Clinical trial NCT01154036: MK0653C in High Cardiovascular Risk Patients With High Cholesterol (Switch Study)(MK-0653C-162)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2010-06-30
Enrollment: 1547
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase I)
timeFrame: Baseline and Week 6 (end of Phase I )
Secondary outcomes:
measure: Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase II).
timeFrame: Baseline (Week 6) and Week 12
measure: Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase I)
timeFrame: Week 6 (End of Phase I)
measure: Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase II)
timeFrame: Week 12 (End of Phase II)
measure: Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase I)
timeFrame: Week 6 (End of Phase I)
measure: Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase II)
timeFrame: Week 12 (end of Phase II)
measure: Percent Change From Baseline in Total Cholesterol (TC) (Phase I)
timeFrame: Baseline and Week 6 (end of Phase I)
measure: Percent Change From Baseline in Total Cholesterol (TC) (Phase II)
timeFrame: Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II)
measure: Percent Change From Baseline in Triglycerides (TG) (Phase I)
timeFrame: Baseline and Week 6 (end of Phase I)
measure: Percent Change From Baseline in Triglycerides (TG) (Phase II)
timeFrame: Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II)
measure: Percent Change From Baseline in High-density Lipoprotein-Cholesterol (HDL-C) (Phase I)
timeFrame: Baseline and Week 6 (end of Phase I)
measure: Percent Change From Baseline in HDL-C (Phase II)
timeFrame: Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II)
measure: Percent Change From Baseline in Apolipoprotein B (Apo B) (Phase I)
timeFrame: Baseline and Week 6 (end of Phase I)
measure: Percent Change From Baseline in Apo B (Phase II)
timeFrame: Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II)
measure: Percent Change From Baseline in Apolipoprotein A-I (Apo A-I) (Phase I)
timeFrame: Baseline and Week 6 (end of Phase I)
measure: Percent Change From Baseline in Apo A-I (Phase II)
timeFrame: Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II)
measure: Percent Change From Baseline in Non-HDL-C (Phase I)
timeFrame: Baseline and Week 6 (end of Phase I)
measure: Percent Change From Baseline in Non-HDL-C (Phase II)
timeFrame: Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II)
measure: Percent Change From Baseline in TC/HDL-C Ratio (Phase I)
timeFrame: Baseline and Week 6 (end of Phase I)
measure: Percent Change From Baseline in TC/HDL-C Ratio (Phase II)
timeFrame: Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II)
measure: Percent Change From Baseline in LDL-C/HDL-C Ratio (Phase I)
timeFrame: Baseline and Week 6 (end of Phase I)
measure: Percent Change From Baseline in LDL-C/HDL-C Ratio (Phase II)
timeFrame: Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II)
measure: Percent Change From Baseline in Apo B/Apo A-I Ratio (Phase I)
timeFrame: Baseline and Week 6 (end of Phase I)
measure: Percent Change From Baseline in Apo B/Apo A-I Ratio (Phase II)
timeFrame: Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II)
measure: Percent Change From Baseline in Non-HDL-C/HDL-C Ratio (Phase I)
timeFrame: Baseline and Week 6 (end of Phase I)
measure: Percent Change From Baseline in Non-HDL-C/HDL-C Ratio (Phase II)
timeFrame: Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II)
measure: Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) (Phase I)
timeFrame: Baseline and Week 6 (end of Phase I)
measure: Percent Change From Baseline in Hs-CRP (Phase II)
timeFrame: Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Krempf M, Simpson RJ Jr, Ramey DR, Brudi P, Giezek H, Tomassini JE, Lee R, Farnier M. Patient and physician factors influence decision-making in hypercholesterolemia: a questionnaire-based survey. Lipids Health Dis. 2015 May 19;14:45. doi: 10.1186/s12944-015-0037-y.
citation: Bays HE, Averna M, Majul C, Muller-Wieland D, De Pellegrin A, Giezek H, Lee R, Lowe RS, Brudi P, Triscari J, Farnier M. Efficacy and safety of ezetimibe added to atorvastatin versus atorvastatin uptitration or switching to rosuvastatin in patients with primary hypercholesterolemia. Am J Cardiol. 2013 Dec 15;112(12):1885-95. doi: 10.1016/j.amjcard.2013.08.031. Epub 2013 Sep 21.