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

Phase 2

Completed

Conditions: Hypercholesterolemia

Interventions: Drug: 180mg of ETC-1002(bempedoic acid)
Drug: 120mg of ETC-1002(bempedoic acid)
Drug: 60mg of ETC-1002(bempedoic acid)
Drug: Placebo

Registration Number: NCT04784442

Lead Sponsor: Otsuka Pharmaceutical Co., Ltd.

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 188

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ETC-1002 180mg	180mg of ETC-1002(bempedoic acid)	-
ETC-1002 120mg	120mg of ETC-1002(bempedoic acid)	-
ETC-1002 60mg	60mg of ETC-1002(bempedoic acid)	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Percent Change in LDL-C From Baseline to Week 12	Baseline, week12	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.

Secondary Outcome Measures

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