Effect of Evogliptin on Albuminuria in Patients With Type 2 Diabetes and Renal Insufficiency

Study Overview
=================
Brief Summary
-----------------
In this multi-center, randomized, double-blind, active-controlled, phase II non-inferiority study, we aimed to test the non-inferiority of evogliptin vs linagliptin in terms of reduction of albuminuria at week 24 from baseline in patients with type 2 diabetes having renal insufficiency.

Detailed Description
-----------------
This is a multi-center, randomized, double-blind, active-controlled, phase II non-inferiority study. Evogliptin (Trade name, Suganon) is a new, novel dipeptidyl peptidase-4 (DPP4) inhibitor which reveals a favorable results on glucose-lowering effect in patients with diabetes. However, its effect on renal function in patients with diabetes has been uncertained. To compare the effect of evogliptin and linagliptin on the reduction of albuminuria, we will recruit a total of 210 patients with Type 2 diabetes and renal insufficiency and allocate the participants into evogliptin group and linagliptin group with a ratio of 1:1 after radomization from 10 hospitals. After the oral administration of evogliptin 5mg per day or linagliptin 5mg per day for 24 weeks, the percent change of urine albumin-to-creatinine ratio (UACR) at Week 24 and at baseline will be measured as a primary endpoint. In addition, the percent changes of UACR, hemoglobin A1c, Cystatin-C, Nephrin, N-acetyl-beta-D-glucosaminidase (NAG), glycated albumin, estimated glomerular filtration rate (eGFR) between baseline and Week 12 or Week 24 will be studied as secondary endpoints.

Official Title
-----------------
Evogliptin Versus Linagliptin for the Effect on Albuminuria in Patients With Type 2 Diabetes and Renal Insufficiency: a Multicenter, Randomised, Double-blind, Active-controlled, Non-inferiority Trial

Conditions
-----------------
Type2 Diabetes Mellitus, Albuminuria, Renal Insufficiency

Intervention / Treatment
-----------------
* Drug: Evogliptin
* Drug: Linagliptin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women aged 20 years or older diagnosed with type 2 diabetes. subjects having a level of glycated hemoglobin (HbA1c) 7.0% or more, and 10% or less. subjects having urine albumin to creatinine ratio (UACR) 30 ug/mg or more, and 3000 ug/mg or less. subjects having estimated glomerular filtration rate (eGFR) 30 or more. subjects who had taken angiotensin II receptor blocker(ARB) or angiotensin-converting enzyme(ACE) inhibitors for more than 4 weeks. subjects having body mass index (BMI) 20kg/m2 or more, 40 kg/m2 or less. subjects who entirely understood all the process of clinical study protocol and voluntarily take part in the study and agree to follow rule of the study. Exclusion Criteria: subjects having type 1 diabetes, secondary diabetes, or gestational diabetes subjects who had a history of surgery of resection of more than a half length of stomach or intestine. subjects having more than three-fold higher levels of Aspartate Transaminase(AST) or Alanine Transaminase(ALT) than upper normal limit. subjects who had taken Dipeptidyl Peptidase4(DPP4)-inhibitor or glucagon-like peptide-1(GLP-1) analogue within 8 weeks prior to screening. subjects who had taken oral triple hypoglycemic agents within 8 weeks prior to screening subjects taking strong cytochrome P450 3A4(CYP3A4) inhibitors or strong cytochrome P450 3A4(CYP3A4) inducers subjects who are pregnants or breast feeding givers. subjects who are unsuitable for clinical trial participation based on clinical laboratory test results or other reasons (e.g. taking chemotherapy or radiation for treatment for cancers).

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Evogliptin Group<br>Intervention group will take daily evogliptin 5mg per oral, not linagliptin 5mg per oral | Drug: Evogliptin<br>* This group will take daily evogliptin 5mg per oral, not linagliptin.<br>* Other names: Suganon;|
| Active Comparator: Linagliptin Group<br>Control group will take daily linagliptin 5mg per oral, not evogliptin 5mg per oral | Drug: Linagliptin<br>* This group will take daily linagliptin 5mg per oral, not evogliptin<br>* Other names: Trajenta;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UACR percent change at Week 24 | Percentage change in urine albumin-to-creatinine ratio (UACR) after 24 weeks compared to baseline (%) | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UACR change at Week 24 (%) | Change in urine albumin-to-creatinine ratio (UACR) after 24 weeks compared to baseline (%) | Week 24 | 
| UACR change at Week 12 | Change in urine albumin-to-creatinine ratio (UACR) after 12 weeks compared to baseline (mg/g | Week 12 | 
| HbA1c change at Week 24 | Change in glycated hemoglobin after 24 weeks compared to baseline | Week 24 | 
| HbA1c change at Week 12 | Change in glycated hemoglobin after 12 weeks compared to baseline | Week 12 | 
| HbA1c less than 6.5% at Week 24 | proportion of parcipitants having glycated hemoglobin less than 6.5% after 24 weeks | Week 24 | 
| HbA1c less than 6.5% at Week 12 | proportion of participants having glycated hemoglobin less than 6.5% after 12 weeks | Week 12 | 
| HbA1c less than 7.0% at Week 24 | proportion of participants having glycated hemoglobin less than 7.0% after 24weeks | Week 24 | 
| HbA1c less than 7.0% at Week 12 | proportion of participants having glycated hemoglobin less than 7.0% after 12 weeks | Week 12 | 
| NAG (N-acetyl-β-D-glucosaminidase) change at Week 24 | Change in NAG (N-acetyl-β-D-glucosaminidase) after 24 weeks compared to baseline (U/L) | Week 24 | 
| NAG (N-acetyl-β-D-glucosaminidase) change at Week 12 | Change in NAG (N-acetyl-β-D-glucosaminidase) after 12 weeks compared to baseline (U/L) | Week 12 | 
| Cystatin-C change at Week 24 | Change in urinary Cystatin-C after 24 weeks compared to baseline (mg/L) | Week 24 | 
| Cystatin-C change at Week 12 | Change in urinary Cystatin-C after 12 weeks compared to baseline (mg/L) | Week 12 | 
| Nephrin change at Week 24 | Change in Nephrin after 24 weeks compared to baseline (ug/g cr) | Week 24 | 
| Nephrin change at Week 12 | Change in Nephrin after 12 weeks compared to baseline (ug/g cr) | Week 12 | 
| Glycated albumin change at Week 24 | Change in Glycated albumin after 24 weeks compared to baseline (%) | Week 24 | 
| Glycated albumin change at Week 12 | Change in Glycated albumin after 12 weeks compared to baseline (%) | Week 12 | 
| eGFR at Week 24 | Change in estimated glomerular filtration rate based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method after 24 weeks compared to baseline (mL/min) | Week 24 | 
| eGFR change at Week 12 | Change in estimated glomerular filtration rate based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method after 12 weeks compared to baseline (mL/min) | Week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Type2 Diabetes Mellitus, Intervention, Albuminuria