Trial Outcomes & Findings for Study to Evaluate the Efficacy and Safety of K-877 in Adult Patients With Fasting High Triglyceride Levels and Mild or Moderate Renal Impairment (NCT NCT03011450)

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

471 participants

Primary outcome timeframe

12 Weeks

Results posted on

2022-10-28

Participant Flow

Eligible patients entered a 4- to 6-week lifestyle stabilization period. The stabilization period was followed by a 2-week TG qualifying period, and patient eligibility was assessed based on the mean TG value from these 2 visits. If the patient's mean TG level during the TG qualifying period was ≥450 mg/dL (5.09 mmol/L) and \<500 mg/dL (5.65 mmol/L), an additional TG measurement was taken 1 week later at Visit 3.1. The mean of all 3 TG measurements was used to determine eligibility for the study.

Participant milestones

Participant milestones
Measure	K-877 Participants randomized to receive K-877 0.2 mg tablets twice daily in the 12-week Efficacy Period continued to receive K-877 0.2 mg tablets BID in the 40-week Extension Period	Placebo/Fenofibrate Patients randomized to receive placebo matching K-877 0.2 mg BID in the 12-week Efficacy Period initiated fenofibrate dosing at 48 mg once daily at Visit 7 (Week 12). Starting from Visit 8 (Week 16), Investigators were allowed to adjust fenofibrate dosing (to 145 mg once daily) at their discretion according to the local standard of care.
12-week Efficacy STARTED	311	159
12-week Efficacy COMPLETED	299	159
12-week Efficacy NOT COMPLETED	12	0
40-week Extension STARTED	292	154
40-week Extension COMPLETED	275	146
40-week Extension NOT COMPLETED	17	8

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study to Evaluate the Efficacy and Safety of K-877 in Adult Patients With Fasting High Triglyceride Levels and Mild or Moderate Renal Impairment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo/Fenofibrate n=159 Participants Patients randomized to receive placebo matching K-877 0.2 mg BID in the 12-week Efficacy Period initiated fenofibrate dosing at 48 mg once daily at Visit 7 (Week 12). Starting from Visit 8 (Week 16), Investigators were allowed to adjust fenofibrate dosing (to 145 mg once daily) at their discretion according to the local standard of care.	Total n=470 Participants Total of all reporting groups
Age, Customized <65 years	220 Participants n=5 Participants	119 Participants n=7 Participants	339 Participants n=5 Participants
Age, Customized ≥65 years	91 Participants n=5 Participants	40 Participants n=7 Participants	131 Participants n=5 Participants
Sex: Female, Male Female	94 Participants n=5 Participants	40 Participants n=7 Participants	134 Participants n=5 Participants
Sex: Female, Male Male	217 Participants n=5 Participants	119 Participants n=7 Participants	336 Participants n=5 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White	302 Participants n=5 Participants	157 Participants n=7 Participants	459 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	12 Participants n=5 Participants	7 Participants n=7 Participants	19 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	299 Participants n=5 Participants	151 Participants n=7 Participants	450 Participants n=5 Participants
Race/Ethnicity, Customized Not reported/unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Triglycerides	793.44 mg/dL STANDARD_DEVIATION 390.102 • n=5 Participants	759.36 mg/dL STANDARD_DEVIATION 395.359 • n=7 Participants	781.45 mg/dL STANDARD_DEVIATION 391.511 • n=5 Participants

PRIMARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change in Fasting TG From Baseline to Week 12	-58.89 Percent change Interval -71.69 to -38.42	-22.94 Percent change Interval -43.98 to 9.67

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Remnant Cholesterol	-55.51 Percent change Interval -71.29 to -33.64	-13.29 Percent change Interval -43.3 to 9.76

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in HDL-C	23.50 Percent change Interval 5.24 to 45.13	7.33 Percent change Interval -4.0 to 18.79

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Apo A1	4.05 Percent change Interval -5.57 to 14.62	0.00 Percent change Interval -7.8 to 10.01

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Non-HDL-C	-20.98 Percent change Interval -34.7 to -4.06	-3.43 Percent change Interval -23.66 to 6.75

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Total Cholesterol	-14.55 Percent change Interval -25.74 to -1.19	-2.05 Percent change Interval -17.59 to 7.37

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in LDL-C	31.49 Percent change Interval 0.65 to 72.06	2.30 Percent change Interval -14.5 to 23.09

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=303 Participants K-877 0.2 mg Tablets	Placebo n=154 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in FFAs	-25.25 Percent change Interval -48.37 to 3.74	-5.51 Percent change Interval -32.64 to 28.65

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Apo A2	19.34 Percent change Interval 7.27 to 35.41	0.00 Percent change Interval -8.09 to 6.38

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Apo B	0.57 Percent change Interval -14.9 to 16.66	-1.67 Percent change Interval -11.71 to 12.54

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Apo B48	-36.64 Percent change Interval -71.42 to 17.61	19.91 Percent change Interval -18.96 to 101.41

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Apo B100	2.05 Percent change Interval -13.31 to 18.13	-2.33 Percent change Interval -14.42 to 12.14

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Apo C2	-4.70 Percent change Interval -27.33 to 0.0	0.00 Percent change Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Apo C3	-41.97 Percent change Interval -54.44 to -21.64	-3.10 Percent change Interval -25.16 to 18.08

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Apo E	-29.09 Percent change Interval -44.73 to -6.92	-5.98 Percent change Interval -28.29 to 12.15

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 12 in FGF21	277.97 pg/mL Interval 37.31 to 650.73	12.15 pg/mL Interval -162.8 to 112.46

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 12 in hsCRP	-0.201 mg/L Interval -1.355 to 0.685	-0.100 mg/L Interval -1.235 to 0.821

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Ion Mobility (VLDL Cholesterol-Large)	-36.45 Percent change Interval -55.39 to -5.31	-5.95 Percent change Interval -27.52 to 30.89

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Ion Mobility (VLDL Cholesterol-Intermediate)	-23.23 Percent change Interval -42.1 to 1.79	0.07 Percent change Interval -18.32 to 25.73

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Ion Mobility (VLDL Cholesterol-Small)	-6.07 Percent change Interval -24.09 to 9.75	4.16 Percent change Interval -12.56 to 21.97

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Ion Mobility (Intermediate Density Lipoproteins 1)	-0.22 Percent change Interval -17.02 to 22.34	2.42 Percent change Interval -9.7 to 17.69

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Ion Mobility (Intermediate Density Lipoproteins 2)	17.52 Percent change Interval -2.0 to 39.87	3.21 Percent change Interval -9.58 to 17.69

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Ion Mobility (Low Density Lipoproteins I)	44.20 Percent change Interval 10.67 to 89.89	4.81 Percent change Interval -11.65 to 25.3

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Ion Mobility (Low Density Lipoproteins IIa)	53.94 Percent change Interval 14.68 to 112.53	4.24 Percent change Interval -16.31 to 23.16

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Ion Mobility (Low Density Lipoproteins IIb)	48.44 Percent change Interval 8.96 to 110.09	1.89 Percent change Interval -14.54 to 23.96

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Ion Mobility (Low Density Lipoproteins IIIa)	23.79 Percent change Interval -19.17 to 76.61	-0.80 Percent change Interval -13.28 to 17.39

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Ion Mobility (Low Density Lipoproteins IIIb)	-5.73 Percent change Interval -48.62 to 47.19	0.71 Percent change Interval -21.79 to 16.61

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Ion Mobility (Low Density Lipoproteins IVa)	-30.48 Percent change Interval -59.53 to 7.01	-2.89 Percent change Interval -20.28 to 16.04

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Ion Mobility (Low Density Lipoproteins IVb)	-35.08 Percent change Interval -54.14 to -15.21	-0.74 Percent change Interval -21.22 to 19.16

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Ion Mobility (Low Density Lipoproteins IVc)	-23.39 Percent change Interval -38.34 to -11.75	0.89 Percent change Interval -15.75 to 15.88

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Ion Mobility (High Density Lipoproteins 2b)	-10.65 Percent change Interval -19.15 to -0.88	0.91 Percent change Interval -9.59 to 11.6

SECONDARY outcome

Timeframe: 12 Weeks

Two lipoprotein subclasses, HDL3 and HDL2a, were analyzed together as one measurement without distinction.

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Ion Mobility (High Density Lipoproteins 3 and 2a)	-2.13 Percent change Interval -10.9 to 7.5	-0.53 Percent change Interval -8.5 to 9.19

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Ion Mobility (Diameter of the Major LDL Particle (Å))	2.67 Percent change Interval 0.9 to 4.73	0.14 Percent change Interval -0.6 to 0.89

SECONDARY outcome

Timeframe: 12 Weeks

Two types of lipoprotein particles were analyzed together as one measurement without distinction.

