Clinical trial NCT04784442: A Dose-finding Trial of ETC-1002(Bempedoic Acid) in Patients With Hypercholesterolemia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypercholesterolemia
Lead sponsor: Otsuka Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-03-05
Enrollment: 188
Sex: ALL
Minimum age (years): 20
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percent Change in LDL-C From Baseline to Week 12
timeFrame: Baseline, week12
Secondary outcomes:
measure: Percent Change in HDL Cholesterol From Baseline to Week 12
timeFrame: Baseline, week12
measure: Percent Change in Non-HDL Cholesterol From Baseline to Week 12
timeFrame: Baseline, week12
measure: Percent Change in Total Cholesterol From Baseline to Week 12
timeFrame: Baseline, week12
measure: Percent Change in Triglycerides From Baseline to Week 12
timeFrame: Baseline, week12
measure: Percent Change in Apolipoprotein B From Baseline to Week 12
timeFrame: Baseline, week12
measure: Percent Change in High Sensitivity C Reactive Protein From Baseline to Week 12
timeFrame: Baseline, week12
measure: Percent Change in Hemoglobin A1c From Baseline to Week 12
timeFrame: Baseline, week12
measure: Proportion of Subjects Whose LDL-C Value Achieved the Lipid Management Goals Based on Risk Assessment at Week 12
timeFrame: Baseline, week12
measure: Proportion of Subjects Whose LDL-C Value Achieve < 70 mg/dL at Week 12
timeFrame: Baseline, week12
Other outcomes:
Locations:
city: Chuo-ku,Tokyo
country: Japan
facility: Tokyo-Eki Center-Building Clinic
Study officials:
affiliation: Otsuka Pharmaceutical Co., Ltd.
name: Takehisa Matsumaru
role: STUDY_DIRECTOR
References: