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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT01154036
First received: June 29, 2010
Last updated: December 23, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Hypercholesterolemia
Drug: ezetimibe 10 mg
Drug: atorvastatin
Drug: Comparator: rosuvastatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase I) [ Time Frame: Baseline and Week 6 (end of Phase I ) ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase II). [ Time Frame: Baseline (Week 6) and Week 12 ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase I) [ Time Frame: Week 6 (End of Phase I) ] [ Designated as safety issue: No ]
  • Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase II) [ Time Frame: Week 12 (End of Phase II) ] [ Designated as safety issue: No ]
  • Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase I) [ Time Frame: Week 6 (End of Phase I) ] [ Designated as safety issue: No ]
  • Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase II) [ Time Frame: Week 12 (end of Phase II) ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Total Cholesterol (TC) (Phase I) [ Time Frame: Baseline and Week 6 (end of Phase I) ] [ Designated as safety issue: No ]
    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

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in Triglycerides (TG) (Phase I) [ Time Frame: Baseline and Week 6 (end of Phase I) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in High-density Lipoprotein-Cholesterol (HDL-C) (Phase I) [ Time Frame: Baseline and Week 6 (end of Phase I) ] [ Designated as safety issue: No ]
    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

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in Apolipoprotein B (Apo B) (Phase I) [ Time Frame: Baseline and Week 6 (end of Phase I) ] [ Designated as safety issue: No ]
    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

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in Apolipoprotein A-I (Apo A-I) (Phase I) [ Time Frame: Baseline and Week 6 (end of Phase I) ] [ Designated as safety issue: No ]
    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

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in Non-HDL-C (Phase I) [ Time Frame: Baseline and Week 6 (end of Phase I) ] [ Designated as safety issue: No ]
    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

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in TC/HDL-C Ratio (Phase I) [ Time Frame: Baseline and Week 6 (end of Phase I) ] [ Designated as safety issue: No ]
    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

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in LDL-C/HDL-C Ratio (Phase I) [ Time Frame: Baseline and Week 6 (end of Phase I) ] [ Designated as safety issue: No ]
    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

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in Apo B/Apo A-I Ratio (Phase I) [ Time Frame: Baseline and Week 6 (end of Phase I) ] [ Designated as safety issue: No ]
    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

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in Non-HDL-C/HDL-C Ratio (Phase I) [ Time Frame: Baseline and Week 6 (end of Phase I) ] [ Designated as safety issue: No ]
    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

  • 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) ] [ Designated as safety issue: No ]
    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.

  • Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) (Phase I) [ Time Frame: Baseline and Week 6 (end of Phase I) ] [ Designated as safety issue: No ]
    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.

  • 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) ] [ Designated as safety issue: No ]
    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.


Enrollment: 1547
Study Start Date: July 2010
Study Completion Date: October 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: ezetimibe 10 mg Drug: atorvastatin
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: ezetimibe 10 mg Drug: atorvastatin
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: ezetimibe 10 mg Drug: atorvastatin
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: ezetimibe 10 mg Drug: atorvastatin
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

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

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01154036

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

No publications provided by Merck Sharp & Dohme Corp.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01154036     History of Changes
Other Study ID Numbers: 0653C-162, 2010_517
Study First Received: June 29, 2010
Results First Received: September 5, 2013
Last Updated: December 23, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Atorvastatin
Rosuvastatin
Ezetimibe
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Enzyme Inhibitors
Lipid Regulating Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014