Clinical trial NCT06021951: 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
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Healthy Lactating Women
Keywords: Bempedoic acid
Ezetimibe
Bempedoic acid and ezetimibe
Breast Milk
Lead sponsor: Esperion Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-09-01
Enrollment: 16
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

Eligibility criteria: 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.

Primary outcomes:
measure: Daily Infant Dose
timeFrame: 24 hours post Day 6 dose administration
measure: Relative Infant Dose (RID)
timeFrame: 24 hours post Day 6 dose administration
Secondary outcomes:
measure: Cumulative Amount of Bempedoic Acid (ETC-1002) and Metabolites (ESP-15228, ETC-1002-Glucuronide) in Breast Milk
timeFrame: 24 hours post Day 6 dose administration
measure: Cumulative Amount of Ezetimibe (EZE) and Metabolite (EZE-Glucuronide) in Breast Milk
timeFrame: 24 hours post Day 6 dose administration
measure: Maximum Concentrations (Cmax) of Bempedoic Acid and Metabolites in Breast Milk
timeFrame: 24 hours post Day 6 dose administration
measure: Cmax of Ezetimibe and Metabolite in Breast Milk
timeFrame: 24 hours post Day 6 dose administration
measure: Time of Maximum Concentration (Tmax) of Bempedoic Acid and Metabolites in Breast Milk
timeFrame: 24 hours post Day 6 dose administration
measure: Tmax of Ezetimibe and Metabolite in Breast Milk
timeFrame: 24 hours post Day 6 dose administration
measure: Area Under the Breast Milk Concentration-time Curve Over the 24-hour Collection Interval (AUC24h) of Bempedoic Acid and Metabolites in Breast Milk
timeFrame: 24 hours post Day 6 dose administration
measure: AUC24h of Ezetimibe and Metabolite in Breast Milk
timeFrame: 24 hours post Day 6 dose administration
measure: Average Concentration (Cavg) of Bempedoic Acid and Metabolites in Breast Milk
timeFrame: 24 hours post Day 6 dose administration
measure: Cavg of Ezetimibe and Metabolite in Breast Milk
timeFrame: 24 hours post Day 6 dose administration
measure: Trough Concentration (Ctrough) of Bempedoic Acid and Metabolites in Breast Milk
timeFrame: 24 hours post Day 6 dose administration
measure: Ctrough of Ezetimibe and Metabolite in Breast Milk
timeFrame: 24 hours post Day 6 dose administration
measure: Ctrough of Bempedoic Acid and Metabolites in Plasma
timeFrame: 24 hours post Day 6 dose administration
measure: Ctrough of Ezetimibe and Metabolite in Plasma
timeFrame: 24 hours post Day 6 dose administration
measure: Ctrough_milk/Ctrough_plasma (M/P Ratio) of Bempedoic Acid and Metabolites
timeFrame: 24 hours post Day 6 dose administration
measure: M/P Ratio of Ezetimibe and Metabolite
timeFrame: 24 hours post Day 6 dose administration
Other outcomes:
Locations:
city: Las Vegas
country: United States
facility: PPD Development, Las Vegas Research Unit
state: Nevada
Study officials:
affiliation: Esperion Therapeutics, Inc.
name: Christine Broestl, MS
role: STUDY_DIRECTOR
References: