11 of 16 
Table 2: 
Clinical Laboratory Parameters (Safety) (Continued) 
Clinical Laboratory Test 
Clinical Laboratory Test 
Urinalysis (Microscopic)-only if urine dipstick 
abnormal 
Coagulation  
 
Bacteria 
 
Casts 
 
Crystals 
 
Epithelial cells 
 
Red blood cell (RBC) 
 
WBC 
 
Prothrombin time (PT) 
 
International normalized ration (INR) 
Other Screening Labs 
Additional samples 
 
Hepatitis B surface antigen (HBsAg), 
hepatitis C virus (HCV) 
 
Serum pregnancy test (only for females 
of childbearing potential) 
 
Urine pregnancy test prior to 
randomization (only for females of 
childbearing potential) 
 
Follicle-stimulating hormone (FSH; 
Females <55 years and >1 year without 
menses) 
 
Thyroid-stimulating hormone (TSH) 
 
Hemoglobin A1C (HbA1C) 
 
Reserve blood samples for potential 
future measurement of ETC-1002 safety 
or pharmacodynamic biomarkers 
 
PK sample  
 
Reserve genetic blood sample (optional) 
Rationale 
Additional confirmation of pregnancy status of women of childbearing potential prior to 
randomization was required by Health Canada. 

1002-040 Protocol Version:  Amendment #2   
Administrative Change Letter:  
1002-040-Am2-CA-01-Admin 
Canadian Sites Only 
 
 
3891 Ranchero Drive 
Suite 150 
Ann Arbor, MI 48108 
Confidential 
Final 12 April 2016 
Page 12 of 16 
6. 
APPENDIX 1 
Previous Text [Schedule of Events (Subject Visit Schedule)]  
 
Screen 
Treatment 
Visit 
S11,2 
T1 
T2 
T3 
T4 
T5 
T6 
T7 EOS3 
Week  
Wk 
-2 
Wk 
0 
Wk 
4 
Wk 
8 
Wk 
12 
Wk 
24 
Wk 
36 
Wk 
52 
Procedure 
Day 
-16 to -4 
Day 
1 
Day 
29±3 
Day 
57±3 
Day 
85±3 
Day 
169±7 
Day 
253±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 
Adverse Event Recording 
 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
 
X 
 
 
 
 
 
X 
Weight4 
X 
X 
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 
 
 
 
 
 
 
 
TSH 
X 
 
 
 
 
 
 
 
Clinical Safety Labs9 
X 
X 
X 
X 
X 
X 
X 
X 
Basic Fasting Lipids10 
X 
X 
X 
X 
X 
X 
X 
X 
HbA1C 
X 
X 
 
 
X 
 
 
X 
10 mL reserve sample 
 
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 
 
Plasma PK 
 
 
 
 
X 
X 
 
X 
Establish Patient Eligibility 
 
X 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
IWRS Contact 
X 
X 
 
 
X 
X 
X 
X12 
Double-blind Drug Dispensing13 
 
X 
 
 
X 
X 
X 
 
Drug Return/Compliance 
 
 
X 
X 
X 
X 
X 
X 
Schedule next visit 
X 
X 
X 
X 
X 
X 
X 
X14 

1002-040 Protocol Version:  Amendment #2   
Administrative Change Letter:  
1002-040-Am2-CA-01-Admin 
Canadian Sites Only 
 
 
3891 Ranchero Drive 
Suite 150 
Ann Arbor, MI 48108 
Confidential 
Final 12 April 2016 
Page 13 of 16 
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 
visit is completed, the mean of lipid values from both visits 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 in the morning 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 Pregnancy test completed in premenopausal women only. FSH test is completed in women <55 years old and >1 year without 
menses 
9 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits. Coagulation is included at Screening 
(Visit S1), Baseline (Visit T1), Week 12 (Visit T4), and at EOS (Visit T7). Please refer to 
 laboratory manual for 
detailed schedule of tests. 
10 Basic fasting 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. The bottle dispensed at Visit T1 will be returned to clinic at Visits T2 and T3 for evaluation of compliance and 
returned for continued use. 
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 

1002-040 Protocol Version:  Amendment #2   
Administrative Change Letter:  
1002-040-Am2-CA-01-Admin 
Canadian Sites Only 
 
 
3891 Ranchero Drive 
Suite 150 
Ann Arbor, MI 48108 
Confidential 
Final 12 April 2016 
Page 14 of 16 
New Text [Schedule of Events (Subject Visit Schedule)]  
 
Screen 
Treatment 
Visit 
S11,2 
T1 
T2 
T3 
T4 
T5 
T6 
T7 EOS3 
Week  
Wk 
-2 
Wk 
0 
Wk 
4 
Wk 
8 
Wk 
12 
Wk 
24 
Wk 
36 
Wk 
52 
Procedure 
Day 
-16 to -4 
Day 
1 
Day 
29±3 
Day 
57±3 
Day 
85±3 
Day 
169±7 
Day 
253±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 
Adverse Event Recording 
 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
 
X 
 
 
 
 
 
X 
Weight4 
X 
X 
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 
X 
X 
Basic Fasting Lipids10 
X 
X 
X 
X 
X 
X 
X 
X 
HbA1C 
X 
X 
 
 
X 
 
 
X 
10 mL reserve sample 
 
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 
 
Plasma PK 
 
 
 
 
X 
X 
 
X 
Establish Patient Eligibility 
 
X 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
IWRS Contact 
X 
X 
 
 
X 
X 
X 
X12 
Double-blind Drug Dispensing13 
 
X 
 
 
X 
X 
X 
 
Drug Return/Compliance 
 
 
X 
X 
X 
X 
X 
X 
Schedule next visit 
X 
X 
X 
X 
X 
X 
X 
X14 

1002-040 Protocol Version:  Amendment #2   
Administrative Change Letter:  
1002-040-Am2-CA-01-Admin 
Canadian Sites Only 
 
 
3891 Ranchero Drive 
Suite 150 
Ann Arbor, MI 48108 
Confidential 
Final 12 April 2016 
Page 15 of 16 
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 
visit is completed, the mean of lipid values from both visits 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 in the morning 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 and urine pregnancy tests completed in premenopausal women  or women of childbearing potential only. FSH test is 
completed in women <55 years old and >1 year without menses 
9 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits. Coagulation is included at Screening 
(Visit S1), Baseline (Visit T1), Week 12 (Visit T4), and at EOS (Visit T7). Please refer to 
 laboratory manual for 
detailed schedule of tests. 
10 Basic fasting 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. The bottle dispensed at Visit T1 will be returned to clinic at Visits T2 and T3 for evaluation of compliance and 
returned for continued use. 
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 

1002-040 Protocol Version:  Amendment #2   
Administrative Change Letter:  
1002-040-Am2-CA-01-Admin 
Canadian Sites Only 
 
 
3891 Ranchero Drive 
Suite 150 
Ann Arbor, MI 48108 
Confidential 
Final 12 April 2016 
Page 16 of 16 
Rationale 
Additional confirmation of pregnancy status of women of childbearing prior to randomization 
was required by Health Canada.