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To Evaluate Ezetimibe/Simvastatin and Niacin (Extended Release Tablet) in Patients With Type IIa or Type IIb Hyperlipidemia (0653A-091)(COMPLETED)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00271817
First Posted: January 4, 2006
Last Update Posted: April 11, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
Results First Submitted: February 13, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition: Hypercholesterolemia
Interventions: Drug: Comparator: ezetimibe/simvastatin + niacin (ER)
Drug: Comparator: Placebo to ezetimibe/simvastatin
Drug: Comparator: niacin (ER) tablet
Drug: Comparator: ezetimibe (+) simvastatin
Drug: Comparator: Placebo to Niacin (ER)
Drug: Comparator: ezetimibe/simvastatin and niacin (ER)
Drug: Comparator: ezetimibe and simvastatin
Drug: Comparator: Placebo to niacin (ER)

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Niacin (Part 1): Niacin titrated to 2000 mg taken orally once daily for 24 weeks. During the first 12 weeks of the study, patients randomized to the niacin containing arms started taking niacin 500 mg and had their niacin dose increased 500 mg every 4 weeks to 2000 mg. Patients in this treatment group were ramdomly reassigned for Part 2 of the study to one of two treatment groups- two-thirds of the patients enrolled in the niacin treatment group were randomly assigned to receive ezetimibe/simvastatin + niacin (ER) and the other one-third were randomly assigned to receive ezetimibe/simvastatin alone.
Ezetimibe/Simvastatin

(Part 1): Ezetimibe/Simvastatin 10/20 mg taken orally once daily for 24 weeks.

(Part 2): Ezetimibe/Simvastatin 10/20 mg taken orally once daily for 40 additional weeks for a total of 64 weeks.

Ezetimibe/Simvastatin + Niacin

(Part 1): Ezetimibe/Simvastatin 10/20 mg + Niacin (titrated to 2000 mg as noted above) taken orally once daily for 24 weeks.

(Part 2): Ezetimibe/Simvastatin 10/20 mg + Niacin 2000 mg taken orally once daily for 40 additional weeks for a total of 64 weeks.


Participant Flow for 2 periods

Period 1:   Part 1
    Niacin   Ezetimibe/Simvastatin   Ezetimibe/Simvastatin + Niacin
STARTED   272   272   676 
COMPLETED   166 [1]   213 [2]   391 [3] 
NOT COMPLETED   106   59   285 
Adverse Event                68                25                156 
Lost to Follow-up                6                8                24 
Protocol Violation                5                4                7 
Patient Moved                3                1                5 
Withdrawal by Subject                23                17                45 
LDL < 50 mg/dL                1                4                48 
[1] 6 patients who completed Part 1 did not continue to Part 2; 1 patient never received drug in Part 2
[2] 1 patient who completed Part 1 did not continue to Part 2
[3] 11 patients who completed Part 1 did not continue to Part 2

Period 2:   Part 2
    Niacin   Ezetimibe/Simvastatin   Ezetimibe/Simvastatin + Niacin
STARTED   0 [1]   266 [2]   485 [3] 
COMPLETED   0   234   401 
NOT COMPLETED   0   32   84 
Adverse Event                0                17                33 
Lack of Efficacy                0                1                6 
Lost to Follow-up                0                6                18 
Protocol Violation                0                3                5 
Patient Moved                0                0                5 
Withdrawal by Subject                0                2                13 
LDL < 50 mg/dL                0                3                4 
[1] Patients completing the niacin group in Part 1, were re-allocated to one of the two arms in Part 2
[2] Includes 54 patients re-allocated from the niacin group in Part 1
[3] Includes 105 patients re-allocated from the niacin group in Part 1



  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
Niacin (Part 1): Niacin titrated to 2000 mg taken orally once daily for 24 weeks. During the first 12 weeks of the study, patients randomized to the niacin containing arms started taking niacin 500 mg and had their niacin dose increased 500 mg every 4 weeks to 2000 mg.
Ezetimibe/Simvastatin

(Part 1): Ezetimibe/Simvastatin 10/20 mg taken orally once daily for 24 weeks.

(Part 2): Ezetimibe/Simvastatin 10/20 mg taken orally once daily for 40 additional weeks for a total of 64 weeks.

Ezetimibe/Simvastatin + Niacin

(Part 1): Ezetimibe/Simvastatin 10/20 mg + Niacin (titrated to 2000 mg as noted above) taken orally once daily for 24 weeks.

(Part 2): Ezetimibe/Simvastatin 10/20 mg + Niacin 2000 mg taken orally once daily for 40 additional weeks for a total of 64 weeks.

