Trial Outcomes & Findings for Effects of Ezetimibe With Simvastatin in the Therapy of Adolescents With HeFH (Study P02579) (NCT NCT00129402)
NCT ID: NCT00129402
Last Updated: 2022-02-08
Results Overview
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
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
248 participants
Primary outcome timeframe
baseline to 6 weeks
Results posted on
2022-02-08
Participant Flow
Participant milestones
| Measure |
Ezetimibe/Simvastatin 10/10
Subjects who received ezetimibe 10 mg plus simvastatin 10 mg once daily
|
Ezetimibe/Simvastatin 10/20
Subjects who received ezetimibe 10 mg with simvastatin 10 mg once daily
|
Ezetimibe/Simvastatin 10/40
Subjects who received ezetimibe 10 mg plus simvastatin 40 mg once daily
|
Ezetimibe Matching Placebo/ Simvastatin 10
Subjects who received simvastatin monotherapy 10 mg once daily
|
Ezetimibe Matching Placebo/ Simvastatin 20
Subjects who received simvastatin monotherapy 20 mg once daily
|
Ezetimibe Matching Placebo/ Simvastatin 40
Subjects who received simvastatin monotherapy 40 mg once daily
|
Long-term Experience Ezetimbe/Simvastatin
Subjects who received long-term coadministration of ezetimibe with simvastatin once daily
|
|---|---|---|---|---|---|---|---|
|
Start Period1 to End Period1 (Week 1-6)
STARTED
|
43
|
40
|
43
|
40
|
40
|
42
|
0
|
|
Start Period1 to End Period1 (Week 1-6)
COMPLETED
|
43
|
39
|
41
|
39
|
39
|
40
|
0
|
|
Start Period1 to End Period1 (Week 1-6)
NOT COMPLETED
|
0
|
1
|
2
|
1
|
1
|
2
|
0
|
|
Start Period2 to End Period2 (Week 7-33)
STARTED
|
0
|
0
|
122
|
0
|
0
|
118
|
0
|
|
Start Period2 to End Period2 (Week 7-33)
COMPLETED
|
0
|
0
|
114
|
0
|
0
|
113
|
0
|
|
Start Period2 to End Period2 (Week 7-33)
NOT COMPLETED
|
0
|
0
|
8
|
0
|
0
|
5
|
0
|
|
Start Period3 to End Period3(Week 34-53)
STARTED
|
0
|
0
|
0
|
0
|
0
|
0
|
228
|
|
Start Period3 to End Period3(Week 34-53)
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
222
|
|
Start Period3 to End Period3(Week 34-53)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
6
|
Reasons for withdrawal
| Measure |
Ezetimibe/Simvastatin 10/10
Subjects who received ezetimibe 10 mg plus simvastatin 10 mg once daily
|
Ezetimibe/Simvastatin 10/20
Subjects who received ezetimibe 10 mg with simvastatin 10 mg once daily
|
Ezetimibe/Simvastatin 10/40
Subjects who received ezetimibe 10 mg plus simvastatin 40 mg once daily
|
Ezetimibe Matching Placebo/ Simvastatin 10
Subjects who received simvastatin monotherapy 10 mg once daily
|
Ezetimibe Matching Placebo/ Simvastatin 20
Subjects who received simvastatin monotherapy 20 mg once daily
|
Ezetimibe Matching Placebo/ Simvastatin 40
Subjects who received simvastatin monotherapy 40 mg once daily
|
Long-term Experience Ezetimbe/Simvastatin
Subjects who received long-term coadministration of ezetimibe with simvastatin once daily
|
|---|---|---|---|---|---|---|---|
|
Start Period1 to End Period1 (Week 1-6)
Adverse Event
|
0
|
1
|
1
|
0
|
0
|
1
|
0
|
|
Start Period1 to End Period1 (Week 1-6)
Lost to Follow-up
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Start Period1 to End Period1 (Week 1-6)
Protocol Violation
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Start Period1 to End Period1 (Week 1-6)
Withdrawal by Subject
|
0
|
0
|
1
|
0
|
1
|
0
|
0
|
|
Start Period2 to End Period2 (Week 7-33)
Adverse Event
|
0
|
0
|
2
|
0
|
0
|
0
|
0
|
|
Start Period2 to End Period2 (Week 7-33)
Laboratory Adverse Event
|
0
|
0
|
3
|
0
|
0
|
1
|
0
|
|
Start Period2 to End Period2 (Week 7-33)
Lost to Follow-up
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Start Period2 to End Period2 (Week 7-33)
Withdrawal by Subject
|
0
|
0
|
1
|
0
|
0
|
3
|
0
|
|
Start Period2 to End Period2 (Week 7-33)
Protocol Violation
|
0
|
0
|
1
|
0
|
0
|
1
|
0
|
|
Start Period3 to End Period3(Week 34-53)
Lost to Follow-up
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Start Period3 to End Period3(Week 34-53)
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
0
|
0
|
3
|
|
Start Period3 to End Period3(Week 34-53)
Subject moved
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
|
Start Period3 to End Period3(Week 34-53)
Protocol Violation
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Effects of Ezetimibe With Simvastatin in the Therapy of Adolescents With HeFH (Study P02579)
Baseline characteristics by cohort
| Measure |
Pooled Subjects Who Received Ezetimibe With Simvastatin
n=126 Participants
Pooled subjects who received ezetimibe 10 mg plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
|
Pooled Subjects Who Received Simvastatin Monotherapy
n=122 Participants
Pooled subjects who received ezetimibe placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
|
Total
n=248 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
14.0 years
STANDARD_DEVIATION 1.9 • n=5 Participants
|
14.3 years
STANDARD_DEVIATION 1.8 • n=7 Participants
|
14.2 years
STANDARD_DEVIATION 1.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
53 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
106 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
73 Participants
n=5 Participants
|
69 Participants
n=7 Participants
|
142 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: baseline to 6 weeksPopulation: 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.
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
Outcome measures
| Measure |
Pooled Subjects Who Received Ezetimibe With Simvastatin
n=126 Participants
Pooled subjects who received ezetimibe 10 mg plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
|
Pooled Subjects Who Received Simvastatin Monotherapy
n=120 Participants
Pooled subjects who received ezetimibe placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
|
|---|---|---|
|
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
|
-49.45 percent change
Standard Error 1.19
|
-34.43 percent change
Standard Error 1.22
|
SECONDARY outcome
Timeframe: baseline to 6 weeksPopulation: ITT
Outcome measures
| Measure |
Pooled Subjects Who Received Ezetimibe With Simvastatin
n=126 Participants
Pooled subjects who received ezetimibe 10 mg plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
|
Pooled Subjects Who Received Simvastatin Monotherapy
n=120 Participants
Pooled subjects who received ezetimibe placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
|
|---|---|---|
|
Percent Change From Baseline in Total Cholesterol (TC)
|
-38.23 percent change
Standard Error .96
|
-26.28 percent change
Standard Error .99
|
SECONDARY outcome
Timeframe: baseline to 6 weeksPopulation: ITT
Outcome measures
| Measure |
Pooled Subjects Who Received Ezetimibe With Simvastatin
n=126 Participants
Pooled subjects who received ezetimibe 10 mg plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
|
Pooled Subjects Who Received Simvastatin Monotherapy
n=120 Participants
Pooled subjects who received ezetimibe placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
|
|---|---|---|
|
Percent Change From Baseline in Non High-density Lipoprotein Cholesterol (Non HDL-C)
|
-46.84 percent change
Standard Error 1.13
|
-32.68 percent change
Standard Error 1.16
|
SECONDARY outcome
Timeframe: baseline to 6 weeksPopulation: ITT
Outcome measures
| Measure |
Pooled Subjects Who Received Ezetimibe With Simvastatin
n=126 Participants
Pooled subjects who received ezetimibe 10 mg plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
|
Pooled Subjects Who Received Simvastatin Monotherapy
n=120 Participants
Pooled subjects who received ezetimibe placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
|
|---|---|---|
|
Percent Change From Baseline in Triglycerides (TG)
|
-16.56 percent change
Standard Deviation 30.26
|
-12.28 percent change
Standard Deviation 31.49
|
SECONDARY outcome
Timeframe: baseline to 6 weeksPopulation: ITT
Outcome measures
| Measure |
Pooled Subjects Who Received Ezetimibe With Simvastatin
n=122 Participants
Pooled subjects who received ezetimibe 10 mg plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
|
Pooled Subjects Who Received Simvastatin Monotherapy
n=118 Participants
Pooled subjects who received ezetimibe placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
|
|---|---|---|
|
Percent Change From Baseline in Apolipoprotein B (Apo B)
|
-38.92 percent change
Standard Error 1.1
|
-26.69 percent change
Standard Error 1.11
|
SECONDARY outcome
Timeframe: baseline to 6 weeksPopulation: ITT
Outcome measures
| Measure |
Pooled Subjects Who Received Ezetimibe With Simvastatin
n=126 Participants
Pooled subjects who received ezetimibe 10 mg plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
|
Pooled Subjects Who Received Simvastatin Monotherapy
n=120 Participants
Pooled subjects who received ezetimibe placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
|
|---|---|---|
|
Percent Change From Baseline in HDL-C
|
6.58 percent change
Standard Error 1.16
|
6.47 percent change
Standard Error 1.19
|
Adverse Events
Ezetimibe With Simvastatin
Serious events: 4 serious events
Other events: 58 other events
Deaths: 0 deaths
Simvastatin Monotherapy
Serious events: 1 serious events
Other events: 59 other events
Deaths: 0 deaths
Long-term Coadministration of Ezetimibe With Simvastatin
Serious events: 3 serious events
Other events: 42 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ezetimibe With Simvastatin
n=126 participants at risk
Column 1 provides the combined AE data collected for subjects in the ezetimibe with simvastatin treatment groups during Period 1 and Period 2
|
Simvastatin Monotherapy
n=122 participants at risk
Column 2 provides the combined AE data collected for subjects in the simvastatin monotherapy treatment
groups during Period 1 and Period 2.
