Clinical trial NCT03118713: 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
Overall status: TERMINATED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Keywords: Metformin
Ipragliflozin
Type 2 Diabetes Mellitus
ASP1941
Glimepiride
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2017-04-18
Enrollment: 33
Sex: ALL
Minimum age (years): 19
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: The percentage of change of Urine Albumin-to-Creatinine Ratio (UACR)
timeFrame: Baseline up to 24 weeks
Secondary outcomes:
measure: The percentage of patients whose UACR level is normalized or improved more than 50%
timeFrame: Baseline up to 24 weeks
measure: Change from baseline in Estimated glomerular filtration rate (e-GFR)
timeFrame: Baseline up to 24 weeks
measure: Change from baseline in Hemoglobin A1c (HbA1c)
timeFrame: Baseline up to 24 weeks
measure: Change from baseline in Fasting Plasma Glucose (FPG)
timeFrame: Baseline up to 24 weeks
measure: Change from baseline in body weight
timeFrame: Baseline up to 24 weeks
measure: Change from baseline in blood pressure
timeFrame: Baseline up to 24 weeks
measure: Change from baseline in Uric Acid
timeFrame: Baseline up to 24 weeks
measure: Change from baseline in health status as measured through EuroQol 5 Dimension 5 Level Health State Utility Index (EQ-5D-5L) questionnaire
timeFrame: Baseline up to 24 weeks
measure: Change from baseline in health status as measured through EuroQol-Visual Analogue Scale (EQ VAS) questionnaire
timeFrame: Baseline up to 24 weeks
measure: Change from baseline in Quality of Life as measured through Audit of Diabetes-Dependent Quality of Life-19 (ADDQoL-19) questionnaire
timeFrame: Baseline up to 24 weeks
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: Site 13
city: Deagu
country: Korea, Republic of
facility: Site 02
city: Guri-si
country: Korea, Republic of
facility: Site 11
city: Seoul
country: Korea, Republic of
facility: Site 01
city: Seoul
country: Korea, Republic of
facility: Site 05
city: Seoul
country: Korea, Republic of
facility: Site 07
city: Seoul
country: Korea, Republic of
facility: Site 09
city: Suwon-si
country: Korea, Republic of
facility: Site 12
Study officials:
affiliation: Astellas Pharma Korea, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References: