A Study of LY2484595 in Japanese Subjects

NCT01375075 | Completed Phase 2 Results DMC

• 2 other identifiers: 13049I1V-JE-EIAE
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to determine if 12 weeks of treatment with LY2484595 administered as a monotherapy will significantly increase high-density lipoprotein cholesterol (HDL-C) and decrease low-density lipoprotein cholesterol (LDL-C) in Japanese participants.

Conditions

Dyslipidemias

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline to 12 Weeks in High Density Lipoprotein Cholesterol (HDL-C) and Low Density Lipoprotein Cholesterol (LDL-C) With LY2484595 and Placebo

  Percent change from baseline = 100\*(post-baseline assessment - baseline assessment)/baseline assessment. Higher values in the percent change from baseline represented an improvement for HDL-C and lower values in the percent change from baseline represented an improvement for LDL-C. Least Squares (LS) mean was adjusted for baseline value of the variable analyzed.

  Baseline and Week 12

Secondary Outcomes (12)

• Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) and Low Density Lipoprotein Cholesterol (LDL-C) With LY2484595 in Combination With Atorvastatin

  Baseline, Weeks 2, 4, and 8

• Pharmacokinetics - Area Under the Curve (AUC) of LY2484595 and Atorvastatin

  Weeks 2, 4, 8, 12 (predose and postdose), and Week 16

• The Number and Severity of Episodes of Rashes at Any Time From Baseline Through Week 12

  Baseline through Week 12

• Change From Baseline to 12 Weeks in Blood Pressure

  Baseline and Week 12

• Change From Baseline to 12 Weeks in Aldosterone

  Baseline and Week 12

Study Arms (6)

30 milligrams (mg) LY2484595

EXPERIMENTAL

Administered orally once daily for 12 weeks

Drug: LY2484595; Drug: Placebo

100 mg LY2484595

EXPERIMENTAL

Administered orally once daily for 12 weeks

Drug: LY2484595; Drug: Placebo

500 mg LY2484595

EXPERIMENTAL

Administered orally once daily for 12 weeks

Drug: LY2484595; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Administered orally once daily for 12 weeks

Drug: Placebo

10 mg Atorvastatin

ACTIVE COMPARATOR

Administered orally once daily for 12 weeks

Drug: Placebo; Drug: Atorvastatin

100 mg LY2484595 + 10 mg Atorvastatin

EXPERIMENTAL

Administered orally once daily for 12 weeks

Drug: LY2484595; Drug: Placebo; Drug: Atorvastatin

Interventions

LY2484595 DRUG

Administered orally

100 mg LY2484595; 100 mg LY2484595 + 10 mg Atorvastatin; 30 milligrams (mg) LY2484595; 500 mg LY2484595

Placebo DRUG

Administered orally

10 mg Atorvastatin; 100 mg LY2484595; 100 mg LY2484595 + 10 mg Atorvastatin; 30 milligrams (mg) LY2484595; 500 mg LY2484595; Placebo

Atorvastatin DRUG

Administered orally

10 mg Atorvastatin; 100 mg LY2484595 + 10 mg Atorvastatin

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have Low HDL-C or High LDL-C criteria as follows:
• Low HDL lipid criteria:
• HDL-C \<45 milligrams per deciliter (mg/dL) (men) and \<50 mg/dL (women), and
• LDL-C according to Japan Atherosclerosis Society (JAS) guidelines as follows:
• LDL-C \<190 mg/dL (0-1 risk factors)
• LDL-C \<160 mg/dL (2 risk factors)
• LDL-C \<130 mg/dL (3+ risk factors),and
• Fasting Triglycerides (TG) \<400 mg/dL
• High LDL-C lipid criteria:
• HDL-C \<100 mg/dL, and
• LDL-C according to JAS guidelines as follows:
• LDL-C 100-190 mg/dL (0-1 risk factors)
• LDL-C 100-160 mg/dL (2 risk factors)
• LDL-C 100-130 mg/dL (3+ risk factors), and
• Fasting TG \<400 mg/dL

You may not qualify if:

• At screening, are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or unapproved use of a drug or device (other than the investigational product used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
• Have participated within 90 days prior to screening in any clinical trials of cholesteryl ester transfer protein (CETP) inhibitors (e.g., anacetrapib or dalcetrapib)
• Have completed or withdrawn from this study or have completed or withdrawn from any other study investigating LY2484595
• Are unable, unreliable, and/or unwilling to provide informed consent, make themselves available for the duration of the study, or will not abide by the procedures and study restrictions
• Have recent history of any clinically significant rash, history of any clinically severe drug-related rash, history of a chronic skin disorder (such as psoriasis, eczema or urticaria), history of significant skin hypersensitivities to household or cosmetic products, or allergens per the investigator, or presence of widespread tattoos or other skin condition that limits the assessment for rashes. Subjects who develop any rash during the Diet Lead-in/Washout Phase cannot be randomized
• Have or have had any clinical manifestation of coronary heart disease (CHD), such as stable or unstable angina, acute coronary syndrome, myocardial infarction, or a coronary revascularization procedure including stent placement, symptomatic carotid artery disease or symptomatic peripheral arterial disease. Subjects with a diagnosis of abdominal aortic aneurysm are excluded from this study
• Have systolic blood pressure (SBP) \>140 millimeters of mercury (mm Hg) or diastolic blood pressure (DBP) \>90 mm Hg as determined by the mean of 3 standardized measurements in the sitting position at randomization
• Have or have had documented hyperaldosteronism
• Have symptoms consistent with moderate or severe heart failure or are receiving treatment for symptomatic congestive heart failure (CHF) or known left ventricular ejection fraction (LVEF) \<35%. The absence of LVEF measurement does not prohibit entry into this study
• Have one of the following abnormalities: QTc prolongation \[Bazett's corrected QT interval (QTcB)\] of \>450 msec in male subjects or \>470 msec in female subjects, or abnormally wide QRS complexes (resulting from bundle branch blocks, intraventricular conduction delays, or pacemakers) or atrial fibrillation on screening electrocardiogram (ECG), previous history of QTc prolongation with another medication that required discontinuation, congenital long QT syndrome, previous history of ventricular tachycardia or unexplained syncope
• Have family history of long QT syndrome or sudden death likely secondary to ventricular arrhythmia
• Have active hepatobiliary disease, serologic evidence of past or active hepatitis B or C, or past or active gallbladder disease. Subjects who have been diagnosed with Gilbert syndrome or had a cholecystectomy greater than 90 days prior to screening can be included
• Have aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), alkaline phosphatase (ALP), or total bilirubin \>1.5 times the upper limit of normal (ULN)
• Have a history or presence of a chronic muscular or neuromuscular disease including prior rhabdomyolysis or drug-induced myopathy or an unexplained/documented elevation in creatine kinase (CK) ≥3 times the ULN
• Have a history of discontinuation from statin, change of statin, or a dose reduction of statin due to history of hypersensitivity, intolerance or adverse effect. Have a history of increased hepatic enzymes associated with use of an hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin)

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (5)

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.

Hyōgo, 660-0814, Japan

Location

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.

Kanagawa, 231-0023, Japan

Location

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, 615-8125, Japan

Location

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, 560-0005, Japan

Location

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, 111-0052, Japan

Location

MeSH Terms

Conditions

Dyslipidemias

Interventions

evacetrapib; Atorvastatin

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

800-545-5979

Study Officials

• 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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2011
• First Posted: June 17, 2011
• Study Start: June 1, 2011
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: October 25, 2018
• Results First Posted: October 25, 2018

Record last verified: 2018-03

Locations

JP (5)