Hypertriglyceridemia
Conditions
Keywords
Lovaza, Hyperlipidemias, Triglycerides, Lipids, omega-3 fatty acids, Hypercholesterolemia, Hypertriglyceridemia, omega-3-acid ethyl esters, Omacor, Dyslipidemias
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)
Interventions
DRUGLovaza (omega-3-acid ethyl esters) [formerly known as Omacor] plus atorvastatin
Lovaza + atorvastatin
DRUGatorvastatin
atorvastatin + placebo
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | Baseline and Week 8 | 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
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in High Density Lipoprotein (HDL)Cholesterol From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | Baseline and Week 8 | 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 | Baseline and Week 8 | 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 | Baseline and Week 8 | 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 | Baseline and Week 8 | 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 | Baseline and Week 8 | 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 | Baseline and Week 8 | 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 | Baseline and Week 8 | 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 | Baseline and Week 8 | — |
| Percent Change in Docosahexaenoic Acid (DHA) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | Baseline and Week 8 | 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 | Baseline and Week 8 | 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 | Baseline and Week 8 | 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 Total Cholesterol (TC) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | Baseline and Week 8 | 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 Lipoprotein-Phosphoslipase A2 From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | Baseline and Week 8 | 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 | Baseline and Week 8 | 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 | Baseline and Week 8 | 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 | Baseline and Week 8 | 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 | Baseline and Week 8 | 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 | Baseline and Week 8 | 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 | Baseline and Week 8 | 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 | Baseline and Week 8 | 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 | Baseline and Week 12 | 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 | Baseline and Week 16 | 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 Low Density Lipoprotein Particle Size From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | Baseline and Week 8 | 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lovaza(Omacor) + Atorvastatin Subjects who met all study requirements after screening visit and who were randomized to receive 4 gms Lovaza (Omega-3-acid ethyl esters) + Atorvastatin 10 mgs for 8 weeks, then 4 gms Lovaza + Atorvastatin 20 mgs for 4 weeks, then 4 gms Lovaza + Atorvastatin 40 mgs for 4 additional weeks. | 123 |
| Placebo + Atorvastatin Subjects who met all study requirements after screening visit and who were randomized to receive Placebo + Atorvastatin 10 mgs for 8 weeks, then Placebo + Atorvastatin 20 mgs for 4 weeks, then Placebo + Atorvastatin 40 mgs for 4 additional weeks. | 122 |
| Total | 245 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Weeks 13-16 / 40mg Dose Level | Adverse Event | 3 | 2 |
| Weeks 13-16 / 40mg Dose Level | Per Sponsors Request | 1 | 0 |
| Weeks 13-16 / 40mg Dose Level | Withdrawal by Subject | 1 | 0 |
| Weeks 1-8 / 10 mg Dose Level | Adverse Event | 1 | 1 |
| Weeks 1-8 / 10 mg Dose Level | Family Crisis - could not participate | 1 | 0 |
| Weeks 1-8 / 10 mg Dose Level | Lost to Follow-up | 1 | 1 |
| Weeks 1-8 / 10 mg Dose Level | Requirement for Excluded Medications | 0 | 1 |
| Weeks 1-8 / 10 mg Dose Level | Withdrawal by Subject | 2 | 1 |
| Weeks 9-12 / 20mg Dose Level | Adverse Event | 4 | 3 |
| Weeks 9-12 / 20mg Dose Level | Lost to Follow-up | 1 | 1 |
| Weeks 9-12 / 20mg Dose Level | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Placebo + Atorvastatin | Lovaza(Omacor) + Atorvastatin |
|---|---|---|---|
| Age, Continuous | 56.1 years STANDARD_DEVIATION 10.23 | 56.0 years STANDARD_DEVIATION 10.84 | 56.3 years STANDARD_DEVIATION 9.64 |
| Gender Female | 103 Participants | 51 Participants | 52 Participants |
| Gender Male | 142 Participants | 71 Participants | 71 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 12 participants | 4 participants | 8 participants |
| Race/Ethnicity, Customized Black or African American | 10 participants | 4 participants | 6 participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 1 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Non-white | 3 participants | 2 participants | 1 participants |
| Race/Ethnicity, Customized White | 218 participants | 110 participants | 108 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 123 | 0 / 122 |
| serious Total, serious adverse events | 4 / — | 2 / — |
Outcome results
Primary
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.
