A Study of ASP1941 in Combination With Insulin in Patients With Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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The objective of this study is to confirm efficacy of ASP1941 based on the changes in HbA1c and to assess its safety in subjects with type 1 diabetes mellitus receiving ASP1941 once daily in combination with insulin for 24 weeks. This study will also assess the safety/efficacy of long-term treatment (52 weeks).

Detailed Description
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This study consists of two parts. In Part 1, ASP1941 or placebo will be administered orally in a blind manner. In Part 2, the long-term safety and efficacy of ASP1941 will be evaluated in patients who have participated in the study and completed the Part 1.

Official Title
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Phase III Study of ASP1941 Double-blind, Parallel-group Study in Combination With Insulin in Patients With Type 1 Diabetes Mellitus

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: ipragliflozin
* Drug: Placebo
* Other: Insulin Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The subject has been diagnosed with type 1 diabetes mellitus The subject has been receiving insulin therapy for the treatment of diabetes mellitus. The subject has not switched from an insulin product to another insulin product or switched between continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI). The subject has an HbA1c value between 7.5% and 11.0% and the difference of HbA1c value is within ± 2.0%. The subject has a fasting blood C-peptide level < 0.6 ng/mL. The subject has a body mass index (BMI) between 20.0 kg/m2 and 35.0 kg/m2. Exclusion Criteria: The subject has type 2 diabetes mellitus. The subject has participated in a clinical study or post marketing study of another drug or medical equipment within 12 weeks (84 days) before providing written informed consent, or is currently participating in such a study. The subject has received treatment with ASP1941 (ipragliflozin) or participated in a clinical study of ASP1941 (excluding subjects who discontinued before the investigational period). The subject participated in this study previously. The subject has received a hypoglycemic agent other than insulin or an α-glucosidase inhibitor. The subject has proliferative retinopathy (except for those who have undergone photocoagulation etc. and whose symptoms are stable). The subject has experienced severe hypoglycemia. The subject has experienced diabetic ketoacidosis. The subject has chronic disease that requires the continuous use of corticosteroids, immunosuppressants, etc. The subject has symptomatic urinary tract infection or symptomatic genital infection. The subject has a history of recurrent urinary tract infection or recurrent genital infection. The subject has a history of cerebral vascular attack, unstable angina, myocardial infarction, vascular intervention, or another serious heart disease. The subject has a concomitant malignant tumor or a history of malignant tumor The subject has a history of an allergy to ASP1941 (ipragliflozin) and/or similar drugs (drugs possessing SGLT2 inhibitory action). The subject has psychiatric disorder that is inappropriate for participation in the study. The subject has drug addiction or alcohol abuse. The subject has severe infection or serious trauma, or is perioperative. The subject has a history of medically significant renal disease such as renovascular occlusive disease, nephrectomy and/or renal transplant. The subject has any symptoms of dysuria, anuria, oliguria, or urinary retention. The subject has severe renal impairment or end-stage renal failure requiring dialysis. The subject has an Aspartate Aminotransferase and/or Alanine Aminotransferase value that exceeds 2 times, or a total bilirubin value that exceeds 1.5 times the upper limit of the reference range. The subject has uncontrolled severe hypertension. The subject has serious gastrointestinal disease or a history of operation for serious gastrointestinal disease.

Ages Eligible for Study
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Minimum Age: 20 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 ASP1941<br>ASP1941 will be administered for 24 weeks under double blind conditions. | Drug: ipragliflozin<br>* Oral administration once daily<br>* Other names: ASP1941;Other: Insulin Therapy<br>* Continuous subcutaneous insulin infusion or multiple daily injections as standard of care<br>|
| Placebo Comparator: Part 1 Placebo<br>Placebo will be administered for 24 weeks under double blind conditions. | Drug: Placebo<br>* Oral administration once daily<br>Other: Insulin Therapy<br>* Continuous subcutaneous insulin infusion or multiple daily injections as standard of care<br>|
| Experimental: Part 2 ASP1941<br>ASP1941 will be administered for 28 weeks under open label conditions. | Drug: ipragliflozin<br>* Oral administration once daily<br>* Other names: ASP1941;Other: Insulin Therapy<br>* Continuous subcutaneous insulin infusion or multiple daily injections as standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in HbA1c |  | Baseline and Week 24 (end of treatment period 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in HbA1c |  | Baseline and up to Week 56 | 
| Change from baseline in Fasting plasma glucose |  | Baseline and up to Week 56 | 
| Change from baseline in self-monitored blood glucose level |  | Baseline and up to Week 56 | 
| Change from baseline in leptin |  | Baseline and up to Week 52 | 
| Change from baseline in glycoalbumin |  | Baseline and up to Week 52 | 
| Change from baseline in adiponectin |  | Baseline and up to Week 52 | 
| Change from baseline in glucagon |  | Baseline and up to Week 52 | 
| Change from baseline in number of units of insulin administered concomitantly | Comprehensively assessed by basal insulin daily dose, bolus insulin daily dose and total insulin daily dose. | Baseline and up to Week 56 | 
| Change from baseline in body weight |  | Baseline and up to Week 56 | 
| Change from baseline in waist circumference |  | Baseline and up to Week 52 | 
| Safety assessed by incidence of adverse events |  | Up to Week 56 | 
| Safety assessed by sitting blood pressure |  | Up to Week 56 | 
| Safety assessed by sitting pulse rate |  | Up to Week 56 | 
| Safety assessed by standard 12-lead electrocardiogram |  | Up to Week 56 | 
| Safety assessed by laboratory tests: Hematology |  | Up to Week 56 | 
| Safety assessed by laboratory tests: Biochemistry |  | Up to Week 56 | 
| Safety assessed by laboratory tests: Urinalysis |  | Up to Week 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SGLT2 inhibitor, ASP1941, type 1 diabetes mellitus