A 24 Week, Multicenter, Prospective, Open-labeled, Single-arm, Exploratory Phase 4 Clinical Trial to Evaluate the Safety and Efficacy of Lobeglitazone in Decreasing Intrahepatic Fat Contents in Type 2 Diabetes With NAFLD

Lobeglitazone is highly selective peroxisome proliferator-activated receptor-gamma agonist that decreases insulin resistance in the periphery and liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. In vivo, It demonstrates that Lobeglitazone improves even more glycemic and lipid control in comparison to rosiglitazone and pioglitazone. Currently, thiazolidinediones such as pioglitazone is the only drug which is considered as an effective therapeutic agent for improving non-alcoholic fatty liver disease (NALFD) in type 2 diabetes (T2D).

The aim of this multicenter, prospective, open-labeled, single-arm, exploratory phase 4 study is to evaluate the efficacy and safety of Lobeglitazone once daily for 24 weeks on intrahepatic fat contents assessed by transient elastography (fibroscan) in T2D with NAFLD.

Fifty subjects with T2D and NAFLD will take Lobeglitazone (0.5mg/tablet, orally, 1 tablet once daily) for 24 weeks.

Primary endpoint is changes from baseline in controlled attenuation parameters (CAP) measured by transient elastography (fibroscan) after treatment with Lobeglitazone.

Secondary endpoints are changes from baseline in glycemic profiles (HbA1c, Glycated albumin), Lipid parameters (Total Cholesterol, Triglycerides, HDL-C, LDL-C), Liver function parameters (AST, ALT, r-GT), and adverse events during the trial.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes; Non-alcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: Oral administration of Lobeglitazone

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 120-752
    • Severance Hospital, Department of Internal Medicine, Yonsei University College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Type Ⅱ diabetes mellitus
2. Non-alcoholic fatty liver disease: subjects who have CAP(Controlled Attenuation Parameter) ≥ 250dB/m measured by transient elastography (fibroscan) at screening test
3. Age ≥ 20 years
4. Patients who have not been taking any oral hypoglycemic agent for more than 12 weeks with HbA1c 7.0 to 8.5% at screening test or who have been taking metformin monotherapy for at least 8 weeks with HbA1c 7 to 9% at screening test
5. Agreement with written informed consent

Exclusion Criteria:

1. Patients whose alcohol consumption >210g/week for males and 140g/week for females
2. chronic B viral hepatitis, chronic C viral hepatitis, Type I diabetes, or secondary diabetes
3. having a history of acute or chronic metabolic acidosis including diabetic ketoacidosis
4. patients who have been taking other oral hypoglycemic agents except metformin or insulin within recent 8 weeks
5. who experienced hypersensitivity reaction against metformin or glitazone drugs
6. who has been treated with corticosteroids for at least 14 days within 2 month prior to Screening
7. having a history of lactic acidosis
8. having genetic predispositions such as galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption
9. who are in condition of malnutrition, starvation, cachexia, severe infection, major trauma, hypopituitarism, or adrenal insufficiency
10. diagnosed with cancer within 2 years or having chemo or radiotherapy for cancer treatment
11. a history of drug abuse or chronic alcoholism
12. a history of heart failure (NYHA class III and IV) or uncontrolled arrhythmia
13. a history of acute cardiovascular or cerebrovascular disease within 12 weeks prior to Screening (unstable angina, myocardial infarction, transient ischemic attack, cerebral infarct, cerebral hemorrhage, coronary bypass, percutaneous coronary intervention)
14. Renal dysfunction: Serum creatinine greater than 1.5mg/dl for males and 1.4mg/dl for females.
15. Anemia less than 10.5g/dl for any reason
16. Pregnant women or nursing mothers
17. Fertile women who not practice contraception with appropriate methods
18. in treatment concomitant drug from other clinical trials within 4 weeks from enrollment
19. who did not agree with written informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lobeglitazone	Drug: Oral administration of Lobeglitazone; Lobeglitazone 0.5mg/tablet, orally, 1 tablet once daily for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes from baseline in controlled attenuation parameters (CAP)	Changes from baseline in controlled attenuation parameters (CAP) measured by transient elastography (fibroscan) after treatment with Lobeglitazone	24 weeks

Collaborators and Investigators

• Sponsor: Yonsei University

Publications and helpful links

General Publications

• Lee YH, Kim JH, Kim SR, Jin HY, Rhee EJ, Cho YM, Lee BW. Lobeglitazone, a Novel Thiazolidinedione, Improves Non-Alcoholic Fatty Liver Disease in Type 2 Diabetes: Its Efficacy and Predictive Factors Related to Responsiveness. J Korean Med Sci. 2017 Jan;32(1):60-69. doi: 10.3346/jkms.2017.32.1.60.

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: November 4, 2014
• First Submitted That Met QC Criteria: November 4, 2014
• First Posted (Estimate): November 6, 2014

Study Record Updates

• Last Update Posted (Estimate): February 2, 2016
• Last Update Submitted That Met QC Criteria: January 31, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Liver Diseases; Diabetes Mellitus, Type 2; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 4-2014-0778