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CompletedNCT00276458Updated May 13, 2024Results posted

To Evaluate Ezetimibe Plus Atorvastatin Versus Atorvastatin in Patients With High Cholesterol Not Controlled on Atorvastatin 20 mg (0653-079)(COMPLETED)

A Phase 3 interventional study of Comparator: atorvastatin and Comparator: Placebo in Hypercholesterolemia, sponsored by Organon and Co. Completed. Open to participants aged 18 Years to 79 Years. Per ClinicalTrials.gov, last updated 2024-05-13.

Sponsored by Organon and Co · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
196
Allocation
Randomized
Ages
18 Years to 79 Years
Sex
All
01

Study summary

The purpose of this study is to evaluate and compare the efficacy and safety of ezetimibe plus atorvastatin versus atorvastatin in hypercholesterolemic patients at moderately high risk for coronary heart disease not adequately controlled on atorvastatin 20 mg.

02

Conditions studied

  • Hypercholesterolemia
03

In context

Hypercholesterolemia

1,238 studies on the registry are indexed under Hypercholesterolemia; 109 are open to participants now.

This study's enrollment of 196 is above the median of 99 across 991 interventional studies indexed under Hypercholesterolemia.

Browse Hypercholesterolemia studies →

Lead sponsor

Organon and Co is the lead sponsor of 478 studies on the registry; none are open to participants now.

Of its 21 completed or terminated interventional studies of FDA-regulated products, 17 (81%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 79 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patient with LDL-C >100 mg/dL \& on a stable dose of atorvastatin 20 mg

Exclusion criteria

Exclusion Criteria:

  • Pregnant or lactating women or intending to become pregnant
  • Patient with sensitivity or intolerance to ezetimibe or atorvastatin
  • Patient with diabetes or coronary heart disease
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
196 participants (actual)

Study arms

  • Active comparator
    1

    Atorvastatin 40mg tablet + Atorvastatin 20mg Pbo and ezetimibe 10mg Pbo tablets po qd (by mouth, once a day).

    Drug: Comparator: atorvastatin · Drug: Comparator: Placebo

  • Experimental
    2

    Atorvastatin 40mg Pbo tablet + Atorvastatin 20mg and ezetimibe 10mg tablets po qd (by mouth, once a day).

    Drug: Comparator: ezetimibe · Drug: Comparator: Placebo.

Interventions

  • DrugComparator: atorvastatin

    Atorvastatin 40mg tablet po qd (by mouth, once a day) for 6 weeks

  • DrugComparator: Placebo

    Atorvastatin 20mg Pbo and ezetimibe 10mg Pbo tablets po qd (by mouth, once a day). for 6 weeks

  • DrugComparator: ezetimibe

    Atorvastatin 20mg and ezetimibe 10mg tablets po qd (by mouth, once a day). for 6 weeks.

  • DrugComparator: Placebo.

    Atorvastatin 40mg Pbo tablets po qd (by mouth, once a day). for 6 weeks.

06

What researchers measure

Primary outcomes

  1. Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Week 6

    \[(6 week value - baseline value)/baseline value\]\*100%.

    Time frame: 6 weeks

Secondary outcomes

  1. Percent Change in High Density Lipoprotein -Cholesterol (HDL-C)at Week 6

    \[(6 week value - baseline value)/baseline value\]\*100%.

    Time frame: 6 weeks

  2. Percent Change in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 6

    \[(6 week value - baseline value)/baseline value\]\*100%.

    Time frame: 6 Weeks

  3. Percent Change From Baseline in Total-Cholesterol at Week 6

    (\[6 week value - baseline value)/baseline value\]\*100%.

    Time frame: 6 Weeks

  4. Percent Change From Baseline in Triglycerides (TG) at Week 6

    \[(6 week value - baseline value)/baseline value\]\*100%.

    Time frame: 6 weeks

  5. Percent Change From Baseline in Apolipoprotein B at Week 6

    \[(6 week value - baseline value)/baseline value\]\*100%.

    Time frame: 6 Weeks

  6. Percent Change From Baseline in Total-Cholesterol:High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6

    \[(6 week value - baseline value)/baseline value\]\*100%.

    Time frame: 6 Weeks

  7. Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C):High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6

    \[(6 week value - baseline value)/baseline value\]\*100%.

    Time frame: 6 Weeks

  8. Percent Change From Baseline in Apolipoprotein B: Apolipoprotein A-I Ratio at Week 6

    \[(6 week value - baseline value)/baseline value\]\*100%.

    Time frame: 6 Weeks

  9. Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (HDL-C):High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6

    \[(6 week value - baseline value)/baseline value\]\*100%.

    Time frame: 6 Weeks

  10. Percent Change From Baseline in C-Reactive Protein (CRP) at Week 6

    \[(6 week value - baseline value)/baseline value\]\*100%.

    Time frame: 6 Weeks

  11. Number of Participants Who Attained Target LDL-C <100 mg/dL at Week 6

    Time frame: 6 weeks

07

Results

Posted Jul 8, 2009
Limitations and caveats
194 out of 196 randomized patients took at least one dose of blinded study therapy and were included in the safety analysis

Participant flow

Phase III First Patient In: 4/5/2006; Last Patient Last Visit 1/17/2008 72 centers worldwide (US, Canada, Austria, Costa Rica) Eligible patients include those on a stable dose of atorvastatin 20 mg; or patients with adjusted LDL-C pre-screen ranges who were treated with other lipid modifying therapy, or were statin and/or ezetimibe naïve.

Participant flow — Overall Study
MilestoneAtorvastatin + EzetimibeAtorvastatin
Started9898
Completed9291
Not completed67
Withdrew: Adverse event02
Withdrew: Lost to follow-up22
Withdrew: Protocol violation43

Outcome measures

PrimaryPercent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Week 6

\[(6 week value - baseline value)/baseline value\]\*100%.

Time frame:
6 weeks
Reported as:
Least squares mean · Percent
Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Week 6
PercentAtorvastatin + EzetimibeAtorvastatin
Percent Change From Baseline in Low Density Lipoprotein-Cholesterol (LDL-C) at Week 6-30.8 (-34.5 to -27.0)-10.9 (-14.7 to -7.1)
Statistical analysis
  • Atorvastatin + Ezetimibe vs Atorvastatin · ANCOVA · p = <0.001 · Mean difference (final values): -19.9 · 95% CI -25.2 to -14.5(Atorva + EZ minus Atorva)
SecondaryPercent Change in High Density Lipoprotein -Cholesterol (HDL-C)at Week 6

\[(6 week value - baseline value)/baseline value\]\*100%.

Time frame:
6 weeks
Reported as:
Least squares mean · Percent
Percent Change in High Density Lipoprotein -Cholesterol (HDL-C)at Week 6
PercentAtorvastatin + EzetimibeAtorvastatin
Percent Change in High Density Lipoprotein -Cholesterol (HDL-C)at Week 63.2 (0.2 to 6.2)0.8 (-2.2 to 3.8)
Statistical analysis
  • Atorvastatin + Ezetimibe vs Atorvastatin · ANCOVA · p = 0.273 · Mean difference (final values): 2.4 · 95% CI -1.9 to 6.6(Atorva + EZ minus Atorva)
SecondaryPercent Change in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 6

\[(6 week value - baseline value)/baseline value\]\*100%.

Time frame:
6 Weeks
Reported as:
Least squares mean · Percent
Percent Change in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 6
PercentAtorvastatin + EzetimibeAtorvastatin
Percent Change in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 6-26.7 (-30.1 to -23.3)-10.2 (-13.6 to -6.9)
Statistical analysis
  • Atorvastatin + Ezetimibe vs Atorvastatin · ANCOVA · p = <0.001 · Mean difference (final values): -16.4 · 95% CI -21.2 to -11.7(Atorva + EZ minus Atorva)
SecondaryPercent Change From Baseline in Total-Cholesterol at Week 6

(\[6 week value - baseline value)/baseline value\]\*100%.

Time frame:
6 Weeks
Reported as:
Least squares mean · percent
Percent Change From Baseline in Total-Cholesterol at Week 6
percentAtorvastatin + EzetimibeAtorvastatin
Percent Change From Baseline in Total-Cholesterol at Week 6-19.7 (-22.2 to -17.1)-7.4 (-10.0 to -4.9)
Statistical analysis
  • Atorvastatin + Ezetimibe vs Atorvastatin · ANCOVA · p = <0.001 · Mean difference (final values): -12.2 · 95% CI -15.8 to -8.6(Atorva + EZ minus Atorva)
SecondaryPercent Change From Baseline in Triglycerides (TG) at Week 6

\[(6 week value - baseline value)/baseline value\]\*100%.

Time frame:
6 weeks
Reported as:
Least squares mean · Percent
Percent Change From Baseline in Triglycerides (TG) at Week 6
PercentAtorvastatin + EzetimibeAtorvastatin
Percent Change From Baseline in Triglycerides (TG) at Week 6-17.8 (-23.7 to -11.4)-5.5 (-14.4 to 0.0)
Statistical analysis
  • Atorvastatin + Ezetimibe vs Atorvastatin · Nonparametric ANCOVA · p = 0.159 (ANCOVA using ranks based on normal scores (Tukey method) with model terms for treatment and baseline triglycerides value) · Median difference (final values): -8.9 · 95% CI -17.7 to -0.4The median difference is based on the Hodges-Lehmann estimates of shift; The distribution-free 95% CI is based on Wilcoxon's rank sum test statistic. (Atorva + EZ minus Atorva)
SecondaryPercent Change From Baseline in Apolipoprotein B at Week 6

\[(6 week value - baseline value)/baseline value\]\*100%.

Time frame:
6 Weeks
Reported as:
Least squares mean · Percent
Percent Change From Baseline in Apolipoprotein B at Week 6
PercentAtorvastatin + EzetimibeAtorvastatin
Percent Change From Baseline in Apolipoprotein B at Week 6-21.4 (-24.3 to -18.5)-7.7 (-10.6 to -4.8)
Statistical analysis
  • Atorvastatin + Ezetimibe vs Atorvastatin · ANCOVA · p = <0.001 · Mean difference (final values): -13.7 · 95% CI -17.8 to -9.6(Atorva + EZ minus Atorva)
Post-hocPercent Change in Apolipoprotein A-I at Week 6

\[(6 week value - baseline value)/baseline value\]\*100%.

Time frame:
6 Weeks
Reported as:
Least squares mean · Percent
Percent Change in Apolipoprotein A-I at Week 6
PercentAtorvastatin + EzetimibeAtorvastatin
Percent Change in Apolipoprotein A-I at Week 6-1.9 (-4.2 to 0.4)-1.2 (-3.5 to 1.1)
Statistical analysis
  • Atorvastatin + Ezetimibe vs Atorvastatin · ANCOVA · p = 0.681 · Mean difference (final values): -0.7 · 95% CI -3.9 to 2.6(Atorva + EZ minus Atorva)
SecondaryPercent Change From Baseline in Total-Cholesterol:High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6

\[(6 week value - baseline value)/baseline value\]\*100%.

Time frame:
6 Weeks
Reported as:
Least squares mean · Percent
Percent Change From Baseline in Total-Cholesterol:High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6
PercentAtorvastatin + EzetimibeAtorvastatin
Percent Change From Baseline in Total-Cholesterol:High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6-20.6 (-23.7 to -17.5)-7.5 (-10.6 to -4.4)
Statistical analysis
  • Atorvastatin + Ezetimibe vs Atorvastatin · ANCOVA · p = <0.001 · Mean difference (final values): -13.1 · 95% CI -17.5 to -8.7(Atorva + EZ minus Atorva)
SecondaryPercent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C):High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6

\[(6 week value - baseline value)/baseline value\]\*100%.

Time frame:
6 Weeks
Reported as:
Least squares mean · Percent
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C):High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6
PercentAtorvastatin + EzetimibeAtorvastatin
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C):High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6-31.9 (-35.8 to -27.9)-11.0 (-14.9 to -7.0)
Statistical analysis
  • Atorvastatin + Ezetimibe vs Atorvastatin · ANCOVA · p = <0.001 · Mean difference (final values): -20.9 · 95% CI -26.5 to -15.3(Atorva + EZ minus Atorva)
SecondaryPercent Change From Baseline in Apolipoprotein B: Apolipoprotein A-I Ratio at Week 6

\[(6 week value - baseline value)/baseline value\]\*100%.

Time frame:
6 Weeks
Reported as:
Least squares mean · Percent
Percent Change From Baseline in Apolipoprotein B: Apolipoprotein A-I Ratio at Week 6
PercentAtorvastatin + EzetimibeAtorvastatin
Percent Change From Baseline in Apolipoprotein B: Apolipoprotein A-I Ratio at Week 6-19.0 (-22.3 to -15.6)-5.8 (-9.2 to -2.5)
Statistical analysis
  • Atorvastatin + Ezetimibe vs Atorvastatin · ANCOVA · p = <0.001 · Mean difference (final values): -13.1 · 95% CI -17.9 to -8.3(Atorva + EZ minus Atorva)
SecondaryPercent Change From Baseline in Non-High Density Lipoprotein Cholesterol (HDL-C):High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6

\[(6 week value - baseline value)/baseline value\]\*100%.

Time frame:
6 Weeks
Reported as:
Least squares mean · Percent
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (HDL-C):High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6
PercentAtorvastatin + EzetimibeAtorvastatin
Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (HDL-C):High Density Lipoprotein Cholesterol (HDL-C) Ratio at Week 6-27.2 (-31.4 to -23.0)-9.9 (-14.1 to -5.7)
Statistical analysis
  • Atorvastatin + Ezetimibe vs Atorvastatin · ANCOVA · p = <0.001 · Mean difference (final values): -17.3 · 95% CI -23.2 to -11.4(Atorva + EZ minus Atorva)
SecondaryPercent Change From Baseline in C-Reactive Protein (CRP) at Week 6

\[(6 week value - baseline value)/baseline value\]\*100%.

Time frame:
6 Weeks
Reported as:
Least squares mean · percent
Percent Change From Baseline in C-Reactive Protein (CRP) at Week 6
percentAtorvastatin + EzetimibeAtorvastatin
Percent Change From Baseline in C-Reactive Protein (CRP) at Week 6-6.7 (-23.7 to 14.2)-9.2 (-25.8 to 11.1)
Statistical analysis
  • Atorvastatin + Ezetimibe vs Atorvastatin · Longitudinal Data Analysis (LDA) · p = 0.841 · Mean difference (final values): 2.5 · 95% CI -23.8 to 28.8Data for analysis was transformed by the natural log and the difference in geometric mean % change from BL calculated based on the difference in the back-transformed least squares means. (Atorva + EZ minus Atorva)
Post-hocPercent Change in C-Reactive Protein (CRP) at Week 6

\[(6 week value - baseline value)/baseline value\]\*100%.

Time frame:
6 weeks
Reported as:
Least squares mean · Percent
Percent Change in C-Reactive Protein (CRP) at Week 6
PercentAtorvastatin + EzetimibeAtorvastatin
Percent Change in C-Reactive Protein (CRP) at Week 6-19.2 (-25.0 to -4.0)-9.1 (-22.2 to 5.3)
Statistical analysis
  • Atorvastatin + Ezetimibe vs Atorvastatin · Nonparametric ANCOVA · p = 0.839 · Mean difference (final values): -8.3 · 95% CI -26.1 to 8.3The median difference is based on the Hodges-Lehmann estimates of shift; The distribution-free 95% CI is based on Wilcoxon's rank sum test statistic. (Atorva + EZ minus Atorva)
SecondaryNumber of Participants Who Attained Target LDL-C <100 mg/dL at Week 6
Time frame:
6 weeks
Reported as:
Number · Participants
Number of Participants Who Attained Target LDL-C <100 mg/dL at Week 6
ParticipantsAtorvastatin + EzetimibeAtorvastatin
<100 mg/dL7745
≥100 mg/dL1547
Statistical analysis
  • Atorvastatin + Ezetimibe vs Atorvastatin · Regression, Logistic · p = <0.001 · Odds ratio (or): 8.60 · 95% CI 3.80 to 19.47Estimated ratio is the predictive odds of attaining LDL-C target on Atorva + EZ versus Atorva.

