Trial Outcomes & Findings for Efficacy of TAK-085 in Participants With Hypertriglyceridemia (NCT NCT01350973)

NCT ID: NCT01350973

Last Updated: 2016-09-20

Results Overview

The percentage change between triglycerides collected at the end of study drug administration (the end of treatment period or discontinuation) relative to Baseline. Analysis of Covariance (ANCOVA) model was employed, using the Baseline triglyceride level as covariate and the treatment group as an independent variable.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 611 participants
• Primary outcome timeframe: Baseline and 12 weeks
• Results posted on: 2016-09-20

Participant Flow

Participants took part in the study at 69 investigational sites in Japan from 21 November 2009 to 28 December 2010.

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, orally, once daily for up to 12 weeks.	TAK-085 4 g TAK-085 2 g, orally, twice daily for up to 12 weeks.	EPA-E 1.8 g Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 12 weeks.
Overall Study STARTED	206	210	195
Overall Study Received Treatment	205	210	195
Overall Study COMPLETED	200	202	187
Overall Study NOT COMPLETED	6	8	8

Reasons for withdrawal

Measure	TAK-085 2 g TAK-085 2 g, orally, once daily for up to 12 weeks.	TAK-085 4 g TAK-085 2 g, orally, twice daily for up to 12 weeks.	EPA-E 1.8 g Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 12 weeks.
Overall Study Adverse Event	4	7	7
Overall Study Voluntary Withdrawal	2	1	1

Baseline Characteristics

Efficacy of TAK-085 in Participants With Hypertriglyceridemia

Baseline characteristics by cohort

Measure	TAK-085 2 g n=206 Participants TAK-085 2 g, orally, once daily for up to 12 weeks.	TAK-085 4 g n=210 Participants TAK-085 2 g, orally, twice daily for up to 12 weeks.	EPA-E 1.8 g n=195 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 12 weeks.	Total n=611 Participants Total of all reporting groups
Age, Continuous	53.9 years STANDARD_DEVIATION 10.76 • n=5 Participants	55.0 years STANDARD_DEVIATION 10.50 • n=7 Participants	55.6 years STANDARD_DEVIATION 10.52 • n=5 Participants	54.8 years STANDARD_DEVIATION 10.60 • n=4 Participants
Age, Customized ≥20 - <65 years	168 participants n=5 Participants	169 participants n=7 Participants	148 participants n=5 Participants	485 participants n=4 Participants
Age, Customized ≥65 - ≤74 years	38 participants n=5 Participants	41 participants n=7 Participants	47 participants n=5 Participants	126 participants n=4 Participants
Sex: Female, Male Female	46 Participants n=5 Participants	53 Participants n=7 Participants	38 Participants n=5 Participants	137 Participants n=4 Participants
Sex: Female, Male Male	160 Participants n=5 Participants	157 Participants n=7 Participants	157 Participants n=5 Participants	474 Participants n=4 Participants
Region of Enrollment Japan	206 participants n=5 Participants	210 participants n=7 Participants	195 participants n=5 Participants	611 participants n=4 Participants
Menopause Status Yes	36 participants n=5 Participants	42 participants n=7 Participants	31 participants n=5 Participants	109 participants n=4 Participants
Menopause Status No	8 participants n=5 Participants	6 participants n=7 Participants	6 participants n=5 Participants	20 participants n=4 Participants
Menopause Status Not Applicable	162 participants n=5 Participants	162 participants n=7 Participants	158 participants n=5 Participants	482 participants n=4 Participants
Height, Categorical <160 cm	49 participants n=5 Participants	49 participants n=7 Participants	41 participants n=5 Participants	139 participants n=4 Participants
Height, Categorical ≥160 - <170 cm	91 participants n=5 Participants	86 participants n=7 Participants	78 participants n=5 Participants	255 participants n=4 Participants
Height, Categorical ≥170 cm	66 participants n=5 Participants	75 participants n=7 Participants	76 participants n=5 Participants	217 participants n=4 Participants
Height	165.5 cm STANDARD_DEVIATION 8.60 • n=5 Participants	165.7 cm STANDARD_DEVIATION 8.64 • n=7 Participants	166.0 cm STANDARD_DEVIATION 8.89 • n=5 Participants	165.7 cm STANDARD_DEVIATION 8.69 • n=4 Participants
Weight, Categorical <60.0 kg	33 participants n=5 Participants	33 participants n=7 Participants	33 participants n=5 Participants	99 participants n=4 Participants
Weight, Categorical ≥60.0 - <70.0 kg	58 participants n=5 Participants	61 participants n=7 Participants	58 participants n=5 Participants	177 participants n=4 Participants
Weight, Categorical ≥70.0 - <80.0 kg	56 participants n=5 Participants	68 participants n=7 Participants	49 participants n=5 Participants	173 participants n=4 Participants
Weight, Categorical ≥80.0 kg	58 participants n=5 Participants	48 participants n=7 Participants	55 participants n=5 Participants	161 participants n=4 Participants
Weight	73.04 kg STANDARD_DEVIATION 13.139 • n=5 Participants	72.20 kg STANDARD_DEVIATION 12.435 • n=7 Participants	72.90 kg STANDARD_DEVIATION 13.375 • n=5 Participants	72.71 kg STANDARD_DEVIATION 12.962 • n=4 Participants
Body Mass Index (BMI), Categorical <25.0 kg/m^2	75 participants n=5 Participants	89 participants n=7 Participants	69 participants n=5 Participants	233 participants n=4 Participants
Body Mass Index (BMI), Categorical ≥25.0 - <30.0 kg/m^2	94 participants n=5 Participants	93 participants n=7 Participants	99 participants n=5 Participants	286 participants n=4 Participants
Body Mass Index (BMI), Categorical ≥30.0 kg/m^2	36 participants n=5 Participants	28 participants n=7 Participants	27 participants n=5 Participants	91 participants n=4 Participants
Body Mass Index	26.55 kg/m^2 STANDARD_DEVIATION 3.658 • n=5 Participants	26.26 kg/m^2 STANDARD_DEVIATION 3.846 • n=7 Participants	26.34 kg/m^2 STANDARD_DEVIATION 3.628 • n=5 Participants	26.38 kg/m^2 STANDARD_DEVIATION 3.710 • n=4 Participants
Smoking Classification Never Smoked	60 participants n=5 Participants	66 participants n=7 Participants	54 participants n=5 Participants	180 participants n=4 Participants
Smoking Classification Current Smoker	78 participants n=5 Participants	76 participants n=7 Participants	69 participants n=5 Participants	223 participants n=4 Participants
Smoking Classification Ex-Smoker	68 participants n=5 Participants	68 participants n=7 Participants	72 participants n=5 Participants	208 participants n=4 Participants
Waist Circumference, Categorical Male <85.0 cm	23 participants n=5 Participants	26 participants n=7 Participants	32 participants n=5 Participants	81 participants n=4 Participants
Waist Circumference, Categorical Male ≥85.0 cm	136 participants n=5 Participants	131 participants n=7 Participants	125 participants n=5 Participants	392 participants n=4 Participants
Waist Circumference, Categorical Female <90.0 cm	25 participants n=5 Participants	30 participants n=7 Participants	25 participants n=5 Participants	80 participants n=4 Participants
Waist Circumference, Categorical Female ≥90.0 cm	21 participants n=5 Participants	23 participants n=7 Participants	13 participants n=5 Participants	57 participants n=4 Participants
Waist Circumference	91.85 cm STANDARD_DEVIATION 8.901 • n=5 Participants	91.24 cm STANDARD_DEVIATION 9.376 • n=7 Participants	91.51 cm STANDARD_DEVIATION 9.232 • n=5 Participants	91.53 cm STANDARD_DEVIATION 9.161 • n=4 Participants
Coronary Artery Disease (CAD) Category Category I	6 participants n=5 Participants	15 participants n=7 Participants	4 participants n=5 Participants	25 participants n=4 Participants
Coronary Artery Disease (CAD) Category Category II	95 participants n=5 Participants	70 participants n=7 Participants	79 participants n=5 Participants	244 participants n=4 Participants
Coronary Artery Disease (CAD) Category Category III	102 participants n=5 Participants	124 participants n=7 Participants	110 participants n=5 Participants	336 participants n=4 Participants
Coronary Artery Disease (CAD) Category History of CAD	3 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	6 participants n=4 Participants
Hypertension Yes	123 participants n=5 Participants	127 participants n=7 Participants	131 participants n=5 Participants	381 participants n=4 Participants
Hypertension No	83 participants n=5 Participants	83 participants n=7 Participants	64 participants n=5 Participants	230 participants n=4 Participants
Diabetes Mellitus (Including Impaired Glucose Tolerance) Yes	62 participants n=5 Participants	70 participants n=7 Participants	67 participants n=5 Participants	199 participants n=4 Participants
Diabetes Mellitus (Including Impaired Glucose Tolerance) No	144 participants n=5 Participants	140 participants n=7 Participants	128 participants n=5 Participants	412 participants n=4 Participants
Low High Density Lipoprotein - Cholesterol (HDL-C) Yes	58 participants n=5 Participants	56 participants n=7 Participants	60 participants n=5 Participants	174 participants n=4 Participants
Low High Density Lipoprotein - Cholesterol (HDL-C) No	148 participants n=5 Participants	154 participants n=7 Participants	135 participants n=5 Participants	437 participants n=4 Participants
Administration of 3-hydroxy 3-methylglutaryl coenzyme A (HMGCoA) Reductase Inhibitor Yes	89 participants n=5 Participants	89 participants n=7 Participants	83 participants n=5 Participants	261 participants n=4 Participants
Administration of 3-hydroxy 3-methylglutaryl coenzyme A (HMGCoA) Reductase Inhibitor No	117 participants n=5 Participants	121 participants n=7 Participants	112 participants n=5 Participants	350 participants n=4 Participants
Triglycerides, Categorical <150 mg/dL	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Triglycerides, Categorical ≥150 - <300 mg/dL	143 participants n=5 Participants	146 participants n=7 Participants	135 participants n=5 Participants	424 participants n=4 Participants
Triglycerides, Categorical ≥300 - <500 mg/dL	59 participants n=5 Participants	57 participants n=7 Participants	51 participants n=5 Participants	167 participants n=4 Participants
Triglycerides, Categorical ≥500 mg/dL	3 participants n=5 Participants	7 participants n=7 Participants	8 participants n=5 Participants	18 participants n=4 Participants
Triglycerides	269.0 mg/dL STANDARD_DEVIATION 77.52 • n=5 Participants	277.5 mg/dL STANDARD_DEVIATION 97.29 • n=7 Participants	271.8 mg/dL STANDARD_DEVIATION 91.53 • n=5 Participants	272.8 mg/dL STANDARD_DEVIATION 89.12 • n=4 Participants
Low Density Lipoprotein - Cholesterol (LDL-C), Categorical <140 mg/dL	140 participants n=5 Participants	149 participants n=7 Participants	124 participants n=5 Participants	413 participants n=4 Participants
Low Density Lipoprotein - Cholesterol (LDL-C), Categorical ≥140 mg/dL	65 participants n=5 Participants	61 participants n=7 Participants	71 participants n=5 Participants	197 participants n=4 Participants
Low Density Lipoprotein - Cholesterol (LDL-C)	127.4 mg/dL STANDARD_DEVIATION 29.08 • n=5 Participants	125.7 mg/dL STANDARD_DEVIATION 28.50 • n=7 Participants	130.1 mg/dL STANDARD_DEVIATION 30.54 • n=5 Participants	127.7 mg/dL STANDARD_DEVIATION 29.37 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline and 12 weeks

