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

Hypercholesterolemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01154036
• Other study ID #: 0653C-162
• Secondary ID: 2010_517
• Status: Completed
• Phase: Phase 3
• Start date: July 2010
• Est. completion date: October 2012

Study information

• Verified date: February 2022
• Source: Organon and Co
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1547
• Est. completion date: October 2012
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypercholesterolemia

Intervention

Drug:
• ezetimibe 10 mg

• atorvastatin

• Comparator: rosuvastatin

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Organon and Co

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (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	Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C) (Phase II).	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
Secondary	Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase I)		Week 6 (End of Phase I)
Secondary	Percentage of Participants That Reach Target LDL-C Level of < 100 mg/dL (Phase II)		Week 12 (End of Phase II)
Secondary	Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase I)		Week 6 (End of Phase I)
Secondary	Percentage of Participants That Reach Target LDL-C Level of < 70 mg/dL (Phase II)		Week 12 (end of Phase II)
Secondary	Percent Change From Baseline in Total Cholesterol (TC) (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)
Secondary	Percent Change From Baseline in Total Cholesterol (TC) (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)
Secondary	Percent Change From Baseline in Triglycerides (TG) (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)
Secondary	Percent Change From Baseline in Triglycerides (TG) (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)
Secondary	Percent Change From Baseline in High-density Lipoprotein-Cholesterol (HDL-C) (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)
Secondary	Percent Change From Baseline in HDL-C (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)
Secondary	Percent Change From Baseline in Apolipoprotein B (Apo B) (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)
Secondary	Percent Change From Baseline in Apo B (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)
Secondary	Percent Change From Baseline in Apolipoprotein A-I (Apo A-I) (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)
Secondary	Percent Change From Baseline in Apo A-I (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)
Secondary	Percent Change From Baseline in Non-HDL-C (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)
Secondary	Percent Change From Baseline in Non-HDL-C (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)
Secondary	Percent Change From Baseline in TC/HDL-C Ratio (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)
Secondary	Percent Change From Baseline in TC/HDL-C Ratio (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)
Secondary	Percent Change From Baseline in LDL-C/HDL-C Ratio (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)
Secondary	Percent Change From Baseline in LDL-C/HDL-C Ratio (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)
Secondary	Percent Change From Baseline in Apo B/Apo A-I Ratio (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)
Secondary	Percent Change From Baseline in Apo B/Apo A-I Ratio (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)
Secondary	Percent Change From Baseline in Non-HDL-C/HDL-C Ratio (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)
Secondary	Percent Change From Baseline in Non-HDL-C/HDL-C Ratio (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)
Secondary	Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) (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)
Secondary	Percent Change From Baseline in Hs-CRP (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)