Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02227784
Recruitment Status : Terminated (Study termination due to program termination.)
First Posted : August 28, 2014
Results First Posted : March 22, 2018
Last Update Posted : October 8, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE August 26, 2014
First Posted Date  ICMJE August 28, 2014
Results First Submitted Date  ICMJE February 18, 2018
Results First Posted Date  ICMJE March 22, 2018
Last Update Posted Date October 8, 2019
Study Start Date  ICMJE October 2014
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE
 (submitted: August 26, 2014)
Percent Change From Baseline to 3 Months in Low-Density Lipoprotein Cholesterol (LDL-C) [ Time Frame: Baseline, 3 Months ]
Change History Complete list of historical versions of study NCT02227784 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE
 (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  ICMJE A Study of Evacetrapib (LY2484595) in Participants With High Cholesterol
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Hyperlipidemia
Intervention  ICMJE
  • Drug: Evacetrapib
    Administered orally
    Other Name: LY2484595
  • Drug: Atorvastatin
    Administered orally
  • Drug: Ezetimibe
    Administered orally
  • Drug: Placebo
    Administered orally
Study Arms  ICMJE
  • 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: December 9, 2015)
366
Original Estimated Enrollment  ICMJE
 (submitted: August 26, 2014)
396
Actual Study Completion Date  ICMJE December 2015
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02227784
Other Study ID Numbers  ICMJE 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  ICMJE
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  ICMJE Eli Lilly and Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP