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

The Addition of Evacetrapib to Atorvastatin Compared to Placebo, High Intensity Atorvastatin, and Atorvastatin With Ezetimibe to Evaluate LDL-C Lowering in Patients With Primary Hyperlipidemia - The ACCENTUATE Study

The purpose of the ACCENTUATE study is to evaluate whether the study drug known as evacetrapib is effective in treating participants with high cholesterol and atherosclerotic cardiovascular disease (ASCVD) and/or diabetes.

Study Overview

• Status: Terminated
• Conditions: Hyperlipidemia
• Intervention / Treatment: Drug: Placebo; Drug: Evacetrapib; Drug: Ezetimibe; Drug: Atorvastatin

• Study Type: Interventional
• Enrollment (Actual): 366
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • Ponce, Puerto Rico, 00717-1322
    • Research and Cardiovascular Corp.
  • San Juan, Puerto Rico, 00909
    • GCM Medical Group PSC
  • San Juan, Puerto Rico, 00909
    • Clinical Research Puerto Rico, Inc.
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Heart Center Research, LLC
  • Arizona
    • Mesa, Arizona, United States, 85213
      • Desert Clinical Research
    • Phoenix, Arizona, United States, 85020
      • Central Phoenix Med Clinic LLC
  • California
    • Carmichael, California, United States, 95608
      • Advanced Clinical Research
    • Encino, California, United States, 91436
      • Tooraj Joseph Raoof M.D., Inc.
    • Irvine, California, United States, 92618
      • Irvine Clinical Research Center
    • Long Beach, California, United States, 90822
      • VA Long Beach Healthcare System
    • Rancho Cucamonga, California, United States, 91730
      • Rancho Cucamonga Clinical
    • Spring Valley, California, United States, 91978
      • Encompass Clinical Research
    • Tustin, California, United States, 92780
      • University Clinical Investigators, Inc.
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research
  • Colorado
    • Aurora, Colorado, United States, 80045-2517
      • University of Colorado Health Sciences Center
    • Colorado Springs, Colorado, United States, 80909
      • Cardiac Research
  • Florida
    • Boynton Beach, Florida, United States, 33472
      • Zasa Clinical Research
    • Daytona Beach, Florida, United States, 32117
      • Cardiology Research Assoc.
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research LLC
    • Fort Lauderdale, Florida, United States, 33308
      • Alan Graff, MD, PA
    • Inverness, Florida, United States, 34452
      • Nature Coast Clinical Research, LLC
    • Miami, Florida, United States, 33135
      • Suncoast Research Group, LLC
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Wellington, Florida, United States, 33449
      • Cardiology Partners Clinical Research Institute, LLC
  • Georgia
    • Covington, Georgia, United States, 30014
      • Georgia Heart Specialists
    • Gainesville, Georgia, United States, 30501
      • United Osteoporosis Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East West Medical Institute
  • Idaho
    • Meridian, Idaho, United States, 83646
      • Solaris Clinical Research
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Northwest Heart Clinical Research, LLC
    • Chicago, Illinois, United States, 60607
      • Cedar-Crosse Research Center
    • Crystal Lake, Illinois, United States, 60012
      • Midwest CRC
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Midwest Institute for Clinical Research
    • Indianapolis, Indiana, United States, 46237
      • Indiana Heart Physicians Inc
  • Kansas
    • Hutchinson, Kansas, United States, 67502
      • Hutchinson Clinic
  • Kentucky
    • Louisville, Kentucky, United States, 40205
      • Community Medical Associates
  • Louisiana
    • Bossier City, Louisiana, United States, 71111
      • Grace Research
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • Maryland Cardiovascular Specialists
    • Baltimore, Maryland, United States, 21236
      • Overlea Personal Physicians
  • Massachusetts
    • Hyannis, Massachusetts, United States, 02601
      • Cape Cod Research Institute
    • Methuen, Massachusetts, United States, 01844
      • ActivMed Practices & Research, Inc
  • Missouri
    • Saint Louis, Missouri, United States, 63117
      • Medex Healthcare Research, Inc.
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Palm Research Center
  • New Jersey
    • Somerset, New Jersey, United States, 08873
      • Heart and Vascular Center of New Brunswick LLC
  • New York
    • New York, New York, United States, 10036
      • Medex Healthcare Research, Inc.
    • Saratoga Springs, New York, United States, 12866
      • Saratoga Clinical Research LLC
    • Williamsville, New York, United States, 14221
      • Buffalo Cardiology and Pulmonary Associates, P.C.
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Asheville Cardiology Associates
    • Charlotte, North Carolina, United States, 28204
      • Metrolina Internal Medicine, P.A.
    • High Point, North Carolina, United States, 27265
      • High Point Clinical Trials Center
    • Rocky Mount, North Carolina, United States, 27804
      • Boice Willis Clinic, PA
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington, LLC
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Lillestol Research LLC
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Aventiv Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73135
      • South Oklahoma Heart Research, LLC
  • Oregon
    • Portland, Oregon, United States, 97225
      • Portland Preventive Cardiology, LLC
  • Rhode Island
    • Cumberland, Rhode Island, United States, 02864
      • Partners in Clinical Research
  • South Carolina
    • Mount Pleasant, South Carolina, United States, 29464
      • PMG Research of Charleston, LLC
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Black Hills Cardiovascular Research Group
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Holston Medical Group Clinical Research
  • Texas
    • Tomball, Texas, United States, 77375-4536
      • Northwest Houston Heart Center
  • Virginia
    • Richmond, Virginia, United States, 23294
      • National Clinical Research - Richmond
  • Washington
    • Bellevue, Washington, United States, 98007-4209
      • Northwest Clinical Research Center
    • Spokane, Washington, United States, 99204
      • Kootenai Heart Clinics, LLC
  • Wisconsin
    • Kenosha, Wisconsin, United States, 53142
      • Clinical Investigation Specialists Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must be treated with atorvastatin 40 mg/day for at least 30 days prior to screening
• Have an LDL-C >70 mg/deciliter(dL) or non-HDL-C >100 mg/dL
• Have screening triglycerides ≤400 mg/dL (≤4.5 millimoles/Liter)
• Individuals with ASCVD and/or individuals with type 1 or type 2 diabetes

Exclusion Criteria:

• Have a hemoglobin A1c (HbA1c) >9.5%
• New York Heart Association (NYHA) class III or IV congestive heart failure
• History of either a transient ischemic stroke or ischemic stroke <30 days
• History of acute coronary syndrome (ACS) <30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atorvastatin + Evacetrapib; 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.	Drug: Placebo; Administered orally; Drug: Evacetrapib; Administered orally; Other Names: LY2484595; Drug: Atorvastatin; Administered orally
Active Comparator: Atorvastatin 80 mg; 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.	Drug: Placebo; Administered orally; Drug: Atorvastatin; Administered orally
Active Comparator: Atorvastatin + Ezetimibe; 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.	Drug: Placebo; Administered orally; Drug: Ezetimibe; Administered orally; Drug: Atorvastatin; Administered orally
Active Comparator: Atorvastatin 40 mg; 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.	Drug: Placebo; Administered orally; Drug: Atorvastatin; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline to 3 Months in Low-Density Lipoprotein Cholesterol (LDL-C)	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.	Baseline, 3 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline to 3 Months in High-Density Lipoprotein Cholesterol (HDL-C)	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.	Baseline, 3 Months
Percent Change From Baseline to 3 Months in Apolipoprotein AI (apoAI)	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.	Baseline, 3 Months
Percent Change From Baseline to 3 Months in Non-HDL-C	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.	Baseline, 3 Months
Percent Change From Baseline to 3 Months in Apolipoprotein B (apoB)	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.	Baseline, 3 Months
Percent Change From Baseline to 3 Months in Cholesterol Efflux Capacity	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.	Baseline, 3 Months
Percent Change From Baseline to 3 Months in Lipoprotein(a) (Lp[a])	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.	Baseline, 3 Months

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Nicholls SJ, Ray KK, Ballantyne CM, Beacham LA, Miller DL, Ruotolo G, Nissen SE, Riesmeyer JS; ACCENTUATE Investigators. Comparative effects of cholesteryl ester transfer protein inhibition, statin or ezetimibe on lipid factors: The ACCENTUATE trial. Atherosclerosis. 2017 Jun;261:12-18. doi: 10.1016/j.atherosclerosis.2017.04.008. Epub 2017 Apr 8.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: August 26, 2014
• First Submitted That Met QC Criteria: August 26, 2014
• First Posted (Estimate): August 28, 2014

Study Record Updates

• Last Update Posted (Actual): October 8, 2019
• Last Update Submitted That Met QC Criteria: September 25, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Hyperlipidemias; Hyperlipoproteinemias; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Ezetimibe; Evacetrapib
• Other Study ID Numbers: 14502; I1V-MC-EIBH (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR