Primary Hypercholesterolemia and Mixed Dyslipidemia MedDRA version: 20.1 Level: LLT Classification code 10020604 Term: Hypercholesterolemia System Organ Class: 100000004861 MedDRA version: 20.0 Level: LLT Classification code 10058110 Term: Dyslipidemia System Organ Class: 100000004861
Conditions
Interventions
Product Name: AMG 145
Pharmaceutical Form: Solution for injection
Current Sponsor code: AMG 145
Concentration unit: mg/ml milligram(s)/millilitre
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) at screening must have a fasting LDL-C at screening of = 80 mg/dL (2.1 mmol/L) as determined by central laboratory • 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 enrol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary endpoint is the percent change from baseline in LDL-C at week 12.;Timepoint(s) of evaluation of this end point: At week 12;Main Objective: To evaluate the effect of 12 weeks of subcutaneous (SC) AMG 145 administered every 2 weeks (Q2W) and every 4 weeks (Q4W) 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 Q4W 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 Q4W 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 and HDLC in subjects with primary hypercholesterolemia and mixed dyslipidemia • To assess the effects of 12 weeks SC AMG 145 Q2W and Q4W compared with ezetimibe, on percent of subjects attaining LDL-C < 70 mg/dL (1.8 mmol/L) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Efficacy Endpoints Tier 1 endpoints • Change from baseline in LDL-C at week 12 • LDL-C response (LDL-C < 70 mg/dL [1.8 mmol/L]) at week 12 • Percent change from baseline in non-HDL-C at week 12 • Percent change from baseline in ApoB at week 12 • Percent change from baseline in the total cholesterol/HDL-C ratio at week 12 • Percent change from baseline in ApoB/ApoA1 ratio at week 12 Tier 2 endpoints • Percent change from baseline in Lp(a) at week 12 • Percent change from baseline in triglycerides at week 12 ; Timepoint(s) of evaluation of this end point: Secondary Efficacy Endpoints • Change from baseline in LDL-C at week 12 • LDL-C response (LDL-C < 70 mg/dL [1.8 mmol/L]) at week 12 • Percent change from baseline in non-HDL-C at week 12 • Percent change from baseline in ApoB at week 12 • Percent change from baseline in the total cholesterol/HDL-C ratio at week 12 • Percent change from baseline in ApoB/ApoA1 ratio at week 12 • Percent change from baseline in Lp(a) at week 12 • Percent change from baseline in triglycerides at week 12 | — |
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