A Randomized, Double-blind, Placebo-controlled, Multicenter Long-term Safety and Tolerability Study of ETC 1002 in Patients with Hyperlipidemia at High Cardiovascular Risk Who are not Adequately Controlled by Their Lipid-Modifying Therapy

Phase 3

Completed

• Conditions: cardiovascular disease; hyperlipidemia; 10082206; 10013317

• Registration Number: NL-OMON45821
• Lead Sponsor: Esperion Therapeutics Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 23 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 162

Inclusion Criteria

1. Age *18 years or legal age of majority based on regional law,
whichever is greater at Week -2 (Visit S1)
2. Men and non-pregnant, nonlactating women. Women must be either:
* Naturally postmenopausal or;
* Women of childbearing potential must be willing to use 1 acceptable method of birth control.
3. Fasting LDL-C at Week -2 (Visit S1) *70 mg/dL (1.8 mmol/L)
4. Have high cardiovascular risk that is defined as either:
* Diagnosis of HeFH
OR
* Have ASCVD (with established CHD or CHD risk equivalents) i.e. with:
*Acute myocardial infarction (MI)
*Silent MI
*Unstable angina
*Coronary revascularization procedure (e.g, percutaneous coronary intervention or coronary artery bypass graft 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 one 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. CT or MRI must have been performed to rule out hemorrhage and non-ischemic neurological disease
*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 a stable doses for at least 4 weeks prior to screening (6 weeks for fibrates, however, gemfibrozil is not allowed). Regimens other than daily dosing, including those at very low doses, are
acceptable.
A patient's maximally tolerated lipid-modifying therapy will be determined by the investigator using their medical judgment and available sources, including the patient's self-reported history of lipidmodifying therapy.;For the complete list of inclusion and exclusion criteria, please refer to Section 7 of the protocol.

Exclusion Criteria

1. Total fasting triglyceride *500 mg/dL (5.6 mmol/L) at Wk -2 /vS1;2. Renal dysfunction or nephritic syndrome or a history of nephritis, including eGFR (using central laboratory determined Modification of Diet in Renal Disease [MDRD] formula) <30 mL / min/ 1.73m2 at Wk -2 /vS1
Note: At discretion of the investigator, the screening period may be extended up to 2 weeks for a single repeat eGFR. For those patients who have a repeat eGFR the repeat value will be used to determine eligibility.
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. Body mass index (BMI) *50 kg/m2;4. Concomitant use of simvastatin at average daily doses greater than 40 mg.;5.Concomitant use of a PCSK inhibitor (Praluent® [alirocumab] or Repatha® [evolocumab]) at Week 2 (Visit S1) or prior use of a PCSK9 inhibitor within the past 4 weeks of Week 2 (Visit S1) will be excluded from this study.;6. Recent (within 3 months prior to the screening visit [Wk -2 /vS1] 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, transient ischemic attack, 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 systolic blood pressure (SBP) *160 mmHg and diastolic blood pressure (DBP) *100 mmHg after sitting quietly for 5 minutes. ;8. Hemoglobin A1C (HbA1C) *10% at Wk -2 /vS1;9. Uncontrolled hypothyroidism, including thyroid-stimulating hormone >1.5 × the upper limit of normal (ULN) at Wk -2 /vS1. Patients stabilized on thyroid replacement therapy for at least 6 weeks prior to randomization are allowed.;10. Liver disease or dysfunction, including:
* Positive serology for hepatitis B surface antigen and/or hepatitis C antibodies at Wk -2 /vS1 or
* Alanine aminotransferase , aspartate aminotransferase *2 × ULN, and/or total bilirubin *1.2 × ULN at Wk -2 /vS1.;11. Gastrointestinal 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 hemoglobin (Hgb) level <10.0 g/dL (100 g/L) at Week 2 (Visit S1);13. Active malignancy, including those requiring surgery, chemotherapy, and/or radiation in the past 5 years. Patients with a history of non-metastatic 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 years 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, bl

Study & Design

• Study Type: Interventional
• Study Design: Not specified