Trial record 3 of 3 for:    mk-0653c

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: June 23, 2014
Last verified: June 2014
  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: June 23, 2014
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 July 22, 2014