A Study to Assess the Efficacy and Safety of ASP1941 in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Sitagliptin

A Phase 3, Multicenter, Double-Blind, Randomized, Parallel-group, Placebo-Controlled Study to Assess the Efficacy and Safety of ASP1941 in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Sitagliptin

The purpose of this study is to compare the efficacy and safety of ASP1941 50mg once daily in combination with metformin and sitagliptin against placebo in combination with metformin and sitagliptin over a 24 week treatment period in subjects with type 2 diabetes mellitus with inadequate glycemic control on metformin and sitagliptin.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: ASP1941

• Study Type: Interventional
• Enrollment (Actual): 143
• Phase: Phase 3

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of
    • Site KR00002
  • Busan, Korea, Republic of
    • Site KR00003
  • Daegu, Korea, Republic of
    • Site KR00007
  • Daegu, Korea, Republic of
    • Site KR00011
  • Dong Gu Gwangju, Korea, Republic of
    • Site KR00019
  • Gangwon-do, Korea, Republic of
    • Site KR00008
  • Gyeonggi-do, Korea, Republic of
    • Site KR00018
  • Gyeonggi-do, Korea, Republic of
    • Site KR00022
  • Incheon, Korea, Republic of
    • Site KR00014
  • Jeollabuk-do, Korea, Republic of
    • Site KR00020
  • Kyungsangnam-do, Korea, Republic of
    • Site KR00021
  • Seoul, Korea, Republic of
    • Site KR00006
  • Seoul, Korea, Republic of
    • Site KR00001
  • Seoul, Korea, Republic of
    • Site KR00004
  • Seoul, Korea, Republic of
    • Site KR00005
  • Seoul, Korea, Republic of
    • Site KR00009
  • Seoul, Korea, Republic of
    • Site KR00010
  • Seoul, Korea, Republic of
    • Site KR00012
  • Seoul, Korea, Republic of
    • Site KR00013
  • Seoul, Korea, Republic of
    • Site KR00016
  • Seoul, Korea, Republic of
    • Site KR00017
  • Suwon, Korea, Republic of
    • Site KR00015

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject has been diagnosed with type 2 diabetes mellitus.
• Subject has an HbA1c value between 7.0% and 10.5 % at visit 1.
• Subject shows FPG (Fasting Plasma Glucose) value is less than 270mg/dL.
• Subject shows a BMI of 20.0 to 45.0 kg/m2.
• Subject is on stable diet and exercise program at least 8 weeks prior to study participation.
• Postmenopausal female or surgically sterile female or agree not to become pregnant.

Exclusion Criteria:

• Subject has type 1 diabetes mellitus.
• Subject has proliferative diabetic retinopathy.
• Subject has a history of clinically significant renal disease(s) such as renovascular occlusive disease, nephrectomy, or renal transplant.
• Subject has significant dysuria caused by a neurogenic bladder or a benign prostatic hypertrophy etc.
• Subject has a symptomatic urinary tract infection or genital infection.
• Subject has chronic disease(s) that require the continuous use of systemic corticosteroids or immunosuppressants.
• Subject has cardiovascular disease or cerebrovascular disease that may affect the administration of ASP1941 or its safety assessment in the opinion of the investigator or sub-investigator.
• Subject has uncontrollable psychiatric disorder(s) with medication.
• Male subject is not willing to use appropriate contraception during the study.
• Subject has severe infection, serious trauma, or perioperative subject.
• Subject has a malignant tumor or has a history of malignant tumor.
• Subject has severe gastrointestinal disease, or history of operation for serious gastrointestinal disease.
• Subject has diabetic ketoacidosis.
• Subject has lactic acidosis or has history of lactic acidosis.
• Subject has hepatitis or is a carrier of hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or is positive for HIV-1 and/or HIV-2.
• Subject has a history of thyroid dysfunction and acute pancreatitis.
• Subject is on weight-loss program or weight-loss medication (e.g. orlistat, phentermine/topiramate, lorcaserin) within 12 weeks of study participation.
• Subject has a history of serious cardiac diseases (NYHA Class III to IV), congestive heart failure, arrhythmia in need of medical treatment.
• Subject has a history of cerebrovascular attack, unstable angina, myocardial infarction, angioplasty, within 52 weeks (364 days) of study participation.
• Subject has uncontrollable severe hypertension, i.e., systolic blood pressure of higher than 180 mmHg or diastolic blood pressure of higher than 110mmHg measured in a sitting position after a 5-minute rest.

• Subject has following AST or ALT value:

  • AST: Male > 100 U/L, Female > 80 U/L
  • ALT: Male > 102.5 U/L, Female > 82.5 U/L

• Subject has following serum creatinine value:

  • Creatinine: Male > 1.3 mg/dL, Female > 1.2 mg/dL
• Subject has estimated GFR values, of < 60 mL/min/1.73m2.

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: ASP1941 group; once daily over a 24 week treatment	Drug: ASP1941; oral; Other Names: Suglat; ipragliflozin
Placebo Comparator: Placebo group; once daily over a 24 week treatment	Drug: Placebo; oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in HbA1c at the end of treatment	at 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Fasting plasma glucose at the end of treatment		at 24 weeks
Change from baseline in Fasting serum insulin at the end of treatment		at 24 weeks
Change from baseline in Body weight at the end of treatment		at 24 weeks
Change from baseline in Waist circumference at the end of treatment		at 24 weeks
Safety assessed by development of adverse events, vital signs, laboratory tests, and 12-lead ECG	ECG: Electrocardiogram	up to 24 weeks
Number of subjects achieving the target HbA1c(<6.5% and <7.0%) at each visit		at 4, 8, 12, 16 and 24 weeks
Percentage of subjects achieving the target HbA1c(<6.5% and <7.0%) at each visit		at 4, 8, 12, 16 and 24 weeks

Collaborators and Investigators

• Sponsor: Astellas Pharma Korea, 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.

Helpful Links

• Link to results on the Astellas Clinical Study Results website

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2015
• Primary Completion (Actual): January 5, 2017
• Study Completion (Actual): January 5, 2017

Study Registration Dates

• First Submitted: May 14, 2015
• First Submitted That Met QC Criteria: May 20, 2015
• First Posted (Estimate): May 22, 2015

Study Record Updates

• Last Update Posted (Actual): November 14, 2018
• Last Update Submitted That Met QC Criteria: November 9, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Type 2 diabetes mellitus; ASP1941
• 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-2009

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