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Evaluation of the Safety and Efficacy of Long-term Use of Omega-3 Fatty Acid Ethyl Esters

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02153073
Recruitment Status : Completed
First Posted : June 2, 2014
Results First Posted : July 4, 2019
Last Update Posted : July 18, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Observational
Study Design Observational Model: Cohort;   Time Perspective: Prospective
Condition Hyperlipidemia
Intervention Drug: Omega-3 fatty acid ethyl esters
Enrollment 3084
Recruitment Details Participants took part in the study at 570 investigative sites in Japan, from 29 May 2013 to 31 May 2017.
Pre-assignment Details Participants with a historical diagnosis of hyperlipidemia were enrolled. Participants received interventions as part of routine medical care.
Arm/Group Title Omega-3 Fatty Acid Ethyl Esters 2 g
Hide Arm/Group Description 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.
Period Title: Overall Study
Started 3084
Completed 2786
Not Completed 298
Reason Not Completed
Case Report Forms Uncollected             230
Protocol Deviation             68
Arm/Group Title Omega-3 Fatty Acid Ethyl Esters 2 g
Hide Arm/Group Description 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 Number of Baseline Participants 2786
Hide Baseline Analysis Population Description
Safety Analysis Set; The safety analysis set was defined as all participants who completed the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2786 participants
66.2  (13.27)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2786 participants
Female
1382
  49.6%
Male
1404
  50.4%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Japan Number Analyzed 2786 participants
2786
Healthcare Category   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2786 participants
Outpatient
2765
  99.2%
Inpatient
21
   0.8%
[1]
Measure Description: Participants were categorized as outpatient and inpatient.
BMI   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Kilograms (kg)/meter (m)^2
Number Analyzed 1941 participants
24.94  (4.097)
[1]
Measure Description: Body Mass Index = weight (kg)/[height (m)^2]
[2]
Measure Analysis Population Description: The number analyzed is the number of participants with data available for analysis.
Medical Complications   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2786 participants
Had No Presence of Medical Complications
566
  20.3%
Had Presence of Medical Complications
2220
  79.7%
[1]
Measure Description: Complications defined as a disease or a health condition for each participant at the start of study. Complications were classified as congenital anomalies, endocrine disorders, hematologic disorders, psychiatric and nervous system disorders, cardiovascular disorders, respiratory disorders, gastrointestinal (GI) disorders, renal disease and other complications. Other complications included all complications except for those mentioned above.
Drinking Habits   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2786 participants
Yes
687
  24.7%
No
1609
  57.8%
Unknown
490
  17.6%
[1]
Measure Description: Participants who answered Yes or No for a question “Drink Alcohol Almost Every Day?" were reported.
Triglycerides (TG) in Fasted Condition [Milligrams (mg)/ Deciliter (dL)]  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2786 participants
< 150 mg/dL
298
  10.7%
>= 150 mg/dL and < 400 mg/dL
824
  29.6%
>= 400 mg/dL and < 500mg/dL
64
   2.3%
>= 500 mg/dL and < 750mg/dL
43
   1.5%
>= 750mg/dL
16
   0.6%
Not Measured
1541
  55.3%
TG in Non-Fasted Condition (mg/dL)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2786 participants
< 150 mg/dL
287
  10.3%
>= 150 mg/dL and < 400 mg/dL
762
  27.4%
>= 400 mg/dL and < 500mg/dL
78
   2.8%
>= 500 mg/dL and < 750mg/dL
82
   2.9%
>= 750mg/dL
31
   1.1%
Not Measured
1546
  55.5%
Smoking Classification  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2786 participants
Never Smoked
1430
  51.3%
Current Smoker
307
  11.0%
Ex-Smoker
496
  17.8%
Unknown
553
  19.8%
Predisposition to Hypersensitivity   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2786 participants
Had No Predisposition to Hypersensitivity
2520
  90.5%
Had Predisposition to Hypersensitivity
133
   4.8%
Unknown
133
   4.8%
[1]
Measure Description: The baseline characteristic was analyzed in participants who had a liability or tendency to suffer from hypersensitivity.
Duration of Diagnosis of Hyperlipidemia   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 2074 participants
3.13  (4.755)
[1]
Measure Description: Mean duration between start of study and first time of diagnosis of hyperlipidemia was reported.
[2]
Measure Analysis Population Description: Population Analysis Description: The number analyzed is the number of participants with data available for analysis.
Surgery within One Month before Dosing  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 2786 participants
Had No Surgery within One Month before Dosing
2762
  99.1%
Had Surgery within One Month before Dosing
24
   0.9%
Pregnancy Status during the Administration Period   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1382 participants
Not Pregnant
1381
  99.9%
Pregnant
1
   0.1%
[1]
Measure Analysis Population Description: This baseline characteristic was analyzed only in female participants.
1.Primary Outcome
Title Number of Participants Who Had One or More Adverse Events (AE) and Serious Adverse Events (SAE)
Hide Description [Not Specified]
Time Frame Up to Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set; The safety analysis set was defined as all participants who completed the study.
Arm/Group Title Omega-3 Fatty Acid Ethyl Esters 2 g
Hide Arm/Group Description:
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 Number of Participants Analyzed 2786
Measure Type: Count of Participants
Unit of Measure: Participants
AE
130
   4.7%
SAE
26
   0.9%
2.Secondary Outcome
Title Percent Change From Baseline in Lipid Parameters - Triglycerides (TG)
Hide Description 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.
Time Frame Baseline, up to 12 months (Final Assessment Point)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omega-3 Fatty Acid Ethyl Esters 2 g
Hide Arm/Group Description:
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 Number of Participants Analyzed 1018
Mean (Standard Deviation)
Unit of Measure: Percent change
-20.54  (40.259)
3.Secondary Outcome
Title Percent Change From Baseline in Lipid Parameters - LDL Cholesterol (LDL-C)
Hide Description 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.
Time Frame Baseline, up to 12 months (Final Assessment Point)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omega-3 Fatty Acid Ethyl Esters 2 g
Hide Arm/Group Description:
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 Number of Participants Analyzed 469
Mean (Standard Deviation)
Unit of Measure: Percent change
7.73  (82.486)
4.Secondary Outcome
Title Percent Change From Baseline in Lipid Parameters - VLDL Cholesterol (VLDL-C)
Hide Description 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.
Time Frame Baseline, up to 12 months (Final Assessment Point)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omega-3 Fatty Acid Ethyl Esters 2 g
Hide Arm/Group Description:
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 Number of Participants Analyzed 22
Mean (Standard Deviation)
Unit of Measure: Percent change
-14.15  (57.833)
5.Secondary Outcome
Title Percent Change From Baseline in Lipid Parameters - Apo-B
Hide Description 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.
Time Frame Baseline, up to 12 months (Final Assessment Point)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omega-3 Fatty Acid Ethyl Esters 2 g
Hide Arm/Group Description:
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 Number of Participants Analyzed 35
Mean (Standard Deviation)
Unit of Measure: Percent change
-7.21  (12.979)
6.Secondary Outcome
Title Percent Change From Baseline in Lipid Parameters - Apo-CIII
Hide Description 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.
Time Frame Baseline, up to 12 months (Final Assessment Point)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omega-3 Fatty Acid Ethyl Esters 2 g
Hide Arm/Group Description:
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 Number of Participants Analyzed 31
Mean (Standard Deviation)
Unit of Measure: Percent change
-5.49  (23.117)
7.Secondary Outcome
Title Percent Change From Baseline in Lipid Parameters - Lipoprotein
Hide Description 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.
Time Frame Baseline, up to 12 months (Final Assessment Point)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omega-3 Fatty Acid Ethyl Esters 2 g
Hide Arm/Group Description:
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 Number of Participants Analyzed 28
Mean (Standard Deviation)
Unit of Measure: Percent change
-2.98  (28.385)
8.Secondary Outcome
Title Percent Change From Baseline in Lipid Parameters -Remnant-Like Particles-Cholesterol (RLP-C)
Hide Description 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.
Time Frame Baseline, up to 12 months (Final Assessment Point)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omega-3 Fatty Acid Ethyl Esters 2 g
Hide Arm/Group Description:
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 Number of Participants Analyzed 39
Mean (Standard Deviation)
Unit of Measure: Percent change
-22.42  (94.776)
9.Secondary Outcome
Title Percent Change From Baseline in Lipid Parameters - Total Cholesterol (TC)
Hide Description Percent change from baseline in TC values as one of lipid parameters at final assessment point (up to Month 12) was reported.
Time Frame Baseline, up to 12 months (Final Assessment Point)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omega-3 Fatty Acid Ethyl Esters 2 g
Hide Arm/Group Description:
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 Number of Participants Analyzed 1327
Mean (Standard Deviation)
Unit of Measure: Percent change
-4.26  (17.488)
10.Secondary Outcome
Title Percent Change From Baseline in Lipid Parameters - Non-HDL Cholesterol (Non-HDL-C)
Hide Description Percent change from baseline in Non-HDL-C values as one of lipid parameters at final assessment point (up to Month 12) was reported.
Time Frame Baseline, up to 12 months (Final Assessment Point)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Omega-3 Fatty Acid Ethyl Esters 2 g
Hide Arm/Group Description:
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 Number of Participants Analyzed 51
Mean (Standard Deviation)
Unit of Measure: Percent change
-1.42  (23.495)
Time Frame Up to Month12
Adverse Event Reporting Description 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.
 
Arm/Group Title Omega-3 Fatty Acid Ethyl Esters 2 g
Hide Arm/Group Description 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.
All-Cause Mortality
Omega-3 Fatty Acid Ethyl Esters 2 g
Affected / at Risk (%)
Total   10/2786 (0.36%) 
Show Serious Adverse Events Hide Serious Adverse Events
Omega-3 Fatty Acid Ethyl Esters 2 g
Affected / at Risk (%)
Total   26/2786 (0.93%) 
Cardiac disorders   
Angina pectoris  1  2/2786 (0.07%) 
Atrial fibrillation  1  2/2786 (0.07%) 
Cardiac failure acute  1  1/2786 (0.04%) 
Myocardial infarction  1  4/2786 (0.14%) 
Gastrointestinal disorders   
Diarrhoea  1  1/2786 (0.04%) 
Rectal prolapse  1  1/2786 (0.04%) 
General disorders   
Asthenia  1  1/2786 (0.04%) 
Death  1 [1]  1/2786 (0.04%) 
Drowning  1 [1]  1/2786 (0.04%) 
Hepatobiliary disorders   
Liver injury  1  1/2786 (0.04%) 
Infections and infestations   
Sinusitis  1  1/2786 (0.04%) 
Injury, poisoning and procedural complications   
Road traffic accident  1  1/2786 (0.04%) 
Subdural haematoma  1  1/2786 (0.04%) 
Metabolism and nutrition disorders   
Diabetes mellitus inadequate control  1  1/2786 (0.04%) 
Hypoalbuminaemia  1  1/2786 (0.04%) 
Musculoskeletal and connective tissue disorders   
Lumbar spinal stenosis  1  1/2786 (0.04%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Gastric cancer  1  1/2786 (0.04%) 
Oesophageal carcinoma  1  1/2786 (0.04%) 
Lung neoplasm malignant  1  1/2786 (0.04%) 
Nervous system disorders   
Dementia  1  1/2786 (0.04%) 
Transient ischaemic attack  1  1/2786 (0.04%) 
Renal and urinary disorders   
Cystitis haemorrhagic  1  1/2786 (0.04%) 
Respiratory, thoracic and mediastinal disorders   
Interstitial lung disease  1  1/2786 (0.04%) 
Skin and subcutaneous tissue disorders   
Skin ulcer  1  1/2786 (0.04%) 
Vascular disorders   
Deep vein thrombosis  1  1/2786 (0.04%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
[1]
The reasons of events are not determined because assessment findings were insufficient to specify the reason.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0.2%
Omega-3 Fatty Acid Ethyl Esters 2 g
Affected / at Risk (%)
Total   38/2786 (1.36%) 
Gastrointestinal disorders   
Diarrhoea  1  9/2786 (0.32%) 
Nausea  1  9/2786 (0.32%) 
Hepatobiliary disorders   
Hepatic function abnormal  1  7/2786 (0.25%) 
Infections and infestations   
Bronchitis  1  7/2786 (0.25%) 
Viral upper respiratory tract infection  1  6/2786 (0.22%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
EMail: trialdisclosures@takeda.com
Layout table for additonal information
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02153073     History of Changes
Other Study ID Numbers: 142-011
JapicCTI-142457 ( Registry Identifier: JapicCTI )
First Submitted: May 29, 2014
First Posted: June 2, 2014
Results First Submitted: May 25, 2018
Results First Posted: July 4, 2019
Last Update Posted: July 18, 2019