Phase 3
N=470
Study to Evaluate the Efficacy and Safety of K-877 in Adult Patients With Fasting High Triglyceride Levels and Mild or Moderate Renal Impairment
Severe Hypertriglyceridemia
Bottom Line
View on ClinicalTrials.gov: NCT03011450 ↗Enrolled (actual)
470
Serious AEs
4.8%
Results posted
Oct 2022
Primary outcome: Primary: Percent Change in Fasting TG From Baseline to Week 12 — -58.89; -22.94 Percent change — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- K-877 (Drug); Fenofibrate (Drug); Placebo (for K-877) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Kowa Research Institute, Inc.
- Primary completion
- Jul 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percent Change in Fasting TG From Baseline to Week 12 |
-58.89; -22.94 | <0.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Remnant Cholesterol |
-55.51; -13.29 | <0.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in HDL-C |
23.50; 7.33 | <0.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Apo A1 |
4.05; 0.00 | 0.0156 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Non-HDL-C |
-20.98; -3.43 | <0.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Total Cholesterol |
-14.55; -2.05 | <0.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in LDL-C |
31.49; 2.30 | <0.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in FFAs |
-25.25; -5.51 | 0.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Apo A2 |
19.34; 0.00 | <0.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Apo B |
0.57; -1.67 | 0.5380 |
| SECONDARY Percent Change From Baseline to Week 12 in Apo B48 |
-36.64; 19.91 | <0.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Apo B100 |
2.05; -2.33 | 0.1165 |
| SECONDARY Percent Change From Baseline to Week 12 in Apo C2 |
-4.70; 0.00 | 0.0142 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Apo C3 |
-41.97; -3.10 | <0.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Apo E |
-29.09; -5.98 | <0.0001 sig |
| SECONDARY Change From Baseline to Week 12 in FGF21 |
277.97; 12.15 | <0.0001 sig |
| SECONDARY Change From Baseline to Week 12 in hsCRP |
-0.201; -0.100 | 0.4589 |
| SECONDARY Percent Change From Baseline to Week 12 in Ion Mobility (VLDL Cholesterol-Large) |
-36.45; -5.95 | <.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Ion Mobility (VLDL Cholesterol-Intermediate) |
-23.23; 0.07 | <.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Ion Mobility (VLDL Cholesterol-Small) |
-6.07; 4.16 | <.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Ion Mobility (Intermediate Density Lipoproteins 1) |
-0.22; 2.42 | 0.2486 |
| SECONDARY Percent Change From Baseline to Week 12 in Ion Mobility (Intermediate Density Lipoproteins 2) |
17.52; 3.21 | <.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Ion Mobility (Low Density Lipoproteins I) |
44.20; 4.81 | <.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Ion Mobility (Low Density Lipoproteins IIa) |
53.94; 4.24 | <.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Ion Mobility (Low Density Lipoproteins IIb) |
48.44; 1.89 | <.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Ion Mobility (Low Density Lipoproteins IIIa) |
23.79; -0.80 | 0.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Ion Mobility (Low Density Lipoproteins IIIb) |
-5.73; 0.71 | 0.2763 |
| SECONDARY Percent Change From Baseline to Week 12 in Ion Mobility (Low Density Lipoproteins IVa) |
-30.48; -2.89 | <.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Ion Mobility (Low Density Lipoproteins IVb) |
-35.08; -0.74 | <.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Ion Mobility (Low Density Lipoproteins IVc) |
-23.39; 0.89 | <.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Ion Mobility (High Density Lipoproteins 2b) |
-10.65; 0.91 | <.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Ion Mobility (High Density Lipoproteins 3 and 2a) |
-2.13; -0.53 | 0.1651 |
| SECONDARY Percent Change From Baseline to Week 12 in Ion Mobility (Diameter of the Major LDL Particle (Å)) |
2.67; 0.14 | <.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Lipoprotein Fraction (VLDL & Chylomicron Particles) |
-42.76; -5.59 | <.0001 sig |
| SECONDARY Change From Baseline to Week 12 in Lipoprotein Fraction (VLDL & Chylomicron Particles-Large) |
-12.62; -3.75 | <.0001 sig |
| SECONDARY Change From Baseline to Week 12 in Lipoprotein Fraction (VLDL Particles-Medium) |
-41.27; -9.13 | <.0001 sig |
| SECONDARY Change From Baseline to Week 12 in Lipoprotein Fraction (VLDL Particles-Small) |
0.46; 0.07 | 0.5107 |
| SECONDARY Percent Change From Baseline to Week 12 in Lipoprotein Fraction (LDL Particles) |
17.58; 4.97 | 0.0018 sig |
| SECONDARY Change From Baseline to Week 12 in Lipoprotein Fraction (IDL Particles) |
-17.06; -2.74 | 0.0742 |
| SECONDARY Change From Baseline to Week 12 in Lipoprotein Fraction (LDL Particles-Large) |
54.52; 0.00 | <.0001 sig |
| SECONDARY Change From Baseline to Week 12 in Lipoprotein Fraction (LDL Particles-Small) |
83.88; 12.43 | 0.2707 |
| SECONDARY Percent Change From Baseline to Week 12 in Lipoprotein Fraction (HDL Particles) |
5.96; -1.60 | 0.0009 sig |
| SECONDARY Change From Baseline to Week 12 in Lipoprotein Fraction (HDL Particles-Large) |
0.22; 0.00 | 0.2879 |
| SECONDARY Change From Baseline to Week 12 in Lipoprotein Fraction (HDL Particles-Medium) |
-0.21; -0.23 | 0.9786 |
| SECONDARY Change From Baseline to Week 12 in Lipoprotein Fraction (HDL Particles-Small) |
1.54; 0.16 | 0.0075 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Lipoprotein Fraction (VLDL Particle Size) |
-5.02; -2.26 | 0.0241 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Lipoprotein Fraction (LDL Particle Size) |
1.02; 0.00 | <.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Lipoprotein Fraction (HDL Particle Size) |
-1.19; -0.14 | 0.0502 |
| SECONDARY Percent Change From Baseline to Week 12 in Lipoprotein Fraction (Triglyceride) |
-54.86; -15.24 | <.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Lipoprotein Fraction (VLDL & Chylomicron Triglyceride) |
-55.19; -16.20 | <.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Lipoprotein Fraction HDL Cholesterol (Total) |
5.51; -2.20 | 0.0209 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Lipid and Lipoprotein Ratios of TG:HDL-C |
-66.21; -26.81 | <0.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Lipid and Lipoprotein Ratios of TC:HDL-C |
-32.36; -9.02 | <0.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Lipid and Lipoprotein Ratios of Non-HDL-C:HDL-C |
-32.36; -9.02 | <0.0001 sig |
| SECONDARY Change From Baseline to Week 12 in Lipid and Lipoprotein Ratios of LDL-C:Apo B |
0.219; 0.026 | <0.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Lipid and Lipoprotein Ratios of Apo B:Apo A1 |
-1.68; -1.25 | 0.0001 sig |
| SECONDARY Percent Change From Baseline to Week 12 in Lipid and Lipoprotein Ratios of Apo C3:Apo C2 |
-27.76; -0.47 | <0.0001 sig |
| SECONDARY Percent Change From Baseline to Week 52 in Fasting TG |
-59.96; -49.55 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Remnant Cholesterol |
-58.39; -43.31 | — |
| SECONDARY Percent Change From Baseline to Week 52 in HDL-C |
18.78; 15.59 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Apo A1 |
3.29; 2.56 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Non-HDL-C |
-21.80; -14.22 | — |
| SECONDARY Percent Change From Baseline to Week 52 in TC |
-15.28; -8.64 | — |
| SECONDARY Percent Change From Baseline to Week 52 in LDL-C |
31.90; 22.96 | — |
| SECONDARY Percent Change From Baseline to Week 52 in FFAs |
-21.61; -21.41 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Apo A2 |
15.92; 8.33 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Apo B |
-1.73; 0.00 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Apo B48 |
-19.43; -15.19 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Apo B100 |
-1.32; -0.87 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Apo C2 |
-9.56; 0.00 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Apo C3 |
-42.80; -26.25 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Apo E |
-30.82; -30.00 | — |
| SECONDARY Change From Baseline to Week 52 in FGF21 |
371.80; 194.40 | — |
| SECONDARY Change From Baseline to Week 52 in hsCRP |
-0.100; -0.225 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Ion Mobility (VLDL Cholesterol-Large) |
-36.60; -22.03 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Ion Mobility (VLDL Cholesterol-Intermediate) |
-25.03; -13.31 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Ion Mobility (VLDL Cholesterol-Small) |
-12.96; -2.31 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Ion Mobility (Intermediate Density Lipoproteins 1) |
