Bempedoic Acid for High Cholesterol in Children

(CLEAR Path 1 Trial)

Recruiting at 27 trial locations

Overseen By Esperion Medical Information

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Esperion Therapeutics, Inc.

Must be taking: Statins

Must not be taking: Gemfibrozil

Disqualifiers: HoFH, Triglycerides, Hypothyroidism, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

54 Participants Needed

Trial Summary

What is the purpose of this trial?

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

Will I have to stop taking my current medications?

Participants must continue taking their current stable lipid-modifying therapy (like statins) at the same dose throughout the trial.

What data supports the effectiveness of the drug Bempedoic acid for high cholesterol in children?

Bempedoic acid has been shown to effectively lower cholesterol levels in adults, particularly in those with familial hypercholesterolemia (a genetic condition causing high cholesterol) and those who cannot tolerate statins. It works by reducing cholesterol production in the liver, and studies have demonstrated its safety and efficacy in lowering LDL cholesterol (the 'bad' cholesterol) in these populations. ^{1 2 3 4 5}

Is bempedoic acid safe for humans?

Bempedoic acid has been shown to be safe in several studies for lowering cholesterol, with a reduced risk of muscle-related side effects compared to some other treatments. It is approved for use in the USA and EU, and studies have not shown an increase in side effects when combined with other cholesterol-lowering drugs. ^{1 2 3 4 6}

How is the drug bempedoic acid different from other treatments for high cholesterol?

Bempedoic acid is unique because it lowers cholesterol by targeting the liver specifically, which reduces the risk of muscle-related side effects that are common with other cholesterol-lowering drugs like statins. ^{1 2 3 4 7}

Research Team

Michael Louie, MD

Principal Investigator

Esperion Therapeutics, Inc.

Jeffrey C Hanselman, MS

Principal Investigator

Esperion Therapeutics, Inc.

Eligibility Criteria

This trial is for children aged 6-17 with HeFH (a genetic cholesterol disorder) who have high LDL cholesterol levels despite taking other lipid-modifying medications. They must not have diabetes, extremely high triglycerides, or be pregnant or breastfeeding.

Inclusion Criteria

Your "bad" cholesterol (LDL-C) level is higher than 130 mg/dL after not eating for a while.

I am between 6 and 17 years old.

I am on a stable treatment for my cholesterol.

Exclusion Criteria

I have diabetes or my blood sugar levels are higher than normal.

Your fasting triglyceride level is 400 mg/dL (4.5 mmol/L) or higher.

I am currently pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bempedoic acid once daily with dose adjustments based on body weight for a total of 16 weeks

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Bempedoic acid

Trial Overview The study tests the effects of bempedoic acid, a medication intended to lower cholesterol levels in pediatric patients with HeFH. It's given once daily and researchers will monitor how it's processed by the body and its impact on cholesterol.

Participant Groups

Group I: Cohort 3 Experimental Treatment 1 Intervention

Participants at greater than 60 kg body weight at screening receiving once daily 180 mg bempedoic acid for 8 weeks.

Group II: Cohort 2 Experimental Treatment 1 Intervention

Participants at 30 to 60 kg body weight at screening receiving once daily120 mg bempedoic acid for 8 weeks followed by 150 mg bempedoic acid for 8 weeks.

Group III: Cohort 1 Experimental Treatment 1 Intervention

Participants at 16 to \<30 kilograms (kg) body weight at screening receiving once daily 60 milligrams (mg) bempedoic acid for 8 weeks followed by 90 mg bempedoic acid for 8 weeks.

Bempedoic acid is already approved in United States, European Union for the following indications:

Approved in United States as Nexletol for:

• Hypercholesterolemia in combination with diet and the highest tolerated statin therapy in adults with heterozygous familial hypercholesterolemia, or with established atherosclerotic cardiovascular disease, who need additional lowering of LDL cholesterol

Approved in European Union as Nilemdo for:

• Primary hypercholesterolaemia (heterozygous familial and non familial) or mixed dyslipidaemia, as an adjunct to diet in combination with a statin or statin with other lipid-lowering therapies in patients unable to reach LDL-C goals with the maximum tolerated dose of a statin; or alone or in combination with other lipid-lowering therapies in patients who are statin intolerant, or for whom a statin is contraindicated

Who Is Running the Clinical Trial?

Esperion Therapeutics, Inc.

Lead Sponsor

Trials

26

Recruited

21,900+

Founded

2008

Headquarters

Ann Arbor, USA

Known For

Cholesterol Therapies

Top Products

NEXLETOL, NEXLIZET, NILEMDO, NUSTENDI

Findings from Research

Bempedoic acid has been approved in the USA and EU for treating high cholesterol, based on positive results from the phase III CLEAR clinical trial program.

It is available both as a standalone treatment (NEXLETOL® in the USA, Nilemdo® in the EU) and in combination with ezetimibe (NEXLIZET® in the USA, Nustendi® in the EU), highlighting its versatility in managing hypercholesterolaemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bempedoic Acid: First Approval. Markham, A.[2022]

Bempedoic acid has been approved as a new treatment for hypercholesterolemia, showing both efficacy and safety in clinical studies, making it a valuable option for managing cholesterol levels.

Unlike statins, bempedoic acid selectively targets the liver, which lowers the risk of muscle-related side effects, providing a safer alternative for patients who may be sensitive to traditional cholesterol-lowering medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[ANMCO Expert opinion: Bempedoic acid place in therapy for hypercholesterolemia management]. Di Fusco, SA., Aquilani, S., Spinelli, A., et al.[2023]

Bempedoic acid significantly lowers various cholesterol levels, including total cholesterol and low-density lipoprotein (LDL) cholesterol, with a large study involving 3,788 participants across 10 randomized controlled trials.

While bempedoic acid has a favorable effect on lipid profiles, it is associated with some risks, such as elevated liver enzymes and uric acid levels, but it may reduce the risk of new or worsening diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bempedoic acid for the treatment of hypercholesterolemia: A systematic review and meta-analysis. Cicero, AFG., Fogacci, F., Hernandez, AV., et al.[2020]

Bempedoic acid effectively lowers LDL-cholesterol levels by selectively inhibiting cholesterol production in the liver, showing complementary effects when used with ezetimibe without increasing side effects.

It is particularly beneficial for patients at higher risk of cardiovascular events, including those with impaired glucose metabolism, the elderly, and individuals with a history of acute coronary syndrome or familial hypercholesterolemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Opportunities and perspectives for bempedoic acid use in clinical practice]. Di Fusco, SA., Scicchitano, P., Colivicchi, F.[2021]

Bempedoic acid is an oral medication that effectively lowers low-density lipoprotein cholesterol (LDL-C) in patients with atherosclerotic cardiovascular disease (ASCVD) and those with heterozygous familial hypercholesterolemia (HeFH), as shown in pooled data from phase III trials involving multiple patients.

It is particularly beneficial for individuals who cannot tolerate statins or require additional LDL-C lowering, and ongoing trials like CLEAR Outcomes will further clarify its role in non-statin lipid-lowering therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bempedoic Acid for Heterozygous Familial Hypercholesterolemia: From Bench to Bedside. Agarwala, A., Quispe, R., Goldberg, AC., et al.[2021]

Bempedoic acid is a promising oral medication that lowers cholesterol without causing muscle-related side effects, making it suitable for patients who cannot tolerate statins due to muscle symptoms.

The CLEAR Outcomes trial, involving 14,014 patients with a history of cardiovascular disease and statin intolerance, aims to assess whether bempedoic acid can reduce serious cardiovascular events over a treatment period of at least 36 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of the CLEAR-outcomes trial: Evaluating the effect of bempedoic acid on cardiovascular events in patients with statin intolerance. Nicholls, S., Lincoff, AM., Bays, HE., et al.[2021]

Bempedoic acid significantly reduces levels of harmful lipids, including LDL cholesterol, non-HDL cholesterol, and apolipoprotein B, based on a meta-analysis of 7 trials involving 3892 patients.

The drug also demonstrates anti-inflammatory effects by significantly lowering high sensitivity C-reactive protein (hsCRP) levels, indicating its potential benefits beyond just lipid lowering.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Bempedoic Acid on atherogenic lipids and inflammation: A meta-analysis. Masson, W., Lobo, M., Lavalle-Cobo, A., et al.[2021]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Bempedoic Acid: First Approval. [2022]

2. Italy pubmed.ncbi.nlm.nih.gov

[ANMCO Expert opinion: Bempedoic acid place in therapy for hypercholesterolemia management]. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of bempedoic acid for the treatment of hypercholesterolemia: A systematic review and meta-analysis. [2020]

4. Italy pubmed.ncbi.nlm.nih.gov

[Opportunities and perspectives for bempedoic acid use in clinical practice]. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Bempedoic Acid for Heterozygous Familial Hypercholesterolemia: From Bench to Bedside. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Rationale and design of the CLEAR-outcomes trial: Evaluating the effect of bempedoic acid on cardiovascular events in patients with statin intolerance. [2021]

7. Spain pubmed.ncbi.nlm.nih.gov

Effect of Bempedoic Acid on atherogenic lipids and inflammation: A meta-analysis. [2021]