Dyslipidemia MedDRA version: 18.1 Level: LLT Classification code 10020604 Term: Hypercholesterolemia System Organ Class: 100000004861 MedDRA version: 18.1 Level: LLT Classification code 10058110 Term: Dyslipidemia System Organ Class: 100000004861
Conditions
Interventions
Product Name: Evolocumab
Product Code: AMG 145
Pharmaceutical Form: Solution for injection in pre-filled pen
INN or Proposed INN: Evolocumab
Current Sponsor code: AMG 145
Concentration unit: mg/ml mil
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 4.1.1 Signed informed consent 4.1.2 Male or female = 40 to = 85 years of age at signing of informed consent 4.1.3 History of clinically evident cardiovascular disease as evidenced by ANY of the following: o diagnosis of myocardial infarction o diagnosis of non-hemorrhagic stroke (TIA does not qualify as stroke for inclusion) o symptomatic peripheral arterial disease (PAD), as evidenced by intermittent claudication with ankle-brachial index (ABI) 5 years prior to screening will be determined by the sponsor 4.1.4 At least 1 major risk factor or at least 2 minor risk factors below: Major Risk Factors (1 Required): o diabetes (type 1 or type 2) o age = 65 years at randomization (and = 85 years at time of informed consent) o MI or non-hemorrhagic stroke within 6 months of screening o additional diagnosis of myocardial infarction or non-hemorrhagic stroke excluding qualifying MI or non-hemorrhagic stroke (a) o current daily cigarette smoking o history of symptomatic PAD (intermittent claudication with ABI 2.0 mg/L by central laboratory before randomization o Most recent LDL-C = 130 mg/dL (3.4 mmol/L) or non-HDL-C = 160 mg/dL (4.1 mmol/L) by central laboratory before randomization o metabolic syndrome (b) 4.1.5 Most recent fasting LDL-C = 70 mg/dL (= 1.8 mmol/L) or non-HDL-C = 100 mg/dL (= 2.6 mmol/L) by central laboratory during screening after = 2 weeks of stable lipid lowering therapy per Appendix E 4.1.6 Most recent fasting triglycerides = 400 mg/dL (4.5 mmol/L) by central laboratory before randomization (a)Note: there is no time limit on additional qualifying medical history. (b)Definition: metabolic syndrome for this protocol is defined as = 3 of the following (Alberti et al, 2009): • waist circumference > 102 cm (> 40 in.) for men and > 88 cm (> 35 in.) for women (Asian men, including Japanese > 90 cm; Asian women, except Japanese > 80 cm; Japanese women > 90 cm) • triglycerides = 150 mg/dL (1.7 mmol/L) by central laboratory at final screening • HDL-C =65 years) yes F.1.3.1 Number of subjects for this age range 12375
Exclusion criteria
Exclusion criteria: 4.2.1 Subject must not be randomized within 4 weeks of their most recent MI or stroke 4.2.2 NYHA class III or IV, or last known left ventricular ejection fraction 180 mmHg or diastolic BP (DBP) > 110 mmHg 4.2.7 Use of cholesteryl ester transfer protein (CETP) inhibition treatment, mipomersen, or lomitapide within 12 months prior to randomization. Fenofibrate therapy must be stable for at least 6 weeks prior to final screening at a dose that is appropriate for the duration of the study in the judgment of the investigator. Other fibrate therapy (and derivatives) are prohibited 4.2.8 Prior use of PCSK9 inhibition treatment other than evolocumab or use of evolocumab 1.5 times the upper limit of normal (ULN), respectively, and free thyroxine (T4) levels that are outside normal range at final screening 4.2.10 Severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) 3 times the ULN as determined by central laboratory analysis at final screening 4.2.12 Recipient of any major organ transplant (eg, lung, liver, heart, bone marrow, renal) 4.2.13 Personal or family history of hereditary muscular disorders 4.2.14 LDL or plasma apheresis within 12 months prior to randomization 4.2.15 Severe, concomitant non-cardiovascular disease that is expected to reduce life expectancy to less than 3 years 4.2.16 CK > 5 times the ULN at final screening 4.2.17 Known major active infection or major hematologic, renal, metabolic, gastrointestinal or endocrine dysfunction in the judgment of the investigator 4.2.18 Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) within the last 10 years 4.2.19 Subject has received drugs via a systemic route that have known major interactions with background statin therapy (see Appendix F) within 1 month prior to randomization or is likely to require such treatment during the study period 4.2.20 Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s) 4.2.21 Female subject who has either (1) not used acceptable method(s) of birth control for at least 1 month prior to screening or (2) is not willing to use such a method during treatment with IP and for an additional 15 weeks after the end of treatment with IP, unless the subject is sterilized or postmenopausal; menopause is defined as 12 months of spontaneous and continuous amenorrhea in a female = 55 years old or 12 months of spontaneous and continuous amenorrhea with a follicle-stimulating hormone (FSH) level > 40 IU/L (or according to the definition of "postmenopausal range" for the laboratory involved) in a female < 55 years old unless the subject has undergone bilateral oophorectomy • acc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of treatment with evolocumab, compared with placebo, on the risk for cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization, whichever occurs first, in subjects with clinically evident cardiovascular disease.;Secondary Objective: Secondary objectives are to evaluate the effect of treatment with evolocumab, compared with placebo, in subjects with clinically evident cardiovascular disease on the risk for: • cardiovascular death, myocardial infarction, or stroke • cardiovascular death • death by any cause • myocardial infarction • stroke • coronary revascularization • cardiovascular death or hospital admissions for worsening heart failure • fatal or non-fatal ischemic stroke or transient ischemic attack (TIA) ;Primary end point(s): The primary endpoint is the time to cardiovascular death, myocardial infarction, hospitalization for unstable angina, stroke, or coronary revascularization, whichever occurs first. (Note: The primary endpoint includes all adjudicated strokes, ischemic and hemorrhagic.);Timepoint(s) of evaluation of this end point: The primary endpoint is the time to cardiovascular death, myocardial infarction, hospitalization for unstable angina, stroke, or coronary revascularization, whichever occurs first. (Note: The primary endpoint includes all adjudicated strokes, ischemic and hemorrhagic.) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • time to cardiovascular death, myocardial infarction, or stroke, whichever occurs first • time to cardiovascular death • time to death by any cause • time to first myocardial infarction • time to first stroke • time to first coronary revascularization • time to cardiovascular death or hospitalization for worsening heart failure, whichever occurs first • time to ischemic fatal or non-fatal stroke or TIA, whichever occurs first;Timepoint(s) of evaluation of this end point: •time to cardiovascular death, myocardial infarction, or stroke, whichever occurs first •time to cardiovascular death •time to death by any cause •time to first myocardial infarction •time to first stroke •time to first coronary revascularization •time to cardiovascular death or hospitalization for worsening heart failure, whichever occurs first •time to ischemic fatal or non-fatal stroke or TIA, whichever occurs first | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hong Kong, Hungary, Iceland, India, Ireland, Israel, Italy, Japan, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Norway, Philippines, Poland, Portugal, Romania, Russian Federation, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactIHQ Medical Info - Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed