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| ID | Type | Description | Link |
|---|---|---|---|
| EUDRACT NUMBER:2004-002627-40; | |||
| SCH 58235; | |||
| DOC ID 2526810 |
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
This is a randomized, double-blind, controlled, parallel-group, multicenter, Phase-3 study to evaluate the efficacy and safety of ezetimibe with simvastatin taken alone in subjects ages 10-17 years with Heterozygous Familial Hypercholesterolemia.
This study consisted of 3 distinct periods. In Period 1, subjects received daily treatment for 6 weeks as part of either the ezetimibe with simvastatin group or part of the simvastatin monotherapy group. Subjects in the ezetimibe with simvastatin group received one of three treatments: coadministration of ezetimibe 10 mg/day plus simvastatin 10 mg/day, 20 mg/day, or 40 mg/day. Subjects in the simvastatin monotherapy group received one of three treatments: ezetimibe placebo plus simvastatin 10 mg/day, 20 mg/day, or 40 mg/day. The primary and key secondary efficacy analysis were based on the evaluations performed during Period 1 and were presented as data for subjects pooled from either the ezetimibe with simvastatin treatment groups compared with data for subjects pooled from the simvastatin monotherapy treatment groups.
In Period 2, subjects received ezetimibe 10 mg/day plus simvastatin 40 mg/day or ezetimibe placebo plus simvastatin 40 mg/day for 27 additional weeks maintaining the same treatment assignment (coadministration vs monotherapy) as in Period 1.
In Period 3, all subjects received ezetimibe 10 mg/day plus open-label simvastatin daily for 20 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pooled subjects who received ezetimibe with simvastatin | Experimental | Pooled subjects who received ezetimibe 10 mg plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg |
|
| Pooled subjects who received simvastatin monotherapy | Active Comparator | Pooled subjects who received ezetimibe matching placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ezetimibe with simvastatin | Drug | Ezetimibe 10 mg plus simvastatin 10 mg once a day for six weeks, or Ezetimibe 10 mg plus simvastatin 20 mg once a day for six weeks, or Ezetimibe 10 mg plus simvastatin 40 mg once a day for six weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | 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 | baseline to 6 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change From Baseline in Total Cholesterol (TC) | baseline to 6 weeks | |
| Percent Change From Baseline in Non High-density Lipoprotein Cholesterol (Non HDL-C) | baseline to 6 weeks | |
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Inclusion Criteria:
Exclusion Criteria:
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 18940534 | Derived | van der Graaf A, Cuffie-Jackson C, Vissers MN, Trip MD, Gagne C, Shi G, Veltri E, Avis HJ, Kastelein JJ. Efficacy and safety of coadministration of ezetimibe and simvastatin in adolescents with heterozygous familial hypercholesterolemia. J Am Coll Cardiol. 2008 Oct 21;52(17):1421-9. doi: 10.1016/j.jacc.2008.09.002. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Ezetimibe/Simvastatin 10/10 | Subjects who received ezetimibe 10 mg plus simvastatin 10 mg once daily |
| FG001 | Ezetimibe/Simvastatin 10/20 | Subjects who received ezetimibe 10 mg with simvastatin 10 mg once daily |
| FG002 | Ezetimibe/Simvastatin 10/40 | Subjects who received ezetimibe 10 mg plus simvastatin 40 mg once daily |
| FG003 | Ezetimibe Matching Placebo/ Simvastatin 10 | Subjects who received simvastatin monotherapy 10 mg once daily |
| FG004 | Ezetimibe Matching Placebo/ Simvastatin 20 | Subjects who received simvastatin monotherapy 20 mg once daily |
| FG005 | Ezetimibe Matching Placebo/ Simvastatin 40 | Subjects who received simvastatin monotherapy 40 mg once daily |
| FG006 | Long-term Experience Ezetimbe/Simvastatin | Subjects who received long-term coadministration of ezetimibe with simvastatin once daily |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Start Period1 to End Period1 (Week 1-6) |
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| Start Period2 to End Period2 (Week 7-33) |
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| Start Period3 to End Period3(Week 34-53) |
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| ID | Title | Description |
|---|---|---|
| BG000 | Pooled Subjects Who Received Ezetimibe With Simvastatin | Pooled subjects who received ezetimibe 10 mg plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg |
| BG001 | Pooled Subjects Who Received Simvastatin Monotherapy |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) | 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 | 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. | Posted | Least Squares Mean | Standard Error | percent change | baseline to 6 weeks |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ezetimibe With Simvastatin | Column 1 provides the combined AE data collected for subjects in the ezetimibe with simvastatin treatment groups during Period 1 and Period 2 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pyrexia | General disorders | MedDRA 9.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D006937 | Hypercholesterolemia |
| ID | Term |
|---|---|
| D006949 | Hyperlipidemias |
| D050171 | Dyslipidemias |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
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| ID | Term |
|---|---|
| D000069438 | Ezetimibe |
| D019821 | Simvastatin |
| ID | Term |
|---|---|
| D001384 | Azetidines |
| D001385 | Azetines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| simvastatin | Drug | Ezetimibe matching placebo plus simvastatin 10 mg once a day for six weeks, or Ezetimibe matching placebo plus simvastatin 20 mg once a day for six weeks, or Ezetimibe matching placebo plus simvastatin 40 mg once a day for six weeks |
|
| Percent Change From Baseline in Triglycerides (TG) |
| baseline to 6 weeks |
| Percent Change From Baseline in Apolipoprotein B (Apo B) | baseline to 6 weeks |
| Percent Change From Baseline in HDL-C | baseline to 6 weeks |
| Lost to Follow-up |
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| Protocol Violation |
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| Withdrawal by Subject |
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| COMPLETED |
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| NOT COMPLETED |
|
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| COMPLETED |
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| NOT COMPLETED |
|
|
Pooled subjects who received ezetimibe placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Pooled Subjects Who Received Simvastatin Monotherapy | Pooled subjects who received ezetimibe placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg |
|
|
|
| Secondary | Percent Change From Baseline in Total Cholesterol (TC) | ITT | Posted | Least Squares Mean | Standard Error | percent change | baseline to 6 weeks |
|
|
|
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| Secondary | Percent Change From Baseline in Non High-density Lipoprotein Cholesterol (Non HDL-C) | ITT | Posted | Least Squares Mean | Standard Error | percent change | baseline to 6 weeks |
|
|
|
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| Secondary | Percent Change From Baseline in Triglycerides (TG) | ITT | Posted | Median | Standard Deviation | percent change | baseline to 6 weeks |
|
|
|
|
| Secondary | Percent Change From Baseline in Apolipoprotein B (Apo B) | ITT | Posted | Least Squares Mean | Standard Error | percent change | baseline to 6 weeks |
|
|
|
|
| Secondary | Percent Change From Baseline in HDL-C | ITT | Posted | Least Squares Mean | Standard Error | percent change | baseline to 6 weeks |
|
|
|
|
| 4 |
| 126 |
| 58 |
| 126 |
| EG001 | Simvastatin Monotherapy | Column 2 provides the combined AE data collected for subjects in the simvastatin monotherapy treatment groups during Period 1 and Period 2. | 1 | 122 | 59 | 122 |
| EG002 | Long-term Coadministration of Ezetimibe With Simvastatin | 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. | 3 | 227 | 42 | 227 |
| Arthritis bacterial | Infections and infestations | MedDRA 9.0 | Systematic Assessment |
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| Pilonidal cyst | Infections and infestations | MedDRA 9.0 | Systematic Assessment |
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| Subcutaneous abscess | Infections and infestations | MedDRA 9.0 | Systematic Assessment |
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| Tonsillitis | Infections and infestations | MedDRA 9.0 | Systematic Assessment |
|
| Accidental overdose | Injury, poisoning and procedural complications | MedDRA 9.0 | Systematic Assessment |
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| Overdose | Injury, poisoning and procedural complications | MedDRA 9.0 | Systematic Assessment |
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| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA 9.0 | Systematic Assessment |
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| Encephalopathy | Nervous system disorders | MedDRA 9.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 9.0 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 9.0 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 9.0 | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 9.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 9.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 9.0 | Systematic Assessment |
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| Acne | Skin and subcutaneous tissue disorders | MedDRA 9.0 | Systematic Assessment |
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| D009750 |
| Nutritional and Metabolic Diseases |
| D008148 |
| Lovastatin |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |