Open-Label Extension of a Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Lovaza® and Simvastatin Therapy in Hypertriglyceridemic Subjects

OM6X: An Open-Label Extension of a Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of Combined Lovaza (Previously Omacor®) and Simvastatin Therapy in Hypertriglyceridemic Subjects

In a previous trial (LOV111858/OM6), subjects received in a double-blind fashion either 4 g/day of Lovaza® (omega-3-ethyl esters) [formerly known as Omacor] co-administered with simvastatin 40 mg/day or placebo co-administered with simvastatin 40 mg/day for 8 weeks. This extension trial, LOV111818/OM6X assessed the continued efficacy and safety of Lovaza® (omega-3-ethyl esters) co-administered with simvastatin 40 mg vs. switching from simvastatin plus placebo to simvastatin plus Lovaza® for lowering non-High Density Lipoprotein-Cholesterol (non-HDL-C) levels at 4 months (primary endpoint) and additionally at 12 and 24 months.

Study Overview

• Status: Completed
• Conditions: Hypertriglyceridemia
• Intervention / Treatment: Drug: Simvastatin + Lovaza® (omega-3-acid ethyl esters)

Detailed Description

Two studies comprise this OM6 Program. Study LOV111858/OM6 (double-blind study) which is outlined in NCT00246701 and Study LOV111818/OM6X (open-label extension) outlined in this posting.

• Study Type: Interventional
• Enrollment (Actual): 188
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • GSK Investigational Site
  • California
    • Encinitas, California, United States, 92024
      • GSK Investigational Site
    • Fresno, California, United States, 93710
      • GSK Investigational Site
    • Greenbrae, California, United States, 94904
      • GSK Investigational Site
    • Sacramento, California, United States, 95831
      • GSK Investigational Site
    • Thousand Oaks, California, United States, 91360
      • GSK Investigational Site
  • Florida
    • Hollywood, Florida, United States, 33023
      • GSK Investigational Site
    • Pinellas Park, Florida, United States, 33781
      • GSK Investigational Site
    • Tampa, Florida, United States, 33606
      • GSK Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • GSK Investigational Site
    • Dunwoody, Georgia, United States, 30328
      • GSK Investigational Site
    • Suwanee, Georgia, United States, 30024
      • GSK Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60610
      • GSK Investigational Site
  • Indiana
    • Bloomington, Indiana, United States, 47403
      • GSK Investigational Site
    • Evansville, Indiana, United States, 47714
      • GSK Investigational Site
    • Indianapolis, Indiana, United States, 46260
      • GSK Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • GSK Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21209
      • GSK Investigational Site
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • GSK Investigational Site
    • Wentzville, Minnesota, United States, 62285
      • GSK Investigational Site
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • GSK Investigational Site
  • New York
    • New York, New York, United States, 10032
      • GSK Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • GSK Investigational Site
    • Hickory, North Carolina, United States, 28601
      • GSK Investigational Site
    • Salisbury, North Carolina, United States, 28144
      • GSK Investigational Site
    • Statesville, North Carolina, United States, 28677
      • GSK Investigational Site
    • Wilmington, North Carolina, United States, 28412
      • GSK Investigational Site
    • Winston-Salem, North Carolina, United States, 27106
      • GSK Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45246
      • GSK Investigational Site
    • Cincinnati, Ohio, United States, 45212
      • GSK Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • GSK Investigational Site
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • GSK Investigational Site
  • Tennessee
    • Bristol, Tennessee, United States, 37620
      • GSK Investigational Site
  • Texas
    • Plano, Texas, United States, 75093
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78229
      • GSK Investigational Site
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • GSK Investigational Site
    • Richmond, Virginia, United States, 23249
      • GSK Investigational Site
    • Richmond, Virginia, United States, 23294
      • GSK Investigational Site
  • Washington
    • Lakewood, Washington, United States, 98499
      • GSK Investigational Site
    • Seattle, Washington, United States, 98104
      • GSK Investigational Site

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

For LOV111818/OM6X - Subjects were included in the study if they had met all relevant inclusion/exclusion criteria prior to and throughout the double-blind Study LOV111858/OM6 and completed Study LOV111858/OM6 to Week 8.

FYI - entry criteria for LOV111818/OM6 (double-blind study)

Inclusion Criteria:

• Men and women ages 18-79 years, inclusive
• Current therapy with a statin drug
• Triglyceride levels between 200 and 499 mg/dL
• Normally active and in good health on the basis of medical history, brief physical examination, electrocardiogram, and routine laboratory tests
• Provide written informed consent and authorization for protected health information disclosure

Exclusion Criteria:

• Sensitivity to statin drugs or omega-3 fatty acids
• Lipoprotein lipase impairment or apo C-2 deficiency or type III hyperlipidemia
• Unexplained muscle pain or weakness
• History of pancreatitis
• Recent history of certain heart, kidney, liver, lung, or gastrointestinal diseases, or cancer (except non-melanoma skin cancer)
• Poorly controlled diabetes, or receiving insulin therapy
• Pregnant or lactating females. Women of childbearing potential who are not using a medically approved method of contraception.
• Use of certain types of hormones, anticonvulsant drugs, immunologic drugs, antibiotic, antifungal and antiviral drugs, and cardiac drugs
• Use of warfarin (Coumadin)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Simvastatin + Lovaza® ("Non-switchers"); Open label Simvastatin + Lovaza® (omega-3-acid ethyl esters) NOTE: this group was originally assigned to Simvastatin + Lovaza® in the double-blind trial, hence in this open-label extension, they are termed "Non-switchers"	Drug: Simvastatin + Lovaza® (omega-3-acid ethyl esters); Open-label Simvastatin + Lovaza® (omega-3-acid ethyl esters) [formerly known as Omacor]
Experimental: Simvastatin + Lovaza® ("Switchers"); Open label Simvastatin + Lovaza® (omega-3-acid ethyl esters) NOTE: this group was originally assigned to Simvastatin + placebo in the double-blind trial, hence in this open-label extension, they are termed "Switchers"	Drug: Simvastatin + Lovaza® (omega-3-acid ethyl esters); Open-label Simvastatin + Lovaza® (omega-3-acid ethyl esters) [formerly known as Omacor]

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Percent Change of Non-HDL-C (High Density Lipoprotein-Cholesterol) in Switchers vs. Non-Switchers Subjects From LOV111858 End-of-Treatment (Week 8) to Month 4 of Extension Study (LOV111818)	Median percent change from LOV111858 (NCT00903409) End-of-Treatment (double-blind study, Week 8) to the Month 4 visit of LOV111818 (open-label extension trial)	Month 4 (LOV111818)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median Percent Change of Lipid Measurements From LOV111858 End-of-Treatment Week 8 to Months 4, 12, and 24 of the Open-Label Extension Study (LOV111818) in "Switchers" vs. Non-switchers	Median percent change from LOV111858 Baseline to LOV111818 Months 4, 12, and 24 visits of the open-label extension trial	Months 4, 12, and 24 (LOV111818) of the open-label extension trial
Median Percent Change of Lipid Measurements From LOV111858 End-of-Treatment Week 8 to LOV111818 Months 4, 12, and 24 of the Open-Label Extension Trial	Median percent change from LOV111858 End-of-Treatment (Week 8) to LOV111818 Months 4, 12, and 24 visits of the open-label extension trial	LOV111858 End-of-Treatment (Week 8) to LOV111818 Months 4, 12, and 24 of the open-label extension trial

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Bays HE, Maki KC, McKenney J, Snipes R, Meadowcroft A, Schroyer R, Doyle RT, Stein E. Long-term up to 24-month efficacy and safety of concomitant prescription omega-3-acid ethyl esters and simvastatin in hypertriglyceridemic patients. Curr Med Res Opin. 2010 Apr;26(4):907-15. doi: 10.1185/03007991003645318.
• Maki KC, Dicklin MR, Davidson MH, Doyle RT, Ballantyne CM; COMBination of prescription Omega-3 with Simvastatin (COMBOS) Investigators. Baseline lipoprotein lipids and low-density lipoprotein cholesterol response to prescription omega-3 acid ethyl ester added to Simvastatin therapy. Am J Cardiol. 2010 May 15;105(10):1409-12. doi: 10.1016/j.amjcard.2009.12.063. Epub 2010 Mar 30.

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 (Actual): November 15, 2005
• Primary Completion (Actual): June 27, 2008
• Study Completion (Actual): June 27, 2008

Study Registration Dates

• First Submitted: May 14, 2009
• First Submitted That Met QC Criteria: May 14, 2009
• First Posted (Estimate): May 18, 2009

Study Record Updates

• Last Update Posted (Actual): October 9, 2017
• Last Update Submitted That Met QC Criteria: September 8, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: simvastatin; High triglycerides; Lovaza; omega-3-acid ethyl esters
• 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; Simvastatin
• Other Study ID Numbers: 111818; LOV111858 (Other Identifier: GSK)

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. Dataset Specification
   Information identifier: 111818
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Study Protocol
   Information identifier: 111818
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Clinical Study Report
   Information identifier: 111818
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 111818
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: 111818
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: 111818
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register