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

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00435045
First received: February 13, 2007
Last updated: September 3, 2010
Last verified: September 2010
  Purpose

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.


Condition Intervention Phase
Hypertriglyceridemia
Drug: Lovaza (omega-3-acid ethyl esters) [formerly known as Omacor] plus atorvastatin
Drug: atorvastatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Percent Change in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percent Change in Total Cholesterol (TC) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    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).

  • Percent Change in High Density Lipoprotein (HDL)Cholesterol From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]

    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.


  • Percent Change in Low Density Lipoprotein (LDL) Cholesterol (Beta-quantification) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    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.

  • Percent Change in Triglycerides From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Triglycerides - A naturally occurring ester of three fatty acids and glycerol that is the chief constituent of fats and oils.

  • Percent Change in Very Low Density Lipoproteins (VLDL) Cholesterol From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    VLDL - very-low-density lipoprotein: a plasma lipoprotein with a high lipid content, associated with atherosclerosis.

  • Percent Change in Apolipoprotein-A-1 From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Apolipoprotein A1 - major protein component of high density lipoprotein (HDL) in plasma. The protein promotes cholesterol efflux from tissues to the liver for excretion.

  • Percent Change in Apolipoprotein C-III From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    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.

  • Percent Change in Total Cholesterol/High Density Lipoprotein Cholesterol Ratio From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Total cholesterol/High density lipoprotein cholesterol

  • Percent Change in Triglycerides/High Density Lipoprotein Cholesterol Ratio From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
  • Percent Change in Docosahexaenoic Acid (DHA) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Docosahexaenoic Acid is an omega-3 essential fatty acid.

  • Percent Change in Eicosapentaenoic Acid (EPA) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    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.

  • Percent Change in Low Density Lipoprotein Particle Concentration Total From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    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.

  • Percent Change in Low Density Lipoprotein Particle Size From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    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.

  • Percent Change in Lipoprotein-Phosphoslipase A2 From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Lipoprotein Phosphoslipase A2 - modified form of LDL.

  • Percent Change in High Density Lipoprotein (HDL) Particle Concentration Total From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    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.

  • Percent Change in High Density Lipoprotein (HDL) Particle Size From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    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.

  • Percent Change in Very Low Density Lipoproteins and Chylomicron Particle Concentration Total From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    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.

  • Percent Change in Very Low Density Lipoproteins Size From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Very low density lipoproteins are plasma lipoproteins with a high lipid content, associated with atherosclerosis.

  • Percent Change in Intermediate Density Lipoprotein Particle Concentration From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    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.

  • Percent Change in Remnant-like Particle Cholesterol From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Remnant-like particle cholesterol within the plasma has been identified as a cardiovascular risk factor.

  • Percent Change in Total Adiponectin From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 8 ] [ Designated as safety issue: No ]
    Adiponectin is a protein hormone that modulates a number of metabolic processes, including glucose regulation and fatty acid catabolism.

  • Percent Change in Non-High Density Lipoprotein Cholesterol From Baseline to Week 12 During 20 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 12 ] [ Designated as safety issue: No ]
    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.

  • Percent Change in Non-High Density Lipoprotein Cholesterol From Baseline to Week 16 During 40 mg Atorvastatin Treatment Period [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    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.


Enrollment: 245
Study Start Date: February 2007
Study Completion Date: October 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: atorvastatin arm
atorvastatin + placebo
Drug: atorvastatin
atorvastatin + placebo
Other Names:
  • atorvastatin
  • 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

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)

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00435045

Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00435045     History of Changes
Other Study ID Numbers: OM9L, LOV111819
Study First Received: February 13, 2007
Results First Received: October 22, 2008
Last Updated: September 3, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Lovaza
Hyperlipidemias
Triglycerides
Lipids
omega-3 fatty acids
Hypercholesterolemia
Hypertriglyceridemia
omega-3-acid ethyl esters
Omacor
Dyslipidemias

Additional relevant MeSH terms:
Hypertriglyceridemia
Dyslipidemias
Hyperlipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Atorvastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014