CTRI/2017/10/010233进行中（未招募）3 期
A Randomized, Double-Blind, Placebo Controlled Study To Assess The Effects Of Bempedoic Acid (Etc-1002) On The Occurrence Of Major Cardiovascular Events In Patients With, Or At High Risk For, Cardiovascular Disease Who Are Statin Intolerant
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 12,604
- 试验地点
- 23
- 主要终点
- To evaluate whether long-term treatment with bempedoic acid 180 mg/day versus placebo reduces the risk of major adverse cardiovascular events (MACE) in patients with, or at high risk for, cardiovascular disease (CVD) who are statin intolerant. This will be assessed with a composite primary efficacy endpoint that includes time to first occurrence of cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization
研究概览
简要总结
This is a Phase 3, multicenter, randomized,double-blind, placebo-controlled, parallel group study.
This Phase 3 study is being conductedas a part of a comprehensive Phase 3 programto determine whetherbempedoic acid will reduce the risk of major adversecardiovascular events (MACE) in patientswith, or at high risk for,CVD who are unable to tolerate statins.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 85.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Provision of signed informed consent prior to any study-specific procedure.
- •Patient reported statin intolerance (SI) due to an adverse safety effect that started or increased during statin therapy and resolved or improved when statin therapy was discontinued resulting in an inability to tolerate: • 2 or more statins at any dose, or • 1 statin at any dose and unwilling to attempt a second statin or advised by a physician to not attempt a second statin.
- •Written confirmation by both patient and investigator that the patient is statin intolerant as defined above, aware of the benefit of statin use to reduce the risk of MACE including death, and also aware that many other patients who are unable to tolerate a statin are able to tolerate a different statin or dose.
- •Age ≥18 years or legal age of majority based on regional law, whichever is greater, and ≤85 years at Week -5 (Visit S1).
- •5.Men and nonpregnant, nonlactating women.
- •Women must be one of the following: a.Naturally postmenopausal defined as ≥1 year without menses and: •≥55 years, or •<55 years with follicle-stimulating hormone (FSH) ≥40.0 IU/L, or b.Surgically sterile including hysterectomy, bilateral oophorectomy, and/or tubal ligation, or c.Women of childbearing potential willing to use one acceptable method of birth control during the study and for 30 days after the end of treatment including: •oral birth control medications, •placement of an intrauterine device 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, •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.
- •Fasting LDL-C ≥100 mg/dL (2.6 mmol/L) at Week -5 (Visit S1) while taking stable (4 weeks prior to Visit S1) and optimized background LDL-C-lowering therapies that may include very low dose statin (see definition above), ezetimibe, niacin, bile acid resins, fibrates, and/or proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors.
- •Note: A single repeat of LDL-C may be completed prior to initiation of the single-blind Run–in Period.
- •For those patients who have a repeat LDL-C, the repeat value will be used to determine eligibility.
- •7.History of, or at high risk for, CVD including documented evidence of one or more of the following: a.Coronary artery disease, defined by: •MI (either ST-elevation MI or non-ST-elevation MI) occurring greater than 90 days prior to screening, or •Percutaneous coronary or surgical coronary revascularization, occurring greater than 90 days prior to screening, or •Angiographic stenosis of >50% in a least 1 major coronary artery (native or graft vessel), as documented by selective coronary angiography or computed tomography angiography (CTA), or b.Symptomatic peripheral arterial disease (PAD) , defined by: •Peripheral vascular disease with symptoms of claudication or resting limb ischemia with either ankle brachial index <0.9 performed by a vascular lab or angiogram (including CTA) showing ≥50% stenosis, or •Peripheral arterial revascularization (surgical or percutaneous), occurring greater than 90 days prior to screening, or •Abdominal aortic aneurysm confirmed by imaging or aortic aneurysm repair, occurring greater than 90 days prior to screening, or •Lower extremity amputation due to peripheral vascular disease, occurring greater than 90 days prior to screening, or c.Cerebrovascular atherosclerotic disease defined by: •Ischemic stroke occurring greater than 90 days prior to screening, or •Carotid endarterectomy, carotid stenting, or more than 70% stenosis in a carotid artery determined by carotid ultrasound or angiogram, occurring greater than 90 days prior to screening, or d.High risk for a CVD event, defined by: •Reynolds Risk score >30% or a SCORE Risk score >7.5% over 10 years, or •Coronary artery calcium score >400 Agatston units (AU) at any time in the past.
排除标准
- •Patients who meet any of the following criteria will not be eligible to participate: 1.Total fasting TG >500 mg/dL (5.6 mmol/L) at Week -5 (Visit S1).
- •Note: A single repeat of TG may be completed prior to initiation of the single-blind Run-in Period.
- •For those patients who have a repeat TG, the repeat value will be used to determine eligibility.
- •2.Renal dysfunction or a glomerulonephropathy defined as either nephritic or nephrotic syndrome, including estimated glomerular filtration rate (eGFR; using central laboratory determined Modification of Diet in Renal Disease [MDRD] formula) <30 mL/min/1.73 m2 at Week -5 (Visit S1).
- •Note: A single repeat of eGFR may be completed prior to randomization.
- •For those patients who have a repeat eGFR, the repeat value will be used to determine eligibility.
- •3.Forms of CVD that include any of the following: a.Recent (within 90 days prior to screening) transient ischemic attack (TIA) b.Recent (within 90 days of screening) unstable or symptomatic cardiac arrhythmia (including any associated medication changes).
- •Patients with stable well-controlled atrial arrhythmias will be allowed to participate in the study.
