Efficacy and Safety of AMR101 (Ethyl Icosapentate) in Patients With Fasting Triglyceride (Tg) Levels ≥ 500 and ≤ 2000 mg/dL

Hypertriglyceridemia Clinical Trial

— MARINE  

Official title:

Evaluation of the Efficacy and Safety of AMR101 (Ethyl Icosapentate) in Patients With Fasting Triglyceride Levels ≥ 500 mg/dL and ≤ 2000 mg/dL

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01047683
• Other study ID #: AMR-01-01-0016
• Secondary ID: The MARINE Study
• Status: Completed
• Phase: Phase 3
• Start date: December 2009
• Est. completion date: July 2011

Study information

• Verified date: March 2022
• Source: Amarin Pharma Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective is to determine the efficacy of AMR101 (ethyl icosapentate) compared to placebo in lowering fasting triglyceride levels in patients with very high fasting triglyceride levels ≥ 500 and ≤ 2000 mg/dL.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 229
• Est. completion date: July 2011
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Men and women, ages >18
• Fasting triglyceride =500 mg/dL and =2000 mg/dL
• Provide written informed consent and authorization for protected health information disclosure

Exclusion Criteria:

• Women who are pregnant or lactating, or planning to become pregnant
• Use of non-statin lipid-altering drugs which cannot be stopped including fibrates, niacin, fish oil and other products containing omega-3 fatty acids or other dietary supplements with potential lipid-altering effects
• History of pancreatitis
• History of bariatric surgery or currently on weight loss drugs
• Uncontrolled hypertension (BP > 160/100)
• HIV infection or on treatment with HIV-protease inhibitors, cyclophosphamide,or isotretinoin
• Consumption of more than 2 alcoholic beverages per day
• History of cancers (except if been disease free for >5 years OR history was basal or squamous cell skin cancer)
• Participation in another clinical trial involving an investigational agent in the last 30 days
• Other parameters will be assessed at the study center to ensure eligibility for this study.

Related Conditions & MeSH terms

• Hypertriglyceridemia

Intervention

Drug:
• AMR101 (ethyl icosapentate) - 4 g/day
AMR101 (ethyl icosapentate) 4 capsules/day for 12 weeks (Weeks 1-12)
• AMR101 (ethyl icosapentate) - 2 g/day
AMR101 (ethyl icosapentate) 2 capsules/day with placebo 2 capsules/day for 12 weeks (Weeks 1-12)
• Placebo
Placebo 4 capsules/day for 12 weeks (Weeks 1-12)

Locations

Country	Name	City	State
Denmark	Amarin Investigational Site	Aalborg
Denmark	Amarin Investigational Site	Herlev
Finland	Amarin Investigational Site	Oulu
Germany	Amarin Investigational Site	Dresden
Germany	Amarin Investigational Site	Giessen
Germany	Amarin Investigational Site	Magdeburg
Germany	Amarin Investigational Site	Muenchen
Germany	Amarin Investigational Site	Muenchen
Germany	Amarin Investigational Site	Nuernberg
India	Amarin Investigational Site	Ahmedabad
India	Amarin Investigational Site	Bangalore
India	Amarin Investigational Site	Bangalore
India	Amarin Investigational Site	Bangalore
India	Amarin Investigational Site	Gopalapuram
India	Amarin Investigational Site	Indore
India	Amarin Investigational Site	Mysore
Italy	Amarin Investigational Site	Genova
Italy	Amarin Investigational Site	Palermo
Mexico	Amarin Investigational Site	Guadalajara, Jalisco
Mexico	Amarin Investigational Site	Mexico City
Mexico	Amarin Investigational Site	Mexico City
Mexico	Amarin Investigational Site	Monterrey Nuevo Leon
Netherlands	Amarin Investigational Site	Amsterdam
Netherlands	Amarin Investigational Site	Groningen
Netherlands	Amarin Investigational Site	Rotterdam
Netherlands	Amarin Investigational Site	Rotterdam
Netherlands	Amarin Investigational Site	Utrecht
Russian Federation	Amarin Investigational Site	Moscow
Russian Federation	Amarin Investigational Site	Moscow
Russian Federation	Amarin Investigational Site	St Petersburg
Russian Federation	Amarin Investigational Site	St. Petersburg
Russian Federation	Amarin Investigational Site	St. Petersburg
South Africa	Amarin Investigational Site	Bloemfontein
South Africa	Amarin Investigational Site	Cape Town
South Africa	Amarin Investigational Site	Johannesburg
South Africa	Amarin Investigational Site	Parktown
South Africa	Amarin Investigational Site	Pretoria
South Africa	Amarin Investigational Site	Somerset West
Ukraine	Amarin Investigational Site	Ivano-Frankivsk
Ukraine	Amarin Investigational Site	Kiev
Ukraine	Amarin Investigational Site	Kyiv
Ukraine	Amarin Investigational Site	Odessa
United States	Amarin Investigational Site	Addison	Illinois
United States	Amarin Investigational Site	Butte	Montana
United States	Amarin Investigational Site	Chicago	Illinois
United States	Amarin Investigational Site	Cincinnati	Ohio
United States	Amarin Investigational Site	Cincinnati	Ohio
United States	Amarin Investigational Site	Corpus Christi	Texas
United States	Amarin Investigational Site	Golden	Colorado
United States	Amarin Investigational Site	Houston	Texas
United States	Amarin Investigational Site	Louisville	Kentucky
United States	Amarin Investigational Site	Lyndhurst	Ohio
United States	Amarin Investigational Site	Miami	Florida
United States	Amarin Investigational Site	Miami	Florida
United States	Amarin Investigational Site	Ocala	Florida
United States	Amarin Investigational Site	Raleigh	North Carolina
United States	Amarin Investigational Site	Richmond	Virginia
United States	Amarin Investigational Site	Sacramento	California
United States	Amarin Investigational Site	Tulsa	Oklahoma
United States	Amarin Investigational Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Amarin Pharma Inc.

Countries where clinical trial is conducted

United States,  Denmark,  Finland,  Germany,  India,  Italy,  Mexico,  Netherlands,  Russian Federation,  South Africa,  Ukraine, 

References & Publications (9)

Ballantyne CM, Bays HE, Braeckman RA, Philip S, Stirtan WG, Doyle RT Jr, Soni PN, Juliano RA. Icosapent ethyl (eicosapentaenoic acid ethyl ester): Effects on plasma apolipoprotein C-III levels in patients from the MARINE and ANCHOR studies. J Clin Lipidol — View Citation

Ballantyne CM, Bays HE, Philip S, Doyle RT Jr, Braeckman RA, Stirtan WG, Soni PN, Juliano RA. Icosapent ethyl (eicosapentaenoic acid ethyl ester): Effects on remnant-like particle cholesterol from the MARINE and ANCHOR studies. Atherosclerosis. 2016 Oct;2 — View Citation

Bays HE, Ballantyne CM, Braeckman RA, Stirtan WG, Doyle RT Jr, Philip S, Soni PN, Juliano RA. Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester): Effects Upon High-Sensitivity C-Reactive Protein and Lipid Parameters in Patients With Metabolic Syndrome. M — View Citation

Bays HE, Ballantyne CM, Braeckman RA, Stirtan WG, Soni PN. Icosapent ethyl, a pure ethyl ester of eicosapentaenoic acid: effects on circulating markers of inflammation from the MARINE and ANCHOR studies. Am J Cardiovasc Drugs. 2013 Feb;13(1):37-46. doi: 1 — View Citation

Bays HE, Ballantyne CM, Doyle RT Jr, Juliano RA, Philip S. Icosapent ethyl: Eicosapentaenoic acid concentration and triglyceride-lowering effects across clinical studies. Prostaglandins Other Lipid Mediat. 2016 Sep;125:57-64. doi: 10.1016/j.prostaglandins — View Citation

Bays HE, Ballantyne CM, Kastelein JJ, Isaacsohn JL, Braeckman RA, Soni PN. Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week stud — View Citation

Bays HE, Braeckman RA, Ballantyne CM, Kastelein JJ, Otvos JD, Stirtan WG, Soni PN. Icosapent ethyl, a pure EPA omega-3 fatty acid: effects on lipoprotein particle concentration and size in patients with very high triglyceride levels (the MARINE study). J — View Citation

Braeckman RA, Manku MS, Bays HE, Stirtan WG, Soni PN. Icosapent ethyl, a pure EPA omega-3 fatty acid: effects on plasma and red blood cell fatty acids in patients with very high triglyceride levels (results from the MARINE study). Prostaglandins Leukot Es — View Citation

Mosca L, Ballantyne CM, Bays HE, Guyton JR, Philip S, Doyle RT Jr, Juliano RA. Usefulness of Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) in Women to Lower Triglyceride Levels (Results from the MARINE and ANCHOR Trials). Am J Cardiol. 2017 Feb 1;11 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Low-density Lipoprotein Cholesterol Levels	Median percent change from baseline to Week 12 in serum low density lipoprotein cholesterol levels following treatment with AMR101 (ethyl icosapentate) 2 g/day or 4 g/day	baseline and 12 weeks
Other	Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Non-High-Density Lipoprotein Cholesterol Levels	Median percent change from baseline to Week 12 in serum non-high density lipoprotein cholesterol levels following treatment with AMR101 (ethyl icosapentate) 2 g/day or 4 g/day	baseline and 12 weeks
Primary	Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Triglyceride Lowering Effect	Median percent change from baseline to Week 12 in fasting serum triglyceride levels following treatment with AMR101 (ethyl icosapentate) 2 g/day or 4 g/day	baseline and 12 weeks
Secondary	Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Very Low-density Lipoprotein Cholesterol Levels	Median percent change from baseline to Week 12 in serum very low-density lipoprotein cholesterol levels following treatment with AMR101 (ethyl icosapentate) 2 g/day or 4 g/day	baseline and 12 weeks
Secondary	Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Lipoprotein-associated Phospholipase A2 Levels	Median percent change from baseline to Week 12 in serum Lipoprotein-associated Phospholipase A2 levels following treatment with AMR101 (ethyl icosapentate) 2 g/day or 4 g/day	baseline and 12 weeks
Secondary	Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Group in Apolipoprotein B Levels	Median in percent change from baseline to Week 12 in serum Apolipoprotein B levels following treatment with AMR101 (ethyl icosapentate) 2 g/day or 4 g/day	baseline and 12 weeks