Hypercholesterolemia
Conditions
Brief summary
The main purpose of this study is to evaluate the efficacy and safety of the study drug known as evacetrapib in Japanese participants with primary hypercholesterolemia. The double blind treatment period will last for 12 weeks and the open-label extension period will last for an additional 40 weeks.
Interventions
DRUGEvacetrapib
Administered orally
DRUGPlacebo
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Japanese outpatients who are diagnosed with primary hypercholesterolemia with LDL-C levels (measured by a direct method at baseline) that meet the following criteria. (Participant categories are based on the definition in Japan Atherosclerosis Society 2012 guidelines.) * Category I: 160 mg/deciliter (dL)≤LDL-C\<200 mg/dL * Category II: 140 mg/dL≤LDL-C\<175 mg/dL * Category III: 120 mg/dL≤LDL-C\<150 mg/dL * Have triglycerides (TG) ≤400 mg/dL. * Have HDL-C \<100 mg/dL.
Exclusion criteria
* Participants on LDL apheresis or plasma apheresis. * Participants with secondary hypercholesterolemia or familial hypercholesterolemia. * Any planned angiography. If angiography is planned, participants may be screened and enrolled after all such planned procedures are completed. * History of any of the following any conditions: * Stable angina or acute coronary syndrome (unstable angina, myocardial infarction), old myocardial infarction or a coronary revascularization procedure including stent placement, or symptomatic carotid artery disease * peripheral arterial disease * ischemic stroke or transient ischemic attack (TIA) * intracranial hemorrhage * abdominal aortic aneurysm * Have systolic blood pressure (SBP) \>160 millimeters of mercury (mm Hg) or diastolic blood pressure (DBP) \>100 mm Hg. * Have a hemoglobin A1c ≥8.4% (National Glycohemoglobin Standardization Program). * During the study period, participants who plan to use, are likely to require, or unwilling or unable to stop with adequate washout any prescription, over the counter medication, supplements or health foods with the intent to treat serum lipids (LDL-C, HDL-C, TG) including but not limited to these classes of drugs: statin, ezetimibe, bile acid sequestrant, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Participants taking probucol, fibrate or nicotinic agents within 8 weeks before screening are excluded from the study. * Have been exposed to cholesteryl ester transfer protein inhibitors (e.g., anacetrapib or dalcetrapib).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C) Measured by Beta Quantification | Baseline, Week 12 | Least Square Mean (LS mean) using mixed model repeated measures (MMRM) adjusted for baseline, treatment, visit , and treatment\*visit, where the participant is a random effect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in LDL-C (Direct) | Baseline, Week 12 | LS mean using MMRM adjusted for baseline, treatment, visit , and treatment\*visit, where the participant is a random effect. |
| Percent Change From Baseline in Non HDL-C | Baseline, Week 12 | LS mean using MMRM adjusted for baseline, treatment, visit , and treatment\*visit, where the participant is a random effect. |
| Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) | Baseline, Week 12 | LS mean using MMRM adjusted for baseline, treatment, visit , and treatment\*visit, where the participant is a random effect. |
| Percent Change From Baseline in Apolipoprotein A-I | Baseline, Week 12, Week 52 | LS Mean from ANCOVA model adjusted for baseline and treatment. |
| Percent Change From Baseline in Apolipoprotein B | Baseline, Week 12, Week 52 | LS Mean from ANCOVA model adjusted for baseline and treatment. |
| Percent Change From Baseline in Lipoprotein-a | Baseline, Week 12, Week 52 | LS Mean from analysis of covariance (ANCOVA) model adjusted for baseline and treatment. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Evacetrapib 130 milligrams (mg) evacetrapib given orally once a day for 12 weeks. Participants begin open label extension (130 mg evacetrapib given orally once a day for 40 weeks) after week 12. | 27 |
| Placebo Placebo given orally once a day for 12 weeks. Participants begin open label extension (130 mg evacetrapib given orally once a day for 40 weeks) after week 12. | 27 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind Treatment Period | Failure to Meet Randomization Criteria | 1 | 2 |
| Open-Label Extension | Study Termination | 25 | 25 |
| Open-Label Extension | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Evacetrapib | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 52.2 years STANDARD_DEVIATION 10.19 | 52.8 years STANDARD_DEVIATION 10.08 | 53.3 years STANDARD_DEVIATION 10.13 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 27 Participants | 54 Participants | 27 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 27 Participants | 54 Participants | 27 Participants |
| Sex: Female, Male Female | 7 Participants | 17 Participants | 10 Participants |
| Sex: Female, Male Male | 20 Participants | 37 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 5 / 27 | 7 / 26 | 6 / 26 | 4 / 25 |
| serious Total, serious adverse events | 0 / 27 | 0 / 26 | 0 / 26 | 0 / 25 |
Outcome results
Primary
Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C) Measured by Beta Quantification
Least Square Mean (LS mean) using mixed model repeated measures (MMRM) adjusted for baseline, treatment, visit , and treatment\*visit, where the participant is a random effect.
Time frame: Baseline, Week 12
Population: All randomized participants receiving at least 1 dose of study drug with evaluable LDL-C values measured by beta quantification at baseline, and at least 1 post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Evacetrapib | Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C) Measured by Beta Quantification | -34.27 percent change in LDL-C | Standard Error 3.908 |
| Placebo | Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C) Measured by Beta Quantification | 0.00 percent change in LDL-C | Standard Error 3.984 |
Secondary
Percent Change From Baseline in Apolipoprotein A-I
LS Mean from ANCOVA model adjusted for baseline and treatment.
Time frame: Baseline, Week 12, Week 52
Population: All randomized participants receiving at least 1 dose of study drug with evaluable Apolipoprotein A-I values at baseline, and at least 1 post-baseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Evacetrapib | Percent Change From Baseline in Apolipoprotein A-I | Week 12 | 49.1 percent change in Apolipoprotein A-I | Standard Error 3.44 |
| Evacetrapib | Percent Change From Baseline in Apolipoprotein A-I | Week 52 | NA percent change in Apolipoprotein A-I | — |
| Placebo | Percent Change From Baseline in Apolipoprotein A-I | Week 12 | -2.5 percent change in Apolipoprotein A-I | Standard Error 3.51 |
| Placebo | Percent Change From Baseline in Apolipoprotein A-I | Week 52 | NA percent change in Apolipoprotein A-I | — |
Secondary
Percent Change From Baseline in Apolipoprotein B
LS Mean from ANCOVA model adjusted for baseline and treatment.
Time frame: Baseline, Week 12, Week 52
Population: All randomized participants receiving at least 1 dose of study drug with evaluable Apolipoprotein B values at baseline, and at least 1 post-baseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Evacetrapib | Percent Change From Baseline in Apolipoprotein B | Week 12 | -29.0 percent change in Apolipoprotein B | Standard Error 2.65 |
| Evacetrapib | Percent Change From Baseline in Apolipoprotein B | Week 52 | NA percent change in Apolipoprotein B | — |
| Placebo | Percent Change From Baseline in Apolipoprotein B | Week 12 | -1.3 percent change in Apolipoprotein B | Standard Error 2.7 |
| Placebo | Percent Change From Baseline in Apolipoprotein B | Week 52 | NA percent change in Apolipoprotein B | — |
Secondary
Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C)
LS mean using MMRM adjusted for baseline, treatment, visit , and treatment\*visit, where the participant is a random effect.
Time frame: Baseline, Week 12
Population: All randomized participants receiving at least 1 dose of study drug with evaluable HDL-C values at baseline, and at least 1 post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Evacetrapib | Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) | 123.57 percent change of HDL-C | Standard Error 6.697 |
| Placebo | Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) | -0.45 percent change of HDL-C | Standard Error 6.805 |
Secondary
Percent Change From Baseline in LDL-C (Direct)
LS mean using MMRM adjusted for baseline, treatment, visit , and treatment\*visit, where the participant is a random effect.
Time frame: Baseline, Week 12
Population: All randomized participants receiving at least 1 dose of study drug with evaluable LDL-C direct values at baseline, and at least 1 post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Evacetrapib | Percent Change From Baseline in LDL-C (Direct) | -33.86 percent change of LDL-C direct | Standard Error 3.163 |
| Placebo | Percent Change From Baseline in LDL-C (Direct) | 0.22 percent change of LDL-C direct | Standard Error 3.226 |
Secondary
Percent Change From Baseline in Lipoprotein-a
LS Mean from analysis of covariance (ANCOVA) model adjusted for baseline and treatment.
Time frame: Baseline, Week 12, Week 52
Population: All randomized participants receiving at least 1 dose of study drug with evaluable Lipoprotein-a values at baseline, and at least 1 post-baseline measurement.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Evacetrapib | Percent Change From Baseline in Lipoprotein-a | Week 12 | -35.71 percent change in Lipoprotein-a | Standard Error 6.574 |
| Evacetrapib | Percent Change From Baseline in Lipoprotein-a | Week 52 | NA percent change in Lipoprotein-a | — |
| Placebo | Percent Change From Baseline in Lipoprotein-a | Week 12 | 3.54 percent change in Lipoprotein-a | Standard Error 5.532 |
| Placebo | Percent Change From Baseline in Lipoprotein-a | Week 52 | NA percent change in Lipoprotein-a | — |
Secondary
Percent Change From Baseline in Non HDL-C
LS mean using MMRM adjusted for baseline, treatment, visit , and treatment\*visit, where the participant is a random effect.
Time frame: Baseline, Week 12
Population: All randomized participants receiving at least 1 dose of study drug with evaluable Non HDL-C values at baseline, and at least 1 post-baseline measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Evacetrapib | Percent Change From Baseline in Non HDL-C | -26.48 percent change in non HDL-C | Standard Error 3.171 |
| Placebo | Percent Change From Baseline in Non HDL-C | -0.03 percent change in non HDL-C | Standard Error 3.237 |