To Evaluate Ezetimibe Plus Atorvastatin Versus Atorvastatin in Patients With High Cholesterol Not Controlled on Atorvastatin 20 mg.

This study has been completed.

Study NCT00276458 Information provided by Merck

First Received on January 10, 2006. Last Updated on April 14, 2010 History of Changes

Results First Received: December 18, 2008

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Condition:	Hypercholesterolemia
Interventions:	Drug: Comparator: atorvastatin Drug: Comparator: Placebo Drug: Comparator: ezetimibe Drug: Comparator: Placebo.

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Phase III First Patient In: 4/5/2006; Last Patient Last Visit 1/17/2008 72 centers worldwide (US, Canada, Austria, Costa Rica) Eligible patients include those on a stable dose of atorvastatin 20 mg; or patients with adjusted LDL-C pre-screen ranges who were treated with other lipid modifying therapy, or were statin and/or ezetimibe naïve.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients received and were blinded to atorvastatin 20 mg for a 4/5- week run-in period. Patients needed an LDL-C ≥ 100 mg/dL and ≤ 160 mg/dL at Visit 2 (week -1). Eligible patients were randomized at Visit 3 (Week 0) to either atorvastatin 40 mg or addition of ezetimibe 10 mg to their 20 mg dose of atorvastatin for a 6-week treatment period.

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

Patients received and were blinded to atorvastatin 20 mg for a 4/5- week run-in period.

Patients needed an LDL-C ≥ 100 mg/dL and ≤ 160 mg/dL at Visit 2 (week -1). Eligible patients were randomized at Visit 3 (Week 0) to either atorvastatin 40 mg or addition of ezetimibe 10 mg to their 20 mg dose of atorvastatin for a 6-week treatment period.

Reporting Groups

	Description
Atorvastatin + Ezetimibe	Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
Atorvastatin	Atorvastatin 40 mg Daily for 6 weeks

Participant Flow: Overall Study

	Atorvastatin + Ezetimibe	Atorvastatin
STARTED	98	98
COMPLETED	92	91
NOT COMPLETED	6	7
Adverse Event	0	2
Lost to Follow-up	2	2
Protocol Violation	4	3

Baseline Characteristics

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Reporting Groups

	Description
Atorvastatin + Ezetimibe	Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
Atorvastatin	Atorvastatin 40 mg Daily for 6 weeks

Baseline Measures

	Atorvastatin + Ezetimibe	Atorvastatin	Total
Number of Participants [units: participants]	98	98	196
Age [units: years] Mean ( Full Range )	56.4 ( 24 to 78 )	58.0 ( 34 to 76 )	57.2 ( 24 to 78 )
Gender [units: participants]
Female	40	49	89
Male	58	49	107
Race/Ethnicity, Customized [units: participants]
White	58	60	118
American Indian or Alaska Native	1	0	1
Asian	7	8	15
Black	3	9	12
Multi-Racial	29	21	50
Apolipoprotein A-I [units: mg/dL] Mean ± Standard Deviation	161.8 ± 25.2	163.4 ± 24.6	162.6 ± 24.8
Apolipoprotein A-I:Apolipoprotein B ratio [units: Ratio] Mean ± Standard Deviation	0.8 ± 0.2	0.7 ± 0.2	0.8 ± 0.2
Apolipoprotein B [units: mg/dL] Mean ± Standard Deviation	122.9 ± 22.4	119.9 ± 21.0	121.4 ± 21.7
C Reactive Protein [units: mg/dL] Mean ± Standard Deviation	1.6 ± 2.6	1.2 ± 1.7	1.5 ± 2.1
High Density Lipoprotein (HDL) [units: mg/dL] Mean ± Standard Deviation	51.1 ± 12.1	51.7 ± 11.5	51.4 ± 11.8
Low Density Lipoprotein (LDL) [units: mg/dL] Mean ± Standard Deviation	119.9 ± 19.4	117.9 ± 16.8	118.9 ± 18.1
Low Density Lipoprotein Cholesterol (LDL-C):High Density Lipoprotein Cholesterol (HDL-C) ratio [units: Ratio] Mean ± Standard Deviation	2.4 ± 0.6	2.5 ± 0.7	2.4 ± 0.7
Non- High Density Lipoprotein (Non-HDL) Cholesterol [units: mg/dL] Mean ± Standard Deviation	151.6 ± 24.1	148.4 ± 21.1	150.0 ± 22.7
NonHigh Density Lipoprotein-Cholesterol (NonHDL-C):High Density Lipoprotein-Cholesterol (HDL-C)ratio [units: Ratio] Mean ± Standard Deviation	3.2 ± 1.0	3.0 ± 0.9	3.1 ± 1.0
Total Cholesterol [units: mg/dL] Mean ± Standard Deviation	202.6 ± 25.2	200.0 ± 21.5	201.3 ± 23.4
Total cholesterol:High Density Lipoprotein Cholesterol (HDL-C) ratio [units: Ratio] Mean ± Standard Deviation	4.2 ± 1.0	4.0 ± 0.9	4.1 ± 1.0
Triglycerides (TG) [units: mg/dL] Mean ± Standard Deviation	152.5 ± 68.8	147.8 ± 75.3	149.0 ± 75.3

