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)

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06021951

Enrollment

Registered

2023-09-01

Start date

2023-08-04

Completion date

2024-03-22

Last updated

2025-04-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy Lactating Women

Keywords

Bempedoic acid, Ezetimibe, Bempedoic acid and ezetimibe, Breast Milk

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

Interventions

DRUGBempedoic Acid 180 MG Oral Tablet

Bempedoic Acid 180 MG Oral Tablet \[Nexletol\]

DRUGBempedoic Acid/Ezetimibe 180 MG-10 MG Oral Tablet

Bempedoic Acid/Ezetimibe 180 MG-10 MG Oral Tablet \[NEXLIZET\]

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to 45 Years

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
Daily Infant Dose	24 hours post Day 6 dose administration	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.
Relative Infant Dose (RID)	24 hours post Day 6 dose administration	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.

Secondary

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

Countries

United States

Participant flow

Recruitment details

This was a Phase 4, open-label study that estimated the daily infant dosage and relative infant dose (RID) for bempedoic acid and bempedoic acid/ezetimibe fixed combination drug product (FCDP) and characterized the excretion of bempedoic acid (ETC-1002), ezetimibe, and metabolites ESP-15228, ETC-1002-glucuronide, and ezetimibe-glucuronide in the mature breast milk of healthy women.

Pre-assignment details

A total of 16 subjects were enrolled into the study and randomized in a 1:1 ratio to receive bempedoic acid 180 milligrams (mg) or bempedoic acid 180 mg/ezetimibe 10 mg FCDP

Participants by arm

Arm	Count
Bempedoic Acid Participants received bempedoic acid 180 mg oral tablet for 6 days	8
Bempedoic Acid/Ezetimibe FCDP Participants received bempedoic acid 180 mg/ezetimibe 10 mg FCDP oral tablets for 6 days	8
Total	16

Baseline characteristics

Characteristic	Bempedoic Acid/Ezetimibe FCDP	Total	Bempedoic Acid
Age, Continuous	27.1 Years STANDARD_DEVIATION 4.09	30.3 Years STANDARD_DEVIATION 5.17	33.5 Years STANDARD_DEVIATION 4.17
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants	3 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants	13 Participants	8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	1 Participants	4 Participants	3 Participants
Race (NIH/OMB) Black or African American	3 Participants	4 Participants	1 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	3 Participants	7 Participants	4 Participants
Sex: Female, Male Female	8 Participants	16 Participants	8 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 8	0 / 8
other Total, other adverse events	4 / 8	3 / 8
serious Total, serious adverse events	0 / 8	0 / 8

Outcome results

Primary

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.