Trial Outcomes & Findings for A Study to Evaluate the Effectiveness of Ezetimibe/Atorvastatin 10 mg/40 mg Combination Tablet Compared to Marketed Ezetimibe 10 mg and Atorvastatin 40 mg Tablets in Participants With High Cholesterol (MK-0653C-190 AM1) (NCT NCT01370603)
NCT ID: NCT01370603
Last Updated: 2022-02-09
Results Overview
Serum LDL-C calculated using Friedewald formula at baseline and after 6 weeks of treatment in each of the 2 treatment periods.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
328 participants
Primary outcome timeframe
Baseline and Week 6
Results posted on
2022-02-09
Participant Flow
Participant milestones
| Measure |
Co-administration/Combination Sequence
Co-administration Ezetimibe 10 mg and Atorvastatin 40 mg then Ezetimibe/Atorvastatin 10 mg/40 mg fixed-dose combination
|
Combination/Co-administration Sequence
Ezetimibe/Atorvastatin 10 mg/40 mg fixed-dose combination then Co-administration Ezetimibe 10 mg and Atorvastatin 40 mg
|
|---|---|---|
|
Period 1
STARTED
|
164
|
164
|
|
Period 1
COMPLETED
|
150
|
154
|
|
Period 1
NOT COMPLETED
|
14
|
10
|
|
Crossover Washout
STARTED
|
150
|
154
|
|
Crossover Washout
COMPLETED
|
141
|
150
|
|
Crossover Washout
NOT COMPLETED
|
9
|
4
|
|
Period 2
STARTED
|
141
|
150
|
|
Period 2
COMPLETED
|
138
|
146
|
|
Period 2
NOT COMPLETED
|
3
|
4
|
Reasons for withdrawal
| Measure |
Co-administration/Combination Sequence
Co-administration Ezetimibe 10 mg and Atorvastatin 40 mg then Ezetimibe/Atorvastatin 10 mg/40 mg fixed-dose combination
|
Combination/Co-administration Sequence
Ezetimibe/Atorvastatin 10 mg/40 mg fixed-dose combination then Co-administration Ezetimibe 10 mg and Atorvastatin 40 mg
|
|---|---|---|
|
Period 1
Adverse Event
|
5
|
3
|
|
Period 1
Lost to Follow-up
|
2
|
0
|
|
Period 1
Protocol Violation
|
2
|
2
|
|
Period 1
Withdrawal by Subject
|
5
|
5
|
|
Crossover Washout
Adverse Event
|
2
|
1
|
|
Crossover Washout
Lost to Follow-up
|
2
|
0
|
|
Crossover Washout
Protocol Violation
|
1
|
0
|
|
Crossover Washout
Withdrawal by Subject
|
4
|
1
|
|
Crossover Washout
Non-compliance with Study Drug
|
0
|
2
|
|
Period 2
Adverse Event
|
1
|
4
|
|
Period 2
Lost to Follow-up
|
1
|
0
|
|
Period 2
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
A Study to Evaluate the Effectiveness of Ezetimibe/Atorvastatin 10 mg/40 mg Combination Tablet Compared to Marketed Ezetimibe 10 mg and Atorvastatin 40 mg Tablets in Participants With High Cholesterol (MK-0653C-190 AM1)
Baseline characteristics by cohort
| Measure |
Co-administration/Combination Sequence
n=164 Participants
Co-administration Ezetimibe 10 mg and Atorvastatin 40 mg then Ezetimibe/Atorvastatin 10 mg/40 mg fixed-dose combination
|
Combination/Co-administration Sequence
n=164 Participants
Ezetimibe/Atorvastatin 10 mg/40 mg fixed-dose combination then Co-administration Ezetimibe 10 mg and Atorvastatin 40 mg
|
Total
n=328 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
30 to 39 years
|
10 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Age, Customized
40 to 49 years
|
35 Participants
n=5 Participants
|
29 Participants
n=7 Participants
|
64 Participants
n=5 Participants
|
|
Age, Customized
50 to 59 years
|
74 Participants
n=5 Participants
|
61 Participants
n=7 Participants
|
135 Participants
n=5 Participants
|
|
Age, Customized
60 to 64 years
|
20 Participants
n=5 Participants
|
35 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
|
Age, Customized
≥ 65 years
|
25 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
55 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
94 Participants
n=5 Participants
|
92 Participants
n=7 Participants
|
186 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
70 Participants
n=5 Participants
|
72 Participants
n=7 Participants
|
142 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 6Population: Per-Protocol (PP) population, which excluded participants due to important deviations from the protocol that may have substantially affected the results of the primary efficacy endpoint(s). A participant may have been a protocol violator in 1 treatment period and not in the other treatment period.
Serum LDL-C calculated using Friedewald formula at baseline and after 6 weeks of treatment in each of the 2 treatment periods.
Outcome measures
| Measure |
Ezetimibe/Atorvastatin Fixed Dose Combination
n=280 Participants
Ezetimibe/atorvastatin 10 mg/40 mg combination tablet once daily for 6 weeks
|
Co-Administration Ezetimibe and Atorvastatin
n=280 Participants
Ezetimibe 10 mg co-administered with atorvastatin 40 mg once daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After 6 Weeks of Treatment
|
-58.9 Percentage Change
Interval -60.9 to -56.9
|
-58.7 Percentage Change
Interval -60.7 to -56.7
|
SECONDARY outcome
Timeframe: Baseline and Week 6Population: Per-Protocol (PP) population, which excluded participants due to important deviations from the protocol that may have substantially affected the results of the primary efficacy endpoint(s). A participant may have been a protocol violator in 1 treatment period and not in the other treatment period.
Serum TC measured at baseline and after 6 week of treatment in each of the 2 treatment periods.
Outcome measures
| Measure |
Ezetimibe/Atorvastatin Fixed Dose Combination
n=280 Participants
Ezetimibe/atorvastatin 10 mg/40 mg combination tablet once daily for 6 weeks
|
Co-Administration Ezetimibe and Atorvastatin
n=280 Participants
Ezetimibe 10 mg co-administered with atorvastatin 40 mg once daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in Total Cholesterol (TC) After 6 Weeks of Treatment
|
-43.0 Percentage Change
Interval -44.5 to -41.5
|
-42.9 Percentage Change
Interval -44.4 to -41.4
|
SECONDARY outcome
Timeframe: Baseline and Week 6Population: Per-Protocol (PP) population, which excluded participants due to important deviations from the protocol that may have substantially affected the results of the primary efficacy endpoint(s). A participant may have been a protocol violator in 1 treatment period and not in the other treatment period.
Serum HDL-C measured at baseline and after 6 weeks of treatment in each of the 2 treatment periods.
Outcome measures
| Measure |
Ezetimibe/Atorvastatin Fixed Dose Combination
n=280 Participants
Ezetimibe/atorvastatin 10 mg/40 mg combination tablet once daily for 6 weeks
|
Co-Administration Ezetimibe and Atorvastatin
n=280 Participants
Ezetimibe 10 mg co-administered with atorvastatin 40 mg once daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) After 6 Weeks of Treatment
|
2.3 Percentage Change
Interval 0.8 to 3.8
|
2.6 Percentage Change
Interval 1.2 to 4.1
|
SECONDARY outcome
Timeframe: Baseline and Week 6Population: Per-Protocol (PP) population, which excluded participants due to important deviations from the protocol that may have substantially affected the results of the primary efficacy endpoint(s). A participant may have been a protocol violator in 1 treatment period and not in the other treatment period.
Non-HDL-C calculated at baseline and after 6 weeks of treatment in each of the 2 treatment periods.
Outcome measures
| Measure |
Ezetimibe/Atorvastatin Fixed Dose Combination
n=280 Participants
Ezetimibe/atorvastatin 10 mg/40 mg combination tablet once daily for 6 weeks
|
Co-Administration Ezetimibe and Atorvastatin
n=280 Participants
Ezetimibe 10 mg co-administered with atorvastatin 40 mg once daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) After 6 Weeks of Treatment
|
-55.4 Percentage Change
Interval -57.2 to -53.5
|
-55.2 Percentage Change
Interval -57.0 to -53.4
|
SECONDARY outcome
Timeframe: Baseline and Week 6Population: Per-Protocol (PP) population, which excluded participants due to important deviations from the protocol that may have substantially affected the results of the primary efficacy endpoint(s). A participant may have been a protocol violator in 1 treatment period and not in the other treatment period.
Serum Apo B measured at baseline and after 6 weeks of treatment in each of the 2 treatment periods.
Outcome measures
| Measure |
Ezetimibe/Atorvastatin Fixed Dose Combination
n=278 Participants
Ezetimibe/atorvastatin 10 mg/40 mg combination tablet once daily for 6 weeks
|
Co-Administration Ezetimibe and Atorvastatin
n=279 Participants
Ezetimibe 10 mg co-administered with atorvastatin 40 mg once daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in Apolipoprotein (Apo) B After 6 Weeks of Treatment
|
-48.7 Percentage Change
Interval -50.4 to -47.0
|
-48.3 Percentage Change
Interval -50.0 to -46.6
|
SECONDARY outcome
Timeframe: Baseline and Week 6Population: Per-Protocol (PP) population, which excluded participants due to important deviations from the protocol that may have substantially affected the results of the primary efficacy endpoint(s). A participant may have been a protocol violator in 1 treatment period and not in the other treatment period.
Serum TG measured at baseline and after 6 weeks of treatment in each of the 2 treatment periods.
Outcome measures
| Measure |
Ezetimibe/Atorvastatin Fixed Dose Combination
n=280 Participants
Ezetimibe/atorvastatin 10 mg/40 mg combination tablet once daily for 6 weeks
|
Co-Administration Ezetimibe and Atorvastatin
n=280 Participants
Ezetimibe 10 mg co-administered with atorvastatin 40 mg once daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in Triglycerides (TG) After 6 Weeks of Treatment
|
-36.2 Percentage Change
Interval -40.4 to -31.6
|
-36.2 Percentage Change
Interval -38.8 to -33.5
|
Adverse Events
Ezetimibe/Atorvastatin Fixed Dose Combination
Serious events: 3 serious events
Other events: 0 other events
Deaths: 0 deaths
Co-Administration Ezetimibe and Atorvastatin
Serious events: 2 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ezetimibe/Atorvastatin Fixed Dose Combination
n=303 participants at risk
Ezetimibe/atorvastatin 10 mg/40 mg combination tablet once daily for 6 weeks
|
Co-Administration Ezetimibe and Atorvastatin
n=313 participants at risk
Ezetimibe 10 mg co-administered with atorvastatin 20 mg once daily for 6 weeks
|
|---|---|---|
|
Cardiac disorders
Angina unstable
|
0.33%
1/303 • Number of events 1 • 18 weeks
All Patients as Treated Population defined as all randomized participants who received at least 1 dose of study drug. Adverse events were reported by actual treatment regardless of study period or assigned treatment sequence. Not all randomized participants entered Period 2 and therefore did not receive their assigned crossover treatment.
|
0.00%
0/313 • 18 weeks
All Patients as Treated Population defined as all randomized participants who received at least 1 dose of study drug. Adverse events were reported by actual treatment regardless of study period or assigned treatment sequence. Not all randomized participants entered Period 2 and therefore did not receive their assigned crossover treatment.
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/303 • 18 weeks
All Patients as Treated Population defined as all randomized participants who received at least 1 dose of study drug. Adverse events were reported by actual treatment regardless of study period or assigned treatment sequence. Not all randomized participants entered Period 2 and therefore did not receive their assigned crossover treatment.
|
0.32%
1/313 • Number of events 1 • 18 weeks
All Patients as Treated Population defined as all randomized participants who received at least 1 dose of study drug. Adverse events were reported by actual treatment regardless of study period or assigned treatment sequence. Not all randomized participants entered Period 2 and therefore did not receive their assigned crossover treatment.
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/303 • 18 weeks
All Patients as Treated Population defined as all randomized participants who received at least 1 dose of study drug. Adverse events were reported by actual treatment regardless of study period or assigned treatment sequence. Not all randomized participants entered Period 2 and therefore did not receive their assigned crossover treatment.
|
0.32%
1/313 • Number of events 1 • 18 weeks
All Patients as Treated Population defined as all randomized participants who received at least 1 dose of study drug. Adverse events were reported by actual treatment regardless of study period or assigned treatment sequence. Not all randomized participants entered Period 2 and therefore did not receive their assigned crossover treatment.
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.33%
1/303 • Number of events 1 • 18 weeks
All Patients as Treated Population defined as all randomized participants who received at least 1 dose of study drug. Adverse events were reported by actual treatment regardless of study period or assigned treatment sequence. Not all randomized participants entered Period 2 and therefore did not receive their assigned crossover treatment.
|
0.00%
0/313 • 18 weeks
All Patients as Treated Population defined as all randomized participants who received at least 1 dose of study drug. Adverse events were reported by actual treatment regardless of study period or assigned treatment sequence. Not all randomized participants entered Period 2 and therefore did not receive their assigned crossover treatment.
|
|
Infections and infestations
Sepsis
|
0.33%
1/303 • Number of events 1 • 18 weeks
All Patients as Treated Population defined as all randomized participants who received at least 1 dose of study drug. Adverse events were reported by actual treatment regardless of study period or assigned treatment sequence. Not all randomized participants entered Period 2 and therefore did not receive their assigned crossover treatment.
|
0.00%
0/313 • 18 weeks
All Patients as Treated Population defined as all randomized participants who received at least 1 dose of study drug. Adverse events were reported by actual treatment regardless of study period or assigned treatment sequence. Not all randomized participants entered Period 2 and therefore did not receive their assigned crossover treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
|
0.33%
1/303 • Number of events 1 • 18 weeks
All Patients as Treated Population defined as all randomized participants who received at least 1 dose of study drug. Adverse events were reported by actual treatment regardless of study period or assigned treatment sequence. Not all randomized participants entered Period 2 and therefore did not receive their assigned crossover treatment.
|
0.00%
0/313 • 18 weeks
All Patients as Treated Population defined as all randomized participants who received at least 1 dose of study drug. Adverse events were reported by actual treatment regardless of study period or assigned treatment sequence. Not all randomized participants entered Period 2 and therefore did not receive their assigned crossover 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: [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 timelines.
- Publication restrictions are in place
Restriction type: OTHER