Evaluation of Efficacy and Safety of Omacor, Co-Administered With Atorvastatin, in Subjects With Hypertriglyceridemia

A Randomized, Double-Blind, Placebo-Controlled, Forced Titration Study to Assess the Efficacy and Safety of Omacor, Co-Administered With Open-Label Atorvastatin Therapy, in Hypertriglyceridemic Subjects

The purpose of this study is to evaluate the efficacy and safety of Omacor (omega-3-acid ethyl esters) combined with atorvastatin for lowering non-high-density lipoprotein cholesterol (non-HDL-C) in hypertriglyceridemic subjects.

Study Overview

• Status: Completed
• Conditions: Hypertriglyceridemia
• Intervention / Treatment: Drug: atorvastatin; Drug: Lovaza (omega-3-acid ethyl esters) [formerly known as Omacor] plus atorvastatin

Detailed Description

Randomized, double-blind, placebo-controlled, parallel-group study design with eleven clinic visits (one screening visit, three lead-in/baseline visits, and seven treatment visits) After a 4-week diet only lead-in period, subjects with a triglyceride (TG) level in the high to very high range and with non-HDL-C level above NCEP ATPIII goals will be randomized to receive either open-label atorvastatin 10 mg per day plus double-blinded Lovaza 4g (4 x 1g capsules) per day OR open-label atorvastatin 10 mg per day plus a double-blinded matching placebo (4 corn oil capsules per day) for 8 weeks After the initial 8-week treatment period, the dose of open-label atorvastatin will be titrated to 20 mg per day (with the Lovaza or matching placebo corn oil doses remaining at 4 capsules per day) for an additional 4 weeks At Week 12, a second open-label titration to 40 mg of open-label atorvastatin per day will be maintained for an additional 4 weeks (again with the Lovaza or matching placebo corn oil doses remaining at 4 capsules per day)

• Study Type: Interventional
• Enrollment (Actual): 245
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women, ages 18-79 years, inclusive
• Fasting, untreated non-high-density lipoprotein cholesterol (non-HDL-C) level above NCEP ATPIII goals
• Fasting, untreated triglyceride (TG) level in the high to very high range
• Provide written informed consent and authorization for protected health information disclosure

Exclusion Criteria:

• Pregnancy
• Use of lipid-altering drugs which cannot be stopped
• History of certain cardiovascular conditions or cardiac surgery within prior 6 months
• Body mass index above 40 kg per square meter
• Allergy or sensitivity to omega-3 fatty acids or to statin drugs
• Poorly-controlled conditions including diabetes, hypertension, or thyroid disease
• Certain muscle, liver, kidney, lung, or gastrointestinal conditions
• Certain medications
• Active cancers treated within prior 2 years (except non-melanoma skin cancer)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: atorvastatin arm; atorvastatin + placebo	Drug: atorvastatin; atorvastatin + placebo; Other Names: Lovaza (omega-3-acid ethyl esters) [formerly known as Omacor] plus atorvastatin
Experimental: Lovaza arm; Lovaza + atorvastatin	Drug: Lovaza (omega-3-acid ethyl esters) [formerly known as Omacor] plus atorvastatin; Lovaza + atorvastatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	Non-high density lipoprotein cholesterol is the Total Cholesterol minus the HDL(high density lipoproteins or the sum of the LDL, VLDL and IDL. That is, Low Density Lipoproteins, Very Low Density Lipoproteins and Intermediate Density Lipoproteins.	Baseline and Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Total Cholesterol (TC) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	Total Cholesterol is the sum of the High Density Lipoproteins (HDL), Low Density Lipoproteins (LDL), Very Low Density Lipoproteins (VLDL), and Intermediate Density Lipoproteins (IDL).	Baseline and Week 8
Percent Change in High Density Lipoprotein (HDL)Cholesterol From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	HDL - A complex of lipids and proteins in approximately equal amounts that functions as a transporter of cholesterol in the blood. High levels are associated with a decreased risk of atherosclerosis and coronary heart disease. High density lipoprotein cholesterol is the Total Cholesterol minus the sum of the LDL, VLDL and IDL.	Baseline and Week 8
Percent Change in Low Density Lipoprotein (LDL) Cholesterol (Beta-quantification) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	LDL - A complex of lipids and proteins, with greater amounts of lipid than protein, that transports cholesterol in the blood. High levels are associated with an increased risk of atherosclerosis and coronary heart disease.	Baseline and Week 8
Percent Change in Triglycerides From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	Triglycerides - A naturally occurring ester of three fatty acids and glycerol that is the chief constituent of fats and oils.	Baseline and Week 8
Percent Change in Very Low Density Lipoproteins (VLDL) Cholesterol From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	VLDL - very-low-density lipoprotein: a plasma lipoprotein with a high lipid content, associated with atherosclerosis.	Baseline and Week 8
Percent Change in Apolipoprotein-A-1 From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	Apolipoprotein A1 - major protein component of high density lipoprotein (HDL) in plasma. The protein promotes cholesterol efflux from tissues to the liver for excretion.	Baseline and Week 8
Percent Change in Apolipoprotein C-III From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	Apolipoprotein C-III (APOC3) is a very low density lipoprotein (VLDL) protein. APOC3 inhibits lipoprotein lipase and hepatic lipase; it is thought to delay catabolism of triglyceride-rich particles.	Baseline and Week 8
Percent Change in Total Cholesterol/High Density Lipoprotein Cholesterol Ratio From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	Total cholesterol/High density lipoprotein cholesterol	Baseline and Week 8
Percent Change in Triglycerides/High Density Lipoprotein Cholesterol Ratio From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period		Baseline and Week 8
Percent Change in Docosahexaenoic Acid (DHA) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	Docosahexaenoic Acid is an omega-3 essential fatty acid.	Baseline and Week 8
Percent Change in Eicosapentaenoic Acid (EPA) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	Eicosapentaenoic acid (EPA) is one of several omega-3 fatty acids used by the body. It is found in cold water fatty fish and in fish oil supplements, along with docosahexaenoic acid (DHA). Omega-3 fatty acids are part of a healthy diet that helps lower risk of heart disease.	Baseline and Week 8
Percent Change in Low Density Lipoprotein Particle Concentration Total From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	Low-density lipoproteins - A complex of lipids and proteins, with greater amounts of lipid than protein, that transports cholesterol in the blood. High levels are associated with an increased risk of atherosclerosis and coronary heart disease.	Baseline and Week 8
Percent Change in Low Density Lipoprotein Particle Size From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	Low-density lipoproteins - A complex of lipids and proteins, with greater amounts of lipid than protein, that transports cholesterol in the blood. High levels are associated with an increased risk of atherosclerosis and coronary heart disease. Researchers have linked LDL particle size to the subsequent development of heart disease.	Baseline and Week 8
Percent Change in Lipoprotein-Phosphoslipase A2 From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	Lipoprotein Phosphoslipase A2 - modified form of LDL.	Baseline and Week 8
Percent Change in High Density Lipoprotein (HDL) Particle Concentration Total From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	High Density Lipoprotein partical size suggests the bigger the better. HDL is a complex of lipids and proteins in approximately equal amounts that functions as a transporter of cholesterol in the blood. High levels are associated with a decreased risk of atherosclerosis and coronary heart disease.	Baseline and Week 8
Percent Change in High Density Lipoprotein (HDL) Particle Size From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	Partical size suggests the bigger the better. HDL is a complex of lipids and proteins in approximately equal amounts that functions as a transporter of cholesterol in the blood. High levels are associated with a decreased risk of atherosclerosis and coronary heart disease.	Baseline and Week 8
Percent Change in Very Low Density Lipoproteins and Chylomicron Particle Concentration Total From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	Very low density lipoproteins are plasma lipoproteins with a high lipid content, associated with atherosclerosis. Chylomicrons are One of the microscopic particles of emulsified fat found in the blood and lymph and formed during the digestion of fats.	Baseline and Week 8
Percent Change in Very Low Density Lipoproteins Size From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	Very low density lipoproteins are plasma lipoproteins with a high lipid content, associated with atherosclerosis.	Baseline and Week 8
Percent Change in Intermediate Density Lipoprotein Particle Concentration From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	Intermediate Density Lipoprotein, or IDLs, transport cholesterol and triglycerides through the body. IDLs are a type of cholesterol that are a product of VLDL degradation and result in LDL cholesterol when broken down.	Baseline and Week 8
Percent Change in Remnant-like Particle Cholesterol From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	Remnant-like particle cholesterol within the plasma has been identified as a cardiovascular risk factor.	Baseline and Week 8
Percent Change in Total Adiponectin From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period	Adiponectin is a protein hormone that modulates a number of metabolic processes, including glucose regulation and fatty acid catabolism.	Baseline and Week 8
Percent Change in Non-High Density Lipoprotein Cholesterol From Baseline to Week 12 During 20 mg Atorvastatin Treatment Period	Non-high density lipoprotein cholesterol is the Total Cholesterol minus the HDL(high density lipoproteins or the sum of the LDL, VLDL and IDL. That is, Low Density Lipoproteins, Very Low Density Lipoproteins and Intermediate Density Lipoproteins.	Baseline and Week 12
Percent Change in Non-High Density Lipoprotein Cholesterol From Baseline to Week 16 During 40 mg Atorvastatin Treatment Period	Non-high density lipoprotein cholesterol is the Total Cholesterol minus the HDL(high density lipoproteins or the sum of the LDL, VLDL and IDL. That is, Low Density Lipoproteins, Very Low Density Lipoproteins and Intermediate Density Lipoproteins.	Baseline and Week 16

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Bays HE, McKenney J, Maki KC, Doyle RT, Carter RN, Stein E. Effects of prescription omega-3-acid ethyl esters on non--high-density lipoprotein cholesterol when coadministered with escalating doses of atorvastatin. Mayo Clin Proc. 2010 Feb;85(2):122-8. doi: 10.4065/mcp.2009.0397.
• Maki KC, Bays HE, Dicklin MR, Johnson SL, Shabbout M. Effects of prescription omega-3-acid ethyl esters, coadministered with atorvastatin, on circulating levels of lipoprotein particles, apolipoprotein CIII, and lipoprotein-associated phospholipase A2 mass in men and women with mixed dyslipidemia. J Clin Lipidol. 2011 Nov-Dec;5(6):483-92. doi: 10.1016/j.jacl.2011.09.001. Epub 2011 Sep 13.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: February 13, 2007
• First Submitted That Met QC Criteria: February 13, 2007
• First Posted (Estimate): February 14, 2007

Study Record Updates

• Last Update Posted (Estimate): February 2, 2017
• Last Update Submitted That Met QC Criteria: December 2, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Hypercholesterolemia; Lipids; Omacor; Triglycerides; omega-3 fatty acids; Dyslipidemias; Lovaza; omega-3-acid ethyl esters; Hypertriglyceridemia; Hyperlipidemias
• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypertriglyceridemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: OM9L

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Study Protocol
   Information identifier: OM9L
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: OM9L
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: OM9L
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: OM9L
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: OM9L
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: OM9L
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: OM9L
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register