Time frame: Baseline and Week 8
Population: Modified Intent To Treat (MITT) Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Only subjects with non-missing baseline and endpoint values are included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -40.2 percent change |
| Placebo + Atorvastatin | Percent Change in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -33.7 percent change |
p-value: 0.0002ANOVA
Secondary
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.
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Only subjects with non-missing baseline and endpoint values are included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Apolipoprotein-A-1 From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -0.3 percent change |
| Placebo + Atorvastatin | Percent Change in Apolipoprotein-A-1 From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | 1.5 percent change |
Secondary
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.
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Please note: processing errors, inadequate sample volume, sample and shipment storage issues etc., resulted in some MITT subjects without data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Apolipoprotein C-III From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -29.4 percent change |
| Placebo + Atorvastatin | Percent Change in Apolipoprotein C-III From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -16.0 percent change |
Secondary
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.
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Please note: processing errors, inadequate sample volume, sample and shipment storage issues etc., resulted in some MITT subjects without data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Docosahexaenoic Acid (DHA) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | 85.5 percent change |
| Placebo + Atorvastatin | Percent Change in Docosahexaenoic Acid (DHA) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | 4.2 percent change |
Secondary
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.
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Please note: processing errors, inadequate sample volume, sample and shipment storage issues etc., resulted in some MITT subjects without data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Eicosapentaenoic Acid (EPA) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | 402.2 percent change |
| Placebo + Atorvastatin | Percent Change in Eicosapentaenoic Acid (EPA) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -5.6 percent change |
Secondary
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.
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Only subjects with non-missing baseline and endpoint values are included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in High Density Lipoprotein (HDL)Cholesterol From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | 12.4 percent change |
| Placebo + Atorvastatin | Percent Change in High Density Lipoprotein (HDL)Cholesterol From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | 10.0 percent change |
Secondary
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.
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Only subjects with non-missing baseline and endpoint values are included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in High Density Lipoprotein (HDL) Particle Concentration Total From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | 1.0 percent change |
| Placebo + Atorvastatin | Percent Change in High Density Lipoprotein (HDL) Particle Concentration Total From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | 5.1 percent change |
Secondary
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.
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Please note: processing errors, inadequate sample volume, sample and shipment storage issues etc., resulted in some MITT subjects without data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in High Density Lipoprotein (HDL) Particle Size From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | 0.0 percent change |
| Placebo + Atorvastatin | Percent Change in High Density Lipoprotein (HDL) Particle Size From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | 1.2 percent change |
Secondary
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.
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Please note: processing errors, inadequate sample volume, sample and shipment storage issues etc., resulted in some MITT subjects without data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Intermediate Density Lipoprotein Particle Concentration From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -60.4 percent change |
| Placebo + Atorvastatin | Percent Change in Intermediate Density Lipoprotein Particle Concentration From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -50.3 percent change |
Secondary
Percent Change in Lipoprotein-Phosphoslipase A2 From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
Lipoprotein Phosphoslipase A2 - modified form of LDL.
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Please note: processing errors, inadequate sample volume, sample and shipment storage issues etc., resulted in some MITT subjects without data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Lipoprotein-Phosphoslipase A2 From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -20.7 percent change |
| Placebo + Atorvastatin | Percent Change in Lipoprotein-Phosphoslipase A2 From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -9.7 percent change |
Secondary
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.
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Please note: processing errors, inadequate sample volume, sample and shipment storage issues etc., resulted in some MITT subjects without data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Low Density Lipoprotein (LDL) Cholesterol (Beta-quantification) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -29.3 percent change |
| Placebo + Atorvastatin | Percent Change in Low Density Lipoprotein (LDL) Cholesterol (Beta-quantification) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -31.5 percent change |
Secondary
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.
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Please note: processing errors, inadequate sample volume, sample and shipment storage issues etc., resulted in some MITT subjects without data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Low Density Lipoprotein Particle Concentration Total From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -34.6 percent change |
| Placebo + Atorvastatin | Percent Change in Low Density Lipoprotein Particle Concentration Total From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -32.2 percent change |
Secondary
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.
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Please note: processing errors, inadequate sample volume, sample and shipment storage issues etc., resulted in some MITT subjects without data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Low Density Lipoprotein Particle Size From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | 1.5 percent change |
| Placebo + Atorvastatin | Percent Change in Low Density Lipoprotein Particle Size From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | 0.5 percent change |
Secondary
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.
Time frame: Baseline and Week 12
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Please note: processing errors, inadequate sample volume, sample and shipment storage issues etc., resulted in some MITT subjects without data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Non-High Density Lipoprotein Cholesterol From Baseline to Week 12 During 20 mg Atorvastatin Treatment Period | -46.9 percent change |
| Placebo + Atorvastatin | Percent Change in Non-High Density Lipoprotein Cholesterol From Baseline to Week 12 During 20 mg Atorvastatin Treatment Period | -39.0 percent change |
Secondary
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.
Time frame: Baseline and Week 16
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Please note: processing errors, inadequate sample volume, sample and shipment storage issues etc., resulted in some MITT subjects without data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Non-High Density Lipoprotein Cholesterol From Baseline to Week 16 During 40 mg Atorvastatin Treatment Period | -50.4 percent change |
| Placebo + Atorvastatin | Percent Change in Non-High Density Lipoprotein Cholesterol From Baseline to Week 16 During 40 mg Atorvastatin Treatment Period | -46.3 percent change |
Secondary
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.
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Please note: processing errors, inadequate sample volume, sample and shipment storage issues etc., resulted in some MITT subjects without data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Remnant-like Particle Cholesterol From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -50.0 percent change |
| Placebo + Atorvastatin | Percent Change in Remnant-like Particle Cholesterol From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -38.9 percent change |
Secondary
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.
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Please note: processing errors, inadequate sample volume, sample and shipment storage issues etc., resulted in some MITT subjects without data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Total Adiponectin From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -5.1 percent change |
| Placebo + Atorvastatin | Percent Change in Total Adiponectin From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -1.6 percent change |
Secondary
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
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Only subjects with non-missing baseline and endpoint values are included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Total Cholesterol/High Density Lipoprotein Cholesterol Ratio From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -38.3 percent change |
| Placebo + Atorvastatin | Percent Change in Total Cholesterol/High Density Lipoprotein Cholesterol Ratio From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -34.5 percent change |
Secondary
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).
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Only subjects with non-missing baseline and endpoint values are included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Total Cholesterol (TC) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -31.5 percent change |
| Placebo + Atorvastatin | Percent Change in Total Cholesterol (TC) From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -27.4 percent change |
Secondary
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.
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Only subjects with non-missing baseline and endpoint values are included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Triglycerides From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -45.4 percent change |
| Placebo + Atorvastatin | Percent Change in Triglycerides From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -26.9 percent change |
Secondary
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
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Only subjects with non-missing baseline and endpoint values are included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Triglycerides/High Density Lipoprotein Cholesterol Ratio From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -51.9 percent change |
| Placebo + Atorvastatin | Percent Change in Triglycerides/High Density Lipoprotein Cholesterol Ratio From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -34.0 percent change |
Secondary
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.
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Please note: processing errors, inadequate sample volume, sample and shipment storage issues etc., resulted in some MITT subjects without data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Very Low Density Lipoproteins and Chylomicron Particle Concentration Total From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -32.4 percent change |
| Placebo + Atorvastatin | Percent Change in Very Low Density Lipoproteins and Chylomicron Particle Concentration Total From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -25.9 percent change |
Secondary
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.
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Please note: processing errors, inadequate sample volume, sample and shipment storage issues etc., resulted in some MITT subjects without data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Very Low Density Lipoproteins Size From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -17.5 percent change |
| Placebo + Atorvastatin | Percent Change in Very Low Density Lipoproteins Size From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -3.3 percent change |
Secondary
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.
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Please note: processing errors, inadequate sample volume, sample and shipment storage issues etc., resulted in some MITT subjects without data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Very Low Density Lipoproteins (VLDL) Cholesterol From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -54.3 percent change |
| Placebo + Atorvastatin | Percent Change in Very Low Density Lipoproteins (VLDL) Cholesterol From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -37.0 percent change |
Post Hoc
Percent Change in Apolipoprotein-B From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period
Apolipoprotein B is the primary apolipoprotein of low density lipoproteins (LDL or bad cholesterol), which is responsible for carrying cholesterol to tissues.
Time frame: Baseline and Week 8
Population: Modified Intent To Treat Population - all randomized subjects who took at least 1 dose of study medication and provided at least 1 post-randomization efficacy data point. Only subjects with non-missing baseline and endpoint values are included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lovaza(Omacor) + Atorvastatin | Percent Change in Apolipoprotein-B From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -32.1 percent change |
| Placebo + Atorvastatin | Percent Change in Apolipoprotein-B From Baseline to Week 8 During 10 mg Atorvastatin Treatment Period | -30.7 percent change |