0.69; 3.54 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Ion Mobility (Intermediate Density Lipoproteins 2) |
17.33; 15.87 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Ion Mobility (Low Density Lipoproteins I) |
46.51; 25.53 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Ion Mobility (Low Density Lipoproteins IIa) |
61.36; 33.66 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Ion Mobility (Low Density Lipoproteins IIb) |
45.61; 27.29 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Ion Mobility (Low Density Lipoproteins IIIa) |
18.50; 19.64 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Ion Mobility (Low Density Lipoproteins IIIb) |
-6.92; 1.17 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Ion Mobility (Low Density Lipoproteins IVa) |
-25.63; -24.80 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Ion Mobility (Low Density Lipoproteins IVb) |
-37.26; -24.22 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Ion Mobility (Low Density Lipoproteins IVc) |
-26.81; -17.41 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Ion Mobility (High Density Lipoproteins 2b) |
-11.67; -5.62 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Ion Mobility (High Density Lipoproteins 3 and 2a) |
-4.62; -3.71 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Ion Mobility (Diameter of the Major LDL Particle (Å)) |
2.69; 1.54 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Lipoprotein Fraction (VLDL & Chylomicron Particles) |
-40.10; -28.98 | — |
| SECONDARY Change From Baseline to Week 52 in Lipoprotein Fraction (VLDL & Chylomicron Particles-Large) |
-13.00; -8.60 | — |
| SECONDARY Change From Baseline to Week 52 in Lipoprotein Fraction (VLDL Particles-Medium) |
-41.95; -26.90 | — |
| SECONDARY Change From Baseline to Week 52 in Lipoprotein Fraction (VLDL Particles-Small) |
-0.15; 0.00 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Lipoprotein Fraction (LDL Particles) |
14.43; 12.79 | — |
| SECONDARY Change From Baseline to Week 52 in Lipoprotein Fraction (IDL Particles) |
-12.00; -6.00 | — |
| SECONDARY Change From Baseline to Week 52 in Lipoprotein Fraction (LDL Particles-Large) |
53.00; 8.00 | — |
| SECONDARY Change From Baseline to Week 52 in Lipoprotein Fraction (LDL Particles-Small) |
59.00; 97.00 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Lipoprotein Fraction (HDL Particles) |
4.96; 0.00 | — |
| SECONDARY Change From Baseline to Week 52 in Lipoprotein Fraction (HDL Particles-Large) |
0.20; 0.30 | — |
| SECONDARY Change From Baseline to Week 52 in Lipoprotein Fraction (HDL Particles-Medium) |
-0.20; -0.40 | — |
| SECONDARY Change From Baseline to Week 52 in Lipoprotein Fraction (HDL Particles-Small) |
1.80; 1.40 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Lipoprotein Fraction (VLDL Particle Size) |
-7.15; -5.46 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Lipoprotein Fraction (LDL Particle Size) |
1.03; 0.51 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Lipoprotein Fraction (HDL Particle Size) |
-1.14; -1.15 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Lipoprotein Fraction (Triglyceride) |
-55.03; -42.76 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Lipoprotein Fraction (VLDL & Chylomicron Triglyceride) |
-54.30; -41.55 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Lipoprotein Fraction (HDL Cholesterol) |
2.90; -1.19 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Lipid and Lipoprotein Ratios of TG:HDL-C |
-66.38; -56.61 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Lipid and Lipoprotein Ratios of TC:HDL-C |
-31.53; -23.70 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Lipid and Lipoprotein Ratios of Non-HDL-C:HDL-C |
-36.49; -27.67 | — |
| SECONDARY Change From Baseline to Week 52 in Lipid and Lipoprotein Ratios of LDL-C:Apo B |
0.210; 0.150 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Lipid and Lipoprotein Ratios of Apo B:Apo A1 |
-3.56; -2.94 | — |
| SECONDARY Percent Change From Baseline to Week 52 in Lipid and Lipoprotein Ratios of Apo C3:Apo C2 |
-27.81; -13.17 | — |
Summary
The purpose of this study is to evaluate the efficacy and safety of K-877 in adult patients With Fasting High Triglyceride Levels ≥500 mg/dL and <2000 mg/dL and Mild or Moderate Renal Impairment.
