NCT01763866

LDL-C Assessment With PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy-2

A Double-blind, Randomized, Placebo and Ezetimibe Controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 on LDL-C in Combination With Statin Therapy in Subjects With Primary Hypercholesterolemia and Mixed Dyslipidemia

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 2,067 (actual)
• Sponsor: Amgen · Industry
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

The primary objective was to evaluate the effect of 12 weeks of evolocumab administered subcutaneously every 2 weeks (Q2W) and monthly (QM) when used in combination with a statin, compared with placebo, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in patients with primary hypercholesterolemia and mixed dyslipidemia.

Detailed description

Prior to the first randomization, participants entered a screening period to determine eligibility. During screening, all participants received subcutaneous placebo corresponding to the once monthly dose volume. Participants who completed the screening period and met eligibility criteria were randomized to 1 of 5 open-label statin cohorts (atorvastatin 10 mg or 80 mg, rosuvastatin 5 mg or 40 mg, or simvastatin 40 mg) for a 4 week lipid stabilization period based on statin therapy at the time of study entry (no statin use vs non-intensive statin use vs intensive statin use). After the 4-week lipid-stabilization period, eligible patients taking rosuvastatin or simvastatin during the lipid-stabilization phase were then randomized to 1 of 4 treatment groups: evolocumab (140 mg, subcutaneous, every 2 weeks) or matching placebo (subcutaneous, every 2 weeks), or evolocumab (420 mg, subcutaneous, monthly) or matching placebo (subcutaneous, monthly). Patients taking atorvastatin during the lipid-stabilization phase were then randomized to 1 of 6 treatment groups: evolocumab (140 mg, subcutaneous, every 2 weeks) and placebo (oral, daily), evolocumab (420 mg, subcutaneous, monthly) and placebo (oral, daily), placebo (subcutaneous, every 2 weeks) and placebo (oral, daily) or ezetimibe (10 mg, oral, daily), or placebo (subcutaneous, monthly) and placebo (oral, daily) or ezetimibe (10 mg, oral, daily). A participant was considered randomized into the study after successfully completing the screening period, meeting all inclusion/exclusion criteria, and undergoing both randomization procedures. Participants randomized to simvastatin who were taking verapamil or diltiazem prior to randomization received simvastatin 10 mg once daily (QD) while participants who were taking amlodipine, amiodarone or ranolazine prior to randomization received simvastatin 20 mg QD. All other participants randomized to simvastatin received simvastatin 40 mg QD.

Conditions

• Hyperlipidemia

Interventions

Type	Name	Description
BIOLOGICAL	Evolocumab	Administered by subcutaneous injection
DRUG	Ezetimibe	Administered orally once a day
DRUG	Placebo to Evolocumab	Administered by subcutaneous injection
DRUG	Placebo to Ezetimibe	Administered orally once a day
DRUG	Atorvastatin	Administered orally once a day
DRUG	Rosuvastatin	Administered orally once a day
DRUG	Simvastatin	Administered orally once a day

Timeline

• Start date: 2013-01-15
• Primary completion: 2013-11-12
• Completion: 2013-12-04
• First posted: 2013-01-09
• Last updated: 2022-11-08
• Results posted: 2015-12-22

Locations

244 sites across 21 countries: United States, Australia, Belgium, Canada, Czechia, Denmark, France, Germany, Hong Kong, Hungary, Italy, Mexico, Netherlands, Russia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom