Dyslipidemia MedDRA version: 16.1 Level: LLT Classification code 10020604 Term: Hypercholesterolemia System Organ Class: 100000004861 MedDRA version: 16.1 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 •NCEP ATP III Framingham risk score of 10% or less (see Appendix E of Protocol) •Fasting LDL-C = 100 mg/dL (2.6 mmol/L) and =65 years) yes F.1.3.1 Number of subjects for this age range 150
Exclusion criteria
Exclusion criteria: -History of coronary heart disease (CHD) or CHD risk-equivalent disease as per NCEP ATP III (see Appendix D of Protocol) -NYHA II - IV heart failure -Uncontrolled serious 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 -Diabetes mellitus or fasting serum glucose at screening = 126 mg/dL (7.0 mmol/L) or HbA1c = 6.5% -Uncontrolled hypertension defined as sitting systolic blood pressure (SBP) > 160 mmHg or diastolic BP (DBP) > 100 mmHg -Subject has taken lipid-regulating drugs in the last 3 months prior to LDLC screening, such as: HMG CoA reductase inhibitors, psyllium preparations including Metamucil® (> 2 tbs. per day), fibrates and derivatives, cholesterol absorption inhibitors such as ezetimibe, bile-acid sequestering resins; red yeast rice, > 200 mg per day niacin, and > 300 mg per day omega-3 fatty acids (eg, docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA] combined). Subjects currently on lipid lowering therapy when study enrollment begins may not be screened or randomized at any time in the future -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: Primary objective: To evaluate the effect of 12 weeks of subcutaneous (SC) AMG 145 monotherapy every 2 weeks (Q2W) and monthly (QM), compared with placebo and ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in subjects with a 10-year Framingham risk score of 10% or less.;Secondary Objective: • To evaluate the safety and tolerability of SC AMG 145 monotherapy Q2W and QM, compared with placebo and ezetimibe, in subjects with a 10-year Framingham risk score of 10% or less • To assess the effects of 12 weeks of SC AMG 145 monotherapy Q2W and QM, compared with placebo and ezetimibe, on change from baseline in LDL-C, and percent change from baseline in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total cholesterol/HDL-C ratio, ApoB/Apolipoprotein A1 (ApoA1) ratio, lipoprotein(a) [Lp(a)], triglycerides, very low-density lipoprotein cholesterol (VLDL-C), and HDL-C in subjects with a 10-year Framingham risk score of 10% or less • To assess the effects of 12 weeks SC AMG 145 monotherapy Q2W and QM, compared with placebo and ezetimibe, on percent of subjects attaining LDL-C < 70 mg/dL (1.8 mmol/L) in subjects with a 10-year Framingham risk score of 10% or less;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: 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 | — |
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 endpoints • 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 endpoints • 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 Efficacy Endpoints Co-secondary endpoints of the means at weeks 10 and 12 and at week 12 for: Tier 1 endpoints • 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 endpoints • 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, Brazil, Canada, Denmark, France, Korea, Republic of, South Africa, Taiwan, Turkey, United States
Contacts
Public ContactIHQ Medical Info - Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed