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

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)

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.

Study Overview

• Status: Completed
• Conditions: Primary Hypercholesterolemia
• Intervention / Treatment: Drug: ezetimibe; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 138
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 10 years (Child)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ezetimibe; Ezetimibe 10-mg tablet once daily for 12 weeks	Drug: ezetimibe; oral tablets: ezetimibe 10 mg once daily for 12 weeks; Other Names: MK-0653; SCH 58235; Zetia
Placebo Comparator: Placebo; Placebo to match ezetimibe 10-mg tablet once daily for 12 weeks	Drug: Placebo; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Organon and Co
• Collaborators: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Kusters DM, Caceres M, Coll M, Cuffie C, Gagne C, Jacobson MS, Kwiterovich PO, Lee R, Lowe RS, Massaad R, McCrindle BW, Musliner TA, Triscari J, Kastelein JJ. Efficacy and safety of ezetimibe monotherapy in children with heterozygous familial or nonfamilial hypercholesterolemia. J Pediatr. 2015 Jun;166(6):1377-84.e1-3. doi: 10.1016/j.jpeds.2015.02.043. Epub 2015 Apr 1.

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2009
• Primary Completion (Actual): April 13, 2012
• Study Completion (Actual): April 13, 2012

Study Registration Dates

• First Submitted: March 20, 2009
• First Submitted That Met QC Criteria: March 20, 2009
• First Posted (Estimated): March 23, 2009

Study Record Updates

• Last Update Posted (Actual): May 21, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: heterozygous familial hypercholesterolemia; nonfamilial hypercholesterolemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Ezetimibe
• Other Study ID Numbers: P05522; 2008-006271-70 (EudraCT Number); MK-0653-170 (Other Identifier: Merck Study Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php