Fixed-dose combination ezetimibe+atorvastatin lowers LDL-C equivalent to co-administered components in randomized trials: use of a dose-response model.

摘要: Abstract Co-administration of ezetimibe with atorvastatin is a generally well-tolerated treatment option that reduces LDL-C levels and improves other lipids greater efficacy than doubling the dose. The objective study was to demonstrate equivalent lipid-modifying fixed-dose combination (FDC) ezetimibe/atorvastatin compared component agents co-administered individually in support regulatory filing. Two randomized, 6-week, double-blind cross-over trials 10/20 mg (n = 353) or 10/40 mg (n = 280) vs. separate co-administration 10 mg plus 20 mg (n = 346) 40 mg (n = 280), respectively, hypercholesterolemic patients. Percent changes from baseline (primary endpoint) (secondary endpoints) were assessed by analysis covariance; triglycerides evaluated longitudinal-data analysis. Expected differences between FDC corresponding doses predicted dose-response relationship model; sample size estimated given expected difference equivalence margins (±4%). LDL-C-lowering based on 97.5% expanded confidence intervals (CI) for contained within margins; not prespecified. Ezetimibe/atorvastatin ezetimibe+atorvastatin reducing (54.0% 53.8%) as (58.9% 58.7%), model. Changes consistent (97.5% CIs <±3%, included 0); triglyceride varied more. All treatments well tolerated. Hypercholesterolemic patients administered 10/20 had lowering. This formulation proved be an efficacious lipid-lowering therapy.