Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis(NAFLD/NASH) NAFLD,NASH,NAFLD/NASH
Conditions
Interventions
During the treatment period, the investigational drug is orally administered to groups A and B twice daily for 16 weeks. The number of administered tablets in each group is as follows:
A group: WY-86
Sponsors
Kobayashi Takashi
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Patients who have received a full explanation about this study and who have provided written consent. 2.Patients >= 20 years of age == 130 mmHg and/or diastolic blood pressure is >= 85 mmHg (according to the diagnostic criteria for metabolic syndrome) 4.Patients diagnosed with NAFLD/NASH who meet the following criteria (1) or (2) (1) Patients diagnosed with NAFLD (2) Patients with a definitive diagnosis of NASH by biopsy within 32 weeks before screening 5.Patients with magnetic resonance imaging (MRI)-proton density fat fraction (PDFF) liver fat mass >= 8% at screening. 6.Patients with magnetic resonance elastography (MRE)value == 25 kg/m2 at the time of screening. 8.Patients receiving diet or exercise therapy 12 weeks before screening, with no improvement. 9.Patients who are willing to maintain a stable diet and physical activity during the clinical trial.
Exclusion criteria
Exclusion criteria: 1.Pregnant, lactating, potentially pregnant women, or patients who do not agree to contraception during the trial period. 2.Patients who have taken guanabenz acetate within 16 weeks prior to screening or who have participated in other clinical studies (observational studies are excluded). 3.Patients with drug allergies to guanabenz acetate. 4.Patients with liver failure or cirrhosis. 5.Patients with the following laboratory test values: (1)Alanine aminotransferase (ALT) > 430 IU/L (males) or > 240 IU/L (female), or aspartate aminotransferase (AST) > 300 IU/L (males and females) (2)Prothrombin time-international normalized ratio (PT-INR) >= 1.5 (excluding anticoagulant therapy) (3)Total bilirubin value > 2.0 mg/dL (excluding definitive diagnosis of Gilbert syndrome) (4)Platelet count < 80,000/uL (5)Estimated glomerular filtration ratio (eGFR) < 45 (calculated by body surface area correction: standardized eGFR) 6.Patients with a history of acute or chronic liver disease other than NAFLD/NASH and complications: (1)Patients suffering from hepatitis B (defined by hepatitis B surface (HBs) antigen positive at the time of screening) or hepatitis C (defined by hepatitis C virus (HCV) antibody positive at the time of screening). However, anti-HCV antibody positive patients who are judged to be negative for hepatitis C virus ribonucleic acid (HCV-RNA) can be registered if they can be confirmed to be negative for at least one year before screening. (2)Patients with autoimmune hepatitis. (3)Patients with primary biliary cholangitis, primary sclerosing cholangitis, Wilsons disease, alpha1-antitrypsin deficiency, hemochromatosis or iron overload, drug-induced or alcoholic liver disease, or a history of known biliary atresia. (4)Patients with suspicion or definitive diagnosis of hepatocellular carcinoma. 7.Patients with a history of human immunodeficiency virus (HIV) infection. 8.Patients with findings of portal hypertension (complications: ascites, hepatic encephalopathy, varicose veins, splenomegaly). 9.Patients with a history of NAFLD-related drugs (amiodarone, methotrexate, systemic glucocorticoids, tetracycline, tamoxifen, higher doses of estrogen, anabolic steroids or valproic acid than used for hormone replacement) or other hepatotoxins for at least 4 weeks prior to screening. 10.Patients who have used the following drugs (1)Patients who used insulin, glucagon-like peptide-1 (GLP-1) receptor agonists, SGLT2 inhibitors, or thiazolidine 12 weeks before screening, (2)Patients who used ursodeoxycholic acid or vitamin E 12 weeks before screening, (3)Patients whose doses of dyslipidemia drugs or antihypertensive drugs were changed 12 weeks before screening, (4)Patients whose dose of oral diabetes treatment drug (dipeptidyl peptidase 4 (DPP-4) inhibitor, sulfonylurea (SU) preparation, alpha-glucosidase inhibitor, metformin) was changed 12 weeks before screening, (5)Patients who used drugs known to have a significant effect on body weight (including over-the-counter drugs for weight loss) 12 weeks before screening, (6)Patients using central nervous system depressants (barbital, sodium thiopental, morphine hydrochloride hydrate, brotizolam, diazepam, etc.). 11.Patients with 10% weight change 24 weeks before screening. 12.Patients scheduled to undergo surgery after obesity surgery (such as gastroplasty and Roux-en-Y gastric bypass surgery) or during the trial period. 13.Patients with a history of type 1 diabetes. 14.Patients with hemoglobin A1c (HbA1c)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of those where the liver fat content (%) measured by MRI-PDFF at 16 weeks decreased by 3.46% or more from baseline (%) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1) Amount of change and rate of change from baseline in the measured values at 16 weeks were determined. The rate of change is defined as (value at 16 weeks - baseline value) / (baseline value). The following items were measured: Percentage of subjects where the liver fat content (%) measured by MRI-PDFF at 16 weeks decreased by >= 3.46% from baseline for the 4 mg and 8 mg groups Amount of change and rate of change in liver fat content measured by MRI-PDFF Rate of change in ALT, AST, and gamma-GTP Rate of change in weight Rate of change in blood lipids (chylomicron cholesterol, chylomicron triglyceride, lipoprotein cholesterol, LDL triglyceride, VLDL cholesterol, VLDL triglyceride, free cholesterol, apoprotein A1, apoprotein B, adipsin, free fatty acid) Rate of change in insulin resistance (HOMA-IR) Rate of change in liver hardness (MRE) Rate of change of fibrosis markers (ELF score, Fibrosis-4 [FIB-4]) 2)Search for new markers related to liver disease and obesity metabolic disease 3)Occurrence rate of adverse events | — |
Contacts
Public ContactOrie Watanabe
Yokohama City University hospital
Outcome results
None listed