Study to assess the tolerability and efficacy of AMG 145 in patients with hypercholesterolemia unable to tolerate an effective dose of a statin.

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 150

Inclusion Criteria

- Subject has provided informed consent.
- Male or female = 18 to = 75 years of age
- Subject not on a statin or on a low dose statin - as defined by a maximal total weekly dose corresponding to 7 times the smallest available tablet size. For the listed statins below, the following maximum total prescribed weekly dosages apply:
a) atorvastatin - 70 mg or less
b) simvastatin - 140 mg or less
c) pravastatin - 140 mg or less
d) rosuvastatin - 35 mg or less
e) lovastatin -1 40 mg or less
f) fluvastatin - 280 mg or less
- Subject not at LDL-C goal as evidenced by their NCEP ATP III risk category and the following LDL-C levels by central laboratory at screening:
a) Fasting LDL-C = 100 mg/dL (2.6 mmol/L) for subjects with diagnosed CHD or are CHD risk equivalent or
b) Fasting LDL-C = 130 mg/dL (3.4 mmol/L) for subjects without diagnosed CHD or risk equivalent and 2 or more risk factors or
c) Fasting LDL-C = 160 mg/dL (4.1 mmol/L) for subjects without diagnosed CHD or risk equivalent and with 1 or no risk factors
- Subject has a history of statin intolerance as evidenced by both of the following (per subject or physician report):
- Tried at least one statin and was unable to tolerate any dose or increase statin dose above the total weekly maximum doses listed above due to intolerable myalgia (muscle pain, soreness, weakness, or cramps) or myopathy (myalgia plus a raised CK)
- Symptoms resolved or improved when statin dose was decreased or discontinued
- Lipid lowering therapy has been stable prior to LDL-C screening for at least 4 weeks if currently on a statin and/or bile-acid sequestering resin and/or stanol; if subject is on ezetimibe at start of screening, ezetimibe must be discontinued for = 4 weeks before LDL-C screening
- 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 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion Criteria

- NYHA III or IV heart failure, or known left ventricular ejection fraction < 30%
- Uncontrolled cardiac arrhythmia defined as recurrent and highly symptomatic ventricular tachycardia, atrial fibrillation with rapid ventricular response, or supraventricular tachycardia that are not controlled by medications, in the past 3 months prior to randomization
- Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization
- Planned cardiac surgery or revascularization within 20 weeks of screening
- Type 1 diabetes or newly diagnosed (within 3 months of randomization) type 2 diabetes, or poorly controlled type 2 diabetes (HbA1c > 8.5%)
- Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) > 160 mmHg or diastolic BP (DBP) > 100 mmHg, confirmed with repeat measurement
- Subject has taken in the last 6 weeks prior to LDL-C screening red
yeast
rice, > 200 mg/day niacin, >1000 mg/day omega-3 fatty acids (eg,
docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]), or
prescription lipid-regulating drugs (eg, fibrates and derivatives) other
than statins, ezetimibe, bile-acid sequestering resin, or stanols and
stanol esters
- Treatment in the last 3 months prior to LDL-C screening with any of the following drugs: systemic cyclosporine, systemic steroids (IV, intramuscular [IM], or PO), vitamin A derivatives and retinol derivatives for the treatment of dermatologic conditions (eg, Accutane); (Note: vitamin A in a multivitamin preparation is permitted)
- Hyperthyroidism or hypothyroidism as defined by TSH below the lower limit of normal or >1.5 times the ULN, respectively, at screening
- Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) < 30 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
- CK > 3 times the ULN at screening, confirmed by a repeat measurement at least 1 week apart
- Known active infection or major hematologic, renal, metabolic, gastrointestinal or endocrine dysfunction in the judgment of the investigator
- Diagnosis of deep vein thrombosis or pulmonary embolism within 3 months prior to randomization
- Current therapeutic anticoagulation with vitamin K antagonist (eg, warfarin), heparin, low-molecular weight heparin, direct thrombin inhibitor, or Factor Xa inhibitor (Note: anti-platelet agents [eg, aspirin, clopidogrel, prasugrel, ticagrelor, dipyridamole] are permitted)
- Unreliability as a study participant based on the investigator's (or designee’s) knowledge of the subject (eg, alcohol or other drug abuse, inability or unwillingness to adhere to the protocol, or psychosis)
- 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 is not willing to use at least one highly effective method of birth control during treatment and for an additional 15 weeks after the end of treatment unless subject is sterilized or postmenopausal; highly effective methods of birth control include abstinence, birth control pills, shots, implants, or patches, intrauterine devices (IUDs), sexual activity with a male partner who ha

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

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