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

Hypercholesterolemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04784442
• Other study ID #: 346-102-00001
• Secondary ID: jRCT2031200445
• Status: Completed
• Phase: Phase 2
• Start date: March 24, 2021
• Est. completion date: May 17, 2022

Study information

• Verified date: May 2024
• Source: Otsuka Pharmaceutical Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 188
• Est. completion date: May 17, 2022
• Est. primary completion date: April 18, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 74 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• 180mg of ETC-1002(bempedoic acid)
180mg, tablet, once daily, for 12 weeks
• 120mg of ETC-1002(bempedoic acid)
120mg, tablet, once daily, for 12 weeks
• 60mg of ETC-1002(bempedoic acid)
60mg, tablet, once daily, for 12 weeks
• Placebo
placebo, tablet, once daily, for 12 weeks

Locations

Country	Name	City	State
Japan	Tokyo-Eki Center-Building Clinic	Chuo-ku,Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Otsuka Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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