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

• ClinicalTrials.gov Identifier: NCT03118713
• Recruitment Status: Terminated
• First Posted: April 18, 2017
• Last Update Posted: April 14, 2020
• Sponsor: Astellas Pharma Korea, Inc.
• Information provided by (Responsible Party): Astellas Pharma Inc ( Astellas Pharma Korea, Inc. )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Type 2 Diabetes Mellitus	Drug: metformin; Drug: ipragliflozin; Drug: glimepiride	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 33 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: April 25, 2017
• Actual Primary Completion Date: December 12, 2018
• Actual Study Completion Date: December 12, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. The percentage of change of Urine Albumin-to-Creatinine Ratio (UACR) [ Time Frame: Baseline up to 24 weeks ]
   Early morning urinary sample will be collected for the test

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 19 Years to 74 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Korea, Republic of

Site 13

Busan, Korea, Republic of

Site 02

Deagu, Korea, Republic of

Site 11

Guri-si, Korea, Republic of

Site 01

Seoul, Korea, Republic of

Site 05

Seoul, Korea, Republic of

Site 07

Seoul, Korea, Republic of

Site 09

Seoul, Korea, Republic of

Site 12

Suwon-si, Korea, Republic of

Sponsors and Collaborators

Astellas Pharma Korea, Inc.

Investigators

• Study Director: Medical Monitor; Astellas Pharma Korea, Inc.

More Information

Additional Information:

Link to results on the Astellas Clinical Study Results website 

• Responsible Party: Astellas Pharma Korea, Inc.
• ClinicalTrials.gov Identifier: NCT03118713
• Other Study ID Numbers: 1941-MA-3122-KR
• First Posted: April 18, 2017
• Last Update Posted: April 14, 2020
• Last Verified: April 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• 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."

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Korea, Inc. ):

Metformin; Ipragliflozin; Type 2 Diabetes Mellitus; ASP1941; Glimepiride

Additional relevant MeSH terms:

Albuminuria; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Proteinuria; Urination Disorders; Urologic Diseases; Urological Manifestations; Metformin; Glimepiride; Ipragliflozin; Hypoglycemic Agents; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Immunosuppressive Agents; Immunologic Factors; Sodium-Glucose Transporter 2 Inhibitors; Molecular Mechanisms of Pharmacological Action