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

Phase 3
Completed
Conditions
Type 1 Diabetes Mellitus
Interventions
Drug: Placebo
Other: Insulin Therapy
Registration Number
NCT02897219
Lead Sponsor
Astellas Pharma Inc
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
175
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Part 1 ASP1941Insulin TherapyASP1941 will be administered for 24 weeks under double blind conditions.
Part 1 PlaceboInsulin TherapyPlacebo will be administered for 24 weeks under double blind conditions.
Part 2 ASP1941Insulin TherapyASP1941 will be administered for 28 weeks under open label conditions.
Part 1 ASP1941ipragliflozinASP1941 will be administered for 24 weeks under double blind conditions.
Part 1 PlaceboPlaceboPlacebo will be administered for 24 weeks under double blind conditions.
Part 2 ASP1941ipragliflozinASP1941 will be administered for 28 weeks under open label conditions.
Primary Outcome Measures
NameTimeMethod
Change from baseline in HbA1cBaseline and Week 24 (end of treatment period 1)
Secondary Outcome Measures
NameTimeMethod
Change from baseline in HbA1cBaseline and up to Week 56
Change from baseline in waist circumferenceBaseline and up to Week 52
Change from baseline in leptinBaseline and up to Week 52
Change from baseline in adiponectinBaseline and up to Week 52
Change from baseline in glucagonBaseline and up to Week 52
Change from baseline in number of units of insulin administered concomitantlyBaseline and up to Week 56

Comprehensively assessed by basal insulin daily dose, bolus insulin daily dose and total insulin daily dose.

Change from baseline in Fasting plasma glucoseBaseline and up to Week 56
Safety assessed by incidence of adverse eventsUp to Week 56
Safety assessed by sitting blood pressureUp to Week 56
Safety assessed by sitting pulse rateUp to Week 56
Change from baseline in self-monitored blood glucose levelBaseline and up to Week 56
Safety assessed by laboratory tests: HematologyUp to Week 56
Safety assessed by laboratory tests: UrinalysisUp to Week 56
Change from baseline in body weightBaseline and up to Week 56
Safety assessed by standard 12-lead electrocardiogramUp to Week 56
Safety assessed by laboratory tests: BiochemistryUp to Week 56
Change from baseline in glycoalbuminBaseline and up to Week 52

Trial Locations

Locations (36)

Site JP00005

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Aichi, Japan

Site JP00022

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Fukuoka, Japan

Site JP00006

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Hiroshima, Japan

Site JP00021

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Hyogo, Japan

Site JP00004

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Kanagawa, Japan

Site JP00015

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Kanagawa, Japan

Site JP00020

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Osaka, Japan

Site JP00029

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Osaka, Japan

Site JP00007

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Yamaguchi, Japan

Site JP00013

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Chiba, Japan

Site JP00033

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Hokkaido, Japan

Site JP00028

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Aichi, Japan

Site JP00003

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Chiba, Japan

Site JP00035

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Chiba, Japan

Site JP00023

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Fukuoka, Japan

Site JP00031

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Fukuoka, Japan

Site JP00002

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Gunma, Japan

Site JP00011

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Gunma, Japan

Site JP00034

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Hokkaido, Japan

Site JP00009

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Ibaraki, Japan

Site JP00010

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Ibaraki, Japan

Site JP00016

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Kanagawa, Japan

Site JP00019

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Mie, Japan

Site JP00008

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Nagasaki, Japan

Site JP00024

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Nagasaki, Japan

Site JP00025

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Nagasaki, Japan

Site JP00026

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Niigata, Japan

Site JP00032

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Nagasaki, Japan

Site JP00036

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Osaka, Japan

Site JP00012

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Saitama, Japan

Site JP00017

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Shizuoka, Japan

Site JP00018

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Shizuoka, Japan

Site JP00001

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Tochigi, Japan

Site JP00014

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Tokyo, Japan

Site JP00030

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Tokushima, Japan

Site JP00027

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Toyama, Japan

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