Trial Outcomes & Findings for Long-term Efficacy and Safety Study of TAK-085 in Participants With Hypertriglyceridemia (NCT NCT01350999)

NCT ID: NCT01350999

Last Updated: 2016-09-20

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 503 participants
• Primary outcome timeframe: 52 Weeks
• Results posted on: 2016-09-20

Participant Flow

Participants took part in the study at 50 investigative sites in Japan from 11 November 2009 to 11 January 2011.

Participants with hypertriglyceridemia were randomized to receive omega-3-acid ethyl esters 90 (TAK-085) 2 g once daily or TAK-085 2 g twice daily or EPA-E 0.6 g three-times daily.

Participant milestones

Measure	TAK-085 2 g TAK-085 2 g capsule, orally, once daily for up to 52 weeks.	TAK-085 4 g TAK-085 2 g capsules, orally, twice daily for up to 52 weeks.	EPA-E 1.8 g Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 52 weeks.
Overall Study STARTED	165	171	167
Overall Study Treated	165	171	167
Overall Study COMPLETED	157	157	146
Overall Study NOT COMPLETED	8	14	21

Reasons for withdrawal

Measure	TAK-085 2 g TAK-085 2 g capsule, orally, once daily for up to 52 weeks.	TAK-085 4 g TAK-085 2 g capsules, orally, twice daily for up to 52 weeks.	EPA-E 1.8 g Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 52 weeks.
Overall Study Adverse Event	4	9	10
Overall Study Voluntary withdrawal	3	4	6
Overall Study Difficulty Making it to Study Visit	1	1	5

Baseline Characteristics

Long-term Efficacy and Safety Study of TAK-085 in Participants With Hypertriglyceridemia

Baseline characteristics by cohort

Measure	TAK-085 2 g n=165 Participants TAK-085 2 g capsule, orally, once daily for up to 52 weeks.	TAK-085 4 g n=171 Participants TAK-085 2 g capsules, orally, twice daily for up to 52 weeks.	EPA-E 1.8 g n=167 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 52 weeks.	Total n=503 Participants Total of all reporting groups
Age, Continuous	56.0 years STANDARD_DEVIATION 10.95 • n=5 Participants	55.9 years STANDARD_DEVIATION 10.12 • n=7 Participants	55.8 years STANDARD_DEVIATION 9.27 • n=5 Participants	55.9 years STANDARD_DEVIATION 10.11 • n=4 Participants
Age, Customized ≥20 - <65 years	119 participants n=5 Participants	134 participants n=7 Participants	136 participants n=5 Participants	389 participants n=4 Participants
Age, Customized ≥65 - ≤74 years	46 participants n=5 Participants	37 participants n=7 Participants	31 participants n=5 Participants	114 participants n=4 Participants
Sex: Female, Male Female	47 Participants n=5 Participants	50 Participants n=7 Participants	48 Participants n=5 Participants	145 Participants n=4 Participants
Sex: Female, Male Male	118 Participants n=5 Participants	121 Participants n=7 Participants	119 Participants n=5 Participants	358 Participants n=4 Participants
Region of Enrollment Japan	165 participants n=5 Participants	171 participants n=7 Participants	167 participants n=5 Participants	503 participants n=4 Participants
Menopause Status Yes	38 participants n=5 Participants	42 participants n=7 Participants	39 participants n=5 Participants	119 participants n=4 Participants
Menopause Status No	5 participants n=5 Participants	7 participants n=7 Participants	5 participants n=5 Participants	17 participants n=4 Participants
Menopause Status Unknown	4 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants	9 participants n=4 Participants
Menopause Status Not Applicable	118 participants n=5 Participants	121 participants n=7 Participants	119 participants n=5 Participants	358 participants n=4 Participants
Height, Categorical <160 cm	48 participants n=5 Participants	45 participants n=7 Participants	48 participants n=5 Participants	141 participants n=4 Participants
Height, Categorical ≥160 - <170 cm	67 participants n=5 Participants	77 participants n=7 Participants	66 participants n=5 Participants	210 participants n=4 Participants
Height, Categorical ≥170 cm	50 participants n=5 Participants	49 participants n=7 Participants	53 participants n=5 Participants	152 participants n=4 Participants
Height	164.2 cm STANDARD_DEVIATION 9.40 • n=5 Participants	164.0 cm STANDARD_DEVIATION 8.69 • n=7 Participants	164.4 cm STANDARD_DEVIATION 9.65 • n=5 Participants	164.2 cm STANDARD_DEVIATION 9.23 • n=4 Participants
Weight, Categorical <60 kg	32 participants n=5 Participants	34 participants n=7 Participants	32 participants n=5 Participants	98 participants n=4 Participants
Weight, Categorical ≥60.0 - <70.0 kg	57 participants n=5 Participants	53 participants n=7 Participants	43 participants n=5 Participants	153 participants n=4 Participants
Weight, Categorical ≥70.0 - <80.0 kg	44 participants n=5 Participants	50 participants n=7 Participants	57 participants n=5 Participants	151 participants n=4 Participants
Weight, Categorical ≥80.0 kg	32 participants n=5 Participants	34 participants n=7 Participants	35 participants n=5 Participants	101 participants n=4 Participants
Weight	70.02 kg STANDARD_DEVIATION 12.291 • n=5 Participants	70.46 kg STANDARD_DEVIATION 12.097 • n=7 Participants	71.61 kg STANDARD_DEVIATION 13.311 • n=5 Participants	70.70 kg STANDARD_DEVIATION 12.568 • n=4 Participants
Body Mass Index, Categorical <25.0 kg/m^2	77 participants n=5 Participants	72 participants n=7 Participants	60 participants n=5 Participants	209 participants n=4 Participants
Body Mass Index, Categorical ≥25.0 - <30.0 kg/m^2	71 participants n=5 Participants	74 participants n=7 Participants	83 participants n=5 Participants	228 participants n=4 Participants
Body Mass Index, Categorical ≥30.0 kg/m^2	17 participants n=5 Participants	25 participants n=7 Participants	24 participants n=5 Participants	66 participants n=4 Participants
Body Mass Index	25.90 kg/m^2 STANDARD_DEVIATION 3.673 • n=5 Participants	26.11 kg/m^2 STANDARD_DEVIATION 3.526 • n=7 Participants	26.33 kg/m^2 STANDARD_DEVIATION 3.301 • n=5 Participants	26.12 kg/m^2 STANDARD_DEVIATION 3.500 • n=4 Participants
Smoking Classification Never Smoked	59 participants n=5 Participants	56 participants n=7 Participants	47 participants n=5 Participants	162 participants n=4 Participants
Smoking Classification Current Smoker	52 participants n=5 Participants	47 participants n=7 Participants	58 participants n=5 Participants	157 participants n=4 Participants
Smoking Classification Ex-Smoker	54 participants n=5 Participants	68 participants n=7 Participants	62 participants n=5 Participants	184 participants n=4 Participants
Waist Circumference, Categorical Male <85.0 cm	22 participants n=5 Participants	29 participants n=7 Participants	19 participants n=5 Participants	70 participants n=4 Participants
Waist Circumference, Categorical Male ≥85.0 cm	96 participants n=5 Participants	92 participants n=7 Participants	100 participants n=5 Participants	288 participants n=4 Participants
Waist Circumference, Categorical Female <90.0 cm	26 participants n=5 Participants	30 participants n=7 Participants	26 participants n=5 Participants	82 participants n=4 Participants
Waist Circumference, Categorical Female ≥90.0 cm	21 participants n=5 Participants	20 participants n=7 Participants	22 participants n=5 Participants	63 participants n=4 Participants
Waist Circumference	90.39 cm STANDARD_DEVIATION 8.607 • n=5 Participants	90.75 cm STANDARD_DEVIATION 9.169 • n=7 Participants	91.16 cm STANDARD_DEVIATION 9.284 • n=5 Participants	90.77 cm STANDARD_DEVIATION 9.015 • n=4 Participants
Coronary Artery Disease (CAD) Category Category I	7 participants n=5 Participants	9 participants n=7 Participants	3 participants n=5 Participants	19 participants n=4 Participants
Coronary Artery Disease (CAD) Category Category II	70 participants n=5 Participants	71 participants n=7 Participants	56 participants n=5 Participants	197 participants n=4 Participants
Coronary Artery Disease (CAD) Category Category III	86 participants n=5 Participants	86 participants n=7 Participants	102 participants n=5 Participants	274 participants n=4 Participants
Coronary Artery Disease (CAD) Category History of CAD	2 participants n=5 Participants	5 participants n=7 Participants	6 participants n=5 Participants	13 participants n=4 Participants
Hypertension Yes	110 participants n=5 Participants	115 participants n=7 Participants	115 participants n=5 Participants	340 participants n=4 Participants
Hypertension No	55 participants n=5 Participants	56 participants n=7 Participants	52 participants n=5 Participants	163 participants n=4 Participants
Diabetes Mellitus (Including Impaired Glucose Tolerance) Yes	50 participants n=5 Participants	63 participants n=7 Participants	71 participants n=5 Participants	184 participants n=4 Participants
Diabetes Mellitus (Including Impaired Glucose Tolerance) No	115 participants n=5 Participants	108 participants n=7 Participants	96 participants n=5 Participants	319 participants n=4 Participants
Low High Density Lipoprotein - Cholesterol (HDL-C) Yes	42 participants n=5 Participants	39 participants n=7 Participants	45 participants n=5 Participants	126 participants n=4 Participants
Low High Density Lipoprotein - Cholesterol (HDL-C) No	123 participants n=5 Participants	132 participants n=7 Participants	122 participants n=5 Participants	377 participants n=4 Participants
Administration of 3-hydroxy 3-methylglutaryl coenzyme A (HMGCoA) Reductase Inhibitor Yes	64 participants n=5 Participants	66 participants n=7 Participants	65 participants n=5 Participants	195 participants n=4 Participants
Administration of 3-hydroxy 3-methylglutaryl coenzyme A (HMGCoA) Reductase Inhibitor No	101 participants n=5 Participants	105 participants n=7 Participants	102 participants n=5 Participants	308 participants n=4 Participants
Triglycerides, Categorical <150 mg/dL	16 participants n=5 Participants	12 participants n=7 Participants	14 participants n=5 Participants	42 participants n=4 Participants
Triglycerides, Categorical ≥150 - <300 mg/dL	103 participants n=5 Participants	107 participants n=7 Participants	109 participants n=5 Participants	319 participants n=4 Participants
Triglycerides, Categorical ≥300 - <500 mg/dL	38 participants n=5 Participants	43 participants n=7 Participants	37 participants n=5 Participants	118 participants n=4 Participants
Triglycerides, Categorical ≥500 mg/dL	7 participants n=5 Participants	7 participants n=7 Participants	7 participants n=5 Participants	21 participants n=4 Participants
Triglycerides	254.7 mg/dL STANDARD_DEVIATION 97.80 • n=5 Participants	270.0 mg/dL STANDARD_DEVIATION 101.19 • n=7 Participants	264.2 mg/dL STANDARD_DEVIATION 111.62 • n=5 Participants	263.0 mg/dL STANDARD_DEVIATION 103.71 • n=4 Participants
Low Density Lipoprotein - Cholesterol (LDL-C), Categorical <140 mg/dL	101 participants n=5 Participants	116 participants n=7 Participants	102 participants n=5 Participants	319 participants n=4 Participants
Low Density Lipoprotein - Cholesterol (LDL-C), Categorical ≥140 mg/dL	64 participants n=5 Participants	55 participants n=7 Participants	65 participants n=5 Participants	184 participants n=4 Participants
Low Density Lipoprotein - Cholesterol (LDL-C)	133.2 mg/dL STANDARD_DEVIATION 29.85 • n=5 Participants	129.0 mg/dL STANDARD_DEVIATION 30.26 • n=7 Participants	129.3 mg/dL STANDARD_DEVIATION 33.00 • n=5 Participants	130.5 mg/dL STANDARD_DEVIATION 31.06 • n=4 Participants

PRIMARY outcome

Timeframe: 52 Weeks

Population: Safety Analysis Set included all participants who received at least one dose of the investigational product.

Outcome measures

Measure	TAK-085 2 g n=165 Participants TAK-085 2 g capsule, orally, once daily for up to 52 weeks.	TAK-085 4 g n=171 Participants TAK-085 2 g capsules, orally, twice daily for up to 52 weeks.	EPA-E 1.8 g n=167 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 52 weeks.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	106 participants	110 participants	109 participants

PRIMARY outcome

Timeframe: 52 Weeks

Population: Safety Analysis Set included all participants who received at least one dose of the investigational product.

Outcome measures

Measure	TAK-085 2 g n=165 Participants TAK-085 2 g capsule, orally, once daily for up to 52 weeks.	TAK-085 4 g n=171 Participants TAK-085 2 g capsules, orally, twice daily for up to 52 weeks.	EPA-E 1.8 g n=167 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 52 weeks.
Number of Participants With TEAEs Associated With Abnormal Changes in Vital Signs	0 participants 12.58	0 participants 12.64	0 participants 12.80

PRIMARY outcome

Timeframe: 52 Weeks

Population: Safety Analysis Set included all participants who received at least one dose of the investigational product.

Outcome measures

Measure	TAK-085 2 g n=165 Participants TAK-085 2 g capsule, orally, once daily for up to 52 weeks.	TAK-085 4 g n=171 Participants TAK-085 2 g capsules, orally, twice daily for up to 52 weeks.	EPA-E 1.8 g n=167 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 52 weeks.
Number of Participants With TEAEs Associated With Abnormal Changes in Body Weight	0 participants 0.907	0 participants 0.870	0 participants 0.919

PRIMARY outcome

Timeframe: 52 Weeks

Population: Safety Analysis Set included all participants who received at least one dose of the investigational product.

Participants whose results of electrocardiograms were judged as abnormal and clinically significant by investigator after study drug administration were counted in this measure.

Outcome measures

Measure	TAK-085 2 g n=165 Participants TAK-085 2 g capsule, orally, once daily for up to 52 weeks.	TAK-085 4 g n=171 Participants TAK-085 2 g capsules, orally, twice daily for up to 52 weeks.	EPA-E 1.8 g n=167 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 52 weeks.
Number of Participants With Clinically Significant Findings in Electrocardiogram After Study Drug Administration	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: 52 Weeks

Population: Safety Analysis Set included all participants who received at least one dose of the investigational product.