- •c.Patients with implantable pacemakers or automatic implantable cardioverter defibrillators may be considered if deemed by the investigator to be stable for greater than 90 days prior to screening, d.New York Heart Association (NYHA) Functional Classification Class IV heart failure, e.Uncontrolled hypertension, defined as mean sitting systolic blood pressure (SBP) ≥180 mmHg and/or diastolic blood pressure (DBP) ≥110 mmHg, f.Planned coronary revascularization (patient may rescreen 3 months post-procedure).
- •Note: At the discretion of the investigator, BP medications can be adjusted and/or additional assessment of BP may be completed prior to randomization, with the repeat assessment value used to determine eligibility.
- •Alternatively, patients can be rescreened if BP status has changed.
- •4.HbA1C ≥10% at Week -5 (Visit S1).
- •5.Uncontrolled hypothyroidism, including thyroid-stimulating hormone (TSH) >1.5 × the upper limit of normal (ULN) at Week -5 (Visit S1).
- •Note: At the discretion of the investigator, thyroid replacement therapy can be adjusted and/or additional measurement of TSH may be completed prior to randomization, with the repeat TSH value used to determine eligibility.
- •6.Liver disease or dysfunction, including: a.
- •Positive serology for hepatitis B surface antigen (HBsAg) and/or hepatitis C antibodies (HCV-ABVivi) at Week -4 (Visit S2), or b.
- •Note: At the discretion of the investigator, a single repeat of ALT and/or AST may be completed prior to randomization.
- •For those patients who have a repeat ALT and/or AST, the repeat value will be used to determine eligibility.
- •Also, if test for Hepatitis C antibody is positive, but optional reflexive test for Hepatitis C RNA is negative, patient can be enrolled.
- •7.Gastrointestinal conditions or procedures (including weight loss surgery; eg, Lap-Band® or gastric bypass) that may affect drug absorption.
- •8.Hematologic or coagulation disorders or a hemoglobin (Hgb) level <10 g/dL at Week -5 (Visit S1).
- •9.Active malignancy, including those requiring surgery, chemotherapy, and/or radiation in the past 5 years.
- •10.Unexplained creatine kinase (CK) >3 × ULN at Week -5 (Visit S1) (ie, not associated with recent trauma or physically strenuous activity).
- •Patients with amphetamine derivatives prescribed by and under the care of a health care practitioner can be enrolled after evaluation by the investigator.
- •12.Blood transfusion for any reason within 30 days prior to randomization.
- •13.Use of any experimental or investigational drugs within 30 days prior to screening or 5 half-lives, whichever is longer.
- •14.Randomization into another Phase 3 bempedoic acid clinical study.
- •15.Use of, or a plan to initiate, these prohibited therapies/supplements during the study: a.
- •Mipomersen (must be stopped at least 6 months prior to Week -5 [Visit S1]), lomitapide or apheresis therapy (must be stopped at least 3 months prior to Week -5 [Visit S1]), b.Red yeast rice (must be stopped at least 2 weeks prior to Week -5 [Visit S1]), c.Statins are prohibited at average daily doses of rosuvastatin ≥5 mg, atorvastatin ≥10 mg, simvastatin ≥10 mg, lovastatin ≥20 mg, pravastatin ≥40 mg, fluvastatin ≥40 mg, or pitavastatin ≥2 mg.
- •16.Planned initiation or dose adjustments of these allowed drugs less than 4 weeks prior to screening and during the clinical trial (stable use of these drugs is permitted): a.
- •Statins are allowed only at average daily doses of rosuvastatin <5 mg, atorvastatin <10 mg, simvastatin <10 mg, lovastatin <20 mg, pravastatin <40 mg, fluvastatin <40 mg, or pitavastatin <2 mg, b.Other lipid regulating drugs or supplements.
- •18.Lack of tolerance with IMP (single-blind 19.A medical or situational (ie, geographical) finding that in the investigator’s opinion may compromise the patient’s safety or ability to complete the study.
- •An employee or contractor of the facility conducting the study, or a family member of the Principal Investigator, Co-Investigator, or Sponsor.
结局指标
主要结局
To evaluate whether long-term treatment with bempedoic acid 180 mg/day versus placebo reduces the risk of major adverse cardiovascular events (MACE) in patients with, or at high risk for, cardiovascular disease (CVD) who are statin intolerant. This will be assessed with a composite primary efficacy endpoint that includes time to first occurrence of cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization
时间窗: Entire duration
次要结局
- To evaluate whether long-term treatment with bempedoic acid 180 mg/day versus placebo reduces the risk of other clinical endpoints of CV morbidity & mortality & all-cause mortality(During entire study)
- To evaluate the effect of long-term treatment with bempedoic acid 180 mg/day versus placebo on low-density lipoprotein cholesterol (LDL-C) and high-sensitivity C-reactive protein (hsCRP)(During entire study)
- To evaluate the long-term safety and tolerability of bempedoic acid 180 mg/day compared to placebo(During entire study)
- To evaluate the 12-month efficacy of treatment with bempedoic acid 180 mg/day versus placebo on absolute change in hemoglobin A1c (HbA1C) in the inadequately controlled diabetes efficacy population (patients with diabetes & having an HbA1C of 7% or greater at baseline)(During entire study)
- To evaluate whether long-term treatment with bempedoic acid 180 mg/day versus placebo reduces the risk of new-onset diabetes in the prediabetes efficacy population (patients with prediabetes at baseline)(During entire study)
研究者
研究点 (23)
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