Outcome measures

Outcome measures
Measure	K-877 n=310 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Lipoprotein Fraction (VLDL & Chylomicron Particles)	-42.76 Percent change Interval -61.49 to -15.41	-5.59 Percent change Interval -29.0 to 24.71

SECONDARY outcome

Timeframe: 12 Weeks

Population: Since there were one or multiple records with a baseline value of 0, the percent change cannot be determined for such records. In such cases, the secondary endpoints were evaluated for change from baseline to week 12.

Two types of lipoprotein particles were analyzed together as one measurement without distinction.

Outcome measures

Outcome measures
Measure	K-877 n=310 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 12 in Lipoprotein Fraction (VLDL & Chylomicron Particles-Large)	-12.62 nmol/L Interval -31.63 to -3.27	-3.75 nmol/L Interval -18.37 to 8.3

SECONDARY outcome

Timeframe: 12 Weeks

Population: Since there were one or multiple records with a baseline value of 0, the percent change cannot be determined for such records. In such cases, the secondary endpoints were evaluated for change from baseline to week 12.

Outcome measures

Outcome measures
Measure	K-877 n=310 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 12 in Lipoprotein Fraction (VLDL Particles-Medium)	-41.27 nmol/L Interval -79.42 to -9.78	-9.13 nmol/L Interval -36.78 to 26.18

SECONDARY outcome

Timeframe: 12 Weeks

Population: Since there were one or multiple records with a baseline value of 0, the percent change cannot be determined for such records. In such cases, the secondary endpoints were evaluated for change from baseline to week 12.

Outcome measures

Outcome measures
Measure	K-877 n=310 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 12 in Lipoprotein Fraction (VLDL Particles-Small)	0.46 nmol/L Interval -25.09 to 20.86	0.07 nmol/L Interval -16.8 to 20.72

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=309 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Lipoprotein Fraction (LDL Particles)	17.58 Percent change Interval -13.32 to 60.38	4.97 Percent change Interval -15.42 to 25.3

SECONDARY outcome

Timeframe: 12 Weeks

Population: Since there were one or multiple records with a baseline value of 0, the percent change cannot be determined for such records. In such cases, the secondary endpoints were evaluated for change from baseline to week 12.

Outcome measures

Outcome measures
Measure	K-877 n=310 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 12 in Lipoprotein Fraction (IDL Particles)	-17.06 nmol/L Interval -123.66 to 39.24	-2.74 nmol/L Interval -87.3 to 76.76

SECONDARY outcome

Timeframe: 12 Weeks

Population: Since there were one or multiple records with a baseline value of 0, the percent change cannot be determined for such records. In such cases, the secondary endpoints were evaluated for change from baseline to week 12.

Outcome measures

Outcome measures
Measure	K-877 n=310 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 12 in Lipoprotein Fraction (LDL Particles-Large)	54.52 nmol/L Interval 0.0 to 306.49	0.00 nmol/L Interval -13.04 to 43.85

SECONDARY outcome

Timeframe: 12 Weeks

Population: Since there were one or multiple records with a baseline value of 0, the percent change cannot be determined for such records. In such cases, the secondary endpoints were evaluated for change from baseline to week 12.

Outcome measures

Outcome measures
Measure	K-877 n=310 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 12 in Lipoprotein Fraction (LDL Particles-Small)	83.88 nmol/L Interval -254.52 to 394.98	12.43 nmol/L Interval -135.98 to 230.34

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=310 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Lipoprotein Fraction (HDL Particles)	5.96 Percent change Interval -8.43 to 23.02	-1.60 Percent change Interval -13.63 to 11.21

SECONDARY outcome

Timeframe: 12 Weeks

Population: Since there were one or multiple records with a baseline value of 0, the percent change cannot be determined for such records. In such cases, the secondary endpoints were evaluated for change from baseline to week 12.

Outcome measures

Outcome measures
Measure	K-877 n=310 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 12 in Lipoprotein Fraction (HDL Particles-Large)	0.22 µmol/L Interval -0.94 to 1.56	0.00 µmol/L Interval -1.02 to 1.1

SECONDARY outcome

Timeframe: 12 Weeks

Population: Since there were one or multiple records with a baseline value of 0, the percent change cannot be determined for such records. In such cases, the secondary endpoints were evaluated for change from baseline to week 12.