Outcome Measures

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1. Primary:

Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Week 6 [ Time Frame: 6 weeks ]

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2. Secondary:

Percent Change in High Density Lipoprotein -Cholesterol (HDL-C)at Week 6 [ Time Frame: 6 weeks ]

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3. Secondary:

Percent Change in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 6 [ Time Frame: 6 Weeks ]

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4. Secondary:

Percent Change From Baseline in Total-Cholesterol at Week 6 [ Time Frame: 6 Weeks ]

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5. Secondary:

Percent Change From Baseline in Triglycerides (TG) at Week 6 [ Time Frame: 6 weeks ]

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6. Secondary:

Percent Change From Baseline in Apolipoprotein B at Week 6 [ Time Frame: 6 Weeks ]

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7. Secondary:

Percent Change From Baseline in Total-Cholesterol:High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6 [ Time Frame: 6 Weeks ]

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8. Secondary:

Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C):High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6 [ Time Frame: 6 Weeks ]

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9. Secondary:

Percent Change From Baseline in Apolipoprotein B: Apolipoprotein A-I Ratio at Week 6 [ Time Frame: 6 Weeks ]

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10. Secondary:

Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (HDL-C):High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6 [ Time Frame: 6 Weeks ]

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11. Secondary:

Percent Change From Baseline in C-Reactive Protein (CRP) at Week 6 [ Time Frame: 6 Weeks ]

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12. Secondary:

Number of Participants Who Attained Target LDL-C <100 mg/dL at Week 6 [ Time Frame: 6 weeks ]

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13. Post-Hoc:

Percent Change in Apolipoprotein A-I at Week 6 [ Time Frame: 6 Weeks ]

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14. Post-Hoc:

Percent Change in C-Reactive Protein (CRP) at Week 6 [ Time Frame: 6 weeks ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
194 out of 196 randomized patients took at least one dose of blinded study therapy and were included in the safety analysis

Results Point of Contact:

Name/Title: Senior Vice President, Clinical and Quantitative Sciences
Organization: Merck Sharp & Dohme Corp
phone: 1-800-672-6372

Publications:

Conard SE, Bays HE, Leiter LA, Bird SR, Rubino J, Lowe RS, Tomassini JE, Tershakovec AM. Efficacy and safety of ezetimibe added on to atorvastatin (20 mg) versus uptitration of atorvastatin (to 40 mg) in hypercholesterolemic patients at moderately high risk for coronary heart disease. Am J Cardiol. 2008 Dec 1;102(11):1489-94. Epub 2008 Oct 23.

Responsible Party:	Executive Vice President, Clinical and Quantitative Sciences, Merck Sharp & Dohme Corp
ClinicalTrials.gov Identifier:	NCT00276458 History of Changes
Other Study ID Numbers:	2005_104, MK0653-079
Study First Received:	January 10, 2006
Results First Received:	December 18, 2008
Last Updated:	April 14, 2010
Health Authority:	United States: Food and Drug Administration