Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Effects of Ezetimibe With Simvastatin in the Therapy of Adolescents With HeFH (Study P02579)

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.
 
ClinicalTrials.gov Identifier: NCT00129402
Recruitment Status : Completed
First Posted : August 11, 2005
Results First Posted : February 11, 2010
Last Update Posted : September 21, 2015
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Hypercholesterolemia
Interventions Drug: ezetimibe with simvastatin
Drug: simvastatin
Enrollment 248
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Ezetimibe/Simvastatin 10/10 Ezetimibe/Simvastatin 10/20 Ezetimibe/Simvastatin 10/40 Ezetimibe Matching Placebo/ Simvastatin 10 Ezetimibe Matching Placebo/ Simvastatin 20 Ezetimibe Matching Placebo/ Simvastatin 40 Long-term Experience Ezetimbe/Simvastatin
Hide Arm/Group Description Subjects who received ezetimibe 10 mg plus simvastatin 10 mg once daily Subjects who received ezetimibe 10 mg with simvastatin 10 mg once daily Subjects who received ezetimibe 10 mg plus simvastatin 40 mg once daily Subjects who received simvastatin monotherapy 10 mg once daily Subjects who received simvastatin monotherapy 20 mg once daily Subjects who received simvastatin monotherapy 40 mg once daily Subjects who received long-term coadministration of ezetimibe with simvastatin once daily
Period Title: Start Period1 to End Period1 (Week 1-6)
Started 43 40 43 40 40 42 0
Completed 43 39 41 39 39 40 0
Not Completed 0 1 2 1 1 2 0
Reason Not Completed
Adverse Event             0             1             1             0             0             1             0
Lost to Follow-up             0             0             0             0             0             1             0
Protocol Violation             0             0             0             1             0             0             0
Withdrawal by Subject             0             0             1             0             1             0             0
Period Title: Start Period2 to End Period2 (Week 7-33)
Started 0 0 122 [1] 0 0 118 [2] 0
Completed 0 0 114 [3] 0 0 113 [3] 0
Not Completed 0 0 8 0 0 5 0
Reason Not Completed
Adverse Event             0             0             2             0             0             0             0
Laboratory Adverse Event             0             0             3             0             0             1             0
Lost to Follow-up             0             0             1             0             0             0             0
Withdrawal by Subject             0             0             1             0             0             3             0
Protocol Violation             0             0             1             0             0             1             0
[1]
# of subjects were combined from the 3 arms in Period 1 who received ezetimibe with simvastatin
[2]
# of subjects were combined from the 3 arms in Period 1 who received simvastatin monotherapy
[3]
One subject who completed Period 1, did not enter Period 2, but entered and completed Period 3.
Period Title: Start Period3 to End Period3(Week 34-53)
Started 0 0 0 0 0 0 228 [1]
Completed 0 0 0 0 0 0 222 [2]
Not Completed 0 0 0 0 0 0 6
Reason Not Completed
Lost to Follow-up             0             0             0             0             0             0             1
Withdrawal by Subject             0             0             0             0             0             0             3
Subject moved             0             0             0             0             0             0             1
Protocol Violation             0             0             0             0             0             0             1
[1]
In Period 3, all subjects from Period 1 and Period 2 were combined into one treatment group.
[2]
One subject who completed Period 1, did not enter Period 2, but entered and completed Period 3.
Arm/Group Title Pooled Subjects Who Received Ezetimibe With Simvastatin Pooled Subjects Who Received Simvastatin Monotherapy Total
Hide Arm/Group Description Pooled subjects who received ezetimibe 10 mg plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg Pooled subjects who received ezetimibe placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg Total of all reporting groups
Overall Number of Baseline Participants 126 122 248
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 126 participants 122 participants 248 participants
14.0  (1.9) 14.3  (1.8) 14.2  (1.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 126 participants 122 participants 248 participants
Female
53
  42.1%
53
  43.4%
106
  42.7%
Male
73
  57.9%
69
  56.6%
142
  57.3%
1.Primary Outcome
Title Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
Hide Description Least squares mean percent change from Baseline in LDL-C at the end of Step 1 (Week 6) in the pooled groups who received ezetimibe plus simvastatin compared with pooled groups who received simvastatin monotherapy
Time Frame baseline to 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the intent to treat (ITT) population. Although 248 subjects received randomized treatment, two of the subjects did not have at least one baseline and at least one postbaseline lipid determination and thus could not be analyzed in the ITT population. Therefore, the actual ITT population consisted of 246 subjects.
