Hypercholesterolaemia MedDRA version: 14.0 Level: PT Classification code 10020603 Term: Hypercholesterolaemia System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Sponsors
Amgen Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Subject has provided informed consent - Male or female = 18 to = 75 years of age - NCEP ATP III Framingham risk score of 10% or less - Fasting LDL-C = 100 mg/dL and (2.6 mmol/L) =65 years) yes F.1.3.1 Number of subjects for this age range 167
Exclusion criteria
Exclusion criteria: - History of coronary heart disease (CHD) or CHD risk-equivalent disease as per NCEP ATP III - NYHA II - IV heart failure - Uncontrolled seriuous 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 plasma 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, confirmed with repeat measurement - Subject has taken lipid-regulating drugs in the last 3 months prior to LDL-C 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, niacin (> 200 mg per day), and omega-3 fatty acid (> 300 mg per day) (eg, docosahexaenoic acid [DHA] and eicosapentaenoic acid [EPA]). Subjects currently on lipid lowering therapy when study enrollment begins may not be screened or randomized at any time in the future - Treatment in the last 3 months prior to LDL-C screening with any of the following drugs: systemic cyclosporine, systemic steroids (e.g, 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 thyroid stimulating hormone (TSH) below the lower limit of normal (LLN) or >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, confirmed by a repeat measurement at least 1 week apart - 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 n
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of 12 weeks of subcutaneous AMG 145 every-2-weeks (Q2W) or every-4-weeks (Q4W), compared with placebo, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) when used as monotherapy in hypercholesterolemic subjects with a 10 year Framingham risk score of 10% or less.;Secondary Objective: - To evaluate the safety and tolerability of 6 dose regimens of SC AMG 145 monotherapy, compared with placebo and with ezetimibe, in subjects with hypercholesterolemia and a 10 year Framingham risk score of 10% or less - To evaluate the effects of 12 weeks of SC AMG 145 monotherapy, ezetimibe, and placebo on absolute change in LDL-C, and percent change in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), total cholesterol/HDL-C ratio, and ApoB/Apolipoprotein A-1 (ApoA1) ratio in subjects with hypercholesterolemia and a 10 year Framingham risk score of 10% or less - To characterize pharmacokinetics of AMG 145 following SC injection in subjects with hypercholesterolemia ;Primary end point(s): The percent change from baseline in LDL-C at week 12.;Timepoint(s) of evaluation of this end point: From baseline to week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Absolute change from baseline in LDL-C 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 ;Timepoint(s) of evaluation of this end point: - Absolute change from baseline in LDL-C at week 12:From baseline to week 12 - Percent change from baseline in non-HDL-C at week 12: From baseline to week 12 - Percent change from baseline in ApoB at week 12: From baseline to week 12- Percent change from baseline in the total cholesterol/HDL-C ratio at week 12: From baseline to week 12- Percent change from baseline in ApoB/ApoA1 ratio at week 12: From baseline to week 12 | — |
Countries
Australia, Belgium, Canada, Denmark, Germany, South Africa, United States
Contacts
Public ContactIHQ Medical Info - Clinical Trials
Amgen (EUROPE) GmbH
Outcome results
None listed