Conditions: Hypercholesterolemia Atherosclerotic Cardiovascular Disease
Keywords: hyperlipidemia cholesterol heterozygous familial hypercholesterolemia atherosclerotic cardiovascular disease ASCVD HeFH LDL
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 1462
Healthy volunteers: no

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

Detailed description:

Arms:
arm 1: bempedoic acid 180 mg tablet

Interventions: intervention 1: bempedoic acid
Intervention descriptions: intervention 1: bempedoic acid 180 mg tablets taken orally, once per day.

Protocol document:
Prot_000.pdf: 
Confidential 
Page 1 of 100 
1.
TITLE PAGE
BEMPEDOIC ACID 
1002-050
A MULTICENTER OPEN-LABEL EXTENSION (OLE) STUDY TO 
ASSESS THE LONG-TERM SAFETY AND EFFICACY OF 
BEMPEDOIC ACID (ETC-1002) 180 MG 
Study Phase: 
3 
IND Number: 
106,654 
EudraCT 
Number: 
2016-004115-12 
Indication: 
Treatment of hyperlipidemia 
Investigators: 
Approximately 125 sites located in the United States, Canada, 
Germany, Netherlands, Poland, United Kingdom 
Sponsor: 
Esperion Therapeutics, Inc. 
3891 Ranchero Drive, Suite 150 
Ann Arbor, MI 48108 
Phone:  734-862-4840 
Fax:  734-582-9720 
Sponsor Contact: 
Medical Monitor: 
Version 
Date 
Original Protocol: 
01 November 2016 
Amendment 1: 
09 May 2017 
Amendment 2: 
15 January 2018 
Confidentiality Statement 
THIS CONFIDENTIAL INFORMATION IS ABOUT AN INVESTIGATIONAL DRUG PROVIDED FOR THE EXCLUSIVE USE OF INVESTIGATORS OF 
THIS DRUG AND IS PATIENT TO RECALL AT ANY TIME. THE INFORMATION IN THIS DOCUMENT MAY NOT BE DISCLOSED UNLESS SUCH 
DISCLOSURE IS REQUIRED BY FEDERAL OR STATE LAW OR REGULATIONS. PATIENT TO THE FOREGOING, THIS INFORMATION MAY BE
DISCLOSED ONLY TO THOSE PERSONS INVOLVED IN THE STUDY WHO HAVE NEED TO KNOW, WITH THE OBLIGATION NOT TO FURTHER
DISSEMINATE THIS INFORMATION. THESE RESTRICTIONS ON DISCLOSURE WILL APPLY EQUALLY TO ALL FUTURE ORAL OR WRITTEN
INFORMATION, SUPPLIED TO YOU BY ESPERION THERAPEUTICS, INC., WHICH IS DESIGNATED AS “PRIVILEGED” OR “CONFIDENTIAL.” 
NCT Number: NCT03067441
This NCT number has been applied to the document for
purposes of posting on Clinicaltrials.gov


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Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 3 of 100 
An independent expert Data Monitoring Committee (DMC) will formally review accumulating 
unblinded safety and efficacy data from this and other ongoing studies of bempedoic acid.  A blinded 
independent expert Clinical Events Committee (CEC) will adjudicate designated clinical endpoints 
across the program, including all major adverse cardiac events (MACE) and non-MACE endpoints 
defined as:  cardiovascular (CV) death (MACE), non-CV death (non-MACE), nonfatal myocardial 
infarction [MI] (MACE), nonfatal stroke (MACE), hospitalization for unstable angina (MACE), 
coronary revascularization (MACE), noncoronary 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 as well as a clinical endpoint. 
Primary Endpoint: 
Patient incidence of adverse events (AEs) 
Secondary Endpoints: 
• 
Percent change from baseline in LDL-C at Weeks 52 and 78 
• 
Change from baseline in LDL-C at Weeks 52 and 78  
• 
Percent change from baseline in non-HDL-C at Weeks 52 and 78  
• 
Percent change from baseline in TC at Weeks 52 and 78 
• 
Percent change from baseline in ApoB at Weeks 52 and 78 
• 
Percent change from baseline in hs-CRP at Weeks 52 and 78 
• 
Percent change from baseline in TG at Weeks 52 and 78 
• 
Percent change from baseline in HDL-C at Weeks 52 and 78 
Number of patients (planned):  The number of patients entering this study will depend on the 
number of patients completing Study 1002-040 and their willingness to enroll and continue taking 
investigational product.  Approximately 1300 patients of the 1950 eligible from parent study 1002-040 
are expected to participate in this study. 
Diagnosis and Criteria for Inclusion: 
Key inclusion criteria 
1. Successfully completed the parent study (1002-040) and meet both of the following criteria:   
• 
The patient was compliant with the parent study requirements including study visits, 
procedures, and investigational medicinal product (IMP) in the opinion of the principal 
investigator; 
• 
The patient was able to tolerate IMP through the end of the parent study. 
Key exclusion criteria 
1. Female patient is not willing to use at least 1 acceptable method of birth control during treatment 
and for an additional 30 days after the end of treatment unless patient is sterilized or 
postmenopausal; 
• 
Menopause is 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);  
• 
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 where it is the preferred and usual lifestyle 
of the patient (not including periodic abstinence such as calendar, ovulation, symptothermal, 
postovulation methods, or withdrawal).  


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 4 of 100 
2. Patient is pregnant or breast feeding, or might become pregnant during treatment and/or within 
30 days after the end of treatment 
3. Unreliability as a study participant based on the investigator’s (or designee’s) knowledge of the 
patient (eg, inability or unwillingness to adhere to the protocol) 
4. Experienced a treatment-related SAE that led to study drug discontinuation in the parent study 
5. Disorder that would interfere with understanding and giving informed consent or compliance with 
protocol requirements 
6. Have any medical condition that in the opinion of the investigator may affect patient safety or 
ability to complete scheduled assessments 
7. Patient’s medical condition requires lipid measurement and/or adjustment of background lipid-
regulating therapy during the first 12 weeks of study participation 
8. Known sensitivity to any of the products to be administered during dosing 
9. Currently enrolled in another investigational device or drug study (excluding ETC-1002-040), or 
less than 30 days since ending another investigational device or drug study(s), or receiving or 
planning to receive other investigational agent(s) during this study 
Test product, dose, and mode of administration:   
• 
Bempedoic acid 180-mg tablets 
All study drug (bempedoic acid) will be ingested once daily with or without food.  On clinic days 
patients will come to the clinic in the fasted state and study drug will be administered after laboratories 
are obtained. 
Duration of treatment: 
The total duration of treatment for an individual subject will be 1.5 years (18 months).  The total 
duration in the study will be 19 months. 
Criteria for evaluation: 
Efficacy: 
Lipid and Cardiometabolic Assessments: 
• 
Calculated LDL-C, HDL-C, non-HDL-C, TC, TG, ApoB, and hs-CRP 
− 
If TG exceeds 400 mg/dL (4.5 mmol/L) or LDL-C is ≤50 mg/dL (1.3 mmol/L), direct 
measure of LDL-C will be conducted. 
Safety: 
Safety Assessments: 
• 
Adverse events and SAEs will be collected and reported.  Clinical endpoints will be collected 
and adjudicated by an independent CEC.  Clinical endpoints will also be reported as SAEs as 
appropriate.  Other safety assessments will include clinical safety laboratories (including 
hematology, blood chemistry, glycosylated hemoglobin, Type A1C (HbA1C), fasting glucose, 
and urinalysis), physical examination (PE) findings, vital signs, electrocardiogram (ECG) 
readings, and weight. 
Clinical Laboratory Assessments: 
• 
Hematology:  Hematocrit (Hct), hemoglobin (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 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 5 of 100 
• 
Urinalysis (Microscopic):  Obtain centrally only if positive urine dipstick; bacteria, casts, 
crystals, epithelial cells, RBC, and WBC 
• 
Serum Chemistry (fasting):  Albumin (ALB), alkaline phosphatase (ALK-P), alanine 
aminotransferase (ALT; or serum glutamic pyruvic transaminase [SGPT]), aspartate 
aminotransferase (AST; or serum glutamic oxaloacetic transaminase [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, total protein, uric acid  
• 
HbA1C 
Safety and Monitoring: 
Lipid results will be masked in order to maintain the blind from the parent study (1002-040) for the 
first 12 weeks of trial and unmasked after the Week 12 visit.  See Section 10.1.4.4.1 for additional 
details. 
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. 
Musculoskeletal Safety: 
Patients with CK abnormalities will also be reviewed for any other lab changes, such as creatinine, 
and any reported AEs or SAEs.  Musculoskeletal events will be identified and evaluated by routine 
safety monitoring of PE findings and AEs.  
Hepatic:  
Hepatic function will be monitored throughout with the clinical safety labs.  More detailed 
investigation will occur if the safety clinical laboratory results are 3 times or more than the upper 
limit of normal (ULN).  
Further details on occurrence and monitoring are available in the Investigator’s Brochure (IB) and 
protocol. 
Statistical methods: 
Sample Size 
General Considerations 
Statistical analyses in this open-label, multicenter single arm study will be descriptive in nature.  No 
statistical inference is planned.   
Patient disposition, demographics and baseline characteristics will be summarized.   
Summary statistics for continuous variables will include the number of patients, mean, median, 
standard deviation or standard error, first and third quartiles minimum, and maximum.  For categorical 
variables, the frequency and percentage will be given. Ninety-five percent (95%) confidence intervals 
will be calculated for select continuous and categorical endpoint estimates. 
All patients will be summarized together as well as by their prior treatment in the parent study.  
For all efficacy endpoints, the percent changes in lipid parameters are calculated from baseline of the 
parent study. The full analysis set (FAS) will include all patients enrolled in this study that had at least 
1 dose of bempedoic acid 180 mg in this study.  All analyses will be performed using the FAS.  There 
will be no imputation for missing data.  


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 6 of 100 
Clinical endpoints from this and other Phase 3 studies will be monitored and adjudicated by an 
independent CEC to facilitate aggregated analyses across the bempedoic acid program.   
Analyses of the Primary Endpoint 
Adverse events will be coded using the latest version of Medical Dictionary for Regulatory Activities 
(MedDRA).  Patient incidences of treatment-emergent adverse events (TEAEs), treatment-related AEs, 
SAEs, and AEs leading to withdrawal of study medication will be tabulated by system organ class and 
preferred term.   
Analysis of Secondary Endpoints 
Secondary endpoints will be summarized at Weeks 52 and 78.  Descriptive statistics will be presented. 
Other Safety Analyses 
Measurements of laboratory parameters and vital signs will be summarized at each scheduled visit.  
Lab shift tables will be provided.  Summaries of vital signs will also be provided. 
Safety Monitoring 
The study includes adjudication of events by an independent CEC and formal review of ongoing data 
by an independent DMC.  The DMC will formally review the accumulating data from this ongoing 
study in conjunction with other bempedoic acid studies to ensure there is no avoidable increased risk 
or harm to patients. 
 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 08 January 2018 
Confidential 
Page 7 of 100 
TABLE OF CONTENTS 
1. 
TITLE PAGE ................................................................................................................1 
2. 
SYNOPSIS ...................................................................................................................2 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................12 
4. 
INTRODUCTION ......................................................................................................16 
4.1. 
Lipid-Regulating Drugs and Cardiovascular Disease .................................................16 
4.2. 
Background on Bempedoic Acid ................................................................................17 
4.2.1. 
Mechanism of Action .................................................................................................17 
4.2.2. 
Nonclinical Experience ...............................................................................................18 
4.2.3. 
Previous Human Experience .......................................................................................19 
4.2.4. 
Dose Selection ............................................................................................................20 
4.2.5. 
Background Therapy ..................................................................................................20 
4.2.6. 
Risk Benefit Summary ................................................................................................20 
5. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................21 
5.1. 
Study Objectives .........................................................................................................21 
5.1.1. 
Primary Objective .......................................................................................................21 
5.1.2. 
Secondary Objectives .................................................................................................21 
5.2. 
Study Endpoints ..........................................................................................................21 
5.2.1. 
Primary Endpoint ........................................................................................................21 
5.2.2. 
Secondary Endpoints ..................................................................................................21 
6. 
INVESTIGATIONAL PLAN .....................................................................................22 
6.1. 
Overall Study Design ..................................................................................................22 
6.2. 
Study Hypothesis ........................................................................................................23 
6.3. 
Study Duration ............................................................................................................23 
6.4. 
End of Study ...............................................................................................................23 
6.5. 
Number of Patients .....................................................................................................23 
6.6. 
Patient Identification Numbers ...................................................................................23 
6.6.1. 
Enrollment ..................................................................................................................23 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 8 of 100 
6.7. 
Patient Inclusion Criteria ............................................................................................23 
6.8. 
Patient Exclusion Criteria ...........................................................................................23 
6.9. 
Investigator/Sponsor Suspension or Termination of Patient Enrollment ...................24 
7. 
TREATMENT OF PATIENTS ..................................................................................26 
7.1. 
Description of IMP .....................................................................................................26 
7.2. 
Concomitant Medications ...........................................................................................26 
7.2.1. 
Prohibited Medications and supplements ...................................................................27 
7.3. 
Blinding ......................................................................................................................27 
7.4. 
Overdose .....................................................................................................................27 
8. 
INVESTIGATIONAL MEDICINAL PRODUCT .....................................................28 
8.1. 
Investigational Medicinal Product Supply and Control ..............................................28 
9. 
STUDY PROCEDURES ............................................................................................29 
9.1. 
Informed Consent .......................................................................................................29 
9.2. 
Procedures and Schedule of Assessments ..................................................................29 
9.2.1. 
Enrollment (EOS/Day 1 OLE)....................................................................................29 
9.2.2. 
Month 3 (Week 12 ±7 days) .......................................................................................30 
9.2.3. 
Month 6 (Week 24) and Month 9 (Week 36) / Telephone Visit ( ±7 days) ...............31 
9.2.4. 
Month 12 (Week 52 ±7 days) .....................................................................................31 
9.2.5. 
Month 15 Telephone Visit (Week 64 ±7 days) ..........................................................32 
9.2.6. 
Treatment Month 18/EOT (Week 78 ±7days) ............................................................33 
9.2.7. 
Off Study Drug Period Month 19 (Week 82 +14 days) .............................................33 
9.3. 
Patient Withdrawal Criteria ........................................................................................34 
9.3.1. 
Early Withdrawal from the Study ...............................................................................34 
9.3.2. 
Procedures for Early Withdrawal ...............................................................................35 
10. 
ASSESSMENT OF SAFETY .....................................................................................36 
10.1. 
Safety Parameters .......................................................................................................36 
10.1.1. 
Demographic/Medical History ...................................................................................36 
10.1.2. 
Weight and Body Mass Index .....................................................................................36 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 9 of 100 
10.1.3. 
Physical Examination .................................................................................................36 
10.1.4. 
Clinical Laboratory Tests ...........................................................................................37 
10.1.4.1. 
Laboratory Parameters (Safety) ..................................................................................37 
10.1.4.2. 
Sample Collection, Storage, and Shipping .................................................................39 
10.1.4.3. 
General Monitoring and Management of Abnormal Clinical Labs ............................39 
10.1.4.4. 
Monitoring and Management of Potential Hypoglycemia and Metabolic 
Acidosis ......................................................................................................................41 
10.1.4.5. 
Total Blood Volume of Clinical Laboratory Samples ................................................42 
11. 
ADVERSE AND SERIOUS ADVERSE EVENTS ...................................................43 
11.1. 
Adverse Events ...........................................................................................................43 
11.1.1. 
Definition of Adverse Events .....................................................................................43 
11.1.2. 
Adverse Drug Reaction ...............................................................................................43 
11.1.3. 
Reporting for Adverse Events ....................................................................................43 
11.1.4. 
Severity .......................................................................................................................44 
11.1.5. 
Relationship ................................................................................................................45 
11.1.6. 
Monitoring and Follow-up of Adverse Events ...........................................................45 
11.1.7. 
Treatment-Emergent Adverse Events .........................................................................45 
11.2. 
Serious Adverse Events ..............................................................................................46 
11.2.1. 
Definition of Serious Adverse Event ..........................................................................46 
11.2.2. 
Reporting Serious Adverse Events .............................................................................46 
11.2.3. 
Reporting of Serious Adverse Events to Regulatory Authorities ...............................47 
11.2.4. 
Reporting of Patient Death .........................................................................................48 
11.2.5. 
Reports of Pregnancy and Lactation ...........................................................................48 
11.3. 
Adverse Events of Special Interest .............................................................................48 
11.4. 
Data Monitoring Committee .......................................................................................49 
11.5. 
Clinical Event Committee (CEC) ...............................................................................49 
11.6. 
Assessment of Lipid Endpoints ..................................................................................49 
11.6.1. 
Lipid Parameters .........................................................................................................49 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 10 of 100 
11.6.2. 
Clinical Laboratory Tests (Lipids) ..............................................................................49 
12. 
STATISTICS ..............................................................................................................51 
12.1. 
General Considerations ...............................................................................................51 
12.2. 
Determination of Sample Size ....................................................................................51 
12.3. 
Analysis Populations ..................................................................................................51 
12.4. 
Primary Endpoint ........................................................................................................51 
12.5. 
Secondary Efficacy Endpoints ....................................................................................51 
12.6. 
Other Safety Endpoints ...............................................................................................52 
13. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.........................................54 
13.1. 
Study Monitoring ........................................................................................................54 
13.2. 
Audits and Inspections ................................................................................................54 
14. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................56 
15. 
ETHICS ......................................................................................................................57 
15.1. 
Institutional Review Board/Independent Ethics Committee Approval ......................57 
15.2. 
Ethical Conduct of the Study ......................................................................................57 
15.3. 
Written Informed Consent ..........................................................................................58 
15.4. 
Patient Confidentiality ................................................................................................58 
16. 
DATA HANDLING AND RECORDKEEPING .......................................................59 
16.1. 
Inspection of Records .................................................................................................59 
16.2. 
Retention of Records ..................................................................................................59 
16.3. 
Case Report Forms and Study Records ......................................................................59 
17. 
ADMINISTRATIVE CONSIDERATIONS ..............................................................61 
17.1. 
Investigators ................................................................................................................61 
17.2. 
Amendments ...............................................................................................................62 
17.3. 
Financial Disclosure ...................................................................................................62 
18. 
PUBLICATION AND DISCLOSURE POLICY .......................................................63 
19. 
LIST OF REFERENCES ............................................................................................64 
20. 
APPENDICES ............................................................................................................66 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 11 of 100 
APPENDIX 1. SCHEDULE OF EVENTS (PATIENT VISIT SCHEDULE) ...........................67 
APPENDIX 2. SPONSOR’S SIGNATURE ...............................................................................69 
APPENDIX 3. INVESTIGATOR’S SIGNATURE....................................................................70 
APPENDIX 4. SUMMARY OF CHANGES IN AMENDMENT 1 ..........................................71 
APPENDIX 5. SUMMARY OF CHANGES IN AMENDMENT 2 ..........................................86 
 
LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................12 
Table 2: 
Investigational Medicinal Products ............................................................................26 
Table 3: 
Clinical Laboratory Parameters (Safety) ....................................................................38 
Table 4: 
Clinical Laboratory Parameters (Lipids) and Cardiometabolic Biomarkers ..............50 
 
LIST OF FIGURES 
Figure 1. 
Study 1002-050 Study Design ....................................................................................22 
 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 12 of 100 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 1: 
Abbreviations and Specialist Terms  
Abbreviation or Specialist Term 
Explanation 
ACL 
Adenosine triphosphate-citrate lyase 
ADR 
Adverse drug reaction 
AE 
Adverse event 
AESI 
Adverse events of special interest 
ALB 
Albumin 
ALK-P 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
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 
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 
CNS 
Central nervous system 
CoA 
Acetyl-coenzyme A 
CO2 
Carbon dioxide 
CV 
Cardiovascular 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 13 of 100 
Abbreviation or Specialist Term 
Explanation 
CYP 
Cytochrome P450 
DBP 
Diastolic blood pressure 
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
eGFR 
Estimated glomerular filtration rate 
EMA 
European Medicines Agency 
EOS 
End of Study 
EOT 
End of Treatment 
ETC-1002 
Bempedoic acid 
EU 
European Union 
FAS 
Full analysis set 
FDA 
Food and Drug Administration 
FPFV 
First patient first visit 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GI 
Gastrointestinal 
HbA1C 
Glycosylated hemoglobin, Type A1C 
HBsAg 
Hepatitis B surface antigen 
Hct 
Hematocrit 
HCV 
Hepatitis C virus 
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 


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Abbreviation or Specialist Term 
Explanation 
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 cardiac event 
MCH 
Mean corpuscular hemoglobin 
MCHC 
Mean corpuscular hemoglobin concentration 
MCV 
Mean corpuscular volume 
MDRD 
Modification of diet in renal disease 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Myocardial infarction 
MRI 
Magnetic resonance imaging 
Na 
Sodium 
N/A 
Not available 
N/D 
Not done 
NLA 
National Lipid Association 
NOAEL 
No-observed-adverse-effect level 
non-HDL-C 
Non-high-density lipoprotein cholesterol 
OLE 
Open-label extension (study) 
Parent study 
Study 1002-040 
PCSK9 
Proprotein convertase subtilisin/kexin type 9 
PE 
Physical exam 
PK 
Pharmacokinetic(s) 


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Abbreviation or Specialist Term 
Explanation 
PO 
By mouth 
PT 
Prothrombin time 
QD 
Once daily 
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 
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 
TQT 
Thorough QT/QTc 
ULN 
Upper limit of normal 
US 
United States 
WBC 
White blood cell 
WHO 
World Health Organization 


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4. 
INTRODUCTION 
4.1. 
Lipid-Regulating Drugs and Cardiovascular Disease  
Bempedoic acid (ETC-1002) is an inhibitor of adenosine triphosphate-citrate lyase (ACL) 
(adenosine triphosphate [ATP] citrate lyase), an enzyme upstream of 3-hydroxy-3-methylglutaryl 
coenzyme A (HMG-CoA) reductase in the cholesterol biosynthesis pathway.  It is an oral first-
in-class small molecule designed to lower low-density lipoprotein cholesterol (LDL-C) levels in 
patients with high cardiovascular (CV) risk unable to meet their treatment goals with currently 
available lipid-lowering therapies. 
Hyperlipidemic patients at high CV risk due to either heterozygous familial 
hypercholesterolemia (HeFH) and/or established atherosclerotic cardiovascular disease 
(ASCVD) unable to meet their LDL-C treatment goals with currently available therapies are the 
target patient populations for this study.  
Elevated LDL-C is a major modifiable risk factor for the development of atherosclerosis and 
ASCVD (Sharrett 2001).  Despite aggressive interventional and pharmacologic therapies, CV 
disease is the number 1 cause of death globally (WHO 2015).  An estimated 17.5 million people 
died from CV diseases in 2012, representing 31% of all global deaths.  Of these deaths, an 
estimated 7.4 million were due to coronary heart disease (CHD) and 6.7 million were due to 
stroke (WHO 2015).  Cardiovascular disease remains the leading cause of death among 
Europeans, Americans, and around the world.  The Global Burden of Disease study estimated 
that 29.6% of all deaths worldwide (approximately 15.6 million deaths) were caused by CV 
disease in 2010, more than all communicable, maternal, neonatal and nutritional disorders 
combined, and double the number of deaths caused by cancers (Nichols 2014).  In the United 
States (US), based on 2011 death rate data, more than 2150 Americans die from CV diseases 
daily, an average of 1 death every 40 seconds.  Approximately 155,000 Americans dying from 
CV disease are less than 65 years of age.  In 2011, 34% of deaths due to CV disease occurred 
prior to the age of 75 years, less than the current 78.7-year average life expectancy (Mozffarian 
2015).  
Patients with documented ASCVD are at very high risk for events and require intensive 
pharmacologic intervention (Stone 2014).  For a variety of reasons, many with ASCVD are 
unable to attain aggressive LDL-C treatment goals despite the addition of lipid-lowering agents 
to maximally tolerated statin therapy (Jacobson 2014).  
Familial hypercholesterolemia refers to individuals with extremely elevated LDL-C due to 
underlying genetic mutations of the LDL receptor (LDLR), apolipoprotein B (ApoB), and 
proprotein convertase subtilisin/kexin type 9 (PCSK9) (FH Foundation 2015).  In adult HeFH 
patients, LDL-C usually exceeds 190 mg/dL (4.9 mmol/L) and can be as high as 400 mg/dL 
(10.4 mmol/L).  HeFH is the most common form of the disease with a prevalence of 
approximately 1 in 300 to 500 persons worldwide and as high as 1 in 100 persons in some 
populations (NORD 2015).  Patients with HeFH inherit a genetic mutation from 1 parent.  
Inheritance is generally via an autosomal-dominant mechanism (Robinson 2013).  HeFH 
increases the risk of atherosclerosis leading to CV events.  The mean age for the onset of CV 
disease is relatively young, at 42 to 46 years in men and 51 to 52 years in women (Robinson 
2013).  The cumulative risk of experiencing a coronary event by the age of 60 years without 


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effective treatment is at least 50% in men and approximately 30% in women with a marked 
increase in postmenopausal women.  Before effective treatment with statins became available, 
mortality from coronary disease was increased by nearly 100-fold in young adults 20 to 39 years 
of age, and approximately 4-fold for patients aged 40 to 59 years (Neil 2008).  The National 
Lipid Association (NLA) recommends achievement of ≥50% reduction in LDL-C in adult 
patients using statins.  HeFH patients at even higher risk for CV disease (such as those with 
established ASCVD, diabetes, smoking, family history, and other risk factors) have a treatment 
goal of ≤70 mg/dL (1.8 mmol/L).  Those unable to achieve these treatment goals with maximally 
tolerated statin therapy require additional lipid-lowering therapy and still may be unable to reach 
LDL-C treatment goals.  
Lowering LDL-C is the primary therapeutic lipid target in ASCVD and HeFH patients 
(Goldberg 2011).  LDL-C is largely accepted as a valid surrogate endpoint of CV events by 
clinicians and regulatory authorities (Stone 2014).  Long-term elevations in LDL-C lead to 
progressive accumulation of atherosclerotic lesions in the walls of arteries that require long-term 
management.  While lifestyle changes are the primary intervention, these measures rarely reduce 
plasma LDL-C by >15%.  Particularly in ASCVD and HeFH patients, pharmacologic treatments 
are required to adequately treat hyperlipidemia (Pollex 2008).  Evidence supporting LDL-C as a 
therapeutic target and surrogate for CV outcomes comes from interventional studies with 
LDL-C-lowering therapies, epidemiological studies, genetic variants (both gain of function and 
loss of function).  Large randomized clinical studies aimed at lowering LDL-C show a 
consistent, log-linear relationship between LDL-C reduction and CV risk reduction, independent 
of the way LDL-C lowering was achieved based on mechanism of action (Kathiresan 2008; 
Baigent 2010; Robinson 2005; Stamler 1986).  A published patient-level meta-analysis including 
26 trials and more than 160,000 participants, showed a consistent relationship between LDL-C 
reduction and CV outcomes (Baigent 2010).  This analysis showed that with a 1 mmol/L 
reduction in LDL-C associated with a 22% reduction in the 5-year incidence of major coronary 
events, revascularizations, and ischemic strokes.  Intensive statin therapy relative to 
low/moderate intensity statin treatment produces greater benefit in patients at high CV risk 
(Cannon 2004).  Unfortunately, some patients are unable to take high intensity statins due to 
dosing limits based on co-morbidities, contraindications, and/or tolerance (Jacobson 2014).  
Nonstatin therapies may provide additional lowering of CV risk as demonstrated in the 
IMPROVE-IT trial, which added ezetimibe to statin therapy (Cannon 2015).  
Patients with ASCVD and HeFH on maximally tolerated lipid-lowering therapy including 
maximally tolerated doses of statins who require additional lipid-lowering therapy have an unmet 
medical need.  Bempedoic acid may offer a once daily option for these patients.  The oral route 
of administration may be preferable to injectable biologic therapy for some patients.  Bempedoic 
acid has been well tolerated to date, and Phase 2 data demonstrate significant LDL-C lowering, 
prompting further evaluation in Phase 3 clinical studies.  
4.2. 
Background on Bempedoic Acid 
4.2.1. 
Mechanism of Action 
Bempedoic acid is a first-in-class small molecule inhibitor of ACL, an enzyme upstream of 
HMG-CoA in the cholesterol biosynthesis pathway.  Bempedoic acid is a prodrug that requires 


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


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4.2.3. 
Previous Human Experience 


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4.2.4. 
Dose Selection 
4.2.5. 
Background Therapy 
Bempedoic acid in this study is currently being evaluated as an add-on to lipid-modifying 
therapy in high-risk patients (ie, those with HeFH and/or ASCVD) who have not achieved their 
LDL-C goal despite maximally tolerated lipid-modifying therapy.  
4.2.6. 
Risk Benefit Summary 
To date, the nonclinical and clinical data indicate that bempedoic acid has a favorable risk-
benefit profile.  The ability of bempedoic acid to achieve clinically meaningful LDL-C-lowering 
responses while demonstrating a favorable tolerability profile in a variety of patient populations 
supports continued development of bempedoic acid, an oral ACL inhibitor, in Phase 3 studies. 
Please refer to the most recent IB for additional information regarding previous human 
experience. 


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Clinical Study Protocol 1002-050 
 
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5. 
TRIAL OBJECTIVES AND PURPOSE 
5.1. 
Study Objectives 
5.1.1. 
Primary Objective 
• To characterize the safety and tolerability of long-term administration of bempedoic 
acid (ETC-1002) 180 mg 
5.1.2. 
Secondary Objectives 
• To characterize the efficacy of long-term administration of bempedoic acid 
180 mg/day as assessed by changes in LDL-C, HDL-C, non-high-density lipoprotein 
cholesterol (non-HDL-C), ApoB, total cholesterol (TC), TG and high-sensitivity 
C-reactive protein (hs-CRP) in patients with hyperlipidemia 
5.2. 
Study Endpoints 
5.2.1. 
Primary Endpoint 
• The primary efficacy endpoint for this study is patient incidence of AEs 
5.2.2. 
Secondary Endpoints 
• Percent change from baseline in LDL-C at Weeks 52 and 78 
• Change from baseline in LDL-C at Weeks 52 and 78  
• Percent change from baseline in non-HDL-C at Weeks 52 and 78 
• Percent change from baseline in TC at Weeks 52 and 78 
• Percent change from baseline in ApoB at Weeks 52 and 78 
• Percent change from baseline in hs-CRP at Weeks 52 and 78 
• Percent change from baseline in TG at Weeks 52 and 78 
• Percent change from baseline in HDL-C at Weeks 52 and 78 


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6.2. 
Study Hypothesis 
The primary clinical hypothesis is that long-term exposure of bempedoic acid (ETC-1002) 
180 mg will be safe and well tolerated. 
6.3. 
Study Duration 
Patients will be enrolled after successfully completing study ETC-1002-040.  The total study 
duration for an individual subject is 82 weeks (1 year and 7 months). 
6.4. 
End of Study 
The study will end when the last patient completes their Week 82 visit.  The estimated overall 
duration of the study (first patient first visit [FPFV] to last patient last visit [LPLV]) is 
approximately 2.5 years. 
6.5. 
Number of Patients 
The study will enroll approximately 1300 patients with hyperlipidemia from approximately 
125 clinical sites.  
6.6. 
Patient Identification Numbers 
All patients who enter the study will retain the same unique patient identification number from 
the parent study (ETC-1002-040). 
6.6.1. 
Enrollment 
Patients that successfully complete parent study and satisfy all entry criteria will be enrolled.  
6.7. 
Patient Inclusion Criteria 
Each patient must meet the following criteria to be enrolled in this study: 
1. Successfully completed the parent study (1002-040) and meet both of the following 
criteria: 
• The patient was compliant with the parent study requirements including study visits, 
procedures, and IMP in the opinion of the principal investigator. 
• The patient was able to tolerate IMP through the end of the parent study. 
6.8. 
Patient Exclusion Criteria 
1. Female patient is not willing to use at least 1 acceptable method of birth control during 
treatment and for an additional 30 days after the end of treatment unless patient is 
sterilized or postmenopausal; 
• Menopause is 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) 


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≥40.0 IU/L, or surgically sterile (including hysterectomy and/or bilateral 
oophorectomy);  
• 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 
where it is the preferred and usual lifestyle of the patient (not including periodic 
abstinence such as calendar, ovulation, symptothermal, postovulation methods, or 
withdrawal). 
2. Patient is pregnant or breastfeeding, or might become pregnant during treatment and/ or 
within 30 days  after the end of treatment 
3. Unreliability as a study participant based on the investigator’s (or designee’s) knowledge 
of the patient (eg, inability or unwillingness to adhere to the protocol) 
4. Experienced a treatment-related SAE that led to study drug discontinuation in the parent 
study 
5. Disorder that would interfere with understanding and giving informed consent or 
compliance with protocol requirements 
6. Have any medical condition that in the opinion of the investigator may affect patient 
safety or ability to complete scheduled assessments 
7. Patient’s medical condition requires lipid measurement and/or adjustment of background 
lipid-regulating therapy during the first 12 weeks of study participation 
8. Known sensitivity to any of the products to be administered during dosing 
9. Currently enrolled in another investigational device or drug study (excluding ETC-1002-
040), or less than 30 days since ending another investigational device or drug study(s), or 
receiving or planning to receive other investigational agent(s) during this study. 
6.9. 
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 


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• Falsification of records 
• Failure to adhere to the protocol 
• Lack of study oversight by the Principal Investigator and/or designee 
If any serious or nonserious AEs have occurred at such a clinical site, all documentation relating 
to the event(s) must be obtained. 


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7. 
TREATMENT OF PATIENTS 
7.1. 
Description of IMP 
Table 2: 
Investigational Medicinal Products 
Product Name: 
Bempedoic acid 
Dosage Form: 
Film-coated tablets 
Unit Dose: 
180 mg 
Container/Closurea 
100-count bottle with screw on, childproof cap 
Route of Administration: 
Oral, daily, with or without food 
Physical Description: 
Manufacturer (Fill/Finish): 
Study drug should be taken once a day (once every 24 hours) at approximately the same time 
every day and may be taken with or without food.  Patients will fast (no food or drink, other than 
water) for a minimum of 10 hours prior to collection of all laboratory samples. 
Please see Pharmacy Manual for detailed storage requirements and instructions. 
7.2. 
Concomitant Medications 
During the study investigators may prescribe any necessary concomitant medication.  However, 
lipid-altering therapies cannot be adjusted during the first 12 weeks of the study.  In addition, 
during the 4-week period after last dose, every effort should be made to maintain the patients’ 
background lipid-modifying therapy unless it is medically necessary to safely manage the 
patient.  Patients will be questioned about their concomitant medication use at each clinic visit.  
All concomitant medication taken chronically or intermittently during the study must be recorded 
with indication, total daily dose, and start and stop dates of administration.  Prior and 
concomitant medications will be collected using an electronic case report form (eCRF).  


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7.2.1. 
Prohibited Medications and supplements 
All medications deemed medically necessary may be prescribed during this study, with the 
following exceptions: 
• Mipomersen  
• Lomitapide or apheresis therapy  
• Red yeast rice containing products 
• Uptitration of simvastatin to a dose that is greater than or equal to 40 mg/day 
• Gemfibrozil  
• Ezetimibe/simvastatin (Zocor®) where simvastatin doses are ≥40 mg/day (Vytorin® 
10/40 and 10/80 and Inegy® 10 mg/40 mg and 10 mg/80 mg are prohibitory)  
7.3. 
Blinding 
Laboratory results for lipid panel and hs-CRP will be masked to investigators, patients, and the 
study team until the Week 12 visit is completed.  All site staff involved with this trial should 
refrain from obtaining lipid panels between date of last ETC-1002-040 dose at end of parent 
study Week 52 (Visit T7) and Week 12 in this OLE trial. 
While this is an open-label study where all patients will receive active treatment with bempedoic 
acid (180 mg by mouth [PO] once daily [QD]), blinding of the treatment that patients received 
during the parent study must be maintained for all patients unless, in the opinion of the 
Investigator, the safety of the patient may be at risk.  Only under the rarest of circumstances 
should the Investigator consider breaking the parent study blind and only when 
medical/supportive care cannot be provided without determining if the patient was previously 
receiving active drug treatment.  In the event that the parent study blind needs to be broken prior 
to completion of the parent study, the Investigator should contact the appropriate Medical 
Monitor by telephone.  If the parent study 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 
interactive web response system (IWRS) utilized in the parent study.  In all cases of breaking the 
parent study 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. 
7.4. 
Overdose 
There is no specific antidote for an overdose of bempedoic acid.  Management of an overdose 
should be focused on the treatment of symptoms.  These symptoms should be managed 
according to current standards of care with appropriate supportive measures.  When considered 
appropriate by the Principal Investigator, discontinuation of study drug may be considered. 


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8. 
INVESTIGATIONAL MEDICINAL PRODUCT  
8.1. 
Investigational Medicinal Product Supply and Control 
The Sponsor will supply bempedoic acid (180-mg film-coated tablets) for this study.  Study drug 
will be distributed and released in accordance with regional and local requirements during the 
conduct of the study. 
Please see Pharmacy Manual for detailed storage requirements and management instructions. 


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9. 
STUDY PROCEDURES 
9.1. 
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.   
9.2. 
Procedures and Schedule of Assessments 
Patients who provide informed consent and sign the ICD will be eligible to enroll in the study.   
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.  Enrollment, drug supply (re)ordering, and patient tracking will 
occur via IWRS.  Instructions for these systems will be provided separately. 
9.2.1. 
Enrollment (EOS/Day 1 OLE) 
Day 1 for this study should occur on the same day as the end of study visit for the parent study 
(1002-040).  All efforts should be made to avoid delays in rolling over.  The study procedures 
below, from the parent study EOS visit, will be used to qualify for this study.  If Day 1 of the 
OLE study occurs >30 days from the end of study visit from the parent study, all procedures will 
need to be repeated including taking a new medical history. 
• Review of inclusion/exclusion criteria  
• Concomitant medication review 
• Assess AE/SAEs 
• Physical exam 
• Weight (kg) 
• Vital signs  
• Clinical laboratory evaluations:  
− Hematology, blood chemistry, coagulation (only in patients receiving 
anticoagulant therapy), and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− ApoB 
− Hs-CRP 
− 
Glycosylated hemoglobin, Type A1C (HbA1C) 
• Urine pregnancy test  
• Contact IWRS to register the patient 


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• Dispense study drug  
Please note the following for patients enrolling into Study 1002-050 within 30 days of 
completing the EOS visit in the parent study: 
• If the patient is not receiving anticoagulant therapy and/or is a woman who is not of 
childbearing potential, clinical laboratory samples do not need to be collected as the 
results from the parent study EOS visit will be used for this visit. 
• If the patient is receiving anticoagulant therapy, then a coagulation laboratory sample 
is required at this visit using a Study 1002-050 unscheduled laboratory kit. 
• If the patient is a woman of childbearing potential, then a urine pregnancy test is 
required at this visit. 
Please note the following for patients enrolling into Study 1002-050 greater than 30 days 
after completing the EOS visit in the parent study: 
• Clinical laboratory samples should be collected using a Study 1002-050 Day 1 kit.  
Supplies for collecting the coagulation sample are included in this kit. 
• If the patient is a woman of childbearing potential, then a urine pregnancy test is 
required at this visit. 
9.2.2. 
Month 3 (Week 12 ±7 days) 
If the patient is withdrawing early from the study at this visit, proceed to Section 9.3.2 for the list 
of the required assessments. 
If the patient is withdrawing from IMP treatment at this visit, proceed to Section 9.3.2 for the list 
of the required assessments.  The patient will be asked to continue to be followed for safety using 
the protocol-specified visit schedule.  If the patient consents for follow-up, schedule the next 
protocol-specified visit.  
Patients who do not provide consent to continue to return to the clinic for safety assessments 
after withdrawing from IMP treatment will be asked to participate in phone calls from the site at 
protocol-specified visits, or at a minimum at 78 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: 
• Concomitant medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints 
• Weight 
• Vital signs 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 


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− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− apoB and hsCRP 
• Return of IMP; assessment and recording of IMP compliance 
• Dispense IMP containers 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. 
9.2.3. 
Month 6 (Week 24) and Month 9 (Week 36) / Telephone Visit ( ±7 days) 
Patients will undergo the following assessments via telephone: 
• Concomitant medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints 
• Assessment of study drug dosing adherence 
Note:  If the patient discontinues at or between study visits, please proceed to Section 9.3.2 for 
detailed instructions. 
9.2.4. 
Month 12 (Week 52 ±7 days) 
If the patient is withdrawing early from the study at this visit, proceed to Section 9.3.2 for the list 
of the required assessments. 
If the patient is withdrawing from IMP treatment at this visit, proceed to Section 9.3.2 for the list 
of the required assessments.  The patient will be asked to continue to be followed for safety using 
the protocol-specified visit schedule.  If the patient consents for follow-up, schedule the next 
protocol-specified visit.  
Patients who do not provide consent to continue to return to the clinic for safety assessments 
after withdrawing from IMP treatment will be asked to participate in phone calls from the site at 
protocol-specified visits, or at a minimum at 78 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. 


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Patients will undergo the following assessments and procedures: 
• Concomitant medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints 
• Weight 
• Vital signs 
• Physical Exam 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL C, HDL C, non-HDL C, and TG) 
− ApoB and hs-CRP 
− HbA1C 
• Return of IMP; assessment and recording of IMP compliance 
• Dispense IMP containers 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. 
9.2.5. 
Month 15 Telephone Visit (Week 64 ±7 days) 
Patients will undergo the following assessments via telephone: 
• Concomitant medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints 
• Assessment of study drug dosing adherence 
Note:  If the patient discontinues at or between study visits, please proceed to Section 9.3.2 for 
detailed instructions. 


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9.2.6. 
Treatment Month 18/EOT (Week 78 ±7days) 
Patients will undergo the following assessments and procedures when completing the End of 
Treatment (EOT) visit, withdrawing from study prior to Week 78 (early withdrawal), or 
withdrawing from IMP treatment: 
• Concomitant medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints 
• Weight 
• Vital signs 
• Physical exam 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL C, HDL C, non-HDL C, and TG) 
− ApoB and hs-CRP 
− HbA1C 
• Return of IMP; assessment and recording of IMP compliance 
• Complete study status in IWRS (ie, early withdrawal or completed study). 
9.2.7. 
Off Study Drug Period Month 19/EOS (Week 82 +14 days) 
Patients will return for a final EOS visit 4 weeks after IMP treatment has been completed 
(including patients who withdraw from IMP treatment prior to Week 78) to undergo the 
following assessments and procedures.   
• Concomitant medication review 
• Assess AEs, SAEs, and potential clinical endpoints 
• 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 and hs-CRP 
− HbA1C 


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9.3. 
Patient Withdrawal Criteria 
9.3.1. 
Early Withdrawal from the Study 
Patients must remain in the study until the last scheduled visit at Month 19 (Week 82) to be 
considered as having completed participation in the study.  Patients must remain in the study 
through Month 18 (Week 78) to be considered as having completed participation in the treatment 
portion of the study.  
Patients who withdraw from IMP prior to Month 18 (Week 78) 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 Month 18 (Week 78) for any reason may 
restart IMP providing that 1) the patient and the investigator are in agreement regarding this 
course of action, and 2) 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 78 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: 
• Unacceptable AE 
• Patient’s withdrawal of consent 
• Failure to comply with the protocol 
• Lost to follow-up 
• Illness, condition, or procedural complication affecting the patient’s ability to 
participate or requiring prohibited medication 
• The Sponsor or Investigator terminates the study  


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• In the Investigator’s judgment, it is deemed in the best interest of the patient to 
discontinue his/her participation in the study 
• Any other reason 
If a patient is lost to follow-up, every reasonable effort must be made by the clinical site 
personnel to contact the patient and determine the reason for discontinuation/withdrawal.  The 
measures taken to follow-up must be documented. 
9.3.2. 
Procedures for Early Withdrawal 
If a patient withdraws or is removed from the study for any reason prior to Week 78, all EOT 
procedures should be completed.  In addition, the patient should return 4 weeks after last dose of 
IMP for the Week 82/EOS procedures.  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 9.2.6 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 Month 19 
(Week 82). 


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10. 
ASSESSMENT OF SAFETY 
10.1. 
Safety Parameters 
At all clinic visits, investigators will review all safety information including vital signs, AEs, and 
concomitant medications and will ensure that the collected data are recorded into the appropriate 
eCRF.  Additionally, clinical laboratory samples will be collected and sent for analysis and the 
investigator will review the results to ensure continued patient safety while participating in the 
study.  
10.1.1. 
Demographic/Medical History 
Demographic and medical history collected from the parent study will be used for this study.  If a 
patient is entering the study beyond the 30-day rollover window, changes to medical history and 
AEs that occur during that period will be collected.  
10.1.2  
Vital Signs 
Vital signs will include diastolic blood pressure (DBP) and systolic blood pressure (SBP) as well 
as heart rate. 
The patient should sit quietly for 5 minutes prior to collection of vital signs.  At all time points, 
vitals will be collected prior to blood collection.  Blood pressure (BP) and heart rate will be 
measured using a calibrated, fully automated machine with a cuff that is appropriate to the size 
of the upper arm.  If a fully automated machine is not available, BP may be measured manually.  
The same method (either automated or manual) and the same arm (right or left) must be used 
throughout the study.  The patient should be in a seated position with feet touching the floor.  
Patients should be seated quietly for at least 5 minutes in a chair with their backs supported, their 
feet flat on the ground, and their arms bared and supported at heart level. 
10.1.2. 
Weight and Body Mass Index 
Weight will be measured on a calibrated scale while fasted and after voiding.  Body weight will 
be measured while fasting, using consistent scales, after voiding, and without shoes and 
outerwear (eg, coats).  
Body mass index (BMI) will be calculated using the formula:  
BMI (kg/m2) = weight in kg / (height in meters)2 
10.1.3. 
Physical Examination 
Physical exam (PE) will include an assessment of the following: 
• General appearance 
• Skin 
• Eyes, ears, nose, and throat 
• Head and neck 
• Extremities 


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• 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 deemed necessary by the investigator  
Documentation of the PE findings will be included in the source documentation at the clinical 
site.  Only changes from baseline PE findings that meet the definition of an AE will be recorded 
on the AE page of the eCRF. 
Note:  Additional information will be collected regarding muscle-related AEs.  See Section 12.6. 
10.1.4. 
Clinical Laboratory Tests 
10.1.4.1. Laboratory Parameters (Safety) 
Patients will be in a seated position during the blood collection.  Clinical laboratory parameters 
and tests will include those listed in Table 3.  Collection schedule, schedule of laboratory 
parameters by visit, and instructions are in the Clinical Laboratory Manual provided by Central 
Laboratory. 


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Table 3: 
Clinical Laboratory Parameters (Safety) 
Clinical Laboratory Test 
Clinical Laboratory Test 
• 
Hematology 
• 
Hematocrit (Hct) 
• 
Hemoglobin (Hgb) 
• 
Mean corpuscular hemoglobin (MCH) 
• 
Mean corpuscular hemoglobin 
concentration (MCHC) 
• 
Mean corpuscular volume (MCV) 
• 
Platelet count 
• 
Red blood (RBC) cell count 
• 
White blood (WBC) cell count with 
differential (absolute and %) 
Blood Chemistry (serum, fasting) 
• 
Albumin (Alb) 
• 
Alkaline phosphatase (ALK-P) 
• 
Alanine aminotransferase (ALT; SGPT) 
• 
Aspartate aminotransferase (AST; SGOT) 
• 
Blood urea nitrogen (BUN) 
• 
Calcium (Ca) 
• 
Carbon dioxide (CO2) 
• 
Chloride (Cl) 
• 
Creatinine 
• 
Creatine kinase (CK) 
• 
Glucose 
• 
Lactate dehydrogenase (LDH) 
• 
Phosphorus 
• 
Potassium (K) 
• 
Sodium (Na) 
• 
Total and direct bilirubin (TB)a 
• 
Total protein 
• 
Uric acid 
Coagulation—only in patients receiving 
anticoagulant therapy that in the investigator’s 
judgment require monitoring at Month 0 and 3 to 
5 days post-Month 0 
• 
Prothrombin time (PT) 
• 
International normalized ration (INR) 
Urinalysis (Dipstick) 
• 
Clarity 
• 
Bilirubin 
• 
Color 
• 
Glucose 
• 
Ketones 
• 
Leukocyte esterase 
• 
Nitrate 
• 
Occult blood 
• 
pH 
• 
Protein 
• 
Specific gravity 
• 
Urobilinogen 
Urinalysis (Microscopic)-only if urine dipstick 
abnormal 
• 
Bacteria 
• 
Casts 
• 
Crystals 
• 
Epithelial cells 
• 
RBC 
• 
WBC 
Other Labs: 
• 
Urine pregnancy test  
• 
Hemoglobin A1C (HbA1C) 
a If TB ≥1.2 × ULN, a reflex indirect (unconjugated) bilirubin will be obtained. 


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10.1.4.2. 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.  Samples 
will be processed by the Central Laboratory.   
Blood draws for lipids, TG, and glucose must meet the criteria listed below.  If these criteria 
have not been met, these blood samples will NOT be collected.  If these criteria can be met by 
rescheduling the clinic visit to occur within 3 days, the lipid, TG, and/or glucose blood samples 
will be collected at the rescheduled clinic visit only.  
• Blood samples will be drawn after a minimum 10-hour fast (water is allowed) 
10.1.4.3. 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. 
10.1.4.3.1. Monitoring and Management of Elevated Liver Function Tests 
If at any time after randomization a patient experiences a new alanine aminotransferase (ALT) 
and/or aspartate aminotransferase (AST) >3 × the upper limit of normal (ULN), the patient will 
undergo repeat confirmatory liver function test (LFT) assessment as soon as is reasonably 
possible, preferably within 3 to 7 days of the laboratory result becoming available.  
Repeat LFT assessment will include:  1) measurement of ALT, AST, alkaline phosphatase 
(ALK-P), total and direct bilirubin, prothrombin time (PT)/international normalized ratio (INR), 
eosinophil count, creatine kinase (CK), antihepatitis A virus (total), hepatitis B surface antigen 
(HBsAg) (confirmation of screening measurement), hepatitis C virus (HCV) (confirmation of 
screening measurement), and anti-cytomegalovirus/immunoglobulin M; 2) history of 
concomitant medication use; 3) history of exposure to environmental chemical agents, including 
ethanol; and 4) query for related symptoms.  Additionally, further testing such as liver ultrasound 
or magnetic resonance imaging (MRI) scanning may be warranted to rule out additional 
pathology depending on clinical presentation and should be discussed with the Sponsor 
personnel or the authorized Medical Monitor.  
• If repeat LFT assessment confirms ALT and/or AST >3 × ULN, consideration should 
be given to withdrawing the patient and administering no further doses of study drug.  


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At the investigator’s discretion, study drug may be interrupted and the patient 
rechallenged with study drug after LFTs have returned to baseline levels.  
• If repeat LFT assessment confirms ALT and/or AST >5 × ULN, patient should be 
withdrawn from IMP treatment, but will be asked to continue to be followed for 
safety using the protocol-specified visit schedule (see Appendix 1). 
• If repeat LFT assessment confirms ALT and/or AST >3 × ULN in addition to any of 
the following, the patient should be given no further IMP treatment, but will be asked 
to continue to be followed for safety using the protocol-specified visit schedule (see 
Appendix 1): 
− TB >2 × ULN 
Note:  In the case of patients with Gilbert’s disease, total bilirubin (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 
10.1.4.3.2. Monitoring and Management of Elevated Serum Creatinine 
If at any time after randomization, a patient experiences a decrease in estimated glomerular 
filtration rate (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) 
10.1.4.3.3. Monitoring and Management of Elevated Creatine Kinase 
If at any time after enrollment 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 


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− 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). 
10.1.4.4. 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.  


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10.1.4.4.1. Lipid Measurements 
Investigators, site staff, patients, and the study team will be masked to study lipid levels as well 
as ApoB and hs-CRP until the Week 12 study visit, after which time lipid values will be made 
available and concomitant medications may be adjusted as necessary.  
• 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.  Uptitration of simvastatin to an average daily dose that is greater than or 
equal to 40 mg is not permitted. 
10.1.4.5. Total Blood Volume of Clinical Laboratory 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, and efficacy.  Total whole blood volume 
collected over the study duration is not to exceed approximately 250 mL for each patient. 


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11. 
ADVERSE AND SERIOUS ADVERSE EVENTS 
11.1. 
Adverse Events 
11.1.1. 
Definition of Adverse Events 
An AE is defined as any untoward medical occurrence in a clinical investigation patient 
administered a pharmaceutical product, including control, and which does not necessarily have a 
causal relationship with treatment.  The investigator is responsible for ensuring that any adverse 
events observed by the investigator or reported by the patient are recorded in the patient’s 
medical record.  
An AE can be: 
• Any unfavorable and unintended sign/symptom, including an abnormal laboratory 
finding, or disease temporally associated with the use of a medicinal product, whether 
or not considered related to the medicinal product 
• Any new disease or exacerbation of an existing disease 
• Laboratory abnormality or diagnostic test abnormalities (eg, electrocardiogram 
[ECG] or X-ray) should be reported as an AE if one of the following occurs   
− Treatment required due to the abnormality 
− Discontinuation of IMP 
− Per Investigator judgement 
11.1.2. 
Adverse Drug Reaction 
All noxious and unintended responses to a medicinal product related to any dose should be 
considered an adverse drug reaction (ADR). “Responses” to a medicinal product means that a 
causal relationship between the medicinal product and an AE is at least a reasonable possibility 
(ie, the relationship cannot be ruled out). 
An unexpected ADR is defined as an adverse reaction, the nature or severity of which is not 
consistent with the applicable product information (eg, IB for an unapproved investigational 
product or package insert/summary of product characteristics for an approved product). 
11.1.3. 
Reporting for Adverse Events 
All AEs occurring during the course of the study (starting from signing informed consent 
through 30 days after last dose of bempedoic acid) will be collected on the AE eCRF.  Patients 
should be instructed to report any AE that they experience to the investigator.  Investigators 
should make an assessment for AEs at each visit and record the event on the appropriate AE 
eCRF.  
Wherever possible, a specific disease or syndrome rather than individual associated signs and 
symptoms should be identified by the investigator and recorded on the eCRF.  A cluster of signs 
and symptoms that results from a single cause should be reported as a single AE (eg, fever, 


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elevated white blood cells [WBC], cough, abnormal chest X-ray, etc, can all be reported as 
“pneumonia” if that is the final diagnosis).  However, if an observed or reported sign or symptom 
is not considered a component of a specific disease or syndrome by the investigator, it should be 
recorded as a separate AE on the eCRF.  Additionally, the condition that led to a medical or 
surgical procedure should be recorded as the AE, not the procedure itself.  
Any medical condition already present at screening or baseline should not be reported as an AE 
unless the medical condition or signs or symptoms present at baseline worsens in severity or 
seriousness at any time during the study.  In this case, it should be reported as an AE. 
Clinically significant abnormal laboratory or other examination findings that are detected during 
the study or are present at baseline and significantly worsen during the study should be reported 
as AEs.  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 IMP.  
For each AE, the following information will be recorded: 
• Description of the event (eg, headache) 
• Date of onset 
• Date of resolution (or that the event is continuing) 
• Action taken as a result of the event 
• Seriousness of the event 
• Severity of the event 
• Outcome of the event 
• Investigator’s assessment of relationship to IMP. 
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 IMP administration should be determined by the investigator or study 
physician after thorough consideration of all facts that are available. 
11.1.4. 
Severity 
It is the investigator’s responsibility to assess the intensity (severity) of an AE.  
The severity of the AE will be characterized as mild, moderate, or severe according to the 
following definitions: 
• Mild:  Events are usually transient and do not interfere with the patient’s daily 
activities 
• Moderate:  Events introduce a low level of inconvenience or concern to the patient 
and may interfere with daily activities  


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• 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. 
11.1.5. 
Relationship 
It is the investigator’s responsibility to assess the relationship between the IMP and the AE.  The 
degree of “relatedness” of the AE to the IMP may be described using the following scale: 
• Not Related:  No temporal association and other etiologies are likely the cause  
• Unlikely:  While cannot be definitively ruled as not related to IMP, a causal 
association is remote, and other etiologies are more likely to be the cause.  For 
reporting and summarization, events assessed as Unlikely to be related to IMP will be 
considered as Not Related to IMP.  
• Possible:  Temporal association, but other etiologies are likely the cause.  However, 
involvement of the IMP cannot be excluded. 
• Probable:  Temporal association, other etiologies are possible but unlikely.  The event 
may respond if the IMP is discontinued. 
• Definite:  Established temporal association with administration of the IMP with no 
other more probable cause.  Typically, the event should resolve when the IMP is 
discontinued and recur on rechallenge. 
11.1.6. 
Monitoring and Follow-up of Adverse Events 
Patients having AEs will be monitored with relevant clinical assessments and laboratory tests, as 
determined by the investigator.  All follow-up results are to be reported to the Sponsor personnel 
or the authorized Medical Monitor.  Any actions taken and follow-up results must be recorded 
either on the appropriate page of the eCRF or in appropriate follow-up written correspondence, 
as well as in the patient’s source documentation.  Follow-up laboratory results should be filed 
with the patient’s source documentation. 
For all AEs that require the patient to be discontinued from the study, relevant clinical 
assessments and laboratory tests must be repeated at appropriate intervals until final resolution or 
stabilization of the event(s). 
Patients with AEs related to IMP that are ongoing at study discontinuation or completion must be 
followed until resolution or for 30 days after study completion, whichever comes first, with the 
exception of patients reporting SAEs (see Section 11.2.2). 
11.1.7. 
Treatment-Emergent Adverse Events 
TEAE are defined as AEs that begin or worsen after the first dose of study drug administration as 
defined in the SAP. 


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11.2. 
Serious Adverse Events 
11.2.1. 
Definition of Serious Adverse Event  
An SAE is defined as any AE occurring at any dose that results in any of the following 
outcomes:  
• Results in death 
• Is life-threatening 
• Requires 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:  An Emergency Room visit without hospital admission does not meet inpatient 
hospitalization criteria, nor does hospitalization for an elective or outpatient procedure scheduled 
or planned before signing of informed consent.  However, unexpected complications and/or 
prolongation of hospitalization that occur during elective or outpatient surgery should be 
recorded as AEs and assessed for seriousness.  Admission to the hospital for social or situational 
reasons (eg, no place to stay, live too far away to come for hospital visits) will not be considered 
inpatient hospitalizations.  
Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical judgment, they 
may jeopardize the patient and may require medical or surgical intervention to prevent one of the 
outcomes listed in this definition.  Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room, blood dyscrasias, 
convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
11.2.2. 
Reporting Serious Adverse Events 
All SAEs occurring from the time of informed consent until 30 days following study completion/ 
discontinuation must be reported by the Principal Investigator or designee to the designated 
Safety contact within 24 hours of knowledge of the event.  All SAEs that the investigator 
considers related to IMP that occur after the 30-day follow-up period of the study period must be 
reported to the Sponsor.  
To report the SAE, the SAE form in electronic data capture (EDC) should be completed within 
24 hours of becoming aware of the event.  If you have questions, please call the designated 
Safety contact for assistance.  
Detailed instructions and contact information for the Safety designee will be provided in the SAE 
Completion Guidelines.  


