Cardiovascular Diseases
Conditions
Brief summary
The purpose of the ACCELERATE study is to evaluate the efficacy and safety of evacetrapib in participants with high-risk vascular disease (HRVD).
Interventions
DRUGEvacetrapib
Administered Orally
DRUGPlacebo
Administered Orally
Sponsors
The Cleveland Clinic
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of high risk vascular disease (HRVD) (that is, meet at least one of the disease diagnostic criteria of: 1)History of acute coronary syndrome (ACS) (that is, ≥30 days through 365 days after discharge for ACS) 2)cerebrovascular atherosclerotic disease 3)peripheral arterial disease 4)diabetes mellitus with documented coronary artery disease and are clinically stable (as judged by the responsible physician). * Must be treated with a statin for at least 30 days prior to screening. If not treated with a statin must have documented statin intolerance, or contraindication to statin * Have a screening high-density lipoprotein cholesterol (HDL-C) ≤80 milligram per deciliter (mg/dL) (≤2.1 millimole per liter \[mmol/L\]) * Have screening triglycerides (TG) ≤400 mg/dL (≤4.5 mmol/L) * Meet 1 of the following criteria: * screening low-density lipoprotein cholesterol (LDL-C) no more than 10 mg/dL (0.3 mmol/L) above the target chosen by the investigator (either LDL-C \<100 mg/dL \[\<2.6 mmol/L\] or LDL-C \<70 mg/dL \[\<1.8 mmol/L\]), OR * if LDL-C is greater than target, the participant must be on maximum tolerated statin dose (for at least 30 days), have documented statin intolerance, or contraindication to statin
Exclusion criteria
* Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study * Have previously completed or withdrawn from this study, or withdrawn from any other study investigating evacetrapib * Female participants who are known to be pregnant or breastfeeding * Women of child-bearing potential only, who test positive for pregnancy between screening and randomization, or who do not agree to use a reliable method of birth control during the study * History of transient ischemic attack (TIA) or ischemic stroke \<30 days and ACS \<30 days * Any reading of systolic blood pressure ≥180 millimeter of mercury (mm Hg) or diastolic blood pressure ≥110 mm Hg at screening or randomization * History of hemorrhagic stroke or intracranial hemorrhage * New York Heart Association class III or IV congestive heart failure * Serum creatinine \>2.2 mg/dL (\>194.5 micromole per liter \[μmol/L\]) at screening * Clinically active liver disease. Participants are not excluded due to Gilbert's Syndrome or a history of cholelithiasis/cholecystectomy * History of malignancy within the preceding 3 years prior to screening * Known malabsorption syndrome with the exception of lactose intolerance * Participants with a known history of primary or secondary hyperaldosteronism * Participants with a history of intolerance/hypersensitivity to cholesterol ester transfer protein (CETP) inhibitors * Any clinically significant medical condition that according to the investigator could interfere with participation in the study * Participants whose life expectancy is anticipated to be less than 4 years * Unable or unwilling to comply with study requirements, or deemed by the investigator to be unfit for the study * Have a history of drug, alcohol, or substance abuse within the past 6 months, as assessed by the investigator * Concurrent or anticipated need for treatment with niacin \>250 mg/day or for chronic administration of drugs on the exclusion list * Previous exposure to the CETP inhibitors dalcetrapib or evacetrapib within the last 3 months or anacetrapib within the last 12 months * Any planned coronary angiography or coronary revascularization procedure. If angiography or revascularization is planned, participants may be screened and enrolled after all such planned procedures are completed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Composite Primary Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), Stroke, Coronary Revascularization, or Hospitalization for Unstable Angina (UA) | Baseline to Study Completion (Up to 4 years) | For component endpoints, the number of participants includes those experiencing fatal events and account for all occurrences regardless of whether or not another component event occurred previously. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percent Change From Baseline to 3 Months in Low-Density (LDL-C) and High-Density Lipoprotein Cholesterol (HDL-C) Levels | Baseline, 3 Months | — |
| Number of Participants With Composite Endpoint of All-Cause Mortality, MI, Stroke, Coronary Revascularization, or Hospitalization for UA | Baseline through End of Study (Up to 4 years) | For component endpoints, the number of participants includes those experiencing fatal events and account for all occurrences regardless of whether or not another component event occurred previously. |
| Number of Participants With Composite Endpoint of CV Death, MI, or Coronary Revascularization | Baseline through End of Study (Up to 4 years) | For component endpoints, the number of participants includes those experiencing fatal events and account for all occurrences regardless of whether or not another component event occurred previously. |
| Number of Participants With Composite Endpoint of CV Death, MI, Stroke, or Hospitalization for UA | Baseline through End of Study (Up to 4 years) | For component endpoints, the number of participants includes those experiencing fatal events and account for all occurrences regardless of whether or not another component event occurred previously. |
| Number of Participants With Triple Composite Endpoint of CV Death, MI, or Stroke | Baseline through End of Study (Up to 4 years) | For component endpoints, the number of participants includes those experiencing fatal events and account for all occurrences regardless of whether or not another component event occurred previously. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czechia, Denmark, Estonia, France, Germany, Hong Kong, Hungary, Israel, Italy, Japan, Lithuania, Mexico, Netherlands, New Zealand, Poland, Puerto Rico, Romania, Russia, Slovakia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Pre-assignment details
Non-Completers: Participants Known to be Alive at Study End is a subset of those who did not withdraw consent and later found to be alive from public sources. Lost to follow-up is a subset of those who did not withdraw consent for whom study end vital status could not be ascertained.
Participants by arm
| Arm | Count |
|---|---|
| Evacetrapib Evacetrapib 130 mg tablet, administered orally once daily for up to 4 years. Participants received standard of care for HRVD. | 6,038 |
| Placebo Placebo, tablet administered orally once daily for up to 4 years. Participants received standard of care for HRVD. | 6,054 |
| Total | 12,092 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Known to be Alive at Study End | 54 | 62 |
| Overall Study | Lost to Follow-up | 9 | 7 |
| Overall Study | Withdrawal by Subject | 49 | 51 |
Baseline characteristics
| Characteristic | Placebo | Total | Evacetrapib |
|---|---|---|---|
| Age, Continuous | 64.994 years STANDARD_DEVIATION 9.4591 | 64.892 years STANDARD_DEVIATION 9.4223 | 64.791 years STANDARD_DEVIATION 9.3849 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 522 Participants | 1022 Participants | 500 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5386 Participants | 10780 Participants | 5394 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 146 Participants | 290 Participants | 144 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 226 Participants | 469 Participants | 243 Participants |
| Race (NIH/OMB) Asian | 640 Participants | 1290 Participants | 650 Participants |
| Race (NIH/OMB) Black or African American | 153 Participants | 294 Participants | 141 Participants |
| Race (NIH/OMB) More than one race | 26 Participants | 61 Participants | 35 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 5 Participants | 11 Participants | 6 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 33 Participants | 63 Participants | 30 Participants |
| Race (NIH/OMB) White | 4971 Participants | 9904 Participants | 4933 Participants |
| Region of Enrollment Argentina | 91 Participants | 180 Participants | 89 Participants |
| Region of Enrollment Australia | 160 Participants | 319 Participants | 159 Participants |
| Region of Enrollment Austria | 34 Participants | 68 Participants | 34 Participants |
| Region of Enrollment Belgium | 42 Participants | 84 Participants | 42 Participants |
| Region of Enrollment Brazil | 56 Participants | 110 Participants | 54 Participants |
| Region of Enrollment Bulgaria | 118 Participants | 231 Participants | 113 Participants |
| Region of Enrollment Canada | 619 Participants | 1245 Participants | 626 Participants |
| Region of Enrollment China | 221 Participants | 445 Participants | 224 Participants |
| Region of Enrollment Czechia | 185 Participants | 372 Participants | 187 Participants |
| Region of Enrollment Denmark | 100 Participants | 195 Participants | 95 Participants |
| Region of Enrollment Estonia | 29 Participants | 59 Participants | 30 Participants |
| Region of Enrollment France | 52 Participants | 97 Participants | 45 Participants |
| Region of Enrollment Germany | 202 Participants | 400 Participants | 198 Participants |
| Region of Enrollment Hong Kong | 28 Participants | 52 Participants | 24 Participants |
| Region of Enrollment Hungary | 115 Participants | 233 Participants | 118 Participants |
| Region of Enrollment Israel | 74 Participants | 146 Participants | 72 Participants |
| Region of Enrollment Italy | 40 Participants | 83 Participants | 43 Participants |
| Region of Enrollment Japan | 202 Participants | 407 Participants | 205 Participants |
| Region of Enrollment Lithuania | 15 Participants | 28 Participants | 13 Participants |
| Region of Enrollment Mexico | 231 Participants | 466 Participants | 235 Participants |
| Region of Enrollment Netherlands | 169 Participants | 340 Participants | 171 Participants |
| Region of Enrollment New Zealand | 64 Participants | 127 Participants | 63 Participants |
| Region of Enrollment Poland | 240 Participants | 483 Participants | 243 Participants |
| Region of Enrollment Romania | 66 Participants | 130 Participants | 64 Participants |
| Region of Enrollment Russia | 82 Participants | 167 Participants | 85 Participants |
| Region of Enrollment Slovakia | 117 Participants | 233 Participants | 116 Participants |
| Region of Enrollment South Africa | 76 Participants | 153 Participants | 77 Participants |
| Region of Enrollment South Korea | 94 Participants | 181 Participants | 87 Participants |
| Region of Enrollment Spain | 66 Participants | 131 Participants | 65 Participants |
| Region of Enrollment Sweden | 33 Participants | 66 Participants | 33 Participants |
| Region of Enrollment Switzerland | 14 Participants | 29 Participants | 15 Participants |
| Region of Enrollment Taiwan | 53 Participants | 105 Participants | 52 Participants |
| Region of Enrollment Turkey | 2 Participants | 3 Participants | 1 Participants |
| Region of Enrollment Ukraine | 66 Participants | 133 Participants | 67 Participants |
| Region of Enrollment United Kingdom | 58 Participants | 116 Participants | 58 Participants |
| Region of Enrollment United States | 2240 Participants | 4475 Participants | 2235 Participants |
| Sex: Female, Male Female | 1394 Participants | 2784 Participants | 1390 Participants |
| Sex: Female, Male Male | 4660 Participants | 9308 Participants | 4648 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2,659 / 6,036 | 2,529 / 6,052 |
| serious Total, serious adverse events | 2,306 / 6,036 | 2,341 / 6,052 |
Outcome results
Primary
Number of Participants With Composite Primary Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), Stroke, Coronary Revascularization, or Hospitalization for Unstable Angina (UA)
For component endpoints, the number of participants includes those experiencing fatal events and account for all occurrences regardless of whether or not another component event occurred previously.
Time frame: Baseline to Study Completion (Up to 4 years)
Population: All randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Evacetrapib | Number of Participants With Composite Primary Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), Stroke, Coronary Revascularization, or Hospitalization for Unstable Angina (UA) | 779 Participants |
| Placebo | Number of Participants With Composite Primary Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), Stroke, Coronary Revascularization, or Hospitalization for Unstable Angina (UA) | 776 Participants |
Comparison: Primary Endpoint: Time to First Occurrence of the Composite Primary Endpoint of Cardiovascular (CV) Death, Myocardial Infarction (MI), Stroke, Coronary Revascularization, or Hospitalization for Unstable Angina (UA)p-value: 0.905495% CI: [0.911, 1.111]Regression, Cox
Secondary
Mean Percent Change From Baseline to 3 Months in Low-Density (LDL-C) and High-Density Lipoprotein Cholesterol (HDL-C) Levels
Time frame: Baseline, 3 Months
Population: All randomized participants with evaluable LDL-C and HDL-C levels.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evacetrapib | Mean Percent Change From Baseline to 3 Months in Low-Density (LDL-C) and High-Density Lipoprotein Cholesterol (HDL-C) Levels | LDL-C | -31.12 percent | Standard Deviation 27.583 |
| Evacetrapib | Mean Percent Change From Baseline to 3 Months in Low-Density (LDL-C) and High-Density Lipoprotein Cholesterol (HDL-C) Levels | HDL-C | 133.18 percent | Standard Deviation 57.204 |
| Placebo | Mean Percent Change From Baseline to 3 Months in Low-Density (LDL-C) and High-Density Lipoprotein Cholesterol (HDL-C) Levels | LDL-C | 5.99 percent | Standard Deviation 29.007 |
| Placebo | Mean Percent Change From Baseline to 3 Months in Low-Density (LDL-C) and High-Density Lipoprotein Cholesterol (HDL-C) Levels | HDL-C | 1.63 percent | Standard Deviation 17.455 |
Comparison: LDL-Cp-value: <0.000195% CI: [-38.15, -36.08]ANOVA
Comparison: HDL-Cp-value: <0.000195% CI: [130.01, 133.09]ANOVA
Secondary
Number of Participants With Composite Endpoint of All-Cause Mortality, MI, Stroke, Coronary Revascularization, or Hospitalization for UA
For component endpoints, the number of participants includes those experiencing fatal events and account for all occurrences regardless of whether or not another component event occurred previously.
Time frame: Baseline through End of Study (Up to 4 years)
Population: All randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Evacetrapib | Number of Participants With Composite Endpoint of All-Cause Mortality, MI, Stroke, Coronary Revascularization, or Hospitalization for UA | 857 Participants |
| Placebo | Number of Participants With Composite Endpoint of All-Cause Mortality, MI, Stroke, Coronary Revascularization, or Hospitalization for UA | 867 Participants |
Comparison: Time to First Occurrence of the Composite Endpoint of All-Cause Mortality, MI, Stroke, Coronary Revascularization, or Hospitalization for UAp-value: 0.846395% CI: [0.901, 1.089]Regression, Cox
Secondary
Number of Participants With Composite Endpoint of CV Death, MI, or Coronary Revascularization
For component endpoints, the number of participants includes those experiencing fatal events and account for all occurrences regardless of whether or not another component event occurred previously.
Time frame: Baseline through End of Study (Up to 4 years)
Population: All randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Evacetrapib | Number of Participants With Composite Endpoint of CV Death, MI, or Coronary Revascularization | 690 Participants |
| Placebo | Number of Participants With Composite Endpoint of CV Death, MI, or Coronary Revascularization | 691 Participants |
Comparison: Time to First Occurrence of the Composite Endpoint of CV Death, MI, or Coronary Revascularizationp-value: 0.987495% CI: [0.901, 1.112]Regression, Cox
Secondary
Number of Participants With Composite Endpoint of CV Death, MI, Stroke, or Hospitalization for UA
For component endpoints, the number of participants includes those experiencing fatal events and account for all occurrences regardless of whether or not another component event occurred previously.
Time frame: Baseline through End of Study (Up to 4 years)
Population: All randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Evacetrapib | Number of Participants With Composite Endpoint of CV Death, MI, Stroke, or Hospitalization for UA | 571 Participants |
| Placebo | Number of Participants With Composite Endpoint of CV Death, MI, Stroke, or Hospitalization for UA | 570 Participants |
Comparison: Time to First Occurrence of the Composite Endpoint of CV Death, MI, Stroke, or Hospitalization for UAp-value: 0.957495% CI: [0.893, 1.127]Regression, Cox
Secondary
Number of Participants With Triple Composite Endpoint of CV Death, MI, or Stroke
For component endpoints, the number of participants includes those experiencing fatal events and account for all occurrences regardless of whether or not another component event occurred previously.
Time frame: Baseline through End of Study (Up to 4 years)
Population: All randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Evacetrapib | Number of Participants With Triple Composite Endpoint of CV Death, MI, or Stroke | 437 Participants |
| Placebo | Number of Participants With Triple Composite Endpoint of CV Death, MI, or Stroke | 453 Participants |
Comparison: Time to First Occurrence of Triple Composite Endpoint of CV Death, MI, or Strokep-value: 0.591795% CI: [0.846, 1.1]Regression, Cox