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

• ClinicalTrials.gov Identifier: NCT02260648
• Recruitment Status: Terminated
• First Posted: October 9, 2014
• Results First Posted: October 9, 2018
• Last Update Posted: October 9, 2018
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hypercholesterolemia	Drug: Evacetrapib; Drug: Ezetimibe; Drug: Atorvastatin; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 149 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-Blind Efficacy and Safety Study of Evacetrapib in Combination With Atorvastatin in Japanese Patients With Primary Hypercholesterolemia
• Study Start Date: January 2015
• Actual Primary Completion Date: November 2015
• Actual Study Completion Date: November 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Evacetrapib; 130 milligrams (mg) evacetrapib and 10 mg atorvastatin administered PO once a day for 12 weeks.	Drug: Evacetrapib; Administered orally; Other Name: LY2484595; Drug: Atorvastatin; Administered orally
Active Comparator: Ezetimibe; 10 mg ezetimibe and 10 mg atorvastatin administered PO once a day for 12 weeks as a reference arm.	Drug: Ezetimibe; Administered orally; Drug: Atorvastatin; Administered orally
Placebo Comparator: Placebo; Placebo and 10 mg atorvastatin administered PO once a day for 12 weeks.	Drug: Atorvastatin; Administered orally; Drug: Placebo; Administered orally

Outcome Measures

Primary Outcome Measures :

1. Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C) Measured by Beta Quantification [ Time Frame: 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 :

1. Percent Change From Baseline to Week 12 in High-Density Lipoprotein Cholesterol (HDL-C) [ Time Frame: 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.
2. Percent Change From Baseline to Week 12 in LDL-C (Direct) [ Time Frame: 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.
3. Percent Change From Baseline to Week 12 in Non HDL-C [ Time Frame: 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.
4. Percent Change From Baseline to Week 12 in Lipoprotein-a [ Time Frame: Baseline, Week 12 ]
   The analysis of covariance (ANCOVA) model using last observation carried forward (LOCF) was applied to analyze percent changes from baseline.
5. Percent Change From Baseline to Week 12 in Apolipoprotein A-I [ Time Frame: Baseline, Week 12 ]
   The ANCOVA model using last observation carried forward (LOCF) was applied to analyze percent changes from baseline.
6. Percent Change From Baseline to Week 12 in Apolipoprotein B [ Time Frame: Baseline, Week 12 ]
   The ANCOVA model using last observation carried forward (LOCF) was applied to analyze percent changes from baseline.

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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).

Contacts and Locations

Locations

Japan

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.

Hyogo, Japan, 650-0021

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.

Ibaragi, Japan, 311-3516

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.

Ibaraki, Japan, 311-4153

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.

Kyoto, Japan, 6150035

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.

Osaka, Japan, 530-0001

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.

Saitama, Japan, 350-1305

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.

Shizuoka, Japan, 424-0855

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, 103-0028

Sponsors and Collaborators

Eli Lilly and Company

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

More Information

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02260648
• Other Study ID Numbers: 14501; I1V-JE-EIBG ( Other Identifier: Eli Lilly and Company )
• First Posted: October 9, 2014
• Results First Posted: October 9, 2018
• Last Update Posted: October 9, 2018
• Last Verified: February 2018

Additional relevant MeSH terms:

Hypercholesterolemia; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Atorvastatin; Ezetimibe; Evacetrapib; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors