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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:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00271817
First received: January 3, 2006
Last updated: October 31, 2014
Last verified: October 2014
Results First Received: February 13, 2009  
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: 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
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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  
Number of Participants  
[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  
Gender  
[units: participants]
       
Female     136     120     352     608  
Male     136     152     324     612  
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  
Safety Issue No  

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  
Number of Participants Analyzed  
[units: participants]
  207     369  
Percent Change From Baseline in Triglycerides (TG)  
[units: Percent┬áchange]
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
Method [2] ANCOVA
P Value [3] <0.001
Median Difference (Final Values) [4] -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] 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.
[3] 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.
[4] 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