Effect of Evogliptin on Albuminuria in Patients With Type 2 Diabetes and Renal Insufficiency (DA1229)

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency; Albuminuria; Type2 Diabetes Mellitus
• Intervention / Treatment: Drug: Evogliptin; Drug: Linagliptin

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.

• Study Type: Interventional
• Enrollment (Actual): 209
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center

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:

• 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Evogliptin Group; Intervention group will take daily evogliptin 5mg per oral, not linagliptin 5mg per oral	Drug: Evogliptin; This group will take daily evogliptin 5mg per oral, not linagliptin.; Other Names: Suganon
Active Comparator: Linagliptin Group; Control group will take daily linagliptin 5mg per oral, not evogliptin 5mg per oral	Drug: Linagliptin; This group will take daily linagliptin 5mg per oral, not evogliptin; 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

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: Jae Hyeon Kim, MD PhD, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2017
• Primary Completion (Actual): May 14, 2019
• Study Completion (Actual): May 14, 2019

Study Registration Dates

• First Submitted: February 20, 2018
• First Submitted That Met QC Criteria: September 10, 2018
• First Posted (Actual): September 12, 2018

Study Record Updates

• Last Update Posted (Actual): September 23, 2019
• Last Update Submitted That Met QC Criteria: September 19, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Intervention; Albuminuria; Type2 Diabetes Mellitus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Kidney Diseases; Urologic Diseases; Urological Manifestations; Endocrine System Diseases; Urination Disorders; Proteinuria; Diabetes Mellitus; Diabetes Mellitus, Type 2; Renal Insufficiency; Albuminuria; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Linagliptin
• Other Study ID Numbers: 2016-08-144

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No