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Ezetimibe/Simvastatin (10 mg/40 mg) vs. the Doubling of Atorvastatin in High Risk Participants (MK-0653A-134 AM1)(COMPLETED)

A Randomized, Double-Blind, Active-Controlled Study of Patients With Primary Hypercholesterolemia and High Cardiovascular Risk and Not Adequately Controlled With Atorvastatin: A Comparison of Switching to a Combination Tablet Ezetimibe/Simvastatin Versus Doubling the Baseline Dose of Atorvastatin

Status
Completed
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00782184
Enrollment
250
Registered
2008-10-31
Start date
2008-11-30
Completion date
2010-09-30
Last updated
2024-05-16

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

Conditions

Hypercholesterolemia

Brief summary

Participants currently taking atorvastatin 20 mg will be switched to either atorvastatin 40 mg or ezetimibe/simvastatin 10 mg/40 mg (10/40). After 6 weeks of treatment, the percent reduction in low-density lipoprotein cholesterol (LDL-C) will be assessed and compared between the two treatment groups.

Interventions

DRUGezetimibe/simvastatin 10/40

ezetimibe/simvastatin 10/40 tablet once daily for 6 weeks.

DRUGatorvastatin 40 mg

atorvastatin 40 mg tablet once daily for 6 weeks

DRUGatorvastatin 20 mg

All participants will take atorvastatin 20 mg tablet once daily for the 5 week run-in period before randomization

Sponsors

Organon and Co
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No

Inclusion criteria

* Participants who are either statin naive or on approved lipid lowering therapy for 6 weeks prior to study initiation * Participant meets Adult Treatment Panel (ATP) III High Risk criteria

Exclusion criteria

* Females who are pregnant or breastfeeding * Participant consumes more than 14 alcoholic beverages per week * Participant has been treated with an investigational drug within the last 30 days * Participant has congestive heart failure (New York Heart Association \[NYHA\] Type III or IV) * Participant has had gastric bypass * Participant is newly diagnosed with type 1 or 2 diabetes * Participant is Human Immunodeficiency Virus (HIV) positive * Participant has a history of drug or alcohol abuse within the last 5 years

Design outcomes

Primary

MeasureTime frame
Percent Change From Baseline in Low Density Lipoprotein (LDL)-CBaseline (Treatment Day 1), Treatment Week 6

Secondary

MeasureTime frameDescription
Number of Participants Reaching LDL-C Target Goal <77 mg/dLTreatment Week 6Target LDL-C level of \< 77 mg/dL (2.00 mmol/L) at study endpoint after 6 weeks of treatment for the Full Analysis Set (FAS) population.
Number of Participants Reaching LDL-C Target Goal <100 mg/dLTreatment Week 6Target LDL-C level of \< 100 mg/dL (2.59 mmol/L) at study endpoint after 6 weeks of treatment for the Full Analysis Set (FAS) population.
Percent Change From Baseline in Total CholesterolBaseline (Treatment Day 1), Treatment Week 6—
Percent Change From Baseline in TriglyceridesBaseline (Treatment Day 1), Treatment Week 6—
Percent Change From Baseline in High-Density Lipoprotein (HDL) CholesterolBaseline (Treatment Day 1), Treatment Week 6—
Percent Change From Baseline in Non-HDL CholesterolBaseline (Treatment Day 1), Treatment Week 6—
Number of Participants Reaching LDL-C Target Goals of <70 mg/dLTreatment Week 6Target LDL-C level of \< 70 mg/dL (1.81 mmol/L) at study endpoint after 6 weeks of treatment for the Full Analysis Set (FAS) population.
Percent Change From Baseline in Total Cholesterol/HDL-Cholesterol RatioBaseline (Treatment Day 1), Treatment Week 6—
Percent Change From Baseline in Non-HDL Cholesterol/HDL-Cholesterol RatioBaseline (Treatment Day 1), Treatment Week 6—
Percent Change From Baseline in Apolipoprotein BBaseline (Treatment Day 1), Treatment Week 6—
Percent Change From Baseline in Apolipoprotein A-1Baseline (Treatment Day 1), Treatment Week 6—
Percent Change From Baseline in Apolipoprotein B/A-1 RatioBaseline (Treatment Day 1), Treatment Week 6—
Percent Change From Baseline in High-sensitivity C-Reactive Protein (Hs-CRP)Baseline (Treatment Day 1), Treatment Week 6—
Percent Change From Baseline in LDL-Cholesterol/HDL-Cholesterol RatioBaseline (Treatment Day 1), Treatment Week 6—

Participant flow

Pre-assignment details

Participants received 20 mg open-label atorvastatin during a 5-week run-in period.

Participants by arm

ArmCount
Ezetimibe/Simvastatin 10/40
Participants received 20 mg open-label atorvastatin during a 5-week run-in period. Following this run-in period, ezetimibe/simvastatin 10/40 was administered once daily in tablet form during the 6-week double-blind treatment period.
120
Atorvastatin 40 mg
Participants received 20 mg open-label atorvastatin during a 5-week run-in period. Following this run-in period, 40 mg atorvastatin was administered once daily in tablet form during the 6-week double-blind treatment period.
130
Total250

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyAdverse Event12
Overall StudyProtocol Violation01
Overall StudyWithdrawal by Subject32

Baseline characteristics

CharacteristicEzetimibe/Simvastatin 10/40Atorvastatin 40 mgTotal
Age, Continuous58.9 years
STANDARD_DEVIATION 10
59.7 years
STANDARD_DEVIATION 8.4
59.3 years
STANDARD_DEVIATION 9.2
Sex: Female, Male
Female
57 Participants65 Participants122 Participants
Sex: Female, Male
Male
63 Participants65 Participants128 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —
other
Total, other adverse events
0 / 1192 / 1301 / 1
serious
Total, serious adverse events
1 / 1191 / 1300 / 1

Outcome results

Primary

Percent Change From Baseline in Low Density Lipoprotein (LDL)-C

Time frame: Baseline (Treatment Day 1), Treatment Week 6

Population: Participants in the Full Analysis Set (FAS) Population \[all randomized participants with at least one dose of study treatment and baseline data\] with percent change data available at week 6.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
Ezetimibe/Simvastatin 10/40Percent Change From Baseline in Low Density Lipoprotein (LDL)-C-26.81 percent change from baseline95% Confidence Interval 27.09
Atorvastatin 40 mgPercent Change From Baseline in Low Density Lipoprotein (LDL)-C-11.81 percent change from baseline95% Confidence Interval 22.85
p-value: <0.00195% CI: [-21.15, -8.84]Longitudinal Data Analysis (LDA) Model
Secondary

Number of Participants Reaching LDL-C Target Goal <100 mg/dL

Target LDL-C level of \< 100 mg/dL (2.59 mmol/L) at study endpoint after 6 weeks of treatment for the Full Analysis Set (FAS) population.

Time frame: Treatment Week 6

Population: Participants in the Full Analysis Set (FAS) Population \[all randomized participants with at least one dose of study treatment and baseline data\] with baseline and post-baseline data available.

ArmMeasureValue (NUMBER)
Ezetimibe/Simvastatin 10/40Number of Participants Reaching LDL-C Target Goal <100 mg/dL81 participants
Atorvastatin 40 mgNumber of Participants Reaching LDL-C Target Goal <100 mg/dL52 participants
p-value: <0.00195% CI: [2, 6]Regression, Logistic
Secondary

Number of Participants Reaching LDL-C Target Goal <77 mg/dL

Target LDL-C level of \< 77 mg/dL (2.00 mmol/L) at study endpoint after 6 weeks of treatment for the Full Analysis Set (FAS) population.

Time frame: Treatment Week 6

Population: Participants in the Full Analysis Set (FAS) Population \[all randomized participants with at least one dose of study treatment and baseline data\] with baseline and post-baseline data available.

ArmMeasureValue (NUMBER)
Ezetimibe/Simvastatin 10/40Number of Participants Reaching LDL-C Target Goal <77 mg/dL45 participants
Atorvastatin 40 mgNumber of Participants Reaching LDL-C Target Goal <77 mg/dL11 participants
p-value: <0.00195% CI: [3.3, 13.9]Regression, Logistic
Secondary

Number of Participants Reaching LDL-C Target Goals of <70 mg/dL

Target LDL-C level of \< 70 mg/dL (1.81 mmol/L) at study endpoint after 6 weeks of treatment for the Full Analysis Set (FAS) population.

Time frame: Treatment Week 6

Population: Participants in the Full Analysis Set (FAS) Population \[all randomized participants with at least one dose of study treatment and baseline data\] with baseline and post-baseline data available.

ArmMeasureValue (NUMBER)
Ezetimibe/Simvastatin 10/40Number of Participants Reaching LDL-C Target Goals of <70 mg/dL34 participants
Atorvastatin 40 mgNumber of Participants Reaching LDL-C Target Goals of <70 mg/dL6 participants
Comparison: COMPARISON BETWEEN GROUPS FOR NUMBER OF PARTICIPANTS REACHING LDL-C GOAL OF \<70 MG/DLp-value: <0.00195% CI: [3.4, 21]Regression, Logistic
Secondary

Percent Change From Baseline in Apolipoprotein A-1

Time frame: Baseline (Treatment Day 1), Treatment Week 6

Population: Participants in the Full Analysis Set (FAS) Population \[all randomized participants with at least one dose of study treatment and baseline data\] with percent change data available at week 6.

ArmMeasureValue (LEAST_SQUARES_MEAN)
Ezetimibe/Simvastatin 10/40Percent Change From Baseline in Apolipoprotein A-12.56 percent change from baseline
Atorvastatin 40 mgPercent Change From Baseline in Apolipoprotein A-1-2.69 percent change from baseline
p-value: <0.00195% CI: [2.44, 8.06]LDA Model
Secondary

Percent Change From Baseline in Apolipoprotein B

Time frame: Baseline (Treatment Day 1), Treatment Week 6

Population: Participants in the Full Analysis Set (FAS) Population \[all randomized participants with at least one dose of study treatment and baseline data\] with percent change data available at week 6.

ArmMeasureValue (LEAST_SQUARES_MEAN)
Ezetimibe/Simvastatin 10/40Percent Change From Baseline in Apolipoprotein B-17.23 percent change from baseline
Atorvastatin 40 mgPercent Change From Baseline in Apolipoprotein B-9.53 percent change from baseline
p-value: 0.00295% CI: [-12.5, -2.88]LDA Model
Secondary

Percent Change From Baseline in Apolipoprotein B/A-1 Ratio

Time frame: Baseline (Treatment Day 1), Treatment Week 6

Population: Participants in the Full Analysis Set (FAS) Population \[all randomized participants with at least one dose of study treatment and baseline data\] with percent change data available at week 6.

ArmMeasureValue (LEAST_SQUARES_MEAN)
Ezetimibe/Simvastatin 10/40Percent Change From Baseline in Apolipoprotein B/A-1 Ratio-18.59 percent change from baseline
Atorvastatin 40 mgPercent Change From Baseline in Apolipoprotein B/A-1 Ratio-5.67 percent change from baseline
p-value: <0.00195% CI: [-18.31, -7.52]LDA Model
Secondary

Percent Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol

Time frame: Baseline (Treatment Day 1), Treatment Week 6

Population: Participants in the Full Analysis Set (FAS) Population \[all randomized participants with at least one dose of study treatment and baseline data\] with percent change data available at week 6.

ArmMeasureValue (LEAST_SQUARES_MEAN)
Ezetimibe/Simvastatin 10/40Percent Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol5.37 percent change from baseline
Atorvastatin 40 mgPercent Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol2.89 percent change from baseline
p-value: 0.21195% CI: [-1.41, 6.37]LDA Model
Secondary

Percent Change From Baseline in High-sensitivity C-Reactive Protein (Hs-CRP)

Time frame: Baseline (Treatment Day 1), Treatment Week 6

Population: Participants in the Full Analysis Set (FAS) Population \[all randomized participants with at least one dose of study treatment and baseline data\] with percent change data available at week 6.

ArmMeasureValue (LEAST_SQUARES_MEAN)
Ezetimibe/Simvastatin 10/40Percent Change From Baseline in High-sensitivity C-Reactive Protein (Hs-CRP)-6.18 percent change from baseline
Atorvastatin 40 mgPercent Change From Baseline in High-sensitivity C-Reactive Protein (Hs-CRP)-8.86 percent change from baseline
p-value: 0.78595% CI: [-16.5, 21.86]LDA Model
Secondary

Percent Change From Baseline in LDL-Cholesterol/HDL-Cholesterol Ratio

Time frame: Baseline (Treatment Day 1), Treatment Week 6

Population: Participants in the Full Analysis Set (FAS) Population \[all randomized participants with at least one dose of study treatment and baseline data\] with percent change data available at week 6.

ArmMeasureValue (LEAST_SQUARES_MEAN)
Ezetimibe/Simvastatin 10/40Percent Change From Baseline in LDL-Cholesterol/HDL-Cholesterol Ratio-28.77 percent change from baseline
Atorvastatin 40 mgPercent Change From Baseline in LDL-Cholesterol/HDL-Cholesterol Ratio-12.66 percent change from baseline
p-value: <0.00195% CI: [-22.77, -9.44]LDA Model
Secondary

Percent Change From Baseline in Non-HDL Cholesterol

Time frame: Baseline (Treatment Day 1), Treatment Week 6

Population: Participants in the Full Analysis Set (FAS) Population \[all randomized participants with at least one dose of study treatment and baseline data\] with percent change data available at week 6.

ArmMeasureValue (LEAST_SQUARES_MEAN)
Ezetimibe/Simvastatin 10/40Percent Change From Baseline in Non-HDL Cholesterol-22.50 percent change from baseline
Atorvastatin 40 mgPercent Change From Baseline in Non-HDL Cholesterol-10.88 percent change from baseline
p-value: <0.00195% CI: [-17.32, -5.92]LDA Model
Secondary

Percent Change From Baseline in Non-HDL Cholesterol/HDL-Cholesterol Ratio

Time frame: Baseline (Treatment Day 1), Treatment Week 6

Population: Participants in the Full Analysis Set (FAS) Population \[all randomized participants with at least one dose of study treatment and baseline data\] with percent change data available at week 6.

ArmMeasureValue (LEAST_SQUARES_MEAN)
Ezetimibe/Simvastatin 10/40Percent Change From Baseline in Non-HDL Cholesterol/HDL-Cholesterol Ratio-24.41 percent change from baseline
Atorvastatin 40 mgPercent Change From Baseline in Non-HDL Cholesterol/HDL-Cholesterol Ratio-11.20 percent change from baseline
p-value: <0.00195% CI: [-19.83, -6.59]LDA Model
Secondary

Percent Change From Baseline in Total Cholesterol

Time frame: Baseline (Treatment Day 1), Treatment Week 6

Population: Participants in the Full Analysis Set (FAS) Population \[all randomized participants with at least one dose of study treatment and baseline data\] with percent change data available at week 6.

ArmMeasureValue (LEAST_SQUARES_MEAN)
Ezetimibe/Simvastatin 10/40Percent Change From Baseline in Total Cholesterol-15.97 percent change from baseline
Atorvastatin 40 mgPercent Change From Baseline in Total Cholesterol-7.73 percent change from baseline
p-value: <0.00195% CI: [-12.5, -3.97]LDA Model
Secondary

Percent Change From Baseline in Total Cholesterol/HDL-Cholesterol Ratio

Time frame: Baseline (Treatment Day 1), Treatment Week 6

Population: Participants in the Full Analysis Set (FAS) Population \[all randomized participants with at least one dose of study treatment and baseline data\] with percent change data available at week 6.

ArmMeasureValue (LEAST_SQUARES_MEAN)
Ezetimibe/Simvastatin 10/40Percent Change From Baseline in Total Cholesterol/HDL-Cholesterol Ratio-18.63 percent change from baseline
Atorvastatin 40 mgPercent Change From Baseline in Total Cholesterol/HDL-Cholesterol Ratio-8.60 percent change from baseline
p-value: <0.00195% CI: [-14.96, -5.08]LDA Model
Secondary

Percent Change From Baseline in Triglycerides

Time frame: Baseline (Treatment Day 1), Treatment Week 6

Population: Participants in the Full Analysis Set (FAS) Population \[all randomized participants with at least one dose of study treatment and baseline data\] with percent change data available at week 6.

ArmMeasureValue (LEAST_SQUARES_MEAN)
Ezetimibe/Simvastatin 10/40Percent Change From Baseline in Triglycerides-5.41 percent change from baseline
Atorvastatin 40 mgPercent Change From Baseline in Triglycerides-7.54 percent change from baseline
p-value: 0.59395% CI: [-5.67, 9.93]LDA Model

Source: ClinicalTrials.gov · Data processed: Mar 27, 2026