Trial Outcomes & Findings for A Study of Evacetrapib (LY2484595) in Combination With Atorvastatin in Japanese Participants With Primary Hypercholesterolemia (NCT NCT02260648)
NCT ID: NCT02260648
Last Updated: 2018-10-09
Results Overview
The mixed-effects model for repeated measures (MMRM) was used for the Least Squares Mean (LS Mean) estimates at Week 12 for LDL-C adjusting for baseline as response variables, baseline measurement as a covariate, treatment, Visit (4,5,6, or 7), and treatment-by-visit interaction as fixed effects, and participant as a random effect.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
149 participants
Primary outcome timeframe
Baseline, Week 12
Results posted on
2018-10-09
Participant Flow
Participant milestones
| Measure |
Evacetrapib
130 milligram (mg) evacetrapib and 10 mg atorvastatin administered PO once a day for 12 weeks.
|
Placebo
Placebo and 10 mg atorvastatin administered orally (PO) once a day for 12 weeks.
|
Ezetimibe
10 mg ezetimibe and 10 mg atorvastatin administered PO once a day for 12 weeks as a reference arm.
|
|---|---|---|---|
|
Overall Study
STARTED
|
53
|
46
|
50
|
|
Overall Study
Received at Least One Dose of Study Drug
|
53
|
46
|
50
|
|
Overall Study
COMPLETED
|
35
|
33
|
42
|
|
Overall Study
NOT COMPLETED
|
18
|
13
|
8
|
Reasons for withdrawal
| Measure |
Evacetrapib
130 milligram (mg) evacetrapib and 10 mg atorvastatin administered PO once a day for 12 weeks.
|
Placebo
Placebo and 10 mg atorvastatin administered orally (PO) once a day for 12 weeks.
|
Ezetimibe
10 mg ezetimibe and 10 mg atorvastatin administered PO once a day for 12 weeks as a reference arm.
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
3
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
1
|
0
|
|
Overall Study
Protocol Violation
|
1
|
0
|
0
|
|
Overall Study
Discontinue Due to Study Termination
|
13
|
12
|
7
|
Baseline Characteristics
A Study of Evacetrapib (LY2484595) in Combination With Atorvastatin in Japanese Participants With Primary Hypercholesterolemia
Baseline characteristics by cohort
| Measure |
Evacetrapib
n=53 Participants
130 mg evacetrapib and 10 mg atorvastatin administered PO once a day for 12 weeks.
|
Placebo
n=46 Participants
Placebo and 10 mg atorvastatin administered PO once a day for 12 weeks.
|
Ezetimibe
n=50 Participants
10 mg ezetimibe and 10 mg atorvastatin administered PO once a day for 12 weeks as a reference arm.
|
Total
n=149 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
58.5 years
STANDARD_DEVIATION 11.53 • n=5 Participants
|
57.9 years
STANDARD_DEVIATION 10.81 • n=7 Participants
|
58.0 years
STANDARD_DEVIATION 10.40 • n=5 Participants
|
58.2 years
STANDARD_DEVIATION 10.87 • n=4 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
67 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
32 Participants
n=5 Participants
|
24 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
82 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
53 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
149 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
Japan
|
53 Participants
n=5 Participants
|
46 Participants
n=7 Participants
|
50 Participants
n=5 Participants
|
149 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 12Population: All participants who received at least one dose of study drug.
The mixed-effects model for repeated measures (MMRM) was used for the Least Squares Mean (LS Mean) estimates at Week 12 for LDL-C adjusting for baseline as response variables, baseline measurement as a covariate, treatment, Visit (4,5,6, or 7), and treatment-by-visit interaction as fixed effects, and participant as a random effect.
Outcome measures
| Measure |
Evacetrapib
n=53 Participants
130 mg evacetrapib and 10 mg atorvastatin administered PO once a day for 12 weeks.
|
Placebo
n=46 Participants
Placebo and 10 mg atorvastatin administered PO once a day for 12 weeks.
|
Ezetimibe
n=50 Participants
10 mg ezetimibe and 10 mg atorvastatin administered PO once a day for 12 weeks as a reference arm.
|
|---|---|---|---|
|
Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C) Measured by Beta Quantification
|
-26.37 percent change in LDL-C
Standard Error 3.108
|
-3.75 percent change in LDL-C
Standard Error 3.264
|
-27.31 percent change in LDL-C
Standard Error 3.128
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: All participants who received at least one dose of study drug.
The MMRM was used for the LS Mean estimates at Week 12 for HDL-C adjusting for baseline as response variables, baseline measurement as a covariate, treatment, visit, and treatment-by-visit interaction as fixed effects, and participant as a random effect, and treatment-by-visit interaction as fixed effects, and participant as a random effect.
Outcome measures
| Measure |
Evacetrapib
n=53 Participants
130 mg evacetrapib and 10 mg atorvastatin administered PO once a day for 12 weeks.
|
Placebo
n=46 Participants
Placebo and 10 mg atorvastatin administered PO once a day for 12 weeks.
|
Ezetimibe
n=50 Participants
10 mg ezetimibe and 10 mg atorvastatin administered PO once a day for 12 weeks as a reference arm.
|
|---|---|---|---|
|
Percent Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol (HDL-C)
|
108.96 percent change in HDL-C
Standard Error 5.150
|
-0.90 percent change in HDL-C
Standard Error 5.363
|
-3.12 percent change in HDL-C
Standard Error 5.166
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: All participants who received at least one dose of study drug.
The MMRM was used for the LS Mean estimates at Week 12 for LDL-C (direct) adjusting for baseline as response variables, baseline measurement as a covariate, treatment, visit, and treatment-by-visit interaction as fixed effects, and participant as a random effect.
Outcome measures
| Measure |
Evacetrapib
n=53 Participants
130 mg evacetrapib and 10 mg atorvastatin administered PO once a day for 12 weeks.
|
Placebo
n=46 Participants
Placebo and 10 mg atorvastatin administered PO once a day for 12 weeks.
|
Ezetimibe
n=50 Participants
10 mg ezetimibe and 10 mg atorvastatin administered PO once a day for 12 weeks as a reference arm.
|
|---|---|---|---|
|
Percent Change From Baseline to Week 12 in LDL-C (Direct)
|
-27.17 percent change in LDL-C (Direct)
Standard Error 2.708
|
-3.40 percent change in LDL-C (Direct)
Standard Error 2.845
|
-28.96 percent change in LDL-C (Direct)
Standard Error 2.726
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: All participants who received at least one dose of study drug.
The MMRM was used for the LS Mean estimates at Week 12 for Non HDL-C adjusting for baseline as response variables, baseline measurement as a covariate, treatment, visit, and treatment-by-visit interaction as fixed effects, and participant as a random effect.
Outcome measures
| Measure |
Evacetrapib
n=53 Participants
130 mg evacetrapib and 10 mg atorvastatin administered PO once a day for 12 weeks.
|
Placebo
n=46 Participants
Placebo and 10 mg atorvastatin administered PO once a day for 12 weeks.
|
Ezetimibe
n=50 Participants
10 mg ezetimibe and 10 mg atorvastatin administered PO once a day for 12 weeks as a reference arm.
|
|---|---|---|---|
|
Percent Change From Baseline to Week 12 in Non HDL-C
|
-22.01 percent change in non HDL-C
Standard Error 2.455
|
-6.42 percent change in non HDL-C
Standard Error 2.577
|
-27.35 percent change in non HDL-C
Standard Error 2.468
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: All participants who received at least one dose of study drug.
The analysis of covariance (ANCOVA) model using last observation carried forward (LOCF) was applied to analyze percent changes from baseline.
Outcome measures
| Measure |
Evacetrapib
n=53 Participants
130 mg evacetrapib and 10 mg atorvastatin administered PO once a day for 12 weeks.
|
Placebo
n=46 Participants
Placebo and 10 mg atorvastatin administered PO once a day for 12 weeks.
|
Ezetimibe
n=50 Participants
10 mg ezetimibe and 10 mg atorvastatin administered PO once a day for 12 weeks as a reference arm.
|
|---|---|---|---|
|
Percent Change From Baseline to Week 12 in Lipoprotein-a
|
-33.17 percent change in Lipoprotein-a
Standard Error 4.024
|
7.78 percent change in Lipoprotein-a
Standard Error 3.895
|
0.68 percent change in Lipoprotein-a
Standard Error 3.704
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: All participants who received at least one dose of study drug.
