A Dose-finding Trial of ETC-1002(Bempedoic Acid) in Patients With Hypercholesterolemia

A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial to Evaluate the Efficacy and Safety of ETC-1002 in Patients With Hypercholesterolemia

The purpose of this study is to assess the low-density lipoprotein cholesterol (LDL-C)-lowering efficacy and safety of ETC-1002(bempedoic acid) 60 mg, 120 mg and 180 mg versus placebo added to ongoing stable statin therapy or other lipid-modifying therapies in Japanese patients with hypercholesterolemia treated for 12 weeks.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: 180mg of ETC-1002(bempedoic acid); Drug: Placebo; Drug: 120mg of ETC-1002(bempedoic acid); Drug: 60mg of ETC-1002(bempedoic acid)

• Study Type: Interventional
• Enrollment (Actual): 188
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Chuo-ku,Tokyo, Japan
    • Tokyo-Eki Center-building Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients who have obtained informed consent to all of the observation/examination/evaluation items specified in the protocol
• Patients must be on stable statin therapy defined as atorvastatin, pitavastatin, rosuvastatin, pravastatin, simvastatin, or fluvastatin daily[and other lipid-modifying therapies(LMTs) if needed] at least 4 weeks(6 weeks for fibrates) prior to screening and above LDL-C control target. Or Patients for statin intolerant must be on stable LMT(s) at least 4 weeks prior to screening and above LDL-C control target. Statin intolerance defined as an inability to tolerate 1 or more statins due to an adverse safety effect that started or increased during statin therapy and resolved or improved when statin therapy was discontinued or decreased. Patients on the lowest or under the dosage of the approved dose of statin or unable to tolerate any statin at any dose were eligible. Patients could continue taking the lowest or under the dosage of the approved dose of statin therapy or taking other LMTs throughout the study provided that it was stable and well tolerated.
• Fasting mean TG level < 400 mg/dL from measurements at screening
• Other protocol specific inclusion criteria may apply

Exclusion Criteria:

• Women who are pregnant or breastfeeding or who have a positive pregnancy test (urine) result at screening or baseline visits
• Sexually active male subjects or sexually active female subjects of childbearing potential who do not agree to practice 2 different methods of birth control or to remain abstinent during the trial and for 30 days after final IMP administration test (urine) result at screening or baseline visits
• Patients with homozygous familial hypercholesterolemia (HoFH)

• Patients with a history or current symptoms of any of the following clinically significant cardiovascular diseases within 3 months prior to screening or before baseline visit

  • Myocardial infarction, severe or unstable angina pectoris, coronary angioplasty, coronary artery bypass graft, stroke, transient ischemic attack, symptomatic carotid artery stenosis, symptomatic peripheral arterial disease, or decompensated heart failure
  • Abdominal aortic aneurysm
  • Unexplained syncope or long-QT syndrome, family history of long-QT syndrome, or risk factors for Torsade de Pointes, such as persistent hypokalemia or second- or third-degree atrioventricular block (except when controlled by medication, etc)

• Uncontrolled hypertension, defined as follows:

  • Sitting systolic blood pressure after resting 5 minutes of ≥160 mmHg or diastolic blood pressure of ≥100 mmHg at screening
• Patients with uncontrolled and serious hematologic or coagulation disorders or with Hgb of <10.0 g/dL at screening
• Patients with type 1 diabetes or uncontrolled type 2 diabetes with hemoglobin A1c (HbA1c) of ≥9% at screening
• Patients with uncontrolled hypothyroidism with thyroid-stimulating hormone (TSH) of >1.5 × ULN at screening

• Patients with liver disease or dysfunction, including:

  • Positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies at screening
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) of ≥3 × ULN and/or total bilirubin of ≥2 × ULN
• Patients with creatine kinase (CK) elevation( >3 × ULN) at screening
• Patients with renal dysfunction or nephritic syndrome or a history of nephritis and with estimated glomerular filtration rate (eGFR) of ≤30 mL/min/1.73m2 at screening
• Other protocol specific inclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; placebo, tablet, once daily, for 12 weeks
Experimental: ETC-1002 180mg	Drug: 180mg of ETC-1002(bempedoic acid); 180mg, tablet, once daily, for 12 weeks
Experimental: ETC-1002 120mg	Drug: 120mg of ETC-1002(bempedoic acid); 120mg, tablet, once daily, for 12 weeks
Experimental: ETC-1002 60mg	Drug: 60mg of ETC-1002(bempedoic acid); 60mg, tablet, once daily, for 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in LDL-C From Baseline to Week 12	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100. Baseline was defined as the mean of the values from Week -1 and Day 1. When LDL-C at Week 12 was missing, the missing value was imputed using the last observation carried forward from the start of the IMP administration to 2 days after the final IMP administration.	Baseline, week12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in HDL Cholesterol From Baseline to Week 12	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100.	Baseline, week12
Percent Change in Non-HDL Cholesterol From Baseline to Week 12	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100.	Baseline, week12
Percent Change in Total Cholesterol From Baseline to Week 12	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100.	Baseline, week12
Percent Change in Triglycerides From Baseline to Week 12	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100.	Baseline, week12
Percent Change in Apolipoprotein B From Baseline to Week 12	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100.	Baseline, week12
Percent Change in High Sensitivity C Reactive Protein From Baseline to Week 12	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100.	Baseline, week12
Percent Change in Hemoglobin A1c From Baseline to Week 12	Percent change from Baseline was calculated as the ([post-Baseline value minus the Baseline value] divided by the Baseline value) x 100.	Baseline, week12
Proportion of Subjects Whose LDL-C Value Achieved the Lipid Management Goals Based on Risk Assessment at Week 12	The proportion of subjects whose LDL-C value achieves the lipid management goal at Week 12.	Baseline, week12
Proportion of Subjects Whose LDL-C Value Achieve < 70 mg/dL at Week 12	The proportion of subjects whose LDL-C value achieves <70 mg/dL at Week 12.	Baseline, week12

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Co., Ltd.
• Investigators: Study Director: Takehisa Matsumaru, Otsuka Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2021
• Primary Completion (Actual): April 18, 2022
• Study Completion (Actual): May 17, 2022

Study Registration Dates

• First Submitted: March 2, 2021
• First Submitted That Met QC Criteria: March 2, 2021
• First Posted (Actual): March 5, 2021

Study Record Updates

• Last Update Posted (Actual): March 4, 2024
• Last Update Submitted That Met QC Criteria: July 26, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Hypolipidemic Agents; Lipid Regulating Agents; 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
• Other Study ID Numbers: 346-102-00001; jRCT2031200445 (Other Identifier: jRCT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: : Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal.
• IPD Sharing Time Frame: Data will be available after marketing approval in global markets, or beginning 1-3 years following article Publication. There is no end date to the availability of the data.
• IPD Sharing Access Criteria: Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No