Conditions: Healthy Lactating Women
Keywords: Bempedoic acid Ezetimibe Bempedoic acid and ezetimibe Breast Milk
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 16
Healthy volunteers: yes

Brief summary:
This study is designed to characterize the excretion of bempedoic acid or bempedoic acid and ezetimibe into mature breast milk of healthy lactating women and assess the exposure to the breast fed infant by estimating the daily infant dosage and the relative infant dose (RID) of bempedoic acid or bempedoic acid and ezetimibe in breast milk after 6 consecutive daily doses of bempedoic acid or bempedoic acid/ezetimibe FCDP.

Detailed description:
Post marketing approval commitment for the FDA

Arms:
arm 1: None arm 2: None

Interventions: intervention 1: Bempedoic Acid 180 MG Oral Tablet intervention 2: Bempedoic Acid/Ezetimibe 180 MG-10 MG Oral Tablet
Intervention descriptions: intervention 1: Bempedoic Acid 180 MG Oral Tablet \[Nexletol\] intervention 2: Bempedoic Acid/Ezetimibe 180 MG-10 MG Oral Tablet \[NEXLIZET\]

Protocol document:
Prot_000.pdf: 
Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
Confidential 
 
Page 1 of 67 
 
1002FDC-075 
An Open-Label Postmarketing Milk-Only Lactation Study to Evaluate the Concentration 
of Bempedoic Acid and Bempedoic Acid and Ezetimibe in the Breast Milk of Healthy 
Lactating Women Administered Therapeutic Doses of Bempedoic Acid or Bempedoic 
Acid/Ezetimibe Fixed Combination Drug Product (FCDP) 
 
Study Phase: 
4 
Indication: 
Treatment of hyperlipidemia 
Principal Investigator: 
1 to 2 sites in the United States 
Sponsor: 
Esperion Therapeutics, Inc. 
3891 Ranchero Drive, Suite 150 
Ann Arbor, MI 48108 
Phone:  1-734-887-3903 
Fax:  1-734-913-5344 
Sponsor Contact: 
, MD, MPH, MSc  
Senior Vice President of Clinical Development and 
Pharmacovigilance 
 
 
 
Version 
Date 
 
 
Amendment 1 
Final Protocol 
06 June 2023 
18 August 2021   
 
Confidentiality Statement 
THIS CONFIDENTIAL INFORMATION IS ABOUT AN INVESTIGATIONAL DRUG PROVIDED FOR THE EXCLUSIVE USE OF INVESTIGATORS OF 
THIS DRUG AND IS SUBJECT TO RECALL AT ANY TIME.  THE INFORMATION IN THIS DOCUMENT MAY NOT BE DISCLOSED UNLESS SUCH 
DISCLOSURE IS REQUIRED BY FEDERAL OR STATE LAW OR REGULATIONS.  SUBJECT TO THE FOREGOING, THIS INFORMATION MAY BE 
DISCLOSED ONLY TO THOSE PERSONS INVOLVED IN THE STUDY WHO HAVE NEED TO KNOW, WITH THE OBLIGATION NOT TO FURTHER 
DISSEMINATE THIS INFORMATION.  THESE RESTRICTIONS ON DISCLOSURE WILL APPLY EQUALLY TO ALL FUTURE ORAL OR WRITTEN 
INFORMATION, SUPPLIED TO YOU BY ESPERION THERAPEUTICS, INC., WHICH IS DESIGNATED AS “PRIVILEGED” OR “CONFIDENTIAL. 
 
 
 


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
Confidential 
 
Page 2 of 67 
2. 
SYNOPSIS 
 
Name of Sponsor:  Esperion Therapeutics, Inc.  
Name of Investigational Products:  Bempedoic acid and bempedoic acid/ezetimibe fixed combination 
drug product (FCDP) 
Name of Active Ingredients:  bempedoic acid, ezetimibe  
Title of Study:  An Open-Label Postmarketing Milk-Only Lactation Study to Evaluate the Concentration 
of Bempedoic Acid and Bempedoic Acid and Ezetimibe in the Breast Milk of Healthy Lactating Women 
Administered Therapeutic Doses of Bempedoic Acid or Bempedoic Acid/Ezetimibe Fixed Combination 
Drug Product (FCDP) 
Study Number:  1002FDC-075 
Phase of Development:  4 
Clinical Sites:  1 to 2 sites in United States 
Objectives: 
Primary: 
The primary objectives of this study are to estimate infant exposure to bempedoic acid or bempedoic 
acid and ezetimibe: 
• 
estimate the daily infant dosage and relative infant dose (RID) of bempedoic acid in mature 
breast milk after administration of bempedoic acid for 6 consecutive days, and 
• 
estimate the daily infant dosage and RID of bempedoic acid and ezetimibe in mature breast milk 
after administration of bempedoic acid/ezetimibe FCDP for 6 consecutive days. 
Secondary: 
The secondary objectives of this study are to characterize the excretion of bempedoic acid or 
bempedoic acid and ezetimibe in mature breast milk of healthy lactating women who receive a once 
daily dose of bempedoic acid or bempedoic acid/ezetimibe FCDP for 6 consecutive days: 
• 
determine concentrations of bempedoic acid, active metabolite ESP15228 and bempedoic acid 
glucuronide in mature breast milk collected over 24 hours from healthy subjects administered 
bempedoic acid or bempedoic acid/ezetimibe FCDP, and 
• 
determine concentrations of ezetimibe and metabolite ezetimibe-glucuronide in mature breast 
milk collected over 24 hours from healthy subjects administered bempedoic acid/ezetimibe 
FCDP. 
Safety: 
The safety objective of this study is to evaluate the safety of 6 consecutive doses of bempedoic acid 
or bempedoic acid/ezetimibe FCDP in healthy lactating women. 
Study Design: 
This is a Phase 4, open-label study that will estimate the daily infant dosage and RID of bempedoic acid 
and bempedoic acid/ezetimibe in the mature breast milk of healthy women who have received 6 daily 
doses of bempedoic acid or bempedoic acid/ezetimibe FCDP.  The excretion of bempedoic acid, 
ezetimibe, and metabolites ESP15228, bempedoic acid glucuronide, and ezetimibe-glucuronide will be 
characterized in mature breast milk.  Healthy lactating women who choose to stop breastfeeding their 
infant for the duration of the Treatment and Washout Periods will be eligible to participate once all 


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
Confidential 
 
Page 3 of 67 
enrollment criteria are met.  The Screening Period will be up to 42 days followed by a 6-day Treatment 
Period and a 7-day Washout Period.  Subjects will be contacted by phone as a Post-treatment Follow-up 
Visit on Day 13.  Once the call is complete, subjects may resume feeding their infant breast milk that is 
currently being produced. 
Screening Period:  The Screening Period will begin with a Screening Visit (Visit S1) that will occur up 
to 42 days prior to randomization (Visit T1).  Visit S1 will allow the Investigator to assess the subject’s 
eligibility and current breastfeeding practices.  After the subject provides written informed consent, the 
subject will undergo screening assessments as outlined in Appendix 1.  Study staff will schedule an 
optional lactation consultant visit for those subjects who desire support related to feeding/care of the 
infant such as preparing for the treatment and washout periods of the study, pumping breast milk for 
storage, introducing infant formula, introducing bottle feeding or resuming breastfeeding after Day 13 
(FU1). Additional lactation consultant visits may be scheduled for subjects anytime throughout the study. 
 
Treatment Period:  Subjects who meet all eligibility criteria will be instructed to report to the clinical 
research unit (CRU) on Day 1 (Visit T1).  Subjects who continue to meet eligibility criteria must confirm 
their infant is able to feed from a bottle, adequate stored breast milk and/or infant formula is available to 
feed the infant for the duration of the study, and the subject is maintaining adequate breast milk 
production.  If a subject is weaning, duration of weaning will be documented.  Subjects will then be 
randomized in a 1:1 ratio to receive either bempedoic acid (Cohort 1) or bempedoic acid/ezetimibe FCDP 
(Cohort 2).  Eight subjects will be in each cohort.  While at the CRU, subjects will provide a predose 
blood sample for pharmacokinetic (PK) and safety laboratories.  Subjects will use an electric breast pump 
to provide a predose breast milk sample and will then receive the first dose of investigational medicinal 
product (IMP).  When Visit T1 assessments are complete, subjects will be provided with adequate IMP 
supply to support once-daily dosing on Days 2, 3, 4 and 5 by self administration- at home.  Subjects will 
be reminded that their infant(s) must not be fed with their breast milk that is produced after the first dose 
of IMP through Day 13 of the Washout Period.  On Day 2 through Day 5 study staff will contact each 
subject by phone to ensure IMP is taken appropriately and remind the subject to discard breast milk that 
is produced after the first dose of IMP.  In addition, subjects will document the day and time of when 
IMP was taken for Day 2 through Day 5 in the Study Drug Diary.  On the evening of Day 5 (Visit T2), 
subjects will check-in to the CRU for 2 overnights (with Sponsor approval, subjects may check-in to the 
CRU on the morning of Day 6).  Subjects must submit their Study Drug Diary at CRU check-in.  Study 
staff will review the diary and assess IMP adherence.  On the morning of Day 6, subjects will pump both 
breasts with an electric pump until completely emptied.  When pumping is complete, Cohort 1 subjects 
will receive the Day 6 dose of bempedoic acid and Cohort 2 subjects will receive the Day 6 dose of 
bempedoic acid/ezetimibe FCDP.  Breast milk will be collected from each subject over the next 24 hours 
using an electric pump at 3, 6, 9, 12, 16, 20 and 24 hours (±30 minutes) after Day 6 dose administration.  
Both breasts will be emptied completely during each collection.  At each sampling time point, milk 
collected from each breast will be mixed together and the total volume measured and recorded.  On Day 


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
Confidential 
 
Page 4 of 67 
7, blood will be collected approximately 24 hours after Day 6 dosing for PK and safety laboratory 
samples.  Subjects will be discharged from the CRU on the morning of Day 7 after breast milk collection 
and completion of Day 7 assessments.  Subjects will be instructed to continue to pump and discard breast 
milk during the remainder of the Washout Period through Day 13. 
Follow-up Period:  On Day 13, all subjects will be contacted by phone as a post-treatment Follow-up 
Visit (Visit FU1/End-of-Study [EOS]).  Breastfeeding may resume after Visit FU1 on Day 13.  An 
optional lactation consultant visit will be scheduled for those subjects who desire to re-establish 
breastfeeding. On Day 43 (FU2), study staff will contact subjects by phone to assess for SAEs and if the 
patient was able to resume breastfeeding (if intended). 
 
Number of Subjects (planned):  Approximately 16 (8 bempedoic acid [Cohort 1] and 8 bempedoic 
acid/ezetimibe FCDP [Cohort 2]) healthy lactating female subjects will be enrolled.  If a subject 
discontinues the study early or does not receive 6 daily doses of IMP or does not complete the 24-hour 
breast milk collection after Day 6 dosing, a replacement subject will be enrolled and assigned to the same 
treatment. 


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Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
Confidential 
 
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Diagnosis and Criteria for Inclusion: 
Inclusion Criteria: 
Each subject must meet the following criteria to be eligible for this study. 
1. The subject must be willing to provide written informed consent before any study-specific 
procedures are performed. 
2. The subject must be 18 to 45 years old, inclusive. 
3. The subject must be a lactating female who had a normal full-term pregnancy and has been actively 
breastfeeding or pumping for at least 4 weeks; lactation must be well -established per Investigator 
discretion. 
4. The subject must be willing to pump regularly during the study to maintain milk supply and 
discontinue breastfeeding for the entire 13-day Treatment and Washout Periods. 
5. The subject must not be pregnant. 
6. The subject must be surgically sterile by hysterectomy, bilateral oophorectomy, and/or tubal ligation, 
or willing to use 1 acceptable method of birth control unless they have agreed to follow the definition 
of abstinence.  The minimal requirement of adequate contraception should be started on Day 1 and 
continued during the study period and for at least 30 days after the last dose of IMP.  Acceptable 
methods of birth control include:  
− 
an intrauterine device (IUD) with or without hormones; 
− 
established use of oral, implanted, transdermal, injectable, or hormonal method of 
contraception associated with inhibition of ovulation; 
− 
barrier methods including condom or occlusive cap with spermicidal foam or spermicidal 
jelly; 
− 
vasectomized male partner who is the sole partner for this subject; or 
− 
true abstinence (when this is in line with the preferred and usual lifestyle of the subject).  
Note:  periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation 
methods), declaration of abstinence for the duration of the trial, and withdrawal are not 
acceptable methods of contraception. 
Exclusion Criteria: 
Subjects who meet any of the following criteria will not be eligible to participate in this study. 
1. Has clinically significant infection (e.g., pneumonia, pyelonephritis) or chronic infection within 30 
days prior to enrollment. 
2. Has evidence of unstable or uncontrolled, clinically significant cardiovascular, central nervous 
system, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, 
immunological, endocrine/metabolic, or other medical disorder, including serious allergy, asthma, 
hypoxemia, hypertension, seizures, or allergic skin rash, that, in the opinion of the Investigator, 
would confound the study results or compromise subject safety.  
3. Has estimated glomerular filtration rate (eGFR) <30 mL/min/1.732 using the Modification of Diet in 
Renal Disease (MDRD) formula.  
4. Has liver disease or dysfunction characterized by Child-Pugh Class B or Class C. 
5. History of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, or 
neurodegenerative disease. 
6. Has active psychiatric problems that, in the Investigator’s opinion, may interfere with compliance 
with the study procedures. 
7. Is unable to participate in all the study visits or comply with study procedures. 
8. Has history of breast implants, breast augmentation, or breast reduction surgery. 
9. Has a prior history of difficulty establishing lactation. 
10. Gastrointestinal conditions or procedures (including weight loss surgery; e.g., Lap-
Band® or gastric bypass) that may affect drug absorption. 
11. Any history of malignancy (with the exception only of basal or squamous cell carcinoma of the skin 


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Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
Confidential 
 
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in individuals that have been cancer free for >5 years). 
12. History within the last 2 years of drug, alcohol, amphetamine and derivatives, or cocaine abuse.  
Subjects with amphetamine derivatives prescribed by and under the care of a health care practitioner 
can be enrolled after evaluation by the Investigator.  
13. Current smoker.  
14. Blood donation, participation in a multiple blood draw clinical study, major trauma, or surgery with or
without blood loss within 30 days prior to enrollment. 
15. Blood transfusion for any reason within 90 days prior to enrollment. 
16. Use of any 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor (statin) 
concurrently or within 30 days prior to randomization (Visit T1). 
17. Use of cyclosporine, cholestyramine, probenecid, fibrate drugs, or medications contraindicated during 
lactation concurrently or within 30 days prior to randomization (Visit T1). 
18. Concomitant use or use within 30 days prior to randomization (Visit T1) of drugs that decrease breast 
milk production, such as pseudoephedrine. 
19. Concomitant use or use within 30 days prior to randomization (Visit T1) of drugs that increase breast 
milk production, such as domperidone. 
20. Use of any experimental or investigational drugs/vaccines concurrently or within 30 days or 5 half-
lives of the drug, whichever is longer, prior to screening (Visit S1). 
21. Any current condition that in either the Investigator’s, Sponsor’s, or authorized Medical Monitor’s 
opinion may compromise subject safety or ability to complete the study or interfere with study data 
interpretation. 
22. An employee or contractor of the facility conducting the study, or a family member of the Principal 
Investigator, Co-Investigator, or Sponsor. 
 
Investigational Medicinal Product(s) (IMPs), Dose, and Mode of Administration: 
Bempedoic acid 180 mg or bempedoic acid 180 mg/ezetimibe 10 mg FCDP will be administered orally 
once daily for 6 days. 
Duration of Study: 
The expected study duration for all subjects is ≤55 days, including an up to 42-day Screening Period, 
followed by a 6-day Treatment Period, and a 7-day Washout Period. 
Pharmacokinetic Assessments 
Primary Endpoints 
Bempedoic acid and ezetimibe assessments: 
• 
Daily infant dosage calculated as the cumulative amount excreted in breast milk per day 
• 
RID calculated as the ratio of total infant daily dose per kg of body weight and maternal daily 
dose per kg of body weight multiplied by 100 
Secondary Endpoints 
Bempedoic acid, ezetimibe, and metabolite (ESP15228, bempedoic acid glucuronide, and ezetimibe-
glucuronide) assessments: 
• 
Amount excreted in each breast milk collection, calculated as the product of concentration and 
milk volume collected 
• 
Area under the milk concentration-time curve (AUC) over the 24-hour collection interval 
• 
Average milk concentration based on milk AUC 
• 
Peak and trough milk concentrations and the time of peak milk concentrations 
• 
Plasma trough concentrations at 24 hours after the last dose on Day 6 
Safety Assessments: 


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
Confidential 
 
Page 7 of 67 
Adverse events (all and treatment emergent), clinical laboratory parameters, vital signs, and physical 
examinations.  
Statistical Methods: 
A minimum sample size of 16 (8 bempedoic acid [Cohort 1] and 8 bempedoic acid/ezetimibe FCDP 
[Cohort 2]) evaluable subjects (who complete the 6-day treatment period and 24-hour breast milk 
collection) is planned for this study. The sample size was determined to be sufficient to address the 
objectives of the study. Sample size was not based on empirical or hypothesis testing criteria 
Breast milk PK endpoints of daily infant dosage, RID, amount excreted, AUC and peak, trough and 
average concentrations will be summarized using descriptive statistics for bempedoic acid, ESP15228, 
bempedoic acid glucuronide, ezetimibe and ezetimibe glucuronide.  Plasma trough concentrations of 
bempedoic acid, ESP15228, bempedoic acid glucuronide, ezetimibe and ezetimibe glucuronide will be 
summarized using descriptive statistics.   
For all enrolled subjects who receive at least 1 dose of IMP (safety population), safety data (including 
adverse events, clinical laboratory parameters, physical examination, vital signs and body weight) will be 
summarized and listed using descriptive statistics.  
 
 


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Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
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TABLE OF CONTENTS 
1. 
1002FDC-075…..………………………………………………………………….…1 
2. 
SYNOPSIS ...................................................................................................................2 
TABLE OF CONTENTS .................................................................................................................8 
LIST OF TABLES .........................................................................................................................13 
LIST OF FIGURES .......................................................................................................................13 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................14 
4. 
INTRODUCTION ......................................................................................................17 
4.1 
Study Rationale ...........................................................................................................18 
4.2 
Background of Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP .................18 
4.3 
Dose Selection ............................................................................................................18 
4.4 
Risk Benefit Summary ................................................................................................18 
5. 
OBJECTIVES AND ENDPOINTS ............................................................................20 
5.1 
Objectives ...................................................................................................................20 
5.1.1 
Primary Objective .......................................................................................................20 
5.1.2 
Secondary Objectives .................................................................................................20 
5.1.3 
Safety Objective ..........................................................................................................20 
5.2 
Endpoints ....................................................................................................................20 
5.2.1 
Pharmacokinetic Assessments ....................................................................................20 
5.2.1.1 
Primary Endpoints ......................................................................................................20 
5.2.1.2 
Secondary Endpoints ..................................................................................................21 
5.2.2 
Safety Endpoints .........................................................................................................21 
6. 
INVESTIVATIONAL PLAN .....................................................................................22 
6.1 
Overall Study Design ..................................................................................................22 
6.2 
Scientific Rationale .....................................................................................................22 
6.3 
Estimated Study Duration ...........................................................................................23 
6.4 
Number of Centers ......................................................................................................23 
6.5 
Number of Subjects ....................................................................................................23 
6.6 
Subject Number and Identification .............................................................................23 
6.7 
Subject Withdrawal and Replacement ........................................................................23 
6.8 
End of Study ...............................................................................................................23 
7. 
SELECTION OF SUBJECTS ....................................................................................24 


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Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
Confidential 
 
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7.1 
Subject Inclusion Criteria ...........................................................................................24 
7.2 
Subject Exclusion Criteria ..........................................................................................24 
7.3 
Screen Failures ............................................................................................................26 
8. 
TREATMENT OF SUBJECTS ..................................................................................27 
8.1 
Administration of Investigational Medicinal Product ................................................27 
8.2 
Prior and Concomitant Medications ...........................................................................27 
8.2.1 
Prohibited Medications ...............................................................................................27 
8.2.2 
Permitted Medications ................................................................................................28 
8.3 
Concomitant Procedures .............................................................................................28 
8.4 
Treatment Assignment, Randomization, and Blinding...............................................28 
8.4.1 
Treatment Assignment ................................................................................................28 
8.4.2 
Randomization ............................................................................................................28 
8.4.3 
Blinding ......................................................................................................................28 
9. 
INVESTIGATIONAL MEDICINAL PRODUCT .....................................................29 
9.1 
Description of Investigational Medicinal Product ......................................................29 
9.2 
Investigational Medicinal Product Supply and Control ..............................................29 
9.3 
Packaging and Labeling ..............................................................................................29 
9.4 
Investigational Medicinal Product Adherence ............................................................29 
9.5 
Investigational Medicinal Product Accountability .....................................................30 
9.6 
Investigational Medicinal Product Handling, Storage, and Disposal .........................30 
10. 
STUDY PROCEDURES AND SCHEDULE OF ASSESSMENTS .........................31 
10.1 
Informed Consent .......................................................................................................31 
10.2 
Electronic Case Report Forms (eCRFs) .....................................................................31 
10.3 
Procedures and Schedule of Assessments ..................................................................31 
10.3.1 
Screening Week -6 (Visit S1; Day -42 through Day -1) ............................................31 
10.3.2 
Treatment Day 1 (Visit T1) ........................................................................................32 
10.3.3 
Treatment Day 2 through Day 5 .................................................................................33 
10.3.4 
Treatment Day 5 through Day 7 (Visit T2) ................................................................33 
10.3.4.1 
Treatment Day 5 (Evening) ........................................................................................33 
10.3.4.2 
Treatment Day 6 .........................................................................................................34 
10.3.4.3 
Washout Day 7 (after completion of 24-hour breast milk collection) ........................34 
10.3.5 
Washout Day 13 (+ 3 days)/End of Study (Visit FU1) ..............................................35 


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Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
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10.3.6 
Serious Adverse Event Follow-up (SAE FU) and Resumption of Breast-
Feeding Day 43 (+ 5 days) (Visit FU2) ......................................................................35 
10.4 
Discontinuations .........................................................................................................35 
10.4.1 
Subjects Inadvertently Enrolled ..................................................................................35 
10.4.2 
Permanent Discontinuation of Investigational Medicinal Product .............................35 
10.4.3 
Subject Discontinuation from the Study .....................................................................36 
10.4.4 
Subjects Lost to Follow-Up ........................................................................................36 
10.4.5 
Discontinuation of Study Sites or the Study ...............................................................36 
11. 
PHARMACOKINETIC ASSESSMENTS .................................................................37 
11.1 
Breast Milk Sample Collection and Processing ..........................................................37 
11.2 
Blood Sample Collection and Processing ...................................................................37 
12. 
ASSESSMENT OF SAFETY .....................................................................................38 
12.1 
Safety Parameters .......................................................................................................38 
12.1.1 
Demographic Data and Medical History ....................................................................38 
12.1.2 
Estimated Glomerular Filtration Rate .........................................................................38 
12.1.3 
Child-Pugh Classification for Assessment of Liver Disease ......................................38 
12.1.4 
Vital Signs ..................................................................................................................38 
12.1.5 
Weight, Height, and Body Mass Index .......................................................................39 
12.1.6 
Physical Examination .................................................................................................39 
12.1.7 
Clinical Laboratory Tests ...........................................................................................39 
12.1.7.1 
Clinical Laboratory Parameters (Safety) ....................................................................39 
12.1.7.2 
Sample Collection .......................................................................................................41 
12.1.7.3 
General Monitoring and Management of Abnormal Clinical Laboratory 
Assessments ................................................................................................................41 
12.1.7.4 
Total Blood Volume of Clinical Laboratory Samples ................................................41 
13. 
ADVERSE AND SERIOUS ADVERSE EVENTS ...................................................42 
13.1 
Adverse Events ...........................................................................................................42 
13.1.1 
Definition of an Adverse Event ..................................................................................42 
13.1.2 
Reporting for Adverse Events ....................................................................................42 
13.1.3 
Severity .......................................................................................................................43 
13.1.4 
Relationship ................................................................................................................44 
13.1.5 
Monitoring and Follow-up of Adverse Events ...........................................................44 
13.2 
Serious Adverse Events ..............................................................................................44 


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13.2.1 
Definition of Serious Adverse Event ..........................................................................44 
13.2.2 
Events or Outcomes Not Qualifying as Serious Adverse Events ...............................45 
13.2.3 
Clinical Laboratory Assessments as Adverse Events and Serious Adverse 
Events .........................................................................................................................45 
13.2.4 
Reporting Serious Adverse Events .............................................................................45 
13.2.5 
Reporting of Subject Death ........................................................................................46 
13.2.6 
Reports of Pregnancy ..................................................................................................46 
13.2.7 
Reports of Infant Exposure to Investigational Medicinal Product via Breast 
Milk .............................................................................................................................46 
14. 
STATISTICS ..............................................................................................................48 
14.1 
General Considerations ...............................................................................................48 
14.2 
Determination of Sample Size ....................................................................................48 
14.3 
Analysis Population ....................................................................................................48 
14.3.1 
Safety Population ........................................................................................................48 
14.3.2 
Pharmacokinetic Population .......................................................................................48 
14.3.2.1 
Primary Analyses ........................................................................................................48 
14.3.2.2 
Secondary Analyses ....................................................................................................49 
14.4 
Safety Analyses ..........................................................................................................49 
15. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS.........................................50 
15.1 
Study Monitoring ........................................................................................................50 
15.2 
Audits and Inspections ................................................................................................50 
16. 
QUALITY CONTROL AND QUALITY ASSURANCE .........................................51 
17. 
ETHICS ......................................................................................................................52 
17.1 
Institutional Review Board Approval .........................................................................52 
17.2 
Ethical Conduct of the Study ......................................................................................52 
17.3 
Written Informed Consent ..........................................................................................53 
17.4 
Subject Confidentiality ...............................................................................................53 
18. 
DATA HANDLING AND RECORDKEEPING .......................................................54 
18.1 
Inspection of Records .................................................................................................54 
18.2 
Retention of Records ..................................................................................................54 
18.3 
Case Report Forms and Study Records ......................................................................54 
19. 
ADMINISTRATIVE CONSIDERATIONS ..............................................................56 
19.1 
Investigators ................................................................................................................56 


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19.2 
Study Administrative Structure ..................................................................................57 
19.3 
Amendments and Study Termination .........................................................................57 
19.4 
Financial Disclosure ...................................................................................................58 
20. 
PUBLICATION AND DISCLOSURE POLICY .......................................................59 
21. 
LIST OF REFERENCES ............................................................................................60 
22. 
APPENDICES ............................................................................................................61 
APPENDIX 1. SCHEDULE OF ASSESSMENTS ....................................................................62 
APPENDIX 2. CHILD-PUGH CLASSIFICATION ..................................................................64 
APPENDIX 3. SPONSOR’S SIGNATURES .............................................................................65 
APPENDIX 4. INVESTIGATOR’S SIGNATURE....................................................................66 
APPENDIX 5. SUMMARY OF CHANGES IN AMENDMENT 1 PROTOCOL ....................67 
 


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LIST OF TABLES 
Table 1: 
Investigational Medicinal Products ............................................................................29 
Table 2: 
Safety Laboratory Parameters .....................................................................................40 
 
LIST OF FIGURES 
Figure 1: 
Study Schematic .........................................................................................................22 
 
 
 
 


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3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
Abbreviation or Specialist Term 
Explanation 
ACL 
adenosine triphosphate-citrate lyase 
ACS 
acyl-CoA synthetase 
ACSVL1 
very long-chain acyl-CoA synthetase 1 
ADR(s) 
adverse drug reaction(s) 
AE(s) 
adverse event(s) 
AESI(s) 
adverse event(s) of special interest 
Alb 
albumin 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ApoB 
apolipoprotein B 
ASCVD 
atherosclerotic cardiovascular disease 
AST 
aspartate aminotransferase 
AUC 
area under the concentration time curve 
AUC0-24 
area under the concentration time curve from 0 to 24 hours 
BA 
bempedoic acid 
BMI 
body mass index 
BP 
blood pressure 
BUN 
blood urea nitrogen 
Ca 
calcium 
CFR 
Code of Federal Regulations 
CHD 
coronary heart disease 
CI 
confidence interval 
CK 
creatine kinase 
CPK 
creatine phosphokinase 
Cl 
chloride 
CNS 
central nervous system 
CoA 
acetyl-coenzyme A 
CO2 
carbon dioxide 
CRO 
contract research organization 


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Abbreviation or Specialist Term 
Explanation 
CVD 
cardiovascular disease 
CYP 
cytochrome P450 
DBP 
diastolic blood pressure 
eCRF 
electronic case report form 
eGFR 
estimated glomerular filtration rate 
EMA 
European Medicines Agency 
EU 
European Union 
EZE 
ezetimibe 
FCDP 
fixed combination drug product 
FCMP 
fixed combination medicinal product 
FDA 
US Food and Drug Administration 
GCP 
Good Clinical Practice 
Hct 
hematocrit 
HDL-C 
high-density lipoprotein cholesterol 
HeFH 
heterozygous familial hypercholesterolemia 
Hgb 
hemoglobin 
HMG-CoA 
3-hydroxy-3-methylglutaryl coenzyme A 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IMP 
investigational medicinal product 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
IUD 
intrauterine device 
K 
potassium 
LDL-C 
low-density lipoprotein cholesterol 
LSM 
least squares mean 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
MED ID 
medication identification 
MedDRA 
Medical Dictionary for Regulatory Activities 


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Abbreviation or Specialist Term 
Explanation 
MI 
myocardial infarction 
N/A 
not applicable 
N/D 
not done 
NOAEL 
no-observed-adverse-effect level 
non-HDL-C 
non-high-density lipoprotein cholesterol 
PCSK9 
proprotein convertase subtilisin kexin type 9 
PE 
physical exam 
PK 
pharmacokinetic(s) 
RBC 
red blood cell 
RID 
relevant infant dose 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SBP 
systolic blood pressure 
SGOT 
serum glutamic oxaloacetic transaminase 
SGPT 
serum glutamic pyruvic transaminase 
SmPC 
Summary of Product Characteristics 
SOC 
System Organ Class 
SOP(s) 
standard operating procedure(s) 
SP 
Safety Population 
SUSAR 
suspected and unexpected serious adverse reaction 
TB 
total bilirubin 
TC 
total cholesterol 
TEAE(s) 
treatment-emergent adverse event(s) 
TMF 
Trial Master File 
ULN 
upper limit of normal 
US 
United States 
USPI 
United States Prescribing Information 
WBC 
white blood cell 
WHO 
World Health Organization 
 
 
 


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4. 
INTRODUCTION 
 
Bempedoic acid (ETC-1002) is an oral, first-in class, small molecule that inhibits adenosine 
triphosphate-citrate lyase (ACL), an enzyme upstream of 3-hydroxy-3-methylglutaryl coenzyme 
A (HMG-CoA) reductase in the cholesterol biosynthesis pathway. Bempedoic acid, like statins, 
up-regulates low density lipoprotein cholesterol (LDL-C) receptors. 
Bempedoic acid 180 mg and bempedoic acid 180 mg/ezetimibe 10 mg fixed combination drug 
product (FCDP), under the marketed names of Nexletol® and Nexlizet®, respectively, have been 
approved by the United States (US) Food and Drug Administration (FDA) as an adjunct to diet 
and maximally tolerated statin therapy for the treatment of heterozygous familial 
hypercholesterolemia or established atherosclerotic cardiovascular disease in adults who require 
additional lowering of LDL-C (Nexletol 2020 USPI; Nexlizet 2020 USPI). In the European 
Union (EU) bempedoic acid and bempedoic acid/ezetimibe fixed combination medicinal product 
(FCMP) have been approved by the European Commission and are marketed under the names 
Nilemdo® and Nustendi®, respectively, for the treatment of primary hypercholesterolemia 
(heterozygous familial and non-familial) or mixed dyslipidemia as an adjunct to diet: in 
combination with a statin or statin with other lipid-lowering therapies in adults unable to reach 
LDL-C goals with the maximum tolerated dose of statin, or alone or in combination with other 
lipid-lowering therapies in patients who are statin-intolerant or for whom a statin is 
contraindicated. Additionally, Nustendi is indicated in patients already being treated with the 
combination of bempedoic acid and ezetimibe as separate tablets with or without statin 
(Nilemdo 2020 SmPC; Nustendi 2020 SmPC). 
Bempedoic acid and bempedoic acid/ezetimibe FCDP have been studied in adults with 
heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular 
disease (ASCVD) who require additional LDL-C lowering but data do not exist for lactating 
women who may choose to continue breastfeeding their infant in conjunction with bempedoic 
acid or bempedoic acid/ezetimibe FCDP therapy.  There is no information regarding the 
excretion of bempedoic acid in human or animal milk, the effects of bempedoic acid on the 
breastfed infant, or the effects of bempedoic acid on milk production.  Bempedoic acid decreases 
cholesterol synthesis and possibly the synthesis of other biologically active substances derived 
from cholesterol and theoretically may cause harm to the breastfed infant.  In addition, it is not 
known whether ezetimibe is excreted into human milk.  In rat studies, exposure to total ezetimibe 
in nursing pups was up to half of that observed in maternal plasma (Zetia 2020 USPI). 
The USPIs for bempedoic acid (Nexletol 2020 USPI) and bempedoic acid/ezetimibe FCDP 
(Nexlizet 2020 USPI) note breastfeeding is not recommended with either therapy and the SmPCs 
for bempedoic acid (Nilemdo 2020 SmPC) and bempedoic acid/ezetimibe FCMP (Nustendi 2020 
SmPC) state breastfeeding is contraindicated.  As a result of the current labeling in conjunction 
with the paucity of data, patients, along with their health care providers, must make decisions 
about bempedoic acid and bempedoic acid/ezetimibe FCDP therapy during lactation with a lack 
of evidence-based data regarding the excretion of bempedoic acid or bempedoic acid and 
ezetimibe into breast milk and the potential exposure to the breast fed infant. 


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4.1 
Study Rationale 
This Phase 4 study is designed to characterize the excretion of bempedoic acid or bempedoic 
acid and ezetimibe into mature breast milk of healthy lactating women and assess the exposure to 
the breast fed infant by estimating the daily infant dosage and the relative infant dose (RID) of 
bempedoic acid or bempedoic acid and ezetimibe in breast milk after 6 consecutive daily doses 
of bempedoic acid or bempedoic acid/ezetimibe FCDP. 
4.2 
Background of Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP 
Bempedoic acid is an ACL inhibitor that lowers LDL-C by inhibition of cholesterol synthesis in 
the liver.  Adenosine triphosphate-citrate lyase is an enzyme upstream of HMG-CoA reductase in 
the cholesterol biosynthesis pathway.  Bempedoic acid and its active metabolite ESP15228 
require coenzyme A (CoA) activation by very long-chain acyl-CoA synthetase 1 (ACSVL1) to 
ETC-1002-CoA and ESP 15228-CoA, respectively.  Inhibition of ACL by ETC-1002-CoA 
results in decreased cholesterol synthesis in the liver and lowers LDL-C in blood via 
upregulation of low-density lipoprotein receptors. 
Bempedoic acid and bempedoic acid/ezetimibe FCDP have been approved by the FDA and 
European Medicines Agency (EMA) based on the positive safety and efficacy profiles of large 
Phase 3 programs that evaluated adults with primary and secondary hyperlipidemia who required 
additional LDL-C lowering.  Please refer to the most recent Investigator Brochure (IB) for more 
detailed information regarding nonclinical experience and previous human experience along with 
the USPIs and the SmPCs for bempedoic acid and bempedoic acid/ezetimibe FCDP. 
4.3 
Dose Selection 
A dose of bempedoic acid 180 mg once per day was selected based on approved doses by the US 
FDA (Nexletol) and the European Medicines Agency (Nilemdo).  The dose for bempedoic 
acid/ezetimibe FCDP (bempedoic acid 180 mg/ezetimibe 10 mg) was selected based on 
approved doses by the US FDA (Nexlizet) and the European Medicines Agency (Nustendi).  For 
additional information please refer to the most recent IB, the USPIs for Nexletol and Nexlizet 
and the SmPCs for Nilemdo and Nustendi. 
Subjects enrolled in the study will be dosed for 6 consecutive days in order to reach steady-state 
concentrations of bempedoic acid or bempedoic acid and ezetimibe in plasma.  Steady-state 
concentrations in plasma are expected after 5 to 7 days of repeat dosing as estimates of 
elimination half-life of bempedoic acid and ezetimibe are each approximately 24 hours.  A once 
daily dosing regimen for 6 days will achieve plasma concentrations that are approximately 98% 
of steady-state levels.  Six days of repeat dosing have been selected to ensure subjects are at 
steady-state plasma concentrations of bempedoic acid or bempedoic acid and ezetimibe for 
pharmacokinetic (PK) assessments.  
4.4 
Risk Benefit Summary 
Subjects in this clinical study are healthy lactating volunteers who choose to stop breastfeeding 
their infant for the duration of the Treatment and Washout Periods (13 days) and will not receive 
any health benefit from participating in this study.  Both bempedoic acid and bempedoic 
acid/ezetimibe FCDP are approved by the FDA and EMA. 


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This study will provide evidence-based data to inform lactating women in the US with HeFH or 
ASCVD and their health care providers whether to continue with treatment of bempedoic acid or 
bempedoic acid/ezetimibe FCDP during breast feeding. 
Please refer to the most recent IB for more detailed information regarding previous human 
experience along with the USPIs and the SmPCs for bempedoic acid and bempedoic 
acid/ezetimibe FCDP. 
 
 


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5. 
OBJECTIVES AND ENDPOINTS 
5.1 
Objectives 
5.1.1 
Primary Objective 
The primary objectives of this study are to estimate infant exposure to bempedoic acid or 
bempedoic acid and ezetimibe: 
• estimate the daily infant dosage and the relative infant dose (RID) of bempedoic acid 
in mature breast milk after administration of bempedoic acid for 6 consecutive days, 
and  
• estimate the daily infant dosage and RID of bempedoic acid and ezetimibe in mature 
breast milk after administration of bempedoic acid/ezetimibe FCDP for 6 consecutive 
days. 
5.1.2 
Secondary Objectives 
The secondary objectives of this study are to characterize the excretion of bempedoic acid or 
ezetimibe in mature breast milk of healthy lactating women who receive once daily dose of 
bempedoic acid or bempedoic acid/ezetimibe FCDP for 6 consecutive days: 
• determine concentrations of bempedoic acid, active metabolite ESP15228 and 
bempedoic acid glucuronide in mature breast milk collected over 24 hours from 
healthy subjects administered bempedoic acid or bempedoic acid/ezetimibe 
FCDP, and 
• determine concentrations of ezetimibe and metabolite ezetimibe-glucuronide in 
mature breast milk collected over 24 hours from healthy subjects administered 
bempedoic acid/ezetimibe FCDP. 
5.1.3 
Safety Objective 
The safety objective of this study is to evaluate the safety of 6 consecutive doses of bempedoic 
acid or bempedoic acid/ezetimibe FCDP in healthy lactating women. 
5.2 
Endpoints 
5.2.1 
Pharmacokinetic Assessments 
5.2.1.1 Primary Endpoints 
Bempedoic acid and ezetimibe assessments include: 
• daily infant dosage calculated as the cumulative amount excreted in breast milk per 
day, and  
• RID calculated as the ratio of total infant daily dose per kg body weight and maternal 
daily dose per kg of body weight multiplied by 100. 
 