The ANCOVA model using last observation carried forward (LOCF) was applied to analyze percent changes from baseline.
Outcome measures
| Measure |
Evacetrapib
n=53 Participants
130 mg evacetrapib and 10 mg atorvastatin administered PO once a day for 12 weeks.
|
Placebo
n=46 Participants
Placebo and 10 mg atorvastatin administered PO once a day for 12 weeks.
|
Ezetimibe
n=50 Participants
10 mg ezetimibe and 10 mg atorvastatin administered PO once a day for 12 weeks as a reference arm.
|
|---|---|---|---|
|
Percent Change From Baseline to Week 12 in Apolipoprotein A-I
|
42.8 percent change in Apolipoprotein A-I
Standard Error 2.27
|
0.6 percent change in Apolipoprotein A-I
Standard Error 2.44
|
-0.6 percent change in Apolipoprotein A-I
Standard Error 2.34
|
SECONDARY outcome
Timeframe: Baseline, Week 12Population: All participants who received at least one dose of study drug.
The ANCOVA model using last observation carried forward (LOCF) was applied to analyze percent changes from baseline.
Outcome measures
| Measure |
Evacetrapib
n=53 Participants
130 mg evacetrapib and 10 mg atorvastatin administered PO once a day for 12 weeks.
|
Placebo
n=46 Participants
Placebo and 10 mg atorvastatin administered PO once a day for 12 weeks.
|
Ezetimibe
n=50 Participants
10 mg ezetimibe and 10 mg atorvastatin administered PO once a day for 12 weeks as a reference arm.
|
|---|---|---|---|
|
Percent Change From Baseline to Week 12 in Apolipoprotein B
|
-20.4 percent change in Apolipoprotien B
Standard Error 2.42
|
-3.0 percent change in Apolipoprotien B
Standard Error 2.60
|
-20.4 percent change in Apolipoprotien B
Standard Error 2.48
|
Adverse Events
Evacetrapib
Serious events: 0 serious events
Other events: 18 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Ezetimibe
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Evacetrapib
n=53 participants at risk
130 mg evacetrapib and 10 mg atorvastatin administered PO once a day for 12 weeks.
|
Placebo
n=46 participants at risk
Placebo and 10 mg atorvastatin administered PO once a day for 12 weeks.
|
Ezetimibe
n=50 participants at risk
10 mg ezetimibe and 10 mg atorvastatin administered PO once a day for 12 weeks as a reference arm.
|
|---|---|---|---|
|
Cardiac disorders
Ventricular extrasystoles
|
1.9%
1/53 • Number of events 1
|
0.00%
0/46
|
0.00%
0/50
|
|
Ear and labyrinth disorders
Presbyacusis
|
1.9%
1/53 • Number of events 1
|
0.00%
0/46
|
0.00%
0/50
|
|
Ear and labyrinth disorders
Vertigo
|
1.9%
1/53 • Number of events 1
|
0.00%
0/46
|
0.00%
0/50
|
|
Eye disorders
Eye pain
|
0.00%
0/53
|
0.00%
0/46
|
2.0%
1/50 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/53
|
2.2%
1/46 • Number of events 2
|
2.0%
1/50 • Number of events 1
|
|
Gastrointestinal disorders
Colitis ulcerative
|
1.9%
1/53 • Number of events 1
|
0.00%
0/46
|
0.00%
0/50
|
|
Gastrointestinal disorders
Diarrhoea
|
1.9%
1/53 • Number of events 1
|
0.00%
0/46
|
0.00%
0/50
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/53
|
2.2%
1/46 • Number of events 1
|
0.00%
0/50
|
|
Gastrointestinal disorders
Hypoaesthesia oral
|
1.9%
1/53 • Number of events 2
|
0.00%
0/46
|
0.00%
0/50
|
|
Gastrointestinal disorders
Stomatitis
|
1.9%
1/53 • Number of events 1
|
0.00%
0/46
|
0.00%
0/50
|
|
General disorders
Peripheral swelling
|
0.00%
0/53
|
2.2%
1/46 • Number of events 1
|
0.00%
0/50
|
|
Infections and infestations
Bronchitis
|
1.9%
1/53 • Number of events 1
|
0.00%
0/46
|
0.00%
0/50
|
|
Infections and infestations
Cystitis
|
1.9%
1/53 • Number of events 1
|
0.00%
0/46
|
0.00%
0/50
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/53
|
2.2%
1/46 • Number of events 1
|
0.00%
0/50
|
|
Infections and infestations
Genital herpes
|
0.00%
0/53
|
0.00%
0/46
|
2.0%
1/50 • Number of events 1
|
|
Infections and infestations
Nasopharyngitis
|
5.7%
3/53 • Number of events 3
|
4.3%
2/46 • Number of events 2
|
4.0%
2/50 • Number of events 2
|
|
Infections and infestations
Pharyngitis
|
1.9%
1/53 • Number of events 1
|
0.00%
0/46
|
0.00%
0/50
|
|
Infections and infestations
Tinea infection
|
0.00%
0/53
|
0.00%
0/46
|
2.0%
1/50 • Number of events 1
|
|
Infections and infestations
Urethritis
|
0.00%
0/53
|
2.2%
1/46 • Number of events 1
|
0.00%
0/50
|
|
Injury, poisoning and procedural complications
Injury
|
0.00%
0/53
|
0.00%
0/46
|
2.0%
1/50 • Number of events 1
|
|
Injury, poisoning and procedural complications
Wound
|
0.00%
0/53
|
0.00%
0/46
|
2.0%
1/50 • Number of events 1
|
|
Investigations
Blood creatine phosphokinase increased
|
1.9%
1/53 • Number of events 1
|
0.00%
0/46
|
2.0%
1/50 • Number of events 1
|
|
Investigations
Blood pressure increased
|
0.00%
0/53
|
2.2%
1/46 • Number of events 1
|
0.00%
0/50
|
|
Investigations
Blood thyroid stimulating hormone increased
|
0.00%
0/53
|
0.00%
0/46
|
2.0%
1/50 • Number of events 1
|
|
Investigations
Electrocardiogram qt prolonged
|
0.00%
0/53
|
2.2%
1/46 • Number of events 1
|
0.00%
0/50
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.00%
0/53
|
0.00%
0/46
|
2.0%
1/50 • Number of events 1
|
|
Metabolism and nutrition disorders
Type 2 diabetes mellitus
|
0.00%
0/53
|
2.2%
1/46 • Number of events 1
|
0.00%
0/50
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/53
|
0.00%
0/46
|
2.0%
1/50 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness
|
1.9%
1/53 • Number of events 1
|
0.00%
0/46
|
0.00%
0/50
|
|
Musculoskeletal and connective tissue disorders
Temporomandibular joint syndrome
|
0.00%
0/53
|
2.2%
1/46 • Number of events 1
|
0.00%
0/50
|
|
Nervous system disorders
Migraine
|
1.9%
1/53 • Number of events 1
|
0.00%
0/46
|
0.00%
0/50
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/53
|
0.00%
0/46
|
2.0%
1/50 • Number of events 1
|
|
Psychiatric disorders
Mental fatigue
|
0.00%
0/53
|
2.2%
1/46 • Number of events 1
|
0.00%
0/50
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/53
|
0.00%
0/46
|
2.0%
1/50 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract inflammation
|
0.00%
0/53
|
2.2%
1/46 • Number of events 1
|
2.0%
1/50 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Drug eruption
|
1.9%
1/53 • Number of events 1
|
0.00%
0/46
|
0.00%
0/50
|
|
Skin and subcutaneous tissue disorders
Erythema ab igne
|
1.9%
1/53 • Number of events 1
|
0.00%
0/46
|
0.00%
0/50
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/53
|
4.3%
2/46 • Number of events 2
|
0.00%
0/50
|
|
Skin and subcutaneous tissue disorders
Rash
|
3.8%
2/53 • Number of events 3
|
0.00%
0/46
|
0.00%
0/50
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60