Effects of Ezetimibe With Simvastatin in the Therapy of Adolescents With HeFH (Study P02579)

Efficacy, Safety, and Tolerability of Ezetimibe in Coadministration With Simvastatin in the Therapy of Adolescents With Heterozygous Familial Hypercholesterolemia

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00129402

Enrollment

248

Registered

2005-08-11

Start date

2005-08-31

Completion date

2007-06-30

Last updated

2022-02-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hypercholesterolemia

Keywords

cholesterol, drugs, hypercholesterolemia, adolescent, randomized controlled trials

Brief summary

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.

Detailed description

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.

Interventions

DRUGezetimibe with simvastatin

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

DRUGsimvastatin

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

10 Years to 17 Years

Healthy volunteers

Inclusion criteria

* Adolescent (ages 10 - 17 years) boys or girls weighing at least 88 lbs (40 kg). * Subjects must have high cholesterol (low density lipoprotein cholesterol \[LDL-C\] more than 159 mg/dL or 4.1 mmol/L) and a family history of high cholesterol.

Exclusion criteria

* Subjects diagnosed with delayed puberty. * Subjects who are sensitive to simvastatin and/or ezetimibe. * Subjects who drink alcohol excessively or who have a history of alcohol or drug abuse within the past 2 years. * Subjects who are known to be HIV positive, are undergoing LDL apheresis or plasma apheresis, or have had a partial ileal bypass.

Design outcomes

Primary

Measure	Time frame	Description
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)	baseline to 6 weeks	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

Secondary

Measure	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
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

Participant flow

Participants by arm

Arm	Count
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	126
Pooled Subjects Who Received Simvastatin Monotherapy Pooled subjects who received ezetimibe placebo plus simvastatin 10 mg, simvastatin 20 mg, or simvastatin 40 mg	122
Total	248

Withdrawals & dropouts

Period	Reason	FG001	FG002	FG003	FG004	FG005	FG006
Start Period1 to End Period1 (Week 1-6)	Adverse Event	1	1	0	0	1	0
Start Period1 to End Period1 (Week 1-6)	Lost to Follow-up	0	0	0	0	1	0
Start Period1 to End Period1 (Week 1-6)	Protocol Violation	0	0	1	0	0	0
Start Period1 to End Period1 (Week 1-6)	Withdrawal by Subject	0	1	0	1	0	0
Start Period2 to End Period2 (Week 7-33)	Adverse Event	0	2	0	0	0	0
Start Period2 to End Period2 (Week 7-33)	Laboratory Adverse Event	0	3	0	0	1	0
Start Period2 to End Period2 (Week 7-33)	Lost to Follow-up	0	1	0	0	0	0
Start Period2 to End Period2 (Week 7-33)	Protocol Violation	0	1	0	0	1	0
Start Period2 to End Period2 (Week 7-33)	Withdrawal by Subject	0	1	0	0	3	0
Start Period3 to End Period3(Week 34-53)	Lost to Follow-up	0	0	0	0	0	1
Start Period3 to End Period3(Week 34-53)	Protocol Violation	0	0	0	0	0	1
Start Period3 to End Period3(Week 34-53)	Subject moved	0	0	0	0	0	1
Start Period3 to End Period3(Week 34-53)	Withdrawal by Subject	0	0	0	0	0	3

Baseline characteristics

Characteristic	Pooled Subjects Who Received Ezetimibe With Simvastatin	Pooled Subjects Who Received Simvastatin Monotherapy	Total
Age, Continuous	14.0 years STANDARD_DEVIATION 1.9	14.3 years STANDARD_DEVIATION 1.8	14.2 years STANDARD_DEVIATION 1.9
Sex: Female, Male Female	53 Participants	53 Participants	106 Participants
Sex: Female, Male Male	73 Participants	69 Participants	142 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	58 / 126	59 / 122	42 / 227
serious Total, serious adverse events	4 / 126	1 / 122	3 / 227

Outcome results

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