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A multicenter, randomized, double-blind, placebo-controlled, factorial design study to evaluate the lipid-altering efficacy and safety profile of the ezetimibe/simvastatin tablet compared with ezetimibe and simvastatin monotherapy in patients with primary hypercholesterolemia.
Clin Ther. 2004 Nov; 26(11):1758-73.CT

Abstract

OBJECTIVE

The purpose of this study was to evaluate the efficacy and safety profile of ezetimibe/simvastatin(EZE/SIMVA) combination tablet, relative to ezetimibe (EZE) and simvastatin (SIMVA) monotherapy, in patients with primary hypercholesterolemia.

METHODS

This was a randomized, multicenter, double-blind, placebo-controlled, factorial design study After a 6- to 8-week washout period and 4-week, single-blind, placebo run in, hypercholesterolemic patients (low-density lipoprotein cholesterol [LDL-C], 145-250 mg/dL; triglycerides [TG], < or =350 mg/dL) were randomized equally to 1 of 10 daily treatments for 12 weeks: EZE/SIMVA 10/10, 10/20, 10/40, or 10/80 mg; SIMVA 10, 20, 40, or 80 mg; EZE 10 mg; or placebo. The primary efficacy analysis was mean percent change from baseline in LDL-C to study end point Secondary end points included percent changes in other lipid variables and C-reactive protein [CRP].

RESULTS

There were 1528 patients randomized to treatment (792 women, 736 men); mean (SD) age ranged from 54.9 (112) years to 56.4 (10.6) years across pooled treatment groups. The treatment groups were well balanced for baseline demographics. Pooled EZE/SIMVA was associated with greater reductions in LDL-C than pooled SIMVA or EZE alone (P < 0.001). Depending on dose, EZE/SIMVA was associated with reductions in LDL-C of -44.8% to -602%, non-high-density lipoprotein cholesterol of -40.5% to -55.7%, and TG of -22.5% to -30.7%; high-density lipoprotein cholesterol increased by 5.5% to 9.8%. EZE/SIMVA was associated with greater reductions in CRP and remnant-like particle-cholesterol than SIMVA alone (P < 0.001). More patients receiving EZE/SIMVA versus SIMVA achieved LDL-C concentrations <100 mg/dL (78.6% vs 45.9%; P < 0.001). EZE/SIMVA was generally well tolerated, with a safety profile similar to SIMVA monotherapy There were no significant differences between EZE/SIMVA and SIMVA in the incidence of consecutive liver transaminase levels > or =3 times the upper limit of normal (ULN) (1 .5% for EZE/SIMVA and 1.1% for SIMVA; P = NS) or creature kinase levels > or =10 times ULN (0.0% for EZE/SIMVA and 02% for SIMVA; P = NS).

CONCLUSION

The EZE/SIMVA tablet was a highly effective and well-tolerated LDL-C-lowering therapy in this study of patients with primary hypercholesterolemia.

Authors+Show Affiliations

Bays HE
Louisville Metabolic and Atherosclerosis Research Center, 3288 Illinois Avenue, Louisville, KY 40213, USA. HBaysMD@aol.com
Ose L
No affiliation info available
Fraser N
No affiliation info available
Tribble DL
No affiliation info available
Quinto K
No affiliation info available
Reyes R
No affiliation info available
Johnson-Levonas AO
No affiliation info available
Sapre A
No affiliation info available
Donahue SR
No affiliation info available
Ezetimibe Study Group
No affiliation info available

MeSH

Administration, OralAlanine TransaminaseAnticholesteremic AgentsAspartate AminotransferasesAzetidinesCholesterol, LDLData Interpretation, StatisticalDouble-Blind MethodDrug CombinationsEzetimibeFemaleHumansHypercholesterolemiaMaleMiddle AgedSimvastatinTabletsTriglycerides

Pub Type(s)

Clinical Trial
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15639688

Clinical Trial Links

Effects of Simvastatin and Ezetimibe on Cardiovascular Risk Markers in Patients With Dyslipidemia
A Study of MK0653A (Ezetimibe (+) Simvastatin) in Patients With Hypercholesterolemia (0653A-038)
An Extension Study of An Investigational Drug in Patients With Hypercholesterolemia (0653A-038)(COMPLETED)

