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

Study Overview
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Brief Summary
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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
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Post marketing approval commitment for the FDA

Official Title
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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)

Conditions
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Healthy Lactating Women

Intervention / Treatment
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* Drug: Bempedoic Acid 180 MG Oral Tablet
* Drug: Bempedoic Acid/Ezetimibe 180 MG-10 MG Oral Tablet


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily infant dose (mg/d) |  | Day 6 | 
| Relative infant dose (%) |  | Day 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount excreted in each breast milk collection, calculated as the product of concentration and milk volume collected |  | Day 6 | 
| Area under the milk concentration-time curve (AUC) over a 24-hour collection interval |  | Day 6 | 
| Average milk concentration based on milk AUC |  | Day 6 | 
| Peak and trough milk concentrations and the time of peak milk concentrations |  | Day 6 | 
| Plasma trough concentrations |  | Day 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bempedoic acid, Ezetimibe, Bempedoic acid and ezetimibe, Breast Milk