Eligibility Criteria
Inclusion Criteria
- Able to understand and willing to comply with all study requirements and procedures throughout the duration of the study and give written informed consent;
- Aged ≥18 years;
- Patients receiving moderate- or high-intensity statin therapy must meet one of the following criteria¹ unless they have any exceptional conditions (see inclusion criterion 4):
- Aged ≥21 years with clinical atherosclerotic cardiovascular disease (ASCVD) (history of acute coronary syndrome or myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack [TIA] presumed to be of atherosclerotic origin, or peripheral arterial disease or revascularization), on a high-intensity statin (or moderate-intensity statin if not a candidate for high-intensity statin due to safety concerns);
- Aged ≥21 years with a history of LDL-C ≥190 mg/dL, which is not due to secondary modifiable causes, on a high-intensity statin (or moderate-intensity statin if not a candidate for high-intensity statin due to safety concerns);
- Aged 40 to 75 years, inclusive, without clinical ASCVD but with diabetes and a history of LDL-C of 70 to 189 mg/dL, inclusive, on a moderate- or high-intensity statin; or
- Aged 40 to 75 years, inclusive, without clinical ASCVD or diabetes, with a history of LDL-C of 70 to 189 mg/dL, inclusive, with estimated 10-year risk for ASCVD of ≥7.5% by the Pooled Cohort Equation on a moderate- or high-intensity statin;
- Patients currently on a low-intensity statin or not on a statin, must meet one of the following criteria;
- Patient does not meet any criteria for moderate- or high-intensity statin therapy listed above (see inclusion criteria, 3.a. through 3.d.);
- Patient does meet one or more criteria for moderate- or high-intensity statin therapy listed above (see inclusion criteria 3.a. through 3.d.); but the patient is not a candidate for moderate or high-intensity statin due to safety concerns, or due to partial or complete statin intolerance; or
- Patient does meet one or more criteria for moderate- or high intensity statin therapy listed above (see inclusion criteria 3.b. through 3.d., except for 3.a.); but the patient is not a candidate for moderate or high intensity statin for primary prevention after considering individual risk evaluation (e.g. current LDL C ≤70mg/dL) and patient preference;
- Fasting TG levels ≥500 mg/dL (5.65 mmol/L) and = 30mL/min/1.73 and 100 mg/day), omega-3 fatty acids (>1000 mg/day), or any supplements used to alter lipid metabolism including, but not limited to, red rice yeast supplements, garlic supplements, soy isoflavone supplements, sterol/stanol products, or policosanols;
- Body mass index (BMI) >45 kg/m2 at Visit 1 (Week -8 or Week -6);
- Patients with type 1 diabetes mellitus;
- Patients with newly diagnosed (within 3 months prior to Visit 2 [Week -2]) or poorly controlled type 2 diabetes mellitus (T2DM), defined as hemoglobin A1c >9.5% at Visit 1 (Week -8 or Week -6);
Data sourced from ClinicalTrials.gov (NCT03011450). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.