LDL-C Assessment With PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy-2
Condition: Hyperlipidemia
MeSH terms: Hyperlipidemias
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Evolocumab; Ezetimibe; Placebo to Evolocumab; Placebo to Ezetimibe; Atorvastatin; Rosuvastatin; Simvastatin
Intervention type(s): Biological; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Administered by subcutaneous injection; Administered orally once a day; Administered by subcutaneous injection; Administered orally once a day; Administered orally once a day; Administered orally once a day; Administered orally once a day
Other intervention name(s): AMG 145; Repatha; Zetia; Lipitor; Crestor; Zocor
Intervention MeSH terms: Atorvastatin; Rosuvastatin Calcium; Simvastatin; Ezetimibe; Evolocumab; Antibodies, Monoclonal
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: High cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia