Trial Outcomes & Findings for Evaluation of the Safety and Efficacy of Long-term Use of Omega-3 Fatty Acid Ethyl Esters (NCT NCT02153073)

NCT ID: NCT02153073

Last Updated: 2019-07-18

Results Overview

• Recruitment status: COMPLETED
• Target enrollment: 3084 participants
• Primary outcome timeframe: Up to Month 12
• Results posted on: 2019-07-18

Participant Flow

Participants took part in the study at 570 investigative sites in Japan, from 29 May 2013 to 31 May 2017.

Participants with a historical diagnosis of hyperlipidemia were enrolled. Participants received interventions as part of routine medical care.

Participant milestones

Measure	Omega-3 Fatty Acid Ethyl Esters 2 g Oral administration with granular capsule formulation of 2 g of omega-3 fatty acid ethyl esters once daily for 12 months. Participants received interventions as part of routine medical care.
Overall Study STARTED	3084
Overall Study COMPLETED	2786
Overall Study NOT COMPLETED	298

Reasons for withdrawal

Measure	Omega-3 Fatty Acid Ethyl Esters 2 g Oral administration with granular capsule formulation of 2 g of omega-3 fatty acid ethyl esters once daily for 12 months. Participants received interventions as part of routine medical care.
Overall Study Case Report Forms Uncollected	230
Overall Study Protocol Deviation	68

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Omega-3 Fatty Acid Ethyl Esters 2 g n=2786 Participants Oral administration with granular capsule formulation of 2 g of omega-3 fatty acid ethyl esters once daily for 12 months. Participants received interventions as part of routine medical care.
Age, Continuous	66.2 Years STANDARD_DEVIATION 13.27 • n=2786 Participants
Sex: Female, Male Female	1382 Participants n=2786 Participants
Sex: Female, Male Male	1404 Participants n=2786 Participants
Region of Enrollment Japan	2786 Participants n=2786 Participants
Healthcare Category Outpatient	2765 Participants n=2786 Participants
Healthcare Category Inpatient	21 Participants n=2786 Participants
BMI	24.94 Kilograms (kg)/meter (m)^2 STANDARD_DEVIATION 4.097 • n=1941 Participants • The number analyzed is the number of participants with data available for analysis.
Medical Complications Had No Presence of Medical Complications	566 Participants n=2786 Participants
Medical Complications Had Presence of Medical Complications	2220 Participants n=2786 Participants
Drinking Habits Yes	687 Participants n=2786 Participants
Drinking Habits No	1609 Participants n=2786 Participants
Drinking Habits Unknown	490 Participants n=2786 Participants
Triglycerides (TG) in Fasted Condition [Milligrams (mg)/ Deciliter (dL)] < 150 mg/dL	298 Participants n=2786 Participants
Triglycerides (TG) in Fasted Condition [Milligrams (mg)/ Deciliter (dL)] >= 150 mg/dL and < 400 mg/dL	824 Participants n=2786 Participants
Triglycerides (TG) in Fasted Condition [Milligrams (mg)/ Deciliter (dL)] >= 400 mg/dL and < 500mg/dL	64 Participants n=2786 Participants
Triglycerides (TG) in Fasted Condition [Milligrams (mg)/ Deciliter (dL)] >= 500 mg/dL and < 750mg/dL	43 Participants n=2786 Participants
Triglycerides (TG) in Fasted Condition [Milligrams (mg)/ Deciliter (dL)] >= 750mg/dL	16 Participants n=2786 Participants
Triglycerides (TG) in Fasted Condition [Milligrams (mg)/ Deciliter (dL)] Not Measured	1541 Participants n=2786 Participants
TG in Non-Fasted Condition (mg/dL) < 150 mg/dL	287 Participants n=2786 Participants
TG in Non-Fasted Condition (mg/dL) >= 150 mg/dL and < 400 mg/dL	762 Participants n=2786 Participants
TG in Non-Fasted Condition (mg/dL) >= 400 mg/dL and < 500mg/dL	78 Participants n=2786 Participants
TG in Non-Fasted Condition (mg/dL) >= 500 mg/dL and < 750mg/dL	82 Participants n=2786 Participants
TG in Non-Fasted Condition (mg/dL) >= 750mg/dL	31 Participants n=2786 Participants
TG in Non-Fasted Condition (mg/dL) Not Measured	1546 Participants n=2786 Participants
Smoking Classification Never Smoked	1430 Participants n=2786 Participants
Smoking Classification Current Smoker	307 Participants n=2786 Participants
Smoking Classification Ex-Smoker	496 Participants n=2786 Participants
Smoking Classification Unknown	553 Participants n=2786 Participants
Predisposition to Hypersensitivity Had No Predisposition to Hypersensitivity	2520 Participants n=2786 Participants
Predisposition to Hypersensitivity Had Predisposition to Hypersensitivity	133 Participants n=2786 Participants
Predisposition to Hypersensitivity Unknown	133 Participants n=2786 Participants
Duration of Diagnosis of Hyperlipidemia	3.13 Years STANDARD_DEVIATION 4.755 • n=2074 Participants • Population Analysis Description: The number analyzed is the number of participants with data available for analysis.
Surgery within One Month before Dosing Had No Surgery within One Month before Dosing	2762 Participants n=2786 Participants
Surgery within One Month before Dosing Had Surgery within One Month before Dosing	24 Participants n=2786 Participants
Pregnancy Status during the Administration Period Not Pregnant	1381 Participants n=1382 Participants • This baseline characteristic was analyzed only in female participants.
Pregnancy Status during the Administration Period Pregnant	1 Participants n=1382 Participants • This baseline characteristic was analyzed only in female participants.

PRIMARY outcome

Timeframe: Up to Month 12

Population: Safety Analysis Set; The safety analysis set was defined as all participants who completed the study.

Outcome measures

Measure	Omega-3 Fatty Acid Ethyl Esters 2 g n=2786 Participants Oral administration with granular capsule formulation of 2 g of omega-3 fatty acid ethyl esters once daily for 12 months. Participants received interventions as part of routine medical care.
Number of Participants Who Had One or More Adverse Events (AE) and Serious Adverse Events (SAE) AE	130 Participants
Number of Participants Who Had One or More Adverse Events (AE) and Serious Adverse Events (SAE) SAE	26 Participants

SECONDARY outcome

Timeframe: Baseline, up to 12 months (Final Assessment Point)

Population: Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The analyzed numbers were participants who were evaluable for this outcome measure at the given time point.

Percent change from baseline in TG values as one of lipid parameters in fasted condition at final assessment point (up to Month 12) was reported.

Outcome measures

Measure	Omega-3 Fatty Acid Ethyl Esters 2 g n=1018 Participants Oral administration with granular capsule formulation of 2 g of omega-3 fatty acid ethyl esters once daily for 12 months. Participants received interventions as part of routine medical care.
Percent Change From Baseline in Lipid Parameters - Triglycerides (TG)	-20.54 Percent change Standard Deviation 40.259

SECONDARY outcome

Timeframe: Baseline, up to 12 months (Final Assessment Point)

Population: Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The analyzed numbers were participants who were evaluable for this outcome measure at the given time point.

Percent change from baseline in LDL-C values as one of lipid parameters in fasted condition at final assessment point (up to Month 12) was reported.

Outcome measures

Measure	Omega-3 Fatty Acid Ethyl Esters 2 g n=469 Participants Oral administration with granular capsule formulation of 2 g of omega-3 fatty acid ethyl esters once daily for 12 months. Participants received interventions as part of routine medical care.
Percent Change From Baseline in Lipid Parameters - LDL Cholesterol (LDL-C)	7.73 Percent change Standard Deviation 82.486

SECONDARY outcome

Timeframe: Baseline, up to 12 months (Final Assessment Point)

Population: Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available.The analyzed numbers were participants who were evaluable for this outcome measure at the given time point.

Percent change from baseline in VLDL-C values as one of lipid parameters in fasted condition at final assessment point (up to Month 12) was reported.

Outcome measures

Measure	Omega-3 Fatty Acid Ethyl Esters 2 g n=22 Participants Oral administration with granular capsule formulation of 2 g of omega-3 fatty acid ethyl esters once daily for 12 months. Participants received interventions as part of routine medical care.
Percent Change From Baseline in Lipid Parameters - VLDL Cholesterol (VLDL-C)	-14.15 Percent change Standard Deviation 57.833

SECONDARY outcome

Timeframe: Baseline, up to 12 months (Final Assessment Point)

Population: Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The analyzed numbers were participants who were evaluable for this outcome measure at the given time point.

Percent change from baseline in Apo-B values as one of lipid parameters in fasted condition at final assessment point (up to Month 12) was reported.

Outcome measures

Measure	Omega-3 Fatty Acid Ethyl Esters 2 g n=35 Participants Oral administration with granular capsule formulation of 2 g of omega-3 fatty acid ethyl esters once daily for 12 months. Participants received interventions as part of routine medical care.
Percent Change From Baseline in Lipid Parameters - Apo-B	-7.21 Percent change Standard Deviation 12.979

SECONDARY outcome

Timeframe: Baseline, up to 12 months (Final Assessment Point)

Population: Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The analyzed numbers were participants who were evaluable for this outcome measure at the given time point.

Percent change from baseline in Apo-CIII values as one of lipid parameters in fasted condition at final assessment point (up to Month 12) was reported.

Outcome measures

Measure	Omega-3 Fatty Acid Ethyl Esters 2 g n=31 Participants Oral administration with granular capsule formulation of 2 g of omega-3 fatty acid ethyl esters once daily for 12 months. Participants received interventions as part of routine medical care.
Percent Change From Baseline in Lipid Parameters - Apo-CIII	-5.49 Percent change Standard Deviation 23.117

SECONDARY outcome

Timeframe: Baseline, up to 12 months (Final Assessment Point)

Population: Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The analyzed numbers were participants who were evaluable for this outcome measure at the given time point.

Percent change from baseline in Lipoprotein values as one of lipid parameters in fasted condition at final assessment point (up to Month 12) was reported.

Outcome measures

Measure	Omega-3 Fatty Acid Ethyl Esters 2 g n=28 Participants Oral administration with granular capsule formulation of 2 g of omega-3 fatty acid ethyl esters once daily for 12 months. Participants received interventions as part of routine medical care.
Percent Change From Baseline in Lipid Parameters - Lipoprotein	-2.98 Percent change Standard Deviation 28.385

SECONDARY outcome

Timeframe: Baseline, up to 12 months (Final Assessment Point)

Population: Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The analyzed numbers were participants who were evaluable for this outcome measure at the given time point.

Percent change from baseline in RLP-C values as one of lipid parameters in fasted condition at final assessment point (up to Month 12) was reported.

Outcome measures

Measure	Omega-3 Fatty Acid Ethyl Esters 2 g n=39 Participants Oral administration with granular capsule formulation of 2 g of omega-3 fatty acid ethyl esters once daily for 12 months. Participants received interventions as part of routine medical care.
Percent Change From Baseline in Lipid Parameters -Remnant-Like Particles-Cholesterol (RLP-C)	-22.42 Percent change Standard Deviation 94.776

SECONDARY outcome

Timeframe: Baseline, up to 12 months (Final Assessment Point)

Population: Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The analyzed numbers were participants who were evaluable for this outcome measure at the given time point.

Percent change from baseline in TC values as one of lipid parameters at final assessment point (up to Month 12) was reported.

Outcome measures

Measure	Omega-3 Fatty Acid Ethyl Esters 2 g n=1327 Participants Oral administration with granular capsule formulation of 2 g of omega-3 fatty acid ethyl esters once daily for 12 months. Participants received interventions as part of routine medical care.
Percent Change From Baseline in Lipid Parameters - Total Cholesterol (TC)	-4.26 Percent change Standard Deviation 17.488

SECONDARY outcome

Timeframe: Baseline, up to 12 months (Final Assessment Point)

Population: Efficacy assessment population; The efficacy assessment population was defined as participants who completed the study and had efficacy data at baseline and post-baseline time points available. The analyzed numbers were participants who were evaluable for this outcome measure at the given time point.

Percent change from baseline in Non-HDL-C values as one of lipid parameters at final assessment point (up to Month 12) was reported.

Outcome measures

Measure	Omega-3 Fatty Acid Ethyl Esters 2 g n=51 Participants Oral administration with granular capsule formulation of 2 g of omega-3 fatty acid ethyl esters once daily for 12 months. Participants received interventions as part of routine medical care.
Percent Change From Baseline in Lipid Parameters - Non-HDL Cholesterol (Non-HDL-C)	-1.42 Percent change Standard Deviation 23.495

Adverse Events

Omega-3 Fatty Acid Ethyl Esters 2 g

Serious events: 26 serious events

Other events: 38 other events

Deaths: 10 deaths

Serious adverse events

Measure	Omega-3 Fatty Acid Ethyl Esters 2 g n=2786 participants at risk Oral administration with granular capsule formulation of 2 g of omega-3 fatty acid ethyl esters once daily for 12 months. Participants received interventions as part of routine medical care.
Infections and infestations Sinusitis	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hypoalbuminaemia	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Dementia	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Transient ischaemic attack	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Angina pectoris	0.07% 2/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Atrial fibrillation	0.07% 2/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Cardiac failure acute	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Myocardial infarction	0.14% 4/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Vascular disorders Deep vein thrombosis	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Diarrhoea	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Rectal prolapse	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Liver injury	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Skin ulcer	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Cystitis haemorrhagic	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Asthenia	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Death	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Drowning	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Road traffic accident	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Subdural haematoma	0.04% 1/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Measure	Omega-3 Fatty Acid Ethyl Esters 2 g n=2786 participants at risk Oral administration with granular capsule formulation of 2 g of omega-3 fatty acid ethyl esters once daily for 12 months. Participants received interventions as part of routine medical care.
Gastrointestinal disorders Diarrhoea	0.32% 9/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Nausea	0.32% 9/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Hepatic function abnormal	0.25% 7/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Bronchitis	0.25% 7/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Viral upper respiratory tract infection	0.22% 6/2786 • Up to Month12 At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
• Publication restrictions are in place

Restriction type: OTHER