Trial Outcomes & Findings for Ezetimibe/Simvastatin (MK-0653A) Versus Rosuvastatin Versus Doubling Statin Dose in Participants With Cardiovascular Disease and Diabetes Mellitus (MK-0653A-133)(COMPLETED) (NCT NCT00862251)

NCT ID: NCT00862251

Last Updated: 2024-05-16

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 808 participants
• Primary outcome timeframe: Baseline and Week 6
• Results posted on: 2024-05-16

Participant Flow

Participant milestones

Measure	Ezetimibe/Simvastatin Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin Rosuvastatin 10 mg tablets, taken once daily for six weeks.
Overall Study STARTED	322	162	324
Overall Study COMPLETED	303	157	315
Overall Study NOT COMPLETED	19	5	9

Reasons for withdrawal

Measure	Ezetimibe/Simvastatin Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin Rosuvastatin 10 mg tablets, taken once daily for six weeks.
Overall Study Adverse Event	8	3	1
Overall Study Lost to Follow-up	0	0	1
Overall Study Protocol Violation	2	0	1
Overall Study Withdrawal by Subject	9	2	6

Baseline Characteristics

Ezetimibe/Simvastatin (MK-0653A) Versus Rosuvastatin Versus Doubling Statin Dose in Participants With Cardiovascular Disease and Diabetes Mellitus (MK-0653A-133)(COMPLETED)

Baseline characteristics by cohort

Measure	Ezetimibe/Simvastatin n=322 Participants Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose n=162 Participants simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin n=324 Participants Rosuvastatin 10 mg tablets, taken once daily for six weeks.	Total n=808 Participants Total of all reporting groups
Age, Continuous	64.1 years STANDARD_DEVIATION 8.8 • n=93 Participants	64.7 years STANDARD_DEVIATION 8.3 • n=4 Participants	63.6 years STANDARD_DEVIATION 8.4 • n=27 Participants	64.0 years STANDARD_DEVIATION 8.5 • n=483 Participants
Sex: Female, Male Female	162 Participants n=93 Participants	82 Participants n=4 Participants	142 Participants n=27 Participants	386 Participants n=483 Participants
Sex: Female, Male Male	160 Participants n=93 Participants	80 Participants n=4 Participants	182 Participants n=27 Participants	422 Participants n=483 Participants

PRIMARY outcome

Timeframe: Baseline and Week 6

Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.

Outcome measures

Measure	Ezetimibe/Simvastatin n=314 Participants Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose n=159 Participants simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin Rosuvastatin 10 mg tablets, taken once daily for six weeks.
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Statin (Simvastatin or Atorvastatin).	-23.13 Percent change Interval -25.95 to -20.31	-8.37 Percent change Interval -12.32 to -4.41	—

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Analysis performed on subpopulation of participants who were previously treated with simvastatin 20 mg and were switched to either Ezetimibe/simvastatin or had simvastatin dose doubled to 40 mg

Outcome measures

Measure	Ezetimibe/Simvastatin n=158 Participants Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose n=78 Participants simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin Rosuvastatin 10 mg tablets, taken once daily for six weeks.
In Participants Treated With Simvastatin at Baseline, Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Simvastatin	-21.59 Percent change Interval -25.54 to -17.65	-7.98 Percent change Interval -13.57 to -2.38	—

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Analysis performed on subpopulation of participants who were previously treated with atorvastatin 10 mg and were switched to either Ezetimibe/simvastatin or had atorvastatin dose doubled to 20 mg

Outcome measures

Measure	Ezetimibe/Simvastatin n=156 Participants Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose n=81 Participants simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin Rosuvastatin 10 mg tablets, taken once daily for six weeks.
In Participants Treated With Atorvastatin at Baseline, Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Doubling the Dose of Atorvastatin	-24.58 Percent change Interval -28.63 to -20.53	-8.85 Percent change Interval -14.47 to -3.23	—

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Efficacy data were analyzed primarily based upon the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.

Outcome measures

Measure	Ezetimibe/Simvastatin n=314 Participants Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose n=315 Participants simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin Rosuvastatin 10 mg tablets, taken once daily for six weeks.
Percent Change From Baseline in LDL-C After Switching to Treatment With Ezetimibe/Simvastatin vs Switching Treatment to Rosuvastatin	-23.13 Percent change Interval -25.95 to -20.31	-19.32 Percent change Interval -22.14 to -16.51	—

SECONDARY outcome

Timeframe: Week 6

Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.

Outcome measures

Measure	Ezetimibe/Simvastatin n=314 Participants Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose n=159 Participants simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin n=315 Participants Rosuvastatin 10 mg tablets, taken once daily for six weeks.
Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L)	171 participants	43 participants	134 participants

SECONDARY outcome

Timeframe: Week 6

Population: Analysis performed on subpopulation of participants who were previously treated with simvastatin 20 mg and were switched to either Ezetimibe/simvastatin or had simvastatin dose doubled to 40 mg

Outcome measures

Measure	Ezetimibe/Simvastatin n=158 Participants Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose n=78 Participants simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin Rosuvastatin 10 mg tablets, taken once daily for six weeks.
In Participants Treated With Simvastatin at Baseline, Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L)	84 participants	19 participants	—

SECONDARY outcome

Timeframe: Week 6

Population: Analysis performed on subpopulation of participants who were previously treated with atorvastatin 10 mg and were switched to either Ezetimibe/simvastatin or had atorvastatin dose doubled to 20 mg

Outcome measures

Measure	Ezetimibe/Simvastatin n=156 Participants Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose n=81 Participants simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin Rosuvastatin 10 mg tablets, taken once daily for six weeks.
In Participants Treated With Atorvastatin at Baseline, Number of Participants Who Reached the Target LDL-Cholesterol Level of < 70 mg/dL (1.81 mmol/L)	87 participants	24 participants	—

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.

Outcome measures

Measure	Ezetimibe/Simvastatin n=314 Participants Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose n=159 Participants simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin n=315 Participants Rosuvastatin 10 mg tablets, taken once daily for six weeks.
Percent Change From Baseline in Total Cholesterol (TC)	-13.21 Percent Change 95% Confidence Interval 17.69 • Interval -14.99 to -11.43	-4.88 Percent Change 95% Confidence Interval 15.14 • Interval -7.37 to -2.39	-10.58 Percent Change 95% Confidence Interval 15.18 • Interval -12.36 to -8.81

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.

Outcome measures

Measure	Ezetimibe/Simvastatin n=314 Participants Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose n=159 Participants simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin n=315 Participants Rosuvastatin 10 mg tablets, taken once daily for six weeks.
Percent Change From Baseline in Triglycerides	-5.51 Percent change Interval -8.75 to -2.15	-2.63 Percent change Interval -7.23 to 2.21	-3.35 Percent change Interval -6.66 to 0.08

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.

Outcome measures

Measure	Ezetimibe/Simvastatin n=314 Participants Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose n=159 Participants simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin n=315 Participants Rosuvastatin 10 mg tablets, taken once daily for six weeks.
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C)	1.47 percent change Interval -0.27 to 3.21	1.00 percent change Interval -1.43 to 3.43	1.99 percent change Interval 0.26 to 3.73

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.

Outcome measures

Measure	Ezetimibe/Simvastatin n=314 Participants Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose n=159 Participants simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin n=315 Participants Rosuvastatin 10 mg tablets, taken once daily for six weeks.
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)	-18.39 Percent change Interval -20.9 to -15.88	-6.77 Percent change Interval -10.29 to -3.25	-15.14 Percent change Interval -17.72 to -12.7

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.

Outcome measures

Measure	Ezetimibe/Simvastatin n=314 Participants Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose n=159 Participants simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin n=315 Participants Rosuvastatin 10 mg tablets, taken once daily for six weeks.
Percent Change From Baseline in LDL-C/HDL-C Ratio	-21.55 Percent change Interval -25.09 to -18.01	-7.39 Percent change Interval -12.34 to -2.43	-18.99 Percent change Interval -22.52 to -15.46

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.

Outcome measures

Measure	Ezetimibe/Simvastatin n=314 Participants Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose n=159 Participants simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin n=315 Participants Rosuvastatin 10 mg tablets, taken once daily for six weeks.
Percent Change From Baseline in TC/HDL-C Ratio	-12.52 Percent change Interval -14.83 to -10.22	-4.36 Percent change Interval -7.58 to -1.14	-10.70 Percent change Interval -12.99 to -8.4

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.

Outcome measures

Measure	Ezetimibe/Simvastatin n=314 Participants Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose n=159 Participants simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin n=315 Participants Rosuvastatin 10 mg tablets, taken once daily for six weeks.
Percent Change From Baseline in Non-HDL-C/HDL-C Ratio	-16.77 percent change Interval -20.09 to -13.45	-5.32 percent change Interval -9.98 to -0.66	-14.64 percent change Interval -17.95 to -11.32

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.

Outcome measures

Measure	Ezetimibe/Simvastatin n=313 Participants Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose n=159 Participants simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin n=313 Participants Rosuvastatin 10 mg tablets, taken once daily for six weeks.
Percent Change From Baseline in Apolipoprotein B (Apo B)	-14.98 Percent change Interval -16.99 to -12.97	-6.97 Percent change Interval -9.78 to -4.15	-12.03 Percent change Interval -14.05 to -10.02

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.

Outcome measures

Measure	Ezetimibe/Simvastatin n=313 Participants Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose n=159 Participants simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin n=313 Participants Rosuvastatin 10 mg tablets, taken once daily for six weeks.
Percent Change From Baseline Apolipoprotein A-I (Apo A-I)	0.64 Percent change Interval -0.84 to 2.11	-0.93 Percent change Interval -2.99 to 1.12	0.86 Percent change Interval -0.62 to 2.34

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.

Outcome measures

Measure	Ezetimibe/Simvastatin n=313 Participants Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose n=159 Participants simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin n=313 Participants Rosuvastatin 10 mg tablets, taken once daily for six weeks.
Percent Change From Baseline in Apo B/Apo A-I Ratio	-13.67 Percent change Interval -16.27 to -11.06	-4.75 Percent change Interval -8.39 to -1.11	-11.14 Percent change Interval -13.75 to -8.54

SECONDARY outcome

Timeframe: Baseline and Week 6

Population: Efficacy data were analyzed using the full analysis set (FAS) population defined as all randomized participants who received at least one dose of blinded study treatment and had baseline data.

Outcome measures

Measure	Ezetimibe/Simvastatin n=313 Participants Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose n=159 Participants simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin n=315 Participants Rosuvastatin 10 mg tablets, taken once daily for six weeks.
Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP)	-4.42 Percent change Interval -13.94 to 6.15	-1.64 Percent change Interval -14.93 to 13.74	-9.11 Percent change Interval -18.13 to 0.92

Adverse Events

Ezetimibe/Simvastatin

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Doubling Statin Dose

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Rosuvastatin

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ezetimibe/Simvastatin n=321 participants at risk Ezetimibe/simvastatin 10/20 mg tablets, taken once daily for six weeks	Doubling Statin Dose n=162 participants at risk simvastatin 40 mg or atorvastatin 20 mg tablets, taken once daily for six weeks.	Rosuvastatin n=323 participants at risk Rosuvastatin 10 mg tablets, taken once daily for six weeks.
Cardiac disorders Angina pectoris	0.31% 1/321 • Number of events 1 All Patients as Treated (APaT) population was used for the analysis of safety data. The APaT population consisted of all randomized patients who received at least one dose of study treatment.	0.00% 0/162 All Patients as Treated (APaT) population was used for the analysis of safety data. The APaT population consisted of all randomized patients who received at least one dose of study treatment.	0.00% 0/323 All Patients as Treated (APaT) population was used for the analysis of safety data. The APaT population consisted of all randomized patients who received at least one dose of study treatment.
Cardiac disorders Angina unstable	0.00% 0/321 All Patients as Treated (APaT) population was used for the analysis of safety data. The APaT population consisted of all randomized patients who received at least one dose of study treatment.	0.00% 0/162 All Patients as Treated (APaT) population was used for the analysis of safety data. The APaT population consisted of all randomized patients who received at least one dose of study treatment.	0.31% 1/323 • Number of events 1 All Patients as Treated (APaT) population was used for the analysis of safety data. The APaT population consisted of all randomized patients who received at least one dose of study treatment.
Cardiac disorders Coronary artery disease	0.31% 1/321 • Number of events 1 All Patients as Treated (APaT) population was used for the analysis of safety data. The APaT population consisted of all randomized patients who received at least one dose of study treatment.	0.00% 0/162 All Patients as Treated (APaT) population was used for the analysis of safety data. The APaT population consisted of all randomized patients who received at least one dose of study treatment.	0.00% 0/323 All Patients as Treated (APaT) population was used for the analysis of safety data. The APaT population consisted of all randomized patients who received at least one dose of study treatment.
Cardiac disorders Myocardial infarction	0.00% 0/321 All Patients as Treated (APaT) population was used for the analysis of safety data. The APaT population consisted of all randomized patients who received at least one dose of study treatment.	0.62% 1/162 • Number of events 1 All Patients as Treated (APaT) population was used for the analysis of safety data. The APaT population consisted of all randomized patients who received at least one dose of study treatment.	0.00% 0/323 All Patients as Treated (APaT) population was used for the analysis of safety data. The APaT population consisted of all randomized patients who received at least one dose of study treatment.
Vascular disorders Arterial thrombosis limb	0.00% 0/321 All Patients as Treated (APaT) population was used for the analysis of safety data. The APaT population consisted of all randomized patients who received at least one dose of study treatment.	0.00% 0/162 All Patients as Treated (APaT) population was used for the analysis of safety data. The APaT population consisted of all randomized patients who received at least one dose of study treatment.	0.31% 1/323 • Number of events 1 All Patients as Treated (APaT) population was used for the analysis of safety data. The APaT population consisted of all randomized patients who received at least one dose of study treatment.

Other adverse events

Adverse event data not reported

Additional Information

Senior Vice President,Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee An investigator and/or his/her colleagues may publish the results for their study site independently after the multicenter publication, or 24 months after completion of the study, whichever comes first. The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission.
• Publication restrictions are in place

Restriction type: OTHER