A Phase 3 Study to Evaluate the Efficacy and Safety of K-877 in Chinese Patients With High TG and Low HDL-C

Study Overview
=================
Brief Summary
-----------------
A Phase 3 Study to Evaluate the Efficacy and Safety of K-877 in Chinese Patients with High TG and Low HDL-C

Official Title
-----------------
A Phase 3, Multi-Center, Placebo- and Active-Controlled, Randomized, Double-Blind, 12-Week Study to Evaluate the Efficacy and Safety of K-877 in Chinese Patients With High TG and Low HDL-C

Conditions
-----------------
Hyperlipidemia

Intervention / Treatment
-----------------
* Drug: K-877 0.1 mg tablet
* Drug: Fenofibrate 200 mg capsule
* Drug: Placebo tablet
* Drug: Placebo capsule
* Drug: K-877 0.1 mg tablet
* Drug: Placebo tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects are eligible to be included in the study only if all of the following criteria apply: Ability to understand and comply with study procedures and give written informed consent Following the diet and lifestyle recommendations at least 12 weeks prior to the treatment period Males or post-menopausal females Aged ≥18 years at the time of informed consent Fasting serum TG levels ≥200 mg/dL (≥2.26 mmol/L) and ≤500 mg/dL (5.65 mmol/L) at screening Serum HDL-C <50 mg/dL (<1.30 mmol/L) if male or <55 mg/dL (<1.42 mmol/L) if female at screening. Exclusion Criteria: Subjects are excluded from the study if any of the following criteria apply: Current or planned use of any lipid-altering medications other than the study drugs, statins, or ezetimibe during the study. i. Subjects currently on statins or ezetimibe must be at high risk for atherosclerotic CV diseases, and the dose(s) must be stable for at least 4 weeks prior to screening ii. For subjects currently on lipid-altering medications other than statins or ezetimibe, at least 4-week washout period (or for subjects currently on probucol at least 8 week washout period) will be required prior to the first fasting blood sampling at Screening Visit Type 1 diabetes mellitus or poorly controlled Type 2 diabetes mellitus defined by HbA1c (NGSP level) ≥8.0% at screening Uncontrolled hypertension defined by seated systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg at screening Uncontrolled thyroid disorder Creatinine ≥1.5 mg/dL at screening Severe hepatic disorder defined as cirrhosis of Child-Pugh class B or C, or AST or ALT >2 × ULN at screening History of pancreatitis Gallbladder disorder, history of cholelithiasis, primary biliary cirrhosis, or history of disease or surgery that may affect the absorption, distribution, metabolism and excretion of drugs or the metabolism of bile salts Unexplained creatine kinase (CK) >5 × ULN at screening Myocardial infraction or stroke (including transient ischemic attack) within 3 months prior to the informed consent New York Heart Association Class III or IV heart failure History of malignancy within 5 years Participation in another clinical study at the time of informed consent or administration of an investigational drug other than placebo within 16 weeks prior to the informed consent for this study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: K-877 0.1 mg BID<br>K-877 0.1 mg tablet twice daily, Placebo tablet twice daily, Placebo capsule once daily | Drug: Placebo capsule<br>* Placebo capsule once daily<br>* Other names: Placebo capsule (matching fenofibrate);Drug: K-877 0.1 mg tablet<br>* K-877 0.1 mg tablet twice daily<br>* Other names: Pemafibrate;Drug: Placebo tablet<br>* Placebo tablet twice daily<br>* Other names: Placebo tablet (matching K-877);|
| Experimental: K-877 0.2 mg BID<br>K-877 0.1 mg tablet x 2 twice daily, Placebo capsule once daily | Drug: K-877 0.1 mg tablet<br>* K-877 0.1 mg tablet x 2 twice daily<br>* Other names: Pemafibrate;Drug: Placebo capsule<br>* Placebo capsule once daily<br>* Other names: Placebo capsule (matching fenofibrate);|
| Active Comparator: Fenofibrate 200 mg QD<br>Fenofibrate 200 mg capsule once daily, Placebo tablet x 2 twice daily | Drug: Fenofibrate 200 mg capsule<br>* Fenofibrate 200 mg capsule once daily<br>Drug: Placebo tablet<br>* Placebo tablet x 2 twice daily<br>* Other names: Placebo tablet (matching K-877);|
| Placebo Comparator: Placebo<br>Placcebo tablet x 2 twice daily, Placebo capsule once daily | Drug: Placebo tablet<br>* Placebo tablet x 2 twice daily<br>* Other names: Placebo tablet (matching K-877);Drug: Placebo capsule<br>* Placebo capsule once daily<br>* Other names: Placebo capsule (matching fenofibrate);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in fasting TG versus placebo from baseline to Weeks 8 and 12 |  | From baseline to Weeks 8 and 12 | 
| Percent change in fasting TG versus fenofibrate from baseline to Weeks 8 and 12 |  | From baseline to Weeks 8 and 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who have achieved fasting TG <150 mg/dL at the end of the treatment period |  | At Week 12 | 
| Percent change from baseline to Weeks 8 and 12 in TC, LDL-C (direct method), LDL-C (Friedewald method), LDL-C (Martin/Hopkins equation), HDL-C (direct method), non-HDL-C (calculated), and remnant cholesterol (calculated) |  | From baseline to Weeks 8 and 12 | 
| Change from baseline to Weeks 8 and 12 in fasting TG, TC, LDL-C (direct method), LDL-C (Friedewald method), LDL-C (Martin/Hopkins equation), HDL-C (direct method), non-HDL-C (calculated), and remnant cholesterol (calculated) |  | From baseline to Weeks 8 and 12 | 
| Percent change from baseline to the end of the treatment period in Apo A1 and Apo B |  | From baseline to Week 12 | 
| Percent change from baseline to the end of the treatment period in TG/HDL-C, TC/HDL-C, non-HDL-C/HDL-C, LDL-C/HDL-C, LDL-C/Apo B, and Apo B/Apo A1 |  | From baseline to Week 12 | 
| The incidence of adverse events and adverse drug reactions after the administration of the study drug |  | Up to Week 12 | 
| Change from baseline to Week 4, 8, and 12 in clinical laboratory tests (chemistry, hematology), vital signs (BP [mmHg], PR [bpm], weight [kg], waist [cm], and BMI [kg/m^2]; each parameter is evaluated individually.), 12-lead ECGs |  | From baseline to Week 4, 8, and 12 | 
| Number and percentage of patients who experience laboratory abnormalities of special interest including, but not limited to ALT, AST, ALP, CK, and, creatinine during the treatment period |  | Up to Week 12 |