This study is to assess the efficacy of bempedoic acid 180 mg/day versus placebo in decreasing low-density lipoprotein cholesterol (LDL-C) when added to ezetimibe therapy in patients with high LDL-Cholesterol. MedDRA version: 19.1 Level: LLT Classification code 10007648 Term: Cardiovascular disease, unspecified System Organ Class: 10007541 - Cardiac disorders MedDRA version: 19.1 Level: PT Classification code 10007649 Term: Cardiovascular disorder System Organ Class: 10007541 - Cardiac disorde
Conditions
Interventions
Product Name: Bempedoic Acid
Product Code: ETC-1002
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: BEMPEDOIC ACID
CAS Number: 738606-46-7
Current Sponsor code: ETC-1002
Concentration un
Sponsors
Esperion Therapeutics Inc.,
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Each potential patient must satisfy all inclusion criteria to be enrolled in the study. Selected inclusion criteria are listed below; all inclusion criteria are listed in the protocol body. 1. Provision of written informed consent prior to any study-specific procedure 2. Age =18 years or legal age of majority based on regional law, whichever is greater, at Week -5 (Visit S1) 3. Fasting LDL-C (minimum of 10 hours) at Week -5 (Visit S1) =100 mg/dL (2.6 mmol/L) on stable background LMT (greater than or equal to 4 weeks prior to screening) requiring further LDL-C lowering. Note: LDL-C may be repeated 1 time with the screening period extended up to 4 weeks. For those patients who have a repeat LDL-C, the mean of the first value and the repeat value will be used to determine eligibility. 4. Currently receiving stable (greater than or equal to 4 weeks prior to screening) background maximally tolerated LMT that includes ezetimibe 10 mg daily and maximally tolerated statin dose that does not exceed low dose statin therapy. Note: Patients must report attempting greater than low dose statin therapy and being unable to tolerate it due to an adverse safety effect that started or increased during statin therapy and resolved or improved when statin therapy was discontinued or the dose lowered. Low dose statin therapy is defined as an average daily dose of rosuvastatin 5 mg, atorvastatin 10 mg, simvastatin 10 mg, lovastatin 20 mg, pravastatin 40 mg, fluvastatin 40 mg, or pitavastatin 2 mg. Very low dose statin therapy is defined as an average daily dose of rosuvastatin =65 years) yes F.1.3.1 Number of subjects for this age range 55
Exclusion criteria
Exclusion criteria: Patients who meet any of the exclusion criteria are not eligible. Selected exclusion criteria are listed below; all exclusion criteria are listed in the protocol body. 1. Body mass index (BMI) >50 kg/m2 2. Recent history of documented clinically significant cardiovascular disease including, but not limited to • Within 3 months of screening, MI, severe or unstable angina pectoris, coronary angioplasty, coronary artery bypass graft, stroke, transient ischemic attack, cerebrovascular event, symptomatic carotid artery disease, or symptomatic peripheral arterial disease • Uncontrolled hypertension, defined as sitting systolic blood pressure (SBP) =160 mm Hg and diastolic blood pressure (DBP) =100 mm Hg after sitting quietly for 5 minutes. • Within 3 months of screening, an arrhythmia requiring medical intervention • Planned revascularization procedures • New York Heart Association (NYHA) Class IV heart failure 3. Total fasting (minimum of 10 hours) TG =500 mg/dL (5.6 mmol/L) at Week -5 (S1) 4. Hemoglobin A1C (HbA1C) =10% at Week -5 (Visit S1) 5. Persistent poor adherence with ezetimibe and/or single-blind, placebo study drug (ie, ingesting 1.5 × the upper limit of normal (ULN) at Week -5 (Visit S1). Patients stabilized on thyroid replacement therapy for at least 6 weeks prior to randomization are allowed 7. Liver disease or dysfunction, including: • Positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies (HCV-ABVivi) at Week -4 (Visit S2), or • Alanine aminotransferase (ALT), aspartate aminotransferase (AST) =2 × ULN, and/or total bilirubin (TB) =2 × ULN at Week -2 (Visit S1). If TB =1.2 × ULN, a reflex indirect (unconjugated) bilirubin will be obtained, and if consistent with Gilbert’s disease or if the patient has a history of Gilbert’s Disease, the patient may be enrolled in the study. 8. Renal dysfunction or glomerulonephritis, including estimated glomerular filtration rate (eGFR; using central laboratory determined Modification of Diet in Renal Disease [MDRD] formula) 3 × ULN at any time prior to randomization (ie, not associated with recent trauma or physically strenuous activity). Patients with an explained CK elevation must have single repeat CK =3 × ULN prior to randomization; 13. History of drug or alcohol abuse within the last 2 years or reported current consumption of >14 alcoholic drinks/week, or any illicit drug use, history of amphetamine and derivatives abuse or cocaine abuse. Subjects with amphetamine derivatives prescribed by and under the care of a health care practitioner can be enrolled after evaluation by the investigator; 14. Blood donation, participation in a multiple blood draws, clinical study, major trauma, blood transfusion or surgery with or without blood loss within 30 days prior to randomization; 15. Use of any experimental or investigational drugs within 30 days prior to screening; 16. Previous enrol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the 12-week efficacy of bempedoic acid 180 mg/day versus placebo in decreasing LDL-C when added to ezetimibe therapy in patients with elevated LDL-C. ;Secondary Objective: The secondary objectives of this study are: • To evaluate the effect of 12-week treatment with bempedoic acid 180 mg/day versus placebo when added to ezetimibe therapy on - non-high-density lipoprotein cholesterol (non-HDL-C), - total cholesterol (TC), - apolipoprotein B (apoB), and - high-sensitivity C-reactive protein (hs-CRP) • To evaluate the effect of 12-week treatment with bempedoic acid 180 mg/day versus placebo on TG and HDL-C • To evaluate 12-week safety and tolerability of bempedoic acid 180 mg/day compared with placebo. The tertiary objectives of this study are: • To evaluate the effects of 4- and 8-week treatment with bempedoic acid 180 mg/day versus placebo when added to ezetimibe therapy on - LDL-C - Non-HDL-C - TC - TG - HDL-C;Primary end point(s): Percent change from baseline to Week 12 in LDL-C. ;Timepoint(s) of evaluation of this end point: Week 12. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints (specific to stepdown approach): 1. Percent change from baseline to Week 12 in: a. non-HDL-C b. TC c. apoB d. hs-CRP Other secondary efficacy endpoints: 2. Percent change from baseline to Week 12 in: a. TG b. HDL-C Tertiary efficacy endpoints: 1. Assessments of percent change from baseline in lipid levels at the additional time points of Week 4 (T2) and Week 8 (T3) in: a. LDL-C b. Non-HDL-C c. TC d. TG e. HDL-C 2. Assessments of absolute change from baseline to Weeks 4, 8, and 12 in: a. LDL-C b. Non-HDL-C c. TC d. TG e. HDL-C;Timepoint(s) of evaluation of this end point: The descriptive summaries of AE data, endpoints used to evaluate hepatic, musculoskeletal, diabetes/hyperglycemic, renal, neurocognitive safety, and defined clinical endpoints are described in Section 12.7 of the protocol. | — |
Countries
Canada, Czech Republic, Germany, Hungary, United Kingdom, United States
Contacts
Public ContactDirector of Clinical Operations
Esperion Therapeutics
Outcome results
None listed