Adverse events

Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Atorvastatin + Ezetimibe—0/96 (0%)17/96 (17.7%)
Atorvastatin—0/98 (0%)22/98 (22.4%)
Most frequent other events
Showing 10 of 32
Most frequent other events
EventAtorvastatin + EzetimibeAtorvastatin
VertigoEar and labyrinth disorders2/960/98
FatigueGeneral disorders2/961/98
NasopharyngitisInfections and infestations2/960/98
Irritable bowel syndromeGastrointestinal disorders0/962/98
Abdominal tendernessGastrointestinal disorders1/960/98
Chest DiscomfortGeneral disorders1/960/98
EdemaGeneral disorders1/960/98
GastroenteritisInfections and infestations1/961/98
Oral herpesInfections and infestations1/960/98
Upper respiratory tract infectionInfections and infestations1/960/98

Baseline characteristics

Age, Continuous
Age, Continuous(years)Atorvastatin + EzetimibeAtorvastatinTotal
Mean56.4 (24 to 78)58.0 (34 to 76)57.2 (24 to 78)
Sex: Female, Male
Sex: Female, Male(Participants)Atorvastatin + EzetimibeAtorvastatinTotal
Female404989
Male5849107
Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)Atorvastatin + EzetimibeAtorvastatinTotal
White5860118
American Indian or Alaska Native101
Asian7815
Black3912
Multi-Racial292150
Apolipoprotein A-I
Apolipoprotein A-I(mg/dL)Atorvastatin + EzetimibeAtorvastatinTotal
Mean161.8 ± 25.2163.4 ± 24.6162.6 ± 24.8
Apolipoprotein A-I:Apolipoprotein B ratio
Apolipoprotein A-I:Apolipoprotein B ratio(Ratio)Atorvastatin + EzetimibeAtorvastatinTotal
Mean0.8 ± 0.20.7 ± 0.20.8 ± 0.2
Apolipoprotein B
Apolipoprotein B(mg/dL)Atorvastatin + EzetimibeAtorvastatinTotal
Mean122.9 ± 22.4119.9 ± 21.0121.4 ± 21.7
C Reactive Protein
C Reactive Protein(mg/dL)Atorvastatin + EzetimibeAtorvastatinTotal
Mean1.6 ± 2.61.2 ± 1.71.5 ± 2.1
High Density Lipoprotein (HDL)
High Density Lipoprotein (HDL)(mg/dL)Atorvastatin + EzetimibeAtorvastatinTotal
Mean51.1 ± 12.151.7 ± 11.551.4 ± 11.8

7 further baseline measures are reported on the registry.

08

Study locations

No study locations are listed for this record.

09

References and documents

Publications

  • Conard SE, Bays HE, Leiter LA, Bird SR, Rubino J, Lowe RS, Tomassini JE, Tershakovec AM. Efficacy and safety of ezetimibe added on to atorvastatin (20 mg) versus uptitration of atorvastatin (to 40 mg) in hypercholesterolemic patients at moderately high risk for coronary heart disease. Am J Cardiol. 2008 Dec 1;102(11):1489-94. doi: 10.1016/j.amjcard.2008.09.075. Epub 2008 Oct 23. PubMed 19026302 ↗

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 13, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00276458
Lead sponsor
Organon and Co
Responsible party
Sponsor
First posted
Jan 13, 2006
Start date
Feb 2006
Primary completion
Jan 2008
Completion
Jan 2008
Results posted
Jul 8, 2009
Last update
May 13, 2024

Study contacts

Medical Monitor
study director · Merck Sharp & Dohme LLC
View the source record on ClinicalTrials.gov ↗

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