A Study of LY2484595 in Patients With High LDL-C or Low HDL-C - Full Text View

Purpose

The primary purpose of your participation in this study is to help answer the following research question(s)

Whether LY2484595 in combination with a statin drug (atorvastatin, simvastatin or rosuvastatin; currently used to treat abnormal fat or cholesterol in blood) improves the blood fat profile more than statins alone.
Whether LY2484595 alone improves blood fats profile compared to sugar pills.
Whether LY2484595 interferes with break down or functioning of statins.
Whether LY2484595 has any side effects that would not support testing it in future studies.

Condition	Intervention	Phase
Dyslipidemia	Drug: LY2484595 Drug: Atorvastatin Drug: Simvastatin Drug: Rosuvastatin Drug: Placebo for LY2484595 Drug: Placebo for Statins	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase 2 Efficacy and Safety Study of LY2484595 Alone and in Combination With Atorvastatin, Simvastatin, and Rosuvastatin in Patients With Hypercholesterolemia or Low HDL-C

Resource links provided by NLM:

MedlinePlus related topics: Cholesterol Metabolic Disorders Potassium Statins

Drug Information available for: Simvastatin Atorvastatin calcium Rosuvastatin calcium Rosuvastatin

U.S. FDA Resources

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:

Percent change from baseline to 12 week endpoint in high density lipoprotein cholesterol (HDL-C) with LY2484595 in combination with atorvastatin and atorvastatin monotherapy [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
Percent change from baseline to 12 week endpoint in low density lipoprotein cholesterol (LDL-C) with LY2484595 in combination with atorvastatin and atorvastatin monotherapy [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Percent change from baseline to 12 weeks in HDL-C with LY2484595 and Placebo [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
Percent change from baseline to 12 weeks in LDL-C with LY2484595 and Placebo [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
Percent change from baseline to 12 week endpoint in HDL-C with LY2484595 in combination with simvastatin or rosuvastatin and simvastatin/rosuvastatin monotherapy [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
Percent change from baseline to 12 week endpoint in LDL-C with LY2484595 in combination with simvastatin or rosuvastatin and simvastatin/rosuvastatin monotherapy [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: No ]
Pharmacokinetics - Area Under the Curve (AUC) [ Time Frame: 2, 4, 8, and 12 weeks and 4-6 weeks follow-up ] [ Designated as safety issue: No ]
Percent change in plasma Cholesteryl Ester Transfer Protein (CETP) activity [ Time Frame: Baseline, 4, 8, and 12 weeks and 4-6 weeks follow-up ] [ Designated as safety issue: No ]
Percent change in plasma Cholesteryl Ester Transfer Protein (CETP) mass [ Time Frame: Baseline, 4, 8 and 12 weeks and 4-6 weeks follow-up ] [ Designated as safety issue: No ]
Incidence and severity of rashes [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
Change from baseline to 12 week endpoint in blood pressure [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: Yes ]
Change from baseline to 12 week endpoint in serum aldosterone [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: Yes ]
Change from baseline to 12 week endpoint in plasma renin activity [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: Yes ]
Change from baseline to 12 week endpoint in plasma potassium [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: Yes ]
Change from baseline to 12 week endpoint in serum sodium [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: Yes ]
Change from baseline to 12 week endpoint in serum bicarbonate [ Time Frame: Baseline, 12 weeks ] [ Designated as safety issue: Yes ]
Change from baseline to 6 week follow-up in EuroQol-5 dimensions (EQ-5D) score [ Time Frame: Baseline, 6 week follow-up ] [ Designated as safety issue: No ]

Enrollment:	430
Study Start Date:	April 2010
Study Completion Date:	June 2011
Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 30 mg LY2484595 monotherapy	Drug: LY2484595 Administered daily by mouth for 12 weeks Drug: Placebo for Statins Administered daily by mouth for 12 weeks
Experimental: 100 mg LY2484595 monotherapy	Drug: LY2484595 Administered daily by mouth for 12 weeks Drug: Placebo for Statins Administered daily by mouth for 12 weeks
Experimental: 500 mg LY2484595 monotherapy	Drug: LY2484595 Administered daily by mouth for 12 weeks Drug: Placebo for Statins Administered daily by mouth for 12 weeks
Placebo Comparator: Placebo	Drug: Placebo for LY2484595 Administered daily by mouth for 12 weeks Drug: Placebo for Statins Administered daily by mouth for 12 weeks
Active Comparator: 20 mg Atorvastatin monotherapy	Drug: Atorvastatin Administered daily by mouth for 12 weeks Drug: Placebo for LY2484595 Administered daily by mouth for 12 weeks
Experimental: 100 mg LY2484595 + 20 mg Atorvastatin	Drug: LY2484595 Administered daily by mouth for 12 weeks Drug: Atorvastatin Administered daily by mouth for 12 weeks
Active Comparator: 40 mg Simvastatin monotherapy	Drug: Simvastatin Administered daily by mouth for 12 weeks Drug: Placebo for LY2484595 Administered daily by mouth for 12 weeks
Experimental: 100 mg LY2484595 + 40 mg Simvastatin	Drug: LY2484595 Administered daily by mouth for 12 weeks Drug: Simvastatin Administered daily by mouth for 12 weeks
Active Comparator: 10 mg Rosuvastatin monotherapy	Drug: Rosuvastatin Administered daily by mouth for 12 weeks Drug: Placebo for LY2484595 Administered daily by mouth for 12 weeks
Experimental: 100 mg LY2484595 + 10 mg Rosuvastatin	Drug: LY2484595 Administered daily by mouth for 12 weeks Drug: Rosuvastatin Administered daily by mouth for 12 weeks

Detailed Description:

Patients will be stratified according to baseline levels of serum triglycerides (<150 or greater than or equal to 150 mg/dL, HDL-C (<45 or greater than or equal to 45 mg/dL for men; <50 or greater than or equal to 50 mg/dL for women), and region (United States or Europe). After a diet lead-in and prior therapy washout phase, subjects meeting all entry criteria will be randomized to one of 10 double-blind treatment groups for a 12 week treatment phase. After randomization, patients will self-administer the study drugs once a day with a low fat meal as their first meal of the day.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Diagnosed with Low HDL-C or hypercholesterolemia, after diet lead-in/washout of lipid therapies

Exclusion Criteria:

History of coronary heart disease, or hardening of the arteries, or heart does not pump sufficiently well
Hypertension or high blood pressure that is not under control or your study physician does not consider the electrical activity of heart (ECG) to be compatible with participation in the study
History of a bad skin rash, a prior rash due to a drug or a history of chronic skin disorder (such as psoriasis or eczema)
Intolerance to certain lipid modifying drugs (including statins and Cholesteryl Ester Transfer Protein (CETP) inhibitors)
Not willing to stop taking prescription or over the counter drugs you use to control fats in your blood (like fish oil, niacin or statin) or pills to decrease your weight, including herbs
Not willing to follow the diet (low-fat) that the study physician will recommend
Have disease of liver, kidneys, muscles or other organs of body, a serious infection or cancer, or abnormal laboratory tests that study physician does not consider compatible with participation in the study
Breastfeeding woman or are a woman who can still become pregnant, but are not willing to use a valid birth control measure to prevent pregnancies

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01105975

Show 59 Study Locations

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

No publications provided by Eli Lilly and Company

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Nicholls SJ, Brewer HB, Kastelein JJ, Krueger KA, Wang MD, Shao M, Hu B, McErlean E, Nissen SE. Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial. JAMA. 2011 Nov 16;306(19):2099-109.

Responsible Party:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT01105975 History of Changes
Other Study ID Numbers:	12468, I1V-MC-EIAF
Study First Received:	April 15, 2010
Last Updated:	September 20, 2011
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board United Kingdom: Medicines and Healthcare Products Regulatory Agency Germany: German Institute of Medical Documentation and Information Germany: Federal Institute for Drugs and Medical Devices Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Denmark: Danish Medicines Agency Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Poland: The Central Register of Clinical Trials

Keywords provided by Eli Lilly and Company:

Dyslipidemias
Mixed dyslipidemia
Hypercholesterolemia
Atherosclerosis
Atorvastatin
Simvastatin
Rosuvastatin

Metabolic Diseases
Antilipemic Agents
Enzyme Inhibitors
Anticholesteremic Agents
Cholesteryl Ester Transfer Protein Inhibitors
Cholesteryl Ester
Lipid Metabolism Disorders

Additional relevant MeSH terms:

Hypercholesterolemia
Dyslipidemias
Hyperlipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Anticholesteremic Agents
Simvastatin
Atorvastatin
Rosuvastatin

Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 22, 2013