A Study Assessing the Impact of Additional LDL-Cholesterol Reduction on Major Cardiovascular Events when AMG 145 is used in combination With Statin Therapy In Patients with Clinically Evident Cardiovascular Disease

Phase 1

• Conditions: Dyslipidemia; MedDRA version: 14.1Level: LLTClassification code 10058110Term: DyslipidemiaSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2012-001398-97-GR
• Lead Sponsor: Amgen Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-08-09
• Last Update Posted: 5 December 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 22500

Inclusion Criteria

•Signed informed consent
•Male or female = 40 to = 80 years of age at signing of informed consent
•History of clinically evident cardiovascular disease within 5 years of screening as evidenced by ANY of the following:
o diagnosis of myocardial infarction
o diagnosis of stroke
•History of type 2 diabetes or, if not diabetic, ANY of the following:
o age = 65 years (and = 80 years)
o index event within 6 months prior to screening
o additional diagnosis of myocardial infarction or stroke (prior to and excluding index event)
o history of symptomatic peripheral vascular disease (intermittent claudication with ankle-brachial index [ABI] < 0.9, or peripheral vascular revascularization procedure, or amputation due to atherosclerotic disease)
o = 2 of the following risk factors:
-HDL-C < 40 mg/dL (1.0 mmol/L) for men and < 50 mg/dL (1.3 mmol/L) for women by central laboratory at screening
-residual coronary artery disease with = 40% stenosis in = 2 large vessels
-hsCRP > 2.0 mg/L by central laboratory at screening
-current smoker
-age > 60 years
-history of non-MI related coronary revascularization*
-final LDL-C > 130 mg/dL (3.4 mmol/L) or non-HDL-C = 160 mg/dL (4.1 mmol/L) by central laboratory during screening
-metabolic syndrome, defined as = 3 of the following:
- waist circumference > 102 cm (> 40 in.) for men and > 88 cm (> 35 in.) for women
- triglycerides = 150 mg/dL (1.7 mmol/L) by central laboratory at screening
- HDL-C < 40 mg/dL (1.0 mmol/L) for men
and < 50 mg/dL (1.3 mmol/L) for women by central laboratory at screening (Note: if the HDL-C level is one of criterion used to make the diagnosis of metabolic syndrome, it cannot be used as a separate risk factor)
- blood pressure (BP) = 130 / = 85 mmHg
- fasting glucose = 110 mg/dL by central laboratory at screening
•Fasting LDL-C = 70 mg/dL (= 1.8 mmol/L) ) or non-HDL-C = 100 mg/dL (> 2.6 mg/dL) by central laboratory during screening after = 4 weeks of stable dose of 20 mg, 40 mg, or 80 mg QD atorvastatin, with or without ezetimibe 10 mg QD
•Fasting triglycerides = 400 mg/dL (4.5 mmol/L) by central laboratory at screening
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 13500
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 9000

Exclusion Criteria

•NYHA class III or IV, or last known left ventricular ejection fraction < 30%
•Known hemorrhagic stroke
•Uncontrolled or recurrent ventricular tachycardia
•Planned or expected cardiac surgery or revascularization within 3 months after randomization
•Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) > 180 mmHg or diastolic BP (DBP) > 110 mmHg
•In the 6 weeks prior to LDL-C screening, subject has taken red yeast rice, > 200 mg/day niacin, or prescription lipid-regulating drugs (eg, bile-acid sequestering resins, fibrates and derivatives) other than statins or ezetimibe
•Use of cholesterylester transfer protein (CETP) inhibition treatment within 12 months prior to randomization
•Prior use of PCSK9 inhibition treatment other than AMG 145
•Uncontrolled hypothyroidism or hyperthyroidism as defined by thyroid stimulating hormone (TSH) < 1.0 time the lower limit of normal (LLN) or > 1.5 times the upper limit of normal (ULN), respectively, at screening
•Severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73m2 at screening
•Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2 times the ULN as determined by central laboratory analysis at screening
•Recipient of any major organ transplant (eg, lung, liver, heart, bone marrow)
•Severe, concomitant non-cardiovascular disease that is expected to reduce life expectancy to less than 3 years
•CK > 5 times the ULN at screening
•Known active infection or major hematologic, renal, metabolic,
gastrointestinal or endocrine dysfunction in the judgment of the investigator
•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
•Subject has received drugs that are strong inhibitors of cytochrome P-450 3A4 within 1 month prior to randomization or is likely to require such treatment during the study period
•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)
•Female subject who has either (1) not used at least 1 highly effective method of birth control for at least 1 month prior to screening or (2) is not willing to use such a method during treatment and for an additional 15 weeks after the end of treatment, 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
- highly effective methods of birth control include not having intercourse or using birth control methods that work at least 99% of the time when used correctly and include: birth control pills, shots, implants, or patches, intrauterine devices (IUDs), tubal ligation/occlusion, sexual activity with a male partner who has had a vasectomy, condom or occlusive cap (diaphragm or
cervical/vault caps) used with spermicide
•Subject is pregnant or breast feeding, or planning to become pregnant during treatment and/ or within 15 weeks after the end of treatment
•Known sen

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified