A Clinical Study in Children With Heterozygous Familial Hypercholesterolemia (HeFH) Aged 6 to 17 Treated Once Daily With Bempedoic Acid Oral Dosing (CLEAR Path 1)

Esperion Therapeutics, Inc.31 enrolled

Overview

Multiple-dose study to measure pharmacokinetics, pharmacodynamics and safety of bempedoic acid in pediatric participants 6 to 17 years of age with HeFH.

Dose-selection based on body weight will be determined for use in pediatric clinical development.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hypercholesterolemia

Interventions

Bempedoic acidDRUG

Once daily oral dosing with oral tablets.

Eligibility

Sex: ALLMin age: 6 YearsMax age: 17 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Participant's parent(s)/guardian(s) must be willing to provide written informed consent and the participant must provide informed assent before any study-specific procedures are performed; * Participant must be aged 6-17 years old and willing to swallow tablets; * Participant must weigh at least 16 kilograms (kg); * Participant must have a diagnosis of HeFH prior to receiving the first dose of study medication at Treatment Visit T1 per Make Early Diagnosis to Prevent Early Deaths project (MEDPED) criteria by meeting at least one of the following clinical criteria: 1. Documented diagnosis of HeFH determined by positive genetic testing; or 2. Documented LDL-C or TC meeting one or more of the following criteria: i. LDL-C \>200 milligrams per deciliter (mg/dL) (5.2 millimole per liter \[mmol/L\]) or TC \>270 mg/dL (7.0 mmol/L), with no first- second- or third-degree relative with documented FH diagnosis (general population); or ii. LDL-C \>155 mg/dL (4.0 mmol/L) or TC \>220 mg/dL (5.7 mmol/L), and also having a first-degree relative with documented familial hypercholesterolemia (FH) diagnosis; or iii. LDL-C \>165 mg/dL (4.3 mmol/L) or TC \>230 mg/dL (5.9 mmol/L), and also having a second-degree relative with documented FH diagnosis; or iv. LDL-C \>170 mg/dL (4.4 mmol/L) or TC \>240 mg/dL (6.2 mmol/L), and also having a third-degree relative with documented FH diagnosis * Current treatment with approved stable lipid-modifying therapy (LMT), including an optimal dose of statin with or without other LMT(s), at stable dose for at least 4 weeks prior to Treatment Visit T1 (6 weeks for fibrates; however, gemfibrozil is not allowed in participants taking a statin as per coadministration instructions defined in the statin label). Participants must remain on that stable dose throughout the duration of the trial. Optimal dose of statin will be determined by the investigator using their medical judgment and available sources, including the participant's self-reported history of LMT. A participant's optimal dose of statin is defined as meeting one of the following criteria: 1. the highest approved dose of statin prescribed for the age of the participant based on regional practice or local guidelines; or 2. less than the highest approved dose of statin, including no statin, prescribed for the age of the participant based on regional practice or local guidelines (including no statin) if: i. the participant has previously taken 2 or more statin therapies at any dose and not able to tolerate or unresponsive due to their mutations (null); or ii. the participant has previously taken 1 or more statin therapies at any dose and is unwilling to attempt another statin at any dose or advised by a physician to not attempt another statin at any dose. 3. Participant/parent and investigator attestation to the participant's unwillingness to attempt and/or physician advice to not attempt additional statin therapy will be recorded. Exclusion Criteria: * Participant has a diagnosis of homozygous familial hypercholesterolemia (HoFH) or compound HeFH; * Participant has a fasting triglyceride (TG) level ≥400 mg/dL (4.5 mmol/L); * Participant has uncontrolled hypothyroidism, including a value for thyroid-stimulating hormone (TSH) \< lower limit of normal (LLN) or \>1.5 × the upper limit of normal (ULN); * Participant has liver disease or dysfunction, including: 1. positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C virus antibodies (HCV-AB), or 2. serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value ≥2 × ULN and/or serum total bilirubin (TB) value ≥2 × ULN. If the serum TB value is ≥1.2 × ULN, a reflex indirect (unconjugated) bilirubin will be obtained and, if consistent with Gilbert's disease or if the participant has a history of Gilbert's disease, the participant may be enrolled in the study. * Participant has renal dysfunction or glomerulonephritis, including an estimated glomerular filtration rate (eGFR) \<75 milliliters/minute/1.73 square meter (mL/min/1.73 m\^2). Other protocol defined inclusion and exclusion criteria.

Locations (24)

Cedars-Sinai Medical Center

Los Angeles, California, United States

Outcomes

Primary Outcomes

Observed Trough Plasma Concentration of ETC-1002 Following 8 Weeks of Steady State Dosing of Bempedoic Acid

Blood plasma samples were collected and analyzed to determine the plasma trough concentration of ETC-1002 following 8 weeks of steady-state dosing of bempedoic acid. The data presented here is for participants who received tablet formulation only.

Time frame: Week 8 pre-dose

Model-based Steady State Area Under the Concentration-time Curve Over 24 Hours (AUC,24ss) of ETC-1002

Blood plasma samples were collected and analyzed to determine the AUC,24ss of ETC-1002 over 24 hours. The data presented here is for participants who received tablet formulation only.

Time frame: 24 hours

Model-based Steady State Average Plasma Concentration (Cavg,ss) of ETC-1002

Blood plasma samples were collected and analyzed to determine the Cavg,ss of ETC-1002. Cavg was calculated by empirical Bayesian estimated pediatric exposure over 24 hours divided by 24 (AUC24hr.ss / 24). The data presented here is for participants who received tablet formulation only.

Time frame: Week 8, 24 hours post-dose at steady state

Model-based Steady State Maximum Plasma Concentration (Cmax,ss) of ETC-1002

Blood plasma samples were collected and analyzed to determine the Cmax,ss of ETC-1002. The data presented here is for participants who received tablet formulation only.

Time frame: Day 1: 1-hour and 4 hours post-dose; Week 4 pre-dose; Week 8 pre-dose

Secondary Outcomes

Observed Trough Plasma Concentration of ESP15228

Blood plasma samples were collected and analyzed to determine the trough plasma concentration of active metabolite ESP15228 following 8 weeks of steady-state dosing of bempedoic acid. The data presented here is for participants who received tablet formulation only.

Data from ClinicalTrials.gov

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Providere Research Inc

West Covina, California, United States

Excel Medical Clinical Trials, LLC

Boca Raton, Florida, United States

Washington University School of Medicine, Division of Endocrinology, Metabolism and Lipid Research

St Louis, Missouri, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Cardiology Care for Children

Lancaster, Pennsylvania, United States

University of Utah and Primary Children's Hospital

Salt Lake City, Utah, United States

University of Alberta Hospital - Stollery Children's Hospital

Edmonton, Alberta, Canada

McMaster University Medical Center

Hamilton, Ontario, Canada

...and 14 more locations

Time frame: Week 8 pre-dose

Observed Plasma Concentration at 4 Hours (C4hr) of ETC-1002

Blood plasma samples were collected and analyzed to determine the trough plasma concentration of ETC-1002 4 hours post-dose. The data presented here is for participants who received tablet formulation only.

Time frame: Day 1: 4 hours post-dose

Observed C4hr of ESP15228

Blood plasma samples were collected and analyzed to determine the trough plasma concentration of active metabolite ESP15228 4 hours post-dose on Day 1. The data presented here is for participants who received tablet formulation only.

Time frame: Day 1: 4 hours post-dose

Simulated Percent Change From Baseline in Exposure/ Low-Density Lipoprotein-Cholesterol (LDL-C)

Blood samples were collected for the analysis of and exposure/LDL-C-lowering response relationship.

Time frame: Baseline and Week 12

Observed Percent Change From Baseline in LDL-C

Blood samples were collected for analysis of LDL-C levels. Baseline is defined as the last assessment measurements before the first dose of investigational medical product (IMP). Percent change from baseline was calculated as the (\[post-Baseline value minus the Baseline value\] divided by the Baseline value) x 100. The treatment period for participants in cohort 1 (60 mg), cohort 2 (120 mg), and cohort 3 was weeks 1-8. The treatment period for participants in cohort 1 (90 mg) and cohort 2 (150 mg) was weeks 8-16.