Clinical Trials to Compare the Effects of Pioglitazone and Evogliptin on Hepatic Fibrosis in Patients With Chronic Hepatitis B With Significant Hepatic Fibrosis With Type 2 Diabetes

Study Overview
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Brief Summary
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The clinical study determines the effect of Evogliptin in patients with type 2 diabetes mellitus and chronic hepatitis B to confirm the improvement of hepatic fibrosis.

Official Title
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Prospective, Multicenter, Randomized, and Comparative Clinical Trials to Compare the Effects of Pioglitazone and Evogliptin on Hepatic Fibrosis in Patients With Chronic Hepatitis B With Significant Hepatic Fibrosis With Type 2 Diabetes

Conditions
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Chronic Hepatitis B With Significant Hepatic Fibrosis With Type 2 Diabetes

Intervention / Treatment
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* Drug: gluconon tab 15mg
* Drug: suganon tab 5mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adultes between 20 and 80 years of age Patients who satisfy the following conditions among chronic hepatitis B patients diagnosed with type 2 diabetes Patients who are newly diagnosed as type 2 diabetes : 6.5% ≤ HbA1c < 10.0% Patients who are already diagnosed as type 2 diabetes: HbA1c < 10.0% Patients who have significant liver fibrosis of at least 7 kPa in a hepaticity test using fibroscan Patients who voluntarily signed the consent form after informed on the object, method, benefits and risks of the clinical study Exclusion Criteria: Patients who were taking Pioglitazone or Evoglipitin medication or who took diabetes medication within 4 weeks at the time Patients who meet the standard of alcoholic fatty liver (in excess of 210g per week for men and 140g per week for women over the last two years) Liver cirrhosis patients with impaired liver function (CTP class B and C) Patients who took drugs that can cause fatty liver (amiodarone, methotrexate, tamoxifen, valproate, corticosteroids, etc.) Patients with acute or chronic metabolic acidosis with or without coma and history of ketonic acid (within 24 weeks) Allergic or hypersensitive to the target drug or its composition; Patients treated with oral or non - oral corticosteroid treatment for chronic (more than 14 consecutive days) within 8 weeks prior to screening. Poor nutrition, starvation, and debilitating conditions (including severe infections and severe injury patients before and after surgery) Patients who are receiving radiation and chemotherapy for malignant tumors or patients who have been on chemotherapy or radiation treatment for less than two years. Patients with heart failure in 24 weeks (class III to IV in NYHA classification) or unregulated arrhythmia. Patients with acute cardiovascular disease in 12 weeks or less (e.g. unstable angina, myocardial infarction, routine ischemic seizures, cerebrovascular disease, coronary bypass surgery, or coronary artery interventions). Patients with renal failure, chronic neuropathy (estimated glomerular filtration rate <60 mL/min/1.73 m2) or dialysis Anemia patients whose Hb levels are less than 10.5g/dl Women who are pregnant or breastfeeding Patients who do not agree to use proper contraception during clinical trials only for women or men. Patients who took medicines for clinical trials in other clinical trials within four weeks of document consent Patients who are unable to participate in clinical trials on the judgment of other researchers Patients who cannot read the consent form (e.g. illiteracy, foreigners, etc.)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pioglitazone<br> | Drug: gluconon tab 15mg<br>* frosting and formulation : a round, convex tablet of white to gray. path of administration : once a day, two tabs, oral Amount of raw material medication (1 pill) : Pioglitazone hydrochloride 16.53mg storage method : Store 15 to 30°C to avoid light-tight containers and moisture manufacturing source : DONG-A ST<br>|
| Experimental: Evogliptin<br> | Drug: suganon tab 5mg<br>* frosting and formulation : pink circular film coating tablets path of administration : once a day, one tabs, oral Amount of raw material medication (1 pill) : Evogliptin tartrate 6.869mg(5mg as evogliptin) storage method : Confidential containers, stored at room temperature (1-30°C) manufacturing source : DONG-A ST<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline LSM (Liver Stiffness measurement) at week 24 (±7days) | Changes in the Liver Stiffness measurement after 24 weeks (±7days) compared to Baseline within and between arms | Baseline | 
| Changes from baseline LSM (Liver Stiffness measurement) at week 24 (±7days) | Changes in the Liver Stiffness measurement after 24 weeks (±7days) compared to Baseline within and between arms | Baseline to 24 weeks (±7days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline CAP (Controlled Attenuation Parameter) at week 24 (±7days) within and between arms | Change from baseline at Week 24 (±7days) is defined as [(Baseline CAP value) - (Follow-up CAP value)] / (Baseline CAP value) * 100 (%) | 1) Baseline, 2) Baseline to 24 weeks (±7days) | 
| Changes from baseline HbA1c at week 24 (±7days) within and between arms | Change from baseline at Week 24 (±7days) is defined as HbA1c at Week 24 (±7days) minus HbA1c at Week 0 | 1) Baseline, 2) Baseline to 24 weeks (±7days) | 
| Changes from baseline Insulin at week 24 (±7days) within and between arms | Change from baseline at Week 24 (±7days) is defined as insulin at Week 24 (±7days) minus insulin at Week 0 | 1) Baseline, 2) Baseline to 24 weeks (±7days) | 
| Changes from baseline lipid profile (total cholesterol, HDL, LDL, TG) at week 24 (±7days) within and between arms | Change from baseline at Week 24 (±7days) is defined as lipid profile (total cholesterol, HDL, LDL, TG) at Week 24 (±7days) minus lipid profile at Week 0 | 1) Baseline, 2) Baseline to 24 weeks (±7days) | 
| Changes from baseline AST/ALT at week 24 (±7days) within and between arms | Change form baseline at Week 24 (±7days) is defined as the proportion of AST/ALT values who are normalized at Week 24 (±7days) | 1) Baseline, 2) Baseline to 24 weeks (±7days) | 
| Changes from baseline Body weight at week 24 (±7days) within and between arms | Change from baseline at Week 24 (±7days) is defined as body weight at Week 24 minus body weight at Week 0 | 1) Baseline, 2) Baseline to 24 weeks (±7days) | 
| Changes from baseline Liver fibrosis and fatty liver at week 24 (±7days) among the MRE+MRI PDFF enforcement arms within and between arms | Change from baseline at Week 24 (±7days) is defined by MRE+MRI PDFF | 1) Baseline, 2) Baseline to 24 weeks (±7days) | 
| Proportions of adverse effects and drug interruptions or changes between baseline and week 24 (±7days) within and between arms | Compare between baseline at Week 24 (±7days) is defined as the occurrence rate of adverse events and drug interruptions or changes | 1) Baseline, 2) Baseline to 24 weeks (±7days) | 
| Prognostic factor of the Improvement of Liver fibrosis between baseline and week 24 (±7days) within and between arms | Prediction Factor Analysis of the Improvement of Liver fibrosis after 24 (±7days) weeks compared to Baseline within and between arms | 1) Baseline, 2) Baseline to 24 weeks (±7days) | 
| Prognostic factor of the Improvement of Fatty liver between baseline and week 24 (±7days) within and between arms | Prediction Factor Analysis of the Improvement of Fatty liver after 24 weeks (±7days) compared to Baseline within and between arms | 1) Baseline, 2) Baseline to 24 weeks (±7days) | 
| Prognostic factor of the Improvement of HbA1 between baseline and week 24 (±7days) within and between arms | Prediction Factor Analysis of the Improvement of HbA1c after 24 weeks (±7days) compared to Baseline within and between arms | 1) Baseline, 2) Baseline to 24 weeks (±7days) |