Citation

Bays, Harold E., et al. "A Multicenter, Randomized, Double-blind, Placebo-controlled, Factorial Design Study to Evaluate the Lipid-altering Efficacy and Safety Profile of the Ezetimibe/simvastatin Tablet Compared With Ezetimibe and Simvastatin Monotherapy in Patients With Primary Hypercholesterolemia." Clinical Therapeutics, vol. 26, no. 11, 2004, pp. 1758-73.
Bays HE, Ose L, Fraser N, et al. A multicenter, randomized, double-blind, placebo-controlled, factorial design study to evaluate the lipid-altering efficacy and safety profile of the ezetimibe/simvastatin tablet compared with ezetimibe and simvastatin monotherapy in patients with primary hypercholesterolemia. Clin Ther. 2004;26(11):1758-73.
Bays, H. E., Ose, L., Fraser, N., Tribble, D. L., Quinto, K., Reyes, R., Johnson-Levonas, A. O., Sapre, A., & Donahue, S. R. (2004). A multicenter, randomized, double-blind, placebo-controlled, factorial design study to evaluate the lipid-altering efficacy and safety profile of the ezetimibe/simvastatin tablet compared with ezetimibe and simvastatin monotherapy in patients with primary hypercholesterolemia. Clinical Therapeutics, 26(11), 1758-73.
Bays HE, et al. A Multicenter, Randomized, Double-blind, Placebo-controlled, Factorial Design Study to Evaluate the Lipid-altering Efficacy and Safety Profile of the Ezetimibe/simvastatin Tablet Compared With Ezetimibe and Simvastatin Monotherapy in Patients With Primary Hypercholesterolemia. Clin Ther. 2004;26(11):1758-73. PubMed PMID: 15639688.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A multicenter, randomized, double-blind, placebo-controlled, factorial design study to evaluate the lipid-altering efficacy and safety profile of the ezetimibe/simvastatin tablet compared with ezetimibe and simvastatin monotherapy in patients with primary hypercholesterolemia. AU - Bays,Harold E, AU - Ose,Leiv, AU - Fraser,Neil, AU - Tribble,Diane L, AU - Quinto,Katherine, AU - Reyes,Robert, AU - Johnson-Levonas,Amy O, AU - Sapre,Aditi, AU - Donahue,Steven R, AU - ,, PY - 2004/09/30/accepted PY - 2005/1/11/pubmed PY - 2005/3/30/medline PY - 2005/1/11/entrez SP - 1758 EP - 73 JF - Clinical therapeutics JO - Clin Ther VL - 26 IS - 11 N2 - OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety profile of ezetimibe/simvastatin(EZE/SIMVA) combination tablet, relative to ezetimibe (EZE) and simvastatin (SIMVA) monotherapy, in patients with primary hypercholesterolemia. METHODS: This was a randomized, multicenter, double-blind, placebo-controlled, factorial design study After a 6- to 8-week washout period and 4-week, single-blind, placebo run in, hypercholesterolemic patients (low-density lipoprotein cholesterol [LDL-C], 145-250 mg/dL; triglycerides [TG], < or =350 mg/dL) were randomized equally to 1 of 10 daily treatments for 12 weeks: EZE/SIMVA 10/10, 10/20, 10/40, or 10/80 mg; SIMVA 10, 20, 40, or 80 mg; EZE 10 mg; or placebo. The primary efficacy analysis was mean percent change from baseline in LDL-C to study end point Secondary end points included percent changes in other lipid variables and C-reactive protein [CRP]. RESULTS: There were 1528 patients randomized to treatment (792 women, 736 men); mean (SD) age ranged from 54.9 (112) years to 56.4 (10.6) years across pooled treatment groups. The treatment groups were well balanced for baseline demographics. Pooled EZE/SIMVA was associated with greater reductions in LDL-C than pooled SIMVA or EZE alone (P < 0.001). Depending on dose, EZE/SIMVA was associated with reductions in LDL-C of -44.8% to -602%, non-high-density lipoprotein cholesterol of -40.5% to -55.7%, and TG of -22.5% to -30.7%; high-density lipoprotein cholesterol increased by 5.5% to 9.8%. EZE/SIMVA was associated with greater reductions in CRP and remnant-like particle-cholesterol than SIMVA alone (P < 0.001). More patients receiving EZE/SIMVA versus SIMVA achieved LDL-C concentrations <100 mg/dL (78.6% vs 45.9%; P < 0.001). EZE/SIMVA was generally well tolerated, with a safety profile similar to SIMVA monotherapy There were no significant differences between EZE/SIMVA and SIMVA in the incidence of consecutive liver transaminase levels > or =3 times the upper limit of normal (ULN) (1 .5% for EZE/SIMVA and 1.1% for SIMVA; P = NS) or creature kinase levels > or =10 times ULN (0.0% for EZE/SIMVA and 02% for SIMVA; P = NS). CONCLUSION: The EZE/SIMVA tablet was a highly effective and well-tolerated LDL-C-lowering therapy in this study of patients with primary hypercholesterolemia. SN - 0149-2918 UR - https://www.unboundmedicine.com/medline/citation/15639688/A_multicenter_randomized_double_blind_placebo_controlled_factorial_design_study_to_evaluate_the_lipid_altering_efficacy_and_safety_profile_of_the_ezetimibe/simvastatin_tablet_compared_with_ezetimibe_and_simvastatin_monotherapy_in_patients_with_primary_hypercholesterolemia_ DB - PRIME DP - Unbound Medicine ER -