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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03118713
• Other study ID #: 1941-MA-3122-KR
• Status: Terminated
• Phase: Phase 4
• Start date: April 25, 2017
• Est. completion date: December 12, 2018

Study information

• Verified date: April 2020
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 33
• Est. completion date: December 12, 2018
• Est. primary completion date: December 12, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 74 Years

Eligibility

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.

Related Conditions & MeSH terms

• Albuminuria
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• metformin
oral
• ipragliflozin
oral
• glimepiride
oral

Locations

Country	Name	City	State
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

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Korea, Inc.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Change from baseline in Hemoglobin A1c (HbA1c)	Test parameter HbA1c shall be measured at the local laboratory	Baseline up to 24 weeks
Secondary	Change from baseline in Fasting Plasma Glucose (FPG)	Test parameter FPG shall be measured at the local laboratory	Baseline up to 24 weeks
Secondary	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
Secondary	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
Secondary	Change from baseline in Uric Acid	Test parameter Uric Acid shall be measured at the local laboratory	Baseline up to 24 weeks
Secondary	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
Secondary	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
Secondary	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

External Links

•   Link to results on the Astellas Clinical Study Results website