Dyslipidemia MedDRA version: 14.1 Level: LLT Classification code 10020604 Term: Hypercholesterolemia System Organ Class: 100000004861 MedDRA version: 14.1 Level: LLT Classification code 10058110 Term: Dyslipidemia System Organ Class: 100000004861
Conditions
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Subject has provided informed consent. •Male or female = 18 to = 80 years of age at signing of informed consent •Subject not on a statin or on a low dose statin as defined below. For statins not listed, the maximal total weekly dose is 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 - 140 mg or less f) fluvastatin - 280 mg or less •Subject not at LDL-C goal as evidenced by their NCEP ATP III risk category (see Appendix D) 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 d) Fasting LDL-C = 190 mg/dL (4.9 mmol/L) for subjects without diagnosed CHD or risk equivalent and with no risk factors •Subject has a history of statin intolerance as evidenced by both of the following (per subject or physician report): a) Tried at least 2 statins and was unable to tolerate any dose or increase statin dose above the total weekly maximum doses listed inSection 4.1.3 due to intolerable myopathy, ie, myalgia (muscle pain, ache, or weakness without CK elevation), myositis (muscle symptoms with increased CK levels), or rhabdomyolysis (muscle symptoms with marked CK elevation) b) 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 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: •NYHA III or IV heart failure, or last known left ventricular ejection fraction 8.5%), newly diagnosed type 2 diabetes (within 6 months of randomization), or laboratory evidence of diabetes during screening (fasting serum glucose = 126 mg/dL [7.0 mmol/L] or HbA1c = 6.5%) without prior diagnosis of diabetes •Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) > 160 mmHg or diastolic BP (DBP) > 100 mmHg •Subject has taken in the last 6 weeks prior to LDL-C screening red yeast rice, > 200 mg/day niacin, or prescription lipid-regulating drugs (eg, fibrates and derivatives) other than statins, ezetimibe, bile-acid sequestering resin, or stanols and stanol esters •Subject has taken a cholesterylester transfer protein (CETP) inhibitor in the last 12 months prior to LDL-C screening, such as: anacetrapib, dalcetrapib or evacetrapib. •Treatment in the last 3 months prior to LDL-C screening with any of the following drugs: systemic cyclosporine, systemic steroids (eg, IV,intramuscular [IM], or PO) (Note: hormone replacement therapy is permitted), vitamin A derivatives and retinol derivatives for the treatment of dermatologic conditions (eg, Accutane); (Note: vitamin A in a multivitamin preparation is permitted) •Uncontrolled hypothyroidism or hyperthyroidism as defined by thyroid stimulating hormone (TSH) 1.5 times the ULN, respectively, at screening •Moderate to severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) 2 times the ULN as determined by central laboratory analysis at screening •CK > 3 times the ULN at screening •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 •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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of 12 weeks of subcutaneous (SC) AMG 145 every 2 weeks (Q2W) and monthly (QM), compared with ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic subjects unable to tolerate an effective dose of a statin.;Secondary Objective: •To evaluate safety and tolerability of SC AMG 145 Q2W and QM, compared with ezetimibe, in hypercholesterolemic subjects unable to tolerate an effective dose of a statin •To evaluate effect of 12 weeks of SC AMG 145 Q2W and QM compared with ezetimibe, on percent change from baseline in LDL-C in hypercholesterolemic subjects unable to tolerate an effective dose of a statin and not receiving any lipid regulating medications at study entry • To assess the effects of 12 weeks SC AMG 145 Q2W and QM, compared with ezetimibe, on percent of subjects attaining LDL-C < 70 mg/dL (1.8 mmol/L) in hypercholesterolemic subjects unable to tolerate an effective dose of a statin Refer pg 18 of protocol for remaining objectives;Primary end point(s): Co-Primary Endpoints: •Mean percent change from baseline in LDL-C at weeks 10 and 12 • Percent change from baseline in LDL-C at week 12;Timepoint(s) of evaluation of this end point: At week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Co-Secondary Efficacy Endpoints Co-secondary endpoints of the means at weeks 10 and 12 and at week 12 for: Tier 1 •Change from baseline in LDL-C • LDL-C response (LDL-C < 70 mg/dL [1.8 mmol/L]) •Percent change from baseline in non-HDL-C • Percent change from baseline in ApoB •Percent change from baseline in the total cholesterol/HDL-C ratio • Percent change from baseline in ApoB/ApoA1 ratio Tier 2 • Percent change from baseline in Lp(a) • Percent change from baseline in triglycerides • Percent change from baseline in HDL-C • Percent change from baseline in VLDL-C;Timepoint(s) of evaluation of this end point: Co-secondary endpoints of the means at weeks 10 and 12 and at week 12 for: Tier 1 •Change from baseline in LDL-C • LDL-C response (LDL-C < 70 mg/dL [1.8 mmol/L]) •Percent change from baseline in non-HDL-C • Percent change from baseline in ApoB •Percent change from baseline in the total cholesterol/HDL-C ratio • Percent change from baseline in ApoB/ApoA1 ratio Tier 2 • Percent change from baseline in Lp(a) • Percent change from baseline in triglycerides • Percent change from baseline in HDL-C • Percent change from baseline in VLDL-C | — |
Countries
Australia, Belgium, Canada, Denmark, France, Germany, Hong Kong, Japan, Netherlands, Poland, South Africa, Spain, Switzerland, United Kingdom, United States
Contacts
Public ContactIHQ Medical Info - Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed