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

Kowa

Status and phase: Completed; Phase 3

Conditions: Severe Hypertriglyceridemia

Treatments: Drug: Placebo (for K-877); Drug: Fenofibrate; Drug: K-877

Study type: Interventional

Funder types: Industry

Identifiers

NCT03011450

K-877-303

Details and patient eligibility

About

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.

Enrollment: 471 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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);

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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471 participants in 2 patient groups, including a placebo group

12 Week Efficacy

Placebo Comparator group

Description:

K-877 or placebo comparator for 12 weeks

Treatment:

Drug: Placebo (for K-877)

Drug: K-877

40 week extension

Active Comparator group

Description:

K-877 or fenofibrate comparator for 40 weeks

Treatment:

Drug: K-877

Drug: Fenofibrate