- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01154036
MK0653C in High Cardiovascular Risk Patients With High Cholesterol (Switch Study)(MK-0653C-162)
February 7, 2022 updated by: Organon and Co
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
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.
Study Overview
Status
Completed
Conditions
Intervention / 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).
Study Type
Interventional
Enrollment (Actual)
1547
Phase
- Phase 3
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 79 years (ADULT, OLDER_ADULT)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: DOUBLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: 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
|
|
ACTIVE_COMPARATOR: Phase I: Atorvastatin 20 mg
Atorvastatin 20 mg tablet once daily for 6 weeks
|
|
ACTIVE_COMPARATOR: Phase I: Rosuvastatin 10 mg
Rosuvastatin 10 mg tablet once daily for 6 weeks
|
|
EXPERIMENTAL: 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
|
|
EXPERIMENTAL: 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
|
|
ACTIVE_COMPARATOR: 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
|
|
EXPERIMENTAL: 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
|
|
ACTIVE_COMPARATOR: Phase II: Rosuvastatin 20mg
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
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase I)
Time Frame: 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).
|
Baseline and Week 6 (end of Phase I )
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase II).
Time Frame: Baseline (Week 6) and Week 12
|
LDL-C levels measured at Baseline (Week 6; end of Phase 1) and after 6 weeks of study drug administration (Week 12).
Baseline was defined as the average of the values at Visits 5 and 6.
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).
|
Baseline (Week 6) and Week 12
|
Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase I)
Time Frame: Week 6 (End of Phase I)
|
Week 6 (End of Phase I)
|
|
Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase II)
Time Frame: Week 12 (End of Phase II)
|
Week 12 (End of Phase II)
|
|
Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase I)
Time Frame: Week 6 (End of Phase I)
|
Week 6 (End of Phase I)
|
|
Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase II)
Time Frame: Week 12 (end of Phase II)
|
Week 12 (end of Phase II)
|
|
Percent Change From Baseline in Total Cholesterol (TC) (Phase I)
Time Frame: Baseline and Week 6 (end of Phase I)
|
TC 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
|
Baseline and Week 6 (end of Phase I)
|
Percent Change From Baseline in Total Cholesterol (TC) (Phase II)
Time Frame: Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II)
|
TC levels measured at Baseline (end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II).
Baseline was defined as the average of the values at Visits 5 and 6.
|
Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II)
|
Percent Change From Baseline in Triglycerides (TG) (Phase I)
Time Frame: Baseline and Week 6 (end of Phase I)
|
TG 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. Baseline and post-baseline measurements were log-transformed in the response vector, with fixed effects for treatment, time and the interaction of time by treatment.
|
Baseline and Week 6 (end of Phase I)
|
Percent Change From Baseline in Triglycerides (TG) (Phase II)
Time Frame: Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II)
|
TG levels measured at Baseline (Week 6: end of Phase I) and after 6 weeks of study drug administration (Week 12; end of Phase II).
Baseline was defined as the average of the values at Visits 5 and 6.
Baseline and post-baseline measurements were log-transformed in the response vector, with fixed effects for treatment, time and the interaction of time by treatment.
|
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)
Time Frame: Baseline and Week 6 (end of Phase I)
|
HDL-C 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
|
Baseline and Week 6 (end of Phase I)
|
Percent Change From Baseline in HDL-C (Phase II)
Time Frame: Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II)
|
HDL-C levels measured at Baseline (end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II).
Baseline was defined as the average of the values at Visits 5 and 6.
|
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)
Time Frame: Baseline and Week 6 (end of Phase I)
|
Apo-B 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
|
Baseline and Week 6 (end of Phase I)
|
Percent Change From Baseline in Apo B (Phase II)
Time Frame: Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II)
|
Apo-B levels measured at Baseline (Week 6; end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II).
Baseline was defined as the average of the values at Visits 5 and 6.
|
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)
Time Frame: Baseline and Week 6 (end of Phase I)
|
Apo-A-I 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
|
Baseline and Week 6 (end of Phase I)
|
Percent Change From Baseline in Apo A-I (Phase II)
Time Frame: Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II)
|
Apo-A-I levels measured at Baseline (end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II).
Baseline was defined as the average of the values at Visits 5 and 6.
|
Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II)
|
Percent Change From Baseline in Non-HDL-C (Phase I)
Time Frame: Baseline and Week 6 (end of Phase I)
|
Non-HDL-C 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
|
Baseline and Week 6 (end of Phase I)
|
Percent Change From Baseline in Non-HDL-C (Phase II)
Time Frame: Baseline (Week 6; end of Phase I) and Week 12 (end of Phase II)
|
Non-HDL-C levels calculated at Baseline (end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II).
Baseline was defined as the average of the values at Visits 5 and 6.
|
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)
Time Frame: Baseline and Week 6 (end of Phase I)
|
TC/HDL-C ratio calculated 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
|
Baseline and Week 6 (end of Phase I)
|
Percent Change From Baseline in TC/HDL-C Ratio (Phase II)
Time Frame: Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II)
|
TC/HDL-C Ratio calculated at Baseline (end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II).
Baseline was defined as the average of the values at Visits 5 and 6.
|
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)
Time Frame: Baseline and Week 6 (end of Phase I)
|
LDL-C/HDL-C ratio calculated 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
|
Baseline and Week 6 (end of Phase I)
|
Percent Change From Baseline in LDL-C/HDL-C Ratio (Phase II)
Time Frame: Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II)
|
LDL-C/HDL-C Ratio calculated at Baseline (end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II).
Baseline was defined as the average of the values at Visits 5 and 6.
|
Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II)
|
Percent Change From Baseline in Apo B/Apo A-I Ratio (Phase I)
Time Frame: Baseline and Week 6 (end of Phase I)
|
Apo B/Apo A-I ratio calculated 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
|
Baseline and Week 6 (end of Phase I)
|
Percent Change From Baseline in Apo B/Apo A-I Ratio (Phase II)
Time Frame: Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II)
|
Apo B/Apo A-I Ratio calculated at Baseline (Week 6; end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II).
Baseline was defined as the average of the values at Visits 5 and 6.
|
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)
Time Frame: Baseline and Week 6 (end of Phase I)
|
Non HDL-C/HDL-C ratio calculated 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
|
Baseline and Week 6 (end of Phase I)
|
Percent Change From Baseline in Non-HDL-C/HDL-C Ratio (Phase II)
Time Frame: Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II)
|
Non HDL-C/HDL-C Ratio calculated at baseline (Week 6; end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II).
Baseline was defined as the average of the values at Visits 5 and 6.
|
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)
Time Frame: Baseline and Week 6 (end of Phase I)
|
hs-CRP 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. Baseline and post-baseline measurements were log-transformed in the response vector, with fixed effects for treatment, time and the interaction of time by treatment.
|
Baseline and Week 6 (end of Phase I)
|
Percent Change From Baseline in Hs-CRP (Phase II)
Time Frame: Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II)
|
hs-CRP measured at Baseline (Week 6; end of Phase 1) and after 6 weeks of study drug administration (Week 12; end of Phase II).
Baseline was defined as the average of the values at Visits 5 and 6.
Baseline and post-baseline measurements were log-transformed in the response vector, with fixed effects for treatment, time and the interaction of time by treatment.
|
Baseline (Week 6; end of Phase 1) and Week 12 (end of Phase II)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
July 1, 2010
Primary Completion (ACTUAL)
September 1, 2012
Study Completion (ACTUAL)
October 1, 2012
Study Registration Dates
First Submitted
June 29, 2010
First Submitted That Met QC Criteria
June 29, 2010
First Posted (ESTIMATE)
June 30, 2010
Study Record Updates
Last Update Posted (ACTUAL)
February 9, 2022
Last Update Submitted That Met QC Criteria
February 7, 2022
Last Verified
February 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Metabolic Diseases
- Lipid Metabolism Disorders
- Hyperlipidemias
- Dyslipidemias
- Hypercholesterolemia
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Atorvastatin
- Rosuvastatin Calcium
- Ezetimibe
Other Study ID Numbers
- 0653C-162
- 2010_517 (OTHER: Merck Study Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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