Outcome measures

Measure	TAK-085 2 g n=165 Participants TAK-085 2 g capsule, orally, once daily for up to 52 weeks.	TAK-085 4 g n=171 Participants TAK-085 2 g capsules, orally, twice daily for up to 52 weeks.	EPA-E 1.8 g n=167 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 52 weeks.
Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis	24 participants	21 participants	23 participants

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Population: Full analysis set (all participants who were randomized and received at least one dose of the investigational product) with available data at each time point (indicated by "n").

Outcome measures

Measure	TAK-085 2 g n=165 Participants TAK-085 2 g capsule, orally, once daily for up to 52 weeks.	TAK-085 4 g n=171 Participants TAK-085 2 g capsules, orally, twice daily for up to 52 weeks.	EPA-E 1.8 g n=167 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 52 weeks.
Percent Change From Baseline in Triglyceride Level Week 12 (n=162, 166, 161)	-11.628 percent change Standard Deviation 28.6330	-21.689 percent change Standard Deviation 27.9188	-9.204 percent change Standard Deviation 34.5555
Percent Change From Baseline in Triglyceride Level Week 16 (n=160, 165, 161)	-9.363 percent change Standard Deviation 35.5523	-20.735 percent change Standard Deviation 35.0625	-9.522 percent change Standard Deviation 36.2768
Percent Change From Baseline in Triglyceride Level Week 52 (n=153, 151, 145)	-14.219 percent change Standard Deviation 31.1401	-26.023 percent change Standard Deviation 28.3644	-13.872 percent change Standard Deviation 40.9936
Percent Change From Baseline in Triglyceride Level Week 28 (n=159, 159, 153)	-12.644 percent change Standard Deviation 33.3250	-25.119 percent change Standard Deviation 31.4602	-9.422 percent change Standard Deviation 34.4423
Percent Change From Baseline in Triglyceride Level Week 32 (n=159, 160, 151)	-11.464 percent change Standard Deviation 36.7968	-27.219 percent change Standard Deviation 27.8708	-9.867 percent change Standard Deviation 36.9807
Percent Change From Baseline in Triglyceride Level Week 4 (n=163, 168, 166)	-10.875 percent change Standard Deviation 28.1914	-24.550 percent change Standard Deviation 26.7987	-5.743 percent change Standard Deviation 35.8469
Percent Change From Baseline in Triglyceride Level Week 8 (n=162, 166, 163)	-10.474 percent change Standard Deviation 36.1225	-26.555 percent change Standard Deviation 24.1354	-5.796 percent change Standard Deviation 36.2369
Percent Change From Baseline in Triglyceride Level Week 20 (n=161, 164, 157)	-12.965 percent change Standard Deviation 29.2649	-21.483 percent change Standard Deviation 28.1817	-7.400 percent change Standard Deviation 37.9737
Percent Change From Baseline in Triglyceride Level Week 24 (n=158, 162, 155)	-13.393 percent change Standard Deviation 34.8938	-23.863 percent change Standard Deviation 31.2129	-8.269 percent change Standard Deviation 38.8420
Percent Change From Baseline in Triglyceride Level Week 36 (n=156, 158, 151)	-16.190 percent change Standard Deviation 33.2777	-26.535 percent change Standard Deviation 27.0283	-9.616 percent change Standard Deviation 42.1895
Percent Change From Baseline in Triglyceride Level Week 40 (n=159, 158, 151)	-13.934 percent change Standard Deviation 35.8353	-25.062 percent change Standard Deviation 30.7020	-15.345 percent change Standard Deviation 33.6494
Percent Change From Baseline in Triglyceride Level Week 44 (n=158, 156, 149)	-17.156 percent change Standard Deviation 31.8849	-24.402 percent change Standard Deviation 30.1719	-12.363 percent change Standard Deviation 38.4921
Percent Change From Baseline in Triglyceride Level Week 48 (n=156, 155, 147)	-14.722 percent change Standard Deviation 33.1045	-26.478 percent change Standard Deviation 31.4535	-10.185 percent change Standard Deviation 39.0040

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Population: Full analysis set with available data at each time point (indicated by "n").

Outcome measures

Measure	TAK-085 2 g n=165 Participants TAK-085 2 g capsule, orally, once daily for up to 52 weeks.	TAK-085 4 g n=171 Participants TAK-085 2 g capsules, orally, twice daily for up to 52 weeks.	EPA-E 1.8 g n=167 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 52 weeks.
Percent Change From Baseline in Low-Density Lipoprotein - Cholesterol (LDL-C) Week 8 (n=164, 168, 165)	-2.890 percent change Standard Deviation 15.7779	-3.209 percent change Standard Deviation 17.1870	-4.423 percent change Standard Deviation 16.7481
Percent Change From Baseline in Low-Density Lipoprotein - Cholesterol (LDL-C) Week 12 (n=163, 168, 161)	-4.692 percent change Standard Deviation 15.5025	-4.778 percent change Standard Deviation 16.2444	-4.542 percent change Standard Deviation 16.6098
Percent Change From Baseline in Low-Density Lipoprotein - Cholesterol (LDL-C) Week 28 (n=160, 161, 153)	-1.660 percent change Standard Deviation 16.9498	0.421 percent change Standard Deviation 22.1540	-2.888 percent change Standard Deviation 17.1272
Percent Change From Baseline in Low-Density Lipoprotein - Cholesterol (LDL-C) Week 32 (n=160, 163, 151)	-1.961 percent change Standard Deviation 17.8059	1.776 percent change Standard Deviation 21.1586	-1.030 percent change Standard Deviation 19.2558
Percent Change From Baseline in Low-Density Lipoprotein - Cholesterol (LDL-C) Week 36 (n=158, 160, 151)	-1.731 percent change Standard Deviation 16.7500	2.858 percent change Standard Deviation 20.9376	0.035 percent change Standard Deviation 20.9409
Percent Change From Baseline in Low-Density Lipoprotein - Cholesterol (LDL-C) Week 52 (n=155, 154, 145)	-0.374 percent change Standard Deviation 17.5598	2.993 percent change Standard Deviation 20.3400	-0.621 percent change Standard Deviation 16.9016
Percent Change From Baseline in Low-Density Lipoprotein - Cholesterol (LDL-C) Week 4 (n=165, 170, 167)	-2.219 percent change Standard Deviation 14.5984	-2.327 percent change Standard Deviation 17.3965	-3.018 percent change Standard Deviation 16.3629
Percent Change From Baseline in Low-Density Lipoprotein - Cholesterol (LDL-C) Week 16 (n=163, 167, 161)	-4.689 percent change Standard Deviation 17.3729	-4.404 percent change Standard Deviation 18.8456	-4.551 percent change Standard Deviation 17.6688
Percent Change From Baseline in Low-Density Lipoprotein - Cholesterol (LDL-C) Week 20 (n=162, 166, 157)	-4.953 percent change Standard Deviation 16.1426	-3.088 percent change Standard Deviation 17.7755	-5.676 percent change Standard Deviation 17.9077
Percent Change From Baseline in Low-Density Lipoprotein - Cholesterol (LDL-C) Week 24 (n=159, 164, 155)	-4.232 percent change Standard Deviation 14.6688	-0.768 percent change Standard Deviation 19.6396	-3.623 percent change Standard Deviation 20.1695
Percent Change From Baseline in Low-Density Lipoprotein - Cholesterol (LDL-C) Week 40 (n=160, 160, 151)	-0.378 percent change Standard Deviation 17.4848	2.412 percent change Standard Deviation 20.8940	-0.037 percent change Standard Deviation 20.6483
Percent Change From Baseline in Low-Density Lipoprotein - Cholesterol (LDL-C) Week 44 (n=160, 158, 150)	1.677 percent change Standard Deviation 17.2021	2.334 percent change Standard Deviation 21.0440	0.598 percent change Standard Deviation 19.6207
Percent Change From Baseline in Low-Density Lipoprotein - Cholesterol (LDL-C) Week 48 (n=157, 157, 148)	-0.634 percent change Standard Deviation 16.2926	2.413 percent change Standard Deviation 22.0726	-0.306 percent change Standard Deviation 19.0464

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Population: Full analysis set with available data at each time point (indicated by "n").

Outcome measures

Measure	TAK-085 2 g n=165 Participants TAK-085 2 g capsule, orally, once daily for up to 52 weeks.	TAK-085 4 g n=171 Participants TAK-085 2 g capsules, orally, twice daily for up to 52 weeks.	EPA-E 1.8 g n=167 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 52 weeks.
Percent Change From Baseline in Total Cholesterol Week 4 (n=165, 170, 167)	-3.347 percent change Standard Deviation 9.1943	-6.381 percent change Standard Deviation 9.8008	-3.386 percent change Standard Deviation 9.8537
Percent Change From Baseline in Total Cholesterol Week 8 (n=164, 168, 165)	-3.510 percent change Standard Deviation 9.3764	-7.294 percent change Standard Deviation 9.7792	-3.711 percent change Standard Deviation 11.0426
Percent Change From Baseline in Total Cholesterol Week 12 (n=163, 168, 161)	-4.918 percent change Standard Deviation 9.1307	-7.316 percent change Standard Deviation 9.7382	-5.300 percent change Standard Deviation 10.5662
Percent Change From Baseline in Total Cholesterol Week 16 (n=163, 167, 161)	-4.489 percent change Standard Deviation 10.9503	-7.131 percent change Standard Deviation 10.7158	-5.027 percent change Standard Deviation 12.2383
Percent Change From Baseline in Total Cholesterol Week 20 (n=162, 166, 157)	-5.310 percent change Standard Deviation 10.0187	-6.543 percent change Standard Deviation 10.2848	-5.421 percent change Standard Deviation 11.6463
Percent Change From Baseline in Total Cholesterol Week 24 (n=159, 164, 155)	-4.503 percent change Standard Deviation 9.5968	-4.824 percent change Standard Deviation 11.2452	-4.241 percent change Standard Deviation 13.3773
Percent Change From Baseline in Total Cholesterol Week 28 (n=160, 161, 153)	-2.590 percent change Standard Deviation 11.5574	-4.691 percent change Standard Deviation 11.0348	-3.644 percent change Standard Deviation 11.0906
Percent Change From Baseline in Total Cholesterol Week 32 (n=160, 163, 151)	-2.201 percent change Standard Deviation 11.0082	-3.427 percent change Standard Deviation 11.2990	-2.939 percent change Standard Deviation 11.0774
Percent Change From Baseline in Total Cholesterol Week 36 (n=158, 160, 151)	-2.418 percent change Standard Deviation 10.7162	-2.439 percent change Standard Deviation 11.0752	-1.980 percent change Standard Deviation 12.9512
Percent Change From Baseline in Total Cholesterol Week 40 (n=160, 160, 151)	-1.755 percent change Standard Deviation 10.7847	-3.085 percent change Standard Deviation 10.7054	-2.947 percent change Standard Deviation 12.9953
Percent Change From Baseline in Total Cholesterol Week 44 (n=160, 158, 150)	-1.073 percent change Standard Deviation 10.0091	-2.956 percent change Standard Deviation 9.9486	-2.509 percent change Standard Deviation 12.1363
Percent Change From Baseline in Total Cholesterol Week 48 (n=157, 157, 148)	-2.581 percent change Standard Deviation 9.8592	-3.435 percent change Standard Deviation 11.1554	-2.406 percent change Standard Deviation 11.8012
Percent Change From Baseline in Total Cholesterol Week 52 (n=155, 154, 145)	-2.066 percent change Standard Deviation 10.9462	-2.801 percent change Standard Deviation 11.0523	-2.808 percent change Standard Deviation 10.6534

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Population: Full analysis set with available data at each time point (indicated by "n").

Outcome measures

Measure	TAK-085 2 g n=165 Participants TAK-085 2 g capsule, orally, once daily for up to 52 weeks.	TAK-085 4 g n=171 Participants TAK-085 2 g capsules, orally, twice daily for up to 52 weeks.	EPA-E 1.8 g n=167 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 52 weeks.
Percent Change From Baseline in High-Density Lipoprotein - Cholesterol (HDL-C) Week 4 (n=165, 170, 167)	0.849 percent change Standard Deviation 12.2814	2.184 percent change Standard Deviation 12.6361	-0.762 percent change Standard Deviation 11.4762
Percent Change From Baseline in High-Density Lipoprotein - Cholesterol (HDL-C) Week 8 (n=164, 168, 165)	1.886 percent change Standard Deviation 13.6679	1.298 percent change Standard Deviation 12.8820	-0.955 percent change Standard Deviation 12.9760
Percent Change From Baseline in High-Density Lipoprotein - Cholesterol (HDL-C) Week 32 (n=160, 163, 151)	6.456 percent change Standard Deviation 16.2378	6.890 percent change Standard Deviation 14.6459	3.012 percent change Standard Deviation 14.6151
Percent Change From Baseline in High-Density Lipoprotein - Cholesterol (HDL-C) Week 36 (n=158, 160, 151)	8.234 percent change Standard Deviation 15.8749	8.516 percent change Standard Deviation 14.2641	4.946 percent change Standard Deviation 15.6107
Percent Change From Baseline in High-Density Lipoprotein - Cholesterol (HDL-C) Week 44 (n=160, 158, 150)	7.983 percent change Standard Deviation 15.5313	7.182 percent change Standard Deviation 15.7227	4.533 percent change Standard Deviation 14.3921
Percent Change From Baseline in High-Density Lipoprotein - Cholesterol (HDL-C) Week 48 (n=157, 157, 148)	6.191 percent change Standard Deviation 14.7070	7.144 percent change Standard Deviation 15.1433	4.499 percent change Standard Deviation 14.6233
Percent Change From Baseline in High-Density Lipoprotein - Cholesterol (HDL-C) Week 52 (n=155, 154, 145)	6.738 percent change Standard Deviation 15.3629	6.932 percent change Standard Deviation 16.1796	5.183 percent change Standard Deviation 14.7508
Percent Change From Baseline in High-Density Lipoprotein - Cholesterol (HDL-C) Week 12 (n=163, 168, 161)	0.535 percent change Standard Deviation 12.5694	1.085 percent change Standard Deviation 13.1746	-0.561 percent change Standard Deviation 12.7619
Percent Change From Baseline in High-Density Lipoprotein - Cholesterol (HDL-C) Week 16 (n=163, 167, 161)	1.276 percent change Standard Deviation 13.3975	1.699 percent change Standard Deviation 12.4080	-0.134 percent change Standard Deviation 12.7453
Percent Change From Baseline in High-Density Lipoprotein - Cholesterol (HDL-C) Week 20 (n=162, 166, 157)	2.708 percent change Standard Deviation 14.7306	2.913 percent change Standard Deviation 13.3232	1.034 percent change Standard Deviation 14.0619
Percent Change From Baseline in High-Density Lipoprotein - Cholesterol (HDL-C) Week 24 (n=159, 164, 155)	4.569 percent change Standard Deviation 14.8251	5.684 percent change Standard Deviation 14.7141	2.693 percent change Standard Deviation 14.7185
Percent Change From Baseline in High-Density Lipoprotein - Cholesterol (HDL-C) Week 28 (n=160, 161, 153)	4.712 percent change Standard Deviation 16.0076	6.117 percent change Standard Deviation 15.5220	2.975 percent change Standard Deviation 15.7048
Percent Change From Baseline in High-Density Lipoprotein - Cholesterol (HDL-C) Week 40 (n=160, 160, 151)	8.410 percent change Standard Deviation 18.0364	8.359 percent change Standard Deviation 15.6201	5.264 percent change Standard Deviation 15.6110

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

Population: Full analysis set with available data at each time point (indicated by "n").

Non-high-density lipoprotein cholesterol was calculated by subtracting high-density lipoprotein cholesterol from total cholesterol.

Outcome measures

Measure	TAK-085 2 g n=165 Participants TAK-085 2 g capsule, orally, once daily for up to 52 weeks.	TAK-085 4 g n=171 Participants TAK-085 2 g capsules, orally, twice daily for up to 52 weeks.	EPA-E 1.8 g n=167 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 52 weeks.
Percent Change From Baseline in Non-High-Density Lipoprotein - Cholesterol Week 12 (n=163, 168, 161)	-6.355 percent change Standard Deviation 11.1879	-9.665 percent change Standard Deviation 11.8662	-6.301 percent change Standard Deviation 12.7396
Percent Change From Baseline in Non-High-Density Lipoprotein - Cholesterol Week 16 (n=163, 167, 161)	-5.929 percent change Standard Deviation 13.2860	-9.674 percent change Standard Deviation 13.2498	-6.102 percent change Standard Deviation 15.3247
Percent Change From Baseline in Non-High-Density Lipoprotein - Cholesterol Week 20 (n=162, 166, 157)	-7.329 percent change Standard Deviation 12.1200	-9.169 percent change Standard Deviation 12.6390	-6.941 percent change Standard Deviation 14.3629
Percent Change From Baseline in Non-High-Density Lipoprotein - Cholesterol Week 32 (n=160, 163, 151)	-4.373 percent change Standard Deviation 13.3296	-6.273 percent change Standard Deviation 14.3110	-4.186 percent change Standard Deviation 13.7872
Percent Change From Baseline in Non-High-Density Lipoprotein - Cholesterol Week 4 (n=165, 170, 167)	-4.406 percent change Standard Deviation 11.2322	-8.831 percent change Standard Deviation 12.2172	-3.885 percent change Standard Deviation 12.3062
Percent Change From Baseline in Non-High-Density Lipoprotein - Cholesterol Week 8 (n=164, 168, 165)	-4.836 percent change Standard Deviation 11.6718	-9.663 percent change Standard Deviation 11.6911	-4.185 percent change Standard Deviation 13.9301
Percent Change From Baseline in Non-High-Density Lipoprotein - Cholesterol Week 24 (n=159, 164, 155)	-6.911 percent change Standard Deviation 11.1228	-7.769 percent change Standard Deviation 13.3944	-5.842 percent change Standard Deviation 15.4628
Percent Change From Baseline in Non-High-Density Lipoprotein - Cholesterol Week 28 (n=160, 161, 153)	-4.396 percent change Standard Deviation 13.6832	-7.643 percent change Standard Deviation 13.3578	-5.219 percent change Standard Deviation 13.4854
Percent Change From Baseline in Non-High-Density Lipoprotein - Cholesterol Week 36 (n=158, 160, 151)	-5.256 percent change Standard Deviation 13.2490	-5.515 percent change Standard Deviation 14.4721	-3.574 percent change Standard Deviation 16.2259
Percent Change From Baseline in Non-High-Density Lipoprotein - Cholesterol Week 40 (n=160, 160, 151)	-4.285 percent change Standard Deviation 14.7340	-6.397 percent change Standard Deviation 14.1767	-4.907 percent change Standard Deviation 16.5866
Percent Change From Baseline in Non-High-Density Lipoprotein - Cholesterol Week 44 (n=160, 158, 150)	-3.270 percent change Standard Deviation 12.4442	-5.801 percent change Standard Deviation 13.3310	-4.134 percent change Standard Deviation 15.6056
Percent Change From Baseline in Non-High-Density Lipoprotein - Cholesterol Week 48 (n=157, 157, 148)	-4.796 percent change Standard Deviation 12.2273	-6.497 percent change Standard Deviation 14.6818	-4.088 percent change Standard Deviation 15.0735
Percent Change From Baseline in Non-High-Density Lipoprotein - Cholesterol Week 52 (n= 155, 154, 145)	-4.340 percent change Standard Deviation 13.7408	-5.255 percent change Standard Deviation 14.9219	-4.830 percent change Standard Deviation 13.5956

Adverse Events

TAK-085 2 g

Serious events: 5 serious events

Other events: 96 other events

Deaths: 0 deaths

TAK-085 4 g

Serious events: 10 serious events

Other events: 94 other events

Deaths: 0 deaths

EPA-E 1.8 g

Serious events: 7 serious events

Other events: 104 other events

Deaths: 0 deaths

Serious adverse events

Measure	TAK-085 2 g n=165 participants at risk TAK-085 2 g capsule, orally, once daily for up to 52 weeks.	TAK-085 4 g n=171 participants at risk TAK-085 2 g capsules, orally, twice daily for up to 52 weeks.	EPA-E 1.8 g n=167 participants at risk Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 52 weeks.
Infections and infestations Gastroenteritis viral	0.00% 0/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.58% 1/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Infections and infestations Peritonsillar abscess	0.61% 1/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Infections and infestations Pneumonia	0.00% 0/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.60% 1/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.58% 1/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cervix carcinoma	0.00% 0/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.60% 1/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Large intestine carcinoma	0.61% 1/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.58% 1/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Metabolism and nutrition disorders Dehydration	0.61% 1/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Psychiatric disorders Schizophrenia	0.00% 0/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.60% 1/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Nervous system disorders Autonomic nervous system imbalance	0.00% 0/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.60% 1/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Nervous system disorders Cerebral infarction	0.00% 0/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.58% 1/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Nervous system disorders Cervical myelopathy	0.00% 0/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.58% 1/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.58% 1/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Eye disorders Cataract	0.00% 0/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.58% 1/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Cardiac disorders Angina pectoris	0.00% 0/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.60% 1/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Cardiac disorders Atrial fibrillation	0.61% 1/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Cardiac disorders Coronary artery stenosis	0.00% 0/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.60% 1/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Vascular disorders Neurogenic shock	0.61% 1/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.61% 1/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Gastrointestinal disorders Duodenal ulcer	0.00% 0/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.58% 1/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Gastrointestinal disorders Inguinal hernia	0.00% 0/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.60% 1/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Hepatobiliary disorders Cholelithiasis	0.00% 0/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.58% 1/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Injury, poisoning and procedural complications Clavicle fracture	0.00% 0/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.58% 1/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	0.00% 0/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.

Other adverse events

Measure	TAK-085 2 g n=165 participants at risk TAK-085 2 g capsule, orally, once daily for up to 52 weeks.	TAK-085 4 g n=171 participants at risk TAK-085 2 g capsules, orally, twice daily for up to 52 weeks.	EPA-E 1.8 g n=167 participants at risk Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 52 weeks.
Infections and infestations Nasopharyngitis	34.5% 57/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	25.1% 43/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	25.1% 42/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Infections and infestations Pharyngitis	8.5% 14/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	8.8% 15/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	9.0% 15/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Infections and infestations Bronchitis	5.5% 9/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	4.1% 7/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	5.4% 9/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Immune system disorders Seasonal allergy	3.6% 6/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	3.5% 6/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	5.4% 9/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Metabolism and nutrition disorders Diabetes mellitus	1.8% 3/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	5.3% 9/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	5.4% 9/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	7.3% 12/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	11.1% 19/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	8.4% 14/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Gastrointestinal disorders Diarrhoea	4.8% 8/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	5.3% 9/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	5.4% 9/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Gastrointestinal disorders Dental caries	1.2% 2/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	5.3% 9/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	1.8% 3/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Musculoskeletal and connective tissue disorders Back pain	4.2% 7/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	4.7% 8/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	7.2% 12/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Investigations Blood creatine phosphokinase increased	7.9% 13/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	4.1% 7/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	10.8% 18/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.
Investigations Liver function test abnormal	6.1% 10/165 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	4.1% 7/171 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.	3.6% 6/167 • Collection of AEs commenced from the time that the participant was first administered investigational product (Week 0) until the completion of study treatment (52 weeks of administration) At each study visit, the investigator or subinvestigator assessed whether any AEs had occurred. A neutral question, such as "How have you been feeling since your last visit?" asked. Participants reported AEs occurring at any other time during the study.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee The clinical trial contract states that information should never be disclosed without prior consent of the sponsor, although it does not specify the number of days during which disclosure of information is limited.
• Publication restrictions are in place

Restriction type: OTHER