 


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5.2.1.2 Secondary Endpoints 
Bempedoic acid, ezetimibe, and metabolites (ESP15228, bempedoic acid glucuronide, and 
ezetimibe-glucuronide) assessments include: 
• amount excreted in each breast milk collection, calculated as the product of 
concentration and milk volume collected, 
• area under the milk concentration-time curve (AUC) over the 24-hour collection 
interval, 
• average milk concentration based on milk AUC, 
• peak and trough milk concentrations and the time of peak milk concentrations, and 
• plasma trough concentrations at 24 hours after the last dose on Day 6. 
5.2.2 
Safety Endpoints 
Adverse events (all and treatment-emergent), clinical laboratory parameters, vital signs, and 
physical examinations will be collected. 
 
 


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6. 
INVESTIVATIONAL PLAN 
6.1 
Overall Study Design 
This is a Phase 4, open-label study that will estimate the daily infant dosage and RID for 
bempedoic acid and bempedoic acid/ezetimibe FCDP and characterize the excretion of 
bempedoic acid, ezetimibe, and metabolites ESP 15228, bempedoic acid glucuronide, and 
ezetimibe-glucuronide in the mature breast milk of healthy women.  The study will enroll 
16 healthy lactating subjects, who will be randomized in a 1:1 ratio to receive either bempedoic 
acid (Cohort 1) or bempedoic acid/ezetimibe FCDP (Cohort 2), who choose to stop breastfeeding 
their infant for the duration of the Treatment and Washout periods (13 days).  After signing the 
informed consent form (ICF), subjects will enter the Screening Period for up to 42 days, 
followed by a 6-day Treatment Period and a 7-day Washout Period.  At Visit T1, subjects will be 
administered IMP at the clinical research unit CRU.  The IMP will then be self-administered at 
home on Day 2 through Day 5.  Study staff will phone subjects Day 2 through Day 5 to ensure 
IMP is being taken appropriately and remind subjects to discard breast milk produced after the 
first dose of IMP.  Subjects will check-in to the CRU on the evening of Day 5 (with Sponsor 
approval the subject may check-in to the CRU on the morning of Day 6) for Visit T2 and start a 
24-hour breast milk collection after the last dose of IMP on the morning of Day 6.  Serum PK 
samples will be obtained on Day 7, approximately 24 hours after IMP administration on Day 6.  
Subjects will be discharged from the CRU on the morning of Day 7 approximately 24 hours after 
Day 6 dosing and the completion of all Day 7 assessments.  At the end of the Washout Period on 
Day 13, all subjects will be contacted by phone for a Post-treatment Follow-up Visit (Visit FU1).  
Once the call is complete, subjects may resume feeding their infants breast milk that is currently 
being produced. On Day 43 (Visit FU2), study staff will contact subjects by phone to assess for 
SAEs and if the patient was able to resume breastfeeding (if intended). 
 Please refer to Appendix 1 for a detailed Schedule of Assessments. 
Figure 1: 
Study Schematic 
 
6.2 
Scientific Rationale 
Consistent with the FDA’s Draft Guidance for Industry, Clinical Lactation Studies:  
Considerations for Study Design (FDA May 2019) this Phase 4 study is designed to characterize 
the excretion of bempedoic acid or bempedoic acid and ezetimibe in mature human breast milk.  


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The data generated from this study will aid in assessing exposure and potential effects on the 
breastfed infant.  
6.3 
Estimated Study Duration 
Each subject will be in the study for up to 55 days.  The 55 days are inclusive of an up to 42 days 
Screening Period followed by a 6-day Treatment Period and a 7-day Washout Period. 
6.4 
Number of Centers 
Up to 2 clinical research units (CRU) will participate in this study in the US.  Additional sites 
may be invited to participate to ensure study timelines are met. 
6.5 
Number of Subjects 
The study will enroll approximately 16 healthy lactating women randomized in a 1:1 ratio of 
bempedoic acid (Cohort 1) to bempedoic acid/ezetimibe FCDP (Cohort 2).  
6.6 
Subject Number and Identification 
A unique subject identification number will be assigned to each subject to identify each subject 
throughout the study. Subject identification numbers will be assigned sequentially by the study 
site at the time of informed consent at the Screening Visit (Visit S1).  
6.7 
Subject Withdrawal and Replacement 
A subject is free to withdraw from the study at any time.  Approximately 16 (8 bempedoic acid 
[Cohort 1] and 8 bempedoic acid/ezetimibe FCDP [Cohort 2]) healthy lactating female subjects 
will be enrolled.  If a subject discontinues the study early or does not receive 6 daily doses of 
IMP or does not complete the 24-hour breast milk collection after Day 6 dosing, a replacement 
subject will be enrolled and assigned to the same treatment.  The site must notify the Sponsor of 
any early withdrawals. 
6.8 
End of Study 
A subject is considered to have completed the study if all phases of the study are completed 
including the Follow-up Visit (FU1) on Day 13.  
The end of the study is defined as the date of the Follow-up Visit (FU1) on Day 13 for the last 
active subject in the study. 
Study staff will contact subjects by phone 30 days (Day 43, FU2) after FU1 to assess for serious 
adverse events (SAEs) and if the patient was able to resume breastfeeding (if intended). 
 
 


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7. 
SELECTION OF SUBJECTS 
7.1 
Subject Inclusion Criteria 
Each subject must meet the following criteria to be eligible for this study. 
1. The subject must be willing to provide written informed consent before any 
study-specific procedures are performed. 
2. The subject must be 18 to 45 years old, inclusive. 
3. The subject must be a lactating female who had a normal full-term pregnancy and has 
been actively breastfeeding or pumping for at least 4 weeks; lactation must be 
well-established per Investigator discretion. 
4. The subject must be willing to pump regularly during the study to maintain milk supply 
and discontinue breastfeeding for the entire 13-day Treatment and Washout Periods. 
5. The subject must not be pregnant. 
6. The subject must be surgically sterile by hysterectomy, bilateral oophorectomy, and/or 
tubal ligation, or willing to use 1 acceptable method of birth control unless they have 
agreed to follow the definition of abstinence.  The minimal requirement of adequate 
contraception should be started on Day 1 and continued during the study period and for at 
least 30 days after the last dose of IMP.  Acceptable methods of birth control include: 
• an intrauterine device (IUD) with or without hormones; 
• established use of oral, implanted, transdermal, injectable, or hormonal method of 
contraception associated with inhibition of ovulation; 
• barrier methods including condom or occlusive cap with spermicidal foam or 
spermicidal jelly; 
• vasectomized male partner who is the sole partner for this subject; or, 
• true abstinence (when this is in line with the preferred and usual lifestyle of the 
subject).  Note:  periodic abstinence (e.g., calendar, ovulation, symptothermal, 
post-ovulation methods), declaration of abstinence for the duration of the trial, and 
withdrawal are not acceptable methods of contraception. 
7.2 
Subject Exclusion Criteria 
Subjects who meet any of the following criteria will not be eligible to participate in this study. 
1. Has clinically significant infection (e.g., pneumonia, pyelonephritis) or chronic infection 
within 30 days prior to enrollment. 
2. Has evidence of unstable or uncontrolled, clinically significant cardiovascular, central 
nervous system, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, 
coagulation, immunological, endocrine/metabolic, or other medical disorder, including 
serious allergy, asthma, hypoxemia, hypertension, seizures, or allergic skin rash, that, in 
the opinion of the Investigator, would confound the study results or compromise subject 
safety. 


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3. Has estimated glomerular filtration rate (eGFR) <30 mL/min/1.732 using the Modification 
of Diet in Renal Disease [MDRD] formula.  
4. Has liver disease or dysfunction characterized by Child-Pugh Class B or Class C. 
5. History of any major neurological disorders, including stroke, multiple sclerosis, brain 
tumor, or neurodegenerative disease. 
6. Has active psychiatric problems that, in the Investigator’s opinion, may interfere with 
compliance with the study procedures. 
7. Is unable to participate in all the study visits or comply with study procedures. 
8. Has history of breast implants, breast augmentation, or breast reduction surgery. 
9. Has a prior history of difficulty establishing lactation. 
10. Gastrointestinal conditions or procedures (including weight loss surgery; e.g., Lap-
Band® or gastric bypass) that may affect drug absorption. 
11. Any history of malignancy (with the exception only of basal or squamous cell carcinoma 
of the skin in individuals that have been cancer free for >5 years). 
12. History within the last 2 years of drug, alcohol, amphetamine and derivatives, or cocaine 
abuse.  Subjects with amphetamine derivatives prescribed by and under the care of a 
health care practitioner can be enrolled after evaluation by the Investigator.  
13. Current smoker. 
14. Blood donation, participation in a multiple blood draw clinical study, major trauma, or 
surgery with or without blood loss within 30 days prior to enrollment. 
15. Blood transfusion for any reason within 90 days prior to enrollment. 
16. Use of any HMG Co-A reductase inhibitor (statin) concurrently or within 30 days prior to 
enrollment. 
17. Use of cyclosporine, cholestyramine, probenecid, fibrate drugs, or medications 
contraindicated during lactation concomitantly or within 30 days prior to randomization 
(Visit T1). 
18. Concomitant use or use within 30 days prior to randomization (Visit T1) of drugs that 
decrease breast milk production, such as pseudoephedrine 
19. Concomitant use or use within 30 days prior to randomization (Visit T1) of drugs that 
increase breast milk production, such as domperidone. 
20. Use of any experimental or investigational drugs/vaccines concurrently or within 30 days 
or 5 half-lives of the drug, whichever is longer, prior to screening (Visit S1). 
21. Any current condition that in either the Investigator’s, Sponsor’s, or authorized Medical 
Monitor’s opinion may compromise subject safety or ability to complete the study or 
interfere with study data interpretation. 
22. An employee or contractor of the facility conducting the study, or a family member of the 
Principal Investigator, Co-Investigator, or Sponsor. 


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7.3 
Screen Failures 
Subjects who sign the ICF and enter the screening period of the study but do not meet all 
eligibility criteria at the time of randomization (Visit T1) will be considered a screen failure and 
will not be randomized into the study.  
 
 


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8. 
TREATMENT OF SUBJECTS 
8.1 
Administration of Investigational Medicinal Product  
On Day 1 (Visit T1) of the Treatment Period, subjects will be randomized to receive bempedoic 
acid (Cohort 1) or bempedoic acid/ezetimibe FCDP (Cohort 2).  Each dose of IMP is comprised 
of 1 tablet from a bottle.  The CRU staff will administer IMP to subjects in the unit on Day 1 and 
Day 6 of the study.  The IMP will be self-administered by subjects on Day 2 through Day 5 at 
home.  Subjects will be instructed to take IMP once daily at approximately the same time each 
morning (± 2 hours) with or without food.  On the evening of Day 5 (Visit T2), subjects will 
check-in to the CRU and CRU staff will administer IMP on the morning of Day 6. 
Study staff will call subjects on Days 2 through Day 5 to ensure they are taking IMP 
appropriately.  Day and time of IMP administration must be captured in the Study Drug Diary.  
If the subject forgets to take IMP at the same time (± 2 hours) Day 2 through Day 5, it may be 
taken up to 6 hours later the same day.  After that, the subject should not take IMP that day and 
the Sponsor should be contacted to determine if the subject should continue or be replaced in the 
study.  The details describing the reason for the missed dose should be documented in the 
subject’s medical record.  Extra IMP is provided and can be used to replace a dose of IMP that 
cannot be used if lost or damaged. 
Other details regarding IMP including description, supply and control, accountability, handling, 
and disposal are provided in Section 0.  
8.2 
Prior and Concomitant Medications 
Any medication or vaccine (including over the counter or prescription medicines, vitamins, 
and/or herbal supplements) that the subject is receiving at the time of enrollment or receives 
during the study must be recorded in the eCRF along with: 
• reason for use, 
• dates of administration including start and end dates, and 
• dosage information including dose and frequency. 
Subjects will be permitted to take concomitant medications except those listed in Section 8.2.1. 
8.2.1 
Prohibited Medications  
Subjects may not use medications listed below within the time periods indicated and may not use 
the following drugs during the study: 
• HMG Co-A reductase inhibitor (statin) concurrently or within 30 days prior to 
randomization (Visit T1); 
• cyclosporine, cholestyramine, probenecid, fibrate drugs, or medications 
contraindicated during lactation concurrently or within 30 days prior to randomization 
(Visit T1); 
• experimental or investigational drugs concurrently or within 30 days or 5 half-lives of 
the drug, whichever is longer, prior to screening (Visit S1); 


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• concomitant use or use within 30 days prior to randomization (Visit T1) of drugs that 
decrease breast milk production, such as pseudoephedrine; or 
• concomitant use or use within 30 days prior to randomization (Visit T1) of drugs that 
increase breast milk production, such as domperidone. 
8.2.2 
Permitted Medications 
Concomitant use of prescription or nonprescription medications, vaccines and supplements not 
listed in Section 8.2.1 are allowed during the study, upon prior consent of the Investigator (or 
designee) and Sponsor. 
8.3 
Concomitant Procedures 
Any procedure that the subject undergoes after signing the ICF throughout the duration of the 
study must be recorded in the eCRF along with: 
• date of the procedure, and  
• reason for the procedure 
8.4 
Treatment Assignment, Randomization, and Blinding 
8.4.1 
Treatment Assignment 
Subjects will receive open-label IMP during the Treatment Period of the study.  Subjects will be 
randomized (Visit T1) to receive either bempedoic acid (Cohort 1) or bempedoic acid/ezetimibe 
FCDP (Cohort 2).  The IMP will be taken Day 1 through Day 6 of the treatment period. 
8.4.2 
Randomization 
Subjects will be randomized in a 1:1 ratio to receive either bempedoic acid (Cohort 1) or 
bempedoic acid/ezetimibe FCDP (Cohort 2) on Day 1 (Visit T1) of the treatment period.  When 
the target number of subjects (8 in each cohort) is reached and all subjects have completed the 
24-hour breast milk collection at the CRU, randomization will be closed.  If a subject is 
randomized but did not complete the 24-hour breast milk collection in the CRU, she will be 
replaced with a new subject on the same treatment to ensure each cohort of the study has 8 
evaluable subjects. 
8.4.3 
Blinding 
This is an open-label study. 
 
 


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9. 
INVESTIGATIONAL MEDICINAL PRODUCT  
9.1 
Description of Investigational Medicinal Product 
The IMP used for this study are described in Table 1.  Please see the Pharmacy Manual for 
detailed storage requirements and instructions. 
Table 1: 
Investigational Medicinal Products 
 
Investigational Medicinal Product 
Product Name: 
Bempedoic acid 
Bempedoic acid/ezetimibe 
FCDP 
Dosage Form: 
Film-coated tablets 
Film-coated tablets 
Unit Dose: 
180 mg 
180 mg/10 mg 
Container/Closure: 
 Bottle 
 Bottle 
Route of Administration: 
Oral, daily at similar time with 
or without food 
Oral, daily at similar time with 
or without food 
Physical Description: 
Oval, white to off-white tablet 
debossed with “180” on one side 
and “ESP” on the other 
Oval, blue tablet debossed with 
“818” on one side and “ESP” on 
the other 
FCDP = Fixed combination drug product 
 
9.2 
Investigational Medicinal Product Supply and Control 
The Sponsor will supply the IMPs for this study.  The IMPs for this study, bempedoic acid and 
bempedoic acid/ezetimibe FCDP, have been approved by the FDA as Nexletol® and Nexlizet®, 
respectively.  Investigational medicinal product will be distributed and released in accordance 
with regional and local requirements during the conduct of the study. 
Investigational medicinal product will be dispensed by the Investigator or other qualified study 
personnel only to subjects who have provided informed consent. 
9.3 
Packaging and Labeling 
Open-label IMP will be packaged in a bottle containing 30 tablets.  The IMP labels will be 
compliant with the Code of Federal Regulations (CFR) Title 21 Section 312.6 Labeling of an 
Investigational New Drug.  
9.4 
Investigational Medicinal Product Adherence 
On Day 2 through Day 5 subjects will document day and time IMP is taken in the Study Drug 
Diary and the diary will be submitted to study staff at check-in to the CRU on the evening of 
Day 5 (Visit T2).  In addition, study staff will phone subjects on Day 2 through Day 5 to ensure 
subjects are taking IMP appropriately.  Study staff will assess subject adherence through phone 
calls, review of the Study Drug Diary, and by counting the number of tablets returned at check-in 
to the CRU on the evening of Day 5.  If a subject has missed a dose of IMP, the Sponsor will be 
notified immediately to determine if the subject should continue in the study or be replaced. 


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9.5 
Investigational Medicinal Product Accountability 
Subjects will be instructed to return all packaging and unused IMP at check-in to the CRU on 
Day 5 (Visit T2) for assessment of adherence and drug accountability. 
Accurate records of the receipt of all IMP shipped by the Sponsor (or designee) and the 
disposition of that IMP must be maintained. 
All IMP records or logs must comply with applicable regulations, local law, and guidelines, and 
should include the: 
• amount received/placed in storage area; 
• amount currently in storage area; 
• MED ID/Kit number for all IMP; 
• dates and initials of person(s) responsible for IMP inventory (including 
entry/movement/disposition); 
• date and amount of IMP dispensed to each subject, including unique subject 
identifiers; 
• date that IMP was returned by subject, assessment of adherence, and relevant 
documentation of discrepancies; 
• nonstudy disposition (e.g., lost, broken, wasted); and 
• amount returned to Sponsor (or designee)/destroyed or amount destroyed per local 
standard operating procedure (SOP) following accountability by site monitor. 
9.6 
Investigational Medicinal Product Handling, Storage, and Disposal 
The Principal Investigator will ensure that all IMP is stored in a secure area, under recommended 
storage conditions.  Bempedoic acid and bempedoic acid/ezetimibe FCDP must be stored at 68°F 
to 77°F (20°C to 25°C); excursions permitted to 59°F to 86°F (15°C to 30°C).  Bempedoic acid 
must be stored and dispensed in the original package.  Bempedoic acid/ezetimibe must be stored 
and dispensed in the original package protected from extreme heat and humidity.  Access to IMP 
will be limited to those clinical site personnel authorized by the Investigator.  Upon completion 
or termination of the study, all IMP and used and unused IMP packaging must be returned to the 
Sponsor (or designee) for eventual destruction unless otherwise authorized by the Sponsor.  All 
IMP returns must be accompanied by the appropriate documentation. 
 
 


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10. 
STUDY PROCEDURES AND SCHEDULE OF ASSESSMENTS 
10.1 
Informed Consent 
The subject must be adequately informed of the nature and risks of the study and understand the 
ICF.  It is the Investigator’s responsibility that no study-related procedure will be performed until 
the subject has been completely informed of the study, has freely consented to take part in the 
study, and has signed and dated an ICF approved by the Sponsor (or designee) and the 
Institutional Review Board (IRB).  The written ICF should be prepared in the local language(s) 
of the potential subject population.  
10.2 
Electronic Case Report Forms (eCRFs) 
Data will be captured on eCRFs.  
10.3 
Procedures and Schedule of Assessments 
The study is comprised of 3 distinct periods: Screening Period, Treatment Period, and 
Washout/Follow-up Period. 
The Schedule of Assessments is provided in Appendix 1; however, a subject can be seen at any 
time for reasons of safety.  
Lactation consultant visits will be scheduled anytime during the study for those subjects who 
desire support related to feeding/care of the infant such as preparing for the treatment and 
washout periods of the study, pumping breast milk for storage, introducing infant formula, 
introducing bottle feeding or resuming breastfeeding after Day 13 (FU1).  
If the subject discontinues IMP or misses a dose, please contact the Sponsor immediately to 
determine if subject should continue in the study or be replaced. 
10.3.1 Screening Week -6 (Visit S1; Day -42 through Day -1)  
The screening period will begin with a screening visit (Visit S1) that will occur up to 6 weeks 
prior to randomization (Visit T1).  Visit S1 will allow the Investigator to assess the subject’s 
eligibility.  After the subject provides informed consent (Section 10.1), the subject will undergo 
the following assessments: 
• demographics; 
• medical history including gestational age of infant at delivery, date of delivery, stage 
of lactation, length of time post-partum, smoking and alcohol intake; 
• Review of current breastfeeding practices per subject report, including: 
o frequency and duration of feeds for infants fed from the breast, 
o bottles/day and ounces/day for infant’s fed pumped breast milk from a bottle, and 
o use of formula supplementation (bottles/day, ounces/day and duration of 
supplementation); 
• confirm subject is maintaining adequate breast milk production (document duration of 
weaning, if applicable) per subject report; 


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• confirm infant is able to bottle feed prior to randomization (Visit T1) per subject 
report; 
• confirm adequate breast milk/infant formula is available to feed the infant after first 
dose of IMP (Visit T1) through Day 13 (Visit FU1) per subject report; 
• concomitant medication review; 
• adverse event review; 
• physical exam; 
• weight, height, and BMI; 
• vital signs; 
• clinical lab evaluations (blood chemistry, hematology and serology); 
• assessment of renal function (eGFR calculated according to MDRD formula); 
• assessment for liver disease (according to Child Pugh Classification score); 
• serum pregnancy test; 
• urine drug and alcohol screen; and 
• schedule optional lactation consultant visit. 
Note:  subjects must understand that they will not be able to feed their infant breast milk 
produced after the first dose of IMP through Day 13. 
10.3.2 Treatment Day 1 (Visit T1) 
Subjects who continue to meet all inclusion criteria and none of the exclusion criteria may be 
randomized into the study.  Each subject will undergo the following assessments: 
• Review of current breastfeeding practices per subject report, including: 
o frequency and duration of feeds for infants fed from the breast, 
o bottles/day and ounces/day for infant’s fed pumped breast milk from a bottle, and 
o use of formula supplementation (bottles/day, ounces/day and duration of 
supplementation); 
• confirm subject is maintaining adequate breast milk production (document duration of 
weaning, if applicable) per subject report; 
• confirm infant is able to bottle feed prior to randomization (Visit T1) per subject 
report; 
• confirm adequate breast milk/infant formula is available to feed the infant after first 
dose of IMP (Visit T1) through Day 13 (Visit FU1) per subject report; 
• adverse event review; 
• concomitant medicine review; 
• weight; 


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• vital signs; 
• urine pregnancy test; 
• predose breast milk collection (≤1 hour before IMP administration); 
• predose blood sample for chemistry and hematology; 
• predose blood sample for plasma PK; 
• administer first dose of IMP; 
• dispense IMP for self-administration on Day 2 through Day 5; 
• provide Study Drug Diary; and 
• schedule optional lactation consultant visit. 
The IMP will be administered by study staff only after the predose breast milk collection, 
predose chemistry and hematology, and predose plasma PK sample are collected.  Subjects must 
be reminded to not feed their infant breast milk produced after the first dose of IMP through 
Day 13 of the study.  
Subjects will be instructed to take IMP at the same time (± 2 hours) every day with or without 
food for Day 2 though Day 5 and to complete the Study Drug Diary. 
10.3.3 Treatment Day 2 through Day 5 
Study staff will contact the subject by phone to conduct the following: 
• adverse event review; 
• concomitant medication review; 
• confirm subject is taking IMP appropriately; 
• instruct subject to complete the Study Drug Diary; 
• confirm subject is maintaining adequate breast milk production (document duration of 
weaning, if applicable) per subject report; 
• confirm subject is discarding breast milk produced after the first dose of IMP through 
Day 13 per subject report; 
• confirm adequate stored breast milk and/or infant formula is available to feed the 
infant through Day 13 of the study per subject report; and 
• schedule optional lactation consultant visit. 
10.3.4 Treatment Day 5 through Day 7 (Visit T2) 
10.3.4.1 Treatment Day 5 (Evening) 
Subjects will check-in to the CRU on the evening of Day 5 for 2 overnights.  With Sponsor 
approval, the subject may check-in to the CRU the morning of Day 6. 
Subjects will return IMP to the study staff prior to the following assessments: 
• adverse event review; 


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• concomitant medication review; 
• review of Study Drug Diary and assessment of IMP adherence (if subject missed a 
dose or discontinued IMP, refer to Section 9.4); 
• confirm subject is maintaining adequate breast milk production (document duration of 
weaning, if applicable) per subject report; 
• confirm subject is discarding breast milk produced after the first dose of IMP through 
Day 13 per subject report; and 
• confirm adequate stored breast milk and/or infant formula is available to feed the 
infant through Day 13 of the study per subject report. 
10.3.4.2 Treatment Day 6 
The 24-hour breast milk collection will start the morning of Day 6 and end the morning of 
Day 7.  The following assessments/procedure will be performed prior to the initiation of the 
24-hour breast milk collection: 
• adverse event review; 
• concomitant medication review; and 
• subject will pump both breasts with an electric pump until empty prior to 
administration of the last dose of IMP. 
Once both breasts have been completely emptied on the morning of Day 6, Cohort 1 subjects 
will receive the Day 6 dose of bempedoic acid and Cohort 2 subjects will receive the Day 6 dose 
of bempedoic acid/ezetimibe FCDP.  Breast milk will be collected from each subject over the 
next 24 hours using an electric pump at 3, 6, 9, 12, 16, 20 and 24 hours (±30 minutes) after 
Day 6 dose administration. 
At each collection time point, subjects will pump both breasts until empty, breast milk collected 
from each breast will be mixed together and the total volume measured and recorded.  Breast 
milk from each time point will be stored according to procedures outlined in the Laboratory 
Manual and Section 11.1. 
10.3.4.3 Washout Day 7 (after completion of 24-hour breast milk collection) 
The following assessments will be performed after the 24-hour milk collection time point: 
• adverse event review; 
• concomitant medication review; 
• physical exam; 
• weight; 
• vital signs; 
• urine pregnancy test; 
• collect blood sample approximately 24 hours after Day 6 dosing for PK and safety 
laboratory samples; 


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• confirm subject is discarding breast milk produced after the first dose of IMP through 
Day 13 per subject report; 
• confirm adequate stored breast milk and/or infant formula is available to feed the 
infant through Day 13 of the study per subject report; and 
• schedule optional lactation consultant visit. 
Once all assessments are complete the subject will be discharged from the CRU. 
10.3.5 Washout Day 13 (+ 3 days)/End of Study (Visit FU1) 
On Day 13, all subjects will be contacted by phone as a post-treatment follow up visit to review: 
• adverse event review; 
• concomitant medication review; 
• confirm subject discarded breast milk produced after the first dose of IMP through 
Day 13 per subject report; 
• instruct subjects they may resume feeding breast milk currently being produced; 
• document subject’s intent to resume breastfeeding; and 
• schedule optional lactation consultant visit for subjects who desire to re-establish 
breastfeeding. 
10.3.6 Serious Adverse Event Follow-up (SAE FU) and Resumption of Breast-Feeding 
Day 43 (+ 5 days) (Visit FU2) 
Study staff will contact subjects by phone 30 days (Day 43) after FU1 to assess for SAEs and if 
the patient was able to resume breastfeeding (if intended) without problems. 
10.4 
Discontinuations 
10.4.1 Subjects Inadvertently Enrolled  
The inclusion and exclusion criteria for enrollment must be followed exactly and completely.  If 
a subject who does not meet enrollment criteria is inadvertently randomized, the Sponsor should 
be contacted within 24 hours of identification to determine if the subject should continue in the 
study. 
10.4.2 Permanent Discontinuation of Investigational Medicinal Product 
There may be a situation where it is necessary for a subject to discontinue IMP.  The Investigator 
should contact the Sponsor to determine if the subject should be replaced in the study.  The 
subject will be instructed that a 7-day washout is necessary prior to resuming breastfeeding the 
infant.  All Day 7 assessments except the 24-hour PK blood sample and breast milk collection 
should be performed for early termination. 
 


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10.4.3 Subject Discontinuation from the Study 
If the subject discontinues prior to completing the study, the Sponsor should be contacted.  If 
possible, an early discontinuation visit should be conducted.  All Day 7 assessments except the 
24-hour PK blood sample and the 24-hour breast milk collection should be performed.  The 
subject will be permanently discontinued both from the IMP and from the study at that time.  The 
subject will be instructed that a 7-day washout is necessary prior to resuming breastfeeding their 
infant breast milk produced while on IMP.  If the subject discontinues prior to completing the 
24-hour breast milk collection in the CRU, the subject will be replaced. 
10.4.4 Subjects Lost to Follow-Up 
A subject would be considered potentially lost to follow-up if she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  Site personnel are expected to 
make diligent attempts to contact subjects who fail to return for a scheduled visit or were 
otherwise unable to be followed up by the site. 
10.4.5 Discontinuation of Study Sites or the Study 
The Sponsor may suspend enrollment or discontinue a site at any time.  A written statement will 
be provided to the Investigator, the IRB, and regulatory authorities, if required.  
Possible reasons for site discontinuation include, but are not limited to: 
• unsatisfactory enrollment with respect to quantity or quality; 
• inaccurate or incomplete data collection on a chronic basis; 
• falsification of records; 
• failure to adhere to the protocol; and/or 
• 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. 
The Sponsor, in consultation with the IRB Chair, will retain responsibility for discontinuation of 
the study.  The study will be discontinued if necessary, for medical, safety, regulatory, or other 
reasons consistent with applicable laws, regulations, and Good Clinical Practice (GCP). 
 
 


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11. 
PHARMACOKINETIC ASSESSMENTS 
11.1 
Breast Milk Sample Collection and Processing 
Breast milk will be collected using an electric pump.  Breast milk samples will be collected 
within 1 hour before IMP dosing (predose) on Day 1 and on Day 6 at 3, 6, 9, 12, 16, 20 and 
24 hours (±30 minutes) after IMP dosing on Day 6.  Subjects will be instructed to completely 
empty both breasts at each sampling time point.  At each sampling time point, milk collected 
from each breast will be mixed together and the total volume will be measured and recorded.  
From each combined sample 2 aliquots (approximately 5 mL) of breast milk will be transferred 
to appropriately labeled tubes and stored at or below -70° Celsius within 30 minutes of 
collection.  Breast milk samples from each time point will be stored according to procedures 
outlined in the Laboratory Manual. 
11.2 
Blood Sample Collection and Processing 
Blood samples for PK analysis will be collected predose on Day 1 and on Day 7 at 24 hours (±30 
minutes) after Day 6 IMP administration. 
PK samples from each time point will be stored according to procedures outlined in the 
Laboratory Manual. 
 
 


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12. 
ASSESSMENT OF SAFETY 
12.1 
Safety Parameters 
At all site visits, Investigators will review all safety information including vital signs, AEs, 
SAEs, and concomitant medications, and will ensure that the collected data are recorded into the 
appropriate eCRF.  Additionally, laboratory samples will be collected at screening, predose on 
Day 1, and on Day 7 after completion of the 24-hour breast milk collection and sent for analysis.  
The Investigator will review the results to ensure continued subject safety while participating in 
the study. 
Investigators are responsible for monitoring the safety of subjects who have entered this study 
and for alerting the Sponsor or its designee, if appropriate. 
The Investigator is responsible for the appropriate medical care of subjects during the study. 
The Investigator is responsible for following AEs that are serious or that cause the subject to 
discontinue before completing the study until the event is resolved or explained.  Frequency of 
follow-up evaluation is left to the discretion of the Investigator. 
12.1.1 Demographic Data and Medical History 
Demographic data and a complete medical history will be obtained from the subject.  For 
medical history, conditions and surgeries that are relevant and/or clinically significant should be 
captured with at least a start date (month and year) and whether the condition is ongoing or 
resolved.  In addition, a postpartum history from the recent pregnancy, inclusive of gestational 
age at delivery, date of delivery, stage of lactation, length of time postpartum, extent of use of 
infant formula, and smoking and alcohol intake will be obtained. 
12.1.2 Estimated Glomerular Filtration Rate 
Estimated glomerular filtration rate (eGFR) is evaluated during screening using the MDRD 
Study equation (Levey, 2006).  Subjects with an eGFR <30 mL/min/1.73 m2 will not be eligible 
to participate in the study. 
eGFR (mL/min/1.73 m²) = 175 × (serum creatinine)-1.1.54 × (Age)-0.203 × 0.742 (if female) × 1.212 
(if African American). 
12.1.3 Child-Pugh Classification for Assessment of Liver Disease 
Child-Pugh classification is evaluated during screening.  Please refer to Appendix 2.  Subjects 
classified as Child-Pugh Class B or Class C are not eligible to participate in the study. 
12.1.4 Vital Signs 
Vital signs will include diastolic blood pressure (DBP) and systolic blood pressure (SBP) as well 
as heart rate. 
Vital signs will be collected prior to blood collection.  Blood pressure and heart rate will be 
measured using a calibrated, fully automated machine with a cuff that is appropriate to the size 
of the subject’s 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 subject should be in a seated position with feet touching the 


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floor.  Subjects should be seated quietly for several minutes in a chair with their backs supported, 
their feet flat on the ground, and their arms bared and supported at heart level. 
12.1.5 Weight, Height, and Body Mass Index  
Body weight will be measured on a calibrated scale after voiding.  Height will be measured using 
standard clinic procedures. 
Body mass index (BMI) will be calculated systematically using the formula: 
BMI (kg/m2) = weight in kg/(height in meters)2 
12.1.6 Physical Examination 
Physical examinations (PE) will include an assessment of the following: 
• general appearance; 
• skin; 
• eyes, ears, nose, and throat; 
• head and neck; 
• extremities; 
• musculoskeletal examination; 
• respiratory examination; 
• cardiovascular assessment, including rhythm and presence of cardiac abnormalities;  
• abdominal examination; 
• neurologic examination including documentation of the presence of abnormalities in 
mental status and motor and sensory function; and 
• any additional assessments necessary to establish baseline status or evaluate 
symptoms or adverse experiences. 
Documentation of the PE findings will be included in the source documentation at the clinical 
site.  Significant findings at Visit S1 will be recorded on the Medical History/Current Medical 
Conditions page of the eCRF.  Only changes from Visit S1 PE findings that meet the definition 
of an AE will be recorded on the AE page of the eCRF. 
12.1.7 Clinical Laboratory Tests 
12.1.7.1 Clinical Laboratory Parameters (Safety) 
Safety laboratories will be collected at screening (Visit S1), predose on Day 1 (Visit T1) of the 
study, and on Day 7 (Visit T2) after completion of the 24-hour breast milk collection.  Subjects 
will be in a seated position during the blood collection.  Clinical laboratory parameters and tests 
will include those listed in Table 2 and instructions are in the Laboratory Manual. 


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Table 2: Safety Laboratory Parameters  
Clinical Laboratory Tests 
Hematology: 
Clinical Chemistry: 
• 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 
differentials 
 
 
• albumin (Alb) 
• alkaline phosphatase (ALP) 
• 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 bilirubin (TB) and direct bilirubin 
• total protein 
• uric acid 
Serology: 
• hepatitis B surface antigen (HBsAg)  
• hepatitis C virus antibody (HCV-Ab) 
• HIV antigen/antibody 
 
Pregnancy Testing: 
Coagulation Parameters (to assess Child Pugh 
Classification of Liver Disease at screening): 
• serum pregnancy (Visit S1 only) 
• urine pregnancy (Visits T1 and T2 [Day 7] 
only) 
• prothrombin time 
• international normalized ratio (INR) 
Urine drug and alcohol screen: 
• alcohol 
• amphetamines 
• barbiturates 
• benzodiazepines 
• cocaine (metabolite) 
• methadone 
• phencyclidine 
• opiates 
• tetrahydrocannabinol (THC)/cannabinoids 


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12.1.7.2 Sample Collection 
Clinical safety laboratory samples will be collected by appropriate clinical site personnel and 
analyzed at the central laboratory according to site specific procedures. 
12.1.7.3 General Monitoring and Management of Abnormal Clinical Laboratory 
Assessments 
It is the Investigator’s responsibility to review the results of all laboratory tests as they become 
available and to sign and date the review.  For each laboratory test result outside of the 
laboratory normal reference range, the Investigator needs to ascertain if this is a clinically 
significant change from baseline for the individual subject, with baseline defined as the last value 
or observation before the first dose of IMP.  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 abnormal and is a clinically significant change from 
baseline for the subject, the Investigator should determine if it qualifies as an 
AE (Section 13.2.3), 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.   
12.1.7.4 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 and PK.  Total whole blood volume collected over the 
study duration is not to exceed approximately 65 mL for each subject. 
 
 


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13. 
ADVERSE AND SERIOUS ADVERSE EVENTS 
13.1 
Adverse Events 
13.1.1 Definition of an Adverse Event 
An AE is defined as any untoward medical occurrence in a clinical investigation subject 
administered a pharmaceutical product, including control, which does not necessarily have a 
causal relationship with treatment.  The Investigator is responsible for ensuring that any AEs 
observed by the Investigator or reported by the subject are recorded in the subject’s medical 
record. 
An AE can be: 
• any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a medicinal product, 
whether or not considered related to the medicinal product, 
• any new disease or exacerbation of an existing disease, or 
• any deterioration in nonprotocol-required measurements of laboratory value or other 
clinical test (e.g., ECG or x-ray) that results in symptoms, a change in treatment, or 
discontinuation from IMP. 
13.1.2 Reporting for Adverse Events 
All AEs occurring during the course of the study (starting from signing informed consent to the 
end of study) will be collected on the AE eCRF.  Subjects 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; 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 (e.g., surgery, endoscopy, tooth 
extraction, transfusion) should be recorded as an AE, not the procedure. 
Any medical condition already present at screening or baseline should not be reported as an AE 
unless the medical condition or signs or symptoms present at baseline changes in severity or 
seriousness at any time during the study.  In this case, it should be reported as an AE. 
Clinically significant abnormal laboratory or other examination (e.g., ECG) findings that are 
detected during the study or are present at baseline and significantly worsen during the study 
should be reported as AEs.  The Investigator will exercise their 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. 
Analyses of certain AEs will be performed in this study for reasons either associated with other 
lipid-lowering therapies or where deemed important based on nonclinical or clinical data.  These 


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events include the following:  hepatic events, musculoskeletal events, diabetes and glycemia, 
hypoglycemia associated with metabolic acidosis, renal impairment, neurocognitive events, atrial 
fibrillation, and tendon rupture/tendinopathy. 
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 (e.g., 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; and 
• Investigator’s assessment of relationship to IMP. 
A cluster of signs and symptoms that results from a single cause should be reported as a single 
AE (e.g., fever, elevated white blood cells [WBC], cough, abnormal chest x-ray, etc., can all be 
reported as “pneumonia”). 
The Investigator will carefully evaluate the comments of the subject and the response to 
treatment in order that they 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. 
13.1.3 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 subject’s daily 
activities. 
• Moderate:  Events introduce a low level of inconvenience or concern to the subject 
and may interfere with daily activities. 
• Severe:  Events interrupt the subject’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. 
 
