Trial Outcomes & Findings for A Study to Evaluate the Effectiveness of Ezetimibe/Atorvastatin 10 mg/20 mg Combination Tablet Compared to Marketed Ezetimibe 10 mg and Atorvastatin 20 mg Tablets in Participants With High Cholesterol (MK-0653C-185 AM1) (NCT NCT01370590)
NCT ID: NCT01370590
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.
COMPLETED
PHASE3
406 participants
Baseline and Week 6
2022-02-09
Participant Flow
Participant milestones
| Measure |
Coadministered/Combination Sequence
Co-administration Ezetimibe 10 mg and Atorvastatin 20 mg then Ezetimibe/Atorvastatin 10 mg/20 mg fixed-dose combination
|
Combination/Coadministered Sequence
Ezetimibe/Atorvastatin 10 mg/20 mg fixed-dose combination then Co-administration Ezetimibe 10 mg and Atorvastatin 20 mg
|
|---|---|---|
|
Period 1
STARTED
|
203
|
203
|
|
Period 1
COMPLETED
|
187
|
192
|
|
Period 1
NOT COMPLETED
|
16
|
11
|
|
Crossover Washout Period
STARTED
|
187
|
192
|
|
Crossover Washout Period
COMPLETED
|
181
|
186
|
|
Crossover Washout Period
NOT COMPLETED
|
6
|
6
|
|
Period 2
STARTED
|
181
|
186
|
|
Period 2
COMPLETED
|
180
|
184
|
|
Period 2
NOT COMPLETED
|
1
|
2
|
Reasons for withdrawal
| Measure |
Coadministered/Combination Sequence
Co-administration Ezetimibe 10 mg and Atorvastatin 20 mg then Ezetimibe/Atorvastatin 10 mg/20 mg fixed-dose combination
|
Combination/Coadministered Sequence
Ezetimibe/Atorvastatin 10 mg/20 mg fixed-dose combination then Co-administration Ezetimibe 10 mg and Atorvastatin 20 mg
|
|---|---|---|
|
Period 1
Adverse Event
|
8
|
4
|
|
Period 1
Lost to Follow-up
|
2
|
2
|
|
Period 1
Protocol Violation
|
2
|
2
|
|
Period 1
Withdrawal by Subject
|
4
|
2
|
|
Period 1
Could not access randomization system
|
0
|
1
|
|
Crossover Washout Period
Adverse Event
|
1
|
4
|
|
Crossover Washout Period
Lost to Follow-up
|
2
|
0
|
|
Crossover Washout Period
Non-compliance with Study Drug
|
1
|
0
|
|
Crossover Washout Period
Withdrawal by Subject
|
2
|
2
|
|
Period 2
Adverse Event
|
0
|
1
|
|
Period 2
Withdrawal by Subject
|
1
|
1
|
Baseline Characteristics
A Study to Evaluate the Effectiveness of Ezetimibe/Atorvastatin 10 mg/20 mg Combination Tablet Compared to Marketed Ezetimibe 10 mg and Atorvastatin 20 mg Tablets in Participants With High Cholesterol (MK-0653C-185 AM1)
Baseline characteristics by cohort
| Measure |
Coadministered/Combination Sequence
n=203 Participants
Co-administration Ezetimibe 10 mg and Atorvastatin 20 mg then Ezetimibe/Atorvastatin 10 mg/20 mg fixed-dose combination
|
Combination/Coadministered Sequence
n=203 Participants
Ezetimibe/Atorvastatin 10 mg/20 mg fixed-dose combination then Co-administration Ezetimibe 10 mg and Atorvastatin 20 mg
|
Total
n=406 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
30 to 39 years
|
14 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
24 Participants
n=206 Participants
|
|
Age, Customized
40 to 49 years
|
35 Participants
n=99 Participants
|
28 Participants
n=107 Participants
|
63 Participants
n=206 Participants
|
|
Age, Customized
50 to 59 years
|
78 Participants
n=99 Participants
|
81 Participants
n=107 Participants
|
159 Participants
n=206 Participants
|
|
Age, Customized
60 to 64 years
|
40 Participants
n=99 Participants
|
51 Participants
n=107 Participants
|
91 Participants
n=206 Participants
|
|
Age, Customized
≥65 years
|
36 Participants
n=99 Participants
|
33 Participants
n=107 Participants
|
69 Participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
126 Participants
n=99 Participants
|
122 Participants
n=107 Participants
|
248 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
77 Participants
n=99 Participants
|
81 Participants
n=107 Participants
|
158 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 6Population: Per-Protocol 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 could be excluded from 1 or more of the analyses. Results are reported by treatment formulation and not by sequence.
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/Atorva Fixed Dose Combination
n=353 Participants
Ezetimibe/atorvastatin 10 mg/20 mg combination tablet once daily for 6 weeks
|
Co-Administration Ezetimibe and Atorvastin
n=346 Participants
Ezetimibe 10 mg co-administered with
atorvastatin 20 mg once daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) After 6 Weeks of Treatment
|
-54.0 Percentage Change
Interval -55.8 to -52.2
|
-53.8 Percentage Change
Interval -55.7 to -52.0
|
SECONDARY outcome
Timeframe: Baseline and Week 6Population: Per-Protocol 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 could be excluded from 1 or more of the analyses. Results are reported by treatment formulation and not by sequence.
Serum TC measured at baseline and after 6 week of treatment in each of the 2 treatment periods.
Outcome measures
| Measure |
Ezetimibe/Atorva Fixed Dose Combination
n=353 Participants
Ezetimibe/atorvastatin 10 mg/20 mg combination tablet once daily for 6 weeks
|
Co-Administration Ezetimibe and Atorvastin
n=346 Participants
Ezetimibe 10 mg co-administered with
atorvastatin 20 mg once daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in Total Cholesterol (TC) After 6 Weeks of Treatment
|
-38.1 Percentage Change
Interval -39.5 to -36.8
|
-38.5 Percentage Change
Interval -39.8 to -37.1
|
SECONDARY outcome
Timeframe: Baseline and Week 6Population: Per-Protocol 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 could be excluded from 1 or more of the analyses. Results are reported by treatment formulation and not by sequence.
Serum HDL-C calculated at baseline and after 6 weeks of treatment in each of the 2 treatment periods.
Outcome measures
| Measure |
Ezetimibe/Atorva Fixed Dose Combination
n=353 Participants
Ezetimibe/atorvastatin 10 mg/20 mg combination tablet once daily for 6 weeks
|
Co-Administration Ezetimibe and Atorvastin
n=346 Participants
Ezetimibe 10 mg co-administered with
atorvastatin 20 mg once daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) After 6 Weeks of Treatment
|
5.4 Percentage Change
Interval 4.0 to 6.7
|
4.6 Percentage Change
Interval 3.2 to 5.9
|
SECONDARY outcome
Timeframe: Baseline and Week 6Population: Per-Protocol 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 could be excluded from 1 or more of the analyses. Results are reported by treatment formulation and not by sequence.
Non-HDL-C measured at baseline and after 6 weeks of treatment in each of the 2 treatment periods.
Outcome measures
| Measure |
Ezetimibe/Atorva Fixed Dose Combination
n=353 Participants
Ezetimibe/atorvastatin 10 mg/20 mg combination tablet once daily for 6 weeks
|
Co-Administration Ezetimibe and Atorvastin
n=346 Participants
Ezetimibe 10 mg co-administered with
atorvastatin 20 mg once daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C) After 6 Weeks of Treatment
|
-50.1 Percentage Change
Interval -51.8 to -48.5
|
-50.2 Percentage Change
Interval -51.8 to -48.5
|
SECONDARY outcome
Timeframe: Baseline and Week 6Population: Per-Protocol 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 could be excluded from 1 or more of the analyses. Results are reported by treatment formulation and not by sequence.
Serum Apo B measured at baseline and after 6 weeks of treatment in each of the 2 treatment periods.
Outcome measures
| Measure |
Ezetimibe/Atorva Fixed Dose Combination
n=352 Participants
Ezetimibe/atorvastatin 10 mg/20 mg combination tablet once daily for 6 weeks
|
Co-Administration Ezetimibe and Atorvastin
n=345 Participants
Ezetimibe 10 mg co-administered with
atorvastatin 20 mg once daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in Apolipoprotein (Apo) B After 6 Weeks of Treatment
|
-42.6 Percentage Change
Interval -44.2 to -41.0
|
-43.3 Percentage Change
Interval -44.9 to -41.7
|
SECONDARY outcome
Timeframe: Baseline and Week 6Population: Per-Protocol 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 could be excluded from 1 or more of the analyses. Results are reported by treatment formulation and not by sequence.
Serum TG measured at baseline and after 6 weeks of treatment in each of the 2 treatment periods.
Outcome measures
| Measure |
Ezetimibe/Atorva Fixed Dose Combination
n=353 Participants
Ezetimibe/atorvastatin 10 mg/20 mg combination tablet once daily for 6 weeks
|
Co-Administration Ezetimibe and Atorvastin
n=346 Participants
Ezetimibe 10 mg co-administered with
atorvastatin 20 mg once daily for 6 weeks
|
|---|---|---|
|
Percent Change From Baseline in Triglycerides (TG) After 6 Weeks of Treatment
|
-28.3 Percentage Change
Interval -32.4 to -24.0
|
-29.9 Percentage Change
Interval -32.4 to -27.3
|
Adverse Events
Ezetimibe/Atorva Fixed Dose Combination
Co-Administration Ezetimibe and Atorvastin
Serious adverse events
| Measure |
Ezetimibe/Atorva Fixed Dose Combination
n=383 participants at risk
Ezetimibe/atorvastatin 10 mg/20 mg combination tablet once daily for 6 weeks
|
Co-Administration Ezetimibe and Atorvastin
n=388 participants at risk
Ezetimibe 10 mg co-administered with
atorvastatin 20 mg once daily for 6 weeks
|
|---|---|---|
|
Cardiac disorders
Myocardial infarction
|
0.26%
1/383 • Number of events 1
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%
0/388
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
Stress cardiomyopathy
|
0.00%
0/383
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.
|
0.26%
1/388 • Number of events 1
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
Ventricular extrasystoles
|
0.00%
0/383
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.
|
0.26%
1/388 • Number of events 1
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.
|
|
Gastrointestinal disorders
Colitis ischaemic
|
0.00%
0/383
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.
|
0.26%
1/388 • Number of events 1
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.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.26%
1/383 • Number of events 1
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%
0/388
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)
Basal cell carcinoma
|
0.00%
0/383
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.
|
0.26%
1/388 • Number of events 1
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.
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