A Study to Assess the Efficacy and Safety of Ipragliflozin in Combination With Insulin in Subjects With Type 2 Diabetes Mellitus

Postmarketing Clinical Study of Ipragliflozin - Double-blind, Parallel-group Study in Combination With Insulin in Patients With Type 2 Diabetes Mellitus

The purpose of this study is to assess the efficacy (superiority to placebo) of ipragliflozin based on the changes in HbA1C, as well as its safety, in patients with type 2 diabetes mellitus in combination with an insulin preparation once daily for 16 weeks. The long-term (52 weeks) safety and the persistence of the efficacy will also be evaluated.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: placebo; Drug: ipragliflozin

Detailed Description

This study consists of two parts. First part is a placebo-controlled multicenter, double-blind, parallel group study, in which subjects will receive ipragliflozin or placebo once daily in combination with an insulin preparation for 16 weeks. Second part is a multicenter, open-label period (36 weeks) with no placebo group. The dose of ipragliflozin can be doubled in combination with an insulin preparation during the second part.

• Study Type: Interventional
• Enrollment (Actual): 262
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Chubu, Japan
  • Chugoku, Japan
  • Hokkaido, Japan
  • Kansai, Japan
  • Kanto, Japan
  • Kyushu, Japan
  • Shikoku, Japan
  • Touhoku, Japan

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:

• Subject has been diagnosed with type 2 diabetes mellitus for at least 12 weeks (84 days) at signing of informed consent.
• Subject takes constant dosage and administration of insulin preparation for more than 6 weeks (42 days)
• Subject has an HbA1C value between 7.5 and 10.0% at Visit 2 and the difference of HbA1C value within ± 1.0% between Visit 1 and Visit 2
• Subject has a body mass index (BMI) 20.0 - 45.0 kg/m2

Exclusion Criteria:

• Subject has type 1 diabetes mellitus
• Subject has proliferative diabetic retinopathy
• Subject has a history of clinically significant renal disease such as renovascular occlusive disease, nephrectomy and/or renal transplant
• Subject has a history of recurrent urinary tract infection (more than three times within before 24 weeks of obtaining informed consent)
• Subject has a symptomatic urinary tract infection or symptomatic genital infection
• Subject has chronic disease which requires the continuous use of adrenocortical steroids and immunosuppressant (oral medication, injection, or inhalation)
• Subject has a history of cerebral vascular attack, unstable angina, myocardial infarction, vascular intervention, and heart disease (NYHA Class III-IV) within 1 year (52 weeks) prior to Visit 1
• Subject has unstable psychiatric disorder
• Female subject who is currently pregnant or lactating, or who is possibly pregnant
• Male and pre-menopausal female subject who cannot use an appropriate contraception during the study
• Subject has severe infection, perioperative, or serious trauma
• Subject has drug addiction or alcohol abuse
• Subject has a history of malignant tumors (except for those who have not received treatment for malignant tumors for at least 5 years before informed consent acquisition and was not considered to have recurrence)
• Subject has a history of an allergy with ipragliflozin and/or similar drugs (study drugs possessing SGLT 2 inhibitory action)
• Subject has participated in another clinical study, post marketing study, or medical equipment study within 12 weeks (84 days) before providing written informed consent, or who is currently participating in any of those studies
• Subject is unable, unwilling to adhere to compliances such as hospital visits and dose instruction specified in this study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ipragliflozin group; oral	Drug: ipragliflozin; oral; Other Names: ASP1941; Suglat
Experimental: placebo group; oral	Drug: placebo; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in HbA1C from baseline	Baseline and Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting plasma glucose		Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Leptin concentration		Baseline, Week 2, 4, 8, 12, 16, 24, 36, 52
Fructosamine concentration		Baseline, Week 2, 4, 8, 12, 16, 24, 36, 52
Adiponectin concentration		Baseline, Week 2, 4, 8, 12, 16, 24, 36, 52
Body weight		Baseline, Week 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Waist circumference		Baseline, Week 16, 24, 52
Blood glucose values of self monitoring	written in a diary	Baseline, Week 8, 16, 24, 52
Safety assessed by the adverse events, vital signs. and laboratory tests		Up to 52 Weeks

Collaborators and Investigators

• Sponsor: Astellas Pharma Inc

Publications and helpful links

General Publications

• Kashiwagi A, Shestakova MV, Ito Y, Noguchi M, Wilpshaar W, Yoshida S, Wilding JPH. Safety of Ipragliflozin in Patients with Type 2 Diabetes Mellitus: Pooled Analysis of Phase II/III/IV Clinical Trials. Diabetes Ther. 2019 Dec;10(6):2201-2217. doi: 10.1007/s13300-019-00699-8. Epub 2019 Oct 12.
• Ishihara H, Yamaguchi S, Nakao I, Asahina S, Sakatani T. Efficacy and safety of ipragliflozin as add-on therapy to insulin in Japanese patients with type 2 diabetes mellitus (IOLITE): a 36-week, open-label extension of a 16-week, randomized, placebo-controlled, double-blind study. Diabetol Int. 2018 Jul 16;10(1):37-50. doi: 10.1007/s13340-018-0359-x. eCollection 2019 Jan.

Helpful Links

• Link to results on Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2014
• Primary Completion (Actual): March 31, 2015
• Study Completion (Actual): December 7, 2015

Study Registration Dates

• First Submitted: June 25, 2014
• First Submitted That Met QC Criteria: June 25, 2014
• First Posted (Estimate): June 26, 2014

Study Record Updates

• Last Update Posted (Actual): April 25, 2019
• Last Update Submitted That Met QC Criteria: April 23, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: insulin; SGLT2 inhibitor; Blood glucose; ipragliflozin
• 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-CL-0131

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 study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. 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)