Pediatric Study to Evaluate the Efficacy and Safety of Ezetimibe Monotherapy in Children With Primary Hypercholesterolemia (P05522)

Study Overview
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Brief Summary
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The purpose of this study is to determine the effect of ezetimibe 10 mg/day compared to placebo on the reduction of low-density lipoprotein cholesterol (LDL-C) from baseline to 12 weeks of treatment in children >=6 to <=10 years old with primary hypercholesterolemia. The study will also evaluate the effect of ezetimibe on total cholesterol (TC), apolipoprotein B (Apo B), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and triglycerides (TG). The safety of ezetimibe in this subject population will also be evaluated.

Official Title
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A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Efficacy and Safety Study of Ezetimibe Monotherapy in Children (Ages 6 to 10 Years) With Primary Hypercholesterolemia (Heterozygous Familial and Nonfamilial) (Phase 3, Protocol No. P05522)

Conditions
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Primary Hypercholesterolemia

Intervention / Treatment
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* Drug: ezetimibe
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Each subject may be of either sex and of any race/ethnicity, and must be >=6 and <=10 years of age, with a diagnosis of primary hypercholesterolemia (heterozygous familial or nonfamilial) despite being on a lipid-lowering diet for at least 3 months with a LDL-C of >159mg/dL Each subject's parent/guardian must be willing to give written informed consent on his/her behalf. Exclusion Criteria: Each subject must not: Have known hypersensitivity or any contraindication to ezetimibe. Have use of any investigational drugs within 30 days of study entry. Be a member or a family member of the personnel of the investigational or sponsor staff directly involved with this trial. Be a female of child-bearing potential who is pregnant, intends to become pregnant, or is nursing Have known congenital cardiac disorder. Have documented or laboratory values consistent with homozygous familial hypercholesterolemia (HoFH). Be known to be human immunodeficiency virus (HIV) positive.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 10 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: Ezetimibe<br>Ezetimibe 10-mg tablet once daily for 12 weeks | Drug: ezetimibe<br>* oral tablets: ezetimibe 10 mg once daily for 12 weeks<br>* Other names: Zetia;|
| Placebo Comparator: Placebo<br>Placebo to match ezetimibe 10-mg tablet once daily for 12 weeks | Drug: Placebo<br>* oral tablets: placebo to match ezetimibe 10 mg; administered once daily during the 5-week, single-blind, placebo run-in and diet stabilization period and 12-week double-blind treatment period<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12 | Serum LDL-C levels calculated at baseline and after 12 weeks of study drug administration. LDL-C were calculated by the method of Friedewald equation, LDL-C = Total Cholesterol (TC) - (High-density lipoprotein cholesterol [HDL-C] + triglyceride [TG]/5). | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Baseline in Total Cholesterol (TC) at Week 12 | Serum TC levels measured using enzymatic methods at baseline and after 12 weeks of study drug administration. | Baseline and Week 12 | 
| Percentage Change From Baseline in Apolipoprotein B (Apo B) at Week 12 | Serum Apo B measured at baseline and after 12 weeks of study drug administration. | Baseline and Week 12 | 
| Percentage Change From Baseline High-density Lipoprotein Cholesterol (HDL-C) at Week 12 | Serum HDL-C levels measured by photometry after precipitation at baseline and after 12 weeks of study drug administration. | Baseline and Week 12 | 
| Percentage Change From Baseline in Non-HDL-C at Week 12 | Serum Non-HDL-C calculated at baseline and after 12 weeks of study drug administration. Non-HDL-C values were calculated as follows: Non-HDL-C (mg/dL) = TC - HDL-C. | Baseline and Week 12 | 
| Percentage Change From Baseline in Triglycerides (TG) at Week 12 | Serum TG levels measured using enzymatic methods at baseline and after 12 weeks of study drug. | Baseline and Week 12 | 
| Percent Change From Baseline in LDL-C at Week 2 | Serum LDL-C levels calculated at baseline and after 2 weeks of study drug administration. LDL-C were calculated by the method of Friedewald equation, LDL-C = Total Cholesterol (TC) - (High-density lipoprotein cholesterol [HDL-C] + triglyceride [TG]/5). | Baseline and Week 2 | 
| Percent Change From Baseline in LDL-C at Week 4 | Serum LDL-C levels calculated at baseline and after 4 weeks of study drug administration. LDL-C were calculated by the method of Friedewald equation, LDL-C = Total Cholesterol (TC) - (High-density lipoprotein cholesterol [HDL-C] + triglyceride [TG]/5). | Baseline and Week 4 | 
| Percent Change From Baseline in LDL-C at Week 8 | Serum LDL-C levels calculated at baseline and after 8 weeks of study drug administration. LDL-C were calculated by the method of Friedewald equation, LDL-C = Total Cholesterol (TC) - (High-density lipoprotein cholesterol [HDL-C] + triglyceride [TG]/5). | Baseline and Week 8 | 
| Percentage Change From Baseline in TC at Week 2 | Serum TC levels measured using enzymatic methods at baseline and after 2 weeks of study drug administration. | Baseline and Week 2 | 
| Percentage Change From Baseline in TC at Week 4 | Serum TC levels measured using enzymatic methods at baseline and after 4 weeks of study drug administration. | Baseline and Week 4 | 
| Percentage Change From Baseline in TC at Week 8 | Serum TC levels measured using enzymatic methods at baseline and after 8 weeks of study drug administration. | Baseline and Week 8 | 
| Percentage Change From Baseline HDL-C at Week 2 | Serum HDL-C levels measured by photometry after precipitation at baseline and after 2 weeks of study drug administration. | Baseline and Week 2 | 
| Percentage Change From Baseline HDL-C at Week 4 | Serum HDL-C levels measured by photometry after precipitation at baseline and after 4 weeks of study drug administration. | Baseline and Week 4 | 
| Percentage Change From Baseline HDL-C at Week 8 | Serum HDL-C levels measured by photometry after precipitation at baseline and after 8 weeks of study drug administration. | Baseline and Week 8 | 
| Percentage Change From Baseline in Non-HDL-C at Week 2 | Serum Non-HDL-C calculated at baseline and after 2 weeks of study drug administration. Non-HDL-C values were calculated as follows: Non-HDL-C (mg/dL) = TC - HDL-C. | Baseline and Week 2 | 
| Percentage Change From Baseline in Non-HDL-C at Week 4 | Serum Non-HDL-C calculated at baseline and after 4 weeks of study drug administration. Non-HDL-C values were calculated as follows: Non-HDL-C (mg/dL) = TC - HDL-C. | Baseline and Week 4 | 
| Percentage Change From Baseline in Non-HDL-C at Week 8 | Serum Non-HDL-C calculated at baseline and after 8 weeks of study drug administration. Non-HDL-C values were calculated as follows: Non-HDL-C (mg/dL) = TC - HDL-C. | Baseline and Week 8 | 
| Percentage Change From Baseline in TG at Week 2 | Serum TG levels measured using enzymatic methods at baseline and after 2 weeks of study drug administration. | Baseline and Week 2 | 
| Percentage Change From Baseline in TG at Week 4 | Serum TG levels measured using enzymatic methods at baseline and after 4 weeks of study drug administration. | Baseline and Week 4 | 
| Percentage Change From Baseline in TG at Week 8 | Serum TG levels measured using enzymatic methods at baseline and after 8 weeks of study drug administration. | Baseline and Week 8 | 
| Percentage Change From Baseline in Apolipoprotein A-I (Apo A-I) at Week 12 | Serum Apo A-I levels measured at baseline and after 12 weeks of study drug administration. | Baseline and Week 12 | 
| Percentage Change From Baseline in TC:HDL-C Ratio at Week 2 | Serum TC:HDL-C Ratio calculated at baseline and after 2 weeks of study drug administration. | Baseline and Week 2 | 
| Percentage Change From Baseline in TC:HDL-C Ratio at Week 4 | Serum TC:HDL-C Ratio calculated at baseline and after 4 weeks of study drug administration. | Baseline and Week 4 | 
| Percentage Change From Baseline in TC:HDL-C Ratio at Week 8 | Serum TC:HDL-C Ratio calculated at baseline and after 8 weeks of study drug administration. | Baseline and Week 8 | 
| Percentage Change From Baseline in TC:HDL-C Ratio at Week 12 | Serum TC:HDL-C Ratio calculated at baseline and after 12 weeks of study drug administration. | Baseline and Week 12 | 
| Percentage Change From Baseline in LDL-C:HDL-C Ratio at Week 2 | Serum LDL-C:HDL-C Ratio calculated at baseline and after 2 weeks of study drug administration. | Baseline and Week 2 | 
| Percentage Change From Baseline in LDL-C:HDL-C Ratio at Week 4 | Serum LDL-C:HDL-C Ratio calculated at baseline and after 4 weeks of study drug administration. | Baseline and Week 4 | 
| Percentage Change From Baseline in LDL-C:HDL-C Ratio at Week 8 | Serum LDL-C:HDL-C Ratio calculated at baseline and after 8 weeks of study drug administration. | Baseline and Week 8 | 
| Percentage Change From Baseline in LDL-C:HDL-C Ratio at Week 12 | Serum LDL-C:HDL-C Ratio calculated at baseline and after 12 weeks of study drug administration. | Baseline and Week 12 | 
| Percentage Change From Baseline in Apo B:Apo A-I Ratio at Week 12 | Serum Apo B:Apo A-I Ratio calculated at baseline and after 12 weeks of study drug administration | Baseline and Week 12 | 
| Percentage Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 4 | Plasma hs-CRP measured at baseline and after 4 weeks of study drug administration. | Baseline and Week 4 | 
| Percentage Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 12 | Plasma hs-CRP measured at baseline and after 12 weeks of study drug administration. | Baseline and Week 12 | 
| Percent Change From Baseline in Sitosterol at Week 2 | Plasma sitosterol measured at baseline and after 2 weeks of study drug administration. | Baseline and Week 2 | 
| Percentage Change From Baseline in Sitosterol at Week 4 | Plasma sitosterol measured at baseline and after 4 weeks of study drug administration. | Baseline and Week 4 | 
| Percentage Change From Baseline in Sitosterol at Week 8 | Plasma sitosterol measured at baseline and after 8 weeks of study drug administration. | Baseline and Week 8 | 
| Percentage Change From Baseline in Sitosterol at Week 12 | Plasma sitosterol measured at baseline and after 12 weeks of study drug administration. | Baseline and Week 12 | 
| Percentage Change From Baseline in Campesterol at Week 2 | Plasma campesterol measured at baseline and after 2 weeks of study drug administration. | Baseline and Week 2 | 
| Percentage Change From Baseline in Campesterol at Week 4 | Plasma campesterol measured at baseline and after 4 weeks of study drug administration. | Baseline and Week 4 | 
| Percentage Change From Baseline in Campesterol at Week 8 | Plasma campesterol measured at baseline and after 8 weeks of study drug administration. | Baseline and Week 8 | 
| Percentage Change From Baseline in Campesterol at Week 12 | Plasma campesterol measured at baseline and after 12 weeks of study drug administration. | Baseline and Week 12 | 
| Percentage Change From Baseline in Cholestanol at Week 2 | Plasma cholestanol measured at baseline and after 2 weeks of study drug administration. | Baseline and Week 2 | 
| Percentage Change From Baseline in Cholestanol at Week 4 | Plasma cholestanol measured at baseline and after 4 weeks of study drug administration. | Baseline and Week 4 | 
| Percentage Change From Baseline in Cholestanol at Week 8 | Plasma cholestanol measured at baseline and after 8 weeks of study drug administration. | Baseline and Week 8 | 
| Percentage Change From Baseline in Cholestanol at Week 12 | Plasma cholestanol measured at baseline and after 12 weeks of study drug administration. | Baseline and Week 12 | 
| Percentage Change From Baseline in Lathosterol at Week 2 | Plasma lathosterol measured at baseline and after 2 weeks of study drug administration. | Baseline and Week 2 | 
| Percentage Change From Baseline in Lathosterol at Week 4 | Plasma lathosterol measured at baseline and after 4 weeks of study drug administration. | Baseline and Week 4 | 
| Percentage Change From Baseline in Lathosterol at Week 8 | Plasma lathosterol measured at baseline and after 8 weeks of study drug administration. | Baseline and Week 8 | 
| Percentage Change From Baseline in Lathosterol at Week 12 | Plasma lathosterol measured at baseline and after 12 weeks of study drug administration. | Baseline and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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heterozygous familial hypercholesterolemia, nonfamilial hypercholesterolemia