A Study to Assess the Cholesterol Lowering Effect of an Ezetimibe/Simvastatin Combination Tablet Compared to Another Cholesterol Lowering Drug in Patients With High Cholesterol and With High Cardiovascular Risk (0653A-809)(COMPLETED)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00479713
• Collaborator: (none)
• Enrollment: 618
• Arms: 2
• Actual Duration (Months): 12.9

Study Details

Study Description

Brief Summary

This is a multicenter study to evaluate the safety and efficacy of ezetimibe/simvastatin versus rosuvastatin in participants with high cholesterol.

Condition or Disease	Intervention/Treatment	Phase
Hypercholesterolemia	Drug: ezetimibe (+) simvastatin; Drug: Comparator : rosuvastatin calcium; Drug: Comparator: Placebo (unspecified); Drug: Comparator: Placebo (unspecified)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 618 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Active-Controlled, Multicenter Study to Assess the LDL-C Lowering of Switching to a Combo Tab Ezetimibe/Simvastatin (10 mg/20 mg) Compared to Rosuvastatin 10 mg in Patients With Primary High Cholesterol and High Cardiovascular Risk Not Controlled With a Prior Statin Treatment
• Actual Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Mar 1, 2008
• Actual Study Completion Date: Mar 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Arm 1: drug	Drug: ezetimibe (+) simvastatin; ezetimibe/simvastatin 10/20mg. The treatment duration will be 6 weeks.; Other Names: MK0653A Vytorin® ; Drug: Comparator: Placebo (unspecified); rosuvastatin 10mg Placebo. The treatment duration will be 6 weeks.
Active Comparator: 2 Arm 2: active comparator	Drug: Comparator : rosuvastatin calcium; rosuvastatin 10mg. The treatment duration will be 6 weeks.; Drug: Comparator: Placebo (unspecified); ezetimibe/simvastatin 10/20mg Placebo. The treatment duration will be 6 weeks.

Outcome Measures

Primary Outcome Measures

1. Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) at Study Endpoint After Six Weeks of Treatment [Baseline and 6 weeks]

   Percent Change in LDL-C at study endpoint after six weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure *100.

Secondary Outcome Measures

1. The Percentage of Participants Achieving Designated Low Density Lipoprotein-Cholesterol (LDL-C) Levels After 6 Weeks of Treatment [after 6 weeks of treatment]

   The percentage of participants who achieved a target LDL-C goal of < 100 mg/dL, of <70 mg/dL, and of <77 mg/dL at study endpoint after six weeks of treatment. The numerator is the number of participants in a treatment group who achieved a target LDL-C goal and the denominator is the total number of participants within that treatment group.

Other Outcome Measures

1. Percent Change From Baseline in Total Cholesterol [Baseline and 6 weeks]

   Percent change from baseline in total cholesterol at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure *100.

2. Percent Change From Baseline in Triglycerides. [Baseline and 6 weeks]

   Percent change from baseline in triglycerides at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure *100.

3. Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C) [Baseline and 6 weeks]

   Percent change from baseline in HDL-C at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure *100.

4. Percent Change From Baseline in Non-High Density Lipoprotein-Cholesterol (Non-HDL-C) [Baseline and 6 weeks]

   Percent change from baseline in non HDL-C at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure *100.

5. Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C)/High Density Lipoprotein-Cholesterol (HDL-C) Ratio [Baseline and 6 weeks]

   Percent change from baseline in LDL-C/HDL-C ratio at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure *100.

6. Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-Cholesterol (HDL-C) Ratio [Baseline and 6 weeks]

   Percent change from baseline in total cholesterol/HDL-C ratio at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure *100.

7. Percent Change From Baseline in Apolipoprotein B [Baseline and 6 weeks]

   Percent change from baseline in apolipoprotein (Apo) B at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure *100.

8. Percent Change From Baseline in High-sensitivity C (Hs-C) Reactive Protein [Baseline and 6 weeks]

   Percent change from baseline in hs-C reactive protein at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure *100.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participant is currently taking a statin medication for the treatment of high cholesterol

• Participant has an LDL-C level that is greater than or equal to 100 mg/dl and less than or equal to 190 mg/dl

Exclusion Criteria:

• Women who are pregnant or nursing, or women who intend to become pregnant

• Participant has any condition, situation, or is currently taking any medication that might pose a risk to the participant or interfere with participation in the study

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

• Study Director: Medical Monitor, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

• Farnier M, Averna M, Missault L, Vaverkova H, Viigimaa M, Massaad R, Vandormael K, Johnson-Levonas AO, Brudi P. Lipid-altering efficacy of ezetimibe/simvastatin 10/20 mg compared with rosuvastatin 10 mg in high-risk hypercholesterolaemic patients inadequately controlled with prior statin monotherapy - The IN-CROSS study. Int J Clin Pract. 2009 Apr;63(4):547-59. doi: 10.1111/j.1742-1241.2009.02022.x. Epub 2009 Feb 16.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00479713
• Other Study ID Numbers: 0653A-809; 2007_552
• First Posted: May 28, 2007
• Last Update Posted: Feb 15, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Organon and Co: High Cholesterol
• Additional relevant MeSH terms: Hypercholesterolemia; Rosuvastatin Calcium; Simvastatin; Ezetimibe; Calcium

Study Results

Participant Flow

Recruitment Details	Phase IV First Participant In: 31-Mar-2007; Last Participant Last Visit 11-Mar-2008 85 centers worldwide (EX US) Eligible participants include those on a stable dose of one of the following: rosuvastatin 5 mg; simvastatin 20 mg, 40 mg; atorvastatin 10, 20 mg; pravastatin 40 mg; fluvastatin 80 mg.
Pre-assignment Detail	Eligible participants were randomized at Visit 2 (Week 6) to either a combination tablet of ezetimibe/simvastatin (10 mg/20 mg) plus a matching placebo for rosuvastatin 10 mg (Group 1) or rosuvastatin 10 mg plus a matching placebo for the combination tablet (Group 2) for a 6-week treatment period.

Arm/Group Title	Ezetemibe + Simvastatin	Rosuvastatin
Arm/Group Description	Ezetemibe 10 mg + Simvastatin 20 mg plus a matching placebo for rosuvastatin 10 mg QD (once a day) for 6 weeks	Rosuvastatin 10 mg plus a matching placebo for the combination tablet QD (once a day) for 6 weeks
Period Title: Overall Study
STARTED	314	304
COMPLETED	301	295
NOT COMPLETED	13	9

Baseline Characteristics

Arm/Group Title	Ezetemibe + Simvastatin	Rosuvastatin	Total
Arm/Group Description	Ezetemibe 10 mg + Simvastatin 20 mg plus a matching placebo for rosuvastatin 10 mg QD (once a day) for 6 weeks	Rosuvastatin 10 mg plus a matching placebo for the combination tablet QD (once a day) for 6 weeks	Total of all reporting groups
Overall Participants	314	304	618
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	63.2	63.1	63.15
Sex: Female, Male (Count of Participants)
Female	129 41.1%	119 39.1%	248 40.1%
Male	185 58.9%	185 60.9%	370 59.9%
Race/Ethnicity, Customized (participants) [Number]
White	314 100%	302 99.3%	616 99.7%
Black	0 0%	2 0.7%	2 0.3%
Race/Ethnicity, Customized (Number) [Number]
Hispanic or Latino	37 11.8%	43 14.1%	80 12.9%
Not Hispanic or Latino	277 88.2%	261 85.9%	538 87.1%
Apolipoprotein B (mg/dL) [Median (Standard Deviation) ]
Median (Standard Deviation) [mg/dL]	1.20 (0.20)	1.18 (0.21)	1.19 (0.21)
C Reactive Protein (mg/dL) [Median (Standard Deviation) ]
Median (Standard Deviation) [mg/dL]	0.16 (0.26)	0.15 (0.26)	0.16 (0.26)
High Density Lipoprotein-Cholesterol (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	1.43 (0.37)	1.43 (0.36)	1.43 (0.36)
Low Density Lipoprotein-Cholesterol (LDL-C) (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	3.21 (0.42)	3.24 (0.44)	3.23 (0.43)
Low Density Lipoprotein-Cholesterol (LDL-C):High Density Lipoprotein-Cholesterol (HDL-C) ratio (LDL-C:HDL-C ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [LDL-C:HDL-C ratio]	2.38 (0.65)	2.40 (0.65)	2.39 (0.65)
Non-High Density Lipoprotein-Cholesterol (Non-HDL-C) (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	3.95 (0.55)	3.95 (0.56)	3.95 (0.55)
Total Cholesterol (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	5.38 (0.57)	5.38 (0.61)	5.38 (0.59)
Total cholesterol:High Density Lipoprotein-Cholesterol (HDL-C) ratio (Total cholesterol:HDL-C ratio) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Total cholesterol:HDL-C ratio]	3.94 (0.89)	3.96 (0.90)	3.95 (0.90)
Triglycerides (mg/dL) [Median (Standard Deviation) ]
Median (Standard Deviation) [mg/dL]	1.46 (0.86)	1.41 (0.87)	1.42 (0.88)

