Trial Outcomes & Findings for A Study of Ezetimibe Added On to Rosuvastatin Versus Up Titration of Rosuvastatin in Patients With Hypercholesterolemia (MK0653-139) (NCT NCT00783263)
NCT ID: NCT00783263
Last Updated: 2024-05-14
Results Overview
The percent change from baseline in LDL-C (mg/dL) after 6 weeks of treatment in participants who were administered ezetimibe 10 mg to rosuvastatin (5 or 10 mg) in comparison with doubling the baseline dose of rosuvastatin (10 or 20 mg) daily for 6 weeks.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
440 participants
Primary outcome timeframe
Baseline to 6 weeks
Results posted on
2024-05-14
Participant Flow
Participant milestones
| Measure |
Rosuvastatin 5 mg + Ezetimibe 10 mg
Participants who received open label rosuvastatin 5 mg tablets once daily for 4 to 5 weeks then received 10 mg ezetimibe tablets once daily plus 5 mg rosuvastatin for an additional 6 weeks.
|
Rosuvastatin 10 mg
Participants who received open label rosuvastatin 5 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 10 mg once daily for 6 additional weeks.
|
Rosuvastatin 10 mg + Ezetimibe 10 mg
Participants who received open label rosuvastatin 10 mg tablets once daily for 4 to 5 weeks then received 10 mg ezetimibe tablets once daily plus 10 mg rosuvastatin for an additional 6 weeks.
|
Rosuvastatin 20 mg
Participants who received open label rosuvastatin 10 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 20 mg once daily for 6 additional weeks.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
99
|
98
|
122
|
121
|
|
Overall Study
COMPLETED
|
95
|
96
|
119
|
118
|
|
Overall Study
NOT COMPLETED
|
4
|
2
|
3
|
3
|
Reasons for withdrawal
| Measure |
Rosuvastatin 5 mg + Ezetimibe 10 mg
Participants who received open label rosuvastatin 5 mg tablets once daily for 4 to 5 weeks then received 10 mg ezetimibe tablets once daily plus 5 mg rosuvastatin for an additional 6 weeks.
|
Rosuvastatin 10 mg
Participants who received open label rosuvastatin 5 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 10 mg once daily for 6 additional weeks.
|
Rosuvastatin 10 mg + Ezetimibe 10 mg
Participants who received open label rosuvastatin 10 mg tablets once daily for 4 to 5 weeks then received 10 mg ezetimibe tablets once daily plus 10 mg rosuvastatin for an additional 6 weeks.
|
Rosuvastatin 20 mg
Participants who received open label rosuvastatin 10 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 20 mg once daily for 6 additional weeks.
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
3
|
0
|
2
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
1
|
2
|
Baseline Characteristics
A Study of Ezetimibe Added On to Rosuvastatin Versus Up Titration of Rosuvastatin in Patients With Hypercholesterolemia (MK0653-139)
Baseline characteristics by cohort
| Measure |
Rosuvastatin 5 mg + Ezetimibe 10 mg
n=99 Participants
Participants who received open label rosuvastatin 5 mg tablets once daily for 4 to 5 weeks then received 10 mg ezetimibe tablets once daily plus 5 mg rosuvastatin for an additional 6 weeks.
|
Rosuvastatin 10 mg
n=98 Participants
Participants who received open label rosuvastatin 5 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 10 mg once daily for 6 additional weeks.
|
Rosuvastatin 10 mg + Ezetimibe 10 mg
n=122 Participants
Participants who received open label rosuvastatin 10 mg tablets once daily for 4 to 5 weeks then received 10 mg ezetimibe tablets once daily plus 10 mg rosuvastatin for an additional 6 weeks.
|
Rosuvastatin 20 mg
n=121 Participants
Participants who received open label rosuvastatin 10 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 20 mg once daily for 6 additional weeks.
|
Total
n=440 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Customized
< 65 years
|
63 participants
n=5 Participants
|
62 participants
n=7 Participants
|
71 participants
n=5 Participants
|
71 participants
n=4 Participants
|
267 participants
n=21 Participants
|
|
Age, Customized
≥ 65 years
|
36 participants
n=5 Participants
|
36 participants
n=7 Participants
|
51 participants
n=5 Participants
|
50 participants
n=4 Participants
|
173 participants
n=21 Participants
|
|
Sex: Female, Male
Female
|
35 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
37 Participants
n=4 Participants
|
168 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
64 Participants
n=5 Participants
|
58 Participants
n=7 Participants
|
66 Participants
n=5 Participants
|
84 Participants
n=4 Participants
|
272 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Baseline to 6 weeksThe percent change from baseline in LDL-C (mg/dL) after 6 weeks of treatment in participants who were administered ezetimibe 10 mg to rosuvastatin (5 or 10 mg) in comparison with doubling the baseline dose of rosuvastatin (10 or 20 mg) daily for 6 weeks.
Outcome measures
| Measure |
Rosuvastatin (5 or 10 mg) + Ezetimibe 10 mg
n=219 Participants
Participants who received open label rosuvastatin (5 or 10 mg) tablets once daily for 4 to 5 weeks then received 10 mg ezetimibe tablets once daily plus (5 or 10 mg) rosuvastatin for an additional 6 weeks.
|
Rosuvastatin (10 or 20 mg)
n=217 Participants
Participants who received open label rosuvastatin (5 or 10 mg) tablets once daily for 4 to 5 weeks then received rosuvastatin (10 or 20 mg) once daily for 6 additional weeks.
|
Rosuvastatin 10 mg + Ezetimibe 10 mg (Stratum II)
Participants who received open label rosuvastatin 5 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 10 mg once daily for 6 additional weeks.
|
Rosuvastatin 20 mg (Stratum II)
Participants who received open label rosuvastatin 10 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 20 mg once daily for 6 additional weeks.
|
|---|---|---|---|---|
|
Percent Change From Baseline in LDL-Cholesterol (mg/dL) After 6 Weeks of Treatment
|
-21.57 percent change
Standard Deviation 25.09
|
-5.58 percent change
Standard Deviation 25.42
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to 6 weeksThe percent change from baseline in LDL-C (mg/dL) after 6 weeks of treatment by stratum I and stratum II in participants who were administered with ezetimibe 10 mg to rosuvastatin (5 or 10 mg) in comparison with the doubling of the baseline dose of rosuvastatin (10 or 20 mg) daily for 6 weeks.
Outcome measures
| Measure |
Rosuvastatin (5 or 10 mg) + Ezetimibe 10 mg
n=98 Participants
Participants who received open label rosuvastatin (5 or 10 mg) tablets once daily for 4 to 5 weeks then received 10 mg ezetimibe tablets once daily plus (5 or 10 mg) rosuvastatin for an additional 6 weeks.
|
Rosuvastatin (10 or 20 mg)
n=96 Participants
Participants who received open label rosuvastatin (5 or 10 mg) tablets once daily for 4 to 5 weeks then received rosuvastatin (10 or 20 mg) once daily for 6 additional weeks.
|
Rosuvastatin 10 mg + Ezetimibe 10 mg (Stratum II)
n=121 Participants
Participants who received open label rosuvastatin 5 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 10 mg once daily for 6 additional weeks.
|
Rosuvastatin 20 mg (Stratum II)
n=121 Participants
Participants who received open label rosuvastatin 10 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 20 mg once daily for 6 additional weeks.
|
|---|---|---|---|---|
|
Percent Change From Baseline in LDL-Cholesterol (mg/dL) After 6 Weeks of Treatment in Each Stratum
|
-18.57 percentage change
Standard Deviation 26.35
|
-4.96 percentage change
Standard Deviation 22.42
|
-24.00 percentage change
Standard Deviation 23.86
|
-6.07 percentage change
Standard Deviation 27.65
|
SECONDARY outcome
Timeframe: 6 weeks of treatmentParticipants were analyzed to evaluate the LDL-C (\<100 mg/dL for moderately high risk patients and high risk patients without AVD and \<70 mg/dL for high risk patients with AVD) lowering efficacy with the addition of ezetimibe 10 mg to (5 or 10 mg) compared with doubling the baseline rosuvastatin (10 or 20 mg), daily for 6 weeks of treatment.
Outcome measures
| Measure |
Rosuvastatin (5 or 10 mg) + Ezetimibe 10 mg
n=219 Participants
Participants who received open label rosuvastatin (5 or 10 mg) tablets once daily for 4 to 5 weeks then received 10 mg ezetimibe tablets once daily plus (5 or 10 mg) rosuvastatin for an additional 6 weeks.
|
Rosuvastatin (10 or 20 mg)
n=217 Participants
Participants who received open label rosuvastatin (5 or 10 mg) tablets once daily for 4 to 5 weeks then received rosuvastatin (10 or 20 mg) once daily for 6 additional weeks.
|
Rosuvastatin 10 mg + Ezetimibe 10 mg (Stratum II)
Participants who received open label rosuvastatin 5 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 10 mg once daily for 6 additional weeks.
|
Rosuvastatin 20 mg (Stratum II)
Participants who received open label rosuvastatin 10 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 20 mg once daily for 6 additional weeks.
|
|---|---|---|---|---|
|
Number of Participants Who Reached Their Target LDL-C Level
|
130 participants
|
67 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 6 weeks of treatmentParticipants in stratum I were analyzed to evaluate the LDL-C lowering efficacy with the additional of ezetimibe 10 mg to rosuvastatin 5 mg daily for 6 weeks compared with doubling the baseline dose to rosuvastatin 10 mg daily for 6 weeks. Participants in stratum II were analyzed to evaluate the LDL-C lowering efficacy with the additional of ezetimibe 10 mg to rosuvastatin 10 mg daily for 6 weeks compared with doubling the baseline dose to rosuvastatin 20 mg daily for 6 weeks.
Outcome measures
| Measure |
Rosuvastatin (5 or 10 mg) + Ezetimibe 10 mg
n=98 Participants
Participants who received open label rosuvastatin (5 or 10 mg) tablets once daily for 4 to 5 weeks then received 10 mg ezetimibe tablets once daily plus (5 or 10 mg) rosuvastatin for an additional 6 weeks.
|
Rosuvastatin (10 or 20 mg)
n=96 Participants
Participants who received open label rosuvastatin (5 or 10 mg) tablets once daily for 4 to 5 weeks then received rosuvastatin (10 or 20 mg) once daily for 6 additional weeks.
|
Rosuvastatin 10 mg + Ezetimibe 10 mg (Stratum II)
n=121 Participants
Participants who received open label rosuvastatin 5 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 10 mg once daily for 6 additional weeks.
|
Rosuvastatin 20 mg (Stratum II)
n=121 Participants
Participants who received open label rosuvastatin 10 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 20 mg once daily for 6 additional weeks.
|
|---|---|---|---|---|
|
Number of Participants in Each Stratum Who Reached Their Target LDL-C Level
|
54 participants
|
30 participants
|
76 participants
|
37 participants
|
SECONDARY outcome
Timeframe: 6 weeks of treatmentParticipants across all strata who reached the LDL-C Level of \<70 mg/dl after the addition of ezetimibe 10 mg to rosuvastatin (5 or 10 mg) daily for 6 weeks compared with doubling the baseline dose of rosuvastatin (10 or 20 mg) daily for 6 weeks.
Outcome measures
| Measure |
Rosuvastatin (5 or 10 mg) + Ezetimibe 10 mg
n=219 Participants
Participants who received open label rosuvastatin (5 or 10 mg) tablets once daily for 4 to 5 weeks then received 10 mg ezetimibe tablets once daily plus (5 or 10 mg) rosuvastatin for an additional 6 weeks.
|
Rosuvastatin (10 or 20 mg)
n=217 Participants
Participants who received open label rosuvastatin (5 or 10 mg) tablets once daily for 4 to 5 weeks then received rosuvastatin (10 or 20 mg) once daily for 6 additional weeks.
|
Rosuvastatin 10 mg + Ezetimibe 10 mg (Stratum II)
Participants who received open label rosuvastatin 5 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 10 mg once daily for 6 additional weeks.
|
Rosuvastatin 20 mg (Stratum II)
Participants who received open label rosuvastatin 10 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 20 mg once daily for 6 additional weeks.
|
|---|---|---|---|---|
|
Number of Participants Who Reached the LDL-C Level of <70 mg/dl
|
96 participants
|
38 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 6 weeks of treatmentParticipants in stratum I and in stratum II who reached the LDL-C Level of \<70 mg/dl after the addition of ezetimibe to rosuvastatin (5 or 10 mg)daily for 6 weeks compared with doubling the baseline dose of rosuvastatin (10 or 20 mg).
Outcome measures
| Measure |
Rosuvastatin (5 or 10 mg) + Ezetimibe 10 mg
n=98 Participants
Participants who received open label rosuvastatin (5 or 10 mg) tablets once daily for 4 to 5 weeks then received 10 mg ezetimibe tablets once daily plus (5 or 10 mg) rosuvastatin for an additional 6 weeks.
|
Rosuvastatin (10 or 20 mg)
n=96 Participants
Participants who received open label rosuvastatin (5 or 10 mg) tablets once daily for 4 to 5 weeks then received rosuvastatin (10 or 20 mg) once daily for 6 additional weeks.
|
Rosuvastatin 10 mg + Ezetimibe 10 mg (Stratum II)
n=121 Participants
Participants who received open label rosuvastatin 5 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 10 mg once daily for 6 additional weeks.
|
Rosuvastatin 20 mg (Stratum II)
n=121 Participants
Participants who received open label rosuvastatin 10 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 20 mg once daily for 6 additional weeks.
|
|---|---|---|---|---|
|
Number of Participants in Each Stratum Who Reached the LDL-C Level of <70 mg/dl
|
31 participants
|
12 participants
|
65 participants
|
26 participants
|
SECONDARY outcome
Timeframe: Baseline to 6 weeksParticipants who were analyzed to assess the Total Cholesterol (TC), Triglycerides, High-Density Lipoprotein Cholesterol, Non High-Density Lipoprotein Cholesterol, LDL Cholesterol/HDL Cholesterol, Total Cholesterol/HDL Cholesterol, Non-HDL Cholesterol/HDL Cholesterol, Apolipoprotein B (Apo B), Apolipoprotein A-I (Apo A-I), Apolipoprotein B/Apo A-I, high-sensitivity C-reactive protein (hs-CRP)levels after 6 weeks of treatment.
Outcome measures
| Measure |
Rosuvastatin (5 or 10 mg) + Ezetimibe 10 mg
n=219 Participants
Participants who received open label rosuvastatin (5 or 10 mg) tablets once daily for 4 to 5 weeks then received 10 mg ezetimibe tablets once daily plus (5 or 10 mg) rosuvastatin for an additional 6 weeks.
|
Rosuvastatin (10 or 20 mg)
n=217 Participants
Participants who received open label rosuvastatin (5 or 10 mg) tablets once daily for 4 to 5 weeks then received rosuvastatin (10 or 20 mg) once daily for 6 additional weeks.
|
Rosuvastatin 10 mg + Ezetimibe 10 mg (Stratum II)
Participants who received open label rosuvastatin 5 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 10 mg once daily for 6 additional weeks.
|
Rosuvastatin 20 mg (Stratum II)
Participants who received open label rosuvastatin 10 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 20 mg once daily for 6 additional weeks.
|
|---|---|---|---|---|
|
Percent Change From Baseline in Other Lipid, Lipoprotein, Apolipoprotein and High-sensitivity C-reactive Protein (Hs-CRP)Levels
Total Cholesterol (TC)
|
-13.00 percentage change
Standard Deviation 17.51
|
-3.76 percentage change
Standard Deviation 14.35
|
—
|
—
|
|
Percent Change From Baseline in Other Lipid, Lipoprotein, Apolipoprotein and High-sensitivity C-reactive Protein (Hs-CRP)Levels
Triglycerides
|
-5.96 percentage change
Standard Deviation 36.45
|
-3.60 percentage change
Standard Deviation 32.83
|
—
|
—
|
|
Percent Change From Baseline in Other Lipid, Lipoprotein, Apolipoprotein and High-sensitivity C-reactive Protein (Hs-CRP)Levels
High-Density Lipoprotein Cholesterol
|
-0.67 percentage change
Standard Deviation 15.51
|
2.18 percentage change
Standard Deviation 13.38
|
—
|
—
|
|
Percent Change From Baseline in Other Lipid, Lipoprotein, Apolipoprotein and High-sensitivity C-reactive Protein (Hs-CRP)Levels
Non High-Density Liproprotein Cholesterol
|
-17.59 percentage change
Standard Deviation 23.55
|
-5.29 percentage change
Standard Deviation 21.20
|
—
|
—
|
|
Percent Change From Baseline in Other Lipid, Lipoprotein, Apolipoprotein and High-sensitivity C-reactive Protein (Hs-CRP)Levels
LDL Cholesterol/HDL Cholesterol
|
-19.48 percentage change
Standard Deviation 27.63
|
-6.18 percentage change
Standard Deviation 27.82
|
—
|
—
|
|
Percent Change From Baseline in Other Lipid, Lipoprotein, Apolipoprotein and High-sensitivity C-reactive Protein (Hs-CRP)Levels
Total Cholesterol/HDL Cholesterol
|
-10.57 percentage change
Standard Deviation 25.87
|
-4.40 percentage change
Standard Deviation 18.27
|
—
|
—
|
|
Percent Change From Baseline in Other Lipid, Lipoprotein, Apolipoprotein and High-sensitivity C-reactive Protein (Hs-CRP)Levels
Non-HDL Cholestrol/HDL Cholesterol
|
-14.51 percentage change
Standard Deviation 35.39
|
-5.31 percentage change
Standard Deviation 26.63
|
—
|
—
|
|
Percent Change From Baseline in Other Lipid, Lipoprotein, Apolipoprotein and High-sensitivity C-reactive Protein (Hs-CRP)Levels
Apolipoprotein B (Apo B)
|
-14.31 percentage change
Standard Deviation 18.61
|
-4.25 percentage change
Standard Deviation 17.56
|
—
|
—
|
|
Percent Change From Baseline in Other Lipid, Lipoprotein, Apolipoprotein and High-sensitivity C-reactive Protein (Hs-CRP)Levels
Apolipoprotein A-I (Apo A-I)
|
-1.44 percentage change
Standard Deviation 12.49
|
1.06 percentage change
Standard Deviation 11.56
|
—
|
—
|
|
Percent Change From Baseline in Other Lipid, Lipoprotein, Apolipoprotein and High-sensitivity C-reactive Protein (Hs-CRP)Levels
Apolipoprotein B/Apo A-I
|
-11.98 percentage change
Standard Deviation 20.84
|
-4.11 percentage change
Standard Deviation 19.61
|
—
|
—
|
|
Percent Change From Baseline in Other Lipid, Lipoprotein, Apolipoprotein and High-sensitivity C-reactive Protein (Hs-CRP)Levels
hs-C-Reactive Protein
|
-13.98 percentage change
Standard Deviation 72.19
|
-12.82 percentage change
Standard Deviation 73.08
|
—
|
—
|
Adverse Events
Rosuva 5 mg + EZ 10 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Rosuva 10 mg
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Rosuva 10 mg + EZ 10 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Rosuva 20 mg
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Rosuva 5 mg + EZ 10 mg
n=99 participants at risk
Participants who received open label rosuvastatin 5 mg tablets once daily for 4 to 5 weeks then received 10 mg ezetimibe tablets once daily plus 5mg rosuvastatin for an additional 6 weeks.
|
Rosuva 10 mg
n=98 participants at risk
Participants who received open label rosuvastatin 5 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 10 mg once daily for 6 additional weeks.
|
Rosuva 10 mg + EZ 10 mg
n=122 participants at risk
Participants who received open label rosuvastatin 10 mg tablets once daily for 4 to 5 weeks then received 10 mg ezetimibe tablets once daily plus 10 mg rosuvastatin for an additional 6 weeks.
|
Rosuva 20 mg
n=121 participants at risk
Participants who received rosuvastatin 10 mg tablets once daily for 4 to 5 weeks then received rosuvastatin 20 mg once daily for 6 additional weeks.
|
|---|---|---|---|---|
|
Cardiac disorders
Sick sinus syndrome
|
0.00%
0/99
All participants randomized were treated and had safety follow up.
|
0.00%
0/98
All participants randomized were treated and had safety follow up.
|
0.00%
0/122
All participants randomized were treated and had safety follow up.
|
0.83%
1/121 • Number of events 1
All participants randomized were treated and had safety follow up.
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.00%
0/99
All participants randomized were treated and had safety follow up.
|
1.0%
1/98 • Number of events 1
All participants randomized were treated and had safety follow up.
|
0.00%
0/122
All participants randomized were treated and had safety follow up.
|
0.00%
0/121
All participants randomized were treated and had safety follow up.
|
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: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60