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To Evaluate Ezetimibe Plus Atorvastatin Versus Atorvastatin in Patients With High Cholesterol Not Controlled on Atorvastatin 20 mg (0653-079)(COMPLETED)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00276458
First received: January 10, 2006
Last updated: October 31, 2014
Last verified: October 2014
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.


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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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Atorvastatin + Ezetimibe Atorvastatin 20 mg + Ezetemibe 10 mg daily for 6 weeks
Atorvastatin Atorvastatin 40 mg Daily for 6 weeks
Total Total of all reporting groups

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 ]

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

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

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

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

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

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

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 ]

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

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 ]

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

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

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

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


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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


  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:
unchecked 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.
unchecked 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.


Results Point of Contact:  
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
phone: 1-800-672-6372
e-mail: ClinicalTrialsDisclosure@merck.com


Publications:

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00276458     History of Changes
Other Study ID Numbers: 0653-079, 2005_104
Study First Received: January 10, 2006
Results First Received: December 18, 2008
Last Updated: October 31, 2014
Health Authority: United States: Food and Drug Administration