A Mechanistic Study of the Effects of LY518674 on High-Density Lipoprotein Cholesterol (HDL-C) Metabolism

NCT00327002 | Completed Phase 2

• 2 other identifiers: 804137 PALMSGCRC # 0995
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Agents that increase HDL-C via reverse cholesterol transport could provide a new therapeutic option for the prevention of atherosclerotic cardiovascular disease. The investigators propose to investigate the effects of LY518674 on components that may likely affect atherogenesis in patients with the metabolic syndrome including HDL-C metabolism and reverse cholesterol transport pathways, the inflammatory response, and oxidative stress in human subjects. As an agonist of the nuclear peroxisome proliferator activated receptor (PPAR) alpha, LY518674 may affect the transcription of genes that encode various proteins involved in atherogenesis. This study will explore the consequences of altered transcription such as changes in messenger ribonucleic acid (mRNA) and protein levels as well as protein activity.

Conditions

Metabolic Syndrome X

Keywords

Low HDL; Metabolic syndrome; low HDL Cholesterol in setting of metabolic syndrome

Interventions

LY518674 DRUG

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women between the ages of \> = 18 and \< = 80.
• HDL-C \< 40 mg/dL in men; HDL-C \< 50 mg/dL in women.
• At least two of the following criteria (\[a\], \[b\], \[c\], or \[d\]) listed below:
• Abdominal obesity defined by waist circumference: non-Asian men \> = 40 inches (102 cm) and non-Asian women \> = 35 inches (88 cm); Asian men \> = 35 inches (88 cm) and Asian women \> = 31 inches (79 cm),
• Blood pressure \> = 130 systolic, or \> = 85 diastolic mm Hg (on average of 3 measurements) in untreated patients OR if patient is taking \> = 1 approved anti-hypertensive agent,
• Fasting glucose \> = 100 mg/dL and \< 126 mg/dL,
• Fasting triglycerides \> 150 mg/dL and \< 600 mg/dL.
• Have given signed informed consent to participate in the study.
• Women of child-bearing potential, that is, women not surgically sterilized and between menarche and 1 year post menopause, must test negative for pregnancy at the time of enrollment based on a urine pregnancy test and agree to use a reliable method of birth control (for example, use of oral contraceptives or Norplant®; a reliable barrier method of birth control \[diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices\]; partner with vasectomy; or abstinence) during the study and for one month following the last dose of study drug.
• Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.

You may not qualify if:

• Potential study subjects may not be entered into the study if any of the following apply:
• Lipid-altering medications that meet any of the following criteria prior to the screening visit, are planned or are likely to be required during the course of the study:
• Subjects who have not been on a stable dose of statin therapy within 4 weeks.
• Subjects who have received fish oil dietary supplements \> 2 g/d within 4 weeks.
• Use of more than 250 mg per day of niacin within 6 weeks; fibrates within 12 weeks; or thiazolidinediones (TZDs) within 12 weeks.
• Orlistat and bile acid sequestrants are not permitted within 4 weeks.
• Ezetimibe is not permitted within 4 weeks.
• Postmenopausal women who have not been on a stable selective estrogen receptor modulator (SERM) dose within 4 weeks.
• Investigator site personnel directly affiliated with this study and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted.
• Lilly employees.
• Within 30 days of the initial dose of study drug, have received treatment with a drug that has not received regulatory approval for any indication.
• Have previously completed or withdrawn from this study or any other study investigating LY518674.
• Patients with diabetes or receiving PPARs consisting of gamma, alpha, delta agonists or gamma, alpha, delta antagonists, or partial agonists alone and in any combination.
• Uncontrolled hypertension defined as systolic blood pressure \> 180 mm Hg, diastolic blood pressure \> 100 mm Hg.
• Have a serum creatinine \> = 2 mg/dL, or nephrotic syndrome, end stage renal disease and use renal replacement therapy such as hemodialysis or peritoneal dialysis.

Sponsors & Collaborators

• University of Pennsylvania: lead
• Eli Lilly and Company: collaborator

Study Sites (1)

John Millar

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Metabolic Syndrome

Interventions

LY 518674

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Daniel Rader, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2006
• First Posted: May 17, 2006
• Study Start: January 1, 2006
• Primary Completion: September 1, 2006
• Study Completion: November 1, 2006
• Last Updated: December 11, 2015

Record last verified: 2009-12

Locations

US (1)