Trial Outcomes & Findings for Ezetimibe/Simvastatin (10 mg/40 mg) vs. the Doubling of Atorvastatin in High Risk Participants (MK-0653A-134 AM1)(COMPLETED) (NCT NCT00782184)
NCT ID: NCT00782184
Last Updated: 2024-05-16
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
250 participants
Primary outcome timeframe
Baseline (Treatment Day 1), Treatment Week 6
Results posted on
2024-05-16
Participant Flow
Participants received 20 mg open-label atorvastatin during a 5-week run-in period.
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
120
|
130
|
|
Overall Study
COMPLETED
|
116
|
125
|
|
Overall Study
NOT COMPLETED
|
4
|
5
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
2
|
|
Overall Study
Protocol Violation
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
3
|
2
|
Baseline Characteristics
Ezetimibe/Simvastatin (10 mg/40 mg) vs. the Doubling of Atorvastatin in High Risk Participants (MK-0653A-134 AM1)(COMPLETED)
Baseline characteristics by cohort
| Measure |
Ezetimibe/Simvastatin 10/40
n=120 Participants
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.
|
Atorvastatin 40 mg
n=130 Participants
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.
|
Total
n=250 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
58.9 years
STANDARD_DEVIATION 10.0 • n=5 Participants
|
59.7 years
STANDARD_DEVIATION 8.4 • n=7 Participants
|
59.3 years
STANDARD_DEVIATION 9.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
57 Participants
n=5 Participants
|
65 Participants
n=7 Participants
|
122 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
63 Participants
n=5 Participants
|
65 Participants
n=7 Participants
|
128 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (Treatment Day 1), Treatment Week 6Population: 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.
Outcome measures
| Measure |
Ezetimibe/Simvastatin 10/40
n=117 Participants
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.
|
Atorvastatin 40 mg
n=126 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Low Density Lipoprotein (LDL)-C
|
-26.81 percent change from baseline
95% Confidence Interval 27.09 • Interval -31.44 to -22.18
|
-11.81 percent change from baseline
95% Confidence Interval 22.85 • Interval -16.4 to -7.22
|
SECONDARY outcome
Timeframe: Treatment Week 6Population: 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.
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.
Outcome measures
| Measure |
Ezetimibe/Simvastatin 10/40
n=117 Participants
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.
|
Atorvastatin 40 mg
n=126 Participants
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.
|
|---|---|---|
|
Number of Participants Reaching LDL-C Target Goals of <70 mg/dL
|
34 participants
|
6 participants
|
SECONDARY outcome
Timeframe: Treatment Week 6Population: 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.
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.
Outcome measures
| Measure |
Ezetimibe/Simvastatin 10/40
n=117 Participants
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.
|
Atorvastatin 40 mg
n=126 Participants
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.
|
|---|---|---|
|
Number of Participants Reaching LDL-C Target Goal <77 mg/dL
|
45 participants
|
11 participants
|
SECONDARY outcome
Timeframe: Treatment Week 6Population: 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.
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.
Outcome measures
| Measure |
Ezetimibe/Simvastatin 10/40
n=117 Participants
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.
|
Atorvastatin 40 mg
n=126 Participants
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.
|
|---|---|---|
|
Number of Participants Reaching LDL-C Target Goal <100 mg/dL
|
81 participants
|
52 participants
|
SECONDARY outcome
Timeframe: Baseline (Treatment Day 1), Treatment Week 6Population: 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.
Outcome measures
| Measure |
Ezetimibe/Simvastatin 10/40
n=117 Participants
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.
|
Atorvastatin 40 mg
n=126 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Total Cholesterol
|
-15.97 percent change from baseline
Interval -19.17 to -12.76
|
-7.73 percent change from baseline
Interval -10.91 to -4.55
|
SECONDARY outcome
Timeframe: Baseline (Treatment Day 1), Treatment Week 6Population: 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.
Outcome measures
| Measure |
Ezetimibe/Simvastatin 10/40
n=117 Participants
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.
|
Atorvastatin 40 mg
n=126 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Triglycerides
|
-5.41 percent change from baseline
Interval -11.36 to 0.95
|
-7.54 percent change from baseline
Interval -13.32 to -1.38
|
SECONDARY outcome
Timeframe: Baseline (Treatment Day 1), Treatment Week 6Population: 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.
Outcome measures
| Measure |
Ezetimibe/Simvastatin 10/40
n=117 Participants
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.
|
Atorvastatin 40 mg
n=126 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in High-Density Lipoprotein (HDL) Cholesterol
|
5.37 percent change from baseline
Interval 2.39 to 8.35
|
2.89 percent change from baseline
Interval -0.07 to 5.85
|
SECONDARY outcome
Timeframe: Baseline (Treatment Day 1), Treatment Week 6Population: 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.
Outcome measures
| Measure |
Ezetimibe/Simvastatin 10/40
n=117 Participants
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.
|
Atorvastatin 40 mg
n=126 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Non-HDL Cholesterol
|
-22.50 percent change from baseline
Interval -26.78 to -18.22
|
-10.88 percent change from baseline
Interval -15.13 to -6.64
|
SECONDARY outcome
Timeframe: Baseline (Treatment Day 1), Treatment Week 6Population: 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.
Outcome measures
| Measure |
Ezetimibe/Simvastatin 10/40
n=117 Participants
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.
|
Atorvastatin 40 mg
n=126 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in LDL-Cholesterol/HDL-Cholesterol Ratio
|
-28.77 percent change from baseline
Interval -33.78 to -23.76
|
-12.66 percent change from baseline
Interval -17.63 to -7.69
|
SECONDARY outcome
Timeframe: Baseline (Treatment Day 1), Treatment Week 6Population: 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.
Outcome measures
| Measure |
Ezetimibe/Simvastatin 10/40
n=117 Participants
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.
|
Atorvastatin 40 mg
n=126 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Total Cholesterol/HDL-Cholesterol Ratio
|
-18.63 percent change from baseline
Interval -22.37 to -14.89
|
-8.60 percent change from baseline
Interval -12.31 to -4.89
|
SECONDARY outcome
Timeframe: Baseline (Treatment Day 1), Treatment Week 6Population: 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.
Outcome measures
| Measure |
Ezetimibe/Simvastatin 10/40
n=117 Participants
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.
|
Atorvastatin 40 mg
n=126 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Non-HDL Cholesterol/HDL-Cholesterol Ratio
|
-24.41 percent change from baseline
Interval -29.4 to -19.43
|
-11.20 percent change from baseline
Interval -16.15 to -6.25
|
SECONDARY outcome
Timeframe: Baseline (Treatment Day 1), Treatment Week 6Population: 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.
Outcome measures
| Measure |
Ezetimibe/Simvastatin 10/40
n=117 Participants
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.
|
Atorvastatin 40 mg
n=126 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Apolipoprotein B
|
-17.23 percent change from baseline
Interval -20.84 to -13.62
|
-9.53 percent change from baseline
Interval -13.12 to -5.95
|
SECONDARY outcome
Timeframe: Baseline (Treatment Day 1), Treatment Week 6Population: 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.
Outcome measures
| Measure |
Ezetimibe/Simvastatin 10/40
n=117 Participants
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.
|
Atorvastatin 40 mg
n=126 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Apolipoprotein A-1
|
2.56 percent change from baseline
Interval 0.36 to 4.77
|
-2.69 percent change from baseline
Interval -4.88 to -0.5
|
SECONDARY outcome
Timeframe: Baseline (Treatment Day 1), Treatment Week 6Population: 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.
Outcome measures
| Measure |
Ezetimibe/Simvastatin 10/40
n=117 Participants
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.
|
Atorvastatin 40 mg
n=126 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in Apolipoprotein B/A-1 Ratio
|
-18.59 percent change from baseline
Interval -22.7 to -14.48
|
-5.67 percent change from baseline
Interval -9.76 to -1.59
|
SECONDARY outcome
Timeframe: Baseline (Treatment Day 1), Treatment Week 6Population: 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.
Outcome measures
| Measure |
Ezetimibe/Simvastatin 10/40
n=117 Participants
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.
|
Atorvastatin 40 mg
n=126 Participants
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.
|
|---|---|---|
|
Percent Change From Baseline in High-sensitivity C-Reactive Protein (Hs-CRP)
|
-6.18 percent change from baseline
Interval -20.49 to 10.7
|
-8.86 percent change from baseline
Interval -22.67 to 7.41
|
Adverse Events
Ezetimibe/Simvastatin 10/40
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Atorvastatin 40 mg
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ezetimibe/Simvastatin 10/40
n=119 participants at risk
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.
|
Atorvastatin 40 mg
n=130 participants at risk
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.
|
Placebo
n=1 participants at risk
One participant received 20 mg open-label atorvastatin during a 5-week run-in period. Following this run-in period, the participant was randomized to the ezetimbe/simvastatin group, but took only pills from the bottle containing placebo to atorvastatin during the 6-week double-blind treatment period.
|
|---|---|---|---|
|
Infections and infestations
urinary tract infection
|
0.84%
1/119 • Number of events 1
|
0.00%
0/130
|
0.00%
0/1
|
|
Musculoskeletal and connective tissue disorders
back pain
|
0.00%
0/119
|
0.77%
1/130 • Number of events 1
|
0.00%
0/1
|
Other adverse events
| Measure |
Ezetimibe/Simvastatin 10/40
n=119 participants at risk
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.
|
Atorvastatin 40 mg
n=130 participants at risk
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.
|
Placebo
n=1 participants at risk
One participant received 20 mg open-label atorvastatin during a 5-week run-in period. Following this run-in period, the participant was randomized to the ezetimbe/simvastatin group, but took only pills from the bottle containing placebo to atorvastatin during the 6-week double-blind treatment period.
|
|---|---|---|---|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/119
|
1.5%
2/130 • Number of events 2
|
100.0%
1/1 • Number of events 2
|
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 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. Sponsor review can be expedited to meet publication guidelines.
- Publication restrictions are in place
Restriction type: OTHER