Study to Evaluate the Efficacy and Safety of K-877 in Adult Patients With Fasting High Triglyceride Levels and Normal Renal Function
Condition: Severe Hypertriglyceridemia
MeSH terms: Hypertriglyceridemia
Intervention: K-877; Fenofibrate; Placebo (for K-877); Placebo (for Fenofibrate)
Intervention MeSH terms: Fenofibrate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 551.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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 normal renal function.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Able to understand and willing to comply with all study requirements and procedures
             throughout the duration of the study and give written informed consent;

          2. Aged ≥18 years;

          3. 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):

               1. 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);

               2. 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);

               3. 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

               4. 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;

          4. Patients currently on a low-intensity statin or not on a statin, must meet one of the
             following criteria:

               1. Patient does not meet any criteria for moderate- or high-intensity statin therapy
                  listed above (see inclusion criteria, criterion 3.a. through 3.d.);

               2. 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

               3. 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;

        Exclusion Criteria:

          1. Patients who will require lipid-altering treatments other than study drugs (K-877 or
             fenofibrate), statins, ezetimibe, or PCSK9 inhibitors during the course of the study.
             These include bile acid sequestrants, non-study fibrates, niacin (>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;

          2. Body mass index (BMI) >45 kg/m2 at Visit 1 (Week -8 or Week -6);

          3. Patients with type 1 diabetes mellitus;

          4. 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);