Clinical trial NCT00435045: Evaluation of Efficacy and Safety of Omacor, Co-Administered With Atorvastatin, in Subjects With Hypertriglyceridemia
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertriglyceridemia
Keywords: Lovaza
Hyperlipidemias
Triglycerides
Lipids
omega-3 fatty acids
Hypercholesterolemia
Hypertriglyceridemia
omega-3-acid ethyl esters
Omacor
Dyslipidemias
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-02-14
Enrollment: 245
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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)

Primary outcomes:
measure: Percent Change in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
Secondary outcomes:
measure: Percent Change in Total Cholesterol (TC) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in High Density Lipoprotein (HDL)Cholesterol From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in Low Density Lipoprotein (LDL) Cholesterol (Beta-quantification) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in Triglycerides From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in Very Low Density Lipoproteins (VLDL) Cholesterol From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in Apolipoprotein-A-1 From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in Apolipoprotein C-III From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in Total Cholesterol/High Density Lipoprotein Cholesterol Ratio From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in Triglycerides/High Density Lipoprotein Cholesterol Ratio From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in Docosahexaenoic Acid (DHA) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in Eicosapentaenoic Acid (EPA) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in Low Density Lipoprotein Particle Concentration Total From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in Low Density Lipoprotein Particle Size From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in Lipoprotein-Phosphoslipase A2 From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in High Density Lipoprotein (HDL) Particle Concentration Total From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in High Density Lipoprotein (HDL) Particle Size From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in Very Low Density Lipoproteins and Chylomicron Particle Concentration Total From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in Very Low Density Lipoproteins Size From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in Intermediate Density Lipoprotein Particle Concentration From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in Remnant-like Particle Cholesterol From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in Total Adiponectin From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 8
measure: Percent Change in Non-High Density Lipoprotein Cholesterol From Baseline to Week 12 During 20 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 12
measure: Percent Change in Non-High Density Lipoprotein Cholesterol From Baseline to Week 16 During 40 mg Atorvastatin Treatment Period
timeFrame: Baseline and Week 16
Other outcomes:
Locations:
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.