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The investigator is required to submit SAE reports to their IRB/IEC in accordance with local 
requirements.  All investigators involved in studies using the same investigational product will 
receive any safety alert notifications for onward submission to their local IRB as required.  All 
reports sent to investigators will be blinded. 
All SAEs should be recorded on the eCRF and source documents.  Criteria for documenting the 
relationship to IMP and severity will be the same as those previously described. 
The investigator must continue to follow the patient until the SAE has subsided or until the 
condition becomes chronic in nature, stabilizes (in the case of persistent impairment), or the 
patient dies. 
Within 24 hours of receipt of follow-up information, the investigator must update the SAE form 
and submit any supporting documentation (eg, patient discharge summary or autopsy reports) to 
designated Safety contact.  
The Sponsor (and/or legally transferred designee) will report SAEs and suspected and 
unexpected serious adverse reactions (SUSARs) as required by global regulatory authorities, 
IECs/IRBs, and/or investigators/institutions in compliance with all reporting requirements 
according to local regulations, laws, and Good Clinical Practices (GCPs).  The investigator 
should notify their IEC/IRB of SAEs occurring at their site and other SAE reports received from 
the Sponsor, in accordance with local procedures and statutes.  
11.2.3. 
Reporting of Serious Adverse Events to Regulatory Authorities 
The Sponsor (and/or designee) is responsible for submitting expedited reports of SUSARS to the 
appropriate regulatory authorities.  All Investigators participating in ongoing clinical studies with 
the study drug will be notified by the Sponsor (or designee) of SUSARs.  SUSARS must be 
communicated as soon as possible to the appropriate IRB/IEC by the investigator, as applicable 
and/or reported in accordance with local laws and regulations.  Investigators should provide 
written documentation of IRB/IEC notification for each report to the Sponsor. 
SAEs that are anticipated to occur in this patient population will be collected and reported by the 
Investigator as described in Section 11.2.2.  However, these events will not be submitted to the 
regulatory authorities as expedited reports unless they meet SUSAR criteria.  These events that 
are considered to be exempt from expedited reporting include the following clinical endpoints: 
• CV death 
• Nonfatal MI 
• Nonfatal stroke 
• Unstable angina requiring hospitalization 
• Coronary revascularization 
• Heart failure requiring hospitalization 
• Noncoronary arterial revascularization 


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11.2.4. 
Reporting of Patient Death 
The death of any patient during the study or within 30 days after the last dose of bempedoic acid 
must be reported as an SAE. 
11.2.5. 
Reports of Pregnancy and Lactation 
Although not considered an SAE (unless an event occurs with a serious outcome), pregnancy 
will be collected by the designated Safety contact.  If a female patient should become pregnant 
during the course of the study, the Principal Investigator or designee must contact the designated 
Safety contact within 24 hours of knowledge of the pregnancy.  In addition, a pregnancy report 
form must be completed and submitted to the Safety contact. 
Patients who become pregnant must discontinue study medication immediately and will continue 
to be followed until the pregnancy is completed.  Once the outcome of the pregnancy is known, 
the Pregnancy Outcome report form must be completed and submitted to the Safety contact.  
Patients who lactate during the study may be required to discontinue study medication. 
11.3. 
Adverse Events of Special Interest 
Adverse events of special interest (AESI) are included in this protocol for reasons either 
associated with other lipid lowering therapies or where deemed important based on nonclinical 
data.  AESI for this protocol include: metabolic acidosis (clinical laboratories), hypoglycemia, 
muscular (AE and CK evaluation), hepatic, and neurocognitive/neurologic events.  
Hypoglycemia and Metabolic Acidosis:  
 
 
 
 
 
 
 
 
 
 
 
 
Muscle:  Muscle events have been associated with statins (Thompson 2003) and other lipid-
lowering therapies and are mentioned in the product information for these therapies.  Muscle 
symptoms through AE review, CK elevations, and symptoms of potential myopathy will be 
closely monitored.  
Hepatic:  Hepatic function will be monitored throughout with the clinical safety labs.  More 
detailed investigation will occur if the safety clinical laboratory results are >3 × ULN. 
Neurocognitive Events:  Theoretically, it is possible that lipid-lowering agents that disrupt 
cholesterol homeostasis in the brain could impact neurological function, and there have been 
reports of cognitive impairment (eg, memory loss) associated with the use of statin drugs 


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(FDA 2012).  Summarization of events will occur using prespecified Medical Dictionary for 
Regulatory Activities (MedDRA) terms outlined in the statistical analysis plan (SAP). 
11.4. 
Data Monitoring Committee 
An independent DMC will monitor unblinded accumulating patient safety and efficacy data until 
the last patient has completed study treatment.  In addition, data on SAEs and deaths, including 
clinical endpoints, will be monitored by the DMC during this period.  At each DMC review, 
relevant unblinded safety and efficacy information from ongoing studies of bempedoic acid will 
be provided to the DMC by an independent unblinded statistician and programmer.  Additional 
details will be provided in a DMC Charter. 
11.5. 
Clinical Event Committee (CEC) 
A blinded independent expert CEC will adjudicate clinical endpoints across the program 
including all MACE and non-MACE endpoints defined as:  CV death (MACE), non-CV death 
(non-MACE), nonfatal MI (MACE), nonfatal stroke (MACE), hospitalization for unstable 
angina (MACE), coronary revascularization (MACE), non-coronary arterial revascularization 
(non-MACE), and hospitalization for heart failure (non-MACE) using standardized definitions.  
Any clinical endpoints that meet SAE criteria will be reported as SAEs.  Additional details 
regarding clinical endpoints and clinical endpoint definitions are outlined below and will be 
included in the CEC charter.  The charter will also outline the committee’s composition, meeting 
timelines, and members’ roles and responsibilities.  Clinical endpoints from this study and other 
studies within the bempedoic acid Phase 3 development program will be aggregated to allow for 
a safety assessment across the entire development program. 
11.6. 
Assessment of Lipid Endpoints 
11.6.1. 
Lipid Parameters 
After enrollment, patients will return to clinic at Weeks 12, 52, and 78.  Clinical laboratory 
samples will be collected and analyzed for calculated LDL-C and lipid and cardiometabolic 
biomarkers including non-HDL-C, HDL-C, TC, ApoB, and TG at baseline and all clinic visits 
for evaluation of bempedoic acid effects on lipids and cardiometabolic parameters.  
11.6.2. 
Clinical Laboratory Tests (Lipids) 
Clinical laboratory samples will be collected at all clinic visits.  All efforts should be made to 
collect these samples within the visit window. 
Patients are encouraged to be in a seated position during the blood collection.  Clinical laboratory 
parameters and tests will include those listed in Table 4.  Collection schedule and instructions are 
provided in the Clinical Laboratory Manual.  A description of the sample collection, storage, and 
shipping as well as monitoring and management of abnormal laboratories are described in 
Section 10.1.4. 
When vital signs and laboratory samples are to be collected at the same time point, vital sign 
measurements will precede laboratory sample collection.  


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


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12. 
STATISTICS 
12.1. 
General Considerations 
Statistical analyses in this open label, multicenter single arm study will be descriptive in nature.  
No statistical inference is planned.  Patient disposition, demographics and baseline 
characteristics will be summarized.  Summary statistics for continuous variables will include the 
number of patients, mean, median, standard deviation or standard error, first and third quartiles 
minimum, and maximum.  For categorical variables, the frequency and percentage will be given. 
Ninety-five percent (95%) confidence intervals (CIs) will be calculated for select continuous and 
categorical endpoint estimates. All patients will be summarized together as well as by their prior 
treatment group in the parent study. 
12.2. 
Determination of Sample Size 
The number of patients entering this study will depend on the number of patients completing 
Study 1002-040 and their willingness to enroll.  
 
 
  
12.3. 
Analysis Populations  
The Full Analysis Set (FAS), used for all of the efficacy summaries and analyses, is defined as 
all enrolled patients.  The FAS is also known as the intention-to-treat (ITT) set of patients.   
The Safety Population (SP), used for all of the safety summaries, is defined as all enrolled 
patients who received at least 1 dose of study medication.   
12.4. 
Primary Endpoint 
All safety endpoints will be summarized using the SP. 
The MedDRA will be used to code all AEs to a system organ class (SOC) and a preferred term.   
The patient incidence of all TEAE, SAEs, related AEs, AEs leading to withdrawal of IMP, fatal 
AEs, and AESI will be tabulated by system organ class and preferred term in descending order of 
frequency.  If appropriate, exposure-adjusted patient incidence rate will also be provided. 
Adverse events occurred in the parent study and continued into the OLE study without change in 
severity will be captured in the parent study only.  
12.5. 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints will be summarized descriptively using FAS.  The change or 
percent change in lipid parameters will be calculated at each scheduled visit from the baseline of 
the parent study.  No imputation is planned for missing data. Ninety-five percent (95%) CI will 
be provided for the estimates at each scheduled visit during the treatment period.. 


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12.6. 
Other Safety Endpoints 
Laboratory Results 
Actual value or change from baseline (where appropriate) in clinical safety laboratories, 
including hematology, blood chemistry, HbA1C, glucose, and urinalysis will be summarized at 
each scheduled visit.  
Shift tables for selected safety laboratory parameters will be provided.  
Physical Measurements 
Height and weight will be summarized at each scheduled visit. 
Vital Signs 
Hear rate, SBP and DBP will be summarized at each scheduled visit. 
Hepatic Safety 
Actual value and change from baseline in liver-associated enzymes and TB will be summarized 
at each visit.  In addition, the number and percent of patients with normal vs. abnormal values for 
ALT, AST, and TB will be summarized by their baseline and postbaseline status.  Hy’s law 
criteria (>3 × ULN for either ALT or AST, with accompanying TB >2 × ULN or patient’s 
baseline) will also be applied to the data; any potential Hy’s law cases will be listed separately.  
In the case of patients with Gilbert’s disease, TB will be fractionated and the determination of 
2 × ULN based upon direct (conjugated) bilirubin.  For patients with Gilbert’s Disease 2 × the 
conjugated bilirubin will be used as the criterion. 
Musculoskeletal Safety 
Adverse events of muscle-related symptoms will be summarized.  Creatine kinase levels will be 
summarized by the value and change from baseline in the value, by visit.  In addition, the 
number and percent of patients with normal vs. abnormal CK values will be summarized by their 
baseline and post-baseline status.  
Diabetes and Hyperglycemia 
Cases of new onset of diabetes will be recorded as AEs and will be summarized using the 
appropriate SOC.  These events will be summarized by severity and relationship to study drug.  
Glucose and HbA1C will be monitored at baseline and at Weeks 12, 52 and 78, and be 
summarized by history of diabetes. 
Renal Safety 
Baseline eGFR will be summarized for actual value and for baseline eGFR categories.  Shift 
tables of eGFR category from baseline over the study, will be provided.  Shift tables of urine 
protein (negative/positive) from baseline over the study, will be provided.  Values of CK will be 
summarized by baseline eGFR category.   
Neurocognitive Events 
Neurocognitive events will be identified and evaluated by routine safety monitoring of PE 
findings and AEs.  Summarization of neurocognitive events will occur using prespecified 
MedDRA terms and will be performed by SOC and PT, severity, and relationship to study drug. 


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Clinical Endpoints 
Clinical endpoints using standardized definitions will be adjudicated by an independent blinded 
expert CEC for all ongoing Phase 3 studies in the bempedoic acid program.  Investigator-
reported clinical endpoints and adjudicated clinical endpoints will be summarized by event type.  
Additional details regarding the clinical endpoints and their definitions will be included in CEC 
Charter.   


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13. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
13.1. 
Study Monitoring 
The Sponsor (or its authorized representative) has the obligation to follow this study closely to 
ensure that the study is conducted in accordance with the protocol, International Conference on 
Harmonisation (ICH) and 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.  
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. 


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In the event the Investigator is contacted by regulatory authorities who wish to conduct an 
inspection of the clinical site, the Investigator will promptly notify the Sponsor of all such 
requests and will promptly forward a copy of all such inspection reports. 


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14. 
QUALITY CONTROL AND QUALITY ASSURANCE 
To ensure compliance with GCP and all applicable regulatory requirements, the Sponsor / 
designee may conduct a quality assurance audit.  Please see Section 13.2 for more details 
regarding the audit process. 


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15. 
ETHICS 
15.1. 
Institutional Review Board/Independent Ethics Committee Approval 
Before initiation of the study, the Investigator must obtain approval or favorable opinion of the 
research protocol, ICD, and any material related to patient recruitment from an IRB or IEC.  For 
locations participating within the US, the IRB must comply with the provisions specified in 
21 Code of Federal Regulations (CFR) Part 56, ICH and GCP guidelines, and applicable 
pertinent state and federal requirements.  For locations participating outside of the US, the IRB 
or IEC must comply with the applicable requirements of each participating location, including 
ICH and GCP guidelines, except where a waiver is applicable. 
IRBs and IECs must be constituted according to the applicable laws.  It is the responsibility of 
each clinical site to submit the protocol, IB, patient informed consent, patient recruitment 
materials (if applicable), and other documentation as required by the IRB or IEC for review and 
approval.  A copy of the written approval must be provided to the Sponsor.  
The documentation should clearly mention the approval/favorable opinion of the protocol, the 
patient informed consent form, and patient recruitment materials (if applicable), including 
respective version dates.  The written approval and a list of the voting members, their titles or 
occupations, and their institutional affiliations must be obtained from the IRBs or IECs and 
provided to the Sponsor prior to the release of clinical study supplies to the clinical site and 
commencement of the study.  If any member of the IRB or IEC has direct participation in this 
study, written notification regarding his or her abstinence from voting must also be obtained. 
Clinical sites must adhere to all requirements stipulated by their respective IRB or IEC.  This 
includes notification to the IRB or IEC regarding: protocol amendments, updates to the ICD, 
recruitment materials intended for viewing by patients, aggregate safety reports required by 
regulatory competent authorities, serious and unexpected AEs, reports and updates regarding the 
ongoing review of the study at intervals specified by the respective IRB or IEC, and submission 
of final study reports and summaries to the IRB or IEC. 
It is the responsibility of each clinical site to submit information to the appropriate IRB or EC for 
annual review and annual re-approval. 
The Investigator must promptly inform their IRB or IEC of all SAEs or other safety information 
reported from the patient or the Sponsor. 
15.2. 
Ethical Conduct of the Study 
The investigator agrees, when signing the protocol, to conduct the study in accordance with 
ethical principles that have their origin in the current revision of the Declaration of Helsinki and 
are consistent with ICH/GCP, applicable regulatory requirements, and policies and procedures as 
outlined by the ethical requirements for IRB or IEC review and ICDs. 
The Investigator agrees to allow monitoring and auditing of all essential clinical study 
documents by the Sponsor or its authorized representatives and inspection by the FDA, EMA, or 
other appropriate regulatory authorities.  Monitoring and auditing visits by the Sponsor or 


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authorized designee will be scheduled with the appropriate staff at mutually agreeable times 
periodically throughout the study. 
The Investigator will assure proper implementation and conduct of the study, including those 
study-related duties delegated to other appropriately qualified individuals.  The Investigator will 
assure that study staff cooperates with monitoring and audits, and will demonstrate due diligence 
in recruiting and screening study patients.  The Investigator must sign and return to the Sponsor 
the “Investigator’s Signature” page (see Appendix 3) and provide a copy of current curriculum 
vitae.  For this study and all studies conducted under an IND, the Investigator must sign and 
return a completed Form FDA 1572 “Statement of Investigator” to the Sponsor (or designee).  
For European Union (EU) investigators, equivalent information contained within the FDA 1572 
form may be requested unless a waiver has been requested and received by the Sponsor from the 
FDA. 
15.3. 
Written Informed Consent 
The Principal Investigator(s) at each center will ensure that the patient is given full and adequate 
oral and written information about the nature, purpose, possible risk and benefit of the study.  
Patients must also be notified that they are free to discontinue from the study at any time.  The 
patient should be given the opportunity to ask questions and allowed time to consider the 
information provided. 
The patient’s signed and dated informed consent must be obtained before conducting any study 
procedures. 
A separate informed consent will be obtained for collecting the genetic blood sample. 
The Principal Investigator(s) must maintain the original, signed ICD.  A copy of the signed ICD 
must be given to the patient. 
15.4. 
Patient Confidentiality 
The names and identities of all research patients will be kept in strict confidence and will not 
appear on eCRFs or other records provided to or retained by the Sponsor (or the Sponsor’s 
authorized representative).  If a patient’s name appears on any document, it must be redacted and 
replaced with the patient identifier before a copy of the document is supplied to the Sponsor or 
Sponsor’s authorized representative.  The ICD must include appropriate statements explaining 
that patient data will be confidential and what actions will be taken to ensure patient 
confidentiality. 
Any other confidentiality requirements specified by the site, IRB or IEC, or national or local 
regulations will be adhered to and detailed appropriately in the ICD. 


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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.  
Study records are comprised of source documents, eCRFs, and all other administrative 
documents (eg, IRB or IEC correspondence, clinical study materials and supplies shipment 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 60 of 100 
manifests, monitoring logs, and correspondence).  A study-specific binder will be provided with 
instructions for the maintenance of study records. 
Source documentation is defined as any handwritten or computer-generated document that 
contains medical information or test results that have been collected for or in support of the 
protocol specifications (eg, laboratory reports, clinic notes, study drug disposition log, pharmacy 
records, patient sign-in sheets, patient completed questionnaires, telephone logs, X-rays, and 
ECGs).  All draft, preliminary, and pre/final iterations of a final report are also considered to be 
source documents (eg, faxed and hard copy of laboratory reports, faxed and hard copy of initial 
results, and final report).  
The Investigator agrees to allow direct access to all essential clinical study documents for the 
purpose of monitoring and/or auditing by the Sponsor or its authorized representatives and 
inspection by the appropriate regulatory authorities. 
Data reflecting the patient’s participation with the study drug under investigation are to be 
reported to the Sponsor.  The data are to be recorded on the eCRFs and/or other media provided 
or approved by the Sponsor.  
A completed eCRF must be submitted for each patient who receives study drug, regardless of 
duration.  All supportive documentation submitted with the eCRF, such as laboratory or hospital 
records, should be clearly identified with the study and patient number.  Any personal 
information, including patient name, should be removed or rendered illegible to preserve 
individual confidentiality.  The eCRF should not be used as a source document unless otherwise 
specified by the Sponsor.  
Neither the Sponsor nor a service provider contracted to analyze data and complete the study 
report is permitted to interpret a blank answer; therefore, all fields should be completed.  All 
requested information must be entered on the eCRFs. If an item is not available or is not 
applicable, this fact should be indicated as not available (N/A) or not done (N/D); do not leave a 
field blank.  
Each set of completed eCRFs must be signed and dated by the Investigator acknowledging 
review and that the data are accurate and complete.  The completed database is to be returned to 
the Sponsor as soon as practical after completion by the mechanism prescribed for the protocol. 
It is essential that all dates appearing on the Sponsor’s patient data collection forms for 
laboratory tests, cultures, etc, be the dates on which the specimens were obtained or the 
procedures performed.  The eCRFs will be electronically signed by the Investigator and dated as 
verification of the accuracy of the recorded data.  All data collection forms should be completed 
within 48 hours following the evaluation. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 61 of 100 
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 
• Guidance for Industry – E6 Good Clinical Practice: Consolidated Guidance: 
http://www.fda.gov/cder/guidance/959fnl.pdf 


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Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 62 of 100 
17.2. 
Amendments 
Changes to the research covered by this protocol must be implemented by formal protocol 
amendment.  All amendments to the protocol must be initiated by the Sponsor and signed and 
dated by the Investigator.  Protocol amendments must not be implemented without prior IRB or 
IEC approval.  Documentation of amendment approval by the Investigator and IRB or IEC must 
be provided to the Sponsor or its authorized representative.  When the change(s) involve only 
logistic or administrative aspects of the study, the IRB or IEC only needs to be notified.  
During the course of the study, in situations where a departure from the protocol is unavoidable, 
the Investigator will contact the Medical Monitor.  Except in emergency situations, this contact 
should be made before implementing any departure from the protocol.  In all cases, contact with 
the Medical Monitor must be made as soon as possible to discuss the situation and agree on an 
appropriate course of action.  The data recorded on the eCRF and source documents will reflect 
any departure from the protocol and the source documents will describe the departure and the 
circumstances requiring it. 
17.3. 
Financial Disclosure 
Prior to the start of the study, Investigators will release sufficient and accurate financial 
information that permits the Sponsor to demonstrate that an Investigator and all study relevant 
assigned personnel have no personal or professional financial incentive regarding the future 
approval or disapproval of the study drug such that his or her research might be biased by such 
incentive. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 63 of 100 
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. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 64 of 100 
19. 
LIST OF REFERENCES 
Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, et al. Cholesterol Treatment 
Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL 
cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet. 
2010;376:1670-81. 
Cannon CP, Blazing MA, Guiglian RP, McCagg A, White JA, Theroux P, et al, for the 
IMPROVE-IT Investigators. Ezetimibe added to statin therapy after acute coronary. N Engl J 
Med. 2015;372(25):2387-97. 
Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, et al, for the 
Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial 
Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute 
coronary syndromes. N Engl J Med. 2004;350:1495-504. 
Goldberg AC, Hopkins PN, Toth PP, Ballantyne CM, Rader DJ, Robinson JG, et al. Familial 
hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: 
clinical guidance from the National Lipid Association Expert Panel on Familial 
Hypercholesterolemia. J Clin Lipidol. 2011;5 (3 Suppl):S1-S8. 
https://rarediseases.org/rare-diseases/familial-hypercholesterolemia/ accessed August 2015. 
http://thefhfoundation.org/about-fh/what-is-fh/ accessed August 2015. 
Jacobson TA for the NLA Task Force on Statin Safety - 2014 update. J Clin Lipidol. 
2014;8:S1-4.  
Kathiresan S, Melander O, Anevski D, Guiducci C, Burtt NP, Roos C, et al. Polymorphisms 
associated with cholesterol and risk of cardiovascular events. N Engl J Med. 
2008:358;12:1240-9. 
Mozffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al, for the writing 
group Members. Heart Disease and Stroke Statistics—2015 Update. A Report from the 
American Heart Association. Circ. 2015;131:e29-322. 
Neil A, Cooper H, Betteridge J, Capps N, McDowell I, Durrington P, et al. Reduction in all-
cause, cancer, and coronary mortality in statin-treated patients with heterozygous familial 
hypercholesterolaemia: a prospective registry study. Eur Heart J. 2008;29:2625-38. 
Nichols M, Townsend N, Scarborough P, Rayner M. Cardiovascular disease in Europe 2014: 
epidemiological update. Eur Heart J. 2014;35:2950-9. 
Pollex RL, Joy TR, Hegele RA. Emerging antidyslipidemic drugs. Expert Opin Emerg Drugs. 
2008;13(2):363-81. 
Robinson JG. Management of Familial Hypercholesterolemia: A Review of the 
recommendations from the National Lipid Association Expert Panel on Familial 
Hypercholesterolemia. J Managed Care Pharm. 2013;19(2):139-49. 


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Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
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Robinson JG, Smith B, Maheshwari N, Schrott H. Pleiotropic effects of statins: benefit beyond 
cholesterol reduction: A meta-regression analysis. J Am Coll Cardiol. 2005 Nov 
15;46(10):1855-62. Epub 2005 Oct 24. 
Sharrett AR, Ballantyne CM, Coady SA, Heiss G, Sorlie PD, Catellier D, et al. Atherosclerosis 
Risk in Communities Study Group. Coronary heart disease prediction from lipoprotein 
cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density 
subfractions. The Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 
2001;104:1108-13. 
Stamler J, Wentworth D, Neaton J. Is relationship between serum cholesterol and risk for 
premature death from coronary heart disease continuous and graded? JAMA. 1986 
Nov 28;256(20):2823-8. 
Stone NJ, Robinson J, Lichtenstein AH, Bairey Merc CN, Blum CB, Eckel RH, et al. 
2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic 
cardiovascular risk in adults: a report of the American College of Cardiology/American Heart 
Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24;129(25 Suppl 2):S1-45. 
doi: 10.1161/01.cir.0000437738.63853.7a 
World Health Organization (WHO) Fact Sheet No 317 Updated January 2015. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 66 of 100 
20. 
APPENDICES 
Appendix 1: 
Schedule of Events (Patient Visit Schedule) 
Appendix 2: 
Sponsor’s Signature 
Appendix 3: 
Investigator’s Signature 
Appendix 4: 
Summary of Changes in Amendment 1 
Appendix 5: 
Summary of Changes in Amendment 2 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 67 of 100 
APPENDIX 1. SCHEDULE OF EVENTS (PATIENT VISIT SCHEDULE) 
Month 
0 
3 
6 
9 
12 
15 
18/EOT1 
19/EOS2 
Week  
EOS 
Parent 
Wk 12 
Wk 24 
Wk 36 
Wk 52 
Wk 64 
Wk 78 
Wk 82  
Visit Window 
30 Days 
pre-M0 
±7 days 
±7 days 
±7 days 
±7 days 
±7 days 
±7 days 
+14 days 
In-clinic Visit 
X 
X 
 
 
X 
X 
X 
Phone Visit 
X 
X 
X 
 
Procedure 
Informed Consent 
X 
 
 
 
 
 
 
 
Enrollment Criteria 
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Event 
Recording 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
X 
 
 
 
X 
 
X 
 
Weight3 
X 
X 
 
 
X 
 
X 
X 
Vital Signs4 
X 
X 
 
 
X 
 
X 
X 
Urine Pregnancy Test5  
X 
 
 
 
 
 
 
 
Clinical Safety Labs6 
X 
X 
 
 
X 
 
X 
X 
Basic Fasting Lipids7 
X 
X 
 
 
X 
 
X 
X 
Coagulation8 
X 
 
 
 
 
 
 
 
ApoB and hsCRP 
X 
X 
 
 
X 
 
X 
X 
HbA1C 
X 
  
 
 
X  
 
X 
X 
IWRS Contact9 
X 
 X 
 
 
 X 
 
X 
 
Drug Dispensing 
X 
X 
 
 
X 
 
 
Drug Return/ 
Compliance 
 
X 
 
 
X 
 
X 
 
NOTE: For patients who withdraw from study drug treatment, but consent to be followed for safety assessments and 
return to clinic for these visit, the visits will occur according to the protocol schedule.  Safety assessments should 
include clinical safety and basic lipid laboratories, adverse events (AEs), physical examination (PE), and vital signs.  
For patients who withdraw from study drug treatment, but consent to be followed for safety assessments by phone, the 
telephone contacts will occur according the protocol schedule with information regarding current health status and to 
collect information on AEs (eg, recent procedures, hospitalizations, and if the patient has died, the cause of death).  If a 
patient does not provide consent to be followed for safety assessments per the protocol (either by returning to clinic or 
by phone), Visit Week 78/End of Treatment (EOT) will be scheduled as soon as possible and the patient will be asked 
to come back 4 weeks after last investigational medicinal product (IMP) dose for Visit Week 82/End of Study (EOS).  
No further visits will be scheduled. 


Bempedoic Acid 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
Amendment 2, 15 January 2018 
Confidential 
Page 68 of 100 
1 All procedures will be completed for all patients at either EOT or early withdrawal. 
2 All procedures will be completed for all patients 4 weeks after last IMP dose if completing the study or early 
withdrawal. 
3 Body weight will be measured in the morning while fasting, using consistent scales, after voiding, and without shoes 
and outerwear (eg, coats). 
4 Vital signs will include diastolic blood pressure (DBP), systolic blood pressure (SBP), heart rate (HR) and will be 
collected prior to any blood sample collection.  Patient will rest for 5 minutes prior to assessments 
5 Urine pregnancy test in women of childbearing potential only 
6 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits.  Please refer to laboratory 
manual for detailed schedule of tests. 
7 Basic fasting lipids include total cholesterol (TC), calculated low-density lipoprotein cholesterol (LDL-C), high-
density lipoprotein cholesterol (HDL-C), non-HDL-C,), and triglycerides (TG). 
8 Only in patients receiving anticoagulant therapy that in the investigator’s judgment require monitoring at Month 0 
and 3 to 5 days post-Month 0 
9 Interactive web response system (IWRS) contact at either an early withdrawal or an EOS visit to register study 
discontinuation visit date 


Bempedoic Acid 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
Amendment 2, 15 January 2018 
APPENDIX 2. SPONSOR'S SIGNATURE 
Study Title: 
A Multicenter Open-label Extension (OLE) Study to Assess the Long-
term Safety and Efficacy ofBempedoic Aci~ (ETC-1002) 180 mg 
Study Number: 
1002-050 
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:
Esperion Therapeutics, Inc. 
Confidential 
Page 69 of 100 
Date: 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 70 of 100 
APPENDIX 3. INVESTIGATOR’S SIGNATURE 
Study Title: 
A Multicenter Open-label Extension (OLE) Study to Assess the Long-
term Safety and Efficacy of Bempedoic Acid (ETC-1002) 180 mg 
Study Number: 
1002-050 
I have read the protocol described above.  I agree to comply with all applicable regulations and 
to conduct the study as described in the protocol.  
Signed:  
Date:  
 
Name and Credentials:  
Title:  
Affiliation:  
Address:  
Phone Number:  
 
 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 71 of 100 
APPENDIX 4. SUMMARY OF CHANGES IN AMENDMENT 1 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 72 of 100 
SUMMARY OF CHANGES 
CLINICAL STUDY PROTOCOL  
Study Number: 
1002-050 
Study Title: 
A Multicenter Open-label Extension (OLE) Study to 
Assess the Long-term Safety and Efficacy of Bempedoic 
Acid (ETC-1002) 180 mg 
Protocol Version Incorporating 
Current Summary of Changes: 
Amendment 1:  09 May 2017 
Preceding Protocol Version: 
Original Protocol:  01 November 2016 
Investigational Product Name: 
ETC-1002 
Conventions used in this Summary of Changes Document 
1. The text immediately preceding and following a change to the protocol is included for 
each change in order to provide the reviewer with a reference point to identify the change 
in the protocol. 
2. All locations (ie, section numbers and/or header text) refer to the current protocol 
version, which incorporates the items specified in this Summary of Changes document. 
3. The original text is from the preceding protocol version. 
4. In the “New Text”, all substantive text added to the protocol is italicized. 
5. In the “New Text”, text deleted from the protocol is indicated in strikethrough font. 
Summary and Justification of Changes 
The protocol was amended for the following: 
• Added a line for Amendment 1 version and date to reflect amendment version details. 
• Updated the design schematic to represent patients could receive ETC-1002 or 
matching placebo in the parent study. 
• Revised inclusion criteria to specify the requirements pertaining to the parent study 
• Updated exclusion criteria with regards to contraception to be consistent with 
European Medicines Agency (EMA) requirements 
• Based upon the recommendation of the Data Monitoring Committee and Esperion’s 
decision, doses of simvastatin 40 mg/day or greater have been added as a prohibited 
medication.   
• The instructions around maintaining study blind have been expanded. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 73 of 100 
• Procedures have been clarified for patients enrolling into the study after the last visit 
for the parent study. 
• The monitoring and management of CK values for asymptomatic patients was 
modified to be consistent with other protocols across the program.   
• The Schedule of Events was updated to reflect changes or correct errors. 
• Typographical errors and formatting were corrected or revised based on these 
changes or to improve clarity and consistency.   


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Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 75 of 100 
New Text: 
1. Successfully completed the parent study (1002-040) and meet both of the following 
criteria:ETC-1002-040 (at least 80% investigational medicinal product [IMP]-compliant 
and able to tolerate IMP at the end of parent study) 
• The patient was compliant with the parent study requirements including study 
visits, procedures, and investigational medicinal product (IMP) in the opinion of 
the principal investigator. 
• The patient was able to tolerate IMP through the end of the parent study. 
CHANGE 4 
REVISION OF EXCLUSION CRITERIA 
Location: 
Section 2, Synopsis: Key exclusion criteria; Section 6.8, Patient Exclusion Criteria 
Original Text: 
1. Female patient is not willing to use at least 1 highly effective method of birth control 
during treatment and for an additional 30 days after the end of treatment unless patient is 
sterilized or postmenopausal; 
• Menopause is 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);  
• 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: 
1. Female patient is not willing to use at least 1 highly effectiveacceptable method of birth 
control during treatment and for an additional 30 days after the end of treatment unless 
patient is sterilized or postmenopausal; 
• Menopause is 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);  
• 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 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 76 of 100 
where it is the preferred and usual lifestyle of the patient (not including periodic 
abstinence such as calendar, ovulation, symptothermal, postovulation methods, or 
withdrawal). 
Original Text: 
5. Renally impaired patients receiving an average daily dose of simvastatin 40 mg with 
estimated glomerular filtration rate (eGFR) below <45 mL/min/1.73 m2. 
New Text: 
5. Renally impaired patients receiving an average daily dose of simvastatin 40 mg with 
estimated glomerular filtration rate (eGFR) below <45 mL/min/1.73 m2. 
CHANGE 5 
REVISION TO PROHIBITED MEDICATIONS 
Location:  
Section 7.2.1, Prohibited Medications and Supplements 
Original Text: 
All medications deemed medically necessary may be prescribed during this study, with the 
following exceptions: 
• Mipomersen  
• Lomitapide or apheresis therapy  
• Red yeast rice containing products 
• Uptitration of simvastatin to an average daily dose that is greater than 40 mg 
• Gemfibrozil  
New Text: 
All medications deemed medically necessary may be prescribed during this study, with the 
following exceptions: 
• Mipomersen  
• Lomitapide or apheresis therapy  
• Red yeast rice containing products 
• Uptitration of simvastatin to an average dailya dose that is greater than or equal to 
40 mg/day 
• Gemfibrozil  
• Ezetimibe/simvastatin (Zocor®) where simvastatin doses are ≥40 mg/day (Vytorin® 
10/40 and 10/80 and Inegy® 10 mg/40 mg and 10 mg/80 mg are prohibited)  


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 77 of 100 
CHANGE 6 
REVISION TO BLINDING INSTRUCTIONS 
Location:  
Section 7.3, Blinding 
Original Text: 
Laboratory results for lipid panel and hs-CRP will be masked to investigators, patients, and the 
study team until the Week 12 visit is completed.  All site staff involved with this trial should 
refrain from obtaining lipid panels between date of last ETC-1002-040 dose at end of parent 
study Week 52 (Visit T7) and Week 12 in this OLE trial. 
New Text: 
Laboratory results for lipid panel and hs-CRP will be masked to investigators, patients, and the 
study team until the Week 12 visit is completed.  All site staff involved with this trial should 
refrain from obtaining lipid panels between date of last ETC-1002-040 dose at end of parent 
study Week 52 (Visit T7) and Week 12 in this OLE trial. 
While this is an open-label study where all patients will receive active treatment with 
bempedoic acid (180 mg by mouth [PO] once daily [QD]), blinding of the treatment that 
patients received during the parent study must be maintained for all patients unless, in the 
opinion of the Investigator, the safety of the patient may be at risk.  Only under the rarest of 
circumstances should the Investigator consider breaking the parent study blind and only when 
medical/supportive care cannot be provided without determining if the patient was previously 
receiving active drug treatment.  In the event that the parent study blind needs to be broken 
prior to completion of the parent study, the Investigator should contact the appropriate 
Medical Monitor by telephone.  If the parent study 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 interactive web response system (IWRS) utilized in the parent study.  In all cases of 
breaking the parent study 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. 
CHANGE 7 
REVISION TO PROCEDURES AT ENROLLMENT, EOS/DAY 1 OLE 
Location: 
Section 9.2.1, Enrollment (EOS/Day 1 OLE) 
Original Text: 
Day 1 for this study should occur on the same day as the end of study visit for the parent study 
(1002-040).  All efforts should be made to avoid delays in rolling over.  The study procedures 
below, from the parent study EOS visit, will be used to qualify for this study.  If Day 1 of the 
OLE study occurs >30 days from the end of study visit from the parent study, all procedures will 
need to be repeated including taking a new medical history. 
• Review of inclusion/exclusion criteria  


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 78 of 100 
• Concomitant medication review 
• Assess AE/SAEs 
• Physical exam 
• Weight (kg) 
• Vital signs  
• Clinical laboratory evaluations:  
− Hematology, blood chemistry, coagulation (only in patients receiving 
anticoagulant therapy), and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− ApoB 
− Hs-CRP 
− 
Glycosylated hemoglobin, Type A1C (HbA1C) 
• Urine pregnancy test  
• Contact IWRS to register the patient 
• Dispense study drug  
New Text: 
Day 1 for this study should occur on the same day as the end of study visit for the parent study 
(1002-040).  All efforts should be made to avoid delays in rolling over.  The study procedures 
below, from the parent study EOS visit, will be used to qualify for this study.  If Day 1 of the 
OLE study occurs >30 days from the end of study visit from the parent study, all procedures will 
need to be repeated including taking a new medical history. 
• Review of inclusion/exclusion criteria  
• Concomitant medication review 
• Assess AE/SAEs 
• Physical exam 
• Weight (kg) 
• Vital signs  
• Clinical laboratory evaluations:  
− Hematology, blood chemistry, coagulation (only in patients receiving 
anticoagulant therapy), and urinalysis 
− Basic fasting lipids (TC, calculated LDL-C, HDL-C, non-HDL-C, and TG) 
− ApoB 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 79 of 100 
− Hs-CRP 
− 
Glycosylated hemoglobin, Type A1C (HbA1C) 
• Urine pregnancy test  
• Contact IWRS to register the patient 
• Dispense study drug  
Please note the following for patients enrolling into Study 1002-050 within 30 days of 
completing the EOS visit in the parent study: 
• If the patient is not receiving anticoagulant therapy and/or is a woman who is not 
of childbearing potential, clinical laboratory samples do not need to be collected as 
the results from the parent study EOS visit will be used for this visit. 
• If the patient is receiving anticoagulant therapy, then a coagulation laboratory 
sample is required at this visit using a Study 1002-050 unscheduled laboratory kit. 
• If the patient is a woman of childbearing potential, then a urine pregnancy test is 
required at this visit. 
Please note the following for patients enrolling into Study 1002-050 greater than 30 days 
after completing the EOS visit in the parent study: 
• Clinical laboratory samples should be collected using a Study 1002-050 Day 1 kit.  
Supplies for collecting the coagulation sample are included in this kit. 
• If the patient is a woman of childbearing potential, then a urine pregnancy test is 
required at this visit. 
 
CHANGE 8 
REVISION TO MONITORING AND MANAGEMENT OF ELEVATED 
CREATINE KINASE 
Location:   
Section 10.1.4.3.3, Monitoring and Management of Elevated Creatine Kinase 
Original Text: 
If at any time after enrollment 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.  


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 80 of 100 
New Text: 
If at any time after enrollment 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 discontinuedinvestigator with input from the Sponsor may 
consider continuing study medication with continued CK assessments every 
1-2 weeks.  
CHANGE 9 
REVISION TO LIPID MEASUREMENTS 
Location:   
Section 10.1.4.4.1, Lipid Measurements 
Original Text: 
Investigators, site staff, patients, and the study team will be masked to study lipid levels as well 
as ApoB and hs-CRP until the Week 12 study visit, after which time lipid values will be made 
available and concomitant medications may be adjusted as necessary.  
• 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.  Uptitration of simvastatin to an average daily dose that is greater than 
40 mg is not permitted. 
New Text: 
Investigators, site staff, patients, and the study team will be masked to study lipid levels as well 
as ApoB and hs-CRP until the Week 12 study visit, after which time lipid values will be made 
available and concomitant medications may be adjusted as necessary.  
• 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.  Uptitration of simvastatin to an average daily dose that is greater than or 
equal to 40 mg is not permitted. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
 
 
Confidential 
Page 81 of 100 
CHANGE 10 
REVISION TO APPENDIX 1  
Location: 
Appendix 1:  Schedule of Events (Patient Visit Schedule) 
Original Text: 
Month 
0 
3 
6 
9 
12 
15 
18/EOS1 
Week  
EOS Parent 
Wk 12 
Wk 24 
Wk 36 
Wk 52 
Wk 64 
Wk 78 
Visit Window 
30 Days 
pre-M0 
±7 days 
±7 days 
±7 days 
±7 days 
±7 days 
±7 days 
In-clinic Visit 
X 
X 
 
 
X 
X 
Phone Visit 
X 
X 
X 
Procedure 
Informed Consent 
X 
 
 
 
 
 
 
Enrollment Criteria 
X 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
Adverse Event 
Recording 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
X 
 
 
 
X 
 
X 
Weight2 
X 
X 
 
 
X 
 
X 
Vital Signs3 
X 
X 
 
 
X 
 
X 
Urine Pregnancy Test  
X 
 
 
 
 
 
 
Clinical Safety Labs4 
X 
X 
 
 
X 
 
X 
Basic Fasting Lipids5 
X 
X 
 
 
X 
 
X 
Coagulation6 
X 
 
 
 
 
 
 
ApoB and hsCRP 
X 
X 
 
 
X 
 
X 
HbA1C 
X 
  
 
 
X  
 
X 
IWRS Contact7 
X 
 X 
 
 
 X 
 
X 
Drug Dispensing 
X 
X 
 
 
X 
 
Drug 
Return/Compliance 
 
X 
 
 
X 
 
X 
 
NOTE: For patients who withdraw from study drug treatment, but consent to be followed for safety assessments and 
return to clinic for these visit, the visits will occur according to the protocol schedule.  Safety assessments should 
include clinical safety and basic lipid laboratories, adverse events (AEs), physical examination (PE), vital signs, and 
electrocardiograms (ECGs).  For patients who withdraw from study drug treatment, but consent to be followed for 
safety assessments by phone, the telephone contacts will occur according the protocol schedule with information 
regarding current health status and to collect information on AEs (eg, recent procedures, hospitalizations, and if the 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
 
 
Confidential 
Page 82 of 100 
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 week 78 will be considered the End of Study 
(EOS)/Early Withdrawal from study and no further visits will be scheduled. 
1 All procedures will be completed for all patients at either EOS if completing the study or early withdrawal. 
2 Body weight will be measured in the morning while fasting, using consistent scales, after voiding, and without 
shoes and outerwear (eg, coats).   
3 Vital signs will include diastolic blood pressure (DBP), systolic blood pressure (SBP), heart rate (HR) and will be 
collected prior to any blood sample collection.  Patient will rest for 5 minutes prior to assessments 
4 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits.  Please refer to laboratory 
manual for detailed schedule of tests. 
5 Basic fasting lipids include total cholesterol (TC), calculated low-density lipoprotein cholesterol (LDL-C), high-
density lipoprotein cholesterol (HDL-C), non-HDL-C,), and triglycerides (TG). 
6 Only in patients receiving anticoagulant therapy that in the investigator’s judgment require monitoring at Month 0 
and 3 to 5 days post-Month 0 
7 Interactive web response system (IWRS) contact at either an early withdrawal or an EOS visit to register study 
discontinuation visit date 
New Text: 
Month 
0 
3 
6 
9 
12 
15 
18/EOS1 
Week  
EOS Parent 
Wk 12 
Wk 24 
Wk 36 
Wk 52 
Wk 64 
Wk 78 
Visit Window 
30 Days 
pre-M0 
±7 days 
±7 days 
±7 days 
±7 days 
±7 days 
±7 days 
In-clinic Visit 
X 
X 
 
 
X 
X 
Phone Visit 
X 
X 
X 
Procedure 
Informed Consent 
X 
 
 
 
 
 
 
Enrollment Criteria 
X 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
Adverse Event 
Recording 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
X 
 
 
 
X 
 
X 
Weight2 
X 
X 
 
 
X 
 
X 
Vital Signs3 
X 
X 
 
 
X 
 
X 
Urine Pregnancy Test4 
X 
 
 
 
 
 
 
Clinical Safety Labs45 
X 
X 
 
 
X 
 
X 
Basic Fasting Lipids56 
X 
X 
 
 
X 
 
X 
Coagulation67 
X 
 
 
 
 
 
 
ApoB and hsCRP 
X 
X 
 
 
X 
 
X 
HbA1C 
X 
  
 
 
X  
 
X 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
 
 
Confidential 
Page 83 of 100 
IWRS Contact78 
X 
 X 
 
 
 X 
 
X 
Drug Dispensing 
X 
X 
 
 
X 
 
Drug Return/ 
Compliance 
 
X 
 
 
X 
 
X 
 
NOTE: For patients who withdraw from study drug treatment, but consent to be followed for safety assessments and 
return to clinic for these visit, the visits will occur according to the protocol schedule.  Safety assessments should 
include clinical safety and basic lipid laboratories, adverse events (AEs), physical examination (PE), and vital signs, 
and electrocardiograms (ECGs).  For patients who withdraw from study drug treatment, but consent to be followed 
for safety assessments by phone, the telephone contacts will occur according the protocol schedule with information 
regarding current health status and to collect information on AEs (eg, recent procedures, hospitalizations, and if the 
patient has died, the cause of death).  If a patient does not provide consent to be followed for safety assessments per 
the protocol (either by returning to clinic or by phone), Visit week 78 will be considered the End of Study 
(EOS)/Early Withdrawal from study and no further visits will be scheduled. 
1 All procedures will be completed for all patients at either EOS if completing the study or early withdrawal. 
2 Body weight will be measured in the morning while fasting, using consistent scales, after voiding, and without 
shoes and outerwear (eg, coats).   
3 Vital signs will include diastolic blood pressure (DBP), systolic blood pressure (SBP), heart rate (HR) and will be 
collected prior to any blood sample collection.  Patient will rest for 5 minutes prior to assessments 
4 Urine pregnancy test in women of childbearing potential only 
45 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits.  Please refer to laboratory 
manual for detailed schedule of tests. 
56 Basic fasting lipids include total cholesterol (TC), calculated low-density lipoprotein cholesterol (LDL-C), high-
density lipoprotein cholesterol (HDL-C), non-HDL-C,), and triglycerides (TG). 
67 Only in patients receiving anticoagulant therapy that in the investigator’s judgment require monitoring at Month 0 
and 3 to 5 days post-Month 0 
78 Interactive web response system (IWRS) contact at either an early withdrawal or an EOS visit to register study 
discontinuation visit date 
 
CHANGE 11 
REMOVED FINAL DATE 
Location:  
Appendix 2:  Final Date, all pages within Appendix 2 and Appendix 3 
Original text: 
Final Date: 
01 November 2016 
New text: 
Final Date: 
01 November 2016 
 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 84 of 100 
CHANGE 12 
CHANGE IN SPONSOR REPRESENTATIVES PROVIDING 
PROTOCOL SIGNAGE 
Location:  
Appendix 2:  Sponsor Signatures 
Original text: 
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:  
 
Esperion Therapeutics, Inc. 
 
 
New Text: 
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:  
 
Esperion Therapeutics, Inc. 
 
 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
 
 
Confidential 
Page 85 of 100 
 
 
Study Title: 
A Multicenter Open-label Extension (OLE) Study to Assess the Long-
term Safety and Efficacy of Bempedoic Acid (ETC-1002) 180 mg 
Study Number: 
1002-050 
Final Date: 
01 November 2016 
 
This clinical study protocol was subject to critical review and has been approved by the Sponsor.  
The following personnel contributed to writing and/or approving this protocol: 
 
 
Signed:  
Date:  
 
Esperion Therapeutics, Inc. 
 
 
 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 86 of 100 
APPENDIX 5. SUMMARY OF CHANGES IN AMENDMENT 2 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 87 of 100 
SUMMARY OF CHANGES 
CLINICAL STUDY PROTOCOL  
Study Number: 
1002-050 
Study Title: 
A Multicenter Open-label Extension (OLE) Study to 
Assess the Long-term Safety and Efficacy of Bempedoic 
Acid (ETC-1002) 180 mg 
Protocol Version Incorporating 
Current Summary of Changes: 
Amendment 2:  15 Jan 2018 
Preceding Protocol Version: 
Amendment 1:  09 May 2017 
Investigational Product Name: 
ETC-1002 
Conventions used in this Summary of Changes Document 
1. The text immediately preceding and following a change to the protocol is included for 
each change in order to provide the reviewer with a reference point to identify the change 
in the protocol. 
2. All locations (ie, section numbers and/or header text) refer to the current protocol 
version, which incorporates the items specified in this Summary of Changes document. 
3. The original text is from the preceding protocol version. 
4. In the “New Text”, all substantive text added to the protocol is 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: 
• Updated contact details for Sponsor Contact and Medical Monitor 
• Added a line for Amendment 2 version and date to reflect amendment version details. 
• Revised the study design to include an assessment at Week 82, 4 weeks after patients 
have completed their last dose of bempedoic acid.  This assessment was added to 
have safety and efficacy data off study drug to help interpret any potential findings 
during the treatment period.  
• Updated the design schematic to include the 4-week follow-up period from Week 78 
to Week 82. 
• Week 78 is now called the End of Treatment (EOT) visit and Week 82 is described as 
the Off Study Drug Period/End of Study (EOS) visit.   
• The section on Background of Bempedoic Acid has been updated to reflect the 
current version of the Investigator’s Brochure. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 88 of 100 
• The section on Concomitant Medications has been revised to avoid changes in lipid-
lowering medications during the 4-week washout period to limit the introduction of 
medications that may affect endpoints of interest measured at Week 82.  
• The statistical analysis plan for renal events was updated to remove text that indicated 
muscle related events would be analyzed based on baseline eGFR.  There is no data 
or clinical justification to justify assessment of muscle related events by eGFR.      
• Text throughout the protocol was updated to reflect the addition of the 4-week 
follow-up period. 
• Typographical errors and formatting were corrected or revised based on these 
changes or to improve clarity and consistency.   


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
 
 
Confidential 
Page 89 of 100 
CHANGE 1 
REVISION OF TITLE PAGE VERSION INFORMATION 
Location: 
Title Page  
Original Text: 
Sponsor Contact: 
Medical Monitor: 
New Text: 
Sponsor Contact: 
Medical Monitor: 
 
Original Text: 
 
Version 
Date 
 
 
Original Protocol: 
01 November 2017 
 
 
Amendment 1: 
9 May 2017 
 
New Text: 
 
Version 
Date 
 
 
Original Protocol: 
01 November 2017 
 
 
Amendment 1: 
09 May 2017 
 
 
Amendment 2: 
15 January 2018 
 
 


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Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 91 of 100 
New Text: 
Duration of treatment: 
The total duration of treatment for an individual subject will be 1.5 years (18 months).  The total 
duration in the study will be 19 months. 
 
Original Text: 
This is a multicenter open-label extension (OLE) study designed to assess the long-term safety 
and efficacy of bempedoic acid 180 mg.  All patients will receive open-label bempedoic acid 
180 mg for up to 1.5 years after rolling over from Study 1002-040 (parent study).  Investigators, 
site staff, patients, and the study team will be masked to study lipid levels until the Week 12 
study visit, after which time lipid values will be made available to sites.  The study will be 
conducted at approximately 125 clinical sites in the US, Canada, Germany, Netherlands, Poland, 
and United Kingdom.  It’s anticipated that approximately 1300 patients will elect to enroll into 
this study.  Patients will have visits every 3 months.  Patients will be required to visit the site at 
baseline (end of study [EOS] parent), Week 12, Week 52, and Week 78.  Phone visits will occur 
at Weeks 24, 36, and 64. 
New Text: 
This is a multicenter open-label extension (OLE) study designed to assess the long-term safety 
and efficacy of bempedoic acid 180 mg.  All patients will receive open-label bempedoic acid 
180 mg for up to 1.5 years after rolling over from Study 1002-040 (parent study) followed by a 
period off study drug for 4 weeks.  Investigators, site staff, patients, and the study team will be 
masked to study lipid levels until the Week 12 study visit, after which time lipid values will be 
made available to sites.  The study will be conducted at approximately 125 clinical sites in the 
US, Canada, Germany, Netherlands, Poland, and United Kingdom.  It’s anticipated that 
approximately 1300 patients will elect to enroll into this study.  Patients will have visits every 
3 months.  Patients will be required to visit the site at baseline (end of study [EOS] parent), 
Week 12, Week 52, Week 78, and Week 7882.  Phone visits will occur at Weeks 24, 36, and 64. 
Original Text: 
Patients will be enrolled after successfully completing study ETC-1002-040.  The total study 
duration for an individual subject is 1.5 years. 
New Text: 
Patients will be enrolled after successfully completing study ETC-1002-040.  The total study 
duration for an individual subject is 1.5 years 82 weeks (1 year and 7 months). 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
 
 
Confidential 
Page 92 of 100 
Original Text: 
The study will end when the last patient completes their Week 78 visit.  The estimated overall 
duration of the study (first patient first visit [FPFV] to last patient last visit [LPLV]) is 
approximately 2.5 years. 
New Text: 
The study will end when the last patient completes their Week 7882 visit.  The estimated overall 
duration of the study (first patient first visit [FPFV] to last patient last visit [LPLV]) is 
approximately 2.5 years. 
 
Original Text: 
9.2.6 Treatment Month 18/EOS (Week 78 ±7days) 
Patients will undergo the following assessments and procedures when completing the End of 
Study (EOS) visit, withdrawing from study (early withdrawal), or withdrawing from IMP 
treatment: 
• Concomitant and medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints 
• 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 and hs-CRP 
− HbA1C 
• Return of IMP; assessment and recording of IMP compliance 
• Complete study status in IWRS (ie, early withdrawal or completed study). 
New Text: 
9.2.6 Treatment Month 18/EOST (Week 78 ±7days) 
Patients will undergo the following assessments and procedures when completing the End of 
Study (EOS) End of Treatment (EOT) visit, withdrawing from study prior to Week 78 (early 
withdrawal), or withdrawing from IMP treatment: 
• Concomitant and medication review (ongoing) 
• Assess AEs, SAEs, and potential clinical endpoints 
• Weight 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 93 of 100 
• Vital signs 
• Physical Exam 
• Clinical laboratory evaluations: 
− Hematology, blood chemistry, and urinalysis 
− Basic fasting lipids (TC, calculated LDL C, HDL C, non-HDL C, and TG) 
− ApoB and hs-CRP 
− HbA1C 
• Return of IMP; assessment and recording of IMP compliance 
• Complete study status in IWRS (ie, early withdrawal or completed study). 
New Section/Text: 
9.2.7 Off Study Drug Period Month 19/EOS (Week 82 +14 days) 
Patients will return for a final EOS visit 4 weeks after IMP treatment has been completed 
(including patients who withdraw from IMP treatment prior to Week 78) to undergo the 
following assessments and procedures.   
• Concomitant medication review 
• Assess AEs, SAEs, and potential clinical endpoints 
• 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 and hs-CRP 
− HbA1C 
Original Text: 
Patients must remain in the study until the last scheduled visit at Month 18 (Week 78) to be 
considered as having completed participation of the study. 
New Text: 
Patients must remain in the study until the last scheduled visit at Month 19 (Week 82) to be 
considered as having completed participation in the study.  Patients must remain in the study 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 94 of 100 
through Month 18 (Week 78) to be considered as having completed participation in the 
treatment portion of the study. 
Original Text: 
If a patient withdraws or is removed from the study for any reason all EOS 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. 
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 Month 18 
(Week 78). 
New Text: 
If a patient withdraws or is removed from the study for any reason prior to Week 78, all 
EOTEOS procedures should be completed.  In addition, the patient should return 4 weeks after 
last dose of IMP for the Week 82/EOS procedures. 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. 
… 
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 
Month 1819 (Week 82). 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
 
 
Confidential 
Page 95 of 100 
Original Text: 
Month 
0 
3 
6 
9 
12 
15 
18/EOS1 
Week  
EOS Parent 
Wk 12 
Wk 24 
Wk 36 
Wk 52 
Wk 64 
Wk 78 
Visit Window 
30 Days 
pre-M0 
±7 days 
±7 days 
±7 days 
±7 days 
±7 days 
±7 days 
In-clinic Visit 
X 
X 
 
 
X 
 
X 
Phone Visit 
X 
X 
X 
Procedure 
Informed Consent 
X 
 
 
 
 
 
 
Enrollment Criteria 
X 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
Adverse Event 
Recording 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
X 
 
 
 
X 
 
X 
Weight2 
X 
X 
 
 
X 
 
X 
Vital Signs3 
X 
X 
 
 
X 
 
X 
Urine Pregnancy Test4 
X 
 
 
 
 
 
 
Clinical Safety Labs45 
X 
X 
 
 
X 
 
X 
Basic Fasting Lipids56 
X 
X 
 
 
X 
 
X 
Coagulation67 
X 
 
 
 
 
 
 
ApoB and hsCRP 
X 
X 
 
 
X 
 
X 
HbA1C 
X 
  
 
 
X  
 
X 
IWRS Contact78 
X 
 X 
 
 
 X 
 
X 
Drug Dispensing 
X 
X 
 
 
X 
 
Drug Return/ 
Compliance 
 
X 
 
 
X 
 
X 
 
NOTE: For patients who withdraw from study drug treatment, but consent to be followed for safety assessments and 
return to clinic for these visit, the visits will occur according to the protocol schedule.  Safety assessments should 
include clinical safety and basic lipid laboratories, adverse events (AEs), physical examination (PE), and vital signs.  
For patients who withdraw from study drug treatment, but consent to be followed for safety assessments by phone, 
the telephone contacts will occur according the protocol schedule with information regarding current health status 
and to collect information on AEs (eg, recent procedures, hospitalizations, and if the patient has died, the cause of 
death).  If a patient does not provide consent to be followed for safety assessments per the protocol (either by 
returning to clinic or by phone), Visit week 78 will be considered the End of Study (EOS)/Early Withdrawal from 
study and no further visits will be scheduled. 
1 All procedures will be completed for all patients at either EOS if completing the study or early withdrawal. 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 96 of 100 
2 Body weight will be measured in the morning while fasting, using consistent scales, after voiding, and without 
shoes and outerwear (eg, coats).   
3 Vital signs will include diastolic blood pressure (DBP), systolic blood pressure (SBP), heart rate (HR) and will be 
collected prior to any blood sample collection.  Patient will rest for 5 minutes prior to assessments 
4 Urine pregnancy test in women of childbearing potential only 
5 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits.  Please refer to laboratory 
manual for detailed schedule of tests. 
6 Basic fasting lipids include total cholesterol (TC), calculated low-density lipoprotein cholesterol (LDL-C), high-
density lipoprotein cholesterol (HDL-C), non-HDL-C,), and triglycerides (TG). 
7 Only in patients receiving anticoagulant therapy that in the investigator’s judgment require monitoring at Month 0 
and 3 to 5 days post-Month 0 
8 Interactive web response system (IWRS) contact at either an early withdrawal or an EOS visit to register study 
discontinuation visit date 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
 
 
Confidential 
Page 97 of 100 
New Text: 
Month 
0 
3 
6 
9 
12 
15 
18/EOTS1 
20/EOS2 
Week  
EOS 
Parent 
Wk 12 
Wk 24 
Wk 36 
Wk 52 
Wk 64 
Wk 78 
Wk 82  
Visit Window 
30 Days 
pre-M0 
±7 days 
±7 days 
±7 days 
±7 days 
±7 days 
±7 days 
+14 days 
In-clinic Visit 
X 
X 
 
 
X 
X 
X 
Phone Visit 
X 
X 
X 
 
Procedure 
Informed Consent 
X 
 
 
 
 
 
 
 
Enrollment Criteria 
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Event 
Recording 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
X 
 
 
 
X 
 
X 
 
Weight23 
X 
X 
 
 
X 
 
X 
X 
Vital Signs34 
X 
X 
 
 
X 
 
X 
X 
Urine Pregnancy Test45  
X 
 
 
 
 
 
 
 
Clinical Safety Labs56 
X 
X 
 
 
X 
 
X 
X 
Basic Fasting Lipids67 
X 
X 
 
 
X 
 
X 
X 
Coagulation78 
X 
 
 
 
 
 
 
 
ApoB and hsCRP 
X 
X 
 
 
X 
 
X 
X 
HbA1C 
X 
  
 
 
X  
 
X 
X 
IWRS Contact89 
X 
 X 
 
 
 X 
 
X 
 
Drug Dispensing 
X 
X 
 
 
X 
 
 
Drug Return/ 
Compliance 
 
X 
 
 
X 
 
X 
 
NOTE: For patients who withdraw from study drug treatment, but consent to be followed for safety assessments and 
return to clinic for these visit, the visits will occur according to the protocol schedule.  Safety assessments should 
include clinical safety and basic lipid laboratories, adverse events (AEs), physical examination (PE), and vital signs.  
For patients who withdraw from study drug treatment, but consent to be followed for safety assessments by phone, the 
telephone contacts will occur according the protocol schedule with information regarding current health status and to 
collect information on AEs (eg, recent procedures, hospitalizations, and if the patient has died, the cause of death).  If a 
patient does not provide consent to be followed for safety assessments per the protocol (either by returning to clinic or 
by phone), Visit Week 78/End of Treatment (EOT) will be considered the End of Study (EOS)/Early Withdrawal from 
study scheduled as soon as possible and the patient will be asked to come back 4 weeks after last investigational 
medicinal product (IMP) dose for Visit Week 82/End of Study (EOS).  And noNo further visits will be scheduled. 
1 All procedures will be completed for all patients at either EOT EOS if completing the study or early withdrawal  


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 98 of 100 
2 All procedures will be completed for all patients 4 weeks after last IMP dose if completing the study or early 
withdrawal. 
23 Body weight will be measured in the morning while fasting, using consistent scales, after voiding, and without shoes 
and outerwear (eg, coats).   
34 Vital signs will include diastolic blood pressure (DBP), systolic blood pressure (SBP), heart rate (HR) and will be 
collected prior to any blood sample collection.  Patient will rest for 5 minutes prior to assessments 
45 Urine pregnancy test in women of childbearing potential only 
56 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits.  Please refer to laboratory manual 
for detailed schedule of tests. 
67 Basic fasting lipids include total cholesterol (TC), calculated low-density lipoprotein cholesterol (LDL-C), high-
density lipoprotein cholesterol (HDL-C), non-HDL-C,), and triglycerides (TG). 
78 Only in patients receiving anticoagulant therapy that in the investigator’s judgment require monitoring at Month 0 and 
3 to 5 days post-Month 0 
89 Interactive web response system (IWRS) contact at either an early withdrawal or an EOS visit to register study 
discontinuation visit date 
CHANGE 3 
REVISION OF BACKGROUND OF BEMPEDOIC ACID 
Location: 
Section 4.2.3, Previous Human Experience 
… 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
Confidential 
Page 99 of 100 
CHANGE 4 
REVISION OF CONCOMITANT MEDICATIONS 
Location: 
Section 7.2, Concomitant Medications 
Original Text: 
During the study investigators may prescribe any necessary concomitant medication.  However, 
lipid-altering therapies cannot be adjusted during the first 12 weeks of the study. 
New Text: 
During the study investigators may prescribe any necessary concomitant medication.  However, 
lipid-altering therapies cannot be adjusted during the first 12 weeks of the study.  In addition, 
during the 4-week period after last dose, every effort should be made to maintain the patients’ 
lipid-modifying therapy unless it is medically necessary to safely manage the patient.   
 
CHANGE 5 
REMOVAL OF TEXT AROUND ANALYSIS OF MUSCLE EVENTS 
BY eGFR 
Location:  
Section 12.6 Other Endpoints, Renal Events 
Original Text: 
Baseline eGFR will be summarized for actual value and for baseline eGFR categories.  Shift 
tables of eGFR category from baseline over the study, will be provided.  Shift tables of urine 
protein (negative/positive) from baseline over the study, will be provided.  Values of CK will be 
summarized by baseline eGFR category.  Finally, muscle-related AEs will be summarized by 
baseline eGFR category. 
 
New Text: 
Baseline eGFR will be summarized for actual value and for baseline eGFR categories.  Shift 
tables of eGFR category from baseline over the study, will be provided.  Shift tables of urine 
protein (negative/positive) from baseline over the study, will be provided.  Values of CK will be 


Bempedoic Acid 
 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002-050 
 
Amendment 2, 15 January 2018 
 
 
Confidential 
Page 100 of 100 
summarized by baseline eGFR category.  Finally, muscle-related AEs will be summarized by 
baseline eGFR category. 
 

SAP_001.pdf: 
Bempedoic Acid (ETC-1002) 
Esperion Therapeutics, Inc. 
Clinical Study Report: 1002-050 
16.1.9 
Documentation of Statistical Methods 
Original Statistical Analysis Plan (SAP) Version 1.0 
14 February 2017 
SAP Version 1.1 
19 October 2018 
SAP Version 1.2  
05 December 2018 
SAP Addendum for Day 120 Safety Update Interim Analysis 
23 May 2019 
SAP Version 1.3 
04 December 2019 
Page 1 of 129


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Esperion Therapeutics, Inc. 
Version 1.0, Feb 14, 2017
Protocol: ETC-1002-050 
Statistical Analysis Plan
Confidential 
Page 2 of 24
Table of Contents 
1
List of Abbreviations .................................................................................................. 4
2
Introduction ................................................................................................................. 7
3
Study Objectives and Endpoints ................................................................................. 7
3.1
Objectives ............................................................................................................. 7
3.2
Primary Endpoint ................................................................................................. 7
3.3
Secondary Endpoints ............................................................................................ 7
3.3.1
Adverse Events ............................................................................................. 8
3.3.2
Clinical Safety Laboratories ......................................................................... 8
3.3.3
ECG, Vital Signs and PE .............................................................................. 8
3.4
Lipids .................................................................................................................... 8
3.5
Pharmacokinetic (PK) and Other Biomarkers ...................................................... 8
4
Study Design ............................................................................................................... 8
4.1
Study Design ........................................................................................................ 8
4.2
Study Treatments and Assessments ..................................................................... 9
4.3
Randomization and Blinding .............................................................................. 11
4.4
Sample Size Justification ................................................................................... 11
4.5
Interim Analyses, Final Analyses and Unblinding ............................................. 11
4.6
Change from Planned Analyses ......................................................................... 11
5
Statistical and Analytical Plans ................................................................................. 11
5.1
General Statistical Considerations ..................................................................... 11
5.2
Statistical Analysis Plans ................................................................................... 12
5.2.1
Analysis Sets ............................................................................................... 12
5.2.1.1
Safety Population (SP)......................................................................... 12
5.2.1.2
Full Analysis Set (FAS) ....................................................................... 12
5.2.2
Protocol Violations and Deviations ............................................................ 12
5.2.3
Subject Disposition ..................................................................................... 13
5.2.4
Demographic and Baseline Characteristics ................................................ 13
5.2.5
Medical History .......................................................................................... 13
5.2.6
Prior and Concomitant Medications ........................................................... 14
5.2.7
Study Drug Exposure and Compliance ....................................................... 14
5.3
Efficacy Endpoints and Analyses ....................................................................... 14
5.4
Safety Data Endpoints and Analyses ................................................................. 15
5.4.1
Adverse Events (AEs) ................................................................................. 15
5.4.2
Adverse Events of Special Interest ............................................................. 16
5.4.3
Clinical Cardiovascular Endpoints ............................................................. 17
5.4.4
Neurocognitive Events ................................................................................ 17
5.4.5
Laboratory Evaluations ............................................................................... 18
5.4.5.1
Hepatic Safety ...................................................................................... 20
5.4.5.2
Musculoskeletal Safety ........................................................................ 20
5.4.5.3
Diabetes and Glycemia ........................................................................ 20
5.4.5.4
Renal Safety ......................................................................................... 20
5.4.6
Physical Examinations (PEs) ...................................................................... 21
5.4.7
Vital Signs ................................................................................................... 21
5.4.8
Electrocardiogram (ECG) ........................................................................... 21
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Esperion Therapeutics, Inc. 
Version 1.0, Feb 14, 2017
Protocol: ETC-1002-050 
Statistical Analysis Plan
 
Confidential 
Page 3 of 24
 
6
DMC Analyses .......................................................................................................... 21
7
Reference .................................................................................................................. 21
8
Appendices ................................................................................................................ 23
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Esperion Therapeutics, Inc. 
Version 1.0, Feb 14, 2017
Protocol: ETC-1002-050 
Statistical Analysis Plan
 
Confidential 
Page 4 of 24
 
 
1
List of Abbreviations  
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 
BMI 
Body mass index 
BP 
Blood pressure 
BUN 
Blood urea nitrogen 
Ca 
Calcium 
CEC 
Clinical Event Committee 
CFR 
Code of Federal Regulations 
CHD 
Coronary heart disease 
CI 
Confidence interval 
CK 
Creatine kinase 
Cl 
Chloride 
CNS 
Central nervous system 
CoA 
Acetyl-coenzyme A 
CO2 
Carbon dioxide 
CV 
Cardiovascular 
CYP 
Cytochrome P450 
DBP 
Diastolic blood pressure 
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
eGFR 
Estimated glomerular filtration rate 
EMA 
European Medicines Agency 
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Protocol: ETC-1002-050 
Statistical Analysis Plan
 
Confidential 
Page 5 of 24
 
Abbreviation or Specialist Term 
Explanation 
EOS 
End of Study 
ETC-1002 
Bempedoic acid 
EU 
European Union 
FAS 
Full analysis set 
FDA 
Food and Drug Administration 
FPFV 
First patient first visit 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GI 
Gastrointestinal 
HbA1C 
Glycosylated hemoglobin, Type A1C 
HBsAg 
Hepatitis B surface antigen 
Hct 
Hematocrit 
HCV 
Hepatitis C virus 
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 
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 cardiac event 
MCH 
Mean corpuscular hemoglobin 
MCHC 
Mean corpuscular hemoglobin concentration 
MCV 
Mean corpuscular volume 
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Protocol: ETC-1002-050 
Statistical Analysis Plan
 
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Abbreviation or Specialist Term 
Explanation 
MDRD 
Modification of diet in renal disease 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Myocardial infarction 
MRI 
Magnetic resonance imaging 
Na 
Sodium 
NA 
Not applicable 
NLA 
National Lipid Association 
NOAEL 
No-observed-adverse-effect level 
non-HDL-C 
Non-high-density lipoprotein cholesterol 
OLE 
Open-label extension (study) 
Parent study 
Study 1002-040 
PCSK9 
Proprotein convertase subtilisin/kexin type 9 
PE 
Physical exam 
PK 
Pharmacokinetic(s) 
PT 
Prothrombin 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 
SP 
Safety population 
SUSARS 
Suspected and unexpected serious adverse reactions 
T2DM 
Type 2 diabetes mellitus 
TB 
Total bilirubin 
TC 
Total cholesterol 
TEAE 
Treatment-emergent adverse event 
TG 
Triglycerides 
TQT 
Thorough QT/QTc 
ULN 
Upper limit of normal 
US 
United States 
WBC 
White blood cell 
WHO 
World Health Organization 
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Protocol: ETC-1002-050 
Statistical Analysis Plan
 
Confidential 
Page 7 of 24
 
2
Introduction 
The purpose of this document is to describe the statistical methods, data derivations and 
data summaries to be employed in ETC-1002-050. The preparation of this statistical 
analysis plan (SAP) has been based on International Conference on Harmonisation (ICH) 
E3 and E9 Guidelines and in reference to Protocol ETC-1002-050 (Protocol V1.0, 
November 01, 2016).  
The SAP will supersede the protocol in the event of any differences between the two 
documents in the plans for data analysis, and the protocol will be amended if appropriate. 
The SAP will be included as an appendix in the clinical study report for this protocol. 
 
3
Study Objectives and Endpoints 
3.1
Objectives
x
The primary objective for this study is to characterize the safety and tolerability of 
long-term administration of bempedoic acid (ETC-1002) 180 mg  
 
x
The secondary objective is to characterize the efficacy of long-term administration 
of bempedoic acid 180 mg/day as assessed by changes in low-density lipoprotein 
cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-high-
density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total 
cholesterol (TC), triglycerides TG and high-sensitivity C-reactive protein (hs-CRP) 
in patients with hyperlipidemia  
 
3.2
Primary Endpoint 
x
The primary endpoint for this study is patient incidence of AEs 
3.3
Secondary Endpoints 
x
Percent change from baseline in LDL-C at Weeks 52 and 78 
x
Change from baseline in LDL-C at Weeks 52 and 78  
x
Percent change from baseline in non-HDL-C at Weeks 52 and 78 
x
Percent change from baseline in TC at Weeks 52 and 78 
x
Percent change from baseline in ApoB at Weeks 52 and 78 
x
Percent change from baseline in hs-CRP at Weeks 52 and 78 
x
Percent change from baseline in TG at Weeks 52 and 78 
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Esperion Therapeutics, Inc. 
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Protocol: ETC-1002-050 
Statistical Analysis Plan
 
Confidential 
Page 8 of 24
 
x
Percent change from baseline in HDL-C at Weeks 52 and 78 
3.3.1
Adverse Events 
The evaluation of AEs will include only incidence of treatment-emergent AEs (TEAEs), 
defined as AEs that begin or worsen after the first dose of study drug administration in 
OLE period and until 30 days after last dose of study drug. Clinical endpoints (details see 
section 4.2) will be collected and adjudicated by an independent Clinical Events Committee 
(CEC). Clinical endpoints will also be reported as SAEs. Adverse events of special interest 
(AESI) will further be examined (See Section 5.4.2 for more information).   
3.3.2
Clinical Safety Laboratories 
The evaluation of clinical safety laboratories, including blood hematology, chemistry, 
coagulation, and urinalysis, will be based on the observed values. Observed values and 
changes from baseline will be summarized for all post-baseline study visits. 
3.3.3
ECG, Vital Signs and PE 
The evaluation of ECG and vital signs (including heart rate, systolic blood pressure, 
diastolic blood pressure, height, and weight will be based on the observed values. For 
ECGs, shifts from baseline to end-of-study will be summarized.  For vital signs, observed 
values and changes from baseline will be summarized for all post-baseline study visits. 
Listings of PE data will include only those records where the body system at the baseline 
PE was normal, but the body system at a post-baseline PE was marked as ‘Change from 
previous exam, clinically significant.’   
3.4
Lipids
After enrollment, patients will return to clinic at Months 12, 52, and 78.  Clinical laboratory 
samples will be collected and analyzed for calculated LDL-C and lipid and cardiometabolic 
biomarkers including non-HDL-C, HDL-C, TC, ApoB, and TG at baseline and all clinic 
visits for evaluation of bempedoic acid effects on lipids and cardiometabolic parameters.  
3.5
Pharmacokinetic (PK) and Other Biomarkers 
NA. 
4
Study Design 
4.1
Study Design 
This is a multicenter OLE study designed to assess the long-term safety and efficacy of 
bempedoic acid (ETC-1002) 180 mg.  All patients will receive open-label bempedoic acid 
180 mg for up to 1.5 years after rolling over from the parent study (Study 1002-040), where 
they receive either bempedoic acid or placebo treatment.  Investigators, site staff, patients, 
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and the study team will be masked to study lipid levels until the Week 12 study visit, after 
which time lipid values will be made available. 
An independent expert Data Monitoring Committee (DMC) will formally review 
accumulating unblinded safety and efficacy data from this and other ongoing studies of 
bempedoic acid.  A blinded independent expert Clinical Events Committee (CEC) will 
adjudicate designated clinical endpoints across the program, including all major adverse 
cardiac events (MACE) and non-MACE endpoints defined as:  cardiovascular (CV) death 
(MACE), non-CV death (non-MACE), nonfatal myocardial infarction [MI] (MACE), 
nonfatal stroke (MACE), hospitalization for unstable angina (MACE), coronary 
revascularization (MACE), noncoronary 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 as well 
as a clinical endpoint. 
The study will be conducted at approximately 125 clinical sites in the United States, 
Canada, Germany, Netherlands, Poland, and United Kingdom. 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 2.5 years. 
 
Figure 1. Study 1002-040 Study Design 
 
4.2
Study Treatments and Assessments 
Day 1 for this study should occur on the same day as the end of study visit for the parent 
study (1002-040).  Patients who provide informed consent and sign the ICD will be eligible 
to enroll in the study.   
The schedule of study events is provided in Appendix 1.  However, a patient can be seen at 
any time for reasons of safety.  
The investigational products were listed in Table 1 below: 
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Table 1: 
Investigational Medicinal Products 
 
Investigational Medicinal Product 
Product Name: 
Bempedoic acid 
Dosage Form: 
Film-coated tablets 
Unit Dose: 
180 mg 
Container/Closurea
100-count bottle with screw on, child proof cap 
Route of Administration: 
Oral, daily with or without food 
Physical Description: 
Manufacturer
(Fill/Finish):
 
Study drug should be taken once a day (once every 24 hours) at approximately the same 
time every day and may be taken with or without food.  Patients will fast (no food or drink, 
other than water) for a minimum of 10 hours prior to collection of all laboratory samples. 
Please see Pharmacy Manual for detailed storage requirements and instructions. 
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 Appendix 1: Schedule of Events (Subject 
Visit Schedule).   
An independent expert Data Monitoring Committee (DMC) will formally review 
accumulating unblinded safety and efficacy data from this and other any 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 serious adverse event (SAE) 
criteria will be reported as SAEs.
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4.3
Randomization and Blinding 
x
Randomization is not applicable for this OLE study.  
x
Laboratory results for lipid panel and hs-CRP will be masked to investigators, 
patients, and the study team until the Week 12 visit is completed.  All site staff 
involved with this trial should refrain from obtaining lipid panels between date of 
last study medication (bempedoic acid or placebo) dose at end of parent study Week 
52 (Visit T7) and Week 12 in this OLE trial. 
4.4
Sample Size Justification 
The number of patients entering this study will depend on the number of patients 
completing Study 1002-040 and their willingness to enroll.   
4.5
Interim Analyses, Final Analyses and Unblinding 
No formal interim analysis is planned for this study. 
An interim data cut-off may occur in order to provide safety assessment to support NDA 
submission; the actual date will be determined by Esperion team. 
The final analysis will be performed after the database is locked, and the database released. 
4.6
Change from Planned Analyses 
There is no change from planned analyses for this study. 
5
Statistical and Analytical Plans 
5.1
General Statistical Considerations 
The ETC-1002 treatment group will be displayed in the tables, listings and figures (TLFs) 
as “bempedoic acid 180 mg.”   
In general, all safety and efficacy data will be reported as observed. No imputation will be 
performed for missing data.  Descriptive statistics (n, mean, standard deviation [SD] or 
Standard Error [SE], median, minimum, and maximum) will be calculated for continuous 
data. Minimum and maximum will be presented same number of decimal places as 
reported/collected, one additional decimal place for mean and median, and two additional 
decimal places for SD. 
Categorical data will be summarized using n and percentage based on number of non-
missing values. Percentage will be presented with one decimal place. The number of 
missing values will be presented as a separate category with no percentage, but only if 1 or 
more patients are missing data for the summary.  Otherwise, all categories will be 
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presented (even if no patients are counted in the category). Counts of zero in any category 
will be presented without percentage. Ninety-five percent (95%) confidence intervals (CIs) 
will be calculated for select continuous and categorical endpoint estimates. All patients will 
be summarized together as well as by their prior treatment group in the parent study. 
Data will be presented on listings in order of patient/subject, assessment date and 
assessment (in order collected on CRF, unless specified otherwise). Dates will be presented 
in format DDMMMYYYY. 
Relative day calculations will be [date of interest – relative date + 1? (date of interest >= 
relative date)]. This calculation will result in dates prior to the relative date being presented 
as negative days, and those occurring on or after the relative date as Day 1 or later, i.e., 
there will be no Day 0. 
For efficacy endpoint analysis, baseline is defined as the same baseline as parent study. For 
safety analysis, baseline is defined as the last value/result where assessment date is less 
than or equal to the date of first study treatment, unless otherwise specified. If last dose of 
study treatment is missing, then the date of last visit at which study assessments were 
obtained on CRF will be used in its place.  
The visit schedules and window are shown below.  
5.2
Statistical Analysis Plans 
5.2.1
Analysis Sets 
5.2.1.1 Safety Population (SP) 
The Safety Population (SP) is defined as all enrolled patients who received at least 1 dose 
of study medication and will be used for demographics and baseline characteristics, 
treatment exposure, concomitant medications, and all safety summaries.  
5.2.1.2 Full Analysis Set (FAS)
The Full Analysis Set (FAS) is defined as all enrolled patients and is also known as the 
intention-to-treat (ITT) set of patients. FAS will be used for all of the efficacy summaries 
and analyses. 
5.2.2
Protocol Violations and Deviations 
A full list of protocol violations and deviations will be compiled and reviewed by the 
clinical team to identify major versus minor violations/deviations before final database 
Visit 
Day 1/Week 0 
Week 
12 
Week 24 
Week 36 
Week 52 
Week 64 
Week 
78/EOS 
Month 
0 
3 
6 
9 
12 
15 
18/EOS 
Slotted Study Week 
EOS Parent 
Wk 12 
Wk 24 
Wk 36 
Wk 52 
Wk 64 
Wk 78 
Target Study Day 
1 
84 
168 
252 
364 
448 
546 
Analysis Window  
1 
[2,126] 
[127,210] 
[211,308] 
[309,406] 
[407,497] 
[498,∞] 
Protocol defined visit 
Windows 
[30 Days, Pre 
M0] 
84±7 
168±7 
252±7 
364±7 
448±7 
546±7 
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lock. For violations at study entry, patients will be assessed against the inclusion and 
exclusion criteria of the protocol. For on-study deviations, compliance with the protocol 
will be examined with regard to prohibited therapies, and timing and availability of planned 
assessments. 
5.2.3
Subject Disposition
The number of patients enrolled, and included in each analysis population, along with study 
completion status, will be summarized by the treatment group in parent ETC-1002-040 
study and overall. In addition, the number of patients who withdraw from the study and 
withdraw from study drug will be summarized by discontinuation reason. 
5.2.4
Demographic and Baseline Characteristics
Demographic and baseline characteristics collected from the parent study will be used for 
this study.  The following demographic and baseline characteristics will be summarized by 
previous treatment group in parent study, as well as overall, for safety population and for 
FAS population: age (years), gender, race, ethnicity, region, height (cm), weight (kg), body 
mass index (kg/m2), waist circumference (cm), systolic and diastolic blood pressure 
(mmHg), fasting lipid parameters (TC [mg/dL], calculated LDL-C [mg/dL], HDL-C 
[mg/dL], non-HDL-C [mg/dL] and TG [mg/dL]), apoB (mg/dL), hs-CRP (mg/dL), 
ASCVD only/HeFH, baseline statin intensity (low, moderate, high), eGFR category, 
tobacco history, alcohol history, and weekly average number of alcoholic drinks, history of 
diabetics, history of hypertension. Data will be summarized using descriptive statistics for 
continuous variables and using counts and percentages for categorical variables by 
treatment group and overall. Age will be summarized as a continuous variable and by age 
group (18-40, 41-64, 65-74, and >=75). 
 
The baseline estimated glomerular filtration rate (eGFR) categories are: normal: 
≥90 mL/min/1.73m2; mild Renal Impairment: 60-89 mL/min/1.73m2; moderate Renal 
Impairment: 30-59 mL/min/1.73m2, and severe Renal Impairment (15-29 mL/min/1.73m2). 
The reasons for patients who are not on a highest dose of a high intensity statin will be 
summarized and presented in a by-patient listing. 
5.2.5
Medical History
General medical history, cardiovascular history/risk factors, previous statin use and statin 
tolerance history will be summarized by previous treatment group in parent study, as well 
as overall in OLE study, for safety population and FAS population and presented in a by-
patient listing.  Where appropriate, terms will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA) Version 18.1 or later.     
 
If a patient is entering the study beyond the 30 day rollover window, changes to medical 
history that occur during that period will be collected. The changes will be summarized for 
safety population and presented in a by-patient listing.   
 
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5.2.6
Prior and Concomitant Medications 
Prior medications are defined as medications that ended prior to the initiation of study drug 
in this OLE study. Concomitant medications are defined as medications that were ongoing 
at the time of study drug initiation in this OLE study or new medications that started post 
study drug initiation and within 30 days following the date of the last dose of study drug. 
 
Medications, including prior statin medications, will be coded using WHO Drug (March, 
2015, or later if appropriate). The frequency of use of prior medications and use of 
concomitant medications will be summarized by previous treatment group in parent study, 
as well as overall in OLE study, for the safety population according to Anatomical 
Therapeutic Chemical (ATC) class and preferred term. If there is no enough prior 
medication data, prior medications will be presented in a by-patient listing only. Prior and 
concomitant medications will be listed for each patient. Prior and concomitant statin 
medications will be summarized and listed similarly.  
5.2.7
Study Drug Exposure and Compliance 
The length of exposure to study drug will be calculated as the number of days from the first 
dose of study drug to the last dose of study drug, regardless if the patient missed one or 
more doses of study drug.  Length of exposure will be summarized by previous treatment 
group in parent study and overall in OLE study using descriptive statistics for the safety 
population.  
The number and percentage of patients who were compliant with taking study drug will be 
summarized by previous treatment group in parent study and overall in OLE study and 
post-baseline time point for the safety population for the following categories 0 - <50%; 
>=50 - <80%; >= 80%. Compliance at each Visit (x)will be assessed by site staff by 
counting the number of tablets that are returned as unused study drug and querying the 
patient regarding daily intake and calculated using the formula: 100* (Number Dispensed 
at Visit x-1 – Number Returned at Visit x) / (Duration in days between Visit x and Visit x-
1).  Overall compliance during the study will be similarly calculated.     
The study drug administration and compliance data, including reasons for poor compliance, 
will be listed for each patient. 
5.3
Efficacy Endpoints and Analyses
For all efficacy endpoints and analyses, the FAS will be used. For summary by previous 
treatment group in parent study, patient will be summarized in their randomized group in 
parent study, regardless of the treatment they actually received.  
For change from baseline in efficacy endpoints, baseline will be same baseline as parent 
study. For summaries of efficacy endpoints, only observed case data will be used (no 
imputation for missing data). 
LDL-C, HDL-C, TG, TC, non-HDL-C, apoB and hs-CRP values at week 0, Weeks 52, and 
78 will be summarized based on the FAS. For each parameter at each time point, the value 
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of the parameter and the percent change from baseline in the parameter will be summarized 
by previous treatment group in parent study and overall in OLE study. Ninety-five percent 
(95%) CI will be provided for the estimates at week 0, Week 52 and 78 for the change 
values. Lipid and cardiometabolic data from all visits will be listed. 
5.4
Safety Data Endpoints and Analyses  
No statistical analyses will be performed on any of the safety data in this study. 
 
The safety and tolerability of ETC-1002 will be assessed by examination of TEAEs 
(including muscle related events and other AESI), physical exams, vital signs, 
electrocardiograms (ECGs), clinical laboratory values (serum chemistry, hematology, 
coagulation and urinalysis), and weight. All patients included in the SP will be evaluated in 
the safety analyses.   
 
Unless otherwise stated, descriptive summaries will be displayed by previous treatment 
group actually received in parent study and overall and based on the SP. 
5.4.1
Adverse Events (AEs) 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
Version 18.1 or later and will be categorized by system organ class (SOC) and preferred 
term (PT). 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. Summary tables will focus on TEAEs; however, listings will include all AEs (with 
non-TEAEs flagged). An additional listing will be provided for AEs occurred during 
rollover period for patients who entered the study beyond the 30-day rollover window, if 
data available. 
In summary tables, TEAEs will be counted as “Not Related” if relationship to study drug 
was recorded as ‘Not Related’ or “Unlikely”. Events will be counted as “Related” if 
relationship to study drug was recorded as ‘Possible’, ‘Probable’, ‘Definite’ or if 
relationship to study drug is missing. 
The severity of the AE will be characterized as mild, moderate, or severe, to the following 
definitions: 
• 
Mild: Events are usually transient and do not interfere with the patient’s daily 
activities 
• 
Moderate: Events introduce a low level of inconvenience or concern to the patient 
and may interfere with daily activities  
• 
Severe: Events interrupt the patient’s usual daily activity, are incapacitating with 
inability to do usual activities, or significantly affect clinical status and warrant 
intervention and/or close follow-up  
 
Overviews of TEAEs will be presented by previous treatment group in parent study and 
overall containing the following counts and percentages for: 
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x
patients with TEAEs 
x
Patients with TEAEs occurred during the rollover period for patients entered the 
study beyond the 30 day rollover window (if available)   
x
patients with TEAEs by SOC and PT 
x
patients with TEAEs by maximum severity 
x
patients with treatment-related TEAEs 
x
patients with treatment-emergent serious adverse events (TE SAEs)  
x
patients with TE SAEs (TE SAEs) by SOC and PT 
x
patients with TE SAEs by maximum severity 
x
patients with treatment-related TE SAEs  
x
withdrawal from study drug due to TEAEs 
 
In addition, summary tables will be provided, by prior treatment group and overall, for the 
number and percent of patients experiencing: 
x
investigator reported major adverse cardiovascular events and mortality (MACE) by 
event type 
x
adjudicated major adverse cardiovascular events and mortality (MACE) by event 
type  
x
non-CV deaths (non-MACE), 
x
nonfatal myocardial infarction [MI] (MACE), 
x
nonfatal stroke (MACE), 
x
hospitalization for unstable angina (MACE),  
x
coronary revascularization (MACE),  
x
noncoronary arterial revascularization (non-MACE),  
x
hospitalization for heart failure (non-MACE) using standardized definitions. 
 
Any clinical endpoints that meet serious adverse event (SAE) criteria will be reported as 
SAEs as well as a clinical endpoint. 
 
The AE overview summaries will count a patient at most once in each AE category (at the 
“highest/most extreme” designation of each category regardless of preferred term) and 
percentages will be based on the total number of patients in the safety population. 
In addition to a comprehensive listing of all AEs (with non-TEAEs flagged), separate 
listings will be generated for SAEs, AEs resulting in withdrawal of study drug, and AEs 
with a fatal outcome, investigator reported major adverse cardiovascular events and 
mortality, and adjudicated major adverse cardiovascular events and mortality. 
5.4.2
Adverse Events of Special Interest 
Across clinical studies to date, the most frequently reported TEAEs associated with the 
experiences with ETC-1002 included musculoskeletal and connective tissue disorders 
(back pain, pain in extremity, myalgia, arthralgia, and muscle spasms), nervous system 
disorders (headache), GI disorders (nausea and diarrhea), and infections and infestations. 
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Adverse events of special interest (AESI) include hepatic, muscular (AE and CK 
evaluation), new onset diabetes/glycemia, renal, cardiovascular, metabolic acidosis and 
hypoglycemia and neurocognitive/neurologic events. These events will be pulled out of the 
AE databases with help of clinical team by SOC and PT, and will be identified as safety 
monitoring endpoint. 
x
Hepatic safety will be assessed via liver-associated enzymes and TB. 
x
Musculoskeletal safety will be assessed via AEs involving muscle related 
symptoms, CPK laboratories will also be summarized.   
x
New onset diabetes/glycemia will be assessed via AEs and monitoring of glucose 
and HbA1c.   
x
Renal safety will be assessed via eGFR, CK and muscle-related AEs. 
x
Cardiovascular safety will be assessed via AEs (note that the AESI of 
cardiovascular safety is broader than the MACE assessment). 
x
 Neurocognitive events will be assessed by routine monitoring of PE findings and 
AEs.   
x
Hypoglycemia will be assessed by routine clinical laboratories and  summarized 
based on AE evaluations 
x
Metabolic acidosis occurrences will be monitored by routine laboratories and 
summarized based on AE evaluations. 
AESI will be presented in a listing and summarized by SOC, PT and previous treatment 
group in parent study and overall in OLE study. Muscle-related TEAEs will be summarized 
by SOC, PT and baseline eGFR category. 
5.4.3
Clinical 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 clinical endpoints will be summarized by event type and previous treatment 
group in parent study and overall in OLE study. Additional details regarding clinical 
endpoints and clinical endpoint definitions will be included in CEC charter. 
5.4.4
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 pre-specified 
MedDRA terms and will be performed by SOC, severity, and relationship to study drug by 
previous treatment group in parent study and overall in OLE study. 
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5.4.5
Laboratory Evaluations 
Continuous laboratory parameters (serum chemistry, hematology, coagulation (only in 
patients receiving anticoagulant therapy that in the investigator’s judgment require 
monitoring at Month 0 and 3 to 5 days post-Month 0), urinalysis, urinalysis [microscopic]) 
listed in Table 2; glucose, and HbA1c will be summarized using descriptive statistics for 
the observed value and the change from baseline. Missing values for any of the laboratory 
evaluations will not be imputed; that is, only observed case data will be used. Baseline is 
defined as the last value prior to the first dose of study medication in OLE study. 
Categorical urinalysis data will be listed, but will not be summarized. 
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Table 2: 
Clinical Laboratory Parameters (Safety) 
 
Clinical Laboratory Test 
Clinical Laboratory Test 
x
Hematology 
x
Hematocrit (Hct) 
x
Hemoglobin (Hgb) 
x
Mean corpuscular hemoglobin (MCH) 
x
Mean corpuscular hemoglobin 
concentration (MCHC) 
x
Mean corpuscular volume (MCV) 
x
Platelet count 
x
Red blood (RBC) cell count 
x
White blood (WBC) cell count with 
differential (absolute and %) 
Blood Chemistry (serum, fasting) 
x
Albumin (Alb) 
x
Alkaline phosphatase (ALK-P) 
x
Alanine aminotransferase (ALT; SGPT) 
x
Aspartate aminotransferase (AST; 
SGOT) 
x
Blood urea nitrogen (BUN) 
x
Calcium (Ca) 
x
Carbon dioxide (CO2) 
x
Chloride (Cl) 
x
Creatinine 
x
Creatine kinase (CK) 
x
Glucose 
x
Lactate dehydrogenase (LDH) 
x
Phosphorus 
x
Potassium (K) 
x
Sodium (Na) 
x
Total and direct bilirubin (TB)a 
x
Total protein 
x
Uric acid 
Coagulation—only in patients receiving 
anticoagulant therapy that in the investigator’s 
judgment require monitoring at Month 0 and 
3 to 5 days post-Month 0 
x
Prothrombin time (PT) 
x
International normalized ration (INR) 
Urinalysis (Dipstick) 
x
Clarity 
x
Bilirubin 
x
Color 
x
Glucose 
x
Ketones 
x
Leukocyte esterase 
x
Nitrate 
x
Occult blood 
x
pH 
x
Protein 
x
Specific gravity 
x
Urobilinogen 
Urinalysis (Microscopic)-only if urine dipstick 
abnormal 
x
Bacteria 
x
Casts 
x
Crystals 
x
Epithelial cells 
x
RBC 
x
WBC 
Other Labs: 
x
Urine pregnancy test  
x
Hemoglobin A1C (HbA1C) 
a If TB ≥1.2 u ULN, a reflex indirect (unconjugated) bilirubin will be obtained. 
 