 


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13.1.4 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; 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 re-challenge. 
13.1.5 Monitoring and Follow-up of Adverse Events 
Subjects 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 subject’s source documentation.  Follow-up laboratory results should be filed 
with the subject’s source documentation. 
For all AEs that require the subject 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). 
Subjects 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 subjects reporting SAEs (Section 13.2.4). 
13.2 
Serious Adverse Events 
13.2.1 Definition of Serious Adverse Event  
An SAE is defined as any AE occurring at any dose that results in any of the following 
outcomes: 
• results in death; 
• is life-threatening; 
• requires inpatient hospitalization or prolongation of existing hospitalization; 
• results in persistent or significant disability/incapacity, or substantial disruption of the 
ability to conduct normal life functions; 


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• is a congenital anomaly/birth defect; or 
• an important medical event. 
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 subject 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. 
13.2.2 Events or Outcomes Not Qualifying as Serious Adverse Events  
The following are not considered SAEs and therefore do not need to be reported as such:  
• preplanned or elective hospitalization including social and/or convenience situations 
(e.g., due to inclement weather), or 
• overdose of either Esperion IMP or concomitant medication unless the event meets 
SAE criteria (e.g., hospitalization); however, the event should still be captured as a 
nonserious AE on the appropriate eCRF page. 
13.2.3 Clinical Laboratory Assessments as Adverse Events and Serious Adverse Events  
It is the responsibility of the Investigator to assess the clinical significance of all abnormal values 
as defined by the list of reference ranges from the corresponding laboratory.  In some cases, 
significant changes in laboratory values within the normal range will require similar judgment. 
An abnormal laboratory value that is not already associated with an AE is to be recorded as an 
AE only if any one of the following criteria is met: 
• an action on the IMP is made as a result of the abnormality; 
• intervention for management of the abnormality is required; or 
• at the discretion of the Investigator should the abnormality be deemed clinically 
significant. 
13.2.4 Reporting Serious Adverse Events 
All SAEs occurring from the time of informed consent of a subject until 30 days following 
completion or discontinuation of study must be reported by the Principal Investigator or designee 
to the Safety Contact within 24 hours of the Principal Investigator or the clinical site becoming 
aware of the occurrence.  All SAEs that the Investigator considers related to IMP that occur after 
the 30-day follow-up period of the study must be reported to the Sponsor. 
To report an SAE, complete the electronically provided SAE form in the EDC system and submit 
it to  the Safety Contact.  Paper SAE form should only be used in case of EDC system outage. 
Principal Investigator or designee should complete the SAE form on paper and fax it to the 
number listed on the form or email it to drugsafety@esperion.com within 24 hours of becoming 
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The Investigator is required to submit SAE reports to the IRB in accordance with local 
requirements.  All investigators involved in studies using the same IMP will receive any safety 
alert notifications for onward submission to their local IRB as required. 
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 subject until the SAE has subsided or until the 
condition becomes chronic in nature, stabilizes (in the case of persistent impairment), or the 
subject dies. 
Within 24 hours of receipt of follow-up information, the Investigator must update the SAE form 
and submit any supporting documentation (e.g., 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 regulatory authorities, IRBs, and 
investigators/institutions in compliance with all reporting requirements according to local 
regulations, laws, and GCPs.  The Investigator should notify the appropriate IRB of SAEs 
occurring at the site and other AE reports received from the Sponsor, in accordance with local 
procedures and statutes.  
13.2.5 Reporting of Subject Death 
The death of a subject during the study or within 30 days following her completion of the study, 
regardless of the cause, must be reported as detailed in Section 13.2.4. 
13.2.6 Reports of Pregnancy  
Although not considered an SAE (unless an event occurs with a serious outcome), pregnancy 
information on subjects will be collected by the designated Safety Contact.  If a subject should 
become pregnant during the study, the Principal Investigator or designee must contact the Safety 
Contact within 24 hours of the Principal Investigator or designee first becoming aware of the 
pregnancy. 
To report a pregnancy, the pregnancy information should be recorded on the Clinical Pregnancy 
Report Form and sent to the Safety Contact via fax number listed on the form or email 
(drugsafety@esperion.com) within 24 hours of becoming aware of the pregnancy. 
Additionally, the subject’s pregnancy should be followed through to its conclusion with the 
outcome recorded on the Pregnancy Outcome Form and sent to the Safety Contact using either 
the email or fax noted previously.  Please call the designated Safety Contact for assistance or 
questions. 
Subjects who become pregnant will discontinue IMP immediately and will continue to be 
followed until the pregnancy is completed. 
13.2.7 Reports of Infant Exposure to Investigational Medicinal Product via Breast Milk 
Infant exposure to IMP via breast milk will be treated as an AE for the infant and should be 
reported to the designated Safety Contact.  If a subject feeds her infant breast milk produced after 
the first dose of IMP through Day 13 of the Washout Period of the study, the Principal 
Investigator or designee must contact the Safety Contact to report this incident. 


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To report infant exposure to IMP via breast milk, the exposure information should be recorded 
on the Clinical Pregnancy Outcome Form and sent to the Safety Contact via fax number listed on 
the form or email (drugsafety@esperion.com) within 24 hours of becoming aware of the 
exposure. 
Any additional AEs or SAEs experienced by the infant should be reported as per Section 13, and 
the infant should then be followed according to the guidance specified in Section 13.1.5, 
Monitoring and Follow up of Adverse Events or Section 13.2.4, Reporting of Serious Adverse 
Events, accordingly.  Please contact the designated Safety Contact for assistance or questions. 
 
 


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14. 
STATISTICS 
14.1 
General Considerations 
The statistical analysis described in this section will be performed as further outlined in a 
separate Statistical Analysis Plan (SAP).  The SAP will supersede the protocol in the event of 
any difference between the 2 documents in data analysis and the protocol will be amended of 
appropriate.  Statistical analyses in this study will be descriptive in nature.  No statistical 
inference is planned.  Subject disposition, demographics, and baseline characteristics will be 
summarized.  Summary statistics for continuous variables will include the number of subjects, 
mean, median, standard deviation or standard error, first and third quartiles, minimum, and 
maximum.  Summary statistics for PK parameters will also include geometric mean and 
coefficient of Variation (CV) (%).  For categorical variables, the frequency and percentage will 
be given. 
14.2 
Determination of Sample Size 
A minimum sample size of 16 (8 subjects who receive bempedoic acid [Cohort 1]and 8 subjects 
who receive bempedoic acid/ezetimibe FCDP [Cohort 2]) evaluable subjects (who complete the 
6-day treatment period and the 24-hour breast milk collection in the CRU) is planned for this 
study.  Subjects who are randomized but do not complete the 24-hour breast milk collection in 
the CRU will be replaced with a new subject on the same treatment to ensure 8 evaluable 
subjects in each cohort for the final analyses. 
The sample size was not based on empirical or hypothesis testing criteria.  The sample size was 
based on clinical and regulatory considerations and precedence in previous ETC-1002 studies 
(
).  The sample size is considered sufficient to address the primary objectives of 
the study. 
14.3 
Analysis Population  
14.3.1 Safety Population 
The Safety Population (SP), used for all the safety summaries, is defined as all subjects who 
received at least 1 dose of IMP. 
14.3.2 Pharmacokinetic Population 
The PK Population will include all subjects who complete the 24-hour breast milk collection 
after IMP administration on Day 6. 
14.3.2.1 Primary Analyses 
• Daily infant dosage and RID of bempedoic acid will be summarized for Cohort 1 
subjects who receive once daily bempedoic acid for 6 consecutive days. 
• Daily infant dosage and RID of bempedoic acid and ezetimibe will be summarized 
for Cohort 2 subjects who received once daily bempedoic acid/ezetimibe FCDP for 
6 consecutive days. 
• RID will be calculated as the ratio of total infant dose per kg body weight and 
maternal dose per kg body weight, multiplied by 100. 


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14.3.2.2 Secondary Analyses 
The PK parameters of bempedoic acid, ezetimibe, and metabolites (ESP15228, bempedoic acid 
glucuronide, and ezetimibe-glucuronide) in mature breast milk will be calculated using standard 
noncompartmental methods, including: 
• breast milk AUC over the 24-hour collection interval; 
• average milk concentration based on milk AUC; 
• peak and trough milk concentrations as well as time to reach peak milk 
concentrations; and 
• plasma concentrations at 24 hours after the last dose on Day 6. 
Pharmacokinetic calculations will be performed, if appropriate, using commercial software such 
as Phoenix™ WinNonlin® Version 6.4 or higher (Certara USA Inc.). 
Descriptive statistics will be provided for the PK parameters. 
Other parameters may be added as appropriate; the final PK parameters reported will be detailed 
in the SAP. 
14.4 
Safety Analyses 
General safety data in this study includes AEs, clinical laboratory parameters, PEs, vital signs, 
and body weight. 
Treatment-emergent AEs (TEAEs) are defined as AEs that begin or worsen after randomization 
and the first dose of IMP through Day 13.  TEAEs will be summarized by System Organ Class 
(SOC), Preferred Term, and severity.  Serious TEAEs, IMP-related TEAEs, TEAEs leading to 
withdrawal of IMP, and deaths will be also summarized. 
Clinical laboratory parameters including hematology and blood chemistry, PE findings, vital 
signs, and body weight will be summarized and listed using descriptive statistics. 
 
 


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15. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
15.1 
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 subjects are protected, and verify the reported clinical study data are accurate, 
complete, and verifiable from source documents.  This includes review of ICFs, results of tests 
performed as a requirement for participation in this study, and any other medical records 
(e.g., laboratory reports, clinic notes, IMP dispensing log, pharmacy records, subject-completed 
diaries, or telephone logs) 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 FDA recommendations and will be described in detail 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, 
and subject ICFs, 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. 
15.2 
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.  Subject 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 other regulatory authority to verify that 
the study was conducted in accordance with protocol requirements, as well as the applicable 
regulations and guidelines. 
In the event the Investigator is contacted by regulatory authorities who wish to conduct an 
inspection of the clinical site, the Investigator will promptly notify the Sponsor of all such 
requests and will promptly forward a copy of all such inspection reports. 


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16. 
QUALITY CONTROL AND QUALITY ASSURANCE 
To ensure compliance with GCP and all applicable regulatory requirements, the Sponsor (or 
designee) may conduct a quality assurance audit. 
 
 


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17. 
ETHICS 
17.1 
Institutional Review Board Approval 
Before initiation of the study, the Investigator must obtain approval or favorable opinion of the 
research protocol, ICF, and any material related to subject recruitment from an IRB.  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. 
IRBs must be constituted according to the applicable laws.  It is the responsibility of the clinical 
site to submit the protocol, IB, subject informed consent, subject recruitment materials (if 
applicable), and other documentation as required by the IRB 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 
subject ICF, and subject 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 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 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.  This includes 
notification to the IRB regarding: protocol amendments, updates to the ICF, recruitment 
materials intended for viewing by subjects, 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, and submission of final study 
reports and summaries to the IRB. 
It is the responsibility of each clinical site to submit information to the appropriate IRB for 
annual review and annual re-approval. 
The Investigator must promptly inform their IRB of all SAEs or other safety information 
reported from the subject or the Sponsor. 
17.2 
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 review and ICFs. 
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 or other 
appropriate regulatory authorities.  Monitoring and auditing visits by the Sponsor or 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 


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in recruiting and screening study subjects.  The Investigator must sign and return to the Sponsor 
the “Investigator’s Signature” page (see Appendix 4) and provide a copy of their current 
curriculum vitae.  For this study and all studies conducted under an investigational new drug 
application (IND), the Investigator must sign and return a completed Form FDA 1572 
“Statement of Investigator” to the Sponsor (or designee). 
17.3 
Written Informed Consent 
The Principal Investigator will ensure that the subject is given full and adequate oral and written 
information about the nature, purpose, and possible risks and benefits of the study.  Subjects 
must also clearly understand that they are free to discontinue from the study at any time.  The 
subject should be given the opportunity to ask questions and allowed time to consider the 
information provided. 
The subject’s signed and dated informed consent must be obtained before conducting any study 
procedures on the Sponsor agreed ICF.  Updates to the ICF during the conduct of the study will 
be communicated by written letter from the Sponsor to the Investigator.  The ICF should be 
provided in the appropriate language of the subject population. 
The Principal Investigator(s) must maintain the original, signed ICF.  A copy of the signed ICF 
must be given to the subject. 
17.4 
Subject Confidentiality 
The Investigator must ensure that the subject’s confidentiality is maintained. 
The names and identities of all research subjects will be kept in strict confidence and will not 
appear on eCRFs or other records provided to or retained by the Sponsor (or designee).  If a 
subject’s name appears on any document, it must be redacted and replaced with the subject 
identifier before a copy of the document is supplied to the Sponsor (or designee).  The ICF must 
include appropriate statements explaining that subject data will be confidential and what actions 
will be taken to ensure subject confidentiality. 
Any other confidentiality requirements specified by the site, IRB, or national or local regulations 
will be adhered to and detailed appropriately in the ICF. 
 
 


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18. 
DATA HANDLING AND RECORDKEEPING 
18.1 
Inspection of Records 
Applicable regulations require the Sponsor (or designee) 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 subjects 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 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. 
18.2 
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 subject, 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, IMP disposition records, signed subject 
ICFs, 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. 
18.3 
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 
subjects 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 (e.g., IRB correspondence, clinical study materials, and supplies shipment manifests, 
monitoring logs, and correspondence).  A study-specific binder will be provided with 
instructions for the maintenance of study records. 


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Source documentation is defined as any hand-written or computer-generated document that 
contains medical information or test results that have been collected for or in support of the 
protocol specifications (e.g., laboratory reports, clinic notes, IMP disposition log, pharmacy 
records, subject sign-in sheets, and telephone logs).  All draft, preliminary, and pre-final 
iterations of a final report are also considered to be source documents (e.g., 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 subject’s participation with the IMP 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 subject who receives IMP, regardless of duration.  
All supportive documentation submitted with the eCRF, such as laboratory or hospital records, 
should be clearly identified with the study and subject number.  Any personal information, 
including subject 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 subject 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 
in a timely manner as defined in the eCRF Completion Guidelines. 
 
 


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Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
Confidential 
 
Page 56 of 67 
19. 
ADMINISTRATIVE CONSIDERATIONS 
19.1 
Investigators 
The Investigator must agree to the responsibilities and obligations listed below, as specified by 
the appropriate FDA 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 subjects, or persons used as controls, that the IMP are being used 
for investigational purposes and ensure that the requirements relating to obtaining 
informed consent and IRB 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 IMP; 
• 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 will be responsible for the initial and continuing 
review and approval of the clinical investigation; 
• agree to promptly report to the IRB all changes in the research activity and all 
unanticipated problems involving risks to subjects or others; 
• agree to not make changes in the research without IRB approval, except where 
necessary to eliminate apparent hazards to subjects; and 
• 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 
• Guidance for Industry – E6 Good Clinical Practice: Consolidated Guidance:   
http://www.fda.gov/cder/guidance/959fnl.pdf 
 


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP 
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Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
Confidential 
 
Page 57 of 67 
19.2 
Study Administrative Structure 
Please see the Pharmacy Manual for details regarding clinical supply. 
 
Study Management and Data Management: 
 
Central Lab: 
 
 
Bioanalytical lab: 
 
Statistical Analysis and Programming: 
 
Clinical Research Unit: 
 
Medical and Safety (or Safety Designee): 
19.3 
Amendments and Study Termination 
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 
approval.  Documentation of amendment approval by the Investigator and IRB 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 only needs to be notified. 


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
Confidential 
 
Page 58 of 67 
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. 
The Sponsor reserves the right to terminate this study at any time. 
19.4 
Financial Disclosure 
Prior to the start of the study, investigators will release sufficient and accurate financial 
information that permits the Sponsor to demonstrate that an Investigator and all study relevant 
assigned personnel have no personal or professional financial incentive regarding the future 
approval or disapproval of the IMP such that his or her research might be biased by such 
incentive. 
 
 


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
Confidential 
 
Page 59 of 67 
20. 
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 or designee will be responsible for preparing the primary manuscript and study 
results.  The Sponsor or designee shall have the right to publish data from the study without 
approval from the individual investigators.  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 and Bempedoic Acid/Ezetimibe FCDP 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
Confidential 
 
Page 60 of 67 
21. 
LIST OF REFERENCES 
Clinical Lactation Studies: Considerations for Study Design. Draft Guidance for Industry (FDA 
May 2019), Draft Guidance https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/clinical-lactation-studies-considerations-study-design 
Investigator’s Brochure, ETC-1002, v15.5, May 2020 
Levey AS, Coresh J, Greene T, Stevens LA, Zhang Y, Hendriksen S, et al. Using Standardized 
Serum Creatinine Values in the Modification of Diet in Renal Disease Study Equation for 
Estimating Glomerular Filtration Rate. Ann Intern Med. 2006; 145:247-54. 
Nexletol® (bempedoic acid) US package insert [USPI]. Ann Arbor, Michigan: Esperion 
Therapeutics; 2020. https://pi.esperion.com/nexletol/nexletol-pi.pdf. Last accessed 03 Aug 2020. 
Nexlizet® (bempedoic acid/ezetimibe) US package insert [USPI]. Ann Arbor, Michigan: 
Esperion Therapeutics; 2020. https://pi.esperion.com/nexlizet/nexlizet-pi.pdf. Last accessed 03 
Aug 2020. 
Nilemdo® (bempedoic acid) EMA summary of product characteristics [SmPC]. Daiichi Sankyo 
Company, Limited; 2020. https://www.ema.europa.eu/en/documents/product-
information/nilemdo-epar-product-information_en.pdf. Last accessed 03 Aug 2020. 
Nustendi® (bempedoic acid/ezetimibe) EMA summary of product characteristics [SmPC]. 
Daiichi Sankyo Company, Limited; 2020. https://www.ema.europa.eu/en/documents/product-
information/nustendi-epar-product-information_en.pdf. Last accessed 03 Aug 2020. 
Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the 
oesophagus for bleeding oesophageal varices. Br J Surg. 1973 Aug;60(8):646-9. 
Report 1002-061. Population Pharmacokinetic/Pharmacodynamic Analysis of Bempedoic Acid 
and LDL-C Concentration in Healthy Subjects and Patients with Primary Hypercholesterolemia. 
31 Aug 2020. 
Zetia® (ezetimibe) US package insert [USPI]. Whitehouse Station, New Jersey: Merck and Co., 
Inc; 2013. https://www.merck.com/product/usa/pi_circulars/z/zetia/zetia_pi.pdf. Last accessed 
03 Aug 2020. 
 
 
 


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Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
Confidential 
 
Page 61 of 67 
22. 
APPENDICES 
Appendix 1:  Schedule of Assessments 
Appendix 2:  Child-Pugh Classification 
Appendix 2:  Sponsor’s Signature 
Appendix 4:  Investigator’s Signature 
Appendix 5:  Summary of Changes  
 


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Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
Confidential 
 
Page 62 of 67 
APPENDIX 1. SCHEDULE OF ASSESSMENTS 
Study Period 
Screening 
Period 
Treatment Period 
Washout Period 
SAE FU 
Visit 
S1 
T1 
— 
T2 
— 
— 
FU1a 
FU2 
Procedure 
Day 
-42 to -1 
Day 1 
Day 
2-4 
Day5 
Day6 
Day7b 
Day 8-
12 
Day 13 
(+3 days) 
by phone 
Day 43  
(+5 days) 
by phonec 
Informed consent 
X 
 
 
 
 
 
 
 
 
Enrollment criteria 
X 
Predose 
 
 
 
 
 
 
 
Review of breastfeeding 
practice  
X 
Predose 
 
 
 
 
 
 
 
Adequate breast milk 
production/weaning 
X 
Predose 
X 
X 
 
 
 
 
 
Infant able to bottle feed 
X 
Predose 
 
 
 
 
 
 
 
Adequate stored breast milk/ 
formula to feed infantd 
X 
Predose 
X 
X 
X 
X 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
Medical historye 
X 
 
 
 
 
 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
 
Adverse event review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical exam 
X 
 
 
 
 
X 
 
 
 
Weight 
X 
X 
 
 
 
X 
 
 
 
Height/BMI 
X 
 
 
 
 
 
 
 
 
Vital signsf 
X 
X 
 
 
 
X 
 
 
 
Serum pregnancy test 
X 
 
 
 
 
 
 
 
 
Urine pregnancy test 
 
X 
 
 
 
X 
 
 
 
Urine drug and alcohol screen 
X 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
Pump breast milk for predose 
collection at CRU (≤1 hour 
before IMP administration) 
 
X 
 
 
 
 
 
 
 
Lactation consultant visit 
(optional) 
X 
X 
X 
X 
 
X 
X 
Xg 
 
Pump and discard breast milkh 
 
X 
X 
X 
 
Xi 
X 
X 
 
Phone call to subjectj 
 
 
X 
X 
 
 
 
X 
X 
Predose PK blood sample 
 
X 
 
 
 
 
 
 
 
Clinical lab evaluationsn  
X 
X 
 
 
 
X 
 
 
 
Dispense IMP 
 
X 
 
 
 
 
 
 
 


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
Confidential 
 
Page 63 of 67 
IMP administration at CRU 
 
X 
 
 
X 
 
 
 
 
Self-administration of IMP 
 
 
X 
X 
 
 
 
 
 
CRU check-in (evening)k 
 
 
 
X 
 
 
 
 
 
IMP returnk 
 
 
 
X 
 
 
 
 
 
Study Drug Diary 
 
 
X 
X 
 
 
 
 
 
Domicile in CRU 
 
 
 
X 
X 
 
 
 
 
Pump breast milk for 0-24 hr. 
post-dose collection at CRUl 
 
 
 
 
X 
X 
 
 
 
24-hr (after Day 6 dose) PK 
blood samplem 
 
 
 
 
 
X 
 
 
 
CRU Discharge (morning) 
 
 
 
 
 
X 
 
 
 
BMI = body mass index; BP = blood pressure; CRU = clinical research unit; DBP = diastolic blood pressure; FU1 = 
follow-up visit 1; HR = heart rate; min = minutes; PK = pharmacokinetic; S1 = screening visit 1; SAE FU = serious 
adverse event follow-up; SBP = systolic blood pressure; T1 = treatment visit 1; T2 = treatment visit 2 
a Subjects may resume breastfeeding. 
b All procedures will be completed at early termination except 24-hour PK blood sample and breast milk collection. 
c Day 43 phone call to follow-up on SAEs and question if patient was able to resume breastfeeding (if intended) without 
problems. 
d Subjects must have adequate stored breast milk and/or infant formula available to feed the infant after the first dose of 
IMP through Day 13 of the study. 
e In addition to existing medical conditions, medical history should include gestational age at delivery, date of delivery, 
stage of lactation, length of time postpartum, and smoking and alcohol intake. 
f Vital signs will include DBP, SBP, and HR.  Subject will rest for several minutes prior to assessments. 
g Lactation consultant visit for subjects who desire to re-establish breastfeeding at the end of study (Visit FU1). 
h Pump and discard breast milk after the 1st dose of IMP on Day 1 through Day 5 and Day 7 through Day 13. 
i Discard breast milk produced after completion of the 24hr breast milk collection period. 
j For Day 2 through Day 5, remind subject to take IMP appropriately and discard breast milk produced after Day 1.  If 
subject misses a dose of IMP contact the Sponsor immediately. 
k With sponsor approval, the subject may check-in to the CRU the morning of Day 6 and return IMP at that time. 
l Breast milk collections will be performed using an electric pump at specified intervals (±30 min) over 24 hours at 3, 6, 
9, 12, 16, 20, and 24 hours following IMP dosing on Day 6.  Both breasts will be emptied completely during each 
collection.  At each sampling time point, milk collected from each breast will be mixed together and the total volume 
measured.  Milk will be stored frozen until time of analysis. The specific timing of the milk sample relative to the IMP 
dose will be recorded. 
m A blood sample for PK will be collected on Day 7 approximately 24 hours (±30 min) after IMP administration on 
Day 6. 
n Chemistry and hematology at Visit S1, Visit T1 and Visit T2; Serology and coagulation parameters at Visit S1 only. 
 


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
Confidential 
 
Page 64 of 67 
APPENDIX 2. CHILD-PUGH CLASSIFICATION 
 
 
 


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Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
Confidential 
 
Page 65 of 67 
APPENDIX 3. SPONSOR’S SIGNATURES 
Study Title: 
An Open-Label Postmarketing Milk-Only Lactation Study to Evaluate 
the Concentration of Bempedoic Acid and Bempedoic Acid and 
Ezetimibe in the Breast Milk of Healthy Lactating Women Administered 
Therapeutic Doses of Bempedoic Acid or Bempedoic Acid/Ezetimibe 
Fixed Combination Drug Product (FCDP) 
Study Number: 
1002FDC-075 
 
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: See attached electronic approval page 
Date:  
 
 
Name and Credentials: 
Title: 
Affiliation: 
 
 
 
 
 


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Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
Confidential 
 
Page 66 of 67 
APPENDIX 4. INVESTIGATOR’S SIGNATURE 
Study Title: 
An Open Label Postmarketing Milk-Only Lactation Study to Evaluate 
the Concentration of Bempedoic Acid and Bempedoic Acid and 
Ezetimibe in the Breast Milk of Healthy Lactating Women Administered 
Therapeutic Doses of Bempedoic Acid or Bempedoic Acid/Ezetimibe 
Fixed Combination Drug Product (FCDP) 
Study Number: 
1002FDC-075 
 
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 and Bempedoic Acid/Ezetimibe FCDP 
Esperion Therapeutics, Inc. 
Clinical Study Protocol 1002FDC-075 
Amendment 1, 06 June 2023 
 
Confidential 
 
Page 67 of 67 
APPENDIX 5. SUMMARY OF CHANGES IN AMENDMENT 1 
PROTOCOL 
SUMMARY OF CHANGES 
AMENDMENT 1 CLINICAL STUDY PROTOCOL 
Study Number: 
1002FDC-075 
Study Title: 
An Open-Label Postmarketing Milk-Only Lactation Study 
to Evaluate the Concentration of Bempedoic Acid and 
Bempedoic Acid and Ezetimibe in the Breast Milk of 
Healthy Lactating Women Administered Therapeutic 
Doses of Bempedoic Acid or Bempedoic Acid/Ezetimibe 
Fixed Combination Drug Product (FCDP) 
Amendment l Protocol Version 
Incorporating Current Summary 
of Changes: 
06 June 2023 
Preceding Final Protocol Version:  18 August 2021 
Investigational Product Name: 
Bempedoic acid and bempedoic acid/ezetimibe FCDP 
 
 
Summary of Changes 
The protocol was amended for the following: 
• Update IMP packaging description from blister strips to bottles (Section 9). 
• Clarify visit windows for Visit FU1 and Visit FU2 (Sections 10.3.5, 10.3.6 and 
Appendix 1). 
• Clarify wording to include investigational vaccines as part of investigational drugs 
(Sections 2 and 7.2). 
•  Add section to address concomitant medical procedures (Section 8.3 ). 
•  Add serology testing at Visit S1 for the following safety parameters: hepatitis B 
surface antigen (HBsAg), hepatitis C virus antibody (HCV-Ab) and HIV antigen and 
antibody (Section 10.3.1, Table 2, and Appendix 1).   
• Modify wording to clarify SAE reporting procedures in electronica data capture 
system (Section 13.2.4). 
•  Update vendors listed under the Study Administrative Structure (Section 19.2). 
• Modify wording to maintain consistency and/or clarity throughout the protocol 
without impacting study conduct in a meaningful way i.e., defining visits by Visit and 
Day.  
• Other changes to align the document with current Esperion standards, correct 
typographical errors, formatting updates, modify wording to maintain consistency 
across bempedoic acid studies, update administrative protocol details, or clarify 
instructions without impacting study conduct in a meaningful way. 
 

SAP_001.pdf: 
Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP  
Esperion Therapeutics, Inc. 
 Protocol 1002FDC-075: Statistical Analysis Plan v1.0 
26Jun2024 
 
Confidential 
Page 1 of 28 
  
 
 
STATISTICAL ANALYSIS PLAN 
PROTOCOL 1002FDC-075 
 
AN OPEN-LABEL POSTMARKETING MILK-ONLY LACTATION 
STUDY TO EVALUATE THE CONCENTRATION OF BEMPEDOIC ACID 
AND BEMPEDOIC ACID AND EZETIMIBE IN THE  
BREAST MILK OF HEALTHY LACTATING WOMEN ADMINISTERED 
THERAPEUTIC DOSES OF BEMPEDOIC ACID OR  
BEMPEDOIC ACID/EZETIMIBE FIXED COMBINATION DRUG 
PRODUCT (FCDP) 
 
Version:  1.0 
26 June 2024 
 
 
 
 
 
 
 
 
 
Property of Esperion Therapeutics, Inc. 
Confidential 
May not be used, divulged, published, or otherwise disclosed 
without the consent of Esperion Therapeutics, Inc. 
 


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP  
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 Protocol 1002FDC-075: Statistical Analysis Plan v1.0 
26Jun2024 
 
Confidential 
Page 2 of 28 
MODIFICATION HISTORY 
Unique 
Identifier/ 
Version 
Number 
Date of 
Document 
Approval 
Document Owner 
Significant Changes from  
Previous Authorized Version 
1.0 
26 Jun 2024 
 
Not Applicable – First Version. 
 
 
 


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP  
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 Protocol 1002FDC-075: Statistical Analysis Plan v1.0 
26Jun2024 
 
Confidential 
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TABLE OF CONTENTS 
MODIFICATION HISTORY ..........................................................................................................2 
1. 
INTRODUCTION ........................................................................................................7 
2. 
STUDY OBJECTIVES ................................................................................................7 
2.1. 
Primary Objective .........................................................................................................7 
2.2. 
Secondary Objective(s) .................................................................................................7 
2.3. 
Safety: ...........................................................................................................................7 
3. 
STUDY ENDPOINTS ..................................................................................................8 
3.1. 
Primary Endpoint ..........................................................................................................8 
3.2. 
Secondary Endpoints ....................................................................................................8 
3.3. 
Safety Endpoints ...........................................................................................................8 
4. 
STUDY DESIGN .........................................................................................................9 
4.1. 
Overview .......................................................................................................................9 
4.2. 
Treatment Assignment, Randomization, and Blinding...............................................11 
4.2.1. 
Randomization and Treatment Assignment ................................................................11 
4.2.2. 
Blinding ......................................................................................................................11 
5. 
PLANNED ANALYSES ............................................................................................11 
5.1. 
Interim Analyses .........................................................................................................11 
5.2. 
Final Analyses ............................................................................................................11 
6. 
ANALYSIS SETS ......................................................................................................11 
6.1. 
Full Analysis Set .........................................................................................................11 
6.2. 
PK Analysis Set ..........................................................................................................12 
7. 
STUDY DEFINITIONS .............................................................................................12 
7.1. 
Disposition ..................................................................................................................12 
7.2. 
Reference Start Date and Study Day ..........................................................................12 
7.3. 
Baseline .......................................................................................................................12 
7.4. 
Prior and Concomitant Medications ...........................................................................12 
8. 
STATISTICAL CONSIDERATIONS .......................................................................13 
8.1. 
Sample Size ................................................................................................................13 
8.1. 
Number of Centers ......................................................................................................13 
8.2. 
Coding Dictionaries ....................................................................................................13 
8.3. 
General Principles .......................................................................................................13 


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 Protocol 1002FDC-075: Statistical Analysis Plan v1.0 
26Jun2024 
 
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8.4. 
Missing Data Handling ...............................................................................................13 
8.4.1. 
Imputation of Missing Dates ......................................................................................13 
8.4.2. 
PK and Laboratory Data Beyond the Limits of Quantification ..................................14 
9. 
DISPOSITION AND WITHDRAWALS ...................................................................14 
10. 
PROTOCOL DEVIATIONS ......................................................................................14 
11. 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS .....................15 
12. 
MEDICAL HISTORY AND POSTPARTUN HISTORY .........................................15 
12.1. 
Medical History ..........................................................................................................15 
12.2. 
Postpartum History of Recent Pregnancy ...................................................................15 
13. 
LACTATION STAGE ................................................................................................15 
14. 
CURRENT FEEDING PRACTICE ...........................................................................15 
15. 
PRIOR AND CONCOMITANT MEDICATIONS ....................................................16 
15.1. 
Prohibited Medications ...............................................................................................16 
16. 
STUDY MEDICATION EXPOSURE AND TREATMENT COMPLIANCE .........16 
17. 
PHARMACOKINETIC (PK) ANALYSIS ................................................................17 
17.1. 
PK Nominal Timepoints .............................................................................................17 
17.2. 
PK Parameters ............................................................................................................18 
17.3. 
PK Analysis for Primary Endpoints ...........................................................................18 
17.4. 
PK Analysis for Secondary Endpoints .......................................................................19 
18. 
SAFETY ANALYSIS ................................................................................................20 
18.1. 
General ........................................................................................................................20 
18.2. 
Adverse Events ...........................................................................................................21 
18.2.1. 
Treatment Emergent Adverse Events (TEAEs) ..........................................................21 
18.3. 
Safety Laboratory Evaluations ...................................................................................22 
18.3.1. 
Safety Laboratory Evaluation .....................................................................................22 
18.4. 
Vital Signs ..................................................................................................................22 
18.5. 
Physical Examination .................................................................................................22 
19. 
REFERENCES ...........................................................................................................23 
APPENDIX 1. SCHEDULE OF EVENTS .................................................................................24 
APPENDIX 2. PARTIAL DATE CONVENTIONS ..................................................................26 
APPENDIX 3. CLINICAL SAFETY LABORATORY TESTS ................................................28 


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP  
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 Protocol 1002FDC-075: Statistical Analysis Plan v1.0 
26Jun2024 
 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation/Specialist Term 
Definition 
AE(s) 
adverse event(s) 
ATC 
Anatomical Therapeutic Chemical 
AUC  
area under the concentration time curve 
BA 
bempedoic acid 
BLQ 
below limit of quantification 
BMI 
body mass index 
COVID-19 
coronavirus disease of 2019 
CRO 
clinical research organization 
DBP  
diastolic blood pressure 
EDC 
electronic data capture 
eCRF 
electronic case report form 
eGFR 
estimated glomerular filtration rate 
EOS 
End-of-Study 
EOT 
End-of-Treatment 
EZE 
ezetimibe 
FAS 
Full Analysis Set 
FCDP 
fixed combination drug product 
FDA 
Food and Drug Administration 
IMP 
investigational medicinal product 
LLN 
lower limit of normal 
MedDRA 
Medical Dictionary for Regulatory Activities 
PK 
pharmacokinetics 
PKS 
PK Analysis Set 
PT 
Preferred Term 
RID 
relative infant dose 
SAE(s) 
serious adverse event(s) 
SAP 
Statistical Analysis Plan 
SD 
standard deviation 
SOC 
System Organ Class 
TEAE(s) 
treatment-emergent adverse event(s) 
TFL(s) 
table(s), figure(s), and listing(s) 


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP  
Esperion Therapeutics, Inc. 
 Protocol 1002FDC-075: Statistical Analysis Plan v1.0 
26Jun2024 
 
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Page 6 of 28 
Abbreviation/Specialist Term 
Definition 
ULN 
upper limit of normal 
ULQ 
upper limit of quantification 
WBC 
white blood cell 
WHO-DDE 
World Health Organization – Drug Dictionary Enhanced 


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Esperion Therapeutics, Inc. 
 Protocol 1002FDC-075: Statistical Analysis Plan v1.0 
26Jun2024 
 
Confidential 
Page 7 of 28 
1. 
INTRODUCTION 
This statistical analysis plan (SAP) describes the rules and conventions to be used in the 
presentation and analysis of infant exposure, milk and plasma pharmacokinetic and safety data 
from healthy lactating women for Protocol 1002FDC-075, entitled An Open-Label 
Postmarketing Milk-Only Lactation Study to Evaluate the Concentration of Bempedoic Acid and 
Bempedoic Acid and Ezetimibe in the Breast Milk of Healthy Lactating Women Administered 
Therapeutic Doses of Bempedoic Acid or Bempedoic Acid/Ezetimibe Fixed Combination Drug 
Product (FCDP), Amendment 1 (June 6th, 2023). The SAP will supersede the protocol in the 
event of any differences between the 2 documents in the plans for data analysis. 
Analyses will be conducted using SAS® version 9.4 or higher and Phoenix WinNonlin version 
8.4. 
2. 
STUDY OBJECTIVES 
2.1. 
Primary Objective 
The primary objectives of this study are to estimate infant exposure to bempedoic acid (BA) or 
bempedoic acid and ezetimibe (BA+EZE): 
• estimate the daily infant dosage and relative infant dose (RID) of BA in mature breast 
milk after administration of BA for 6 consecutive days (Cohort 1). 
• estimate the daily infant dosage and RID of BA and EZE in mature breast milk after 
administration of bempedoic acid/ezetimibe fixed combination drug product (FCDP) 
for 6 consecutive days (Cohort 2). 
2.2. 
Secondary Objective(s) 
The secondary objectives of this study are to characterize the excretion of BA or BA+EZE in 
mature breast milk of healthy lactating women who receive a once daily dose of BA or FCDP for 
6 consecutive days: 
• determine concentrations of BA (ETC-1002), active metabolite (ESP15228) and 
inactive metabolite  (ETC-1002-glucuronide) in mature breast milk collected over 24 
hours from healthy subjects administered BA (Cohort 1) or FCDP (Cohort 2), 
• determine concentrations of EZE and active metabolite ezetimibe-glucuronide (EZE-
glucuronide) in mature breast milk collected over 24 hours from healthy subjects 
administered FCDP (Cohort 2). 
2.3. 
Safety: 
The safety objective of this study is to evaluate the safety of 6 consecutive doses of BA or FCDP 
in healthy lactating women. 


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3. 
STUDY ENDPOINTS 
3.1. 
Primary Endpoint 
• Daily infant dosage calculated as the cumulative amount of drug excreted in breast 
milk on Day 6 of treatment, and 
• RID calculated as the ratio of estimated infant daily dose per kg body weight and 
maternal daily dose per kg of body weight multiplied by 100. 
3.2. 
Secondary Endpoints 
BA (ETC-1002), EZE, and metabolites (ESP15228, ETC-1002-glucuronide, and EZE-
glucuronide) PK assessments: 
• Amount excreted in each breast milk collection, calculated as the product of 
concentration and milk volume collected 
• Area under the milk concentration-time curve (AUC24h) over the 24-hour collection 
interval 
• Average milk concentration (Cavg) calculated as AUC24h/24h 
• Peak and trough milk concentrations (Cmax, Ctrough), and the time of peak milk 
concentrations (Tmax) 
• Plasma trough concentrations at 24 hours after the last dose on Day 6 (Ctrough) 
3.3. 
Safety Endpoints 
• Incidence of  the treatment-emergent adverse events  
• Clinical safety laboratory assessments (including hematology, blood chemistry, 
coagulation, and urinalysis), vital signs, and physical examinations. 


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4. 
STUDY DESIGN 
4.1. 
Overview 
This is a Phase 4, open-label study that will estimate the daily infant dosage and RID for BA and 
FCDP and characterize the excretion of ETC-1002, metabolites ESP15228, ETC-1002- 
glucuronide, EZE, and EZE-glucuronide in the mature breast milk of healthy women. The study 
will enroll 16 healthy lactating subjects, who will be randomized in a 1:1 ratio to receive either 
BA (Cohort 1) or FCDP (Cohort 2), who choose to stop breastfeeding their infant for the 
duration of the Treatment and Washout periods (13 days). After signing the informed consent 
form (ICF), subjects will enter the Screening Period for up to 42 days, followed by a 6-day 
Treatment Period and a 7-day Washout Period. At Visit T1, subjects will be administered 
investigational medicinal product (IMP) at the clinical research unit CRU. The IMP will then be 
self-administered at home on Day 2 through Day 5. Study staff will phone subjects Day 2 
through Day 5 to ensure IMP is being taken appropriately and remind subjects to discard breast 
milk produced after the first dose of IMP. Subjects will check-in to the CRU on the evening of 
Day 5 (with Sponsor approval the subject may check-in to the CRU on the morning of Day 6) for 
Visit T2  and start a 24-hour breast milk collection after the last dose of IMP on the morning of 
Day 6. Serum PK samples will be obtained on Day 7, approximately 24 hours after IMP 
administration on Day 6. Subjects will be discharged from the CRU on the morning of Day 7 
approximately 24 hours after Day 6 dosing and the completion of all Day 7 assessments. At the 
end of the Washout Period on Day 13, all subjects will be contacted by phone for a Post-
treatment Follow-up Visit. Once the call is complete, subjects may resume feeding their infants 
breast milk that is currently being produced. On Day 43 (Visit FU2), study staff will contact 
subjects by phone to assess for SAEs and if the patient was able to resume breastfeeding (if 
intended). 
 
 Please refer to Appendix 1 for a detailed Schedule of Assessments. 
The study design is presented in Figure 1. 
Figure 1: 
Study Schematic 
 
                           Day 1: Randomization and  
                                                      initial dose of study drug
 
 


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Screening Period: The Screening Period will begin with a Screening Visit (Visit S1) that will 
occur up to 42 days prior to randomization (Visit T1). Visit S1 will allow the Investigator to 
assess the subject’s eligibility and current breastfeeding practices. After the subject provides 
written informed consent, the subject will undergo screening assessments as outlined in 
Appendix 1. 
  
Treatment Period: Subjects who meet all eligibility criteria will be instructed to report to the 
clinical research unit (CRU) on Day 1 (Visit T1). Subjects who continue to meet eligibility 
criteria must confirm their infant is able to feed from a bottle, adequate stored breast milk and/or 
infant formula is available to feed the infant for the duration of the study, and the subject is 
maintaining adequate breast milk production. If a subject is weaning, duration of weaning will be 
documented. Subjects will then be randomized in a 1:1 ratio to receive either BA (Cohort 1) or 
FCDP (Cohort 2). Eight subjects will be in each cohort. While at the CRU, subjects will provide 
a predose blood sample for pharmacokinetic (PK) and safety laboratories. Subjects will use an 
electric breast pump to provide a predose breast milk sample and will then receive the first dose 
of IMP. When Visit T1 assessments are complete, subjects will be provided with adequate IMP 
supply to support once-daily dosing on Days 2, 3, 4 and 5 by self-administration at home. 
Subjects will be reminded that their infant(s) must not be fed with their breast milk that is 
produced after the first dose of IMP through Day 13 of the Washout period. On Day 2 through 
Day 5 study staff will contact each subject by phone to ensure IMP is taken appropriately and 
remind the subject to discard breast milk that is produced after the first dose of IMP. In addition, 
subjects will document the day and time of when IMP was taken for Day 2 through Day 5 in the 
Study Drug Diary. On the evening of Day 5 (Visit T2), subjects will check-in to the CRU for 2 
overnights (with Sponsor approval, subjects may check-in to the CRU on the morning of Day 6). 
Subjects must submit their Study Drug Diary at CRU check-in. Study staff will review the diary 
and assess IMP adherence. On the morning of Day 6, subjects will pump both breasts with an 
electric pump until completely emptied. When pumping is complete, Cohort 1 subjects will 
receive the Day 6 dose of BA and Cohort 2 subjects will receive the Day 6 dose of FCDP. Breast 
milk will be collected from each subject over the next 24 hours using an electric pump at 3, 6, 9, 
12, 16, 20 and 24 hours (±30 minutes) after Day 6 dose administration. Both breasts will be 
emptied completely during each collection. At each sampling time point, milk collected from 
each breast will be mixed together and the total volume measured and recorded. On Day 7, blood 
will be collected approximately 24 hours after Day 6 dosing for PK and safety laboratory 
samples. Subjects will be discharged from the CRU on the morning of Day 7 after breast milk 
collection and completion of Day 7 assessments. Subjects will be instructed to continue to pump 
and discard breast milk during the remainder of the Washout Period through Day 13. 
 
Follow-up Period: On Day 13, all subjects will be contacted by phone as a post-treatment 
Follow-up Visit (Visit FU1/End-of-Study [EOS]). Breastfeeding may resume after Visit FU1 on 
Day 13. An optional lactation consultant visit will be scheduled for those subjects who desire to 
re-establish breastfeeding. On Day 43 (Visit FU2), study staff will contact subjects by phone to 
assess for SAEs and if the patient was able to resume breastfeeding (if intended). 
 


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4.2. 
Treatment Assignment, Randomization, and Blinding 
4.2.1. 
 Randomization and Treatment Assignment 
Randomization plan is reviewed and approved before the first subject enrollment and will be 
archived in eTMF after study database lock. The study site will manually execute the 
randomization and drug dispense according to Pharmacy Manual. 
Sixteen subjects will be randomized in a 1:1 ratio to receive either BA (bempedoic acid 180 mg)  
(Cohort 1) or FCDP (Cohort 2). The IMP will be taken Day 1 through Day 6 of the treatment 
period. When the target number of subjects (8 in each cohort) is reached and all subjects have 
completed the 24-hour breast milk collection at the CRU, randomization will be closed. If a 
subject is randomized but did not complete the 24-hour breast milk collection in the CRU, she 
will be replaced with a new subject on the same treatment to ensure each cohort of the study has 
8 evaluable subjects.  
4.2.2. 
Blinding 
This is an open-label study. 
5. 
PLANNED ANALYSES 
The following analyses will be performed for this study: Final Analysis 
5.1. 
Interim Analyses 
There will be no interim analyses in this study. 
5.2. 
Final Analyses 
All PK and safety analyses specified in this SAP will be performed by a CRO.  
Additional ad-hoc analyses may be performed as needed. 
6. 
ANALYSIS SETS 
Inclusion of subjects in each analysis set will be finalized prior to the database lock of the study. 
Additional subsets may be explored as needed. 
6.1. 
Full Analysis Set 
Full Analysis Set (FAS, same as Safety Population in protocol) will consist of all randomized 
subjects who receive at least 1 dose of study drug – either BA (Cohort 1) or FCDP (Cohort 2). 
FAS will be used for summary of disposition, demographics and baseline characteristics, 
treatment exposure, study drug accountability, postpartum history, infant feeding practice, 
concomitant medications, and all safety data (including adverse events, clinical laboratory tests, 
physical examination, vital signs). The summaries will be conducted by cohort. 


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6.2. 
PK Analysis Set 
The PK Analysis Set (PKS, same as PK population in protocol) will include all subjects in FAS 
who have at least 1 evaluable post-dosing milk ETC-1002 concentration data point. Data points 
affected by protocol deviation may be excluded from PK analyses but will remain in the PK 
concentration data listing.  
7. 
STUDY DEFINITIONS 
7.1. 
Disposition 
Study Completion: Subjects who complete study at the End of Study (EOS) visit  are considered 
as achieving study completion. 
Treatment Completion: Subjects who complete the End of Treatment (D6/EOT) visit on Day 6 
are considered as achieving treatment completion. 
7.2. 
Reference Start Date and Study Day 
Reference Start Date (Day 1) is defined as the date of first dosing of study drug (BA or FCDP).  
Study Day will be calculated from the reference start date and will be used to show start/stop day 
of assessments and events. 
Study Day will be calculated as follows: 
• If the date of the event is on or after the reference date, then Study Day = (date of event – 
reference start date) + 1. 
• If the date of the event is prior to the reference date, then Study Day = (date of event – 
reference start date). 
The Study Day will be used to show start/stop day of assessments and events (including AEs, 
prior and concomitant medications). In the situation where the event date is partial or missing as 
entered in the EDC database, the date will be displayed as such in the listings. Study Day and 
any corresponding duration(s) will be presented based on the imputations specified in Appendix 
2. 
7.3. 
Baseline 
Baseline is defined as the last non-missing measurement taken on or prior to initial IMP on Day 
1 (including unscheduled assessments), unless otherwise specified. 
7.4. 
Prior and Concomitant Medications 
Prior medications are medications which started and ended prior to Day 1. 
Concomitant medications are medications that started after Day 1 and continued during the 
study, or that started before or on Day 1 and continued through Day 1 (“ongoing” at Day 1 or 
ended after Day 1). 


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8. 
STATISTICAL CONSIDERATIONS 
8.1. 
Sample Size 
A minimum sample size of 16 (8 subjects who receive BA [Cohort 1] and 8 subjects 
who receive FCDP [Cohort 2]) evaluable subjects (who complete the 
6-day treatment period and the 24-hour breast milk collection in the CRU) is planned for this 
study. Subjects who are treated but do not complete the 24-hour breast milk collection in the 
CRU will be replaced with a new subject on the same treatment to ensure 8 evaluable subjects in 
each cohort for the PK analyses. All treated subjects will be in the FAS. 
The sample size was not based on empirical or hypothesis testing criteria. The sample size was 
based on clinical and regulatory considerations and precedence in previous ETC-1002 studies 
(
). The sample size is considered sufficient to address the primary objectives of 
the study. 
8.1. 
Number of Centers 
The study will be conducted in up to 2 CRUs in the United States. Additional sites may be 
invited to participate to ensure study timelines are met. 
8.2. 
Coding Dictionaries 
Adverse events, medical history diagnoses or signs/symptoms, and concomitant procedures are 
coded using Medical Dictionary for Regulatory Activities (MedDRA) version 26.0 including 
system organ class (SOC), high level term (HLT) and preferred term (PT). 
Prior and concomitant medications are coded using WHO Drug Dictionary (WHO-DD) Global 
B3 version 01Mar2023. 
8.3. 
General Principles 
Descriptive statistics (n, mean, standard deviation, median, 1st quartile, 3rd quartile, minimum, 
and maximum) will be calculated for continuous data.  Minimum and maximum will be 
presented with the same number of decimal places as reported/collected, 1 additional decimal 
place will be included for mean and median, and 2 additional decimal places will be included for 
standard deviation. 
Categorical data will be summarized using count and percentage based on number of 
non-missing values.  Percentages will be presented with 1 decimal place.  The number of missing 
values will be presented as a separate category when appropriate. Counts of zero in any category 
will be presented without percentage.   
8.4. 
Missing Data Handling 
Unless otherwise specified, missing data will not be imputed.  
8.4.1. 
Imputation of Missing Dates 
For adverse events, and for prior and concomitant medications, if the start and/or end dates are 
incomplete, then the date will appear as-is (partial or missing) in the listings. When a complete 


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date is needed, e.g., to compute the Study Day, imputation rules specified in Appendix 2 will be 
used unless otherwise specified. In essence, AEs of uncertain start date will be considered as 
having started after the first dose of study drug. Medications of uncertain start or end dates will 
be considered as having started before, or continued after the first dose of study drug, 
respectively.  
8.4.2. 
  PK and Laboratory Data Beyond the Limits of Quantification 
Day 1 pre-dose concentrations below the limit of quantitation (BLQ) will be imputed as zero. 
Day 6 pre-dose PK concentrations in breast milk were not collected in this study. To facilitate 
the determination of AUC24h in breast milk, a Day 6 pre-dose concentration value is needed. 
Since subjects will be near steady state after 6 days of bempedoic acid dosing, the Day 6 pre-
dose concentration will be imputed as the trough concentration value on Day 7 at 24 hours post-
dose for individual subjects. If a concentration of BLQ is before the last quantifiable value of the 
subject, it will be marked with an exclusion flag and excluded from analysis. The BLQ 
concentrations that are at the end of the concentration curve will be imputed by half of the lower 
limit of quantitation (LLOQ) for the purpose of quantitative summaries. 
All PK concentration of BLQ values will be presented as reported, i.e., as “BLQ<(xx.x)” in the 
listings. 
Biomarker and safety laboratory measurements reported as “<X” or “>X” will be imputed as X 
for the purpose of quantitative summaries, but will be presented as reported, i.e., as “<X” or 
“>X” in the listings.  
9. 
DISPOSITION AND WITHDRAWALS 
All subjects who were screened will be accounted for in this study.  Reasons for screen failure 
will be summarized by pre-defined categories per the Screen Failure eCRF.  For screen failures 
due to inclusion or exclusion criteria violation, the criteria category will be presented in a listing.   
The number of subjects in each analysis set, along with study completion status, will be 
summarized by treatment group as well as overall. Subjects who discontinue from study 
treatment and/or study will be summarized by discontinuation reason. 
A listing of subject disposition will be provided for all randomized subjects, including the 
treatment and study completion status, and discontinuation reasons, and/or reasons of being 
excluded from FAS, PKS. 
10. 
PROTOCOL DEVIATIONS 
The protocol deviations will be recorded and tracked in the Clinical Trial Monitoring System. 
All protocol deviations will be reviewed by the clinical team to identify important versus non-
important deviations before the final EDC database lock. The final list of protocol deviation will 
be approved by the study team prior to the EDC database lock and will be used to generate the 
protocol deviation summary and listing. 


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For deviations at study entry, subject eligibility will be assessed against the inclusion and 
exclusion criteria of the protocol. For on-study deviations, compliance with the protocol will be 
determined via periodical data and monitoring report review.  
All protocol deviations will be provided in a listing. Important protocol deviations will be 
summarized by treatment group and deviation categories for SES.   
11. 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
Demographic data and other baseline characteristics will be summarized by treatment group for 
the FAS, PKS.  
The following demographic and other baseline characteristics will be reported for this study:   
• Age (years [yrs])  
• Race  
• Weight (kg) 
• Height (cm) 
• Body mass index (BMI) (kg/m2) 
• BMI group (kg/m2) (<25, 25 ~ <30, or ≥30) 
12. 
MEDICAL HISTORY AND POSTPARTUN HISTORY  
12.1. 
Medical History 
Medical information will be presented by Medical Dictionary for Regulatory Activities 
(MedDRA) SOC and PT for the SES.  Medical history conditions are defined as those conditions 
which started prior to signing of the ICF.  Medical history will be coded using MedDRA in most 
recent version when the study started (Section 8.2). 
12.2. 
Postpartum History of Recent Pregnancy 
The postpartum history, including gestation age at delivery and length of postpartum, will be 
collected at screening and summarized by cohort and for overall FAS. 
13. 
LACTATION STAGE 
The lactation stage (lactating/weaning/weaned off) and related information will be collected at 
Screening and T1 (Day 1) visits. Subject listing of lactation stage, including start date of 
lactation or weaning, duration of lactation or weaning, and date of weaned off will also be 
provided. 
14. 
CURRENT FEEDING PRACTICE 
Current feeding practice will be collected at Screening and T1 (Day 1) visit. 


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Number and percentages of subject who produced adequate breast milk, and number and 
percentages of subject who fed their infant with formula supplementation will be summarized by 
cohort and for overall on FAS. 
The frequency of feeding and the volume of pumped breast milk consumed per day, and the 
volume of infant formula consumed per day will be summarized by cohort on FAS. 
15. 
PRIOR AND CONCOMITANT MEDICATIONS 
Prior and concomitant medications will be presented for the SES. In general, the medications 
will be summarized by Anatomical Therapeutic Chemical (ATC) drug class (ATC level 4, 
anatomical or pharmacological groups), preferred names, and by cohort.  
• Prior medications are medications which started and stopped prior to the date of first 
dose of study drug. 
• Concomitant medications are medications that started prior to and continued through 
the date of the first dose of study drug. 
See Appendix 2 for handling of partial dates for prior medications and concomitant medications.   
Prior and concomitant medications will be tabulated separately and reported in a subject listing.  
15.1. 
Prohibited Medications 
Subjects may not use medications listed below within the time periods indicated and may not use 
the following drugs during the study: 
• HMG Co-A reductase inhibitor (statin) concurrently or within 30 days prior to 
randomization (Visit T1); 
• cyclosporine, cholestyramine, probenecid, fibrate drugs, or  medications 
contraindicated during lactation concurrently or within 30 days prior to randomization 
(Visit T1); 
• experimental or investigational drugs concurrently or within 30 days or 5 half-lives of 
the drug, whichever is longer, prior to screening (Visit S1); 
• concomitant use or use within 30 days prior to randomization (Visit T1) of drugs that 
decrease breast milk production, such as pseudoephedrine; or 
• concomitant use or use within 30 days prior to randomization (Visit T1) of drugs that 
increase breast milk production, such as domperidone. 
16. 
STUDY MEDICATION EXPOSURE AND TREATMENT 
COMPLIANCE  
Study drug exposure duration (days) will be summarized by cohort on FAS. 


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In addition, estimated compliance with study drug will be presented for the FAS by cohort. The 
subjects will be grouped as compliant, i.e., those who have 100% of required tablets while on 
treatment  versus non-compliant (<100% compliance). 
Per protocol, subjects will take 1 tablet of the study drug once daily, starting from the visit day at 
which their study drug is initially dispensed (date of Visit T1) to the day of last dose on Day 6.  
The percentage of compliance will be based on drug accountability data and calculated by the 
formula using counts of tablets: 
Total tablets taken = [tablets dispensed - tablets returned on Day 5] + 1 (if the last dose 
on Day 6 is administered) 
% Compliance = [Total tablets taken] *100 / [treatment duration (days)],  
where the protocol-defined treatment duration is 6 days. 
The percentage compliance is capped as a maximum of 100% if it exceeds 100%.  
Note that subjects who did not receive any study drug or did not report any drug accountability 
data will be counted as noncompliant (0%).  
17. 
PHARMACOKINETIC (PK) ANALYSIS  
17.1. 
PK Nominal Timepoints 
Table  1  Schedule of Dosing and Sample Collection 
Time 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Dosing (once per day) 
X 
X 
X 
X 
X 
X 
 
Sample  
Plasma, 
Milk 
Milk* 
Plasma, 
Milk* 
*On Days 6-7, breast milk will be collected during the intervals of 0-3h, 3-6h, 6-9h, 9-12h, 12-16h, 
16-20h, and 20-24h after Day 6 dose administration 
PK milk samples will be collected at the following nominal timepoints –  
• Visit T1 (Day 1)  Pre-dose (≤1 hour before IMP administration) 
• Visit T2 (Day 6 and 7)  at 3, 6, 9, 12, 16, 20 and 24 hours (±30 minutes) after Day 6 dose 
administration. 
PK plasma samples will be collected at the following nominal timepoints –  
• Visit T1 (Day 1)  Pre-dose (≤1 hour before IMP administration) 
• Visit T2 (Day 7)  at 24 hours (±30 minutes) after Day 6 dose administration. 


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17.2. 
PK Parameters  
The PK parameters listed in the table below are estimated for this study, and used for the primary 
and the secondary endpoints estimate: 
Table 2    PK Parameters 
Cohort 
[IMP] 
Specimen Analytes 
PK Parameter 
Cohort 1 
[BA] 
Milk 
ETC-1002, ESP15228, ETC-1002-glucuronide 
Cmax, Tmax, Ctrough, 
AUC24h, Cavg 
Plasma 
ETC-1002, ESP15228, ETC-1002-glucuronide 
Ctrough,  
M/P ratio* 
Cohort 2  
[BA/EZE 
FCDP] 
Milk 
ETC-1002, ESP15228, ETC-1002-glucuronide,  
EZE, EZE-glucuronide 
Cmax, Tmax, Ctrough, 
AUC24h, Cavg 
Plasma 
ETC-1002, ESP15228, ETC-1002-glucuronide 
EZE, EZE-glucuronide 
 
Ctrough,  
M/P ratio* 
* M/P ratio = Ctrough (Milk)/Ctrough (Plasma) at 24 hours after Day 6 dose administration. 
17.3. 
 PK Analysis for Primary Endpoints 
The 1st primary endpoint - daily infant dosage (mg/day) of BA or EZE will be calculated 
as the amount of drug in breast milk collected over 24 hours (starting on Day 6 post study 
treatment) for individual subjects, where the amount of drug in breast milk is calculated 
as the sum of total drug concentration in each milk collection multiplied by the expressed 
milk volume in each milk collection.  
Daily infant dosage (Doseij) = Σ (Cij x Vij), where 
          Doseij = daily infant dose based on collected drug concentration in breast milk and 
expressed breast milk volume 
           Cij = drug concentration in breast milk from each collection 
           Vij = breast milk volume collected at each nominal timepoint 
           i = nominal timepoints within 24 hours post study treatment on Day 6 
           j = subjects (8 in each cohort, 16 in total)   
• The 2nd primary endpoint - relative infant dose (RID) of BA (for Cohort 1 and 2 
respectively) or EZE (for Cohort 2 only) equals the percent of the weight-adjusted 
maternal dosage consumed by infant via breast milk over 24 hours. 
RID (%) = Estimated daily infant dosage (mg/day/kg) / Maternal dosage (mg/day/kg) x 
100.  


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The estimated daily infant dosage will be calculated as the average drug concentration in 
breast milk over 24 hours after the Day 6 dose administration (Cavg) multiplied by 150 
mL/day/kg, the estimated standard infant milk intake over 24 hours. Maternal dosage will 
be calculated as the mean maternal dosage (mg/day per kg baseline body weight 
determined on Day 1). 
Estimated daily infant dosage (mg/day/kg) = Cavg (mg/ml) x 150 (ml/day/kg)  
Maternal dosage (mg/day/kg) = daily dose of study treatment (mg/day) / baseline body 
weight (kg) 
17.4. 
PK Analysis for Secondary Endpoints 
The secondary endpoints of this study are the following, which are based on PK assessments (see 
Table 2) for BA (ETC-1002), EZE, and their metabolite (ESP15228, ETC-1002-glucuronide, and 
EZE-glucuronide) of milk and plasma PK samples.   
• Amount excreted in breast milk during each collection period, calculated as the 
product of analyte concentration and volume of milk collected per collection period. 
• Area under the breast milk concentration-time curve (AUC24h) over the 24-hour 
collection interval. To calculate AUC24h, the initial milk concentration at time equal 0 
hours on Day 6 will be set equal to the value of Ctrough for each individual subject. 
• Average drug concentration in breast milk (Cavg) calculated as AUC24h/24h 
• Peak milk concentration (Cmax) 
• Time of peak milk concentrations (Tmax) 
• Trough milk concentrations at 24 hours after the last dose on Day 6 (Ctrough) 
• Plasma trough concentrations at 24 hours after the last dose on Day 6 (Ctrough) 
Actual sampling times will be used in the final analyses of individual PK parameters. Predose 
sampling times will be set to zero. AUC24h will be estimated by noncompartmental analysis 
(linear up/log down trapezoidal method) and estimates of Cmax and tmax will be reported from 
observed values. If Cmax occurs at more than one time point, tmax will be assigned to the first 
occurrence of Cmax. 
Cavg in milk will be calculated based on area under the milk concentration-time curve (AUC24h) 
over the 24-hour collection interval. 
Cavg (mg/mL) = AUC24h (mg*h/mL) /24h. 
If a subject had fewer than 3 data points above LLOQ, AUC24h and Cavg will be set to “NE” (Not 
Evaluable).  
M/P ratio is defined as the ratio of milk trough concentration and plasma trough concentration. 
 M/P ratio = Ctrough (Milk)/Ctrough (Plasma)  
All the descriptive analyses on PK concentration and PK parameters will be performed upon the 
PKS. 


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 Protocol 1002FDC-075: Statistical Analysis Plan v1.0 
26Jun2024 
 
Confidential 
Page 20 of 28 
Collected milk volume, milk concentration of BA and its metabolites will be summarized by 
nominal sampling timepoints, and by cohort on FAS. Milk concentration of EZE and its 
metabolite will be summarized by nominal sampling timepoints for Cohort 2 only. 
Summary statistics of n, arithmetic mean, standard deviation (SD), CV%, minimum, median, 
maximum, geometric mean (converting back to the original units), and geometric coefficient of 
variation (GCV%) will be presented for PK concentration data and PK parameters (AUC24h, Cavg, 
Cmax, Tmax, Ctrough) by cohort in summary tables.  
• Geometric mean = exp [mean of log(x)], exponential of mean of log-transformed 
concentration data. 
• Geometric standard deviation (GSD) = exp [SD of log(x)], exponential of standard 
deviation of log-transformed concentration data. 
• GCV% = sqrt [exp (GSD^2) -1] x 100. 
The following assessments will also be summarized by cohort: 
• Daily infant dosage (Doseij) 
• Estimated daily infant dosage  
• RID  
• M/P ratio 
Plots of the following milk concentration-time profiles will be created:  
• (A) ETC-1002, (B) ESP15228, (C) ETC-1002-glucuronide on linear scale by cohort. 
• (A) EZE, (B) EZE-glucuronide on linear  scale for Cohort 2. 
• Composite of individual subject (A) ETC-1002, (B) ESP15228, (C) ETC-1002-
glucuronide, (D) EZE, (E) EZE-glucuronide on linear scale by cohort. 
Box plot of the following parameters from breast milk PK will be created by cohort: 
• Cmax, Ctrough, Cavg, and AUC24h (A) ETC-1002, (B) ESP15228, (C) ETC-1002-
glucuronide, (D) EZE, (E) EZE-glucuronide by cohort 
All milk and plasma PK concentration data and parameters will be displayed in subject listings. 
18. 
SAFETY ANALYSIS 
18.1. 
General 
All summary tables for safety outcomes will be based on the FAS. All adverse event tables will 
be summarized by cohort. There will be no statistical comparisons between cohort for safety 
data, unless otherwise specified.   


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP  
Esperion Therapeutics, Inc. 
 Protocol 1002FDC-075: Statistical Analysis Plan v1.0 
26Jun2024 
 
Confidential 
Page 21 of 28 
18.2. 
Adverse Events 
18.2.1. 
Treatment Emergent Adverse Events (TEAEs) 
All types of AE summarization described in this section are for TEAEs only, which is defined as 
AEs that occur or worsen after the first dose of study drug up to the end of the study (Visit 
Follow-Up 2/Day 43). 
Severity is classed as mild, moderate, or severe (increasing severity). TEAEs starting after the 
first dose of study drug with a missing severity will be classified as severe.  If a subject reports a 
TEAE more than once within the same System Organ Class (SOC) and Preferred Term (PT), 
then the TEAE with the worst-case severity will be used in the corresponding severity 
summaries. 
Relationship to study treatment, as indicated by the Investigator, is “Unrelated” if the TEAE is 
“not related” or “unlikely related”.  A “related” TEAE is defined as a TEAE with a relationship 
of “possibly related”, “probably related”, or “definitely related” to study medication.  TEAEs 
with a missing relationship to study medication will be regarded as “related” to study 
medication. 
A TEAE overview summary will be provided for FAS by cohort and for total (Cohort 1 and 2). 
The following categories will be presented in the AE overview summary: 
• Number of subjects with any TEAE 
• Number of subjects with any TEAE related to study treatment 
• Number of subjects with any SAE 
• Number of subjects with any SAE related to study treatment 
• Number of subjects with any TEAE leading to study treatment discontinuation 
• Number of subjects with any TEAE by highest severity 
o Mild 
o Moderate 
o Severe 
• Number of subjects with any AE by strongest relationship with study treatment 
▪ Related (including definitely related, probably related, possible related, 
and missing) 
▪ Unrelated (including unlikely related, not related) 
Subject incidence of TEAEs, serious AEs (SAEs), and TEAEs leading to withdrawal of study 
treatment will be tabulated by SOC and PT in descending order of frequency among the total .  
TEAEs that are related to study treatment will be summarized separately.  If a subject reports the 
same TEAE more than once within that SOC/PT, then the TEAE with the worst-case relationship 
to study treatment will be used in the corresponding relationship summaries. 
An AE listing will be provided includes both TEAEs and non-TEAEs. 


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP  
Esperion Therapeutics, Inc. 
 Protocol 1002FDC-075: Statistical Analysis Plan v1.0 
26Jun2024 
 
Confidential 
Page 22 of 28 
18.3. 
Safety Laboratory Evaluations 
18.3.1. 
Safety Laboratory Evaluation 
Quantitative laboratory measurements, including hematology, blood chemistry, and coagulation, 
will be reported with the relevant laboratory reference ranges in Conventional US units and 
classified as Low/Normal/High by the central lab: 
• Low:  below the lower limit of the laboratory reference range; 
• Normal:  within the laboratory reference range (upper and lower limit included); or 
• High:  above the upper limit of the laboratory reference range. 
A list of laboratory assessments to be included in the outputs is included in Appendix 3. 
Quantitative lab results at baseline (pre-dose on Day 1/Visit T1) and at end of study 24 hours 
after the last dose on Day 6 (Day 7/Visit T2) and change from baseline values at Visit T2 will be 
summarized by cohort. Urinalysis is quantitative and will not be summarized.  
The Modification of Diet in Renal Disease (MDRD) equation (Levey 2006) for estimated 
glomerular filtration rate (eGFR) will be used by the central lab, 
eGFR (mL/min/1.73 m²) = 175 × (serum creatinine)-1.1.54 × (Age)-0.203 × 0.742 (if female)  
                                            × 1.212 (if African American), where creatinine is in mg/dL.  
All lab test results will be listed by subject, lab test name, and visit.  
18.4. 
Vital Signs 
The following vital signs measurements will be reported for this study: 
• Sitting systolic blood pressure (mmHg) 
• Sitting diastolic blood pressure (mmHg) 
• Sitting heart rate (beats per minute [bpm]) 
Summaries will be provided by cohort for vital signs data for observed values at baseline and 
Visit T2 and change from baseline values at Visit T2 . 
18.5. 
Physical Examination 
Clinically significant abnormal findings that occur post initial IMP will be reported as TEAE. 
Al abnormalities in physical examinations will be presented in a subject listing. 


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP  
Esperion Therapeutics, Inc. 
 Protocol 1002FDC-075: Statistical Analysis Plan v1.0 
26Jun2024 
 
Confidential 
Page 23 of 28 
19. 
REFERENCES 
1. Clinical Lactation Studies: Considerations for Study Design. Draft Guidance for Industry 
(FDA May 2019), Draft Guidance https://www.fda.gov/regulatory-information/search-
fda-guidance-documents/clinical-lactation-studies-considerations-study-design 
2. Investigator’s Brochure, ETC-1002, v15.5, May 2020 
3. Protocol 1002FDC-075 Pharmacy Manual v1.0 
4. Report 1002-061. Population Pharmacokinetic/Pharmacodynamic Analysis of Bempedoic 
Acid and LDL-C Concentration in Healthy Subjects and Patients with Primary 
Hypercholesterolemia. 31 Aug 2020. 
 
 


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP  
Esperion Therapeutics, Inc. 
 Protocol 1002FDC-075: Statistical Analysis Plan v1.0 
26Jun2024 
 
Confidential 
Page 24 of 28 
APPENDIX 1. SCHEDULE OF EVENTS 
 
Study Period 
Screenin
g Period 
Treatment Period 
Washout Period 
SAE FU 
Visit 
S1 
T1 
— 
T2 
— 
— 
FU1a 
FU2 
Procedure 
Day 
-42 to -1 
Day 1 
Day 
2-4 
Day5 
Day6 
Day7b 
Day 8-12 
Day 13 
(+3 days) 
by phone 
Day 43  
(+5 days) 
by phonec 
Informed consent 
X 
 
 
 
 
 
 
 
 
Enrollment criteria 
X 
Predos
e 
 
 
 
 
 
 
 
Review of breastfeeding 
practice  
X 
Predos
e 
 
 
 
 
 
 
 
Adequate breast milk 
production/weaning 
X 
Predos
e 
X 
X 
 
 
 
 
 
Infant able to bottle feed 
X 
Predos
e 
 
 
 
 
 
 
 
Adequate stored breast 
milk/ formula to feed 
infantd 
X 
Predos
e 
X 
X 
X 
X 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
Medical historye 
X 
 
 
 
 
 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
 
Adverse event review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical exam 
X 
 
 
 
 
X 
 
 
 
Weight 
X 
X 
 
 
 
X 
 
 
 
Height/BMI 
X 
 
 
 
 
 
 
 
 
Vital signsf 
X 
X 
 
 
 
X 
 
 
 
Serum pregnancy test 
X 
 
 
 
 
 
 
 
 
Urine pregnancy test 
 
X 
 
 
 
X 
 
 
 
Urine drug and alcohol 
screen 
X 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
Pump breast milk for 
predose collection at 
CRU (≤1 hour before 
IMP administration) 
 
X 
 
 
 
 
 
 
 
Lactation consultant visit 
(optional) 
X 
X 
X 
X 
 
X 
X 
Xg 
 
Pump and discard breast 
milkh 
 
X 
X 
X 
 
Xi 
X 
X 
 


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP  
Esperion Therapeutics, Inc. 
 Protocol 1002FDC-075: Statistical Analysis Plan v1.0 
26Jun2024 
 
Confidential 
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Phone call to subjectj 
 
 
X 
X 
 
 
 
X 
X 
Predose PK blood 
sample 
 
X 
 
 
 
 
 
 
 
Clinical lab evaluationsn  
X 
X 
 
 
 
X 
 
 
 
Dispense IMP 
 
X 
 
 
 
 
 
 
 
IMP administration at 
CRU 
 
X 
 
 
X 
 
 
 
 
Self-administration of 
IMP 
 
 
X 
X 
 
 
 
 
 
CRU check-in (evening)k 
 
 
 
X 
 
 
 
 
 
IMP returnk 
 
 
 
X 
 
 
 
 
 
Study Drug Diary 
 
 
X 
X 
 
 
 
 
 
Domicile in CRU 
 
 
 
X 
X 
 
 
 
 
Pump breast milk for 0-
24 hr. post-dose 
collection at CRUl 
 
 
 
 
X 
X 
 
 
 
24-hr (after Day 6 dose) 
PK blood samplem 
 
 
 
 
 
X 
 
 
 
CRU Discharge 
(morning) 
 
 
 
 
 
X 
 
 
 
BMI = body mass index; BP = blood pressure; CRU = clinical research unit; DBP = diastolic blood pressure; FU1 = follow-up 
visit 1; HR = heart rate; min = minutes; PK = pharmacokinetic; S1 = screening visit 1; SAE FU = serious adverse event follow-
up; SBP = systolic blood pressure; T1 = treatment visit 1; T2 = treatment visit 2 
a. Subjects may resume breastfeeding. 
b. All procedures will be completed at early termination except 24-hour PK blood sample and breast milk collection. 
c. Day 43 phone call to follow-up on SAEs and question if patient was able to resume breastfeeding (if intended) without 
problems. 
d. Subjects must have adequate stored breast milk and/or infant formula available to feed the infant after the first dose of IMP 
through Day 13 of the study. 
e. In addition to existing medical conditions, medical history should include gestational age at delivery, date of delivery, stage 
of lactation, length of time postpartum, and smoking and alcohol intake. 
f. Vital signs will include DBP, SBP, and HR.  Subject will rest for several minutes prior to assessments. 
g. Lactation consultant visit for subjects who desire to re-establish breastfeeding at the end of study (Visit FU1). 
h. Pump and discard breast milk after the 1st dose of IMP on Day 1 through Day 5 and Day 7 through Day 13. 
i. Discard breast milk produced after completion of the 24hr breast milk collection period. 
j. For Day 2 through Day 5, remind subject to take IMP appropriately and discard breast milk produced after Day 1.  If subject 
misses a dose of IMP contact the Sponsor immediately. 
k. With sponsor approval, the subject may check-in to the CRU the morning of Day 6 and return IMP at that time. 
l. Breast milk collections will be performed using an electric pump at specified intervals (±30 min) over 24 hours at 3, 6, 9, 
12, 16, 20, and 24 hours following IMP dosing on Day 6.  Both breasts will be emptied completely during each collection.  
At each sampling time point, milk collected from each breast will be mixed together and the total volume measured.  Milk 
will be stored frozen until time of analysis. The specific timing of the milk sample relative to the IMP dose will be recorded. 
m. A blood sample for PK will be collected on Day 7 approximately 24 hours (±30 min) after IMP administration on Day 6. 
n. Chemistry and hematology at Visit S1, Visit T1 and Visit T2; Serology and coagulation parameters at Visit S1 only. 
 


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP  
Esperion Therapeutics, Inc. 
 Protocol 1002FDC-075: Statistical Analysis Plan v1.0 
26Jun2024 
 
Confidential 
Page 26 of 28 
APPENDIX 2. PARTIAL DATE CONVENTIONS 
Imputed dates will NOT be presented in the listings. 
The following rules will be used to impute partial missing AE start/stop dates: 
AE start 
date 
If only Day is missing: 
If the AE start year and month are the same as that for 
the first dose (Day 1) date, then the AE start day will be 
imputed as the day of first dose date; otherwise, the AE 
start day will be imputed as the first day of the month. 
If both Day and Month are 
missing: 
If AE start year is the same first dose year, then the AE 
start Month and Day will be imputed as the Month and 
Day of first dose date; otherwise, the AE start date will 
be imputed as 01 January. 
If Year of AE start date is 
missing, or AE start date is 
complete missing: 
The AE start date will be imputed as the first dose date. 
AE end date 
If only Day is missing: 
If only Day is missing and AE end month and year are 
the same as the month and year of the EOS date, then 
use the subject completion date; otherwise, the last day 
of the month will be imputed. 
If both Day and Month are 
missing: 
If both Day and Month are missing and AE end date 
year is the same as the year of the EOS date, then the 
subject completion date will be used to impute. 
If the year of the AE end date precedes the year of the 
EOS date, then the AE end month and day will be set to 
31 December. 
If the Year of AE end date 
is missing, or AE end date 
is completely missing: 
If only Year is missing, then the EOS year will be 
assigned to the end date. 
If the AE end date is completely missing, then 
“Ongoing” status will be assigned. 
AE = adverse event; EOS = End-of-Study 


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP  
Esperion Therapeutics, Inc. 
 Protocol 1002FDC-075: Statistical Analysis Plan v1.0 
26Jun2024 
 
Confidential 
Page 27 of 28 
The following rules will be used to impute partial missing medication dates: 
Medication 
start date 
If only Day is missing: 
If only Day is missing, then the first day of the month 
will be assumed. 
If only Day and Month are 
missing: 
If both Day and Month are missing, then January 1 will 
be assumed. 
If only Year is missing, or 
date is completely missing: 
If only Year is missing, then informed consent signature 
year will be used to impute. 
If medication start date is completely missing, then the 
informed consent signature date or medication end date 
whichever is earlier, will be used to impute. 
Medication 
end date 
If only Day is missing 
If only Day is missing, then the last day of the month 
will be assumed. 
If both Day and Month are 
missing 
If both Day and Month are missing, then the medication 
end date month and day will be set to December 31. 
If Only Year is missing, or 
medication end date is 
completely missing 
If only Year is missing, then the year of last visit will be 
assigned for the end date. If medication end date is 
completely missing, then “Ongoing” status will be 
assigned, and the end of study date will be imputed 
EOS = End-of-Study 


Bempedoic Acid and Bempedoic Acid/Ezetimibe FCDP  
Esperion Therapeutics, Inc. 
 Protocol 1002FDC-075: Statistical Analysis Plan v1.0 
26Jun2024 
 
Confidential 
Page 28 of 28 
APPENDIX 3. CLINICAL SAFETY LABORATORY TESTS 
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 %)  
Clinical Chemistry 
(serum, fasting) 
• Albumin (ALB)  
• Alkaline phosphatase (ALP)  
• 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 bilirubin (TB) and direct bilirubin 
• Total protein  
• Uric acid  
Urinalysis 
(Dipstick) 
• Clarity 
• Bilirubin 
• Color 
• Glucose 
• Ketones 
• Leukocyte esterase 
• Nitrate 
• Occult Blood 
• pH 
• Protein 
• Specific Gravity 
• Urobilinogen 
Coagulation 
Parameters 
• prothrombin time (PT) 
• international normalized ratio (INR)