Arm/Group Title Pooled Subjects Who Received Ezetimibe With Simvastatin Pooled Subjects Who Received Simvastatin Monotherapy
Hide Arm/Group Description:
Pooled subjects who received ezetimibe 10 mg plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
Pooled subjects who received ezetimibe placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
Overall Number of Participants Analyzed 126 120
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-49.45  (1.19) -34.43  (1.22)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pooled Subjects Who Received Ezetimibe With Simvastatin, Pooled Subjects Who Received Simvastatin Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
2.Secondary Outcome
Title Percent Change From Baseline in Total Cholesterol (TC)
Hide Description [Not Specified]
Time Frame baseline to 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Pooled Subjects Who Received Ezetimibe With Simvastatin Pooled Subjects Who Received Simvastatin Monotherapy
Hide Arm/Group Description:
Pooled subjects who received ezetimibe 10 mg plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
pooled subjects who received simvastatin 10 mg monotherapy, simvastatin 20 mg monotherapy, or simvastatin 40 mg monotherapy
Overall Number of Participants Analyzed 126 120
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-38.23  (.96) -26.28  (.99)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pooled Subjects Who Received Simvastatin Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
3.Secondary Outcome
Title Percent Change From Baseline in Non High-density Lipoprotein Cholesterol (Non HDL-C)
Hide Description [Not Specified]
Time Frame baseline to 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Pooled Subjects Who Received Ezetimibe With Simvastatin Pooled Subjects Who Received Simvastatin Monotherapy
Hide Arm/Group Description:
Pooled subjects who received ezetimibe 10 mg plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
Pooled subjects who received ezetimibe placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
Overall Number of Participants Analyzed 126 120
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-46.84  (1.13) -32.68  (1.16)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pooled Subjects Who Received Ezetimibe With Simvastatin, Pooled Subjects Who Received Simvastatin Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
4.Secondary Outcome
Title Percent Change From Baseline in Triglycerides (TG)
Hide Description [Not Specified]
Time Frame baseline to 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Pooled Subjects Who Received Ezetimibe With Simvastatin Pooled Subjects Who Received Simvastatin Monotherapy
Hide Arm/Group Description:
Pooled subjects who received ezetimibe 10 mg plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
Pooled subjects who received ezetimibe placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
Overall Number of Participants Analyzed 126 120
Median (Standard Deviation)
Unit of Measure: percent change
-16.56  (30.26) -12.28  (31.49)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pooled Subjects Who Received Ezetimibe With Simvastatin, Pooled Subjects Who Received Simvastatin Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .48
Comments [Not Specified]
Method non-parametric model
Comments [Not Specified]
5.Secondary Outcome
Title Percent Change From Baseline in Apolipoprotein B (Apo B)
Hide Description [Not Specified]
Time Frame baseline to 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Pooled Subjects Who Received Ezetimibe With Simvastatin Pooled Subjects Who Received Simvastatin Monotherapy
Hide Arm/Group Description:
Pooled subjects who received ezetimibe 10 mg plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
Pooled subjects who received ezetimibe placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
Overall Number of Participants Analyzed 122 118
Least Squares Mean (Standard Error)
Unit of Measure: percent change
-38.92  (1.1) -26.69  (1.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pooled Subjects Who Received Ezetimibe With Simvastatin, Pooled Subjects Who Received Simvastatin Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
6.Secondary Outcome
Title Percent Change From Baseline in HDL-C
Hide Description [Not Specified]
Time Frame baseline to 6 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
ITT
Arm/Group Title Pooled Subjects Who Received Ezetimibe With Simvastatin Pooled Subjects Who Received Simvastatin Monotherapy
Hide Arm/Group Description:
Pooled subjects who received ezetimibe 10 mg plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
Pooled subjects who received ezetimibe placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
Overall Number of Participants Analyzed 126 120
Least Squares Mean (Standard Error)
Unit of Measure: percent change
6.58  (1.16) 6.47  (1.19)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pooled Subjects Who Received Ezetimibe With Simvastatin, Pooled Subjects Who Received Simvastatin Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .95
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Ezetimibe With Simvastatin Simvastatin Monotherapy Long-term Coadministration of Ezetimibe With Simvastatin
Hide Arm/Group Description Column 1 provides the combined AE data collected for subjects in the ezetimibe with simvastatin treatment groups during Period 1 and Period 2

Column 2 provides the combined AE data collected for subjects in the simvastatin monotherapy treatment

groups during Period 1 and Period 2.

Column 3 provides the combined AE data collected for

all subjects that participated during Period 3. One subject who entered Period 3 did not receive study medication and was not included in the analysis.

All-Cause Mortality
Ezetimibe With Simvastatin Simvastatin Monotherapy Long-term Coadministration of Ezetimibe With Simvastatin
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide Serious Adverse Events
Ezetimibe With Simvastatin Simvastatin Monotherapy Long-term Coadministration of Ezetimibe With Simvastatin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/126 (3.17%)      1/122 (0.82%)      3/227 (1.32%)    
General disorders       
Pyrexia  1  1/126 (0.79%)  1 0/122 (0.00%)  0 0/227 (0.00%)  0
Infections and infestations       
Arthritis bacterial  1  1/126 (0.79%)  1 0/122 (0.00%)  0 0/227 (0.00%)  0
Pilonidal cyst  1  0/126 (0.00%)  0 0/122 (0.00%)  0 1/227 (0.44%)  1
Subcutaneous abscess  1  0/126 (0.00%)  0 0/122 (0.00%)  0 1/227 (0.44%)  1
Tonsillitis  1  1/126 (0.79%)  1 0/122 (0.00%)  0 0/227 (0.00%)  0
Injury, poisoning and procedural complications       
Accidental overdose  1  0/126 (0.00%)  0 1/122 (0.82%)  1 0/227 (0.00%)  0
Overdose  1  0/126 (0.00%)  0 0/122 (0.00%)  0 1/227 (0.44%)  1
Musculoskeletal and connective tissue disorders       
Tendonitis  1  1/126 (0.79%)  1 0/122 (0.00%)  0 0/227 (0.00%)  0
Nervous system disorders       
Encephalopathy  1  1/126 (0.79%)  1 0/122 (0.00%)  0 0/227 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 9.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ezetimibe With Simvastatin Simvastatin Monotherapy Long-term Coadministration of Ezetimibe With Simvastatin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   58/126 (46.03%)      59/122 (48.36%)      42/227 (18.50%)    
Gastrointestinal disorders       
Diarrhoea  1  9/126 (7.14%)  9 3/122 (2.46%)  3 2/227 (0.88%)  2
Nausea  1  8/126 (6.35%)  12 4/122 (3.28%)  4 2/227 (0.88%)  2
Infections and infestations       
Influenza  1  8/126 (6.35%)  9 12/122 (9.84%)  14 12/227 (5.29%)  12
Nasopharyngitis  1  27/126 (21.43%)  30 27/122 (22.13%)  31 16/227 (7.05%)  16
Musculoskeletal and connective tissue disorders       
Myalgia  1  7/126 (5.56%)  10 1/122 (0.82%)  1 0/227 (0.00%)  0
Nervous system disorders       
Headache  1  16/126 (12.70%)  25 16/122 (13.11%)  22 6/227 (2.64%)  6
Respiratory, thoracic and mediastinal disorders       
Cough  1  4/126 (3.17%)  4 8/122 (6.56%)  9 5/227 (2.20%)  6
Skin and subcutaneous tissue disorders       
Acne  1  4/126 (3.17%)  4 9/122 (7.38%)  9 3/227 (1.32%)  3
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 9.0
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00129402    
Other Study ID Numbers: P02579
EUDRACT NUMBER:2004-002627-40;
SCH 58235;
DOC ID 2526810
First Submitted: August 9, 2005
First Posted: August 11, 2005
Results First Submitted: January 14, 2010
Results First Posted: February 11, 2010
Last Update Posted: September 21, 2015