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

• ClinicalTrials.gov Identifier: NCT02227784
• Recruitment Status: Terminated
• First Posted: August 28, 2014
• Results First Posted: March 22, 2018
• Last Update Posted: October 8, 2019
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: August 26, 2014
• First Posted Date: August 28, 2014
• Results First Submitted Date: February 18, 2018
• Results First Posted Date: March 22, 2018
• Last Update Posted Date: October 8, 2019
• Study Start Date: October 2014
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 18, 2018)

Percent Change From Baseline to 3 Months in Low-Density Lipoprotein Cholesterol (LDL-C) [ Time Frame: Baseline, 3 Months ]

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.

• Original Primary Outcome Measures (submitted: August 26, 2014): Percent Change From Baseline to 3 Months in Low-Density Lipoprotein Cholesterol (LDL-C) [ Time Frame: Baseline, 3 Months ]

Current Secondary Outcome Measures (submitted: February 18, 2018)

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

Original Secondary Outcome Measures (submitted: August 26, 2014)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Evacetrapib (LY2484595) in Participants With High Cholesterol
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Hyperlipidemia

Intervention

• Drug: Evacetrapib
  Administered orally
  Other Name: LY2484595
• Drug: Atorvastatin
  Administered orally
• Drug: Ezetimibe
  Administered orally
• Drug: Placebo
  Administered orally

Study Arms

• 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.
  Interventions:

  • Drug: Evacetrapib
  • Drug: Atorvastatin
  • Drug: Placebo
• 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.
  Interventions:

  • Drug: Atorvastatin
  • Drug: Placebo
• 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.
  Interventions:

  • Drug: Atorvastatin
  • Drug: Ezetimibe
  • Drug: Placebo
• 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.
  Interventions:

  • Drug: Atorvastatin
  • Drug: Placebo

• 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 9, 2015): 366
• Original Estimated Enrollment (submitted: August 26, 2014): 396
• Actual Study Completion Date: December 2015
• Actual Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Puerto Rico, United States

Administrative Information

• NCT Number: NCT02227784
• Other Study ID Numbers: 14502; I1V-MC-EIBH ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• 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.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

• Responsible Party: Eli Lilly and Company
• Study Sponsor: Eli Lilly and Company
• Collaborators: Not Provided

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: September 2019