Durable Effect of PCSK9 Antibody CompARed wiTh placEbo Study
- Conditions
- Hypercholesterolemia
- Interventions
- Registration Number
- NCT01516879
- Lead Sponsor
- Amgen
- Brief Summary
To evaluate the efficacy, safety, and tolerability of 52 weeks of subcutaneous (SC) evolocumab (AMG 145) compared with placebo when added to assigned background lipid-lowering therapy.
- Detailed Description
Eligible participants with screening central laboratory low-density lipoprotein cholesterol (LDL-C) values ≥ 75 mg/dL (1.9 mmol/L) were instructed to follow National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP) Therapeutic Lifestyle Changes (TLC) diet and were assigned to 1 of the following 4 background lipid-lowering therapies for a 4-week stabilization period based upon their screening LDL-C and its distance from the individual's required goal as stipulated by their NCEP ATP III risk category:
1. no drug therapy required - diet alone
2. low dose drug therapy required - diet plus atorvastatin 10 mg orally (PO) once daily (QD)
3. high dose drug therapy required - diet plus atorvastatin 80 mg PO QD
4. maximal drug therapy required - diet plus atorvastatin 80 mg PO QD plus ezetimibe 10 mg PO QD.
If the participant met entry criteria at the end of the lipid stabilization period they were randomized 2:1 to receive evolocumab 420 mg or placebo subcutaneously once a month for 52 weeks in addition to their background therapy.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 905
-
Subject has provided informed consent.
-
Fasting LDL-C ≥ 75 mg/dL and meeting the following LDL-C values on background lipid-lowering therapy:
- < 100 mg/dL for subjects with diagnosed coronary heart disease (CHD) or CHD risk equivalent
- < 130 mg/dL for subjects without diagnosed CHD or CHD risk equivalent
- OR on maximal background lipid-lowering therapy defined as atorvastatin 80 mg PO QD and ezetimibe 10 mg PO QD
-
Fasting triglycerides ≤ 400 mg/dL
- New York Heart Association (NYHA) II-IV heart failure, or last known left ventricular ejection fraction < 30%
- Uncontrolled cardiac arrhythmia
- Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization, type 1 diabetes, newly diagnosed or poorly controlled type 2 diabetes
- Uncontrolled hypertension
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Evolocumab Evolocumab Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy. Evolocumab Atorvastatin Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy. Evolocumab Ezetimibe Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy. Evolocumab Diet Only Participants received evolocumab 420 mg subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy. Placebo Placebo Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy. Placebo Diet Only Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy. Placebo Ezetimibe Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy. Placebo Atorvastatin Participants received placebo subcutaneously once a month for 52 weeks in addition to background lipid-lowering therapy.
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in LDL-C at Week 52 Baseline and Week 52 Cholesterol was measured by means of ultracentrifugation.
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 52 Baseline and Week 52 Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 52 Baseline and Week 52 Percent Change From Baseline in Lipoprotein(a) at Week 52 Baseline and Week 52 Percent Change From Baseline in Triglycerides at Week 52 Baseline and Week 52 Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 52 Baseline and Week 52 Change From Baseline in LDL-C at Week 52 Baseline and Week 52 Cholesterol was measured by means of ultracentrifugation.
Percentage of Participants With an LDL-C Response at Week 52 Week 52 An LDL-C response is defined as LDL-C level \< 70 mg/dL (1.8 mmol/L) at Week 52.
Percent Change From Baseline in LDL-C at Week 12 Baseline and Week 12 Cholesterol was measured by means of ultracentrifugation.
Percent Change From Baseline in Total Cholesterol at Week 12 Baseline and Week 12 Percent Change From Baseline in Total Cholesterol at Week 52 Baseline and Week 52 Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) at Week 52 Baseline and Week 52 Percent Change From Baseline in Apolipoprotein B at Week 52 Baseline and Week 52 Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 52 Baseline and Week 52 Cholesterol was measured by means of ultracentrifugation.
Percent Change From Week 12 to Week 52 in LDL-C Week 12 and Week 52 Cholesterol was measured by means of ultracentrifugation.
Trial Locations
- Locations (1)
Research Site
🇿🇦Bloemfontein, South Africa