Randomized controlled trial of pemafibrate and fenofibrate for NAFLD with hypertriglyceridemia

JRCT ID: jRCTs031200280

Registered date:28/12/2020

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: NAFLD with hypertriglyceridemia
• Date of first enrollment: 16/02/2021
• Target sample size: 360
• Study type: Interventional

Intervention(s)

1. Pemafibrate high dose group
Palmodia 0.1 mg tablets are orally administered twice daily, 2 tablets at a time, after breakfast and dinner.
If unavoidable,Pemafibrate extended-release 0.2 mg two tablets once daily or pemafibrate extended-release 0.4 mg one tablet once daily.
2. Pemafibrate low dose group
Palmodia 0.1 mg tablets are orally administered twice daily, once after breakfast and dinner.
If unavoidable, pemafibrate extended-release 0.2 mg one tablet once daily.
3. Fenofibrate group
Lipidil or Tricore or fenofibrate 53.3 mg tablets should be orally administered once daily, 1 tablet at a time, after breakfast.

Outcome(s)

• Primary Outcome: Change in ALT after 24-week administration

Secondary Outcome

1) Change in ALT after 48 weeks of administration
2) Changes in liver fibrosis markers after 48 weeks of administration.
3) AST, GGT, Cr, BUN, HbA1c, platelets, HOMA-IR, HDL-C, non-HDL-C, LDL-C / HDL-C ratio, TG from baseline to 24 and 48 weeks. Amount of change and rate of change
4) (Only for facilities where MRE and USE can be performed) Amount of change in liver fat and liver hardness from baseline in MRE and USE.
5) Presence or absence of cardiovascular events, liver disease-related events, and carcinogenesis during the intervention period / observation period
6) Changes in body weight, BMI, and abdominal circumference from baseline at 24 and 48 weeks of administration
7) Changes in 10-year ASCVD (Atherosclerotic Cardiovascular Disease) risk score
8) Percentage of patients with ALT 100 IU / L or higher and / or more than double that at week 0
9) Safety (incidence of AEs and ADRs at 48 weeks of treatment)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 80age old
• Gender: Both

Include criteria

1. Outpatients whose ages are between 20 and 80 years old at the time of obtaining consent.
2.Patients with fatty liver diagnosed by histological examination within 1 year prior to obtaining consent, or by imaging examination within 6 months prior to obtaining consent, and who have not responded to exercise or diet therapy for more than 3 months
3. Patients with hypertriglyceridemia (150-500 mg / dl) within 91 days before obtaining consent.
4. Patients with high ALT (male 43-100 IU / L, female 24-100 IU / L) within 91 days before obtaining consent.
5.Patients whose daily drinking amount is less than 30 g per day for men and less than 20 g for women in terms of ethanol at the time of obtaining consent
6.Patients who do not have other liver diseases such as hepatitis C, hepatitis B (excluding inactive carriers), autoimmune hepatitis, and primary biliary cholangitis at the time of consent acquisition
7. Patients with written informed consent.

Exclude criteria

1. Taking cyclosporine, rifampicin, amiodarone, and breast cancer treatments (tamoxifen, toremifene, raloxifene).
2. Patients with BMI <18.5kg/m2 at the time of consent.
3. Patients diagnosed with cirrhosis at the time of consent.
4. Patients with findings of portal hypertension (varicose veins, ascites, encephalopathy, splenomegaly) at the time of obtaining consent.
5. Patients with T-Bil > normal upper limit x2 within 91 days before obtaining consent excluding Girbert syndrome.
6. Platelet count < 80,000 / uL within 91 days before obtaining consent.
7. Serum Cr level is 1.5 mg / dL or higher within 91 days before obtaining consent.
8. Patients with gallstones or biliary atresia at the time of consent.
9. Patients with severe infections, patients before and after surgery, patients with serious trauma at the time of consent,
10. Patients using fibrates within 91 days before obtaining consent.
11. Patients with a weight change of 10 % 91 days before obtaining consent.
12. Patients who have undergone or are planning bariatric surgery during the study period.
13. Patients with a history of type I diabetes.
14. Patients with HbA1c > 9.5 % within 91 days prior to obtaining consent.
15. Patients with psychosis, alcoholism, drug addiction, or drug addiction that may affect compliance with the research plan.
16. Patients who participated in other clinical trials 100 days before obtaining consent.
17. Pregnant women or patients who may be pregnant.
18. Patients with malignant tumor.
However, patients who have undergone radical surgery or who have completed administration of anticancer drugs are allowed to be registered, and patients who are being observed and evaluated for malignant tumors are excluded.
19. Patients who are considered inappropriate to participate in this study by the reseacher.
20. Patients who have received concomitant medications for more than 1 week.

Related Information

• Primary Sponsor: Iwaki Michihiro
• Secondary Sponsor: Kessoku Takaomi
• Source(s) of Monetary Support: Kowa Company. Ltd.