A Randomized, Double-Blind, Active-Controlled, Multicenter Study of Patients With Primary Hypercholesterolemia and High Cardiovascular Risk Who Are Not Adequately Controlled With Atorvastatin 10 mg: A Comparison of the Efficacy and Safety of Switching to Coadministration Ezetimibe and Atorvastatin Versus Doubling the Dose of Atorvastatin or Switching to Rosuvastatin
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,547
- 主要终点
- Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase I)
研究概览
简要总结
This study will compare the lipid-altering efficacy and safety of switching to co-administration of ezetimibe and atorvastatin versus treatment with atorvastatin or rosuvastatin in high cardiovascular risk patients with hypercholesterolemia who have not achieved specified low-density lipoprotein cholesterol (LDL-C) levels. The primary hypothesis is that the co-administration of ezetimibe 10 mg and atorvastatin 10 mg will be superior to both atorvastatin 20 mg and rosuvastatin 10 mg with respect to the percentage reduction in low-density lipoprotein-cholesterol (LDL-C) after 6 weeks of treatment.
详细描述
This is a 18 week randomized, double-blind, active-controlled, multicenter study composed of a 6 week screening/run-in and 12 week double-blind treatment period (composed of 2 phases; each 6 weeks in duration). Only those participants who do not meet low density lipoprotein-cholesterol (LDL-C) goals at the end of Phase I (Week 6), were eligible to continue into Phase II (Week 12).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient is at high cardiovascular risk and meets one of the following conditions: has never taken lipid-lowering therapy or has been off such therapy for at least 6 weeks; or, is currently taking a stable dose of certain lipid-lowering agents
- •Patient is willing to maintain a cholesterol lowering diet during the study
- •Female patients receiving non-cyclical hormone therapy have maintained a stable dose and regimen for at least 8 weeks and are willing to continue the same regimen during the study
排除标准
- •Patient is Asian
- •Patient routinely has more than 2 alcoholic drinks per day
- •Female patient is pregnant or breastfeeding
- •Patient has congestive heart failure
- •Patient has had a myocardial infarction, coronary bypass surgery, angioplasty, or acute coronary syndrome within 3 months of screening
- •Patient has uncontrolled cardiac arrhythmias
- •Patient has had a partial ileal or gastric bypass or other significant intestinal malabsorption
- •Patient has uncontrolled high blood pressure
- •Patient has kidney disease
- •Patient has any disease known to influence blood lipid levels
- •Patient has any disorders of the blood, digestive system, or nervous system including stroke and degenerative disease that would limit study participation
- •Patient has poorly controlled or newly diagnosed diabetes
- •Patient is known to be HIV positive
- •Patient has a history of cancer in the last 5 years, except certain skin and cervical cancers
研究组 & 干预措施
Phase II: EZ 10mg+Atorva 10mg
Participants who had previously received EZ 10 mg + Atorva 10 mg in Phase I and continued on EZ 10 mg + Atorva 10 mg once daily for 6 weeks during Phase II regardless of whether or not LDL-C goals were achieved in Phase I
干预措施: ezetimibe 10 mg (Drug)
Phase I: ezetimibe (EZ) 10 mg + atorvastatin (Atorva) 10 mg
Co-administration of EZ 10 mg tablet + Atorva 10 mg tablet; once daily for 6 weeks
干预措施: ezetimibe 10 mg (Drug)
Phase II: EZ 10mg + Atorva 20mg [A]
Participants who had previously received Atorva 20 mg in Phase I and did not reach LDL-C goal and were switched to EZ 10 mg + Atorva 20 mg once daily for 6 weeks in Phase II
干预措施: ezetimibe 10 mg (Drug)
Phase II: EZ 10mg + Atorva 20mg [R]
Participants who had previously received Rosuvastatin 10 mg in Phase I and did not reach LDL-C goal and received EZ 10 mg + Atorva 20 mg once daily for 6 weeks in Phase II
干预措施: ezetimibe 10 mg (Drug)
Phase I: ezetimibe (EZ) 10 mg + atorvastatin (Atorva) 10 mg
Co-administration of EZ 10 mg tablet + Atorva 10 mg tablet; once daily for 6 weeks
干预措施: atorvastatin (Drug)
Phase I: Atorvastatin 20 mg
Atorvastatin 20 mg tablet once daily for 6 weeks
干预措施: atorvastatin (Drug)
Phase II: EZ 10mg+Atorva 10mg
Participants who had previously received EZ 10 mg + Atorva 10 mg in Phase I and continued on EZ 10 mg + Atorva 10 mg once daily for 6 weeks during Phase II regardless of whether or not LDL-C goals were achieved in Phase I
干预措施: atorvastatin (Drug)
Phase II: EZ 10mg + Atorva 20mg [A]
Participants who had previously received Atorva 20 mg in Phase I and did not reach LDL-C goal and were switched to EZ 10 mg + Atorva 20 mg once daily for 6 weeks in Phase II
干预措施: atorvastatin (Drug)
Phase II: Atorva 40mg
Participants who had previously received Atorva 20 mg in Phase I and did not reach LDL-C goal and were switched Atorva 40 mg once daily for 6 weeks in Phase II
干预措施: atorvastatin (Drug)
Phase II: EZ 10mg + Atorva 20mg [R]
Participants who had previously received Rosuvastatin 10 mg in Phase I and did not reach LDL-C goal and received EZ 10 mg + Atorva 20 mg once daily for 6 weeks in Phase II
干预措施: atorvastatin (Drug)
结局指标
主要结局
Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase I)
时间窗: Baseline and Week 6 (end of Phase I )
LDL-C levels measured at Baseline and after 6 weeks of treatment (Week 6; end of Phase I). Baseline was defined as the average value of the measurements taken at Visits 3 and 4. LDL-C was calculated using the Friedewald method when triglyceride (TG)\<350 mg/dL (3.95 mmol/L) and beta quantification ultracentrifugation when TG≥350 mg/dL (3.95 mmol/L).
次要结局
- Percent Change From Baseline in TC/HDL-C Ratio (Phase II)(Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II))
- Percent Change From Baseline in Non-HDL-C (Phase II)(Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II))
- Percent Change From Baseline in TC/HDL-C Ratio (Phase I)(Baseline and Week 6 (end of Phase I))
- Percent Change From Baseline in Apo B/Apo A-I Ratio (Phase I)(Baseline and Week 6 (end of Phase I))
- Percent Change From Baseline in Apo B/Apo A-I Ratio (Phase II)(Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II))
- Percent Change From Baseline in Non-HDL-C/HDL-C Ratio (Phase I)(Baseline and Week 6 (end of Phase I))
- Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase II).(Baseline (Week 6) and Week 12)
- Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase I)(Week 6 (End of Phase I))
- Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase II)(Week 12 (End of Phase II))
- Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase I)(Week 6 (End of Phase I))
- Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase II)(Week 12 (end of Phase II))
- Percent Change From Baseline in Total Cholesterol (TC) (Phase I)(Baseline and Week 6 (end of Phase I))
- Percent Change From Baseline in Total Cholesterol (TC) (Phase II)(Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II))
- Percent Change From Baseline in Triglycerides (TG) (Phase I)(Baseline and Week 6 (end of Phase I))
- Percent Change From Baseline in Triglycerides (TG) (Phase II)(Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II))
- Percent Change From Baseline in High-density Lipoprotein-Cholesterol (HDL-C) (Phase I)(Baseline and Week 6 (end of Phase I))
- Percent Change From Baseline in HDL-C (Phase II)(Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II))
- Percent Change From Baseline in Apolipoprotein B (Apo B) (Phase I)(Baseline and Week 6 (end of Phase I))
- Percent Change From Baseline in Apo B (Phase II)(Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II))
- Percent Change From Baseline in Apolipoprotein A-I (Apo A-I) (Phase I)(Baseline and Week 6 (end of Phase I))
- Percent Change From Baseline in Apo A-I (Phase II)(Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II))
- Percent Change From Baseline in Non-HDL-C (Phase I)(Baseline and Week 6 (end of Phase I))
- Percent Change From Baseline in Non-HDL-C/HDL-C Ratio (Phase II)(Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II))
- Percent Change From Baseline in Hs-CRP (Phase II)(Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II))
- Percent Change From Baseline in LDL-C/HDL-C Ratio (Phase I)(Baseline and Week 6 (end of Phase I))
- Percent Change From Baseline in LDL-C/HDL-C Ratio (Phase II)(Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II))
- Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) (Phase I)(Baseline and Week 6 (end of Phase I))