Total Total of all reporting groups

Baseline Measures
   Niacin   Ezetimibe/Simvastatin   Ezetimibe/Simvastatin + Niacin   Total 
Overall Participants Analyzed 
[Units: Participants]
 272   272   676   1220 
Age 
[Units: Years]
Mean (Standard Deviation)
 56.4  (10.6)   57.5  (10.3)   56.9  (10.9)   56.9  (10.7) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
       
Female      136  50.0%      120  44.1%      352  52.1%      608  49.8% 
Male      136  50.0%      152  55.9%      324  47.9%      612  50.2% 
Race/Ethnicity, Customized 
[Units: Participants]
       
Asian   11   4   11   26 
Black   13   17   38   68 
Hispanic   14   11   49   74 
Other   3   0   2   5 
White   231   240   576   1047 
Body Mass Index 
[Units: Participants]
       
<25 kg/m2   48   39   135   222 
25 to <30 kg/m2   110   119   252   481 
30 to <40 kg/m2   97   94   251   442 
≥ 40 kg/m2   16   19   34   69 
No BMI Data   1   1   4   6 


  Outcome Measures
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1.  Primary:   Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C)   [ Time Frame: Baseline and 24 Weeks ]

2.  Primary:   Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C)   [ Time Frame: Baseline and 24 weeks ]

3.  Secondary:   Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C)   [ Time Frame: Baseline and 24 weeks ]

4.  Secondary:   Percent Change From Baseline in High-Density Lipoprotein-Cholesterol (HDL-C)   [ Time Frame: Baseline and 24 weeks ]

5.  Secondary:   Percent Change From Baseline in Triglycerides (TG)   [ Time Frame: baseline and 24 Weeks ]

6.  Secondary:   Percent Change From Baseline in High-Density Lipoprotein-Cholesterol (HDL-C)   [ Time Frame: Baseline and 64 weeks ]

7.  Secondary:   Percent Change From Baseline in Triglycerides (TG)   [ Time Frame: Baseline and 64 weeks ]
  Hide Outcome Measure 7

Measure Type Secondary
Measure Title Percent Change From Baseline in Triglycerides (TG)
Measure Description Ezetimibe/simvastatin co-administered with niacin extended release compared to ezetimibe/simvastatin monotherapy on the percent change from baseline in Triglycerides after 64 weeks - 64 week measure minus baseline
Time Frame Baseline and 64 weeks  

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.
The analysis population is the modified intention-to-treat population, which includes patients that were randomized to ezetimibe/simvastatin + niacin or ezetimibe/simvastatin treatment groups and have a baseline measurement and at least on measurement beyond Week 24.

Reporting Groups
  Description
Ezetimibe/Simvastatin Ezetimibe/Simvastatin 10/20 mg taken orally once daily for 24 weeks. Ezetimibe/Simvastatin 10/20 mg taken orally once daily for 40 additional weeks for a total of 64 weeks.
Ezetimibe/Simvastatin + Niacin Ezetimibe/Simvastatin 10/20 mg + Niacin (titrated to 2000 mg) taken orally once daily for 24 weeks. Ezetimibe/Simvastatin 10/20 mg + Niacin 2000 mg taken orally once daily for 40 additional weeks for a total of 64 weeks.

Measured Values
   Ezetimibe/Simvastatin   Ezetimibe/Simvastatin + Niacin 
Participants Analyzed 
[Units: Participants]
 207   369 
Percent Change From Baseline in Triglycerides (TG) 
[Units: Percent change]
Median (Standard Deviation)
 -26.8  (32.7)   -44.5  (26.9) 


Statistical Analysis 1 for Percent Change From Baseline in Triglycerides (TG)
Groups [1] All groups
Statistical Test Type [2] Superiority or Other
Statistical Method [3] ANCOVA
P Value [4] <0.001
Median Difference (Final Values) [5] -17.6
95% Confidence Interval -21.8 to -13.6
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  No text entered.
[3] Other relevant method information, such as adjustments or degrees of freedom:
  ANCOVA using ranks based on normal scores (Tukey method) with model terms for treatment, baseline LDL-C, baseline TG and gender.
[4] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  A fixed sequence testing procedure was employed where testing followed a prespecified order and each subsequent hypothesis was tested at the 0.05 level of significance only if all previously tested hypotheses have been rejected.
[5] Other relevant estimation information:
 

Median difference = Ezetimibe/Simvastatin + Niacin minus Ezetimibe/Simvastatin

The median difference is based on the Hodges-Lehmann estimates of shift; The distribution-free 95% CI is based on Wilcoxon’s rank sum test statistic.




8.  Secondary:   Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C)   [ Time Frame: Baseline and 64 weeks ]

9.  Secondary:   Percent Change From Baseline in Low-Density Lipoprotein-Cholesterol (LDL-C)   [ Time Frame: Baseline and 64 weeks ]

10.  Secondary:   Percent Change From Baseline in Non-High-Density Lipoprotein-Cholesterol (Non-HDL-C)   [ Time Frame: Baseline and 24 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
Part 1 population is all patients enrolled in Part 1 of the study. Part 2 is those patients who received either niacin, ezetimibe/simvastatin, or ezetimibe/simvastatin + niacin during Part 1 until they finished the study at week 64 or discontinued.


  More Information