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
Primary Purpose
Type 2 Diabetes Mellitus
Status
Terminated
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
metformin
ipragliflozin
glimepiride
Sponsored by
About this trial
This is an interventional treatment trial for Type 2 Diabetes Mellitus focused on measuring Metformin, Ipragliflozin, Type 2 Diabetes Mellitus, ASP1941, Glimepiride
Eligibility 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.
Sites / Locations
- Site 13
- Site 02
- Site 11
- Site 01
- Site 05
- Site 07
- Site 09
- Site 12
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
ipragliflozin and metformin
glimepiride and metformin
Arm Description
Subjects will receive daily dosage of ipragliflozin and metformin as single tablets
Subjects will receive daily dosage of glimepiride and metformin as single tablets
Outcomes
Primary Outcome Measures
The percentage of change of Urine Albumin-to-Creatinine Ratio (UACR)
Early morning urinary sample will be collected for the test
Secondary Outcome Measures
The percentage of patients whose UACR level is normalized or improved more than 50%
Early morning urinary sample will be collected for the test
Change from baseline in Estimated glomerular filtration rate (e-GFR)
Test parameter e-GFR shall be measured at the local laboratory
Change from baseline in Hemoglobin A1c (HbA1c)
Test parameter HbA1c shall be measured at the local laboratory
Change from baseline in Fasting Plasma Glucose (FPG)
Test parameter FPG shall be measured at the local laboratory
Change from baseline in body weight
Body Weight shall be measured by the same scale for the clinical trial period
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
Change from baseline in Uric Acid
Test parameter Uric Acid shall be measured at the local laboratory
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
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
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
Full Information
NCT ID
NCT03118713
First Posted
April 13, 2017
Last Updated
April 12, 2020
Sponsor
Astellas Pharma Korea, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT03118713
Brief Title
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
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Terminated
Why Stopped
Business decision due to enrollment challenges
Study Start Date
April 25, 2017 (Actual)
Primary Completion Date
December 12, 2018 (Actual)
Study Completion Date
December 12, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Korea, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes Mellitus
Keywords
Metformin, Ipragliflozin, Type 2 Diabetes Mellitus, ASP1941, Glimepiride
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
33 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ipragliflozin and metformin
Arm Type
Experimental
Arm Description
Subjects will receive daily dosage of ipragliflozin and metformin as single tablets
Arm Title
glimepiride and metformin
Arm Type
Experimental
Arm Description
Subjects will receive daily dosage of glimepiride and metformin as single tablets
Intervention Type
Drug
Intervention Name(s)
metformin
Other Intervention Name(s)
Fortamet, Riomet, Glucophage, Diabex XR, Glumetza, Diabex, Glucophage XR
Intervention Description
oral
Intervention Type
Drug
Intervention Name(s)
ipragliflozin
Other Intervention Name(s)
ASP1941, Suglat
Intervention Description
oral
Intervention Type
Drug
Intervention Name(s)
glimepiride
Other Intervention Name(s)
Amaryl
Intervention Description
oral
Primary Outcome Measure Information:
Title
The percentage of change of Urine Albumin-to-Creatinine Ratio (UACR)
Description
Early morning urinary sample will be collected for the test
Time Frame
Baseline up to 24 weeks
Secondary Outcome Measure Information:
Title
The percentage of patients whose UACR level is normalized or improved more than 50%
Description
Early morning urinary sample will be collected for the test
Time Frame
Baseline up to 24 weeks
Title
Change from baseline in Estimated glomerular filtration rate (e-GFR)
Description
Test parameter e-GFR shall be measured at the local laboratory
Time Frame
Baseline up to 24 weeks
Title
Change from baseline in Hemoglobin A1c (HbA1c)
Description
Test parameter HbA1c shall be measured at the local laboratory
Time Frame
Baseline up to 24 weeks
Title
Change from baseline in Fasting Plasma Glucose (FPG)
Description
Test parameter FPG shall be measured at the local laboratory
Time Frame
Baseline up to 24 weeks
Title
Change from baseline in body weight
Description
Body Weight shall be measured by the same scale for the clinical trial period
Time Frame
Baseline up to 24 weeks
Title
Change from baseline in blood pressure
Description
Blood pressure will be measured two times with 1-2 minutes interval by the same arm and procedure during the study
Time Frame
Baseline up to 24 weeks
Title
Change from baseline in Uric Acid
Description
Test parameter Uric Acid shall be measured at the local laboratory
Time Frame
Baseline up to 24 weeks
Title
Change from baseline in health status as measured through EuroQol 5 Dimension 5 Level Health State Utility Index (EQ-5D-5L) questionnaire
Description
The EQ-5D-5L Questionnaire consists of 5 domains: mobility, self-care, usual activities, pain/discomfort, anxiety/depression
Time Frame
Baseline up to 24 weeks
Title
Change from baseline in health status as measured through EuroQol-Visual Analogue Scale (EQ VAS) questionnaire
Description
The EQ VAS measures the score (0 to 100) of change from baseline to 24 weeks
Time Frame
Baseline up to 24 weeks
Title
Change from baseline in Quality of Life as measured through Audit of Diabetes-Dependent Quality of Life-19 (ADDQoL-19) questionnaire
Description
Quality of Life will be assessed through ADDQoL-19. Patients will be asked to complete the questionnaires at visit 2 and 5
Time Frame
Baseline up to 24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Astellas Pharma Korea, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Site 13
City
Busan
Country
Korea, Republic of
Facility Name
Site 02
City
Deagu
Country
Korea, Republic of
Facility Name
Site 11
City
Guri-si
Country
Korea, Republic of
Facility Name
Site 01
City
Seoul
Country
Korea, Republic of
Facility Name
Site 05
City
Seoul
Country
Korea, Republic of
Facility Name
Site 07
City
Seoul
Country
Korea, Republic of
Facility Name
Site 09
City
Seoul
Country
Korea, Republic of
Facility Name
Site 12
City
Suwon-si
Country
Korea, Republic of
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing 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."
Links:
URL
https://astellasclinicalstudyresults.com/hcp/study.aspx?ID=359
Description
Link to results on the Astellas Clinical Study Results website
Learn more about this trial
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
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