Outcome Measures

1. Primary Outcome

Title	Percent Change in Low Density Lipoprotein-Cholesterol (LDL-C) at Study Endpoint After Six Weeks of Treatment
Description	Percent Change in LDL-C at study endpoint after six weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure *100.
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized participants who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value.

Arm/Group Title	Ezetemibe + Simvastatin	Rosuvastatin
Arm/Group Description	Ezetemibe 10 mg + Simvastatin 20 mg plus a matching placebo for rosuvastatin 10 mg QD (once a day) for 6 weeks	Rosuvastatin 10 mg plus a matching placebo for the combination tablet QD (once a day) for 6 weeks
Measure Participants	305	297
Least Squares Mean (95% Confidence Interval) [percent change from baseline]	-27.66	-16.94

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetemibe + Simvastatin, Rosuvastatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<=0.001
	Comments
	Method	ANOVA
	Comments	Model terms: treatment, stratum, baseline (categorized based on quartiles) and center
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-10.72
	Confidence Interval	() 95%; -14.10 to -7.33
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.72
	Estimation Comments

2. Secondary Outcome

Title	The Percentage of Participants Achieving Designated Low Density Lipoprotein-Cholesterol (LDL-C) Levels After 6 Weeks of Treatment
Description	The percentage of participants who achieved a target LDL-C goal of < 100 mg/dL, of <70 mg/dL, and of <77 mg/dL at study endpoint after six weeks of treatment. The numerator is the number of participants in a treatment group who achieved a target LDL-C goal and the denominator is the total number of participants within that treatment group.
Time Frame	after 6 weeks of treatment

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS)

Arm/Group Title	Ezetemibe + Simvastatin	Rosuvastatin
Arm/Group Description	Ezetemibe 10 mg + Simvastatin 20 mg plus a matching placebo for rosuvastatin 10 mg QD (once a day) for 6 weeks	Rosuvastatin 10 mg plus a matching placebo for the combination tablet QD (once a day) for 6 weeks
Measure Participants	305	297
LDL-C <100	72.46	56.23
LDL-C <70	25.25	11.11

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetemibe + Simvastatin, Rosuvastatin
	Comments	Percentage of Participants who Attained Target LDL-C Goal of < 100 mg/dL (2.59 mmol/L)
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<=0.001
	Comments
	Method	Regression, Logistic
	Comments	Model terms: treatment, stratum and baseline LDL-C (continuous)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.1
	Confidence Interval	() 95%; 1.5 to 3.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ezetemibe + Simvastatin, Rosuvastatin
	Comments	Percentage of Participants who Attained Target LDL-C Goal of < 70 mg/dL (1.81 mmol/L)
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<=0.001
	Comments
	Method	Regression, Logistic
	Comments	Model terms: treatment, stratum and baseline LDL-C (continuous)
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.8
	Confidence Interval	() 95%; 1.8 to 4.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Other Pre-specified Outcome

Title	Percent Change From Baseline in Total Cholesterol
Description	Percent change from baseline in total cholesterol at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure *100.
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized participants who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value.

Arm/Group Title	Ezetemibe + Simvastatin	Rosuvastatin
Arm/Group Description	Ezetemibe 10 mg + Simvastatin 20 mg plus a matching placebo for rosuvastatin 10 mg QD (once a day) for 6 weeks	Rosuvastatin 10 mg plus a matching placebo for the combination tablet QD (once a day) for 6 weeks
Measure Participants	305	297
Least Squares Mean (95% Confidence Interval) [percent change from baseline]	-17.53	-10.33

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetemibe + Simvastatin, Rosuvastatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<=0.001
	Comments
	Method	ANOVA
	Comments	Model terms: treatment, stratum, baseline (categorized based on quartiles) and center
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.20
	Confidence Interval	() 95%; -9.56 to -4.84
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.20
	Estimation Comments

4. Other Pre-specified Outcome

Title	Percent Change From Baseline in Triglycerides.
Description	Percent change from baseline in triglycerides at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure *100.
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized participants who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value.

Arm/Group Title	Ezetemibe + Simvastatin	Rosuvastatin
Arm/Group Description	Ezetemibe 10 mg + Simvastatin 20 mg plus a matching placebo for rosuvastatin 10 mg QD (once a day) for 6 weeks	Rosuvastatin 10 mg plus a matching placebo for the combination tablet QD (once a day) for 6 weeks
Measure Participants	305	297
Median (95% Confidence Interval) [percent change from baseline]	-11.00	-5.26

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetemibe + Simvastatin, Rosuvastatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.056
	Comments
	Method	Nonparametric ANOVA
	Comments	ANOVA model based on Tukey's normalized ranks with term for treatment, stratum, baseline (categorized based on quartiles) and center.
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-5.06
	Confidence Interval	() 95%; -9.56 to -0.30
	Parameter Dispersion	Type: Value:
	Estimation Comments	The median difference between treatments is based on the Hodges-Lehmann estimates of shift with a corresponding distribution-free Confidence Interval (CI) based on Wilcoxon's rank.

5. Other Pre-specified Outcome

Title	Percent Change From Baseline in High Density Lipoprotein-Cholesterol (HDL-C)
Description	Percent change from baseline in HDL-C at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure *100.
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized participants who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value.

Arm/Group Title	Ezetemibe + Simvastatin	Rosuvastatin
Arm/Group Description	Ezetemibe 10 mg + Simvastatin 20 mg plus a matching placebo for rosuvastatin 10 mg QD (once a day) for 6 weeks	Rosuvastatin 10 mg plus a matching placebo for the combination tablet QD (once a day) for 6 weeks
Measure Participants	305	297
Least Squares Mean (95% Confidence Interval) [percent change from baseline]	2.12	3.03

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetemibe + Simvastatin, Rosuvastatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.433
	Comments
	Method	ANOVA
	Comments	Model terms: treatment, stratum, baseline (categorized based on quartiles) and center.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.92
	Confidence Interval	() 95%; -3.21 to 1.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.17
	Estimation Comments

6. Other Pre-specified Outcome

Title	Percent Change From Baseline in Non-High Density Lipoprotein-Cholesterol (Non-HDL-C)
Description	Percent change from baseline in non HDL-C at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure *100.
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized participants who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value.

Arm/Group Title	Ezetemibe + Simvastatin	Rosuvastatin
Arm/Group Description	Ezetemibe 10 mg + Simvastatin 20 mg plus a matching placebo for rosuvastatin 10 mg QD (once a day) for 6 weeks	Rosuvastatin 10 mg plus a matching placebo for the combination tablet QD (once a day) for 6 weeks
Measure Participants	305	297
Least Squares Mean (95% Confidence Interval) [percent change from baseline]	-23.42	-14.01

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetemibe + Simvastatin, Rosuvastatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<=0.001
	Comments
	Method	ANOVA
	Comments	Model terms: treatment, stratum, baseline (categorized based on quartiles) and center.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.41
	Confidence Interval	() 95%; -12.50 to -6.31
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.58
	Estimation Comments

7. Other Pre-specified Outcome

Title	Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C)/High Density Lipoprotein-Cholesterol (HDL-C) Ratio
Description	Percent change from baseline in LDL-C/HDL-C ratio at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure *100.
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized participants who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value.

Arm/Group Title	Ezetemibe + Simvastatin	Rosuvastatin
Arm/Group Description	Ezetemibe 10 mg + Simvastatin 20 mg plus a matching placebo for rosuvastatin 10 mg QD (once a day) for 6 weeks	Rosuvastatin 10 mg plus a matching placebo for the combination tablet QD (once a day) for 6 weeks
Measure Participants	305	297
Least Squares Mean (95% Confidence Interval) [percent change from baseline]	-27.41	-17.82

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetemibe + Simvastatin, Rosuvastatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<=0.001
	Comments
	Method	ANOVA
	Comments	Model terms: treatment, stratum, baseline (categorized based on quartiles) and center.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.59
	Confidence Interval	() 95%; -13.49 to -5.69
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.98
	Estimation Comments

8. Other Pre-specified Outcome

Title	Percent Change From Baseline in Total Cholesterol/High Density Lipoprotein-Cholesterol (HDL-C) Ratio
Description	Percent change from baseline in total cholesterol/HDL-C ratio at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure *100.
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized participants who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value.