Outcome measures

Outcome measures
Measure	K-877 n=310 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 12 in Lipoprotein Fraction (HDL Particles-Medium)	-0.21 µmol/L Interval -3.98 to 2.9	-0.23 µmol/L Interval -2.96 to 1.66

SECONDARY outcome

Timeframe: 12 Weeks

Population: Since there were one or multiple records with a baseline value of 0, the percent change cannot be determined for such records. In such cases, the secondary endpoints were evaluated for change from baseline to week 12.

Outcome measures

Outcome measures
Measure	K-877 n=310 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 12 in Lipoprotein Fraction (HDL Particles-Small)	1.54 µmol/L Interval -2.95 to 7.78	0.16 µmol/L Interval -4.19 to 4.35

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=310 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Lipoprotein Fraction (VLDL Particle Size)	-5.02 Percent change Interval -16.79 to 5.79	-2.26 Percent change Interval -11.03 to 7.6

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=305 Participants K-877 0.2 mg Tablets	Placebo n=157 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Lipoprotein Fraction (LDL Particle Size)	1.02 Percent change Interval 0.0 to 3.54	0.00 Percent change Interval -0.53 to 0.54

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=310 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Lipoprotein Fraction (HDL Particle Size)	-1.19 Percent Change Interval -4.48 to 2.36	-0.14 Percent Change Interval -3.22 to 2.36

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=310 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Lipoprotein Fraction (Triglyceride)	-54.86 Percent change Interval -70.9 to -31.38	-15.24 Percent change Interval -37.36 to 18.69

SECONDARY outcome

Timeframe: 12 Weeks

Two types of lipoprotein particles were analyzed together as one measurement without distinction.

Outcome measures

Outcome measures
Measure	K-877 n=310 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Lipoprotein Fraction (VLDL & Chylomicron Triglyceride)	-55.19 Percent change Interval -70.8 to -32.36	-16.20 Percent change Interval -37.74 to 21.7

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=305 Participants K-877 0.2 mg Tablets	Placebo n=154 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Lipoprotein Fraction HDL Cholesterol (Total)	5.51 Percent Change Interval -12.73 to 29.84	-2.20 Percent Change Interval -17.16 to 16.56

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Lipid and Lipoprotein Ratios of TG:HDL-C	-66.21 Percent change Interval -79.82 to -42.95	-26.81 Percent change Interval -51.86 to 13.12

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Lipid and Lipoprotein Ratios of TC:HDL-C	-32.36 Percent change Interval -47.83 to -10.34	-9.02 Percent change Interval -29.95 to 6.61

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Lipid and Lipoprotein Ratios of Non-HDL-C:HDL-C	-32.36 Percent change Interval -47.83 to -10.34	-9.02 Percent change Interval -29.95 to 6.61

SECONDARY outcome

Timeframe: 12 Weeks

Population: Since there were one or multiple records with a baseline value of 0, the percent change cannot be determined for such records. In such cases, the secondary endpoints were evaluated for change from baseline to week 12.

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 12 in Lipid and Lipoprotein Ratios of LDL-C:Apo B	0.219 Ratio Interval 0.05 to 0.359	0.026 Ratio Interval -0.096 to 0.138

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Lipid and Lipoprotein Ratios of Apo B:Apo A1	-1.68 Percent change Interval -19.68 to 17.39	-1.25 Percent change Interval -13.68 to 9.26

SECONDARY outcome

Timeframe: 12 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=311 Participants K-877 0.2 mg Tablets	Placebo n=159 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 12 in Lipid and Lipoprotein Ratios of Apo C3:Apo C2	-27.76 Percent change Interval -45.35 to -7.99	-0.47 Percent change Interval -23.52 to 17.9

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=146 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Fasting TG	-59.96 Percent change Interval -74.38 to -41.52	-49.55 Percent change Interval -64.8 to -26.83

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=269 Participants K-877 0.2 mg Tablets	Placebo n=145 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Remnant Cholesterol	-58.39 Percent change Interval -72.45 to -39.62	-43.31 Percent change Interval -60.66 to -24.59

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=146 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in HDL-C	18.78 Percent change Interval 3.03 to 38.46	15.59 Percent change Interval 5.26 to 32.35

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=143 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Apo A1	3.29 Percent change Interval -6.51 to 12.1	2.56 Percent change Interval -6.62 to 12.31

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=146 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Non-HDL-C	-21.80 Percent change Interval -37.89 to -6.95	-14.22 Percent change Interval -31.57 to 3.72

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=146 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in TC	-15.28 Percent change Interval -29.1 to -4.01	-8.64 Percent change Interval -23.55 to 5.08

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=269 Participants K-877 0.2 mg Tablets	Placebo n=145 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in LDL-C	31.90 Percent change Interval 0.0 to 76.62	22.96 Percent change Interval 1.41 to 51.68

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=219 Participants K-877 0.2 mg Tablets	Placebo n=127 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in FFAs	-21.61 Percent change Interval -46.76 to 8.15	-21.41 Percent change Interval -45.7 to -1.02

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=143 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Apo A2	15.92 Percent change Interval 3.23 to 31.25	8.33 Percent change Interval 0.0 to 20.69

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=143 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Apo B	-1.73 Percent change Interval -14.74 to 15.84	0.00 Percent change Interval -14.13 to 12.16

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=273 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Apo B48	-19.43 Percent change Interval -58.77 to 60.61	-15.19 Percent change Interval -51.08 to 112.6

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=273 Participants K-877 0.2 mg Tablets	Placebo n=143 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Apo B100	-1.32 Percent change Interval -15.58 to 17.35	-0.87 Percent change Interval -13.44 to 12.3

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=270 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Apo C2	-9.56 Percent change Interval -34.5 to 0.0	0.00 Percent change Interval -19.81 to 0.0

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=273 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Apo C3	-42.80 Percent change Interval -57.88 to -22.27	-26.25 Percent change Interval -44.64 to -2.73

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=143 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Apo E	-30.82 Percent change Interval -49.25 to -13.04	-30.00 Percent change Interval -42.59 to -9.76

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=145 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 52 in FGF21	371.80 pg/mL Interval 97.3 to 795.0	194.40 pg/mL Interval 57.0 to 524.1

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 52 in hsCRP	-0.100 mg/L Interval -1.4 to 0.9	-0.225 mg/L Interval -1.7 to 0.75

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Ion Mobility (VLDL Cholesterol-Large)	-36.60 Percent change Interval -57.18 to -9.94	-22.03 Percent change Interval -46.31 to 3.89

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Ion Mobility (VLDL Cholesterol-Intermediate)	-25.03 Percent change Interval -45.41 to -2.97	-13.31 Percent change Interval -32.85 to 10.2

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Ion Mobility (VLDL Cholesterol-Small)	-12.96 Percent change Interval -28.26 to 8.8	-2.31 Percent change Interval -21.61 to 17.28

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Ion Mobility (Intermediate Density Lipoproteins 1)	0.69 Percent change Interval -22.32 to 20.37	3.54 Percent change Interval -14.98 to 19.42

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Ion Mobility (Intermediate Density Lipoproteins 2)	17.33 Percent change Interval -4.92 to 45.07	15.87 Percent change Interval -3.79 to 33.13

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Ion Mobility (Low Density Lipoproteins I)	46.51 Percent change Interval 11.45 to 96.51	25.53 Percent change Interval 7.94 to 57.81

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Ion Mobility (Low Density Lipoproteins IIa)	61.36 Percent change Interval 18.02 to 121.43	33.66 Percent change Interval 8.36 to 69.06

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Ion Mobility (Low Density Lipoproteins IIb)	45.61 Percent change Interval 10.19 to 110.03	27.29 Percent change Interval 3.08 to 75.15

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Ion Mobility (Low Density Lipoproteins IIIa)	18.50 Percent change Interval -17.32 to 76.72	19.64 Percent change Interval -9.16 to 55.84

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Ion Mobility (Low Density Lipoproteins IIIb)	-6.92 Percent change Interval -46.06 to 44.1	1.17 Percent change Interval -33.87 to 37.07

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Ion Mobility (Low Density Lipoproteins IVa)	-25.63 Percent change Interval -59.65 to 4.76	-24.80 Percent change Interval -48.67 to 7.25

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Ion Mobility (Low Density Lipoproteins IVb)	-37.26 Percent change Interval -54.63 to -13.67	-24.22 Percent change Interval -46.23 to -7.72

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Ion Mobility (Low Density Lipoproteins IVc)	-26.81 Percent change Interval -39.69 to -12.43	-17.41 Percent change Interval -34.43 to -3.23

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Ion Mobility (High Density Lipoproteins 2b)	-11.67 Percent change Interval -21.85 to -0.44	-5.62 Percent change Interval -18.23 to 5.91

SECONDARY outcome

Timeframe: 52 Weeks

Two lipoprotein subclasses, HDL3 and HDL2a, were analyzed together as one measurement without distinction.

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Ion Mobility (High Density Lipoproteins 3 and 2a)	-4.62 Percent change Interval -13.84 to 5.23	-3.71 Percent change Interval -13.22 to 5.49

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Ion Mobility (Diameter of the Major LDL Particle (Å))	2.69 Percent change Interval 1.1 to 4.84	1.54 Percent change Interval 0.71 to 3.24

SECONDARY outcome

Timeframe: 52 Weeks

Two types of lipoprotein particles were analyzed together as one measurement without distinction.

Outcome measures

Outcome measures
Measure	K-877 n=258 Participants K-877 0.2 mg Tablets	Placebo n=137 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Lipoprotein Fraction (VLDL & Chylomicron Particles)	-40.10 Percent change Interval -63.62 to -14.91	-28.98 Percent change Interval -48.61 to -2.98

SECONDARY outcome

Timeframe: 52 Weeks

Population: Since there were one or multiple records with a baseline value of 0, the percent change cannot be determined for such records. In such cases, the secondary endpoints were evaluated for change from baseline to week 52.

Two types of lipoprotein particles were analyzed together as one measurement without distinction.

Outcome measures

Outcome measures
Measure	K-877 n=258 Participants K-877 0.2 mg Tablets	Placebo n=137 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 52 in Lipoprotein Fraction (VLDL & Chylomicron Particles-Large)	-13.00 nmol/L Interval -32.7 to -2.4	-8.60 nmol/L Interval -28.8 to -1.4

SECONDARY outcome

Timeframe: 52 Weeks

Population: Since there were one or multiple records with a baseline value of 0, the percent change cannot be determined for such records. In such cases, the secondary endpoints were evaluated for change from baseline to week 52.

Outcome measures

Outcome measures
Measure	K-877 n=258 Participants K-877 0.2 mg Tablets	Placebo n=137 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 52 in Lipoprotein Fraction (VLDL Particles-Medium)	-41.95 nmol/L Interval -77.2 to -5.1	-26.90 nmol/L Interval -64.8 to 4.8

SECONDARY outcome

Timeframe: 52 Weeks

Population: Since there were one or multiple records with a baseline value of 0, the percent change cannot be determined for such records. In such cases, the secondary endpoints were evaluated for change from baseline to week 52.

Outcome measures

Outcome measures
Measure	K-877 n=258 Participants K-877 0.2 mg Tablets	Placebo n=137 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 52 in Lipoprotein Fraction (VLDL Particles-Small)	-0.15 nmol/L Interval -18.1 to 19.6	0.00 nmol/L Interval -16.6 to 24.7

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=258 Participants K-877 0.2 mg Tablets	Placebo n=137 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Lipoprotein Fraction (LDL Particles)	14.43 Percent change Interval -10.07 to 62.78	12.79 Percent change Interval -11.69 to 43.15

SECONDARY outcome

Timeframe: 52 Weeks

Population: Since there were one or multiple records with a baseline value of 0, the percent change cannot be determined for such records. In such cases, the secondary endpoints were evaluated for change from baseline to week 52.

Outcome measures

Outcome measures
Measure	K-877 n=258 Participants K-877 0.2 mg Tablets	Placebo n=137 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 52 in Lipoprotein Fraction (IDL Particles)	-12.00 nmol/L Interval -151.0 to 53.0	-6.00 nmol/L Interval -127.0 to 57.0

SECONDARY outcome

Timeframe: 52 Weeks

Population: Since there were one or multiple records with a baseline value of 0, the percent change cannot be determined for such records. In such cases, the secondary endpoints were evaluated for change from baseline to week 52.

Outcome measures

Outcome measures
Measure	K-877 n=258 Participants K-877 0.2 mg Tablets	Placebo n=137 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 52 in Lipoprotein Fraction (LDL Particles-Large)	53.00 nmol/L Interval 0.0 to 273.0	8.00 nmol/L Interval 0.0 to 199.0

SECONDARY outcome

Timeframe: 52 Weeks

Population: Since there were one or multiple records with a baseline value of 0, the percent change cannot be determined for such records. In such cases, the secondary endpoints were evaluated for change from baseline to week 52.

Outcome measures

Outcome measures
Measure	K-877 n=258 Participants K-877 0.2 mg Tablets	Placebo n=137 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 52 in Lipoprotein Fraction (LDL Particles-Small)	59.00 nmol/L Interval -198.0 to 425.0	97.00 nmol/L Interval -209.0 to 420.0

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=258 Participants K-877 0.2 mg Tablets	Placebo n=137 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Lipoprotein Fraction (HDL Particles)	4.96 Percent change Interval -9.59 to 20.58	0.00 Percent change Interval -9.74 to 13.49

SECONDARY outcome

Timeframe: 52 Weeks

Population: Since there were one or multiple records with a baseline value of 0, the percent change cannot be determined for such records. In such cases, the secondary endpoints were evaluated for change from baseline to week 52.

Outcome measures

Outcome measures
Measure	K-877 n=258 Participants K-877 0.2 mg Tablets	Placebo n=137 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 52 in Lipoprotein Fraction (HDL Particles-Large)	0.20 umol/L Interval -0.9 to 1.5	0.30 umol/L Interval -1.1 to 1.7

SECONDARY outcome

Timeframe: 52 Weeks

Population: Since there were one or multiple records with a baseline value of 0, the percent change cannot be determined for such records. In such cases, the secondary endpoints were evaluated for change from baseline to week 52.

Outcome measures

Outcome measures
Measure	K-877 n=258 Participants K-877 0.2 mg Tablets	Placebo n=137 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 52 in Lipoprotein Fraction (HDL Particles-Medium)	-0.20 umol/L Interval -3.7 to 2.8	-0.40 umol/L Interval -4.2 to 2.2

SECONDARY outcome

Timeframe: 52 Weeks

Population: Since there were one or multiple records with a baseline value of 0, the percent change cannot be determined for such records. In such cases, the secondary endpoints were evaluated for change from baseline to week 52.

Outcome measures

Outcome measures
Measure	K-877 n=258 Participants K-877 0.2 mg Tablets	Placebo n=137 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 52 in Lipoprotein Fraction (HDL Particles-Small)	1.80 umol/L Interval -2.9 to 7.3	1.40 umol/L Interval -2.7 to 5.1

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=258 Participants K-877 0.2 mg Tablets	Placebo n=137 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Lipoprotein Fraction (VLDL Particle Size)	-7.15 Percent change Interval -17.67 to 3.71	-5.46 Percent change Interval -15.32 to 3.65

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=237 Participants K-877 0.2 mg Tablets	Placebo n=131 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Lipoprotein Fraction (LDL Particle Size)	1.03 Percent change Interval 0.0 to 3.57	0.51 Percent change Interval -0.51 to 2.03

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=258 Participants K-877 0.2 mg Tablets	Placebo n=137 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Lipoprotein Fraction (HDL Particle Size)	-1.14 Percent change Interval -4.35 to 2.27	-1.15 Percent change Interval -4.35 to 1.15

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=258 Participants K-877 0.2 mg Tablets	Placebo n=137 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Lipoprotein Fraction (Triglyceride)	-55.03 Percent change Interval -73.79 to -31.24	-42.76 Percent change Interval -58.82 to -13.7

SECONDARY outcome

Timeframe: 52 Weeks

Two types of lipoprotein particles were analyzed together as one measurement without distinction.

Outcome measures

Outcome measures
Measure	K-877 n=258 Participants K-877 0.2 mg Tablets	Placebo n=137 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Lipoprotein Fraction (VLDL & Chylomicron Triglyceride)	-54.30 Percent change Interval -73.74 to -30.73	-41.55 Percent change Interval -58.97 to -17.39

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=212 Participants K-877 0.2 mg Tablets	Placebo n=120 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Lipoprotein Fraction (HDL Cholesterol)	2.90 Percent change Interval -15.75 to 24.94	-1.19 Percent change Interval -15.14 to 25.57

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=146 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Lipid and Lipoprotein Ratios of TG:HDL-C	-66.38 Percent change Interval -81.7 to -45.55	-56.61 Percent change Interval -71.34 to -32.09