The number and percentage of patients with laboratory abnormalities (i.e., laboratory 
values outside the stated laboratory normal range) will be summarized at each time point 
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(i.e., including baseline and post-baseline time points) for each laboratory parameter. The 
determination of laboratory abnormalities will take into account any unscheduled 
laboratory assessments.  Additional lab-related summaries will be provided as follows for 
hepatic safety, musculoskeletal safety, diabetes and glycemia, and renal safety. 
5.4.5.1 Hepatic Safety 
For liver-associated enzymes and total bilirubin (TB), the number and percent of patients 
with abnormal values for ALT (>= 3 × ULN, >= 5 × ULN), AST (>= 3 × ULN, >= 5 × 
ULN), and TB (>= 2×ULN) will be summarized by overall, normal baseline ALT/AST/TB 
and abnormal baseline ALT/AST/TB.  
Hy’s law criteria (≥ 3 × upper limit of normal [ULN] for either ALT or AST, with 
accompanying TB > 2 × ULN, with no other known cause) 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. 
5.4.5.2 Musculoskeletal Safety 
CK levels will be summarized by the value and change from baseline in the value, by 
treatment group and visit as well as baseline eGFR category. In addition, the number and 
percent of patients with abnormal CK values (>= 5 X ULN, >= 10 × ULN) will be 
summarized. These summaries of patients with abnormal CK will be performed overall, 
normal baseline CK, and abnormal baseline CK.  
5.4.5.3 Diabetes and Glycemia 
For fasting glucose and HbA1C (%), a shift table from baseline with the number and 
percent of patients will be categorized as below: 
Fasting glucose: >= 126 mg/dL; 100-125 mg/dL, and < 100 mg/dL; 
HbA1C (%): >=6.5%; >5.5 to <=6.4% and <=5.5%. 
5.4.5.4 Renal Safety 
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/1.73m2 (e.g., including <30 mL/min/1.73m2 and 
updating to include moderate renal impairment to 30-59 mL/min/1.73m2). 
In addition, renal function will be categorized as: (1) A creatinine change from baseline of 
> 1 mg/dL or occurrences of eGFR < 30mg/dL/m2; (2) A Creatinine change <= 1 mg/dL 
from baseline ULN or eGFR >= 30 mg/dL/m2. A shift table from baseline with the number 
and percent of patients using the two categories will be presented. 
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. 
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Version 1.0, Feb 14, 2017
Protocol: ETC-1002-050 
Statistical Analysis Plan
 
Confidential 
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5.4.6
Physical Examinations (PEs) 
Listings of PE data will include only those records where the body system at the baseline 
PE was normal, but the body system at a post-baseline PE was marked as ‘Change from 
previous exam, clinically significant.’  Baseline is defined as the last value prior to the first 
dose of study medication. Only changes from baseline physical examination findings that 
meet the definition of an AE will be recorded on the AE page of the eCRF and will be 
summarized with other AE outcomes. 
5.4.7
Vital Signs 
Actual values and changes from baseline in vital signs (heart rate, systolic blood pressure, 
diastolic blood pressure, weight, height [baseline only], and BMI) will be summarized 
using descriptive statistics by treatment group and post-baseline time point. Baseline is 
defined as the last value prior to the first dose of study medication. 
Vital signs data will be listed for each patient, with increases from baseline of >15 mmHg 
in systolic or diastolic blood pressure flagged. 
5.4.8
Electrocardiogram (ECG) 
Shift tables for ECG data from baseline to end-of-study will be provided by treatment 
group. The data will be categorized as ‘Normal’; ‘Abnormal, not clinically significant’; and 
‘Abnormal, clinically significant.’ Baseline is defined as the last value prior to the first 
dose of study medication. Listings of ECG data will include only those records where the 
baseline ECG was either ‘Normal’ or ‘Abnormal, not clinically significant’, but the end-of-
study ECG was marked as ‘Abnormal, clinically significant’.  
 
6
DMC Analyses 
Refer to DMC charter. 
 
7
Reference 
1. Sharrett AR, Ballantyne CM, Coady SA, Heiss G, Sorlie PD, Catellier D, et al. 
Atherosclerosis Risk in Communities Study Group. Coronary Heart Disease 
Prediction from Lipoprotein Cholesterol Levels, Triglycerides, Lipoprotein(A), 
Apolipoproteins A-I and B, and HDL Density Subfractions. The Atherosclerosis 
Risk in Communities (ARIC) Study. Circulation. 2001;104:1108-13. 
2. World Health Organization (WHO) Fact Sheet No 317 Updated January 2015. 
3. 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. 
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Version 1.0, Feb 14, 2017
Protocol: ETC-1002-050 
Statistical Analysis Plan
 
Confidential 
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4. Pharmacokinetics in Patients with Impaired Renal Function — Study Design, 
Data Analysis, and Impact on Dosing and Labeling. FDA Draft Guidance. 
March 2010 
5. Haase A, Goldberg AC. Identification of people with heterozygous familial 
hypercholesterolemia. Curr Opin Lipidol. 2012;23:282-9. 
6. Glynn RJ, Laird NM, and Rubin DB. (1986). Selection modelling versus 
mixture modelling with nonignorable nonresponse. In H. Wainer (ed.), Drawing 
Inferences from Self-Selected Samples, pp. 115–142. New York: Springer. 
 
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Esperion Therapeutics, Inc. 
Version 1.0, Feb 14, 2017
Protocol: ETC-1002-050 
Statistical Analysis Plan
 
Confidential 
Page 23 of 24
 
8
Appendices
Appendix 1: Schedule of Events (Subject Visit Schedule) 
Month 
0 
3 
6 
9 
12 
15 
18/EOS1
Week  
EOS 
Parent
Wk 12 
Wk 24 
Wk 36 
Wk 52 
Wk 64 
Wk 78 
Visit Window 
30 Days 
pre-M0
±7 days 
±7 days 
±7 days 
±7 days 
±7 days 
±7 days 
In-clinic Visit 
X 
X 
 
 
X 
 
X 
Phone Visit 
 
 
X 
X 
 
X 
 
Procedure 
Informed Consent 
X 
 
 
 
 
 
 
Enrollment Criteria 
X 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
Adverse Event 
Recording 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
X 
 
 
 
X 
 
X 
Weight2 
X 
X 
 
 
X 
 
X 
Vital Signs3 
X 
X 
 
 
X 
 
X 
Urine Pregnancy Test  
X 
 
 
 
 
 
 
Clinical Safety Labs4 
X 
X 
 
 
X 
 
X 
Basic Fasting Lipids5 
X 
X 
 
 
X 
 
X 
Coagulation6 
X 
 
 
 
 
 
 
ApoB  and hsCRP 
X 
X 
 
 
X 
 
X 
HbA1C 
X 
  
 
 
X  
 
X 
IWRS Contact7 
X 
 X 
 
 
 X 
 
X 
Drug Dispensing 
X 
X 
 
 
X 
 
 
Drug 
Return/Compliance 
 
X 
 
 
X 
 
X 
NOTE: For patients who withdraw from study drug treatment, but consent to be followed for safety 
assessments and return to clinic for these visit, the visits will occur according to the protocol schedule.  Safety 
assessments should include clinical safety and basic lipid laboratories, adverse events (AEs), physical 
examination (PE), vital signs, and electrocardiograms (ECGs).  For patients who withdraw from study drug 
treatment, but consent to be followed for safety assessments by phone, the telephone contacts will occur 
according the protocol schedule with information regarding current health status and to collect information on 
AEs (eg, recent procedures, hospitalizations, and if the patient has died, the cause of death).  If a patient does 
not provide consent to be followed for safety assessments per the protocol (either by returning to clinic or by 
phone), Visit week 78 will be considered the End of Study (EOS)/Early Withdrawal from study and no 
further visits will be scheduled. 
1   All procedures will be completed for all patients at either EOS if completing the study or early withdrawal. 
2  Body weight will be measured in the morning while fasting, using consistent scales, after voiding, and 
without shoes and outerwear (eg, coats).   
3  Vital signs will include diastolic blood pressure (DBP), systolic blood pressure (SBP), heart rate (HR) and 
will be collected prior to any blood sample collection.  Patient will rest for 5 minutes prior to assessments 
4  Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits.  Please refer to 
laboratory manual for detailed schedule of tests. 
5 Basic fasting lipids include total cholesterol (TC), calculated low-density lipoprotein cholesterol (LDL-C), 
high-density lipoprotein cholesterol (HDL-C), non-HDL-C,), and triglycerides (TG). 
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Esperion Therapeutics, Inc. 
Version 1.0, Feb 14, 2017
Protocol: ETC-1002-050 
Statistical Analysis Plan
 
Confidential 
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6 Only in patients receiving anticoagulant therapy that in the investigator’s judgment require monitoring at 
Month 0 and 3 to 5 days post-Month 0 
7  Interactive web response system (IWRS) contact at either an early withdrawal or an EOS visit to register 
study discontinuation visit date 
 
 
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Esperion Therapeutics, Inc.
23-May-2019
Protocol: ETC-1002-050
Addendum to Statistical Analysis Plan
Confidential
Page 1 of 23
Statistical Analysis Plan for Study 1002-050, 120 Day Safety Update Interim Analysis
Title:
A MULTICENTER OPEN-LABEL EXTENSION (OLE) STUDY 
TO ASSESS THE LONG-TERM SAFETY AND EFFICACY OF 
BEMPEDOIC ACID (ETC-1002) 180 MG
Protocol:
ETC-1002-050
Clinical Phase:
3
Product:
ETC-1002
Date:
23-May-2019
Date
Esperion Therapeutics
Date
Esperion Therapeutics
Date
DocUUID : 8adc0e63-e069-47db-8837-9177fe71f2a0
f1330a26-8e65-4f1e-b28b-172f4186890d
28 May 2019 13:50:037+0000
REASON: I approve this document
29 May 2019 15:43:036+0000
REASON: I approve this document
fdfe4eec-c142-42c7-bf98-459047a30340
30 May 2019 20:06:038+0000
REASON: I approve this document
Page 80 of 129


Esperion Therapeutics, Inc.
23-May-2019
Protocol: ETC-1002-050
Addendum to Statistical Analysis Plan
Confidential
Page 2 of 23
Statistical Analysis Plan for Study 1002-050, Day 120 Safety Update Interim Analysis
An interim analysis for Day120 safety update will happen ≥ 4 months after the cutoff for 
the NDA submission (15-Mar-2019). The set of tables, listings and figures that were run 
for the NDA submission will be run again for the Day 120 safety update with additional 
tables and listings as described here.  In addition, all of the subject incidence treatment-
emergent adverse event (TEAE) tables as specified in the original SAP (dated as 05-Dec-
2018), will be replaced with exposure-adjusted tables. 
The lipid modifying treatment (LMT) use at the study baseline will be summarized by 
anatomic therapeutic chemical class and preferred term by treatment group in the parent 
study (1002-040) for the safety population.
The summary tables will be generated for incremental adverse events, serious adverse 
events, death, adverse events leading to discontinuation of investigational product and 
major adverse cardiac event by treatment group in the parent study (1002-040) for the 
safety population.
To calculate exposure-adjusted subject incidence, the number of subjects with at least one
incidence of a given treatment-emergent adverse event (TEAE) will be used as the 
numerator, and the exposure-years for all the subjects for that treatment-emergent adverse 
event will be used as the denominator. The exposure-years will be calculated as total 
person time (in person-years) at risk from on or after the first dose of IMP and up to last 
date of IMP+30 days or end of study date or analysis cut-off date whichever is earlier for 
subjects who did not have a given TEAE. For a subject with the TEAE, the exposure-year 
will be calculated as total person time from on or after first dose of IMP to the onset date of 
first occurrence of the given TEAE. In the tables by maximum severity, the first occurrence 
to the maximum severity of the TEAE will be used for the exposure calculation.
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Esperion Therapeutics, Inc.
23-May-2019
Protocol: ETC-1002-050
Addendum to Statistical Analysis Plan
Confidential
Page 3 of 23
The tables and listings for the Day 120 analyses:
Number
Title
Population
Table 14.1.1.1
Patient Disposition
The Enrolled 
Patients
Table 14.1.1.2
Major Protocol Deviation
Safety 
Population
Table 14.1.2.1
Demographic and Baseline Characteristics from 
the Parent ETC-1002-040 Study
Safety 
Population
Table 14.1.2.1.1
Demographic and Baseline Characteristics from 
OLE Study
Safety 
Population
Table 14.1.3.1
Medical History
Safety 
Population
Table 14.1.4.1
Cardiovascular History
Safety 
Population
Table 14.1.6.1
Concomitant Non-statin Medications by Anatomic 
Therapeutic Chemical Class and Preferred Term
Safety 
Population
Table 14.1.6.2
Concomitant Statin Medications by Anatomic 
Therapeutic Chemical Class and Preferred Term
Safety 
Population
Table 14.1.6.3
LMT Category at OLE Study (ETC-1002-050) 
Baseline by Anatomic Therapeutic Chemical Class 
and Preferred Term
Safety 
Population
Table 14.1.7
IMP Exposure
Safety 
Population
Table 14.2.1
Low-density Lipoprotein Cholesterol (LDL-C) 
Values and Changes and Percent Changes from 
Parent Study (ETC-1002-040) Baseline (Observed 
Data, Conventional Unit)
Safety 
Population
Table 14.2.1.1
Low-density Lipoprotein Cholesterol (LDL-C) 
Values and Changes and Percent Changes from 
Parent Study (ETC-1002-040) Baseline by Gender 
(Observed Data, Conventional Unit)
Safety 
Population
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Esperion Therapeutics, Inc.
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Protocol: ETC-1002-050
Addendum to Statistical Analysis Plan
Confidential
Page 4 of 23
Table 14.2.1.2
Low-density Lipoprotein Cholesterol (LDL-C) 
Values and Changes and Percent Changes from 
Parent Study (ETC-1002-040) Baseline by Age 
(Observed Data, Conventional Unit)
Safety 
Population
Table 14.2.1.3
Low-density Lipoprotein Cholesterol (LDL-C) 
Values and Changes and Percent Changes from 
Parent Study (ETC-1002-040) Baseline by 
Baseline CVD Risk Category (Observed Data, 
Conventional Unit)
Safety 
Population
Table 14.2.1.4
Low-density Lipoprotein Cholesterol (LDL-C) 
Values and Changes and Percent Changes from 
Parent Study (ETC-1002-040) Baseline by 
Baseline Statin Intensity Category (Observed Data, 
Conventional Unit)
Safety 
Population
Table 14.2.1.5
Low-density Lipoprotein Cholesterol (LDL-C) 
Values and Changes and Percent Changes from 
Parent Study (ETC-1002-040) Baseline by Race 
(Observed Data, Conventional Unit)
Safety 
Population
Table 14.2.1.6
Low-density Lipoprotein Cholesterol (LDL-C) 
Values and Changes and Percent Changes from 
Parent Study (ETC-1002-040) Baseline by 
Baseline LDL Category (Observed Data, 
Conventional Unit)
Safety 
Population
Table 14.2.1.7
Low-density Lipoprotein Cholesterol (LDL-C) 
Values and Changes and Percent Changes from 
Parent Study (ETC-1002-040) Baseline by History 
of Diabetes (Observed Data, Conventional Unit)
Safety 
Population
Table 14.2.1.8
Low-density Lipoprotein Cholesterol (LDL-C) 
Values and Changes and Percent Changes from 
Parent Study (ETC-1002-040) Baseline by 
Baseline BMI Group (Observed Data, Conventional 
Unit)
Safety 
Population
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Protocol: ETC-1002-050
Addendum to Statistical Analysis Plan
Confidential
Page 5 of 23
Table 14.2.1.9
Low-density Lipoprotein Cholesterol (LDL-C) 
Values and Changes and Percent Changes from 
Parent Study (ETC-1002-040) Baseline by Region 
(Observed Data, Conventional Unit)
Safety 
Population
Table 14.2.2
High-density Lipoprotein Cholesterol (HDL-C) 
Values and Changes and Percent Changes from 
Parent Study (ETC-1002-040) Baseline (Observed 
Data, Conventional Unit)
Safety 
Population
Table 14.2.3
Non-High-density Lipoprotein Cholesterol (Non -
HDL-C) Values and Changes and Percent 
Changes from Parent Study (ETC-1002-040) 
Baseline (Observed Data, Conventional Unit)
Safety 
Population
Table 14.2.4
Total Cholesterol (TC) Values and Changes and 
Percent Changes from Parent Study (ETC-1002-
040) Baseline (Observed Data, Conventional Unit)
Safety
Population
Table 14.2.5
Triglycerides (TG) Values and Changes and 
Percent Changes from Parent Study (ETC-1002-
040) Baseline (Observed Data, Conventional Unit)
Safety 
Population
Table 14.2.6
Apolipoprotein B (apo-B) Values and Changes and 
Percent Changes from Parent Study (ETC-1002-
040) Baseline (Observed Data, Conventional Unit)
Safety 
Population
Table 14.2.7
High-sensitivity C-reactive Protein (hs-CRP) Values 
and Changes and Percent Changes from Parent 
Study (ETC-1002-040) Baseline (Observed Data, 
Conventional Unit)
Safety 
Population
Table 14.2.8.1
Low-density Lipoprotein Cholesterol (LDL-C) 
Values and Changes and Percent Changes from 
Parent Study (ETC-1002-040) Baseline (Standard 
Unit)
Safety 
Population
Table 14.2.8.2
High-density Lipoprotein Cholesterol (HDL-C) 
Values and Changes and Percent Changes from 
Parent Study (ETC-1002-040) Baseline (Standard 
Unit)
Safety 
Population
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Protocol: ETC-1002-050
Addendum to Statistical Analysis Plan
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Page 6 of 23
Table 14.2.8.3
Non-High-density Lipoprotein Cholesterol (Non-
HDL-C) Values and Changes and Percent 
Changes from Parent Study (ETC-1002-040) 
Baseline (Standard Unit)
Safety 
Population
Table 14.2.8.4
Total Cholesterol (TC) Values and Changes and 
Percent Changes from Parent Study (ETC-1002-
040) Baseline (Standard Unit)
Safety 
Population
Table 14.2.8.5
Triglycerides (TG) Values and Changes and 
Percent Changes from Parent Study (ETC-1002-
040) Baseline  (Standard Unit)
Safety 
Population
Table 14.2.8.6
Apolipoprotein B (apo-B) Values and Changes and 
Percent Changes from Parent Study (ETC-1002-
040) Baseline (Standard Unit)
Safety 
Population
Table 14.2.8.7
High-sensitivity C-reactive Protein (phCRP) Values 
and Changes and Percent Changes from Parent 
Study (ETC-1002-040) Baseline (Standard Unit)
Safety 
Population
Table 14.2.9.1
Low-density Lipoprotein Cholesterol (LDL-C) 
Values and Changes and Percent Changes from 
Parent Study (ETC-1002-040) Baseline 
(Conventional Unit)
Completer 
Analysis Set
Table 14.2.9.2
High-density Lipoprotein Cholesterol (HDL-C) 
Values and Changes and Percent Changes from 
Parent Study (ETC-1002-040) Baseline 
(Conventional Unit)
Completer 
Analysis Set
Table 14.2.9.3
Non-High-density Lipoprotein Cholesterol (Non-
HDL-C) Values and Changes and Percent 
Changes from Parent Study (ETC-1002-040) 
Baseline by Age (Standard Unit)
Completer 
Analysis Set
Table 14.2.9.4
Total Cholesterol (TC) Values and Changes and 
Percent Changes from Parent Study (ETC-1002-
040) Baseline (Standard Unit)
Completer 
Analysis Set
Table 14.2.9.5
Triglycerides (TG) Values and Changes and 
Percent Changes from Parent Study (ETC-1002-
Completer 
Analysis Set
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Esperion Therapeutics, Inc.
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Protocol: ETC-1002-050
Addendum to Statistical Analysis Plan
Confidential
Page 7 of 23
040) Baseline (Conventional Unit)
Table 14.2.9.6
Apolipoprotein B (apo-B) Values and Changes and 
Percent Changes from Parent Study (ETC-1002-
040) Baseline (Conventional Unit)
Completer 
Analysis Set
Table 14.2.9.7
High-sensitivity C-reactive Protein (phCRP) Values 
and Changes and Percent Changes from Parent 
Study (ETC-1002-040) Baseline (Conventional 
Unit)
Completer 
Analysis Set
Table 14.2.10.1
Low-density Lipoprotein Cholesterol (LDL-C) 
Values and Changes and Percent Changes from 
Parent Study (ETC-1002-040) Baseline (Standard 
Unit)
Completer 
Analysis Set
Table 14.2.10.2
High-density Lipoprotein Cholesterol (HDL-C) 
Values and Changes and Percent Changes from 
Parent Study (ETC-1002-040) Baseline (Standard 
Unit)
Completer 
Analysis Set
Table 14.2.10.3
Non-High-density Lipoprotein Cholesterol (Non-
HDL-C) Values and Changes and Percent 
Changes from Parent Study (ETC-1002-040) 
Baseline (Standard Unit)
Completer 
Analysis Set
Table 14.2.10.4
Total Cholesterol (TC) Values and Changes and 
Percent Changes from Parent Study (ETC-1002-
040) Baseline (Standard Unit)
Completer 
Analysis Set
Table 14.2.10.5
Triglycerides (TG) Values and Changes and 
Percent Changes from Parent Study (ETC-1002-
040) Baseline  (Standard Unit)
Completer 
Analysis Set
Table 14.2.10.6
Apolipoprotein B (apo-B) Values and Changes and 
Percent Changes from Parent Study (ETC-1002-
040) Baseline (Standard Unit)
Completer 
Analysis Set
Table 14.2.10.7
High-sensitivity C-reactive Protein (phCRP) Values 
and Changes and Percent Changes from Parent 
Study (ETC-1002-040) Baseline (Standard Unit)
Completer 
Analysis Set
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Addendum to Statistical Analysis Plan
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Page 8 of 23
Table 14.2.11.1
Low-density Lipoprotein Cholesterol (LDL-C) 
Values and Changes and Percent Changes from 
Parent Study (ETC-1002-040) Baseline (Observed 
Data, Conventional Unit)
Safety 
Population
Table 14.2.11.2
High-density Lipoprotein Cholesterol (HDL-C) 
Values and Changes and Percent Changes from 
Baseline (Baseline in OLE Study) (Observed Data, 
Conventional Unit)
Safety 
Population
Table 14.2.11.3
Non-High-density Lipoprotein Cholesterol (Non -
HDL-C) Values and Changes and Percent 
Changes from Baseline (Baseline in OLE Study) 
(Observed Data, Conventional Unit)
Safety 
Population
Table 14.2.11.4
Total Cholesterol (TC) Values and Changes and 
Percent Changes from Baseline (Baseline in OLE 
Study) (Observed Data, Conventional Unit)
Safety 
Population
Table 14.2.11.5
Triglycerides (TG) Values and Changes and 
Percent Changes from Baseline (Baseline in OLE 
Study) (Observed Data, Conventional Unit)
Safety 
Population
Table 14.2.11.6
Apolipoprotein B (apo-B) Values and Changes and 
Percent Changes from Baseline (Baseline in OLE 
Study) (Observed Data, Conventional Unit)
Safety 
Population
Table 14.2.11.7
High-sensitivity C-reactive Protein (hs-CRP) Values 
and Changes and Percent Changes from Baseline 
(Baseline in OLE Study) (Observed Data, 
Conventional Unit)
Safety 
Population
Table 14.2.12.1
Low-density Lipoprotein Cholesterol (LDL-C) 
Values and Changes and Percent Changes from 
Parent Study (ETC-1002-040) Baseline (Observed 
Data, Standard Unit)
Safety 
Population
Table 14.2.12.2
High-density Lipoprotein Cholesterol (HDL-C) 
Values and Changes and Percent Changes from 
Baseline (Baseline in OLE Study) (Observed Data, 
Standard Unit)
Safety 
Population
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Table 14.2.12.3
Non-High-density Lipoprotein Cholesterol (Non -
HDL-C) Values and Changes and Percent 
Changes from Baseline (Baseline in OLE Study) 
(Observed Data, Standard Unit)
Safety 
Population
Table 14.2.12.4
Total Cholesterol (TC) Values and Changes and 
Percent Changes from Baseline (Baseline in OLE 
Study) (Observed Data, Standard Unit)
Safety 
Population
Table 14.2.12.5
Triglycerides (TG) Values and Changes and 
Percent Changes from Baseline (Baseline in OLE 
Study) (Observed Data, Standard Unit)
Safety 
Population
Table 14.2.12.6
Apolipoprotein B (apo-B) Values and Changes and 
Percent Changes from Baseline (Baseline in OLE 
Study) (Observed Data, Standard Unit)
Safety 
Population
Table 14.2.12.7
High-sensitivity C-reactive Protein (hs-CRP) Values 
and Changes and Percent Changes from Baseline 
(Baseline in OLE Study) (Observed Data, Standard 
Unit)
Safety 
Population
Table 14.3.1.1.1.1
Overview of Treatment-emergent Adverse Events
Safety 
Population
Table 14.3.1.1.1.2
Overview of Treatment-emergent Adverse Events 
by Gender
Safety 
Population
Table 14.3.1.1.1.3
Overview of Treatment-emergent Adverse Events 
by Age
Safety 
Population
Table 14.3.1.1.1.4
Overview of Treatment-emergent Adverse Events 
by Baseline CVD risk Category
Safety 
Population
Table 14.3.1.1.1.5
Overview of Treatment-emergent Adverse Events 
by Baseline Statin Intensity
Safety 
Population
Table 14.3.1.1.1.6
Overview of Treatment-emergent Adverse Events 
by Race
Safety 
Population
Table 14.3.1.1.1.7
Overview of Treatment-emergent Adverse Events 
by History of Diabetes
Safety 
Population
Table 14.3.1.1.1.8
Overview of Treatment-emergent Adverse Events 
by Baseline BMI Group
Safety 
Population
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Table 14.3.1.1.1.9
Overview of Treatment-emergent Adverse Events 
by Region
Safety 
Population
Table 14.3.1.1.2.1
Overview of Treatment-emergent Serious Adverse 
Events (TE SAE)
Safety 
Population
Table 14.3.1.1.2.2
Overview of Treatment-emergent Serious Adverse 
Events (TE SAE) by Gender
Safety 
Population
Table 14.3.1.1.2.3
Overview of Treatment-emergent Serious Adverse 
Events (TE SAE) by Age
Safety 
Population
Table 14.3.1.1.2.4
Overview of Treatment-emergent Serious Adverse 
Events (TE SAE) by Baseline CVD risk category
Safety 
Population
Table 14.3.1.1.2.5
Overview of Treatment-emergent Serious Adverse 
Events (TE SAE) by Baseline Statin Intensity
Safety 
Population
Table 14.3.1.1.2.6
Overview of Treatment-emergent Serious Adverse 
Events (TE SAE) by Race
Safety 
Population
Table 14.3.1.1.2.7
Overview of Treatment-emergent Serious Adverse 
Events (TE SAE) by History of Diabetes
Safety 
Population
Table 14.3.1.1.2.8
Overview of Treatment-emergent Serious Adverse 
Events (TE SAE) by Baseline BMI Group
Safety 
Population
Table 14.3.1.1.2.9
Overview of Treatment-emergent Serious Adverse 
Events (TE SAE) by Region
Safety 
Population
Table 14.3.1.2.2
Overview of Treatment-emergent Adverse Events 
Resulting in Withdrawal of Study Drug
Safety 
Population
Table 
14.3.1.3.1.1a
Incremental Treatment-emergent Adverse Events 
by System Organ Class, Preferred Term, and 
Maximum Severity
Safety 
Population
Table 
14.3.1.3.2.1a
Incremental Treatment-emergent Serious Adverse 
Events by System Organ Class, Preferred Term 
and Maximum Severity
Safety 
Population
Table 
14.3.1.3.3.3a
Incremental Treatment-emergent Adverse Events 
Resulting in Discontinuation of IMP by System 
Organ Class, Preferred Term and Maximum 
Severity
Safety 
Population
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Table 
14.3.1.3.3.4a
Incremental Treatment-emergent Fatal Adverse 
Events by System Organ Class, Preferred Term, 
and Maximum Severity
Safety 
Population
Table 14.3.2.2.1a
Incremental Treatment-emergent and Positively 
Adjudicated Adverse Cardiovascular Events by 
Event Type
Safety 
Population
Table 14.3.2.2.2
Exposure-Adjusted Subject Incidence of 
Treatment-emergent and Positivrely Adjudicated 
Adverse Cardiovascular Events by Event Type
Safety 
Population
Table 14.3.3.1.1
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events by System Organ Class, 
Preferred Term and Maximum Severity
Safety 
Population
Table 14.3.3.1.2
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events by System Organ Class, 
Preferred Term and Maximum Severity
Safety 
Population - by 
Gender
Table 14.3.3.1.3
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events by System Organ Class, 
Preferred Term and Maximum Severity
Safety 
Population - by 
Age
Table 14.3.3.1.4
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events by System Organ Class, 
Preferred Term and Maximum Severity
Safety 
Population –
by Baseline 
CVD risk 
Category
Table 14.3.3.1.5
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events by System Organ Class, 
Preferred Term and Maximum Severity
Safety 
Population –
by Baseline 
Statin Intensity
Table 14.3.3.1.6
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events by System Organ Class, 
Preferred Term and Maximum Severity
Safety 
Population –
by Race
Table 14.3.3.1.7
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events by System Organ Class, 
Preferred Term and Maximum Severity
Safety 
Population –
by History of 
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Diabetes
Table 14.3.3.1.8
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events by System Organ Class, 
Preferred Term and Maximum Severity
Safety 
Population –
by Baseline 
Body Mass 
Index (BMI) 
Group
Table 14.3.3.1.9
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events by System Organ Class, 
Preferred Term and Maximum Severity
Safety 
Population –
by Region
Table 14.3.3.2.1
Exposure-Adjusted Incidence of Treatment-
emergent Serious Adverse Events by System 
Organ Class, Preferred Term and Maximum 
Severity
Safety 
Population
Table 14.3.3.2.2
Exposure-Adjusted Incidence of Treatment-
emergent Serious Adverse Events by System 
Organ Class, Preferred Term and Maximum 
Severity
Safety 
Population - by 
Gender
Table 14.3.3.2.3
Exposure-Adjusted Incidence of Treatment-
emergent Serious Adverse Events by System 
Organ Class, Preferred Term and Maximum 
Severity
Safety 
Population - by 
Age
Table 14.3.3.2.4
Exposure-Adjusted Incidence of Treatment-
emergent Serious Adverse Events by System 
Organ Class, Preferred Term and Maximum 
Severity
Safety 
Population –
by Baseline 
CVD risk 
Category
Table 14.3.3.2.5
Exposure-Adjusted Incidence of Treatment-
emergent Serious Adverse Events by System 
Organ Class, Preferred Term and Maximum 
Severity
Safety 
Population –
by Baseline 
Statin Intensity
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Table 14.3.3.2.6
Exposure-Adjusted Incidence of Treatment-
emergent Serious Adverse Events by System 
Organ Class, Preferred Term and Maximum 
Severity
Safety 
Population –
by Race
Table 14.3.3.2.7
Exposure-Adjusted Incidence of Treatment-
emergent Serious Adverse Events by System 
Organ Class, Preferred Term and Maximum 
Severity
Safety 
Population –
by History of 
Diabetes
Table 14.3.3.2.8
Exposure-Adjusted Incidence of Treatment-
emergent Serious Adverse Events by System 
Organ Class, Preferred Term and Maximum 
Severity
Safety 
Population –
by Baseline 
Body Mass 
Index (BMI) 
Group
Table 14.3.3.2.9
Exposure-Adjusted Incidence of Treatment-
emergent Serious Adverse Events by System 
Organ Class, Preferred Term and Maximum 
Severity
Safety 
Population –
by Region
Table 14.3.3.3.3
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events Resulting in 
Discontinuation of IMP by System Organ Class, 
Preferred Term and Maximum Severity
Safety 
Population
Table 14.3.3.4.1
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events of Special Interest 
(AESIs) by System Organ Class, Preferred Term 
and Maximum Severity
Safety 
Population
Table 14.3.3.4.2
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events of Special Interest 
(AESIs) by System Organ Class, Preferred Term 
and Maximum Severity
Safety 
Population - by 
Gender
Table 14.3.3.4.3
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events of Special Interest 
(AESIs) by System Organ Class, Preferred Term 
Safety 
Population - by 
Age
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and Maximum Severity
Table 14.3.3.4.4
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events of Special Interest 
(AESIs) by System Organ Class, Preferred Term 
and Maximum Severity
Safety 
Population –
by Baseline 
CVD risk 
Category
Table 14.3.3.4.5
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events of Special Interest 
(AESIs) by System Organ Class, Preferred Term 
and Maximum Severity
Safety 
Population –
by Baseline 
Statin Intensity
Table 14.3.3.4.6
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events of Special Interest 
(AESIs) by System Organ Class, Preferred Term 
and Maximum Severity
Safety 
Population –
by Race
Table 14.3.3.4.7
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events of Special Interest 
(AESIs) by System Organ Class, Preferred Term 
and Maximum Severity
Safety 
Population –
by History of 
Diabetes
Table 14.3.3.4.8
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events of Special Interest 
(AESIs) by System Organ Class, Preferred Term 
and Maximum Severity
Safety 
Population –
by Baseline 
Body Mass 
Index (BMI) 
Group
Table 14.3.3.4.9
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events of Special Interest 
(AESIs) by System Organ Class, Preferred Term 
and Maximum Severity
Safety 
Population –
by Region
Table 14.3.3.5.1
Exposure-Adjusted Incidence of Related 
Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term
Safety 
Population
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Table 14.3.3.5.2
Exposure-Adjusted Incidence of Related 
Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term
Safety 
Population - by 
Gender
Table 14.3.3.5.3
Exposure-Adjusted Incidence of Related 
Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term
Safety 
Population - by 
Age
Table 14.3.3.5.4
Exposure-Adjusted Incidence of Related 
Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term
Safety 
Population –
by Baseline 
CVD risk 
Category
Table 14.3.3.5.5
Exposure-Adjusted Incidence of Related 
Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term
Safety 
Population –
by Baseline 
Statin Intensity
Table 14.3.3.5.6
Exposure-Adjusted Incidence of Related 
Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term
Safety 
Population –
by Race
Table 14.3.3.5.7
Exposure-Adjusted Incidence of Related 
Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term
Safety 
Population –
by History of 
Diabetes
Table 14.3.3.5.8
Exposure-Adjusted Incidence of Related 
Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term
Safety 
Population –
by Baseline 
Body Mass 
Index (BMI) 
Group
Table 14.3.3.5.9
Exposure-Adjusted Incidence of Related 
Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term
Safety 
Population –
by Region
Table 14.3.3.6.2
Exposure-Adjusted Incidence of Related 
Treatment-emergent Adverse Events of Special 
Safety 
Population
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Interest (AESIs) by System Organ Class and 
Preferred Term
Table 14.3.3.6.3
Exposure-Adjusted Incidence of Related 
Treatment-emergent Serious Adverse Events by 
System Organ Class and Preferred Term
Safety 
Population
Table 14.3.3.6.4
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events of Special Interest 
(AESIs) Resulting in Discontinuation of IMP by 
System Organ Class and Preferred Term
Safety 
Population
Table 14.3.3.7.1
Exposure-Adjusted Incidence of Treatment-
emergent Adverse Events by Preferred Term
Safety 
Population
Table 14.3.3.7.2
Exposure-Adjusted Incidence of Treatment-
emergent Serious Adverse Events by Preferred 
Term
Safety 
Population
Table 14.3.3.7.3
Exposure-Adjusted Incidence of Related 
Treatment-emergent Adverse Events by Preferred 
Term
Safety 
Population
Table 14.3.3.8.1
Exposure-Adjusted Subject Incidence of 
Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term
Safety 
Population
Table 14.3.3.8.2
Exposure-Adjusted Subject Incidence of Serious 
Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term
Safety 
Population
Table 14.3.3.8.3
Exposure-Adjusted Subject Incidence of Fatal 
Treatment-emergent Adverse Events by System 
Organ Class and Preferred Term
Safety 
Population
Table 14.3.4.1.1.1
Serum Chemistry Laboratory Values and Changes 
from Baseline (Conventional Unit)
Safety 
Population
Table 14.3.4.1.1.2
Hematology Laboratory Values and Changes from 
Baseline (Conventional Unit)
Safety 
Population
Table 14.3.4.1.1.3
Coagulation Laboratory Values and Changes from 
Baseline (Conventional Unit)
Safety 
Population
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Table 14.3.4.1.1.4
Urinalysis Laboratory Values and Changes from 
Baseline (Conventional Unit)
Safety 
Population
Table 14.3.4.1.1.5
Alanine Aminotransferase (ALT), Aspartame 
Aminotransferase (AST) and Total Bilirubin Values 
and Changes from Baseline (Conventional Unit)
Safety 
Population
Table 14.3.4.1.1.6
Creatinine Kinase Values and Changes from 
Baseline  (Conventional Unit)
Safety 
Population
Table 14.3.4.1.1.7
Creatinine Kinase Values and Changes from 
Baseline by Treatment and Baseline Estimated 
Glomerular Filtration Rate (eGFR) Category 
(Conventional Unit)
Safety 
Population
Table 14.3.4.1.1.8
HbA1C and Fasting Glucose Laboratory Values 
and Changes from Baseline by History of Diabetics 
(Conventional Unit)
Safety 
Population
Table 14.3.4.1.2.1
Serum Chemistry Laboratory Values and Changes 
from Parent Study (ETC-1002-040) Baseline 
(Standard Unit)
Safety 
Population
Table 14.3.4.1.2.2
Hematology Laboratory Values and Changes from 
Parent Study (ETC-1002-040) Baseline (Standard 
Unit)
Safety 
Population
Table 14.3.4.1.2.3
Coagulation Laboratory Values and Changes from 
Parent Study (ETC-1002-040) Baseline (Standard 
Unit)
Safety
Population
Table 14.3.4.1.2.4
Urinalysis Laboratory Values and Changes from 
Parent Study (ETC-1002-040) Baseline (Standard 
Unit)
Safety 
Population
Table 14.3.4.1.2.5
Alanine Aminotransferase (ALT), Aspartame 
Aminotransferase (AST) and Total Bilirubin Values 
and Changes from Baseline (Standard Unit)
Safety 
Population
Table 14.3.4.1.2.6
Creatinine Kinase Values and Changes from 
Parent Study (ETC-1002-040) Baseline  (Standard 
Unit)
Safety 
Population
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Table 14.3.4.1.2.7
Creatinine Kinase Values and Changes from 
Parent Study (ETC-1002-040) Baseline by 
Treatment and Baseline Estimated Glomerular 
Filtration Rate (eGFR) Category (Standard Unit)
Safety 
Population
Table 14.3.4.1.2.8
HbA1C and Fasting Glucose Laboratory Values 
and Changes from Parent Study (ETC-1002-040) 
Baseline by History of Diabetics (Standard Unit)
Safety 
Population
Table 14.3.4.2.1
Serum Chemistry Laboratory Abnormalities
Safety 
Population
Table 14.3.4.2.2
Hematology Laboratory Abnormalities
Safety 
Population
Table 14.3.4.2.3
Coagulation Laboratory Abnormalities
Safety 
Population -
Patients Using 
Anticoagulatio
n Medication
Table 14.3.4.2.4
Urinalysis Laboratory Abnormalities
Safety 
Population
Table 14.3.4.2.5
Alanine Aminotransferase (ALT) Abnormalities 
(Overall, by Normal Baseline ALT and by Abnormal 
Baseline ALT)
Safety 
Population
Table 14.3.4.2.6
Aspartate Aminotransferase (AST) Abnormalities 
(Overall, by Normal Baseline AST and by Abnormal 
Baseline AST)
Safety 
Population
Table 14.3.4.2.7
Total Bilirubin (TB) Abnormalities (Overall, by
Normal Baseline TB and by Abnormal Baseline TB)
Safety 
Population
Table 14.3.4.2.8
Creatinine Kinase Laboratory Abnormalities 
(Overall, by Normal Baseline CK and by Abnormal 
Baseline CK)  
Safety 
Population
Table 14.3.4.2.9.1
Laboratory Abnormalities of Fasting Glucose by 
History of Diabetes
Safety 
Population
Table 14.3.4.2.9.2
Laboratory Abnormalities of HbA1C by History of 
Diabetes
Safety 
Population
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Table 14.3.4.2.10
Laboratory Abnormalities of Renal Function
Safety 
Population
Table 14.3.4.2.11
Laboratory Parameters of Interest: Laboratory 
Abnormalities by Derived Baseline Statin Intensity 
of Parent Study (1002-040)
Safety 
Population
Table 14.3.4.3.1.1
Serum Chemistry Laboratory Values and Changes 
from Baseline (Baseline in OLE Study) 
(Conventional Unit)
Safety 
Population
Table 14.3.4.3.1.2
Hematology Laboratory Values and Changes from 
Baseline (Baseline in OLE Study) (Conventional 
Unit)
Safety 
Population
Table 14.3.4.3.1.3
Coagulation Laboratory Values and Changes from 
Baseline (Baseline in OLE Study) (Conventional 
Unit)
Safety 
Population
Table 14.3.4.3.1.4
Urinalysis Laboratory Values and Changes from 
Baseline (Baseline in OLE Study) (Conventional 
Unit)
Safety 
Population
Table 14.3.4.3.1.5
Alanine Aminotransferase (ALT), Aspartame 
Aminotransferase (AST) and Total Bilirubin Values 
and Changes from Baseline (Baseline in OLE 
Study) (Conventional Unit)
Safety 
Population
Table 14.3.4.3.1.6
Creatinine Kinase Values and Changes from 
Baseline (Baseline in OLE Study) (Conventional 
Unit)
Safety 
Population
Table 14.3.4.3.1.7
Creatinine Kinase Values and Changes from 
Baseline by Treatment and Baseline Estimated 
Glomerular Filtration Rate (eGFR) Category 
(Baseline in OLE Study) (Conventional Unit)
Safety 
Population
Table 14.3.4.3.1.8
HbA1C and Fasting Glucose Laboratory Values 
and Changes from Baseline (Baseline in OLE 
Study) (Conventional Unit)
Safety 
Population
Table 14.3.4.3.2.1
Serum Chemistry Laboratory Values and Changes 
from Baseline (Baseline in OLE Study) (Standard 
Safety 
Population
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Unit)
Table 14.3.4.3.2.2
Hematology Laboratory Values and Changes from  
Baseline (Baseline in OLE Study) (Standard Unit)
Safety 
Population
Table 14.3.4.3.2.3
Coagulation Laboratory Values and Changes from 
Baseline (Baseline in OLE Study) (Standard Unit)
Safety 
Population
Table 14.3.4.3.2.4
Urinalysis Laboratory Values and Changes from 
Baseline (Baseline in OLE Study) (Standard Unit)
Safety 
Population
Table 14.3.4.3.2.5
Alanine Aminotransferase (ALT), Aspartame 
Aminotransferase (AST) and Total Bilirubin Values 
and Changes from Baseline (Baseline in OLE 
Study) (Standard Unit)
Safety 
Population
Table 14.3.4.3.2.6
Creatinine Kinase Values and Changes from 
Baseline (Baseline in OLE Study) (Standard Unit)
Safety 
Population
Table 14.3.4.3.2.7
Creatinine Kinase Values and Changes from 
Baseline by Treatment and Baseline Estimated 
Glomerular Filtration Rate (eGFR) Category 
(Baseline in OLE Study) (Standard Unit)
Safety 
Population
Table 14.3.4.3.2.8
HbA1C and Fasting Glucose Laboratory Values 
and Changes from Baseline (Baseline in OLE 
Study) (Standard Unit)
Safety 
Population
Table 14.3.6.1.1
Estimated Glomerular Filtration Rate (eGFR) 
Values and Change from Parent Study (ETC-1002-
040) Baseline
Safety 
Population
Table 14.3.6.1.2
Estimated Glomerular Filtration Rate (eGFR) 
Values and Change from Baseline (Baseline in 
OLE Study)
Safety 
Population
Table 14.3.6.2.1
Shift Table of Estimated Glomerular Filtration Rate 
(eGFR) Category from Baseline of Parent Study 
(ETC-1002-040) over the Study 
Safety 
Population
Table 14.3.6.2.2
Shift Table of Estimated Glomerular Filtration Rate 
(eGFR) Category from Baseline of OLE Study over 
the Study 
Safety 
Population
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Table 14.3.6.3.1
Shift Table of Urine Protein from Baseline of Parent 
Study (ETC-1002-040) over the Study
Safety 
Population
Table 14.3.6.3.2
Shift Table of Urine Protein from Baseline of OLE 
Study over the Study
Safety 
Population
Table 14.3.6.4
Post-Baseline of OLE Abnormal Liver Function 
Summary
Safety 
Population
Table 14.3.7
Vital Signs Values and Changes from Parent Study 
(ETC-1002-040) Baseline
Safety 
Population
Table 14.3.7.2
Vital Signs Values and Changes from OLE Study 
(ETC-1002-050) Baseline
Safety 
Population
Listing 16.2.1
Patient Disposition
All Enrolled 
Patients
Listing 16.2.2
Protocol Deviations
Safety 
Population
Listing 16.2.3.2
Cardiovascular History and Cardiovascular Risk 
Factors
Safety 
Population
Listing 16.2.4.5
Medical History from Parent Study ETC-1002-040
Safety 
Population
Listing 16.2.4.5.2
New Medical History during Rollover Period
Safety 
Population 
(Patients 
Entered the 
OLE Study 
beyond 30-Day 
Rollover 
Window)
Listing 16.2.4.6
Concomitant Non-statin Medications
Safety 
Population
Listing 16.2.4.7
Concomitant Statin Medications
Safety 
Population
Listing 16.2.5.1
Exposure
Safety 
Population
Listing 16.2.5.2
IMP Administration
Safety 
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Population
Listing 16.2.6.1
Lipids 
FAS
Listing 16.2.7.1
Adverse Events
Safety 
Population
Listing 16.2.7.1.2
Adverse Events Occurred during Rollover Period 
(Between End of Parent Study and Treatment Start 
of OLE Study)
Safety 
Population
Listing 16.2.7.2
Serious Adverse Events 
Safety 
Population
Listing 16.2.7.2.1
Incremental Listing of Serious Adverse Events
Safety 
Population
Listing 16.2.7.3
Adverse Events Resulting in Withdrawal of IMP
Safety 
Population
Listing 16.2.7.3.1
Incremental Listing of Adverse Events Resulting in 
Withdrawal of Study Drug
Safety 
Population
Listing 16.2.7.4
Related Treatment-emergent Adverse Events 
Safety 
Population
Listing 16.2.7.5
Deaths
Safety 
Population
Listing 16.2.7.5.1
Incremental Listing of Deaths
Safety 
Population
Listing 16.2.7.7
Adverse Events of Special Interest 
Safety 
Population
Listing 16.2.7.8
Adjudicated Major Adverse Cardiovascular Events 
and Mortality (MACE) and Non-MACE Events
Safety 
Population
Listing 16.2.8.1.1
Categorical Urinalysis Safety Laboratory
Safety 
Population
Listing 16.2.8.1.2
Chemistry Safety Laboratory
Safety 
Population
Listing 16.2.8.1.3
Hematology Safety Laboratory
Safety 
Population
Listing 16.2.8.1.4
Coagulation Safety Laboratory
Safety
Population
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Listing 16.2.8.1.5
Urinalysis Safety Laboratory
Safety 
Population
Listing 16.2.8.1.6
Safety Laboratory Abnormalities
Safety 
Population
Listing 16.2.8.1.7
Safety Laboratory Parameters of Interest
Safety 
Population
Listing 16.2.8.1.8
Direct Bilirubin Values in Subjects with Gilbert’s 
Disease 
Safety 
Population
Listing 16.2.8.1.9.1
Serum Pregnancy Test
Safety 
Population
Listing 16.2.8.1.9.2
Urine Pregnancy Test
Safety 
Population
Listing 16.2.10
Physical Examination
Safety 
Population
Listing 16.2.11
Vital Signs
Safety 
Population
Figure 14.2.1
Mean (+/- SE) Low-density Lipoprotein Cholesterol 
(LDL-C) Values by Visit (Observed Data)
Safety 
Population
Figure 14.2.2
Mean (+/- SE) High-density Lipoprotein Cholesterol 
(HDL-C) Values by Visit (Observed Data)
Safety 
Population
Figure 14.2.3
Mean (+/- SE) Non-High-density Lipoprotein 
Cholesterol (Non - HDL-C) Values by Visit 
(Observed Data)
Safety 
Population
Figure 14.2.4
Mean (+/- SE) Total Cholesterol (TC) Values by 
Visit (Observed Data)
Safety 
Population
Figure 14.2.5.2
Median (IQR) Triglycerides (TG) Values by Visit 
(Observed Data)
Safety 
Population
Figure 14.2.6
Mean (+/- SE) Apolipoprotein B (apo-B) Values by 
Visit (Observed Data)
Safety 
Population
Figure 14.2.7.2
Median (IQR) High-sensitivity C-reactive Protein 
(hs-CRP) Values by Visit (Observed Data)
Safety 
Population
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Esperion Therapeutics, Inc. 
Version 1.3, Dec 04, 2019 
Protocol: ETC-1002-050 
Statistical Analysis Plan 
Confidential 
Page 2 of 27 
Table of Contents 
1 
List of Abbreviations .................................................................................................. 4 
2 
Introduction ................................................................................................................. 6 
3 
Study Objectives and Endpoints ................................................................................. 6 
3.1 
Objectives ............................................................................................................. 6 
3.2 
Endpoint ............................................................................................................... 6 
Primary Endpoint (Safety) .............................................................................................. 6 
Secondary Endpoints (Efficacy) ...................................................................................... 6 
3.2.1 
Adverse Events ............................................................................................. 7 
3.2.2 
Clinical Safety Laboratories ......................................................................... 7 
3.2.3 
Vital Signs ..................................................................................................... 7 
3.2.4 
Physical Exam ............................................................................................... 8 
3.2.5 
Lipids ............................................................................................................ 8 
4 
Study Design ............................................................................................................... 8 
4.1 
Study Design ........................................................................................................ 8 
4.2 
Study Treatments and Assessments ..................................................................... 9 
4.3 
Randomization and Blinding .............................................................................. 10 
4.4 
Sample Size Justification ................................................................................... 10 
4.5 
Interim Analyses, Final Analyses, and Unblinding ........................................... 10 
4.6 
Change from Planned Analyses in Protocol ....................................................... 11 
5 
Statistical and Analytical Plans ................................................................................. 11 
5.1 
General Statistical Considerations ..................................................................... 11 
5.2 
Statistical Analysis Plans ................................................................................... 12 
5.2.1 
Analysis Sets ............................................................................................... 12 
5.2.1.1 
Safety Population (SP)......................................................................... 12 
5.2.1.2 
Completer Analysis Set (CAS) ............................................................ 12 
5.2.2 
Protocol Violations and Deviations ............................................................ 12 
5.2.3 
Subject Disposition ..................................................................................... 12 
5.2.4 
Demographic and Baseline Characteristics ................................................ 13 
5.2.5 
Subgroup Variables ..................................................................................... 13 
5.2.6 
Medical History .......................................................................................... 14 
5.2.7 
Concomitant Medications ........................................................................... 14 
5.2.8 
Study Drug Exposure and Compliance ....................................................... 14 
5.3 
Efficacy Endpoints and Analyses ....................................................................... 15 
5.4 
Safety Data Endpoints and Analyses ................................................................. 15 
5.4.1 
Adverse Events (AEs) ................................................................................. 15 
5.4.2 
Adverse Events of Special Interest ............................................................. 17 
5.4.2.1 
Neurocognitive Events ........................................................................ 17 
5.4.3 
Clinical Cardiovascular Endpoints ............................................................. 18 
5.4.4 
Laboratory Evaluations ............................................................................... 18 
5.4.4.1 
Hepatic Safety ...................................................................................... 21 
5.4.4.2 
Musculoskeletal Safety ........................................................................ 21 
5.4.4.3 
Diabetes and Glycemia ........................................................................ 21 
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5.4.4.4 
Renal Safety ......................................................................................... 22 
5.4.5 
Physical Examination (PE) ......................................................................... 22 
5.4.6 
Vital Signs and Weight ............................................................................... 22 
6 
DMC Analyses .......................................................................................................... 22 
7 
Reference .................................................................................................................. 23 
8 
Appendices ................................................................................................................ 24 
8.1 
Appendix 1: Schedule of Events (Subject Visit Schedule) ................................ 24 
8.2 
Appendix 2: Adverse Event of Special Interest (AESI) ..................................... 26 
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1 List of Abbreviations  
Abbreviation or Specialist Term 
Explanation 
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 
BMI 
Body mass index 
BP 
Blood pressure 
BUN 
Blood urea nitrogen 
Ca 
Calcium 
CAS 
Completer Analysis Set 
CEC 
Clinical Event Committee 
CI 
Confidence interval 
CK 
Creatine kinase 
Cl 
Chloride 
CO2 
Carbon dioxide 
CV 
Cardiovascular 
DBP 
Diastolic blood pressure 
DMC 
Data Monitoring Committee 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
eGFR 
Estimated glomerular filtration rate 
EOS 
End of Study 
ETC-1002 
Bempedoic acid 
FDA 
Food and Drug Administration 
FPFV 
First patient first visit 
HbA1C 
Glycosylated hemoglobin, Type A1C 
Hct 
Hematocrit 
HDL-C 
High-density lipoprotein cholesterol 
HeFH 
Heterozygous familial hypercholesterolemia 
Hgb 
Hemoglobin 
hs-CRP 
High-sensitivity C-reactive protein 
ICH 
International Conference on Harmonisation 
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Abbreviation or Specialist Term 
Explanation 
IMP 
Investigational medicinal product 
ITT 
Intention-to-treat 
IWRS 
Interactive web response system 
K 
Potassium 
LDH 
Lactate dehydrogenase 
LDL-C 
Low-density lipoprotein cholesterol 
LMT 
Lipid modifying therapy  
LPLV 
Last patient last visit 
LS 
Least square 
MACE 
Major adverse cardiac event 
MCH 
Mean corpuscular hemoglobin 
MCHC 
Mean corpuscular hemoglobin concentration 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Myocardial infarction 
Na 
Sodium 
non-HDL-C 
Non-high-density lipoprotein cholesterol 
OLE 
Open-label extension  
Parent study 
Study 1002-040 
PE 
Physical exam 
PT 
Preferred term 
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 
SI 
International system of units 
SOC 
System organ class 
SP 
Safety population 
TB 
Total bilirubin 
TC 
Total cholesterol 
TEAE 
Treatment-emergent adverse event 
TESAE 
Treatment-emergent serious adverse event 
TG 
Triglycerides 
ULN 
Upper limit of normal 
WBC 
White blood cell 
WHO 
World Health Organization 
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2 Introduction 
The purpose of this document is to describe the statistical methods, data derivations and 
data summaries to be employed in ETC-1002-050. The preparation of this statistical 
analysis plan (SAP) has been based on International Conference on Harmonisation (ICH) 
E3 and E9 Guidelines and in reference to Protocol ETC-1002-050 (Protocol Amendment 2, 
15Jan2018).  
The SAP will supersede the protocol in the event of any differences between the two 
documents in the plans for data analysis, and the protocol will be amended if appropriate. 
The SAP will be included as an appendix in the clinical study report for this protocol. 
3 Study Objectives and Endpoints 
3.1 Objectives 
x The primary objective for this study is to characterize the safety and tolerability of 
long-term administration of bempedoic acid (ETC-1002) 180 mg  
 