Arm/Group Title	Ezetemibe + Simvastatin	Rosuvastatin
Arm/Group Description	Ezetemibe 10 mg + Simvastatin 20 mg plus a matching placebo for rosuvastatin 10 mg QD (once a day) for 6 weeks	Rosuvastatin 10 mg plus a matching placebo for the combination tablet QD (once a day) for 6 weeks
Measure Participants	305	297
Least Squares Mean (95% Confidence Interval) [percent change from baseline]	-17.76	-11.51

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetemibe + Simvastatin, Rosuvastatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<=0.001
	Comments
	Method	ANOVA
	Comments	Model terms: treatment, stratum, baseline (categorized based on quartiles) and center.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.25
	Confidence Interval	() 95%; -9.07 to -3.43
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.44
	Estimation Comments

9. Other Pre-specified Outcome

Title	Percent Change From Baseline in Apolipoprotein B
Description	Percent change from baseline in apolipoprotein (Apo) B at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure *100.
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized participants who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value.

Arm/Group Title	Ezetemibe + Simvastatin	Rosuvastatin
Arm/Group Description	Ezetemibe 10 mg + Simvastatin 20 mg plus a matching placebo for rosuvastatin 10 mg QD (once a day) for 6 weeks	Rosuvastatin 10 mg plus a matching placebo for the combination tablet QD (once a day) for 6 weeks
Measure Participants	301	292
Least Squares Mean (95% Confidence Interval) [percent change from baseline]	-17.87	-9.77

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetemibe + Simvastatin, Rosuvastatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<=0.001
	Comments
	Method	ANOVA
	Comments	Model terms: treatment, stratum, baseline (categorized based on quartiles) and center
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.11
	Confidence Interval	() 95%; -10.91 to -5.30
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.43
	Estimation Comments

10. Other Pre-specified Outcome

Title	Percent Change From Baseline in High-sensitivity C (Hs-C) Reactive Protein
Description	Percent change from baseline in hs-C reactive protein at study endpoint after 6 weeks of treatment is calculated as the difference between week 6 measure and baseline measure divided by baseline measure *100.
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized participants who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value.

Arm/Group Title	Ezetemibe + Simvastatin	Rosuvastatin
Arm/Group Description	Ezetemibe 10 mg + Simvastatin 20 mg plus a matching placebo for rosuvastatin 10 mg QD (once a day) for 6 weeks	Rosuvastatin 10 mg plus a matching placebo for the combination tablet QD (once a day) for 6 weeks
Measure Participants	301	293
Median (95% Confidence Interval) [percent change from baseline]	-8.33	0.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ezetemibe + Simvastatin, Rosuvastatin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.172
	Comments
	Method	Nonparametric ANOVA
	Comments	ANOVA model based on Tukey's normalized ranks with term for treatment, stratum, baseline (categorized based on quartiles) and center
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.67
	Confidence Interval	() 95%; -16.67 to 2.87
	Parameter Dispersion	Type: Value:
	Estimation Comments	The median difference between treatments is based on the Hodges-Lehmann estimates of shift with a corresponding distribution-free CI based on Wilcoxon's rank

