Study of Ipragliflozin in Patients With Type 2 Diabetes Mellitus Receiving Insulin Therapy

Study Overview
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Brief Summary
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The objective of this study is to assess the reduction in insulin dose from baseline at Week 24 while keeping the blood glucose levels controlled (maintaining HbA1c values) when ipragliflozin is administered once daily for 24 weeks in patients with type 2 diabetes mellitus receiving insulin therapy.

Official Title
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Post-marketing Clinical Study of Ipragliflozin; Multicenter, Open-label Study to Assess the Efficacy of Ipragliflozin Add-on in Reducing Insulin Dose in Patients With Type 2 Diabetes Mellitus Receiving Insulin Therapy

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Ipragliflozin
* Drug: Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject has been receiving insulin therapy for the treatment of diabetes mellitus. The subject has type 2 diabetes mellitus and has been receiving insulin monotherapy or insulin therapy in combination with one or two oral hypoglycemic agents. The subject has not modified diet or exercise therapies or dosage regimen of oral hypoglycemic agents, or has not switched to another pharmacotherapy for 12 weeks before Visit 1. The subject has an HbA1c value between 6.5% and <8.0%. The subject has a body mass index (BMI) of >23.0 kg/m2. If the subject is a female, she must satisfy the following criteria. The subject is not of childbearing potential and satisfies any of the following criteria. The subject is post-menopausal (absence of menses for at least 1 year). The subject is surgically sterile. The subject is of childbearing potential but satisfies all of the following criteria: The subject agrees not to get pregnant to 28 days after the last dose of the study drug. The subject has a negative pregnancy test. The subject agrees to use two of the established contraceptive methods listed below to 28 days after the last dose of the study drug when having heterosexual intercourse. If the subject is a female, she must agree not to breastfeed to 28 days after the last dose of the study drug. If the subject is a female, she must agree not to donate their eggs during the period from the assessment to 28 days after the last dose of the study drug. In case a male subject's spouse or partner is of childbearing potential, the subject must agree to use two of the established contraceptive methods to 28 days after the last dose of the study drug. If the subject is a male, he must agree not to donate their sperm to 28 days after the last dose of the study drug. Exclusion Criteria: The subject has type 1 diabetes mellitus. The subject has any symptom of dysuria, anuria, oliguria or urinary retention. The subject has proliferative retinopathy. The subject has diabetic ketoacidosis. The subject has a history or complication of medically significant renal disease such as renovascular occlusive disease, nephrectomy and/or renal transplant. The subject has a history of recurrent urinary tract infection. The subject has symptomatic urinary tract infection or symptomatic genital infection. The subject has chronic disease(s) that require the continuous use of corticosteroids, immunosuppressants, etc. The subject has a history of cerebral vascular attack, unstable angina, myocardial infarction, vascular intervention, and serious heart disease within 1 year (52 weeks) before signing of the informed consent. The subject has a complication or surgical history of serious gastrointestinal disorder. The subject has severe hepatic dysfunction. The subject has uncontrolled blood pressure. The subject has unstable psychiatric disorder. The subject has severe infection or serious trauma, or perioperative. The subject has drug addiction or alcohol abuse. The subject has a history of malignant tumors. The subject has a history of an allergy to ipragliflozin and/or similar drugs (drugs possessing SGLT2 inhibitory action). The subject has used SGLT2 inhibitors, GLP-1 receptor agonists, sulfonylureas (SU), glinide agents, or insulin products other than long-acting insulin within 12 weeks before signing of the informed consent.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ipragliflozin Group<br>Ipragliflozin will be administered orally for 24 weeks. | Drug: Ipragliflozin<br>* Oral administration, 50mg once daily<br>* Other names: Suglat;Drug: Insulin<br>* Patients are receiving insulin therapy from at least 12 weeks before Visit 1 (is allowed ±10% dose modification if clinically needed, and is reduced within a 20% to 40% range at Visit 1 and then is controlled up to Visit 8 based on criteria of this study).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in insulin dose |  | Baseline and Week 24 | 
| Percent change from baseline in insulin dose |  | Baseline and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in insulin dose |  | Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and the last assessment during the treatment period (up to Week 24) | 
| Percent change from baseline in insulin dose |  | Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 and the last assessment during the treatment period (up to Week 24) | 
| Change from baseline in HbA1c |  | Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24) | 
| Change from baseline in fasting plasma glucose |  | Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24) | 
| Change from baseline in cholesterol |  | Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24) | 
| Change from baseline in glycoalbumin |  | Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24) | 
| Change from baseline in leptin |  | Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24) | 
| Change from baseline in adiponectin |  | Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24) | 
| Change from baseline in glucagon |  | Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24) | 
| Change from baseline in C-peptide |  | Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24) | 
| Change from baseline in body weight |  | Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24) | 
| Change from baseline in waist circumference |  | Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24) | 
| Change from baseline in blood pressure |  | Baseline and Week 0, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and the last assessment during the treatment period (up to Week 24) | 
| Change from baseline in DTSQ | DTSQ: Diabetes treatment satisfaction questionnaire | Baseline and Week 24 and the last assessment during the treatment period (up to Week 24) | 
| Number of subjects achieving withdrawal of insulin therapy |  | Up to Week 24 | 
| Percent of subjects achieving withdrawal of insulin therapy |  | Up to Week 24 | 
| Safety assessed by incidence of Adverse events |  | Up to Week 24 | 
| Safety assessed by blood pressure in a sitting position |  | Up to Week 24 | 
| Safety assessed by pulse rate in a sitting position |  | Up to Week 24 | 
| Safety assessed by Hematology |  | Up to Week 24 | 
| Safety assessed by biochemistry |  | Up to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ipragliflozin, SGLT2 inhibitor, Type 2 diabetes mellitus, ASP1941