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A Study of Evacetrapib (LY2484595) in Participants With High Cholesterol (ACCENTUATE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02227784
Recruitment Status : Terminated (Study termination due to program termination.)
First Posted : August 28, 2014
Results First Posted : March 22, 2018
Last Update Posted : October 8, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Hyperlipidemia
Interventions Drug: Evacetrapib
Drug: Atorvastatin
Drug: Ezetimibe
Drug: Placebo
Enrollment 366
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Atorvastatin + Evacetrapib Atorvastatin 40 mg Atorvastatin 80 mg Atorvastatin + Ezetimibe Atorvastatin + Evacetrapib Open-Label (OLE)
Hide Arm/Group Description Atorvastatin 40 milligrams (mg) orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus evacetrapib 130 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants. Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants. Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 80 mg orally with placebo for blinding once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants. Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus ezetimibe 10 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants. Open label extension (OLE) (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Period Title: Double-Blind Phase
Started 123 54 62 127 0
Completed 83 36 41 88 0
Not Completed 40 18 21 39 0
Reason Not Completed
Adverse Event             3             2             1             3             0
Physician Decision             1             0             0             1             0
Protocol Violation             0             0             1             1             0
Sponsor Decision             34             15             14             32             0
Withdrawal by Subject             2             1             5             2             0
Period Title: Open-Label Extension Phase (OLE)
Started 0 [1] 0 [1] 0 [1] 0 [1] 248 [1]
Received at Least 1 Dose of Study Drug 0 0 0 0 247
Completed 0 0 0 0 0
Not Completed 0 0 0 0 248
Reason Not Completed
Adverse Event             0             0             0             0             1
Death             0             0             0             0             1
Sponsor Decision             0             0             0             0             243
Withdrawal by Subject             0             0             0             0             3
[1]
After the double-blind treatment phase, participants entered an OLE phase.
Arm/Group Title Atorvastatin + Evacetrapib Atorvastatin 40 mg Atorvastatin 80 mg Atorvastatin + Ezetimibe Total
Hide Arm/Group Description Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus evacetrapib 130 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants. Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants. Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 80 mg orally with placebo for blinding once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants. Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus ezetimibe 10 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants. Total of all reporting groups
Overall Number of Baseline Participants 123 54 62 127 366
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 123 participants 54 participants 62 participants 127 participants 366 participants
63.2  (8.7) 62.7  (9.3) 61.7  (10.2) 64.7  (8.9) 63.4  (9.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 123 participants 54 participants 62 participants 127 participants 366 participants
Female
38
  30.9%
15
  27.8%
18
  29.0%
53
  41.7%
124
  33.9%
Male
85
  69.1%
39
  72.2%
44
  71.0%
74
  58.3%
242
  66.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 123 participants 54 participants 62 participants 127 participants 366 participants
Hispanic or Latino
13
  10.6%
3
   5.6%
9
  14.5%
13
  10.2%
38
  10.4%
Not Hispanic or Latino
110
  89.4%
51
  94.4%
53
  85.5%
114
  89.8%
328
  89.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 123 participants 54 participants 62 participants 127 participants 366 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
1
   1.6%
1
   0.8%
2
   0.5%
Asian
4
   3.3%
1
   1.9%
0
   0.0%
1
   0.8%
6
   1.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
19
  15.4%
8
  14.8%
15
  24.2%
14
  11.0%
56
  15.3%
White
97
  78.9%
44
  81.5%
46
  74.2%
110
  86.6%
297
  81.1%
More than one race
3
   2.4%
1
   1.9%
0
   0.0%
1
   0.8%
5
   1.4%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 123 participants 54 participants 62 participants 127 participants 366 participants
123 54 62 127 366
1.Primary Outcome
Title Percent Change From Baseline to 3 Months in Low-Density Lipoprotein Cholesterol (LDL-C)
Hide Description Change in LDL-C levels from baseline to the 3-month visit expressed as a percentage of the baseline levels. LDL-C was measured by beta quantification. Statistics are from analysis of covariance with log baseline measurement and treatment is included in the model. Least Square Means (LS means) and median differences were analyzed in log units and converted to standard units. Log Percent change from baseline response is the dependent variable.
Time Frame Baseline, 3 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had evaluable LDL-C data
Arm/Group Title Atorvastatin + Evacetrapib Atorvastatin 40 mg Atorvastatin 80 mg Atorvastatin + Ezetimibe
Hide Arm/Group Description:
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus evacetrapib 130 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 80 mg orally with placebo for blinding once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus ezetimibe 10 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Overall Number of Participants Analyzed 86 40 44 91
Median (95% Confidence Interval)
Unit of Measure: percent
-33.44
(-34.47 to -32.41)
0.04
(-1.01 to 1.09)
-6.19
(-7.24 to -5.15)
-27.30
(-28.33 to -26.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -33.48
Confidence Interval (2-Sided) 95%
-44.4 to -23.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin 80 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -27.24
Confidence Interval (2-Sided) 95%
-36.6 to -18.5
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin + Ezetimibe
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.045
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -6.14
Confidence Interval (2-Sided) 95%
-12.2 to -0.22
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percent Change From Baseline to 3 Months in High-Density Lipoprotein Cholesterol (HDL-C)
Hide Description Change in HDL-C levels from baseline to the 3-month visit expressed as a percentage of the baseline levels. LS medians and median differences were analyzed in log units and converted to standard units. Statistics are from mixed model repeated measures analysis with log baseline measurement, treatment, visit, and treatment by visit interaction included in the model. Log percent change from baseline response is the dependent variable. Within-participant repeated measures at multiple visits are modeled by a compound symmetry covariance structure.
Time Frame Baseline, 3 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had evaluable HDL-C data.
Arm/Group Title Atorvastatin + Evacetrapib Atorvastatin 40 mg Atorvastatin 80 mg Atorvastatin + Ezetimibe
Hide Arm/Group Description:
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus evacetrapib 130 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 80 mg orally with placebo for blinding once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus ezetimibe 10 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Overall Number of Participants Analyzed 86 40 44 91
Median (95% Confidence Interval)
Unit of Measure: percent
125.39
(124.37 to 126.40)
0.11
(-0.92 to 1.13)
-6.10
(-7.12 to -5.07)
-2.18
(-3.20 to -1.17)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 125.28
Confidence Interval (2-Sided) 95%
117.1 to 133.6
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin 80 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 131.48
Confidence Interval (2-Sided) 95%
123.5 to 139.5
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin + Ezetimibe
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 127.57
Confidence Interval (2-Sided) 95%
120.1 to 135.0
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percent Change From Baseline to 3 Months in Apolipoprotein AI (apoAI)
Hide Description Change in apoAI levels from baseline to the 3-month visit expressed as a percentage of the baseline levels. Statistics are from analysis of covariance with log baseline measurement and treatment is included in the model. LS means and median differences were analyzed in log units and converted to standard units. Log Percent change from baseline response is the dependent variable.
Time Frame Baseline, 3 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with evaluable apoAI data.
Arm/Group Title Atorvastatin + Evacetrapib Atorvastatin 40 mg Atorvastatin 80 mg Atorvastatin + Ezetimibe
Hide Arm/Group Description:
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus evacetrapib 130 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 80 mg orally with placebo for blinding once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus ezetimibe 10 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Overall Number of Participants Analyzed 86 40 44 91
Median (95% Confidence Interval)
Unit of Measure: percent
46.08
(45.07 to 47.09)
-0.27
(-1.29 to 0.76)
-6.14
(-7.16 to -5.12)
-2.36
(-3.38 to -1.35)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 46.35
Confidence Interval (2-Sided) 95%
40.79 to 51.98
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin 80 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 52.22
Confidence Interval (2-Sided) 95%
47.12 to 57.33
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin + Ezetimibe
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 48.44
Confidence Interval (2-Sided) 95%
43.82 to 52.86
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percent Change From Baseline to 3 Months in Non-HDL-C
Hide Description Change in Non-HDL-C levels from baseline to the 3-month visit expressed as a percentage of the baseline levels. LS medians and median differences were analyzed in log units and converted to standard units. Statistics are from mixed model repeated measures analysis with log baseline measurement, treatment, visit, and treatment by visit interaction included in the model. Log percent change from baseline response is the dependent variable. Within-participant repeated measures at multiple visits are modeled by a compound symmetry covariance structure.
Time Frame Baseline, 3 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had evaluable non-HDL-C data.
Arm/Group Title Atorvastatin + Evacetrapib Atorvastatin 40 mg Atorvastatin 80 mg Atorvastatin + Ezetimibe
Hide Arm/Group Description:
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus evacetrapib 130 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 80 mg orally with placebo for blinding once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus ezetimibe 10 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Overall Number of Participants Analyzed 86 40 44 91
Median (95% Confidence Interval)
Unit of Measure: percent
-31.42
(-32.44 to -30.40)
-4.95
(-5.98 to -3.92)
-9.40
(-10.44 to -8.37)
-24.37
(-25.40 to -23.35)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -26.47
Confidence Interval (2-Sided) 95%
-33.4 to -20.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin 80 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -22.02
Confidence Interval (2-Sided) 95%
-28.4 to -15.9
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin + Ezetimibe
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -7.05
Confidence Interval (2-Sided) 95%
-11.5 to -2.68
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percent Change From Baseline to 3 Months in Apolipoprotein B (apoB)
Hide Description Change in apoB levels from baseline to the 3-month visit expressed as a percentage of the baseline levels. Statistics are from analysis of covariance with log baseline measurement and treatment is included in the model. LS means and median differences were analyzed in log units and converted to standard units. Log Percent change from baseline response is the dependent variable.
Time Frame Baseline, 3 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had evaluable apoB data.
Arm/Group Title Atorvastatin + Evacetrapib Atorvastatin 40 mg Atorvastatin 80 mg Atorvastatin + Ezetimibe
Hide Arm/Group Description:
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus evacetrapib 130 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 80 mg orally with placebo for blinding once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus ezetimibe 10 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Overall Number of Participants Analyzed 86 40 44 91
Median (95% Confidence Interval)
Unit of Measure: percent
-22.96
(-23.98 to -22.96)
0.21
(-0.82 to 1.24)
-6.54
(-7.56 to -5.51)
-18.84
(-19.86 to -17.82)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -23.16
Confidence Interval (2-Sided) 95%
-30.00 to -16.5
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin 80 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -16.42
Confidence Interval (2-Sided) 95%
-22.3 to -10.6
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin + Ezetimibe
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.062
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -4.11
Confidence Interval (2-Sided) 95%
-8.47 to 0.15
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percent Change From Baseline to 3 Months in Cholesterol Efflux Capacity
Hide Description Change in cholesterol efflux capacity from baseline to the 3-month visit expressed as a percentage of the baseline levels. Statistics are from analysis of covariance with log baseline measurement and treatment is included in the model. LS means and median differences were analyzed in log units and converted to standard units. Log Percent change from baseline response is the dependent variable.
Time Frame Baseline, 3 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had evaluable cholesterol efflux capacity
Arm/Group Title Atorvastatin + Evacetrapib Atorvastatin 40 mg Atorvastatin + Ezetimibe Atorvastatin 80 mg
Hide Arm/Group Description:
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus evacetrapib 130 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus ezetimibe 10 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 80 mg orally with placebo for blinding once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Overall Number of Participants Analyzed 86 40 44 91
Median (95% Confidence Interval)
Unit of Measure: percent
35.09
(34.07 to 36.11)
-2.96
(-3.99 to -1.93)
-7.03
(-8.06 to -6.00)
-4.55
(-5.57 to -3.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 38.05
Confidence Interval (2-Sided) 95%
30.17 to 45.88
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin + Ezetimibe
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 42.12
Confidence Interval (2-Sided) 95%
34.29 to 49.76
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin 80 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value 39.64
Confidence Interval (2-Sided) 95%
33.20 to 46.08
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Percent Change From Baseline to 3 Months in Lipoprotein(a) (Lp[a])
Hide Description Change in Lp(a) levels from baseline to the 3-month visit expressed as a percentage of the baseline levels. Statistics are from analysis of covariance with log baseline measurement and treatment is included in the model. LS means and median differences were analyzed in log units and converted to standard units. Log Percent change from baseline response is the dependent variable.
Time Frame Baseline, 3 Months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had evaluable Lp(a) data.
Arm/Group Title Atorvastatin + Evacetrapib Atorvastatin 40 mg Atorvastatin 80 mg Atorvastatin + Ezetimibe
Hide Arm/Group Description:
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus evacetrapib 130 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 80 mg orally with placebo for blinding once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus ezetimibe 10 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
Overall Number of Participants Analyzed 86 44 40 91
Median (95% Confidence Interval)
Unit of Measure: percent
-28.73
(-29.77 to 27.69)
4.45
(3.40 to 5.50)
3.90
(2.86 to 4.95)
13.42
(12.39 to 14.45)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin 40 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -33.18
Confidence Interval (2-Sided) 95%
-44.9 to -22.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin 80 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -32.63
Confidence Interval (2-Sided) 95%
-44.0 to -21.8
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Atorvastatin + Evacetrapib, Atorvastatin + Ezetimibe
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Final Values)
Estimated Value -42.15
Confidence Interval (2-Sided) 95%
-50.9 to -33.4
Estimation Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description 248 randomized participants from the double-blind phase moved to open-label phase but 1 participant did not receive drug. 247 randomized participants who moved to open-label phase that received drug are part of the safety population.
 
Arm/Group Title Atorvastatin + Evacetrapib Double-Blind (DB) Atorvastatin 40 mg DB Atorvastatin 80 mg DB Atorvastatin + Ezetimibe DB Atorvastatin + Evacetrapib Open-Label (OLE)
Hide Arm/Group Description Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus evacetrapib 130 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants. Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants. Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 80 mg orally with placebo for blinding once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants. Atorvastatin 40 mg orally once daily for 28 days during lead in period. Atorvastatin 40 mg plus ezetimibe 10 mg with placebo for blinding orally once daily for 90 days. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants. Open label extension (atorvastatin 40 mg plus evacetrapib 130 mg) is available for compliant participants.
All-Cause Mortality
Atorvastatin + Evacetrapib Double-Blind (DB) Atorvastatin 40 mg DB Atorvastatin 80 mg DB Atorvastatin + Ezetimibe DB Atorvastatin + Evacetrapib Open-Label (OLE)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Atorvastatin + Evacetrapib Double-Blind (DB) Atorvastatin 40 mg DB Atorvastatin 80 mg DB Atorvastatin + Ezetimibe DB Atorvastatin + Evacetrapib Open-Label (OLE)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/123 (1.63%)      3/54 (5.56%)      3/62 (4.84%)      3/127 (2.36%)      11/247 (4.45%)    
Cardiac disorders           
Coronary artery disease  1  0/123 (0.00%)  0 0/54 (0.00%)  0 0/62 (0.00%)  0 0/127 (0.00%)  0 1/247 (0.40%)  1
Myocardial infarction  1  0/123 (0.00%)  0 0/54 (0.00%)  0 0/62 (0.00%)  0 0/127 (0.00%)  0 1/247 (0.40%)  1
Gastrointestinal disorders           
Vomiting  1  1/123 (0.81%)  1 0/54 (0.00%)  0 0/62 (0.00%)  0 0/127 (0.00%)  0 0/247 (0.00%)  0
General disorders           
Chest discomfort  1  0/123 (0.00%)  0 0/54 (0.00%)  0 0/62 (0.00%)  0 0/127 (0.00%)  0 1/247 (0.40%)  1
Chest pain  1  0/123 (0.00%)  0 0/54 (0.00%)  0 1/62 (1.61%)  1 0/127 (0.00%)  0 0/247 (0.00%)  0
Non-cardiac chest pain  1  0/123 (0.00%)  0 0/54 (0.00%)  0 1/62 (1.61%)  1 0/127 (0.00%)  0 1/247 (0.40%)  1
Infections and infestations           
Chronic sinusitis  1  0/123 (0.00%)  0 1/54 (1.85%)  1 0/62 (0.00%)  0 0/127 (0.00%)  0 0/247 (0.00%)  0
Pyelonephritis  1  0/123 (0.00%)  0 0/54 (0.00%)  0 0/62 (0.00%)  0 1/127 (0.79%)  1 0/247 (0.00%)  0
Urinary tract infection  1  0/123 (0.00%)  0 0/54 (0.00%)  0 0/62 (0.00%)  0 0/127 (0.00%)  0 1/247 (0.40%)  1
Urosepsis  1  0/123 (0.00%)  0 0/54 (0.00%)  0 0/62 (0.00%)  0 0/127 (0.00%)  0 1/247 (0.40%)  1
Injury, poisoning and procedural complications           
Accidental overdose  1  0/123 (0.00%)  0 1/54 (1.85%)  1 0/62 (0.00%)  0 0/127 (0.00%)  0 0/247 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Benign neoplasm of spinal cord  1  0/123 (0.00%)  0 0/54 (0.00%)  0 0/62 (0.00%)  0 0/127 (0.00%)  0 1/247 (0.40%)  1
Ductal adenocarcinoma of pancreas  1  0/123 (0.00%)  0 0/54 (0.00%)  0 0/62 (0.00%)  0 1/127 (0.79%)  1 0/247 (0.00%)  0
Lung adenocarcinoma  1  1/123 (0.81%)  1 0/54 (0.00%)  0 0/62 (0.00%)  0 0/127 (0.00%)  0 0/247 (0.00%)  0
Nervous system disorders           
Balance disorder  1  1/123 (0.81%)  1 0/54 (0.00%)  0 0/62 (0.00%)  0 0/127 (0.00%)  0 0/247 (0.00%)  0
Carotid artery stenosis  1  0/123 (0.00%)  0 0/54 (0.00%)  0 0/62 (0.00%)  0 0/127 (0.00%)  0 1/247 (0.40%)  1
Cerebrovascular accident  1  0/123 (0.00%)  0 0/54 (0.00%)  0 1/62 (1.61%)  1 0/127 (0.00%)  0 0/247 (0.00%)  0
Cervical myelopathy  1  0/123 (0.00%)  0 0/54 (0.00%)  0 0/62 (0.00%)  0 0/127 (0.00%)  0 1/247 (0.40%)  1
Dizziness  1  1/123 (0.81%)  1 0/54 (0.00%)  0 0/62 (0.00%)  0 0/127 (0.00%)  0 0/247 (0.00%)  0
Hypoaesthesia  1  0/123 (0.00%)  0 0/54 (0.00%)  0 0/62 (0.00%)  0 0/127 (0.00%)  0 1/247 (0.40%)  1
Ischaemic stroke  1  0/123 (0.00%)  0 0/54 (0.00%)  0 0/62 (0.00%)  0 0/127 (0.00%)  0 1/247 (0.40%)  1
Transient ischaemic attack  1  0/123 (0.00%)  0 0/54 (0.00%)  0 1/62 (1.61%)  1 0/127 (0.00%)  0 0/247 (0.00%)  0
Psychiatric disorders           
Suicidal ideation  1  0/123 (0.00%)  0 1/54 (1.85%)  1 0/62 (0.00%)  0 0/127 (0.00%)  0 0/247 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
Acute respiratory failure  1  0/123 (0.00%)  0 1/54 (1.85%)  1 0/62 (0.00%)  0 0/127 (0.00%)  0 0/247 (0.00%)  0
Chronic obstructive pulmonary disease  1  0/123 (0.00%)  0 1/54 (1.85%)  1 0/62 (0.00%)  0 0/127 (0.00%)  0 1/247 (0.40%)  1
Pulmonary embolism  1  0/123 (0.00%)  0 1/54 (1.85%)  1 0/62 (0.00%)  0 0/127 (0.00%)  0 0/247 (0.00%)  0
Surgical and medical procedures           
Implantable defibrillator replacement  1  0/123 (0.00%)  0 0/54 (0.00%)  0 0/62 (0.00%)  0 0/127 (0.00%)  0 1/247 (0.40%)  1
Vascular disorders           
Hypotension  1  0/123 (0.00%)  0 0/54 (0.00%)  0 0/62 (0.00%)  0 1/127 (0.79%)  1 0/247 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Atorvastatin + Evacetrapib Double-Blind (DB) Atorvastatin 40 mg DB Atorvastatin 80 mg DB Atorvastatin + Ezetimibe DB Atorvastatin + Evacetrapib Open-Label (OLE)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/123 (4.88%)      5/54 (9.26%)      4/62 (6.45%)      5/127 (3.94%)      9/247 (3.64%)    
Gastrointestinal disorders           
Diarrhoea  1  5/123 (4.07%)  5 4/54 (7.41%)  4 1/62 (1.61%)  1 3/127 (2.36%)  3 4/247 (1.62%)  4
Musculoskeletal and connective tissue disorders           
Arthralgia  1  1/123 (0.81%)  1 1/54 (1.85%)  1 4/62 (6.45%)  5 2/127 (1.57%)  2 5/247 (2.02%)  5
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Early termination was due to program termination.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02227784     History of Changes
Other Study ID Numbers: 14502
I1V-MC-EIBH ( Other Identifier: Eli Lilly and Company )
First Submitted: August 26, 2014
First Posted: August 28, 2014
Results First Submitted: February 18, 2018
Results First Posted: March 22, 2018
Last Update Posted: October 8, 2019