Adverse Events

Adverse Event Reporting Description	Adverse event tables include all participants who took at least one dose of study drug.
Arm/Group Title	Ezetemibe + Simvastatin		Rosuvastatin
Arm/Group Description	Ezetemibe 10 mg + Simvastatin 20 mg plus a matching placebo for rosuvastatin 10 mg QD (once a day) for 6 weeks		Rosuvastatin 10 mg plus a matching placebo for the combination tablet QD (once a day) for 6 weeks
All Cause Mortality
	Ezetemibe + Simvastatin		Rosuvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ezetemibe + Simvastatin		Rosuvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/ (NaN)		5/ (NaN)
General disorders
Chest pain	0/312 (0%)		2/304 (0.7%)
Hepatobiliary disorders
Cholangitis	1/312 (0.3%)		0/304 (0%)
Injury, poisoning and procedural complications
Accidental overdose	1/312 (0.3%)		0/304 (0%)
In-stent arterial restenosis	0/312 (0%)		1/304 (0.3%)
Nervous system disorders
Subarachnoid hemorrhage	1/312 (0.3%)		0/304 (0%)
Epileptic seizure	0/312 (0%)		1/304 (0.3%)
Skin and subcutaneous tissue disorders
Skin eruption	0/312 (0%)		1/304 (0.3%)
Other (Not Including Serious) Adverse Events
	Ezetemibe + Simvastatin		Rosuvastatin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/ (NaN)		30/ (NaN)
Cardiac disorders
Angina unstable	1/312 (0.3%)		0/304 (0%)
Bradycardia	1/312 (0.3%)		0/304 (0%)
Gastrointestinal disorders
Abdominal pain	2/312 (0.6%)		2/304 (0.7%)
Abdominal pain upper	1/312 (0.3%)		1/304 (0.3%)
Diarrhoea	3/312 (1%)		1/304 (0.3%)
Dry mouth	0/312 (0%)		1/304 (0.3%)
Dyspepsia	3/312 (1%)		1/304 (0.3%)
Nausea	2/312 (0.6%)		0/304 (0%)
Salivary hypersecretion	1/312 (0.3%)		0/304 (0%)
Vomitting	2/312 (0.6%)		0/304 (0%)
General disorders
Asthenia	0/312 (0%)		1/304 (0.3%)
Chest pain	1/312 (0.3%)		0/304 (0%)
Pain	0/312 (0%)		1/304 (0.3%)
Immune system disorders
Hypersensitivity	1/312 (0.3%)		0/304 (0%)
Seasonal allergy	1/312 (0.3%)		0/304 (0%)
Infections and infestations
Ear infection	0/312 (0%)		1/304 (0.3%)
Gastroenteritis	0/312 (0%)		1/304 (0.3%)
Gastroenteritis viral	0/312 (0%)		1/304 (0.3%)
Localised infection	0/312 (0%)		1/304 (0.3%)
Nasopharyngitis	1/312 (0.3%)		0/304 (0%)
Paronychia	0/312 (0%)		1/304 (0.3%)
Pharyngitis	1/312 (0.3%)		0/304 (0%)
Sinusitis	1/312 (0.3%)		0/304 (0%)
Tooth abscess	0/312 (0%)		1/304 (0.3%)
Bronchitis	2/312 (0.6%)		0/304 (0%)
Injury, poisoning and procedural complications
Contusion	0/312 (0%)		1/304 (0.3%)
Deafness traumatic	1/312 (0.3%)		0/304 (0%)
Fall	1/312 (0.3%)		0/304 (0%)
Rib fracture	1/312 (0.3%)		0/304 (0%)
Upper limb fracture	0/312 (0%)		1/304 (0.3%)
Investigations
Blood pressure increased	0/312 (0%)		1/304 (0.3%)
Metabolism and nutrition disorders
Anorexia	1/312 (0.3%)		0/304 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/312 (0%)		1/304 (0.3%)
Bursitis	0/312 (0%)		1/304 (0.3%)
Flank pain	1/312 (0.3%)		0/304 (0%)
Myalgia	3/312 (1%)		2/304 (0.7%)
Osteoarthritis	1/312 (0.3%)		0/304 (0%)
Sensation of heaviness	0/312 (0%)		1/304 (0.3%)
Spinal osteoarthritis	0/312 (0%)		1/304 (0.3%)
Nervous system disorders
Carpal tunnel syndrome	0/312 (0%)		1/304 (0.3%)
Headache	1/312 (0.3%)		0/304 (0%)
Memory impairment	0/312 (0%)		1/304 (0.3%)
Paraesthesia	0/312 (0%)		1/304 (0.3%)
Syncope vasovagal	0/312 (0%)		1/304 (0.3%)
Psychiatric disorders
Insomnia	0/312 (0%)		1/304 (0.3%)
Nervousness	0/312 (0%)		1/304 (0.3%)
Renal and urinary disorders
Nephrolithiasis	0/312 (0%)		1/304 (0.3%)
Respiratory, thoracic and mediastinal disorders
Throat tightness	0/312 (0%)		1/304 (0.3%)
Skin and subcutaneous tissue disorders
Rash	0/312 (0%)		1/304 (0.3%)
Vascular disorders
Hypertension	0/312 (0%)		1/304 (0.3%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.