Study of Low-Density Lipoprotein Cholesterol (LDL-C) Reduction Using Evolocumab (AMG 145) in Japanese Patients With Advanced Cardiovascular Risk (AMG145)

Amgen

Status and phase: Completed; Phase 3

Conditions: Hyperlipidemia or Mixed Dyslipidemia at High Risk for Cardiovascular Events

Treatments: Other: Placebo to Evolocumab; Biological: Evolocumab; Drug: Atorvastatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01953328

20120122

Details and patient eligibility

About

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.

Full 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.

Enrollment: 409 patients

Sex: All

Ages: 20 to 85 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria: 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. Exclusion Criteria: 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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409 participants in 8 patient groups, including a placebo group

A5 Placebo Q2W

Placebo Comparator group

Description:

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.

Treatment:

Drug: Atorvastatin

Other: Placebo to Evolocumab

A5 Placebo QM

Placebo Comparator group

Description:

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.

Treatment:

Drug: Atorvastatin

Other: Placebo to Evolocumab

A5 Evolocumab Q2W

Experimental group

Description:

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.

Treatment:

Drug: Atorvastatin

Biological: Evolocumab

A5 Evolocumab QM

Experimental group

Description:

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.

Treatment:

Drug: Atorvastatin

Biological: Evolocumab

A20 Placebo Q2W

Placebo Comparator group

Description:

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.

Treatment:

Drug: Atorvastatin

Other: Placebo to Evolocumab

A20 Placebo QM

Other group

Description:

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.

Treatment:

Drug: Atorvastatin

Other: Placebo to Evolocumab

A20 Evolocumab Q2W

Experimental group

Description:

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.

Treatment:

Drug: Atorvastatin

Biological: Evolocumab

A20 Evolocumab QM

Experimental group

Description:

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.

Treatment:

Drug: Atorvastatin

Biological: Evolocumab