Population: Full analysis set including all participants who were randomized and received at least one dose of the investigational product and with available data.

The percentage change between triglycerides collected at the end of study drug administration (the end of treatment period or discontinuation) relative to Baseline. Analysis of Covariance (ANCOVA) model was employed, using the Baseline triglyceride level as covariate and the treatment group as an independent variable.

Outcome measures

Measure	TAK-085 2 g n=203 Participants TAK-085 2 g, orally, once daily for up to 12 weeks.	TAK-085 4 g n=208 Participants TAK-085 2 g, orally, twice daily for up to 12 weeks.	EPA-E 1.8 g n=194 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 12 weeks.
Percent Change From Baseline in Triglyceride Level at the Final Visit	-10.93 percent change Standard Error 1.6434 • Interval -14.161 to -7.7062	-22.65 percent change Standard Error 1.6238 • Interval -25.8436 to -19.4655	-11.30 percent change Standard Error 1.6807 • Interval -14.6014 to -7.9998

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 10 and 12

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

The percentage change between triglycerides collected at each study visit relative to Baseline.

Outcome measures

Measure	TAK-085 2 g n=205 Participants TAK-085 2 g, orally, once daily for up to 12 weeks.	TAK-085 4 g n=210 Participants TAK-085 2 g, orally, twice daily for up to 12 weeks.	EPA-E 1.8 g n=195 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 12 weeks.
Percent Change From Baseline in Triglyceride Level Over Time Week 4 (n=203, 208, 192)	-13.085 percent change Standard Deviation 26.4479	-26.939 percent change Standard Deviation 20.9540	-11.417 percent change Standard Deviation 27.8599
Percent Change From Baseline in Triglyceride Level Over Time Week 8 (n=199, 205, 191)	-12.055 percent change Standard Deviation 23.5955	-22.501 percent change Standard Deviation 29.7039	-11.321 percent change Standard Deviation 29.6792
Percent Change From Baseline in Triglyceride Level Over Time Week 10 (n=198, 202, 188)	-9.707 percent change Standard Deviation 25.9148	-23.436 percent change Standard Deviation 31.7008	-11.416 percent change Standard Deviation 28.4762
Percent Change From Baseline in Triglyceride Level Over Time Week 12 (n=198, 199, 185)	-11.707 percent change Standard Deviation 27.6764	-22.606 percent change Standard Deviation 25.1665	-12.431 percent change Standard Deviation 31.0903

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 10 and 12

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

The percentage change between low-density lipoprotein cholesterol collected at each study visit relative to Baseline. Low-density lipoprotein cholesterol particles measured directly by nuclear magnetic resonance.

Outcome measures

Measure	TAK-085 2 g n=205 Participants TAK-085 2 g, orally, once daily for up to 12 weeks.	TAK-085 4 g n=210 Participants TAK-085 2 g, orally, twice daily for up to 12 weeks.	EPA-E 1.8 g n=195 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 12 weeks.
Percent Change From Baseline in Low-Density Lipoprotein - Cholesterol (LDL-C) Level Over Time Week 4 (n=203, 208, 194)	1.120 percent change Standard Deviation 16.0172	2.262 percent change Standard Deviation 15.5408	-3.409 percent change Standard Deviation 13.5003
Percent Change From Baseline in Low-Density Lipoprotein - Cholesterol (LDL-C) Level Over Time Week 8 (n=200, 205, 191)	-0.846 percent change Standard Deviation 15.5473	-0.420 percent change Standard Deviation 17.7696	-3.008 percent change Standard Deviation 13.8462
Percent Change From Baseline in Low-Density Lipoprotein - Cholesterol (LDL-C) Level Over Time Week 10 (n=199, 202, 188)	-3.055 percent change Standard Deviation 15.6128	-0.862 percent change Standard Deviation 18.0310	-4.297 percent change Standard Deviation 14.0827
Percent Change From Baseline in Low-Density Lipoprotein - Cholesterol (LDL-C) Level Over Time Week 12 (n=199, 200, 187)	-1.639 percent change Standard Deviation 16.3582	-1.056 percent change Standard Deviation 18.2732	-3.393 percent change Standard Deviation 17.2972

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 10 and 12

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

The percentage change between total cholesterol measured at each study visit relative to Baseline.

