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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Ipragliflozin; Drug: Insulin

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Gunma, Japan
    • Site JP00007
  • Hiroshima, Japan
    • Site JP00008
  • Hyogo, Japan
    • Site JP00009
  • Kanagawa, Japan
    • Site JP00010
  • Mie, Japan
    • Site JP00003
  • Osaka, Japan
    • Site JP00004
  • Shiga, Japan
    • Site JP00015
  • Tochigi, Japan
    • Site JP00002
  • Tochigi, Japan
    • Site JP00005
  • Tochigi, Japan
    • Site JP00013
  • Tokyo, Japan
    • Site JP00001
  • Tokyo, Japan
    • Site JP00006
  • Tokyo, Japan
    • Site JP00011
  • Tokyo, Japan
    • Site JP00012
  • Tokyo, Japan
    • Site JP00014

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ipragliflozin Group; Ipragliflozin will be administered orally for 24 weeks.	Drug: Ipragliflozin; Oral administration, 50mg once daily; Other Names: ASP1941; Suglat; Drug: Insulin; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Publications and helpful links

General Publications

• Ishihara H, Yamaguchi S, Sugitani T, Kosakai Y. Open-Label Study to Assess the Efficacy of Ipragliflozin for Reducing Insulin Dose in Patients with Type 2 Diabetes Mellitus Receiving Insulin Therapy. Clin Drug Investig. 2019 Dec;39(12):1213-1221. doi: 10.1007/s40261-019-00851-z.

Helpful Links

• Link to results on the Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2016
• Primary Completion (Actual): November 9, 2017
• Study Completion (Actual): November 9, 2017

Study Registration Dates

• First Submitted: July 25, 2016
• First Submitted That Met QC Criteria: July 25, 2016
• First Posted (Estimate): July 28, 2016

Study Record Updates

• Last Update Posted (Actual): December 7, 2018
• Last Update Submitted That Met QC Criteria: December 6, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Type 2 diabetes mellitus; ASP1941; Ipragliflozin; SGLT2 inhibitor
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Ipragliflozin
• Other Study ID Numbers: 1941-MA-3054

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; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No