|
Long-term Coadministration of Ezetimibe With Simvastatin
n=227 participants at risk
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.
|
|---|---|---|---|
|
General disorders
Pyrexia
|
0.79%
1/126 • Number of events 1
|
0.00%
0/122
|
0.00%
0/227
|
|
Infections and infestations
Arthritis bacterial
|
0.79%
1/126 • Number of events 1
|
0.00%
0/122
|
0.00%
0/227
|
|
Infections and infestations
Pilonidal cyst
|
0.00%
0/126
|
0.00%
0/122
|
0.44%
1/227 • Number of events 1
|
|
Infections and infestations
Subcutaneous abscess
|
0.00%
0/126
|
0.00%
0/122
|
0.44%
1/227 • Number of events 1
|
|
Infections and infestations
Tonsillitis
|
0.79%
1/126 • Number of events 1
|
0.00%
0/122
|
0.00%
0/227
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.00%
0/126
|
0.82%
1/122 • Number of events 1
|
0.00%
0/227
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/126
|
0.00%
0/122
|
0.44%
1/227 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
0.79%
1/126 • Number of events 1
|
0.00%
0/122
|
0.00%
0/227
|
|
Nervous system disorders
Encephalopathy
|
0.79%
1/126 • Number of events 1
|
0.00%
0/122
|
0.00%
0/227
|
Other adverse events
| Measure |
Ezetimibe With Simvastatin
n=126 participants at risk
Column 1 provides the combined AE data collected for subjects in the ezetimibe with simvastatin treatment groups during Period 1 and Period 2
|
Simvastatin Monotherapy
n=122 participants at risk
Column 2 provides the combined AE data collected for subjects in the simvastatin monotherapy treatment
groups during Period 1 and Period 2.
|
Long-term Coadministration of Ezetimibe With Simvastatin
n=227 participants at risk
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.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
7.1%
9/126 • Number of events 9
|
2.5%
3/122 • Number of events 3
|
0.88%
2/227 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
6.3%
8/126 • Number of events 12
|
3.3%
4/122 • Number of events 4
|
0.88%
2/227 • Number of events 2
|
|
Infections and infestations
Influenza
|
6.3%
8/126 • Number of events 9
|
9.8%
12/122 • Number of events 14
|
5.3%
12/227 • Number of events 12
|
|
Infections and infestations
Nasopharyngitis
|
21.4%
27/126 • Number of events 30
|
22.1%
27/122 • Number of events 31
|
7.0%
16/227 • Number of events 16
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.6%
7/126 • Number of events 10
|
0.82%
1/122 • Number of events 1
|
0.00%
0/227
|
|
Nervous system disorders
Headache
|
12.7%
16/126 • Number of events 25
|
13.1%
16/122 • Number of events 22
|
2.6%
6/227 • Number of events 6
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.2%
4/126 • Number of events 4
|
6.6%
8/122 • Number of events 9
|
2.2%
5/227 • Number of events 6
|
|
Skin and subcutaneous tissue disorders
Acne
|
3.2%
4/126 • Number of events 4
|
7.4%
9/122 • Number of events 9
|
1.3%
3/227 • Number of events 3
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme Corp.
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60