Study to Evaluate the Efficacy and Safety of K-877 in Adult Patients With Fasting High Triglyceride Levels and Mild or Moderate Renal Impairment
Condition: Severe Hypertriglyceridemia
MeSH terms: Hypertriglyceridemia
Intervention: K-877; Fenofibrate; Placebo (for K-877)
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: 471.0
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 Mild or Moderate Renal
      Impairment.
    

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, 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;

          5. Fasting TG levels ≥500 mg/dL (5.65 mmol/L) and <2000 mg/dL (22.60 mmol/L) based on the
             mean of Visit 2 (Week -2) and Visit 3 (Week -1).

               -  Mild to moderate renal impairment eGFR >= 30mL/min/1.73 and < 90 mL/min/1.73 at
                  Visit 1

        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);