Primary Hypercholesterolemia and Mixed 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 • Subjects not taking a statin at screening must have a fasting LDL-C of at least 150 mg/dl (4.0 mmol/L) as determined by central laboratory • Subjects already on a non-intensive statin (see Appendix D) at screening must have a fasting LDL-C at screening of = 100 mg/dL (2.6 mmol/L) as determined by central laboratory • Subjects already on a intensive statin (see Appendix D of Protocol) at screening must have a fasting LDL-C at screening of = 80 mg/dL (2.1 mmol/L) as determined by central laboratory •Negative pregnancy test, AST and ALT = 2 times ULN, CK = 3 times ULN as determined by central laboratory at the end of the lipid stabilization period • 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 1300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 400
Exclusion criteria
Exclusion criteria: •Current or prior history of statin intolerance, or any intolerance to rosuvastatin, atorvastatin, or simvastatin. •Subject, who in the opinion of the investigator, requires maximal statin therapy •Personal or family history of hereditary muscular disorders •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 plasma 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, > 1000 mg/day omega-3 fatty acids ( DHA and EPA combined), stanols or prescription lipid-regulating drugs (eg, bileacid sequestering resins, fibrates and derivatives) other than statins and ezetimibe •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 upper limit of normal (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 in the past year, 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of 12 weeks of subcutaneous (SC) AMG 145 administered every 2 weeks (Q2W) and monthly (QM) when used in combination with a statin, compared with placebo, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in subjects with primary hypercholesterolemia and mixed dyslipidemia.;Secondary Objective: • To evaluate the safety and tolerability of SC AMG 145 Q2W and QM used in combination with a statin, compared with placebo or ezetimibe, in subjects with primary hypercholesterolemia and mixed dyslipidemia • To assess the effects of 12 weeks of SC AMG 145 Q2W and QM used in combination with a statin compared to placebo or 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 A-1 (ApoA1) ratio lipoprotein (a) [Lp(a)], triglycerides, very low-density lipoprotein cholesterol (VLDL-C), and HDL-C in subjects with primary hypercholesterolemia and mixed dyslipidemia • 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);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 endpoints of the means at weeks 10 and 12 and at week 12 for: Tier 1 endpoints • Change from baseline in LDL-C • 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 • LDL-C response (LDL-C < 70 mg/dL [1.8 mmol/L]) • 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 endpoints • Change from baseline in LDL-C • 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 • LDL-C response (LDL-C < 70 mg/dL [1.8 mmol/L]) • 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
Argentina, Australia, Belgium, Brazil, Canada, Czech Republic, Denmark, France, Germany, Hong Kong, Hungary, Italy, Korea, Republic of, Mexico, Netherlands, Russian Federation, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactIHQ Medical Info - Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed