Milk-Only Lactation Study to Evaluate the Concentration of Bempedoic Acid and Bempedoic Acid/Ezetimibe Fixed Combination Drug Product (FCDP) in the Breast Milk of Healthy Lactating Women

An Open-Label Postmarking 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)

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.

Study Overview

• Status: Completed
• Conditions: Healthy Lactating Women
• Intervention / Treatment: Drug: Bempedoic Acid 180 MG Oral Tablet; Drug: Bempedoic Acid/Ezetimibe 180 MG-10 MG Oral Tablet

Detailed Description

Post marketing approval commitment for the FDA

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • PPD Development, Las Vegas Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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.
• 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.
• The subject must not be pregnant.
• The subject must be surgically sterile or willing to use 1 acceptable method of birth control.

Exclusion Criteria:

• Has clinically significant infection (e.g., pneumonia, pyelonephritis) or chronic infection within 30 days prior to enrollment.
• 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.
• Has estimated glomerular filtration rate (eGFR) <30 mL/min/1.732 using the Modification of Diet in Renal Disease (MDRD) formula.
• Has liver disease or dysfunction characterized by Child-Pugh Class B or Class C.
• History of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, or neurodegenerative disease.
• Has active psychiatric problems that, in the Investigator's opinion, may interfere with compliance with the study procedures.
• Has history of breast implants, breast augmentation, or breast reduction surgery.
• Has a prior history of difficulty establishing lactation.
• Gastrointestinal conditions or procedures (including weight loss surgery; e.g., Lap-Band® or gastric bypass) that may affect drug absorption.
• 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).
• History within the last 2 years of drug, alcohol, amphetamine and derivatives, or cocaine abuse.
• Current smoker.
• 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.
• Blood transfusion for any reason within 90 days prior to enrollment.
• Use of any 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor (statin) concurrently or within 30 days prior to randomization.
• Use of cyclosporine, cholestyramine, probenecid, fibrate drugs, or medications contraindicated during lactation concurrently or within 30 days prior to randomization.
• Concomitant use or use within 30 days prior to randomization of drugs that decrease breast milk production, such as pseudoephedrine.
• Concomitant use or use within 30 days prior to randomization of drugs that increase breast milk production, such as domperidone.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bempedoic acid	Drug: Bempedoic Acid 180 MG Oral Tablet; Bempedoic Acid 180 MG Oral Tablet [Nexletol]; Other Names: Nexletol
Experimental: Bempedoic acid/ezetimibe fixed combination drug product	Drug: Bempedoic Acid/Ezetimibe 180 MG-10 MG Oral Tablet; Bempedoic Acid/Ezetimibe 180 MG-10 MG Oral Tablet [NEXLIZET]; Other Names: Nexlizet 180 mg-10 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily Infant Dose	Daily infant dosage of study drug was calculated for Bempedoic Acid arm and FCDP arm respectively from the cumulative amount of study drug (bempedoic acid or bempedoic acid and ezetimibe) excreted in breast milk over 24 hours.	24 hours post Day 6 dose administration
Relative Infant Dose (RID)	Relevant Infant Dose (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) was analyzed for the Bempedoic Acid arm and FCDP arm respectively. Maternal dosage is the ratio of bempedoic acid dose or ezetimibe dose administered daily divided by maternal body weight at baseline.	24 hours post Day 6 dose administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative Amount of Bempedoic Acid (ETC-1002) and Metabolites (ESP-15228, ETC-1002-Glucuronide) in Breast Milk	Cumulative amount of ETC-1002, ESP-15228, and ETC-1002-glucuronide excreted in breast milk during the 24-hour collection period were analyzed for the Bempedoic Acid arm and FCDP arm respectively.	24 hours post Day 6 dose administration
Cumulative Amount of Ezetimibe (EZE) and Metabolite (EZE-Glucuronide) in Breast Milk	Cumulative amount of Ezetimibe, and EZE-glucuronide excreted in breast milk during 24-hour collection period were analyzed (FCDP arm only).	24 hours post Day 6 dose administration
Maximum Concentrations (Cmax) of Bempedoic Acid and Metabolites in Breast Milk	Cmax of ETC-1002, ESP-15228, and ETC-1002-glucuronide in Breast Milk were analyzed for Bempedoic Acid arm and FCDP arm respectively	24 hours post Day 6 dose administration
Cmax of Ezetimibe and Metabolite in Breast Milk	Cmax of Ezetimibe, and EZE-glucuronide analyzed in FCDP arm only.	24 hours post Day 6 dose administration
Time of Maximum Concentration (Tmax) of Bempedoic Acid and Metabolites in Breast Milk	Tmax of ETC-1002, ESP-15228, and ETC-1002-glucuronide in Breast Milk were analyzed for Bempedoic Acid arm and FCDP arm respectively	24 hours post Day 6 dose administration
Tmax of Ezetimibe and Metabolite in Breast Milk	Tmax of Ezetimibe and EZE-glucuronide in Breast Milk were analyzed for FCDP arm only.	24 hours post Day 6 dose administration
Area Under the Breast Milk Concentration-time Curve Over the 24-hour Collection Interval (AUC24h) of Bempedoic Acid and Metabolites in Breast Milk	AUC24h of ETC-1002, ESP-15228, and ETC-1002-glucuronide in Breast Milk were analyzed for Bempedoic Acid arm and FCDP arm respectively.	24 hours post Day 6 dose administration
AUC24h of Ezetimibe and Metabolite in Breast Milk	AUC24h of Ezetimibe and EZE-glucuronide in Breast Milk were analyzed for FCDP arm only.	24 hours post Day 6 dose administration
Average Concentration (Cavg) of Bempedoic Acid and Metabolites in Breast Milk	Cavg (defined as AUC24h/24h) of ETC-1002, ESP-15228, and ETC-1002-glucuronide in Breast Milk were analyzed for Bempedoic Acid arm and FCDP arm respectively.	24 hours post Day 6 dose administration
Cavg of Ezetimibe and Metabolite in Breast Milk	Cavg of Ezetimibe and EZE-glucuronide in Breast Milk were analyzed for FCDP arm only.	24 hours post Day 6 dose administration
Trough Concentration (Ctrough) of Bempedoic Acid and Metabolites in Breast Milk	Ctrough_milk of ETC-1002, ESP-15228, and ETC-1002-glucuronide were analyzed for Bempedoic Acid arm and FCDP arm respectively.	24 hours post Day 6 dose administration
Ctrough of Ezetimibe and Metabolite in Breast Milk	Ctrough_milk of Ezetimibe and EZE-glucuronide were analyzed for FCDP arm only.	24 hours post Day 6 dose administration
Ctrough of Bempedoic Acid and Metabolites in Plasma	Ctrough_plasma of ETC-1002, ESP-15228, and ETC-1002-glucuronide were analyzed for Bempedoic Acid arm and FCDP arm respectively.	24 hours post Day 6 dose administration
Ctrough of Ezetimibe and Metabolite in Plasma	Ctrough_plasma of Ezetimibe and EZE-glucuronide were analyzed for FCDP arm only.	24 hours post Day 6 dose administration
Ctrough_milk/Ctrough_plasma (M/P Ratio) of Bempedoic Acid and Metabolites	M/P Ratio of ETC-1002, ESP-15228, and ETC-1002-glucuronide were analyzed for Bempedoic Acid arm and FCDP arm respectively.	24 hours post Day 6 dose administration
M/P Ratio of Ezetimibe and Metabolite	M/P Ratio of Ezetimibe and EZE-glucuronide were analyzed for FCDP arm only.	24 hours post Day 6 dose administration

Collaborators and Investigators

• Sponsor: Esperion Therapeutics, Inc.
• Investigators: Study Director: Christine Broestl, MS, Esperion Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2023
• Primary Completion (Actual): February 21, 2024
• Study Completion (Actual): March 22, 2024

Study Registration Dates

• First Submitted: August 27, 2023
• First Submitted That Met QC Criteria: August 27, 2023
• First Posted (Actual): September 1, 2023

Study Record Updates

• Last Update Posted (Actual): April 11, 2025
• Last Update Submitted That Met QC Criteria: March 25, 2025
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Ezetimibe; Breast Milk; Bempedoic acid; Bempedoic acid and ezetimibe
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Ezetimibe; 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
• Other Study ID Numbers: 1002FDC-075

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No