A Study of Evacetrapib (LY2484595) in Combination With Atorvastatin in Japanese Participants With Primary Hypercholesterolemia

Phase 3

Terminated

• Conditions: Hypercholesterolemia
• Interventions: Drug: Ezetimibe; Drug: Atorvastatin; Drug: Evacetrapib; Drug: Placebo

• Registration Number: NCT02260648
• Lead Sponsor: Eli Lilly and Company

Brief Summary

The main purpose of this study is to evaluate the efficacy and safety of the study drug known as evacetrapib when administered in combination with atorvastatin for 12 weeks in Japanese participants with primary hypercholesterolemia.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-10-06
• Study First Submitted QC: 2014-10-06
• Study First Posted: 2014-10-09
• Study Start: 2015-01
• Primary Completion: 2015-11
• Study Completion: 2015-11
• Disposition First Submitted: 2016-08-13
• Disposition First Submitted QC: 2016-08-13
• Disposition First Posted: 2016-08-16
• Status Verified: 2018-02
• Results First Submitted: 2018-02-18
• Results First Submitted QC: 2018-02-18
• Last Update Submitted: 2018-02-18
• Results First Posted: 2018-10-09
• Last Update Posted: 2018-10-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 149

Inclusion Criteria

• Must be treated with atorvastatin 10 mg/day for at least 30 days prior to study initiation.

• Japanese outpatients who are diagnosed with primary hypercholesterolemia with LDL-C levels (measured by a direct method) 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
  • Category II: 140 mg/dL≤LDL-C
  • Category III: 120 mg/dL≤LDL-C
  • Secondary prevention: 100 mg/dL≤LDL-C

• 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 homozygous 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 conditions < 90 days prior to study initiation

  • acute coronary syndrome (unstable angina, acute myocardial infarction)
  • symptomatic peripheral arterial disease
  • invasive treatment of carotid artery disease
  • ischemic stroke or transient ischemic attack (TIA)
  • intracranial hemorrhage

• History of abdominal aortic aneurysm.

• Participants with a history of intolerance/hypersensitivity to ezetimibe or statins.

• 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 (OTC) 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 (except for atorvastatin 10 mg), ezetimibe, bile acid sequestrant, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Participants taking probucol, fibrate or nicotinic agents within 8 weeks before study initiation are excluded from the study.

• Have been exposed to cholesteryl ester transfer protein (CETP) inhibitors (for example, anacetrapib or dalcetrapib).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ezetimibe	Ezetimibe	10 mg ezetimibe and 10 mg atorvastatin administered PO once a day for 12 weeks as a reference arm.
Placebo	Placebo	Placebo and 10 mg atorvastatin administered PO once a day for 12 weeks.
Placebo	Atorvastatin	Placebo and 10 mg atorvastatin administered PO once a day for 12 weeks.
Evacetrapib	Atorvastatin	130 milligrams (mg) evacetrapib and 10 mg atorvastatin administered PO once a day for 12 weeks.
Ezetimibe	Atorvastatin	10 mg ezetimibe and 10 mg atorvastatin administered PO once a day for 12 weeks as a reference arm.
Evacetrapib	Evacetrapib	130 milligrams (mg) evacetrapib and 10 mg atorvastatin administered PO once a day for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C) Measured by Beta Quantification	Baseline, Week 12	The mixed-effects model for repeated measures (MMRM) was used for the Least Squares Mean (LS Mean) estimates at Week 12 for LDL-C adjusting for baseline as response variables, baseline measurement as a covariate, treatment, Visit (4,5,6, or 7), and treatment-by-visit interaction as fixed effects, and participant as a random effect.

Secondary Outcome Measures

Name	Time	Method
Percent Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol (HDL-C)	Baseline, Week 12	The MMRM was used for the LS Mean estimates at Week 12 for HDL-C adjusting for baseline as response variables, baseline measurement as a covariate, treatment, visit, and treatment-by-visit interaction as fixed effects, and participant as a random effect, and treatment-by-visit interaction as fixed effects, and participant as a random effect.
Percent Change From Baseline to Week 12 in Lipoprotein-a	Baseline, Week 12	The analysis of covariance (ANCOVA) model using last observation carried forward (LOCF) was applied to analyze percent changes from baseline.
Percent Change From Baseline to Week 12 in Non HDL-C	Baseline, Week 12	The MMRM was used for the LS Mean estimates at Week 12 for Non HDL-C adjusting for baseline as response variables, baseline measurement as a covariate, treatment, visit, and treatment-by-visit interaction as fixed effects, and participant as a random effect.
Percent Change From Baseline to Week 12 in LDL-C (Direct)	Baseline, Week 12	The MMRM was used for the LS Mean estimates at Week 12 for LDL-C (direct) adjusting for baseline as response variables, baseline measurement as a covariate, treatment, visit, and treatment-by-visit interaction as fixed effects, and participant as a random effect.
Percent Change From Baseline to Week 12 in Apolipoprotein A-I	Baseline, Week 12	The ANCOVA model using last observation carried forward (LOCF) was applied to analyze percent changes from baseline.
Percent Change From Baseline to Week 12 in Apolipoprotein B	Baseline, Week 12	The ANCOVA model using last observation carried forward (LOCF) was applied to analyze percent changes from baseline.

Trial Locations

Locations (1)

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.; 🇯🇵 Tokyo, Japan