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

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

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).

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: ipragliflozin; Other: Insulin Therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 175
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan
    • Site JP00005
  • Aichi, Japan
    • Site JP00028
  • Chiba, Japan
    • Site JP00003
  • Chiba, Japan
    • Site JP00013
  • Chiba, Japan
    • Site JP00035
  • Fukuoka, Japan
    • Site JP00023
  • Fukuoka, Japan
    • Site JP00022
  • Fukuoka, Japan
    • Site JP00031
  • Gunma, Japan
    • Site JP00011
  • Gunma, Japan
    • Site JP00002
  • Hiroshima, Japan
    • Site JP00006
  • Hokkaido, Japan
    • Site JP00033
  • Hokkaido, Japan
    • Site JP00034
  • Hyogo, Japan
    • Site JP00021
  • Ibaraki, Japan
    • Site JP00009
  • Ibaraki, Japan
    • Site JP00010
  • Kanagawa, Japan
    • Site JP00004
  • Kanagawa, Japan
    • Site JP00015
  • Kanagawa, Japan
    • Site JP00016
  • Mie, Japan
    • Site JP00019
  • Nagasaki, Japan
    • Site JP00008
  • Nagasaki, Japan
    • Site JP00024
  • Nagasaki, Japan
    • Site JP00025
  • Nagasaki, Japan
    • Site JP00032
  • Niigata, Japan
    • Site JP00026
  • Osaka, Japan
    • Site JP00036
  • Osaka, Japan
    • Site JP00029
  • Osaka, Japan
    • Site JP00020
  • Saitama, Japan
    • Site JP00012
  • Shizuoka, Japan
    • Site JP00018
  • Shizuoka, Japan
    • Site JP00017
  • Tochigi, Japan
    • Site JP00001
  • Tokushima, Japan
    • Site JP00030
  • Tokyo, Japan
    • Site JP00014
  • Toyama, Japan
    • Site JP00027
  • Yamaguchi, Japan
    • Site JP00007

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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
Safety assessed by incidence of adverse events		Up to Week 56
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 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

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Publications and helpful links

Helpful Links

• Link to results on the Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2016
• Primary Completion (Actual): July 22, 2017
• Study Completion (Actual): March 15, 2018

Study Registration Dates

• First Submitted: July 27, 2016
• First Submitted That Met QC Criteria: September 7, 2016
• First Posted (Estimate): September 13, 2016

Study Record Updates

• Last Update Posted (Actual): March 6, 2019
• Last Update Submitted That Met QC Criteria: March 5, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: type 1 diabetes mellitus; ASP1941; SGLT2 inhibitor
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Ipragliflozin
• Other Study ID Numbers: 1941-CL-6002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Access to anonymized individual participant level data collected during the trial, in addition to study-related supporting documentation, is planned for trials conducted with approved product indications and formulations, as well as compounds terminated during development. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
• IPD Sharing Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• IPD Sharing Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR