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

Phase 3

Completed

• Conditions: Primary Hypercholesterolemia
• Interventions: Drug: Placebo; Drug: ezetimibe

• Registration Number: NCT00867165
• Lead Sponsor: Organon and Co

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-03-20
• Study First Submitted QC: 2009-03-20
• Study First Posted: 2009-03-23
• Study Start: 2009-05-21
• Primary Completion: 2012-04-13
• Study Completion: 2012-04-13
• Results First Submitted: 2013-04-10
• Results First Submitted QC: 2013-04-10
• Results First Posted: 2013-05-30
• Status Verified: 2022-02
• Last Update Submitted: 2024-05-08
• Last Update Posted: 2024-05-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 138

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo to match ezetimibe 10-mg tablet once daily for 12 weeks
Ezetimibe	ezetimibe	Ezetimibe 10-mg tablet once daily for 12 weeks

Primary Outcome Measures

Name	Time	Method
Percentage Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 12	Baseline and 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).

Secondary Outcome Measures

Name	Time	Method
Percentage Change From Baseline in Campesterol at Week 4	Baseline and Week 4	Plasma campesterol measured at baseline and after 4 weeks of study drug administration.
Percentage Change From Baseline in Apolipoprotein B (Apo B) at Week 12	Baseline and Week 12	Serum Apo B measured at baseline and after 12 weeks of study drug administration.
Percent Change From Baseline in LDL-C at Week 8	Baseline and 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).
Percentage Change From Baseline HDL-C at Week 8	Baseline and Week 8	Serum HDL-C levels measured by photometry after precipitation at baseline and after 8 weeks of study drug administration.
Percentage Change From Baseline in LDL-C:HDL-C Ratio at Week 2	Baseline and Week 2	Serum LDL-C:HDL-C Ratio calculated at baseline and after 2 weeks of study drug administration.
Percentage Change From Baseline in LDL-C:HDL-C Ratio at Week 8	Baseline and Week 8	Serum LDL-C:HDL-C Ratio calculated at baseline and after 8 weeks of study drug administration.
Percentage Change From Baseline in Apo B:Apo A-I Ratio at Week 12	Baseline and Week 12	Serum Apo B:Apo A-I Ratio calculated at baseline and after 12 weeks of study drug administration
Percentage Change From Baseline High-density Lipoprotein Cholesterol (HDL-C) at Week 12	Baseline and Week 12	Serum HDL-C levels measured by photometry after precipitation at baseline and after 12 weeks of study drug administration.
Percentage Change From Baseline in TC at Week 4	Baseline and Week 4	Serum TC levels measured using enzymatic methods at baseline and after 4 weeks of study drug administration.
Percentage Change From Baseline HDL-C at Week 4	Baseline and Week 4	Serum HDL-C levels measured by photometry after precipitation at baseline and after 4 weeks of study drug administration.
Percentage Change From Baseline in Non-HDL-C at Week 8	Baseline and 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.
Percentage Change From Baseline in Non-HDL-C at Week 12	Baseline and 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.
Percentage Change From Baseline in Triglycerides (TG) at Week 12	Baseline and Week 12	Serum TG levels measured using enzymatic methods at baseline and after 12 weeks of study drug.
Percentage Change From Baseline in TC at Week 2	Baseline and Week 2	Serum TC levels measured using enzymatic methods at baseline and after 2 weeks of study drug administration.
Percentage Change From Baseline HDL-C at Week 2	Baseline and Week 2	Serum HDL-C levels measured by photometry after precipitation at baseline and after 2 weeks of study drug administration.
Percentage Change From Baseline in Non-HDL-C at Week 4	Baseline and 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.
Percentage Change From Baseline in TG at Week 2	Baseline and Week 2	Serum TG levels measured using enzymatic methods at baseline and after 2 weeks of study drug administration.
Percentage Change From Baseline in TG at Week 8	Baseline and Week 8	Serum TG levels measured using enzymatic methods at baseline and after 8 weeks of study drug administration.
Percentage Change From Baseline in Apolipoprotein A-I (Apo A-I) at Week 12	Baseline and Week 12	Serum Apo A-I levels measured at baseline and after 12 weeks of study drug administration.
Percentage Change From Baseline in Total Cholesterol (TC) at Week 12	Baseline and Week 12	Serum TC levels measured using enzymatic methods at baseline and after 12 weeks of study drug administration.
Percent Change From Baseline in LDL-C at Week 2	Baseline and 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).
Percent Change From Baseline in LDL-C at Week 4	Baseline and 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).
Percentage Change From Baseline in TC at Week 8	Baseline and Week 8	Serum TC levels measured using enzymatic methods at baseline and after 8 weeks of study drug administration.
Percentage Change From Baseline in Non-HDL-C at Week 2	Baseline and 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.
Percentage Change From Baseline in TG at Week 4	Baseline and Week 4	Serum TG levels measured using enzymatic methods at baseline and after 4 weeks of study drug administration.
Percentage Change From Baseline in TC:HDL-C Ratio at Week 8	Baseline and Week 8	Serum TC:HDL-C Ratio calculated at baseline and after 8 weeks of study drug administration.
Percentage Change From Baseline in TC:HDL-C Ratio at Week 12	Baseline and Week 12	Serum TC:HDL-C Ratio calculated at baseline and after 12 weeks of study drug administration.
Percentage Change From Baseline in LDL-C:HDL-C Ratio at Week 4	Baseline and Week 4	Serum LDL-C:HDL-C Ratio calculated at baseline and after 4 weeks of study drug administration.
Percentage Change From Baseline in TC:HDL-C Ratio at Week 2	Baseline and Week 2	Serum TC:HDL-C Ratio calculated at baseline and after 2 weeks of study drug administration.
Percentage Change From Baseline in TC:HDL-C Ratio at Week 4	Baseline and Week 4	Serum TC:HDL-C Ratio calculated at baseline and after 4 weeks of study drug administration.
Percentage Change From Baseline in LDL-C:HDL-C Ratio at Week 12	Baseline and Week 12	Serum LDL-C:HDL-C Ratio calculated at baseline and after 12 weeks of study drug administration.
Percentage Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 4	Baseline and Week 4	Plasma hs-CRP measured at baseline and after 4 weeks of study drug administration.
Percentage Change From Baseline in Lathosterol at Week 2	Baseline and Week 2	Plasma lathosterol measured at baseline and after 2 weeks of study drug administration.
Percentage Change From Baseline in Lathosterol at Week 4	Baseline and Week 4	Plasma lathosterol measured at baseline and after 4 weeks of study drug administration.
Percentage Change From Baseline in Lathosterol at Week 8	Baseline and Week 8	Plasma lathosterol measured at baseline and after 8 weeks of study drug administration.
Percentage Change From Baseline in Cholestanol at Week 4	Baseline and Week 4	Plasma cholestanol measured at baseline and after 4 weeks of study drug administration.
Percentage Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) at Week 12	Baseline and Week 12	Plasma hs-CRP measured at baseline and after 12 weeks of study drug administration.
Percent Change From Baseline in Sitosterol at Week 2	Baseline and Week 2	Plasma sitosterol measured at baseline and after 2 weeks of study drug administration.
Percentage Change From Baseline in Sitosterol at Week 8	Baseline and Week 8	Plasma sitosterol measured at baseline and after 8 weeks of study drug administration.
Percentage Change From Baseline in Campesterol at Week 2	Baseline and Week 2	Plasma campesterol measured at baseline and after 2 weeks of study drug administration.
Percentage Change From Baseline in Campesterol at Week 8	Baseline and Week 8	Plasma campesterol measured at baseline and after 8 weeks of study drug administration.
Percentage Change From Baseline in Campesterol at Week 12	Baseline and Week 12	Plasma campesterol measured at baseline and after 12 weeks of study drug administration.
Percentage Change From Baseline in Cholestanol at Week 12	Baseline and Week 12	Plasma cholestanol measured at baseline and after 12 weeks of study drug administration.
Percentage Change From Baseline in Sitosterol at Week 4	Baseline and Week 4	Plasma sitosterol measured at baseline and after 4 weeks of study drug administration.
Percentage Change From Baseline in Sitosterol at Week 12	Baseline and Week 12	Plasma sitosterol measured at baseline and after 12 weeks of study drug administration.
Percentage Change From Baseline in Cholestanol at Week 2	Baseline and Week 2	Plasma cholestanol measured at baseline and after 2 weeks of study drug administration.
Percentage Change From Baseline in Cholestanol at Week 8	Baseline and Week 8	Plasma cholestanol measured at baseline and after 8 weeks of study drug administration.
Percentage Change From Baseline in Lathosterol at Week 12	Baseline and Week 12	Plasma lathosterol measured at baseline and after 12 weeks of study drug administration.