Outcome measures

Measure	TAK-085 2 g n=205 Participants TAK-085 2 g, orally, once daily for up to 12 weeks.	TAK-085 4 g n=210 Participants TAK-085 2 g, orally, twice daily for up to 12 weeks.	EPA-E 1.8 g n=195 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 12 weeks.
Percent Change From Baseline in Total Cholesterol Over Time Week 4 (n=203, 208, 194)	-0.841 percent change Standard Deviation 10.0601	-2.707 percent change Standard Deviation 9.0969	-3.152 percent change Standard Deviation 8.1026
Percent Change From Baseline in Total Cholesterol Over Time Week 8 (n=200, 205, 191)	-1.996 percent change Standard Deviation 9.5190	-2.887 percent change Standard Deviation 9.7964	-3.097 percent change Standard Deviation 9.2770
Percent Change From Baseline in Total Cholesterol Over Time Week 10 (n=199, 202, 188)	-3.054 percent change Standard Deviation 9.0927	-3.949 percent change Standard Deviation 10.5345	-4.355 percent change Standard Deviation 9.1420
Percent Change From Baseline in Total Cholesterol Over Time Week 12 (n=199, 200, 187)	-2.649 percent change Standard Deviation 9.4133	-3.243 percent change Standard Deviation 10.6025	-3.880 percent change Standard Deviation 10.8594

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 10 and 12

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

The percentage change between high-density lipoprotein cholesterol collected at each study visit relative to Baseline.

Outcome measures

Measure	TAK-085 2 g n=205 Participants TAK-085 2 g, orally, once daily for up to 12 weeks.	TAK-085 4 g n=210 Participants TAK-085 2 g, orally, twice daily for up to 12 weeks.	EPA-E 1.8 g n=195 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 12 weeks.
Percent Change From Baseline in High-Density Lipoprotein - Cholesterol (HDL-C) Level Over Time Week 12 (n=199, 200, 187)	2.685 percent change Standard Deviation 10.8647	4.564 percent change Standard Deviation 12.7497	1.741 percent change Standard Deviation 10.8185
Percent Change From Baseline in High-Density Lipoprotein - Cholesterol (HDL-C) Level Over Time Week 4 (n=203, 208, 194)	2.990 percent change Standard Deviation 10.5365	4.075 percent change Standard Deviation 10.9735	0.934 percent change Standard Deviation 11.6203
Percent Change From Baseline in High-Density Lipoprotein - Cholesterol (HDL-C) Level Over Time Week 8 (n=200, 205, 191)	1.547 percent change Standard Deviation 11.6333	3.936 percent change Standard Deviation 12.4198	1.826 percent change Standard Deviation 10.1747
Percent Change From Baseline in High-Density Lipoprotein - Cholesterol (HDL-C) Level Over Time Week 10 (n=199, 202, 188)	2.258 percent change Standard Deviation 10.6907	4.219 percent change Standard Deviation 12.0895	1.860 percent change Standard Deviation 11.0573

SECONDARY outcome

Timeframe: Baseline and Weeks 4, 8, 10 and 12

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

The percentage change between non-high-density lipoprotein cholesterol collected at each study visit relative to Baseline. Non-high-density lipoprotein cholesterol calculated by subtracting high-density lipoprotein cholesterol from total cholesterol.

Outcome measures

Measure	TAK-085 2 g n=205 Participants TAK-085 2 g, orally, once daily for up to 12 weeks.	TAK-085 4 g n=210 Participants TAK-085 2 g, orally, twice daily for up to 12 weeks.	EPA-E 1.8 g n=195 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 12 weeks.
Percent Change From Baseline in Non-High-Density Lipoprotein - Cholesterol Level Over Time Week 8 (n=200, 205, 191)	-3.022 percent change Standard Deviation 11.2524	-4.931 percent change Standard Deviation 11.9003	-4.418 percent change Standard Deviation 11.5415
Percent Change From Baseline in Non-High-Density Lipoprotein - Cholesterol Level Over Time Week 4 (n=203, 208, 194)	-1.955 percent change Standard Deviation 12.7395	-4.634 percent change Standard Deviation 11.3386	-4.274 percent change Standard Deviation 10.8403
Percent Change From Baseline in Non-High-Density Lipoprotein - Cholesterol Level Over Time Week 10 (n=199, 202, 188)	-4.624 percent change Standard Deviation 11.2058	-6.190 percent change Standard Deviation 12.9755	-5.994 percent change Standard Deviation 11.1866
Percent Change From Baseline in Non-High-Density Lipoprotein - Cholesterol Level Over Time Week 12 (n=199, 200, 187)	-4.159 percent change Standard Deviation 11.5205	-5.384 percent change Standard Deviation 13.2602	-5.140 percent change Standard Deviation 14.3444

SECONDARY outcome

Timeframe: 12 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=205 Participants TAK-085 2 g, orally, once daily for up to 12 weeks.	TAK-085 4 g n=210 Participants TAK-085 2 g, orally, twice daily for up to 12 weeks.	EPA-E 1.8 g n=195 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 12 weeks.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	88 participants	76 participants	83 participants

SECONDARY outcome

Timeframe: 12 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=205 Participants TAK-085 2 g, orally, once daily for up to 12 weeks.	TAK-085 4 g n=210 Participants TAK-085 2 g, orally, twice daily for up to 12 weeks.	EPA-E 1.8 g n=195 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 12 weeks.
Number of Participants With TEAEs Associated With Abnormal Changes in Vital Signs	1 participants 10.81	0 participants 10.61	0 participants 10.92

SECONDARY outcome

Timeframe: 12 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=205 Participants TAK-085 2 g, orally, once daily for up to 12 weeks.	TAK-085 4 g n=210 Participants TAK-085 2 g, orally, twice daily for up to 12 weeks.	EPA-E 1.8 g n=195 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 12 weeks.
Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis	11 participants	11 participants	7 participants

SECONDARY outcome

Timeframe: 12 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=205 Participants TAK-085 2 g, orally, once daily for up to 12 weeks.	TAK-085 4 g n=210 Participants TAK-085 2 g, orally, twice daily for up to 12 weeks.	EPA-E 1.8 g n=195 Participants Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 12 weeks.
Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings After Study Drug Administration	0 participants	0 participants	0 participants

Adverse Events

TAK-085 2 g

Serious events: 1 serious events

Other events: 22 other events

Deaths: 0 deaths

TAK-085 4 g

Serious events: 4 serious events

Other events: 9 other events

Deaths: 0 deaths

EPA-E 1.8 g

Serious events: 2 serious events

Other events: 20 other events

Deaths: 0 deaths

Serious adverse events

Measure	TAK-085 2 g n=205 participants at risk TAK-085 2 g, orally, once daily for up to 12 weeks.	TAK-085 4 g n=210 participants at risk TAK-085 2 g, orally, twice daily for up to 12 weeks.	EPA-E 1.8 g n=195 participants at risk Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 12 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelofibrosis	0.49% 1/205 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) 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.	0.00% 0/210 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) 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.	0.00% 0/195 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/205 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) 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.	0.48% 1/210 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) 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.	0.00% 0/195 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.00% 0/205 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) 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.	0.48% 1/210 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) 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.	0.00% 0/195 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/205 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) 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.	0.00% 0/210 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) 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.	0.51% 1/195 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Cerebral infarction	0.00% 0/205 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) 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.	0.00% 0/210 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) 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.	0.51% 1/195 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders VIIth nerve paralysis	0.00% 0/205 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) 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.	0.48% 1/210 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) 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.	0.00% 0/195 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Calculus ureteric	0.00% 0/205 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) 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.	0.48% 1/210 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) 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.	0.00% 0/195 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Contusion	0.00% 0/205 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) 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.	0.48% 1/210 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) 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.	0.00% 0/195 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Measure	TAK-085 2 g n=205 participants at risk TAK-085 2 g, orally, once daily for up to 12 weeks.	TAK-085 4 g n=210 participants at risk TAK-085 2 g, orally, twice daily for up to 12 weeks.	EPA-E 1.8 g n=195 participants at risk Eicosapentaenoic acid-ethyl (EPA-E) capsule 0.6 g, orally, three-times daily for up to 12 weeks.
Infections and infestations Nasopharyngitis	10.7% 22/205 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) 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.	4.3% 9/210 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) 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.	10.3% 20/195 • Collection of AEs commenced from the time that the subject was first administered investigational product (Week 0). Routine collection of AEs continued until the completion of study treatment (12 weeks of administration) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: trialdisclosures@takeda.com

Results disclosure agreements

• Principal investigator is a sponsor employee The 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