Clinical trial NCT04998981: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyperlipidemia
Lead sponsor: Kowa Company, Ltd.
Sponsor class: INDUSTRY
First posted: 2021-08-10
Enrollment: 353
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

Subjects are eligible to be included in the study only if all of the following criteria apply:

1. Ability to understand and comply with study procedures and give written informed consent
2. Following the diet and lifestyle recommendations at least 12 weeks prior to the treatment period
3. Males or post-menopausal females
4. Aged ≥18 years at the time of informed consent
5. Fasting serum TG levels ≥200 mg/dL (≥2.26 mmol/L) and ≤500 mg/dL (5.65 mmol/L) at screening
6. 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:

1. 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
2. Type 1 diabetes mellitus or poorly controlled Type 2 diabetes mellitus defined by HbA1c (NGSP level) ≥8.0% at screening
3. Uncontrolled hypertension defined by seated systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg at screening
4. Uncontrolled thyroid disorder
5. Creatinine ≥1.5 mg/dL at screening
6. Severe hepatic disorder defined as cirrhosis of Child-Pugh class B or C, or AST or ALT \>2 × ULN at screening
7. History of pancreatitis
8. 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
9. Unexplained creatine kinase (CK) \>5 × ULN at screening
10. Myocardial infraction or stroke (including transient ischemic attack) within 3 months prior to the informed consent
11. New York Heart Association Class III or IV heart failure
12. History of malignancy within 5 years
13. 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

Primary outcomes:
measure: Percent change in fasting TG versus placebo from baseline to Weeks 8 and 12
timeFrame: From baseline to Weeks 8 and 12
measure: Percent change in fasting TG versus fenofibrate from baseline to Weeks 8 and 12
timeFrame: From baseline to Weeks 8 and 12
Secondary outcomes:
measure: Percentage of patients who have achieved fasting TG <150 mg/dL at the end of the treatment period
timeFrame: At Week 12
measure: 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)
timeFrame: From baseline to Weeks 8 and 12
measure: 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)
timeFrame: From baseline to Weeks 8 and 12
measure: Percent change from baseline to the end of the treatment period in Apo A1 and Apo B
timeFrame: From baseline to Week 12
measure: 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
timeFrame: From baseline to Week 12
measure: The incidence of adverse events and adverse drug reactions after the administration of the study drug
timeFrame: Up to Week 12
measure: 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
timeFrame: From baseline to Week 4, 8, and 12
measure: 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
timeFrame: Up to Week 12
Other outcomes:
Locations:
city: Anhui
country: China
facility: Huainan First People's Hospital
city: Beijing
country: China
facility: Beijing Anzhen Hospital, Capital Medical University
city: Beijing
country: China
facility: Beijing Hospital
city: Beijing
country: China
facility: Beijing Tongren Hospital, Capital Medical University
city: Beijing
country: China
facility: Beijing Pinggu Hospital
city: Chengdu
country: China
facility: Chengdu Xinhua Hospital
city: Fujian
country: China
facility: The First Affiliated Hospital of Fujian Medical University
city: Guangdong
country: China
facility: Peking Union Medical College Hospital
city: Guangdong
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
city: Guangdong
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
city: Guangxi
country: China
facility: The People's Hospital of Guangxi Zhuang Autonomous Region
city: Hainan
country: China
facility: Hainan General Hospital
city: Hebei
country: China
facility: The Second Hospital of Hebei Medical University
city: Helongjiang
country: China
facility: The First Affiliated Hospital of Harbin Medical University
city: Hubei
country: China
facility: Union Hospital, Tongji Medical College of Huazhong University of Science & Technology
city: Hubei
country: China
facility: Tongji Hospital, Tongji Medical College of HUST
city: Hubei
country: China
facility: Shaanxi Provincial People's Hospital
city: Hunan
country: China
facility: The Third Xiangya Hospital of Central South University
city: Hunan
country: China
facility: The Third Hospital of Changsha
city: Jiangsu
country: China
facility: Nanjing Jiangning Hospital
city: Jiangsu
country: China
facility: Sir Run Run Hospital Nanjing Medical Universtiy
city: Jiangsu
country: China
facility: Affiliated Hospital of Jiangsu University
city: Jiangxi
country: China
facility: Jiangxi Provincial People's Hospital
city: Jiangxi
country: China
facility: The First Affiliated Hospital of Nanchang University
city: Jiangxi
country: China
facility: The First Hospital of Nanchang
city: Jiangxi
country: China
facility: Jiu Jiang No. 1 People's Hospital
city: Jiangxi
country: China
facility: Pingxiang People's Hospital
city: Jilin
country: China
facility: China-Japan Union Hospital of Jilin University
city: Shanghai
country: China
facility: Shanghai Tongren Hospital
city: Sichuan
country: China
facility: People's Hospital of Deyang City
city: Tianjin
country: China
facility: Tianjin Union Medical Center
city: Zhejiang
country: China
facility: The Affiliated Hospital of Hangzhou Normal University
city: Zhejiang
country: China
facility: People's Hospital of Wenzhou City
Study officials:
References:
citation: Dai W, Lv Q, Li Q, Fu L, Zhang Y, Zhang Y, Liu L, Tanigawa R, Kunitomi K, Kamei R, Suganami H, Ma C. Efficacy and Safety of Pemafibrate, a Novel Selective PPARalpha Modulator in Chinese Patients with Dyslipidemia: A Double-Masked, Randomized, Placebo- and Active-Controlled Comparison Trial. J Atheroscler Thromb. 2025 Feb 1;32(2):125-140. doi: 10.5551/jat.64112. Epub 2024 Aug 2.