x The secondary objective is to characterize the efficacy of long-term administration 
of bempedoic acid 180 mg/day as assessed by changes in low-density lipoprotein 
cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-high-
density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total 
cholesterol (TC), triglycerides TG, and high-sensitivity C-reactive protein (hs-CRP) 
in patients with hyperlipidemia  
 
3.2 Endpoint 
Primary Endpoint (Safety) 
x The primary endpoint for this study is patient incidence of treatment-emergent 
adverse events (TEAEs) 
Secondary Endpoints (Efficacy) 
x Percent change from baseline in LDL-C at Weeks 52 and 78 
x Change from baseline in LDL-C at Weeks 52 and 78  
x Percent change from baseline in non-HDL-C at Weeks 52 and 78 
x Percent change from baseline in TC at Weeks 52 and 78 
x Percent change from baseline in ApoB at Weeks 52 and 78 
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x Percent change from baseline in hs-CRP at Weeks 52 and 78 
x Percent change from baseline in TG at Weeks 52 and 78 
x Percent change from baseline in HDL-C at Weeks 52 and 78 
Other Safety Endpoints 
x Laboratory Results 
x Physical Measurements 
x Vital Signs 
x Hepatic Safety 
x Musculoskeletal Safety 
x Diabetes and Hyperglycemia 
x Renal Safety 
x Neurocognitive Events 
x Clinical Endpoints 
3.2.1 Adverse Events 
The evaluation of adverse events (AEs) will include only incidence of TEAEs, defined as 
AEs that begin or worsen on or after the date of first dose of study drug administration in 
open-label extension (OLE) period and until 30 days after last dose of study drug. AESI 
will be examined further (See Section 5.4.2 for more information).  
Clinical endpoints (details see section 4.2) will be collected and adjudicated by an 
independent Clinical Events Committee (CEC). Clinical endpoints will also be reported as 
AEs.   
3.2.2 Clinical Safety Laboratories 
The evaluation of clinical safety laboratories, including blood hematology, chemistry, 
coagulation, and urinalysis will be based on the observed values. Observed values, change 
from baseline, and percent change from baseline of both the parent study and OLE study 
will be summarized for all the scheduled post-baseline visits. 
3.2.3 Vital Signs  
The evaluation of vital signs (including heart rate, systolic blood pressure, and diastolic 
blood pressure, and weight and BMI) will be based on the observed values. The summary 
of the observed values and change from baseline will be performed for all the scheduled 
visits based on the baseline of the parent study and OLE study. Baseline height will be 
summarized and will be used in the BMI calculations over time. 
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3.2.4 Physical Exam 
Listings of PE data will include only those records where the body system at the baseline 
PE was normal, but the body system at a post-baseline PE was marked as ‘Change from 
previous exam, clinically significant.’   
3.2.5 Lipids  
After enrollment, patients will return to clinic at Weeks 12, 52, 78/EOT, and 82/EOS.  
Clinical laboratory samples will be collected and analyzed for calculated LDL-C and lipid 
and cardiometabolic biomarkers including non-HDL-C, HDL-C, TC, ApoB, and TG at 
baseline and all clinic visits for evaluation of bempedoic acid effects on lipids and 
cardiometabolic parameters.  
4 Study Design 
4.1 Study Design 
This is a multicenter OLE study designed to assess the long-term safety and efficacy of 
bempedoic acid (ETC-1002) 180 mg. All patients will receive open-label bempedoic acid 
180 mg for up to 1.5 years after rolling over from the parent study (Study 1002-040) 
followed by a follow-up period off study drug for 4 weeks. Investigators, site staff, patients, 
and the study team will be masked to study lipid levels until the Week 12 study visit, after 
which time lipid values will be made available. 
An independent expert Data Monitoring Committee (DMC) will formally review 
accumulating unblinded safety and efficacy data from this and other ongoing studies of 
bempedoic acid.  A blinded independent expert Clinical Events Committee (CEC) will 
adjudicate designated clinical endpoints across the program, including all major adverse 
cardiac events (MACE) and non-MACE endpoints defined as:  cardiovascular (CV) death 
(MACE), non-CV death (non-MACE), nonfatal myocardial infarction [MI] (MACE), 
nonfatal stroke (MACE), hospitalization for unstable angina (MACE), coronary 
revascularization (MACE), noncoronary 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 as well 
as a clinical endpoint. 
The study will be conducted at approximately 125 clinical sites in the United States, 
Canada, Germany, Netherlands, Poland, and United Kingdom. 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 2.5 years. 
 
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Figure 1. Study 1002-050 Study Design 
 
4.2 Study Treatments and Assessments 
Day 1 for this study should occur on the same day as the end of study visit for the parent 
study (1002-040).  Patients who provide informed consent will be eligible to enroll in the 
study.   
The schedule of study events is provided in Appendix 1.  However, a patient can be seen at 
any time for reasons of safety.  
The investigational products were listed in Table 1 below: 
Table 1: 
Investigational Medicinal Products 
 
 
Investigational Medicinal Product 
Product Name: 
Bempedoic acid 
Dosage Form: 
Film-coated tablets 
Unit Dose: 
180 mg 
Container/Closurea 
100-count bottle with screw on, child proof cap 
Route of Administration: 
Oral, daily with or without food 
Physical Description: 
Manufacturer 
(Fill/Finish): 
 
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Study drug should be taken once a day (once every 24 hours) at approximately the same 
time every day and may be taken with or without food.  Patients will fast (no food or drink, 
other than water) for a minimum of 10 hours prior to collection of all laboratory samples. 
Please see Pharmacy Manual for detailed storage requirements and instructions. 
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 Appendix 1: Schedule of Events (Subject 
Visit Schedule).   
An independent expert Data Monitoring Committee (DMC) will formally review 
accumulating unblinded safety and efficacy data from this and other any 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 serious adverse event (SAE) 
criteria will be reported as SAEs. 
4.3 Randomization and Blinding 
Randomization is not applicable for this OLE study.  
Laboratory results for lipid panel and hs-CRP will be masked to investigators, patients, and 
the study team until the Week 12 visit is completed.  All site staff involved with this trial 
should refrain from obtaining lipid panels between date of last study medication 
(bempedoic acid or placebo) dose at end of parent study Week 52 (Visit T7) and Week 12 
in this OLE trial. 
4.4 Sample Size Justification 
The number of patients entering this study will depend on the number of patients 
completing Study 1002-040 and their willingness to enroll.   
4.5 Interim Analyses, Final Analyses, and Unblinding 
An interim analysis will be conducted in 2H 2018 in order to provide safety assessment to 
support NDA submission. Another interim analysis for Day120 safety update will be 
approximately 120 days after the NDA cutoff. The endpoints and analyses are the same as 
those defined in final analysis if applicable.  
The final analysis will be performed after the database is locked. 
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4.6 Change from Planned Analyses in Protocol 
There is no change from planned analyses for this study. 
5 Statistical and Analytical Plans 
5.1 General Statistical Considerations 
The treatment groups will be displayed as previous treatment in parent study as well as 
overall treatment group in OLE study.   
In general, all safety and efficacy data will be reported as observed. No imputation will be 
performed for missing data. Descriptive statistics (n, mean, standard deviation, median, Q1, 
Q3, minimum, and maximum) will be calculated for continuous data. Minimum and 
maximum will be presented same number of decimal places as reported/collected, one 
additional decimal place for mean and median, and two additional decimal places for 
standard deviation. Ninety-five percent (95%) confidence intervals (CIs) will be calculated 
for select continuous endpoint estimates. 
Categorical data will be summarized using n and percentage based on number of non-
missing values. Percentage will be presented with one decimal place. The number of 
missing values will be presented as a separate category with no percentage, but only if 1 or 
more patients are missing data for the summary. Otherwise, all categories will be presented 
(even if no patients are counted in the category). Counts of zero in any category will be 
presented without percentage.  
Data will be presented on listings by prior treatment group in the parent study, subject ID, 
assessment (in order collected on CRF, unless specified otherwise), and assessment date. 
Dates will be presented in format DDMMMYYYY. 
Relative day calculations will be [date of interest – relative date + (date of interest >= 
relative date)]. This calculation will result in dates prior to the relative date being presented 
as negative days, and those occurring on or after the relative date as Day 1 or later, i.e., 
there will be no Day 0. 
Two sets of baseline are defined for applicable endpoints: baseline in parent study (1002-
040) and baseline in OLE study (1002-050). The parent baseline values will be directly 
extracted from parent study database. The baseline for the OLE study is defined as the last 
non-missing value on or prior to the date of first dose in the OLE.  
If last dose of study treatment is missing, then the end of study date or death date, 
whichever occurs earlier, will be used in its place.  
The visit schedules and windows are shown below:  
Visit 
Day 1/Week 0 
Week 12 
Week 24 
Week 36 
Week 52 
Week 64 
Week 
78/EOT 
Week 
82/EOS 
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Month 
0 
3 
6 
9 
12 
15 
18/EOT 
19/EOS 
Slotted 
Study 
Week 
EOS Parent 
Wk 12 
Wk 24 
Wk 36 
Wk 52 
Wk 64 
Wk 78 
Wk 82 
Target Study 
Day 
1 
84 
168 
252 
364 
448 
546 
574 
Analysis 
Window  
1 
[2,126] 
[127,210] 
[211,308] 
[309,406] 
[407,497] 
[498,562] 
[563,∞] 
Protocol 
defined visit 
Windows 
[30 Days, Pre 
M0] 
84±7 
168±7 
252±7 
364±7 
448±7 
546±7 
574±14 
 
5.2 Statistical Analysis Plans 
5.2.1 Analysis Sets 
5.2.1.1 Safety Population (SP) 
The SP is defined as all enrolled patients who received at least 1 dose of bempedoic acid 
during the OLE period and will be used for demographics and baseline characteristics, 
treatment exposure, concomitant medications, safety and efficacy summaries. If all subjects 
receive at least one dose of bempedoic acid in this study, the SP will be used for all 
efficacy analyses as well.   
5.2.1.2 Completer Analysis Set (CAS) 
The CAS is defined as the patients who completed the full 78 weeks treatment as per End 
of Treatment CRF page.  
5.2.2 Protocol Violations and Deviations 
A full list of protocol violations and deviations will be compiled and reviewed by the 
clinical team to identify key versus non-key violations/deviations before final database 
lock. For violations at study entry, patients will be assessed against the inclusion and 
exclusion criteria of the protocol. For on-study deviations, compliance with the protocol 
will be examined with regard to prohibited therapies, and timing and availability of planned 
assessments. The final list of protocol deviation will be approved by the study team prior to 
interim analysis cut of or final database lock, and will be used to generate the protocol 
deviation summary and listing. 
5.2.3 Subject Disposition  
The number of patients enrolled, and included in each analysis population, along with IMP 
and study completion status, will be summarized by the treatment group in parent ETC-
1002-040 study and overall. In addition, the number of patients who withdraw from the 
study and withdraw from study drug will be summarized by discontinuation reason. 
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5.2.4 Demographic and Baseline Characteristics  
Two sets of baseline values will be defined: baseline of parent study and OLE study. The 
parent study baseline will be taken directly from the parent study, and the OLE baseline is 
defined as last non-missing value prior to the first dose of IMP in the OLE study. The 
following demographic and both baseline characteristics will be summarized using 
descriptive statistics by previous treatment group in parent study, as well as overall, for 
safety population:  
 
x Age group (18-40, 41-64, 65-74, and >=75 years), gender, race, ethnicity, region 
(North America, and Europe), height (cm), weight (kg), body mass index (BMI) 
(kg/m2) (< 25, 25 - < 30, ≥ 30 kg/ m2), , systolic and diastolic blood pressure, 
fasting lipid parameters (TC, LDL-C, HDL-C, non-HDL-C, and TG), apoB, and hs-
CRP. 
 
x Cardiovascular risk factors from the parent study: ASCVD (Yes/No), HeFH 
(Yes/No), baseline statin intensity (derived) (low or moderate, high), eGFR 
category, tobacco history, alcohol history, history of diabetics, and history of 
hypertension.  
 
x 
The baseline estimated glomerular filtration rate (eGFR) categories are: normal: 
≥90 mL/min/1.73m2; mild Renal Impairment: 60-89 mL/min/1.73m2; moderate 
Renal Impairment: 30-59 mL/min/1.73m2, and severe Renal Impairment (15-29 
mL/min/1.73m2). 
5.2.5 Subgroup Variables  
Subgroups defined by below variables will be evaluated for safety and the LDL-C efficacy 
endpoint.  
 
1) Gender (male vs. female) 
 
2) Age (< 65 yrs. vs. ≥ 65 yrs. and < 75 yrs. vs. ≥ 75 yrs.) 
 
3) Baseline CVD risk category (HeFH (with/without ASCVD) vs. ASCVD only) 
 
4) Baseline statin intensity (low vs. moderate vs. high) 
 
5) Race (White vs. other) 
 
6) Baseline LDL category (< 100 mg/dL vs. ≥100 mg/dL) (efficacy only) 
 
7) History of diabetes (yes vs. no) 
 
8) Body Mass Index (BMI) (< 25, 25 - < 30, ≥ 30 kg/m2) 
 
9) Region (North America, Europe) 
 
In case the number of patients within a subgroup is too small, e.g. less than 5% of the 
overall population, the analyses may not be performed or the subgroup levels may be 
combined. 
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5.2.6 Medical History  
General medical history, cardiovascular history/risk factors, previous statin use and statin 
tolerance history will be summarized by previous treatment group in parent study, as well 
as overall in OLE study for safety population and presented in a by-patient listing.  Where 
appropriate, terms will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) Version 20.1 or later.     
 
If a patient is entering the study beyond the 30-day rollover window, new medical history 
that occur between more than 30 days after the end of the parent study and treatment start 
in OLE study (exclusive) that period will be collected and presented in a by-patient listing.  
 
5.2.7 Concomitant Medications 
Concomitant medications are defined as medications that were ongoing at the time of study 
drug initiation in this OLE study or new medications that started post study drug initiation 
and within 30 days following the date of the last dose of study drug. 
 
Medications, including lipid modifying therapy (LMT) medications, will be coded using 
WHO Drug (March, 2017, or later if appropriate). The frequency of use of concomitant 
medications will be summarized by previous treatment group in parent study, as well as 
overall in OLE study, for the safety population according to Anatomical Therapeutic 
Chemical (ATC) class and preferred term. Concomitant medications will be listed for each 
patient. Concomitant LMT medications will be summarized by ATC class and medication 
name and listed separately in a similar fashion.  
5.2.8 Study Drug Exposure and Compliance 
For each patient, the length of exposure to study drug will be calculated as the number of 
days from the first dose of study drug to the last dose of study drug, regardless if the patient 
missed one or more doses of study drug. Length of exposure will be summarized by 
previous treatment group in parent study and overall in OLE study using descriptive 
statistics for the safety population.  
For each patient, overall compliance (%) will be calculated as: (Total Number of Tablets 
Dispensed – Total Number of Tablets Returned)*100/ (Treatment Duration in Days).  The 
number and percentage of patients who were compliant with taking study drug will be 
summarized by previous treatment group in parent study and overall in OLE study for the 
safety population for the following categories 0 - <80%; >= 80%.  
The study drug administration and compliance data will be listed for each patient. 
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5.3 Efficacy Endpoints and Analyses  
Given the primary objective of the study being long term safety, efficacy analyses will be 
using the safety population (SP). The efficacy data will be summarized by previous 
treatment group in parent study as well as an overall group.  
For each efficacy parameter, descriptive summary statistics at each visit will be provided 
for the observed value, change from baseline, and percent change from baseline in both 
conventional and International System of Units (SI). Two sets of summaries will be 
provided using the baseline from the parent study and from the OLE study.  The visits to be 
included in the overtime summary are baseline of parent study (1002-040), baseline of 
OLE study, week 12, week 52, week 78, and Week 82. There will be no imputation for 
missing data, all summaries will use the observed data. Ninety-five percent (95%) CI will 
be provided for the estimates at post-baseline visits.  
In addition, efficacy parameters will also be summarized using the Completer Analysis Set 
(CAS).  
For LDL-C, the same descriptive summary statistics at each scheduled visit will be 
provided within each subgroup for the observed value, change from baseline, and percent 
change from baseline. 
Efficacy data (observed value, change from baseline, and percent change from baseline) 
from all visits will be summarized using descriptive statistics in both conventional and 
standard units. 
Figures (mean ± standard deviation or median/interquartile range) supporting the summary 
tables will be provided for each efficacy parameter.  
Efficacy data from all visits will be provided in listings as well.  
By-visit summary for efficacy endpoints (LDL-C, non-HDL-C, TC, HDL-C, TG, ApoB, 
and hs-CRP,) using the CAS will be provided in conventional and standard units. 
5.4 Safety Data Endpoints and Analyses  
The safety and tolerability of ETC-1002 will be assessed by examination of TEAEs, PEs, 
vital signs, clinical laboratory values (serum chemistry, hematology, coagulation, and 
urinalysis), and weight. SP will be used for all safety analyses.   
 
Unless otherwise stated, descriptive summaries will be performed by previous treatment 
group actually received in parent study and overall group. 
5.4.1 Adverse Events (AEs) 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
Version 20.1 or later and will be categorized by system organ class (SOC) and preferred 
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term (PT). Summary tables will focus on TEAEs; however, listings will include all AEs 
(with non-TEAEs flagged). An additional AE listing will be provided for AEs occurred 
during rollover period.  
季
In summary tables, TEAEs will be counted as “Not Related” if relationship to study drug 
was recorded as ‘Not Related’ or “Unlikely”. Events will be counted as “Related” if 
relationship to study drug was recorded as ‘Possible’, ‘Probable’, ‘Definite’ or if 
relationship to study drug is missing. 
The severity of the AE will be characterized as mild, moderate, or severe, to the following 
definitions: 
• 
Mild: Events are usually transient and do not interfere with the patient’s daily 
activities 
• 
Moderate: Events introduce a low level of inconvenience or concern to the patient 
and may interfere with daily activities  
• 
Severe: Events interrupt the patient’s usual daily activity, are incapacitating with 
inability to do usual activities, or significantly affect clinical status and warrant 
intervention and/or close follow-up  
 
Overviews of TEAEs will include total number of TEAEs, and patient incidence of TEAEs, 
TESAEs, treatment-related TEAEs, treatment-related TESAEs, IMP withdrawal due to 
TEAEs, TEAEs with fatal outcome. Individual TEAE summary will be presented by 
previous treatment group in parent study and overall containing the following counts and 
percentages for: 
x patients with TEAEs by SOC and PT 
x patients with TEAEs by PT 
x patients with TEAEs by SOC, PT, and maximum severity 
x patients with treatment-related TEAEs  
x patients with treatment-related TEAEs by PT 
x patients with treatment-related TEAEs by SOC and PT 
x patients with treatment-emergent serious adverse events (TESAEs) by SOC and PT 
x patients with TESAEs by PT 
x patients with TESAEs by SOC, PT, and maximum severity 
x patients with treatment-related TESAEs 
x patients with treatment-related TESAEs by SOC and PT 
x TEAEs leading to withdrawal of IMP by SOC and PT 
x fatal TEAEs by SOC and PT 
  
Preferred terms for TEAEs that occurred in more than 1% of subjects overall will be 
plotted using the overall group. This plot will be repeated for TESAEs in the overall group.  
 
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In addition, summary tables will be provided, by prior treatment group and overall, for the 
number and percent of patients experiencing: 
x adjudicated major adverse cardiovascular events and mortality (MACE) by event 
type  
x non-CV deaths (non-MACE),季
x nonfatal myocardial infarction [MI] (MACE),季
x nonfatal stroke (MACE),季
x hospitalization for unstable angina (MACE), 季
x coronary revascularization (MACE), 季
x noncoronary arterial revascularization (non-MACE), 季
x hospitalization for heart failure (non-MACE) using standardized definitions.季
The TEAE, treatment-related TEAE, TESAE, and AESI summaries by SOC, PT and 
maximum severity will be provided for relevant subgroups described in 5.2.5 with the 
exception of baseline LDL category. 
The AE overview summaries will count a patient at most once in each AE category (at the 
“highest/most extreme” designation of each category regardless of preferred term) and 
percentages will be based on the total number of patients in the safety population. 
In addition to a comprehensive listing of all AEs (with non-TEAEs flagged), separate 
listings will be generated for serious adverse events, TEAEs resulting in withdrawal of 
study drug, and TEAEs with a fatal outcome, investigator reported major adverse 
cardiovascular events and mortality, and adjudicated major adverse cardiovascular events 
and mortality. 
5.4.2 Adverse Events of Special Interest 
Adverse events of special interest (AESI) will be identified based on a pre-defined list of 
preferred terms provided by the sponsor (Appendix 2).  
AESI will be presented in a listing and summarized by SOC, PT, and previous treatment 
group in parent study and overall in OLE study. A separate table for treatment-emergent 
AESI resulting in the discontinuation of study drug will be summarized by SOC, PT, and 
previous treatment group in the parent study and overall in OLE study. 
In addition to adverse events, AESI is also being evaluated based on safety lab parameters. 
The details are provided in 5.4.5.  
5.4.2.1 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 pre-specified 
MedDRA terms and will be performed by SOC, severity, and relationship to study drug by 
previous treatment group in parent study and overall in OLE study.  
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5.4.3 Clinical 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 clinical endpoints that are treatment-emergent will be summarized by event 
type and previous treatment group in parent study and overall in OLE study. All events will 
be provided in a listing. Additional details regarding clinical endpoints and clinical 
endpoint definitions will be included in CEC charter. 
5.4.4 Laboratory Evaluations 
Continuous laboratory parameters (serum chemistry, hematology, coagulation (only for 
those patients receiving anti-coagulation), urinalysis, urinalysis [microscopic]) listed in 
Table 4 will be summarized in conventional unit and SI unit using descriptive statistics at 
each scheduled visit starting from the baseline of the parent study.  The similar completer 
analysis set approach for efficacy analysis described in section 5.3 will be used for selected 
parameters. Missing values for any of the laboratory evaluations will not be imputed; that 
is, only observed case data will be used. 
Fasting serum glucose and HbA1c will be summarized using descriptive statistics for the 
observed value, change from baseline, and percent change from baseline at each scheduled 
visit by history of diabetics.  
Categorical urinalysis data will be listed, but will not be summarized.  
 
As part of the AESI evaluation, below safety lab abnormality will be summarized by 
treatment group. All post-baseline lab values during the on-treatment period are being 
considered. Further details are provided in Section 5.4.6.1 through 5.4.6.4. 
 
x ALT or AST (> 3 × Upper limit of normal (ULN) and >5 × ULN) 
x Total bilirubin (TB) (> 2 × ULN) 
x Potential Hy’s Law case: (ALT and/or AST > 3 × ULN with concurrent TB > 2 × 
ULN) 
x CK (> 5 × ULN) and (>10 × ULN) 
x Fasting Serum Glucose (mg/dL) (≤ 50, and ≥ 126) by history of diabetics 
x HbA1C (≥ 6.5%) by history of diabetics 
x Creatinine (change from baseline for >1 mg/dL) 
x eGFR (< 15 mL/min/1.73m2, 15 –29 mL/min/1.73m2) 
x Hgb (g/dL) (decrease from baseline for ≥ 2 g/dL) 
x Hgb (< 8 g/dL) 
 
The number and percentage of patients with the following laboratory abnormalities will be 
summarized by the parent study baseline statin intensity, previous treatment group in the 
parent study, and overall in the OLE study: 
  
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x ALT or AST (> 3 × ULN and >5 × ULN) 
x TB (> 2 × ULN) 
x Potential Hy’s Law case: (ALT and/or AST > 3 × ULN with concurrent TB > 2 × 
ULN) 
x CK (> 5 × ULN) and (>10 × ULN) 
x Creatinine (change from baseline for > 1 mg/dL) 
x eGFR (< 15 mL/min/1.73m2, 15 –29 mL/min/1.73m2) 
x Hgb (g/dL) (decrease from baseline for ≥ 2 g/dL) 
x Hgb (< 8 g/dL) 
 
For labs of interest (such as uric acid, hemoglobin, creatinine, BUN, and Fasting glucose 
by diabetes history), a line plot will be generated to visualize the mean values over time.  
A matrix display of liver dysfunction shift from baseline to maximum value will be used to 
visualize the abnormal values of labs including AST, ALK-P ALT, and TB.  
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Table 2: 
Clinical Laboratory Parameters (Safety) 
 
Clinical Laboratory Test 
Clinical Laboratory Test 
x 
Hematology 
x 
Hematocrit (Hct) 
x 
Hemoglobin (Hgb) 
x 
Mean corpuscular hemoglobin (MCH) 
x 
Mean corpuscular hemoglobin 
concentration (MCHC) 
x 
Mean corpuscular volume (MCV) 
x 
Platelet count 
x 
Red blood (RBC) cell count 
x 
White blood (WBC) cell count with 
differential (absolute and %) 
Blood Chemistry (serum, fasting) 
x 
Albumin (Alb) 
x 
Alkaline phosphatase (ALK-P) 
x 
Alanine aminotransferase (ALT; SGPT) 
x 
Aspartate aminotransferase (AST; 
SGOT) 
x 
Blood urea nitrogen (BUN) 
x 
Calcium (Ca) 
x 
Carbon dioxide (CO2) 
x 
Chloride (Cl) 
x 
Creatinine 
x 
Creatine kinase (CK) 
x 
Glucose 
x 
Lactate dehydrogenase (LDH) 
x 
Phosphorus 
x 
Potassium (K) 
x 
Sodium (Na) 
x 
Total and direct bilirubin (TB)a 
x 
Total protein 
x 
Uric acid 
Coagulation—only in patients receiving 
anticoagulant therapy that in the investigator’s 
judgment require monitoring at Month 0 and 
3 to 5 days post-Month 0 
x 
Prothrombin time  
x 
International normalized ration (INR) 
Urinalysis (Dipstick) 
x 
Clarity 
x 
Bilirubin 
x 
Color 
x 
Glucose 
x 
Ketones 
x 
Leukocyte esterase 
x 
Nitrate 
x 
Occult blood 
x 
pH 
x 
Protein 
x 
Specific gravity 
x 
Urobilinogen 
Urinalysis (Microscopic)-only if urine dipstick 
abnormal 
x 
Bacteria 
x 
Casts 
x 
Crystals 
x 
Epithelial cells 
x 
RBC 
x 
WBC 
Other Labs: 
x 
Urine pregnancy test  
x 
Hemoglobin A1C (HbA1C) 
a If TB ≥1.2 u ULN, a reflex indirect (unconjugated) bilirubin will be obtained. 
 
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The number and percentage of patients with laboratory abnormalities (i.e., laboratory 
values outside the stated laboratory normal range) will be summarized at each time point 
(i.e., including baseline and post-baseline time points) for each laboratory parameter. The 
determination of laboratory abnormalities will take into account any unscheduled 
laboratory assessments.  Additional lab-related summaries will be provided as follows for 
hepatic safety, musculoskeletal safety, diabetes and glycemia, and renal safety. 
5.4.4.1 Hepatic Safety 
For liver-associated enzymes and total bilirubin (TB), the number and percent of patients 
with abnormal values for ALT (>3 × ULN, > 5 × ULN), AST (> 3 × ULN, > 5 × ULN), 
and TB (> 2×ULN) will be summarized by overall, normal baseline ALT/AST/TB and 
abnormal baseline ALT/AST/TB.  
Hy’s law criteria (> 3 × upper limit of normal [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. 
The number and percentage of patients experiencing a single incident or confirmed and 
repeated incidence of abnormal liver function test values for ALT (>3 × ULN, >5 × ULN), 
AST (>3 × ULN, >5 x ULN), CK (>5 × ULN, >10 × ULN) and either ALT and/or AST 
(>3 × ULN, >5 × ULN) will be summarized by the previous treatment group in the parent 
study and overall in the OLE study. A single incident is defined as the patient experiencing 
only one abnormal incident of the liver function test value. Repeated and confirmed 
incidence is defined as the patient experiencing at least one of the following: the last on-
study liver function test value is abnormal, the last on-treatment liver function test value is 
abnormal, or an abnormal liver function test value is followed by another abnormal liver 
function test value for the same test. 
A separate listing for direct bilirubin will be provided for those who have Gilbert’s 
syndrome. 
5.4.4.2 Musculoskeletal Safety 
CK levels will be summarized by the value and change from baseline in the value, by 
treatment group and visit as well as baseline eGFR category. In addition, the number and 
percent of patients with abnormal CK values (>5 X ULN, >10 × ULN) will be summarized. 
These summaries of patients with abnormal CK will be performed overall, normal baseline 
CK, and abnormal baseline CK.  
5.4.4.3 Diabetes and Glycemia 
For fasting glucose and HbA1C (%), a shift table from baseline with the number and 
percent of patients will be categorized as below: 
Fasting glucose: >= 126 mg/dL; 100-125 mg/dL, and < 100 mg/dL; 
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HbA1C (%): >=6.5%; >5.5 to <=6.4% and <=5.5%. 
 
These tables will be summarized by history of Diabetes. 
 
Descriptive summary for fasting serum glucose and HbA1C will be provided by history of 
diabetics, previous treatment group in parent study and overall at each scheduled visit. 
5.4.4.4 Renal Safety 
Shift tables of eGFR category from baseline over the study, will be provided by previous 
treatment group in parent study and overall.  
In addition, renal function abnormality will be identified as: (1) A creatinine change from 
baseline of > 1 mg/dL (2) eGFR value <30 mL/min/1.73m2. A shift table from baseline 
with the number and percent of patients using the two categories will be presented. 
5.4.5 Physical Examination (PE) 
Listings of PE data will include only those records where the body system at the baseline 
PE was normal, but the body system at a post-baseline PE was marked as ‘Change from 
previous exam, clinically significant’.  Baseline is defined as the last value prior to the first 
dose of study medication in OLE study. Only changes from baseline PE findings that meet 
the definition of an AE will be recorded on the AE page of the eCRF and will be 
summarized with other AE outcomes. 
5.4.6 Vital Signs and Weight 
The observed values and changes from baseline of both parent study and OLE study in vital 
signs (heart rate, systolic blood pressure, diastolic blood pressure) and weight will be 
summarized using descriptive statistics by previous treatment group in parent study, overall 
and post-baseline time point.  
Vital sign data will be listed for each patient, with increases from baseline of > 15 mmHg 
in systolic or diastolic blood pressure flagged. 
 
6 DMC Analyses 
Refer to DMC charter. 
 
 
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7 Reference 
1. Sharrett AR, Ballantyne CM, Coady SA, Heiss G, Sorlie PD, Catellier D, et al. 
Atherosclerosis Risk in Communities Study Group. Coronary Heart Disease 
Prediction from Lipoprotein Cholesterol Levels, Triglycerides, Lipoprotein(A), 
Apolipoproteins A-I and B, and HDL Density Subfractions. The Atherosclerosis 
Risk in Communities (ARIC) Study. Circulation. 2001;104:1108-13. 
2. World Health Organization (WHO) Fact Sheet No 317 Updated January 2015. 
3. 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. 
4. Pharmacokinetics in Patients with Impaired Renal Function — Study Design, 
Data Analysis, and Impact on Dosing and Labeling. FDA Draft Guidance. 
March 2010 
5. Haase A, Goldberg AC. Identification of people with heterozygous familial 
hypercholesterolemia. Curr Opin Lipidol. 2012;23:282-9. 
6. Glynn RJ, Laird NM, and Rubin DB. (1986). Selection modelling versus 
mixture modelling with nonignorable nonresponse. In H. Wainer (ed.), Drawing 
Inferences from Self-Selected Samples, pp. 115–142. New York: Springer. 
 
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8 Appendices 
8.1 Appendix 1: Schedule of Events (Subject Visit Schedule) 
Month 
0 
3 
6 
9 
12 
15 
18/EOT1 19/EOS2 
Week  
EOS 
Parent 
Wk 12 
Wk 24 
Wk 36 
Wk 52 
Wk 64 
Wk 78 
Wk 82  
Visit Window 
30 Days 
pre-M0 
±7 days ±7 days ±7 days 
±7 days 
±7 days 
±7 days +14 days 
In-clinic Visit 
X 
X 
 
 
X 
 
X 
X 
Phone Visit 
 
 
X 
X 
 
X 
 
 
Procedure 
Informed Consent 
X 
 
 
 
 
 
 
 
Enrollment Criteria 
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Event 
Recording 
X 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
X 
 
 
 
X 
 
X 
 
Weight3 
X 
X 
 
 
X 
 
X 
X 
Vital Signs4 
X 
X 
 
 
X 
 
X 
X 
Urine Pregnancy Test5  
X 
 
 
 
 
 
 
 
Clinical Safety Labs6 
X 
X 
 
 
X 
 
X 
X 
Basic Fasting Lipids7 
X 
X 
 
 
X 
 
X 
X 
Coagulation8 
X 
 
 
 
 
 
 
 
ApoB and hsCRP 
X 
X 
 
 
X 
 
X 
X 
HbA1C 
X 
  
 
 
X  
 
X 
X 
IWRS Contact9 
X 
 X 
 
 
 X 
 
X 
 
Drug Dispensing 
X 
X 
 
 
X 
 
 
 
Drug Return/ 
Compliance 
 
X 
 
 
X 
 
X 
 
NOTE: For patients who withdraw from study drug treatment, but consent to be followed for safety 
assessments and return to clinic for these visit, the visits will occur according to the protocol schedule.  Safety 
assessments should include clinical safety and basic lipid laboratories, adverse events (AEs), physical 
examination (PE), and vital signs.  For patients who withdraw from study drug treatment, but consent to be 
followed for safety assessments by phone, the telephone contacts will occur according the protocol schedule 
with information regarding current health status and to collect information on AEs (eg, recent procedures, 
hospitalizations, and if the patient has died, the cause of death).  If a patient does not provide consent to be 
followed for safety assessments per the protocol (either by returning to clinic or by phone), Visit 
Week 78/End of Treatment (EOT) will be scheduled as soon as possible and the patient will be asked to come 
back 4 weeks after last investigational medicinal product (IMP) dose for Visit Week 82/End of Study (EOS).  
No further visits will be scheduled. 
1 All procedures will be completed for all patients at either EOT or early withdrawal. 
2 All procedures will be completed for all patients 4 weeks after last IMP dose if completing the study or 
early withdrawal. 
3 Body weight will be measured in the morning while fasting, using consistent scales, after voiding, and 
without shoes and outerwear (eg, coats).   
4 Vital signs will include diastolic blood pressure (DBP), systolic blood pressure (SBP), heart rate (HR) and 
will be collected prior to any blood sample collection.  Patient will rest for 5 minutes prior to assessments 
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5 Urine pregnancy test in women of childbearing potential only 
6 Clinical safety labs include hematology, blood chemistry, and urinalysis at all visits.  Please refer to 
laboratory manual for detailed schedule of tests. 
7 Basic fasting lipids include total cholesterol (TC), calculated low-density lipoprotein cholesterol (LDL-C), 
high-density lipoprotein cholesterol (HDL-C), non-HDL-C,), and triglycerides (TG). 
8 Only in patients receiving anticoagulant therapy that in the investigator’s judgment require monitoring at 
Month 0 and 3 to 5 days post-Month 0 
9 Interactive web response system (IWRS) contact at either an early withdrawal or an EOS visit to register 
study discontinuation visit date 
 
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8.2 Appendix 2: Adverse Event of Special Interest (AESI) 
Adverse Event Terms per Protocol 
Associated MedDRA Preferred Terms 
Creatine kinase elevations 
Blood creatine phosphokinase abnormal 
Creatine kinase elevations 
Blood creatine phosphokinase increased 
Creatine kinase elevations 
Blood creatine phosphokinase MM abnormal 
Creatine kinase elevations 
Blood creatine phosphokinase MM increased 
New onset or worsening diabetes mellitus 
Blood glucose abnormal 
New onset or worsening diabetes mellitus 
Blood glucose increased 
New onset or worsening diabetes mellitus 
Diabetes mellitus 
New onset or worsening diabetes mellitus 
Diabetes mellitus inadequate control 
New onset or worsening diabetes mellitus 
Diabetic ketoacidosis 
New onset or worsening diabetes mellitus 
Glucose tolerance impaired 
New onset or worsening diabetes mellitus 
Glucose urine present 
New onset or worsening diabetes mellitus 
Glycosuria 
New onset or worsening diabetes mellitus 
Glycosylated haemoglobin increased 
New onset or worsening diabetes mellitus 
Hyperglycaemia 
New onset or worsening diabetes mellitus 
Impaired fasting glucose 
New onset or worsening diabetes mellitus 
Ketoacidosis 
New onset or worsening diabetes mellitus 
Ketosuria 
New onset or worsening diabetes mellitus 
Ketosis 
New onset or worsening diabetes mellitus 
Type 2 diabetes mellitus 
New onset or worsening diabetes mellitus 
Urine ketone body present 
Hepatic disorders 
Alanine aminotransferase abnormal 
Hepatic disorders 
Alanine aminotransferase increased 
Hepatic disorders 
Aspartate aminotransferase abnormal 
Hepatic disorders 
Aspartate aminotransferase increased 
Hepatic disorders 
Blood bilirubin abnormal 
Hepatic disorders 
Blood bilirubin increased 
Hepatic disorders 
Hepatic enzyme abnormal 
Hepatic disorders 
Hepatic enzyme increased 
Hepatic disorders 
Hypertransaminaseaemia 
Hepatic disorders 
Liver function test abnormal 
Hepatic disorders 
Liver function test increased 
Hepatic disorders 
Transaminases abnormal 
Hepatic disorders 
Transaminases increased 
Hypoglycemia 
Blood glucose abnormal 
Hypoglycemia 
Blood glucose decreased 
Hypoglycemia 
Hypoglycaemia 
Hypoglycemia 
Hypoglycaemic coma 
Hypoglycemia 
Hypoglycaemic encephalopathy 
Hypoglycemia 
Hypoglycaemic seizure 
Hypoglycemia 
Shock hypoglycaemic  
Metabolic acidosis 
Metabolic acidosis 
Muscular disorders 
Muscular weakness 
Muscular disorders 
Muscle necrosis 
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Muscular disorders 
Muscle spasms 
Muscular disorders 
Myalgia 
Muscular disorders 
Myoglobin blood increased 
Muscular disorders 
Myoglobin blood present 
Muscular disorders 
Myoglobin urine present 
Muscular disorders 
Myoglobinaemia 
Muscular disorders 
Myoglininuria 
Muscular disorders 
Myopathy 
Muscular disorders 
Myopathy toxic 
Muscular disorders 
Necrotizing myositis 
Muscular disorders 
Pain in extremity 
Muscular disorders 
Rhabdomyolysis 
Neurocognitive/Neurologic disorders 
Amnesia 
Neurocognitive/Neurologic disorders 
Cognitive disorder 
Neurocognitive/Neurologic disorders 
Confusional state 
Neurocognitive/Neurologic disorders 
Disorientation 
Neurocognitive/Neurologic disorders 
Memory impairment 
Neurocognitive/Neurologic disorders 
Mental status changes 
Renal disorders 
Acute kidney injury 
Renal disorders 
Acute prerenal failure 
Renal disorders 
Blood creatinine abnormal 
Renal disorders 
Blood creatinine increased 
Renal disorders 
Blood urea abnormal 
Renal disorders 
Blood urea increased 
Renal disorders 
Blood urea nitrogen/Creatinine ratio increased 
Renal disorders 
Creatinine renal clearance abnormal 
Renal disorders 
Creatinine renal clearance decreased 
Renal disorders 
Glomerular filtration rate abnormal 
Renal disorders 
Glomerular filtration rate decreased 
Renal disorders 
Gout 
Renal disorders 
Oliguria 
Renal disorders 
Prerenal failure 
Renal disorders 
Renal failure 
Renal disorders 
Renal function test abnormal 
Renal disorders 
Renal impairment 
 
 
 
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