Trial Outcomes & Findings for 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) (NCT NCT05694260)

This was a multi-dose study to measure the pharmacokinetics (PK), pharmacodynamics (PD), and safety of bempedoic acid in pediatric participants aged 6 to 17 years with heterozygous familial hypercholesterolemia (HeFH).

A total of 31 participants were enrolled in the study.

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)

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.