Clinical trial NCT01953328
Conditions: Hyperlipidemia or Mixed Dyslipidemia at High Risk for Cardiovascular Events
Keywords: Japanese, high cholesterol, LDL-C, High Cardiovascular Risk
Sponsor: Amgen
Start date: 2013-10-01; Completion date: 2014-06-01
Enrollment: 409 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: 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. arm 2: 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. arm 3: 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. arm 4: 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. arm 5: 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. arm 6: 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. arm 7: 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. arm 8: 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.
Interventions: intervention 1: Atorvastatin intervention 2: Evolocumab intervention 3: Placebo to Evolocumab
Intervention descriptions: intervention 1: Administered orally once a day intervention 2: Administered by subcutaneous injection intervention 3: Administered by subcutaneous injection

Protocol documents: