A Study to Evaluate the Renal Protective Effect (Urine Albumin-to-Creatinine Ratio (UACR)), Efficacy and Safety of Ipragliflozin in Type 2 Diabetes Mellitus Patients With Albuminuria

A Phase 4, Randomized, Open-label, Active-controlled, Multicenter Study to Evaluate the Renal Protective Effect (UACR), Efficacy and Safety of Ipragliflozin in Type 2 Diabetes Mellitus Patients With Albuminuria

The primary purpose of this study is to assess the renal protective effect of ipragliflozin in combination with metformin on the percent change of UACR from baseline to 24 weeks against glimepiride in combination with metformin in type 2 diabetes mellitus patients with albuminuria. The secondary purpose of this study is to assess the efficacy, safety and impact on quality of life (QoL) of ipragliflozin in combination with metformin against glimepiride in combination with metformin in type 2 diabetes mellitus patients with albuminuria.

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: ipragliflozin; Drug: metformin; Drug: glimepiride

Detailed Description

This is a multicenter study that will compare ipragliflozin/metformin with glimepiride/metformin in the treatment of type 2 diabetes mellitus (T2DM) with albuminuria.

The study will include screening and 24-week treatment period. Subjects entering the study have been on a stable dose of at least 1000 mg/day metformin monotherapy for at least 8 weeks (56 days) prior to Visit 1. For randomization, subject will be stratified by the site and the administration of renin-angiotensin system inhibitors (angiotensin receptor blockers and/or angiotensin-converting-enzyme inhibitors) at Visit 2. Subjects will be centrally randomized to either ipragliflozin/metformin group or glimepiride/metformin group and receive 24-week treatment by each group

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of
    • Site 13
  • Deagu, Korea, Republic of
    • Site 02
  • Guri-si, Korea, Republic of
    • Site 11
  • Seoul, Korea, Republic of
    • Site 01
  • Seoul, Korea, Republic of
    • Site 05
  • Seoul, Korea, Republic of
    • Site 07
  • Seoul, Korea, Republic of
    • Site 09
  • Suwon-si, Korea, Republic of
    • Site 12

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 74 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Inclusion Criteria assessed at Visit 1:

• Subject who is outpatient.
• Subject who has been diagnosed with type 2 diabetes mellitus.
• Subject who has been on a stable dose of at least 1000 mg/day metformin monotherapy for at least 8 weeks (56 days) prior to Visit 1.
• Subject who has an HbA1C value between 7.0% and 9.0% at Visit 1.
• Subject who has a urinary albumin/creatinine ratio greater than or equal to 30 mg/g at Visit 1.
• Subject who has eGFR greater than or equal to 45 mL/min/1.73 m^2.
• Subject is on stable diet and exercise program for at least 8 weeks (56 days) prior to Visit 1.

Inclusion Criterion assessed at Visit 2:

• Subject who has a urinary albumin/creatinine ratio greater than or equal to 30 mg/g at Visit 2.

Exclusion Criteria:

• Subject who has been diagnosed with type 1 diabetes mellitus.
• Subject who started or has changed the types and/or dosage of Renin Angiotensin System (RAS) inhibitors (Angiotensin II Receptor Blockers (ARBs), ACE inhibitors) within 12 weeks prior to Visit 1.
• Subject who has been treated with Sodium-Glucose Cotransporter-2 (SGLT-2) inhibitors within 12 weeks prior to Visit 1.
• Subject who has a history of clinically significant renal disease(s) (other than diabetic nephropathy) such as renovascular occlusive disease, nephrectomy, or renal transplant.
• Subject who has a diabetic ketoacidosis, or history of diabetic ketoacidosis.
• Subject with diabetic coma or precoma.
• Subject with severe infection, serious trauma, or perioperative subject at Visit 1
• Subject who has a history of hypersensitivity to ipragliflozin or glimepiride or other SGLT-2 inhibitors or sulfonylureas.
• Subject has Aspartate Aminotransferase (GOT) (AST) or Alanine Aminotransferase (GPT) (ALT) value exceeding 3 times of upper limit of the normal range, or total bilirubin value exceeding 3 times of upper limit of the normal range at Visit 1.
• Subject has progressive proliferative diabetic retinopathy.
• Subject has a symptomatic urinary tract infection or genital infection at Visit 1.
• Subject has uncontrollable psychiatric disorder(s) with medication.
• Subject abuses drug or alcohol at Visit 1.
• Subject has lactic acidosis or has history of lactic acidosis.
• Subject who has been known to have Hepatitis B, Hepatitis C or Positive Human immunodeficiency virus (HIV).
• Subject is unable or unwilling to adhere to any of the protocol requirements such as hospital visits and dose instruction specified in this study.
• Subject with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
• Subject has participated in another interventional study with study drugs within 12 weeks prior to obtaining written informed consent.
• Subject has a clinical condition which would not allow safe conduct of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ipragliflozin and metformin; Subjects will receive daily dosage of ipragliflozin and metformin as single tablets	Drug: ipragliflozin; oral; Other Names: ASP1941; Suglat; Drug: metformin; oral; Other Names: Glucophage; Glucophage XR; Glumetza; Fortamet; Riomet; Diabex; Diabex XR
EXPERIMENTAL: glimepiride and metformin; Subjects will receive daily dosage of glimepiride and metformin as single tablets	Drug: metformin; oral; Other Names: Glucophage; Glucophage XR; Glumetza; Fortamet; Riomet; Diabex; Diabex XR; Drug: glimepiride; oral; Other Names: Amaryl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The percentage of change of Urine Albumin-to-Creatinine Ratio (UACR)	Early morning urinary sample will be collected for the test	Baseline up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The percentage of patients whose UACR level is normalized or improved more than 50%	Early morning urinary sample will be collected for the test	Baseline up to 24 weeks
Change from baseline in Estimated glomerular filtration rate (e-GFR)	Test parameter e-GFR shall be measured at the local laboratory	Baseline up to 24 weeks
Change from baseline in Hemoglobin A1c (HbA1c)	Test parameter HbA1c shall be measured at the local laboratory	Baseline up to 24 weeks
Change from baseline in Fasting Plasma Glucose (FPG)	Test parameter FPG shall be measured at the local laboratory	Baseline up to 24 weeks
Change from baseline in body weight	Body Weight shall be measured by the same scale for the clinical trial period	Baseline up to 24 weeks
Change from baseline in blood pressure	Blood pressure will be measured two times with 1-2 minutes interval by the same arm and procedure during the study	Baseline up to 24 weeks
Change from baseline in Uric Acid	Test parameter Uric Acid shall be measured at the local laboratory	Baseline up to 24 weeks
Change from baseline in health status as measured through EuroQol 5 Dimension 5 Level Health State Utility Index (EQ-5D-5L) questionnaire	The EQ-5D-5L Questionnaire consists of 5 domains: mobility, self-care, usual activities, pain/discomfort, anxiety/depression	Baseline up to 24 weeks
Change from baseline in health status as measured through EuroQol-Visual Analogue Scale (EQ VAS) questionnaire	The EQ VAS measures the score (0 to 100) of change from baseline to 24 weeks	Baseline up to 24 weeks
Change from baseline in Quality of Life as measured through Audit of Diabetes-Dependent Quality of Life-19 (ADDQoL-19) questionnaire	Quality of Life will be assessed through ADDQoL-19. Patients will be asked to complete the questionnaires at visit 2 and 5	Baseline up to 24 weeks

Collaborators and Investigators

• Sponsor: Astellas Pharma Korea, Inc.

Publications and helpful links

Helpful Links

• Link to results on the Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 25, 2017
• Primary Completion (ACTUAL): December 12, 2018
• Study Completion (ACTUAL): December 12, 2018

Study Registration Dates

• First Submitted: April 13, 2017
• First Submitted That Met QC Criteria: April 13, 2017
• First Posted (ACTUAL): April 18, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 14, 2020
• Last Update Submitted That Met QC Criteria: April 12, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Metformin; ASP1941; Type 2 Diabetes Mellitus; Glimepiride; Ipragliflozin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Urological Manifestations; Endocrine System Diseases; Urination Disorders; Proteinuria; Diabetes Mellitus; Diabetes Mellitus, Type 2; Albuminuria; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Immunosuppressive Agents; Immunologic Factors; Sodium-Glucose Transporter 2 Inhibitors; Metformin; Glimepiride; Ipragliflozin
• Other Study ID Numbers: 1941-MA-3122-KR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."

Drug and device information, study documents

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