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Completed

NCT Number: NCT05694260

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)

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

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Key information

Conditions

Hypercholesterolemia Dyslipidemias Hyperlipidemias Lipid Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

6 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Alberta Hospital - Stollery Children's Hospital, Edmonton, Alberta, Canada

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About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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:
  • Documented diagnosis of HeFH determined by positive genetic testing; or
  • 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:
  • the highest approved dose of statin prescribed for the age of the participant based on regional practice or local guidelines; or
  • 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.
  • 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:
  • positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C virus antibodies (HCV-AB), or
  • 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.

Treatment and study plan

Bempedoic acid

Drug

Once daily oral dosing with oral tablets.

Other names: ETC-1002

Primary outcomes

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

    Time frame: Week 8 pre-dose

    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.

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

    Time frame: 24 hours

    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.

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

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

    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.

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

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

    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.

Secondary outcomes

  1. Observed Trough Plasma Concentration of ESP15228

    Time frame: Week 8 pre-dose

    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.

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

    Time frame: Day 1: 4 hours post-dose

    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.

  3. Observed C4hr of ESP15228

    Time frame: Day 1: 4 hours post-dose

    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.

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

    Time frame: Baseline and Week 12

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

  5. Observed Percent Change From Baseline in LDL-C

    Time frame: Baseline and 8 Weeks post-treatment

    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.

  6. Observed Absolute Change From Baseline in LDL-C (mg/dl)

    Time frame: Baseline and 8 Weeks post-treatment

    Blood samples were collected for analysis of LDL-C levels. Baseline is defined as the last assessment measurements before the first dose of IMP. Change from baseline is defined as post- dose visit value minus baseline value. 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.

  7. Observed Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)

    Time frame: Baseline and 8 Weeks post-treatment

    Blood samples were collected for analysis of Non-HDL-C levels. Baseline is defined as the last assessment measurements before the first dose of 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.

  8. Observed Absolute Change From Baseline in Non-HDL-C (mg/dL)

    Time frame: Baseline and 8 Weeks post-treatment

    Blood samples were collected for analysis of Non-HDL-C levels. Baseline is defined as the last assessment measurements before the first dose of IMP. Change from Baseline is defined as post- dose visit value minus Baseline value. 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.

  9. Observed Percent Change From Baseline in Total Cholesterol (TC)

    Time frame: Baseline and 8 Weeks post-treatment

    Blood samples were collected for analysis of total cholesterol levels. Baseline is defined as the last assessment measurements before the first dose of 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.

  10. Observed Absolute Change From Baseline in TC (mg/dL)

    Time frame: Baseline and 8 Weeks post-treatment

    Blood samples were collected for analysis of TC levels. Baseline is defined as the last assessment measurements before the first dose of IMP. Change from Baseline is defined as post- dose visit value minus Baseline value. 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.

  11. Observed Percent Change From Baseline in High-sensitivity C-reactive Protein (hsCRP)

    Time frame: Baseline and 8 Weeks post-treatment

    Blood samples were collected for analysis of hsCRP. Baseline is defined as the last assessment measurements before the first dose of 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.

  12. Observed Absolute Change From Baseline in hsCRP (mg/L)

    Time frame: Baseline and 8 Weeks post-treatment

    Blood samples were collected for analysis of hsCRP levels. Baseline is defined as the last assessment measurements before the first dose of IMP. Change from Baseline is defined as post- dose visit value minus Baseline value. 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.

  13. Acceptability of Taste of Liquid Formulation Using a Dosing Acceptability Questionnaire

    Time frame: Days 1 and 2; Weeks 2, 4, 8, 8 (Phone), 10, 12, and 16

    Participant acceptance is defined as the overall ability of the participant to use a medicine as intended. The acceptability of overall flavor of IMP was recorded using a dosing acceptability questionnaire, where participants were asked 'Yes' or 'No', whether the flavor of the medication was acceptable. At Week 8 (Phone) participants in cohorts 1 and 2 were contacted by phone to collect questionnaire information. The number of participants who have responded at each time point have been presented.

  14. Acceptability of Ease of Swallowing Tablet Formulation Using a Dosing Acceptability Questionnaire

    Time frame: Days 1 and 2; Weeks 2, 4, 8, 8 (Phone), 10, 12, and 16

    Participant acceptance is defined as the overall ability of the participant to use a medicine as intended. Acceptability of ease of swallowing was recorded using a dosing acceptability questionnaire where participants were asked if they were able to swallow the entire dose or not, by ticking 'yes' or 'no'. At Week 8 (Phone) participants in cohorts 1 and 2 were contacted by phone to collect questionnaire information. The number of participants who responded at each time point have been presented.

  15. Number of Participants Reporting Serious Adverse Events (SAEs) and Non-SAEs

    Time frame: Up to Week 16

    An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. A serious AE is an AE occurring during any study phase (i.e., baseline, treatment, washout, or follow-up), and at any dose of the study medication that fulfills one or more of the following: results in death, is immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, results in a congenital abnormality or birth defect, is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above.

Sponsors and collaborators

Lead sponsor

Esperion Therapeutics, Inc.

Industry

Registry information

Official study title

An Open-Label Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Bempedoic Acid in Pediatric Patients (6 to 17 Years of Age) With Heterozygous Familial Hypercholesterolemia

Acronym: CLEAR Path 1

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Jan 23, 2023
Registry last updated
Jul 17, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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