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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
1547

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
Drug: atorvastatin
Drug: ezetimibe 10 mg
ACTIVE_COMPARATOR: Phase I: Atorvastatin 20 mg
Atorvastatin 20 mg tablet once daily for 6 weeks
Drug: atorvastatin
ACTIVE_COMPARATOR: Phase I: Rosuvastatin 10 mg
Rosuvastatin 10 mg tablet once daily for 6 weeks
Drug: Comparator: rosuvastatin
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
Drug: atorvastatin
Drug: ezetimibe 10 mg
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
Drug: atorvastatin
Drug: ezetimibe 10 mg
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
Drug: atorvastatin
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
Drug: atorvastatin
Drug: ezetimibe 10 mg
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
Drug: Comparator: rosuvastatin

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Organon and Co

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

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 1, 2010

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2012

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 29, 2010

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 29, 2010

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 30, 2010

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 9, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 7, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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