MK0653C in High Cardiovascular Risk Patients With High Cholesterol (Switch Study)(MK-0653C-162)

Organon

Status and phase: Completed; Phase 3

Conditions: Hypercholesterolemia

Treatments: Drug: atorvastatin; Drug: ezetimibe 10 mg; Drug: Comparator: rosuvastatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01154036

0653C-162

2010_517 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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).

Enrollment: 1,547 patients

Sex: All

Ages: 18 to 79 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,547 participants in 8 patient groups

Phase I: ezetimibe (EZ) 10 mg + atorvastatin (Atorva) 10 mg

Experimental group

Description:

Co-administration of EZ 10 mg tablet + Atorva 10 mg tablet; once daily for 6 weeks

Treatment:

Drug: atorvastatin

Drug: ezetimibe 10 mg

Phase I: Atorvastatin 20 mg

Active Comparator group

Description:

Atorvastatin 20 mg tablet once daily for 6 weeks

Treatment:

Drug: atorvastatin

Phase I: Rosuvastatin 10 mg

Active Comparator group

Description:

Rosuvastatin 10 mg tablet once daily for 6 weeks

Treatment:

Drug: Comparator: rosuvastatin

Phase II: EZ 10mg+Atorva 10mg

Experimental group

Description:

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

Treatment:

Drug: atorvastatin

Drug: ezetimibe 10 mg

Phase II: EZ 10mg + Atorva 20mg [A]

Experimental group

Description:

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

Treatment:

Drug: atorvastatin

Drug: ezetimibe 10 mg

Phase II: Atorva 40mg

Active Comparator group

Description:

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

Treatment:

Drug: atorvastatin

Phase II: EZ 10mg + Atorva 20mg [R]

Experimental group

Description:

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

Treatment:

Drug: atorvastatin

Drug: ezetimibe 10 mg

Phase II: Rosuvastatin 20mg

Active Comparator group

Description:

Participants who had previously received Rosuvastatin 10 mg in Phase I and did not reach LDL-C goal and were switched to Rosuvastatin 20 mg once daily for 6 weeks in Phase

Treatment:

Drug: Comparator: rosuvastatin