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=146 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Lipid and Lipoprotein Ratios of TC:HDL-C	-31.53 Percent change Interval -47.32 to -13.74	-23.70 Percent change Interval -41.03 to -5.83

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=146 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Lipid and Lipoprotein Ratios of Non-HDL-C:HDL-C	-36.49 Percent change Interval -53.81 to -16.78	-27.67 Percent change Interval -47.17 to -7.02

SECONDARY outcome

Timeframe: 52 Weeks

Population: Since there were one or multiple records with a baseline value of 0, the percent change cannot be determined for such records. In such cases, the secondary endpoints were evaluated for change from baseline to week 52.

Outcome measures

Outcome measures
Measure	K-877 n=267 Participants K-877 0.2 mg Tablets	Placebo n=142 Participants Placebo matching K-877 0.2 mg tablet BID
Change From Baseline to Week 52 in Lipid and Lipoprotein Ratios of LDL-C:Apo B	0.210 Ratio Interval 0.05 to 0.42	0.150 Ratio Interval 0.03 to 0.31

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=274 Participants K-877 0.2 mg Tablets	Placebo n=143 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Lipid and Lipoprotein Ratios of Apo B:Apo A1	-3.56 Percent change Interval -20.0 to 14.91	-2.94 Percent change Interval -19.27 to 10.64

SECONDARY outcome

Timeframe: 52 Weeks

Outcome measures

Outcome measures
Measure	K-877 n=270 Participants K-877 0.2 mg Tablets	Placebo n=144 Participants Placebo matching K-877 0.2 mg tablet BID
Percent Change From Baseline to Week 52 in Lipid and Lipoprotein Ratios of Apo C3:Apo C2	-27.81 Percent change Interval -43.96 to -4.95	-13.17 Percent change Interval -32.52 to 4.21

Adverse Events

K-877: 12-Week Efficacy

Serious events: 11 serious events

Other events: 0 other events

Deaths: 3 deaths

Placebo:12-Week Efficacy

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

K-877: 40-Week Extension

Serious events: 25 serious events

Other events: 2 other events

Deaths: 3 deaths

Fenofibrate 40-Week Extension

Serious events: 5 serious events

Other events: 8 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	K-877: 12-Week Efficacy n=311 participants at risk * K-877 0.2 mg Tablets BID * Only AEs with onset in the 12-week efficacy period are included.	Placebo:12-Week Efficacy n=159 participants at risk * Placebo matching K-877 0.2 mg BID * Only AEs with onset in the 12-week efficacy period are included.	K-877: 40-Week Extension n=292 participants at risk * Participants randomized to receive K-877 0.2 mg tablets twice daily in the 12-week Efficacy Period continued to receive K-877 0.2 mg tablets BID in the 40-week Extension Period * Only AEs with onset in the 40-week extension period are included.	Fenofibrate 40-Week Extension n=154 participants at risk * Patients randomized to receive placebo matching K-877 0.2 mg BID in the 12-week Efficacy Period initiated fenofibrate dosing at 48 mg once daily at Visit 7 (Week 12). Starting from Visit 8 (Week 16), Investigators were allowed to adjust fenofibrate dosing (to 145 mg once daily) at their discretion according to the local standard of care. * Only AEs with onset in the 40-week extension period are included.
Investigations Glomerular filtration rate decreased	0.00% 0/311 • 52 Weeks Treatment-emergent adverse event (TEAE) was defined as any adverse event that occurred for the first time after the first dose of double-blind study drug or existed prior to the first dose and worsened during the post-dosing period.	0.00% 0/159 • 52 Weeks Treatment-emergent adverse event (TEAE) was defined as any adverse event that occurred for the first time after the first dose of double-blind study drug or existed prior to the first dose and worsened during the post-dosing period.	0.68% 2/292 • 52 Weeks Treatment-emergent adverse event (TEAE) was defined as any adverse event that occurred for the first time after the first dose of double-blind study drug or existed prior to the first dose and worsened during the post-dosing period.	5.2% 8/154 • 52 Weeks Treatment-emergent adverse event (TEAE) was defined as any adverse event that occurred for the first time after the first dose of double-blind study drug or existed prior to the first dose and worsened during the post-dosing period.

Additional Information

Director, Clinical Operations

Kowa Research Institute, Inc.

Phone: 919-433-1600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place