Study of Low-Density Lipoprotein Cholesterol (LDL-C) Reduction Using Evolocumab (AMG 145) in Japanese Patients With Advanced Cardiovascular Risk
- Conditions
- Hyperlipidemia or Mixed Dyslipidemia at High Risk for Cardiovascular Events
- Interventions
- Registration Number
- NCT01953328
- Lead Sponsor
- Amgen
- Brief Summary
The primary objective of the study was to evaluate the effect of 12 weeks of subcutaneous evolocumab administered every 2 weeks and once a month, compared with placebo, on percent change from baseline in LDL-C when used in combination with statin therapy in adults with high cardiovascular risk and with hyperlipidemia or mixed dyslipidemia.
- Detailed Description
After a screening and placebo run-in period, eligible patients were randomized in a 1:1 ratio to 1 of 2 open-label background statin treatments (atorvastatin 5 mg or 20 mg daily \[QD\]) and entered a 4-week lipid stabilization period. After the lipid stabilization period, eligible patients were randomized in a 1:1:1:1 ratio to investigational product (evolocumab or placebo) for the 12-week treatment period.
Both randomizations were stratified by subject diagnosis and lipid-lowering therapy as follows:
* current or prior diagnosis of heterozygous familial hypercholesterolemia (HeFH)
* no diagnosis of HeFH and receiving intensive lipid-lowering therapy
* no diagnosis of HeFH and receiving non-intensive lipid-lowering therapy. A participant was considered randomized into the study after successfully completing the screening period, meeting all inclusion/exclusion criteria including meeting final laboratory safety criteria, and undergoing both randomization procedures.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 409
Male or female, Japanese adult, 20-85 years of age; Subjects on stable dose of statin for greater than equal to 4 weeks; Fasting LDL-C greater than equal to 100 mg/dL; Fasting triglycerides less than equal to 400 mg/dL; Subject is at high risk for cardiovascular events.
New York heart Association (NYHA) III or IV - heart failure; Uncontrolled cardiac arrhythmia; Uncontrolled hypertension; Type 1 diabetes, poorly controlled type 2 diabetes; Uncontrolled hypothyroidism or hyperthyroidism
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A5 Placebo QM Placebo to Evolocumab Participants received atorvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month (QM) for 12 weeks. A20 Evolocumab Q2W Evolocumab Participants received atorvastatin 20 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. A5 Evolocumab Q2W Evolocumab Participants received atorvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. A20 Placebo QM Placebo to Evolocumab Participants received atorvastatin 20 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month for 12 weeks. A5 Evolocumab QM Evolocumab Participants received atorvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for 12 weeks. A20 Placebo Q2W Placebo to Evolocumab Participants received atorvastatin 20 mg (A20) once daily during the 4 week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for 12 weeks. A5 Placebo Q2W Placebo to Evolocumab Participants received atorvastatin 5 mg (A5) once daily during the 4 week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks. A20 Evolocumab QM Evolocumab Participants received atorvastatin 20 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for 12 weeks. A5 Placebo Q2W Atorvastatin Participants received atorvastatin 5 mg (A5) once daily during the 4 week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks (Q2W) for 12 weeks. A5 Placebo QM Atorvastatin Participants received atorvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month (QM) for 12 weeks. A5 Evolocumab Q2W Atorvastatin Participants received atorvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. A5 Evolocumab QM Atorvastatin Participants received atorvastatin 5 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for 12 weeks. A20 Placebo Q2W Atorvastatin Participants received atorvastatin 20 mg (A20) once daily during the 4 week lipid stabilization period and then in combination with placebo subcutaneous injection once every 2 weeks for 12 weeks. A20 Placebo QM Atorvastatin Participants received atorvastatin 20 mg a day during the 4-week lipid stabilization period and then in combination with placebo subcutaneous injection once every month for 12 weeks. A20 Evolocumab Q2W Atorvastatin Participants received atorvastatin 20 mg a day during the 4-week lipid stabilization period and then in combination with 140 mg evolocumab by subcutaneous injection once every 2 weeks for 12 weeks. A20 Evolocumab QM Atorvastatin Participants received atorvastatin 20 mg a day during the 4-week lipid stabilization period and then in combination with 420 mg evolocumab by subcutaneous injection once a month for 12 weeks.
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12 Baseline and Week 12 Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at the Mean of Weeks 10 and 12 Baseline and Weeks 10 and 12
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in VLDL-C at the Mean of Weeks 10 and 12 Baseline and Weeks 10 and 12 Change From Baseline in LDL-C at the Mean of Weeks 10 and 12 Baseline and Weeks 10 and 12 Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12 Baseline and Weeks 10 and 12 Percent Change From Baseline in Apolipoprotein B at Week 12 Baseline and Week 12 Percent Change From Baseline in Total Cholesterol at Week 12 Baseline and Week 12 Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 Baseline and Week 12 Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A-1 Ratio at the Mean of Weeks 10 and 12 Baseline and Weeks 10 and 12 Percentage of Participants Who Achieved LDL-C < 70 mg/dL at Week 12 Week 12 Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at the Mean of Weeks 10 and 12 Baseline and Weeks 10 and 12 Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL Weeks 10 and 12 Percent Change From Baseline in Lipoprotein(a) at the Mean of Weeks 10 and 12 Baseline and Weeks 10 and 12 Percent Change From Baseline in VLDL-C at Week 12 Baseline and Week 12 Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12 Baseline and Weeks 10 and 12 Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12 Baseline and Weeks 10 and 12 Percent Change From Baseline in HDL-C at Week 12 Baseline and Week 12 Percent Change From Baseline in HDL-C at the Mean of Weeks 10 and 12 Baseline and Weeks 10 and 12 Change From Baseline in LDL-C at Week 12 Baseline and Week 12 Percent Change From Baseline in Non-HDL-C at Week 12 Baseline and Week 12 Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12 Baseline and Weeks 10 and 12 Percent Change From Baseline in the Apolipoprotein B/Apolipoprotein A-1 Ratio at Week 12 Baseline and Week 12 Percent Change From Baseline in Lipoprotein(a) at Week 12 Baseline and Week 12 Percent Change From Baseline in Triglycerides at Week 12 Baseline and Week 12
Trial Locations
- Locations (1)
Research Site
🇯🇵Toshima-ku, Tokyo, Japan