A long-term ( 52 week) study to assess the safety and tolerability of investigational drug ETC-1002 when compared with Placebo, in patients with hyperlipidemia (high LDL cholesterol ), who are at high risk of heart problems and who are also receiving the highest dose of lipid modifying treatment that they can tolerate. Patients will be randomly allocated to either placebo or investigational drug; assignment will be unknown to patients and their doctor.
- Conditions
- Treatment of high cardiovascular risk patients (heterozygous familial hypercholesterolemia [HeFH] and atherosclerotic cardiovascular diseases [ASCVD]) with hyperlipidemiaMedDRA version: 20.1Level: LLTClassification code 10020604Term: HypercholesterolemiaSystem Organ Class: 100000004861MedDRA version: 20.1Level: LLTClassification code 10020667Term: HyperlipidemiaSystem Organ Class: 100000004861MedDRA version: 20.0Level: LLTClassification code 10051615Term: Atherosclerotic cardiovascular diseaseSystem Organ Class: 100000004866MedDRA version: 20.0Level: LLTClassification code 10057079Term: Heterozygous familial hypercholesterolemiaSystem Organ Class: 100000004850Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2015-004136-36-GB
- Lead Sponsor
- Esperion Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 2233
Each patient with hyperlipidemia must meet the following criteria to be randomized in this study:
1. Age =18 years or legal age of majority based on regional law, whichever is greater at Week -2 (Visit S1)
2. Men and nonpregnant, nonlactating women. Women must be either:
• Naturally postmenopausal (as reported by the patient, defined as greater than 55 years and =1 year without menses, less than 55 years and =1 year without menses with follicle-stimulating hormone (FSH) =40.0 IU/L), or surgically sterile including hysterectomy, bilateral oophorectomy, or tubal ligation or;
• Women of childbearing potential must be willing to use 1 acceptable method of birth control. The minimal requirement for adequate contraception it is that it should be started on Day 1, continuing during the study period, and for at least 30 days after the last dose of study drug. Acceptable methods of birth control include: oral birth control medications; placement of an intrauterine device (IUD) with or without hormones; barrier methods including condom or occlusive cap with spermicidal foam or spermicidal jelly; vasectomized male partner who is the sole partner for this patient; or true abstinence (not including periodic abstinence such as calendar, ovulation, symptothermal, postovulation methods, or withdrawal).
• There are no protocol-specific birth control requirements for men with partners who are able to become pregnant.
3. Fasting LDL-C value at Week -2 (Visit S1) =70 mg/dL (1.8 mmol/L).
Note: LDL-C may be repeated 1 time with the screening period extended up to 2 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. Have high cardiovascular risk that is defined as either:
• Diagnosis of HeFH. Diagnosis must be made by either genotyping or by clinical assessment using either the World Health Organization (WHO) criteria/Dutch Lipid Clinical Network Criteria with a score that is >8 points or the Simon Broome Register Diagnostic Criteria with an assessment of ‘Definite HeFH’. Patients with a diagnosis of HeFH may or may not have established CHD or CHD risk equivalents.
OR
• Have ASCVD (with established CHD or CHD risk equivalents)
Documented history of CHD (includes 1 or more of the following):
- Acute myocardial infarction (MI)
- Silent MI
- Unstable angina
- Coronary revascularization procedure (eg, percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG] surgery)
- Clinically significant CHD diagnosed by invasive or non-invasive testing (such as coronary angiography, stress test using treadmill, stress echocardiography or nuclear imaging)
Documented CHD risk equivalents (includes 1 or more of the following criteria):
- Peripheral arterial disease
- Previous ischemic stroke with a focal ischemic neurological deficit that persisted more than 24 hours, considered as being of atherothrombotic origin. Computed tomography (CT) or magnetic resonance imaging (MRI) must have been performed to rule out hemorrhage and non-ischemic neurological disease
Note: Patients with type 2 diabetes mellitus (T2DM) are allowed in this study; however for this study T2DM is not considered a CHD risk equivalent
5. Be on maximally tolerated lipid-modifying therapy, including a maximally tolerated statin either alone or in combination with other lipid-lowering therapies, at stable doses for at least 4 weeks prior to screening (6 weeks for fibrates; however, gemfibrozil i
1. Total fasting triglyceride =500 mg/dL (5.6 mmol/L) at Wk -2 (Visit S1)
2. Renal dysfunction or nephritic syndrome or a history of nephritis, including eGFR (using central laboratory determined MDRD formula) <30 mL/min/1.73 m2 at Wk -2 (Visit S1).
Note: Also excluded are renally impaired patients receiving an average daily dose of simvastatin 40 mg with eGFR below <45 mL/min/1.73 m2.
3. BMI =50 kg/m2
4. Concomitant use of simvastatin at average daily doses greater than 40 mg.
5. Concomitant use of a PCSK inhibitor (alirocumab or evolocumab) at Wk -2 (Visit S1) or prior use of a PCSK9 inhibitor within the past 4 weeks of Wk -2 (Visit S1) will be excluded from this study.
6. Recent (within 3 months prior to the screening visit [Wk -2 (Visit S1)] or between screening and randomization visits) MI, unstable angina leading to hospitalization, uncontrolled, symptomatic cardiac arrhythmia (or medication for an arrhythmia that was started or dose changed within 3 months of screening), CABG, PCI, carotid surgery or stenting, cerebrovascular accident, TIA, endovascular procedure or surgical intervention for peripheral vascular disease or plans to undergo a major surgical or interventional procedure (eg, PCI, CABG, carotid or peripheral revascularization). Patients with implantable pacemakers or automatic implantable cardioverter defibrillators may be considered if deemed by the Investigator to be stable for the previous 3 months.
7. Uncontrolled hypertension, defined as sitting SBP =160 mmHg and DBP =100 mmHg after sitting quietly for 5 minutes.
8. HbA1C =10% at Wk -2 (Visit S1)
9. Uncontrolled hypothyroidism, including TSH >1.5 × ULN at Wk -2 (Visit S1). Patients stabilized on thyroid replacement therapy for at least 6 wks prior to randomization are allowed.
10. Liver disease or dysfunction, including:
• Positive serology for HBsAg and/or HCV AB at Wk -2 (Visit S1); or
• ALT, AST =2 × ULN, and/or total bilirubin =1.2 × ULN at Wk -2 (Visit S1).
Note: If HCV AB is positive, a reflex HCV RNA will be performed to rule out active disease. Patients without active disease may be enrolled the study.
If TB =1.2 × ULN, a reflex indirect (unconjugated) bilirubin will be obtained and if consistent with Gilbert’s disease, the patient may be enrolled in the study.
11. GI conditions or procedures (including weight loss surgery; eg, Lap-Band® or gastric bypass) that may affect drug absorption
12. Hematologic or coagulation disorders or a Hgb level <10.0 g/dL (100 g/L) at Wk -2 (Visit S1)
13. Active malignancy, including those requiring surgery, chemotherapy, and/or radiation in the past 5 yrs. Patients with a history of nonmetastatic basal or squamous cell carcinoma of the skin and cervical carcinoma in situ are allowed.
14. Unexplained creatine kinase (CK) >3 × ULN at screening up 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.
15. History within the last 2 yrs of drug, alcohol, amphetamine and derivatives, or cocaine abuse. Patients with amphetamine derivatives prescribed by and under the care of a health care practitioner can be enrolled after evaluation by the Investigator.
16. Blood donation, blood transfusion for any reason, participation in a clinical study with multiple blood draws, major trauma, or surgery with or without blood loss within 30 days prior to randomization
17. Use of any experimental or i
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method