Ezetimibe (SCH 58235) Taken With Either Atorvastatin or Simvastatin in Participants With Familial Hypercholesterolemia (MK-0653-018)

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the efficacy and the safety of ezetimibe (SCH 58235) co-administered with either atorvastatin or simvastatin in participants with homozygous familial hypercholesterolemia (FH).

Official Title
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A Phase III Efficacy And Safety Study of Ezetimibe (SCH58235) 10 mg in Addition to Atorvastatin or Simvastatin in the Therapy of Homozygous Familial Hypercholesterolemia

Conditions
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Familial Hypercholesterolemia

Intervention / Treatment
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* Drug: Atorvastatin
* Drug: Simvastatin
* Drug: Ezetimibe
* Drug: Placebo for Ezetimibe


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: With a diagnosis of homozygous familial hypercholesterolemia All females must have a negative pregnancy test prior to study entry. Women of child bearing potential must agree to practice an effective barrier method of birth control for the duration of the study, until one month after treatment. Postmenopausal women who are receiving postmenopausal hormonal therapy or raloxifene must be maintained on a stable estrogen (ERT), estrogen/progestin (HRT) or raloxifene regimen during the study period. ERT, HRT or raloxifene cannot be changed during study period. Must follow prescribed or stricter diet, and demonstrate completion of Diet Diaries Exclusion Criteria: A history of mental instability, drug or alcohol abuse; or have been treated or are being treated for severe psychiatric illness which, in the opinion of the Investigator, may interfere with optimal participation in the study. With underlying disease likely to limit life span to less than 1 year. Have previously been randomized in any studies examining ezetimibe Pregnant or lactating women. With known hypersensitivity or any contraindication to statin therapy.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atorvastatin 80 mg<br>80 mg atorvastatin taken orally, once daily for 12 weeks | Drug: Atorvastatin<br>* Tablets taken orally once daily in the morning<br>Drug: Placebo for Ezetimibe<br>* Tablets taken orally once daily in the morning or evening<br>|
| Experimental: Ezetimibe + Atorvastatin 40 mg<br>10 mg ezetimibe and 40 mg atorvastatin taken orally, once daily for 12 weeks | Drug: Atorvastatin<br>* Tablets taken orally once daily in the morning<br>Drug: Ezetimibe<br>* Tablet taken orally once daily in the morning or evening<br>|
| Experimental: Ezetimibe + Atorvastatin 80 mg<br>10 mg ezetimibe and 80 mg atorvastatin taken orally, once daily for 12 weeks | Drug: Atorvastatin<br>* Tablets taken orally once daily in the morning<br>Drug: Ezetimibe<br>* Tablet taken orally once daily in the morning or evening<br>|
| Experimental: Simvastatin 80 mg<br>80 mg simvastatin taken orally, once daily for 12 weeks | Drug: Simvastatin<br>* Tablets taken orally once daily in the morning or evening<br>Drug: Placebo for Ezetimibe<br>* Tablets taken orally once daily in the morning or evening<br>|
| Experimental: Ezetimibe + Simvastatin 40 mg<br>10 mg ezetimibe and 40 mg simvastatin taken orally, once daily for 12 weeks | Drug: Simvastatin<br>* Tablets taken orally once daily in the morning or evening<br>Drug: Ezetimibe<br>* Tablet taken orally once daily in the morning or evening<br>|
| Experimental: Ezetimibe + Simvastatin 80 mg<br>10 mg ezetimibe and 80 mg simvastatin taken orally, once daily for 12 weeks | Drug: Simvastatin<br>* Tablets taken orally once daily in the morning or evening<br>Drug: Ezetimibe<br>* Tablet taken orally once daily in the morning or evening<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in Low Density Lipoprotein Cholesterol (LDL-C) measured directly |  | Baseline and Up to Week 12 | 
| Percentage of participants with an Adverse Event (AE) |  | Up to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline in calculated LDL-C |  | Baseline and Up to Week 12 | 
| Percent change from baseline in Total Cholesterol (TC) |  | Baseline and Up to Week 12 | 
| Percent change from baseline in Triglycerides (TG) |  | Baseline and Up to Week 12 | 
| Percent change from baseline in High-density-lipoprotein cholesterol (HDL-C) |  | Baseline and Up to Week 12 | 
| Percent change from baseline in High-density-lipoprotein 2 cholesterol (HDL2-C) |  | Baseline and Up to Week 12 | 
| Percent change from baseline in High-density-lipoprotein 3 cholesterol (HDL3-C) |  | Baseline and Up to Week 12 | 
| Percent change from baseline in Apolipoprotein A-I (Apo A-I) |  | Baseline and Up to Week 12 | 
| Percent change from baseline in Apolipoprotein B (Apo B) |  | Baseline and Up to Week 12 | 
| Percent change from baseline in Lipoprotein(a) [Lp(a)] |  | Baseline and Up to Week 12 |