Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-4

Amgen61 enrolled

Overview

The primary objective of the study was to evaluate the effect of 12 weeks of subcutaneous (SC) evolocumab compared with ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic adults unable to tolerate an effective dose of a statin.

After screening participants who met all inclusion/exclusion criteria were randomized with an allocation ratio of 2:2:1:1 into 4 groups: evolocumab (AMG 145) 420 mg administered by subcutaneous injection monthly and placebo pill daily; evolocumab 140 mg administered by subcutaneous injection every two weeks and placebo pill by mouth daily; placebo 420 mg administered by subcutaneous injection monthly and ezetimibe 10 mg pill daily; placebo 140 mg administered subcutaneous injection every two weeks and ezetimibe 10 mg pill daily. Randomization was stratified by screening LDL-C level and baseline statin use. Participants on low or atypical statin dose therapy must have been on a stable dose for at least 4 weeks prior to screening and throughout the blinded portion of the study; the dose could not be adjusted during screening and for the duration of the study. After Week 12, ezetimibe was discontinued and participants moved to an open-label dose of evolocumab administered by subcutaneous injection either every two weeks or monthly and their standard of care.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Hypercholesterolemia

Interventions

EvolocumabBIOLOGICAL

Administered by subcutaneous injection

EzetimibeDRUG

Tablet for oral administration

Placebo to EvolocumabDRUG

Administered by subcutaneous injection

Placebo Ezetimibe

Eligibility

Sex: ALLMin age: 20 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Male or female ≥ 20 to ≤ 80 years of age * Japanese by self-identification * Not on a statin or on a low dose statin with stable dose for at least 4 weeks. * Subject not at LDL-C goal * History of statin intolerance to at least 2 statins * Lipid lowering therapy has been stable prior to screening for at least 4 weeks * Fasting triglycerides ≤ 400 mg/dL 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

Locations (35)

Outcomes

Primary Outcomes

Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at the Mean of Weeks 10 and 12

For all efficacy endpoints the two dosing regimens (every 2 weeks and every month) for each treatment were pooled for analysis.

Time frame: Baseline and Weeks 10 and 12

Percent Change From Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) at Week 12

Time frame: Baseline and week 12

Secondary Outcomes

Change From Baseline in LDL-C at the Mean of Weeks 10 and 12

Time frame: Baseline and weeks 10 and 12

Change From Baseline in LDL-C at Week 12

Time frame: Baseline and week 12

Percentage of Participants Who Achieved a Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL

Mean low density lipoprotein-cholesterol response was defined as LDL-C \< 70 mg/dL \[1.8 mol/L\].

Time frame: Weeks 10 and 12

Percentage of Participants Who Achieved a LDL-C of Less Than 70 mg/dL at Week 12

Time frame: Week 12

Percent Change From Baseline in Total Cholesterol at the Mean of Weeks 10 and 12

Time frame: Baseline and weeks 10 and 12

Percent Change From Baseline in Total Cholesterol at Week 12

Time frame: Baseline and week 12

Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12

Time frame: Baseline and weeks 10 and 12

Data from ClinicalTrials.gov

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Research Site

Nagoya, Aichi-ken, Japan

Research Site

Nagoya, Aichi-ken, Japan

Research Site

Chiba, Chiba, Japan

Research Site

Kisarazu-shi, Chiba, Japan

Research Site

Matsudo-shi, Chiba, Japan

Research Site

Chikushino-shi, Fukuoka, Japan

Research Site

Koga-shi, Fukuoka, Japan

Research Site

Sukagawa-shi, Fukushima, Japan

Research Site

Sukagawa-shi, Fukushima, Japan

Research Site

Hiroshima, Hiroshima, Japan

...and 25 more locations