Trial Outcomes & Findings for Efficacy and Safety of AMR101 (Ethyl Icosapentate) in Patients With Fasting Triglyceride (Tg) Levels ≥ 500 and ≤ 2000 mg/dL (NCT NCT01047683)

NCT ID: NCT01047683

Last Updated: 2022-04-25

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 229 participants
• Primary outcome timeframe: baseline and 12 weeks
• Results posted on: 2022-04-25

Participant Flow

Participant milestones

Measure	Placebo Placebo: Placebo 4 capsules/day for 12 weeks (Weeks 1-12)	AMR101 (Ethyl Icosapentate) - 2 g/Day AMR101 (ethyl icosapentate) - 2 g/day: AMR101 (ethyl icosapentate) 2 capsules/day with placebo 2 capsules/day for 12 weeks (Weeks 1-12)	AMR101 (Ethyl Icosapentate) - 4 g/Day AMR101 (ethyl icosapentate) - 4 g/day: AMR101 (ethyl icosapentate) 4 capsules/day for 12 weeks (Weeks 1-12)
Overall Study STARTED	76	76	77
Overall Study COMPLETED	71	70	74
Overall Study NOT COMPLETED	5	6	3

Reasons for withdrawal

Measure	Placebo Placebo: Placebo 4 capsules/day for 12 weeks (Weeks 1-12)	AMR101 (Ethyl Icosapentate) - 2 g/Day AMR101 (ethyl icosapentate) - 2 g/day: AMR101 (ethyl icosapentate) 2 capsules/day with placebo 2 capsules/day for 12 weeks (Weeks 1-12)	AMR101 (Ethyl Icosapentate) - 4 g/Day AMR101 (ethyl icosapentate) - 4 g/day: AMR101 (ethyl icosapentate) 4 capsules/day for 12 weeks (Weeks 1-12)
Overall Study Adverse Event	3	1	0
Overall Study Withdrew Consent	1	4	2
Overall Study Lost to Follow-up	0	1	0
Overall Study Triglycerides >2000 mg/dL	1	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo n=76 Participants Placebo: Placebo 4 capsules/day for 12 weeks (Weeks 1-12)	AMR101 (Ethyl Icosapentate) - 2 g/Day n=76 Participants AMR101 (ethyl icosapentate) - 2 g/day: AMR101 (ethyl icosapentate) 2 capsules/day with placebo 2 capsules/day for 12 weeks (Weeks 1-12)	AMR101 (Ethyl Icosapentate) - 4 g/Day n=77 Participants AMR101 (ethyl icosapentate) - 4 g/day: AMR101 (ethyl icosapentate) 4 capsules/day for 12 weeks (Weeks 1-12)	Total n=229 Participants Total of all reporting groups
Age, Continuous	53.4 years STANDARD_DEVIATION 8.34 • n=5 Participants	53.4 years STANDARD_DEVIATION 9.34 • n=7 Participants	51.9 years STANDARD_DEVIATION 10.27 • n=5 Participants	52.9 years STANDARD_DEVIATION 9.34 • n=4 Participants
Sex: Female, Male Female	18 Participants n=5 Participants	18 Participants n=7 Participants	18 Participants n=5 Participants	54 Participants n=4 Participants
Sex: Female, Male Male	58 Participants n=5 Participants	58 Participants n=7 Participants	59 Participants n=5 Participants	175 Participants n=4 Participants
Race/Ethnicity, Customized White	68 participants n=5 Participants	67 participants n=7 Participants	67 participants n=5 Participants	202 participants n=4 Participants
Race/Ethnicity, Customized Other	8 participants n=5 Participants	9 participants n=7 Participants	10 participants n=5 Participants	27 participants n=4 Participants

PRIMARY outcome

Timeframe: baseline and 12 weeks

Population: Intent-to-treat population: randomized patients who received \>= 1 dose of study drug and had baseline and \>= 1 postrandomization efficacy measurement. Only patients with non-missing baseline and Week 12 endpoint values were included.

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

Outcome measures

Measure	AMR101 (Ethyl Icosapentate) - 2 g/Day n=73 Participants AMR101 (ethyl icosapentate) - 2 g/day: AMR101 (ethyl icosapentate) 2 capsules/day with placebo 2 capsules/day for 12 weeks (Weeks 1-12)	AMR101 (Ethyl Icosapentate) - 4 g/Day n=76 Participants AMR101 (ethyl icosapentate) - 4 g/day: AMR101 (ethyl icosapentate) 4 capsules/day for 12 weeks (Weeks 1-12)	Placebo n=75 Participants Placebo: Placebo 4 capsules/day for 12 weeks (Weeks 1-12)
Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Triglyceride Lowering Effect	-7.0 Percent change from baseline Interval -30.1 to 18.6	-26.6 Percent change from baseline Interval -41.1 to 0.0	9.7 Percent change from baseline Interval -19.2 to 42.3

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: Intent-to-treat population: randomized patients who received \>= 1 dose of study drug and had baseline and \>= 1 postrandomization efficacy measurement. Only patients with non-missing baseline and Week 12 endpoint values were included.

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

Outcome measures

Measure	AMR101 (Ethyl Icosapentate) - 2 g/Day n=73 Participants AMR101 (ethyl icosapentate) - 2 g/day: AMR101 (ethyl icosapentate) 2 capsules/day with placebo 2 capsules/day for 12 weeks (Weeks 1-12)	AMR101 (Ethyl Icosapentate) - 4 g/Day n=76 Participants AMR101 (ethyl icosapentate) - 4 g/day: AMR101 (ethyl icosapentate) 4 capsules/day for 12 weeks (Weeks 1-12)	Placebo n=75 Participants Placebo: Placebo 4 capsules/day for 12 weeks (Weeks 1-12)
Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Very Low-density Lipoprotein Cholesterol Levels	0.0 Percent change from baseline Interval -22.5 to 29.2	-19.5 Percent change from baseline Interval -35.7 to 19.6	13.7 Percent change from baseline Interval -13.5 to 55.3

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: Intent-to-treat population: randomized patients who received \>= 1 dose of study drug and had baseline and \>= 1 postrandomization efficacy measurement. Only patients with non-missing baseline and Week 12 endpoint values were included.

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

Outcome measures

Measure	AMR101 (Ethyl Icosapentate) - 2 g/Day n=70 Participants AMR101 (ethyl icosapentate) - 2 g/day: AMR101 (ethyl icosapentate) 2 capsules/day with placebo 2 capsules/day for 12 weeks (Weeks 1-12)	AMR101 (Ethyl Icosapentate) - 4 g/Day n=73 Participants AMR101 (ethyl icosapentate) - 4 g/day: AMR101 (ethyl icosapentate) 4 capsules/day for 12 weeks (Weeks 1-12)	Placebo n=70 Participants Placebo: Placebo 4 capsules/day for 12 weeks (Weeks 1-12)
Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Lipoprotein-associated Phospholipase A2 Levels	-5.1 Percent change from baseline Interval -17.1 to 7.1	-17.1 Percent change from baseline Interval -26.2 to -1.7	-2.4 Percent change from baseline Interval -15.9 to 13.5

SECONDARY outcome

Timeframe: baseline and 12 weeks

Population: Intent-to-treat population: randomized patients who received \>= 1 dose of study drug and had baseline and \>= 1 postrandomization efficacy measurement. Only patients with non-missing baseline and Week 12 endpoint values were included.

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

Outcome measures

Measure	AMR101 (Ethyl Icosapentate) - 2 g/Day n=70 Participants AMR101 (ethyl icosapentate) - 2 g/day: AMR101 (ethyl icosapentate) 2 capsules/day with placebo 2 capsules/day for 12 weeks (Weeks 1-12)	AMR101 (Ethyl Icosapentate) - 4 g/Day n=75 Participants AMR101 (ethyl icosapentate) - 4 g/day: AMR101 (ethyl icosapentate) 4 capsules/day for 12 weeks (Weeks 1-12)	Placebo n=73 Participants Placebo: Placebo 4 capsules/day for 12 weeks (Weeks 1-12)
Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Group in Apolipoprotein B Levels	2.1 Percent change from baseline Interval -4.7 to 7.6	-3.8 Percent change from baseline Interval -11.9 to 3.8	4.3 Percent change from baseline Interval -4.5 to 17.5

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline and 12 weeks

Population: Intent-to-treat population: randomized patients who received \>= 1 dose of study drug and had baseline and \>= 1 postrandomization efficacy measurement. Only patients with non-missing baseline and Week 12 endpoint values were included.

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

Outcome measures

Measure	AMR101 (Ethyl Icosapentate) - 2 g/Day n=73 Participants AMR101 (ethyl icosapentate) - 2 g/day: AMR101 (ethyl icosapentate) 2 capsules/day with placebo 2 capsules/day for 12 weeks (Weeks 1-12)	AMR101 (Ethyl Icosapentate) - 4 g/Day n=76 Participants AMR101 (ethyl icosapentate) - 4 g/day: AMR101 (ethyl icosapentate) 4 capsules/day for 12 weeks (Weeks 1-12)	Placebo n=75 Participants Placebo: Placebo 4 capsules/day for 12 weeks (Weeks 1-12)
Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Low-density Lipoprotein Cholesterol Levels	-2.5 Percent change from baseline Interval -9.8 to 23.5	-4.5 Percent change from baseline Interval -23.3 to 17.2	-3.0 Percent change from baseline Interval -21.3 to 23.3

OTHER_PRE_SPECIFIED outcome

Timeframe: baseline and 12 weeks

Population: Intent-to-treat population: randomized patients who received \>= 1 dose of study drug and had baseline and \>= 1 postrandomization efficacy measurement. Only patients with non-missing baseline and Week 12 endpoint values were included.

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

Outcome measures

Measure	AMR101 (Ethyl Icosapentate) - 2 g/Day n=73 Participants AMR101 (ethyl icosapentate) - 2 g/day: AMR101 (ethyl icosapentate) 2 capsules/day with placebo 2 capsules/day for 12 weeks (Weeks 1-12)	AMR101 (Ethyl Icosapentate) - 4 g/Day n=76 Participants AMR101 (ethyl icosapentate) - 4 g/day: AMR101 (ethyl icosapentate) 4 capsules/day for 12 weeks (Weeks 1-12)	Placebo n=75 Participants Placebo: Placebo 4 capsules/day for 12 weeks (Weeks 1-12)
Difference Between AMR101 (Ethyl Icosapentate) and Placebo Treatment Groups in Non-High-Density Lipoprotein Cholesterol Levels	0.0 Percent change from baseline Interval -9.0 to 14.1	-7.7 Percent change from baseline Interval -21.6 to -0.1	7.8 Percent change from baseline Interval -4.1 to 26.6

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

AMR101 (Ethyl Icosapentate) - 2 g/Day

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

AMR101 (Ethyl Icosapentate) - 4 g/Day

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=76 participants at risk Placebo: Placebo 4 capsules/day for 12 weeks (Weeks 1-12)	AMR101 (Ethyl Icosapentate) - 2 g/Day n=76 participants at risk AMR101 (ethyl icosapentate) - 2 g/day: AMR101 (ethyl icosapentate) 2 capsules/day with placebo 2 capsules/day for 12 weeks (Weeks 1-12)	AMR101 (Ethyl Icosapentate) - 4 g/Day n=77 participants at risk AMR101 (ethyl icosapentate) - 4 g/day: AMR101 (ethyl icosapentate) 4 capsules/day for 12 weeks (Weeks 1-12)
Cardiac disorders Coronary artery disease	0.00% 0/76 • 12 weeks Events were collected by systematic assessment at each study visit.	0.00% 0/76 • 12 weeks Events were collected by systematic assessment at each study visit.	1.3% 1/77 • 12 weeks Events were collected by systematic assessment at each study visit.
General disorders Non-cardiac chest pain	0.00% 0/76 • 12 weeks Events were collected by systematic assessment at each study visit.	1.3% 1/76 • 12 weeks Events were collected by systematic assessment at each study visit.	0.00% 0/77 • 12 weeks Events were collected by systematic assessment at each study visit.

Other adverse events

Measure	Placebo n=76 participants at risk Placebo: Placebo 4 capsules/day for 12 weeks (Weeks 1-12)	AMR101 (Ethyl Icosapentate) - 2 g/Day n=76 participants at risk AMR101 (ethyl icosapentate) - 2 g/day: AMR101 (ethyl icosapentate) 2 capsules/day with placebo 2 capsules/day for 12 weeks (Weeks 1-12)	AMR101 (Ethyl Icosapentate) - 4 g/Day n=77 participants at risk AMR101 (ethyl icosapentate) - 4 g/day: AMR101 (ethyl icosapentate) 4 capsules/day for 12 weeks (Weeks 1-12)
Gastrointestinal disorders Diarrhea	6.6% 5/76 • 12 weeks Events were collected by systematic assessment at each study visit.	5.3% 4/76 • 12 weeks Events were collected by systematic assessment at each study visit.	1.3% 1/77 • 12 weeks Events were collected by systematic assessment at each study visit.
Gastrointestinal disorders Nausea	5.3% 4/76 • 12 weeks Events were collected by systematic assessment at each study visit.	6.6% 5/76 • 12 weeks Events were collected by systematic assessment at each study visit.	1.3% 1/77 • 12 weeks Events were collected by systematic assessment at each study visit.
Gastrointestinal disorders Eructation	3.9% 3/76 • 12 weeks Events were collected by systematic assessment at each study visit.	1.3% 1/76 • 12 weeks Events were collected by systematic assessment at each study visit.	0.00% 0/77 • 12 weeks Events were collected by systematic assessment at each study visit.

Additional Information

Alex Giaquinto

Amarin Pharma, Inc.

Phone: +1 908 326 1324

Email: alex.giaquinto@amarincorp.com

Results disclosure agreements

• Principal investigator is a sponsor employee PIs are restricted in sharing data until an abstract presentation or publication of the manuscript.
• Publication restrictions are in place

Restriction type: OTHER