The Safety and Efficacy of Dapagliflozin Therapy in Combination With Insulin in Japanese Subjects With T1DM

January 14, 2019 updated by: AstraZeneca

A Clinical Pharmacology and Long Term Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of Dapagliflozin Therapy in Combination With Insulin in Japanese Subjects With Type 1 Diabetes Who Have Inadequate Glycemic Control

This study will enroll eligible subjects into a long-term safety study (Part B).

Japanese male and female patients with T1DM and age 18 to 75 years, with inadequate glycemic control on insulin defined as HbA1c ≥ 7.5% and ≤ 10.5% at screening visit. As a condition of enrollment, subjects must be on a total daily insulin dose of ≥ 0.3 U/kg/day for at least 3 months prior to the screening visit. The study design of Part B is a randomized, open-label, 2 arm, parallel-group design. 140 Japanese subjects in total will be randomized in a 1:1 ratio into one of the two treatment arms; dapagliflozin 5 mg or dapagliflozin 10 mg.

Study Overview

Status

Completed

Study Type

Interventional

Enrollment (Actual)

151

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Aizu Wakamatsu-shi, Japan
        • Research Site
      • Chuo-ku, Japan
        • Research Site
      • Fukuoka-shi, Japan
        • Research Site
      • Fukuyama-shi, Japan
        • Research Site
      • Funabashi-shi, Japan
        • Research Site
      • Hamamatsu-shi, Japan
        • Research Site
      • Hirosaki-shi, Japan
        • Research Site
      • Ise-shi, Japan
        • Research Site
      • Kagoshima-shi, Japan
        • Research Site
      • Koriyama-shi, Japan
        • Research Site
      • Kumamoto-shi, Japan
        • Research Site
      • Kunitachi-shi, Japan
        • Research Site
      • Minato-ku, Japan
        • Research Site
      • Nagoya-shi, Japan
        • Research Site
      • Oita-shi, Japan
        • Research Site
      • Otsu-shi, Japan
        • Research Site
      • Oyama-shi, Japan
        • Research Site
      • Sapporo-shi, Japan
        • Research Site
      • Sendai-shi, Japan
        • Research Site
      • Shinjyuku-ku, Japan
        • Research Site
      • Suita-shi, Japan
        • Research Site
      • Tama-shi, Japan
        • Research Site
      • Tsukuba-shi, Japan
        • Research Site
      • Yokohama-shi, Japan
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Signed Written Informed Consent
  • Diagnosis of T1DM. In addition, the following criteria also needs to be met; Central laboratory test of C-peptide < 0.7 ng/mL
  • Insulin use for at least 12 months prior to the enrolment per subject report or medical records and Method of insulin administration (MDI or CSII) must have been unchanged for at least 3 months prior to the enrolment per subject report or medical records. Subjects must be taking a total daily insulin dose of ≥ 0.3 U/kg/day for at least 3 months prior to the enrolment. If on MDI insulin administration subject must be on ≥ 3x injections per day.
  • Japanese men and women
  • Screening Visit: Central laboratory HbA1c ≥ 7.5% and ≤ 10.5%
  • BMI ≥ 20.0 kg/m² at visit 1
  • Age 18 to 75 years, inclusive

Exclusion Criteria:

- Target Disease Exceptions History of T2DM Maturity onset diabetes of young (MODY) Any anti-hyperglycemic agent use, other than α-GI or insulin, within 1 month prior to the enrolment.

Use of thiazolidinediones within 6 months prior to the enrolment History of DKA requiring medical intervention within 1 month prior to the enrolment History of hospital admission for glycemic control (either hyperglycemia or hypoglycemia) within 1 month prior to the enrolment

  • Medical History and Concurrent Diseases Malignancy within 5 years of the enrolment (with the exception of treated basal cell or treated squamous cell carcinoma) History of bladder cancer History of radiation therapy to the lower abdomen or pelvis at any time
  • Physical and Laboratory Test Findings Aspartate aminotransferase (AST) > 3x upper limit of normal (ULN) Alanine aminotransferase (ALT) > 3x ULN Serum total bilirubin (TB) > 2.0 mg/dL (34.2 μmol/L) Estimated GFR (eGFR) by the Japanese Society of Nephrology formula ≤ 45 mL/min/1.73m2 Hemoglobin ≤ 11.0 g/dL (110 g/L) for men; hemoglobin ≤ 10.0 g/dL (100 g/L) for women.

Positive for hepatitis B surface antigen or anti-hepatitis C virus antibody Abnormal Free T4

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: dapagliflozin 5mg + insulin
dapagliflozin tablet 5mg + adjustable insulin
Dapagliflozin, a blood glucose lowering drug. Oral dose
Experimental: dapagliflozin 10mg + insulin
dapagliflozin tablet 10mg + adjustable insulin
Dapagliflozin, a blood glucose lowering drug. Oral dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Adverse Event Summary
Time Frame: From baseline to 52 weeks
To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.
From baseline to 52 weeks
Hypoglycemia
Time Frame: From baseline to 52 weeks
To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.
From baseline to 52 weeks
Diabetic Ketoacidosis (DKA)
Time Frame: From baseline to 52 weeks
To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.
From baseline to 52 weeks
Vital Signs (Heart Rate)
Time Frame: From baseline to 52 weeks
To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.
From baseline to 52 weeks
ECGs
Time Frame: From baseline to 52 weeks
To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.
From baseline to 52 weeks
Clinical Laboratory Measures, Urine Test Results (Any Marked Abnormality)
Time Frame: From baseline to 52 weeks
To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.
From baseline to 52 weeks
Vital Signs (Blood Pressure)
Time Frame: From baseline to 52 weeks
To evaluate safety and tolerability of long-term treatment (52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM with inadequate glycemic control under standard insulin therapy.
From baseline to 52 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adjusted Change From Baseline in HbA1c
Time Frame: From baseline to 24/52 weeks
To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin therapy.
From baseline to 24/52 weeks
Adjusted Percent Change From Baseline in Total Daily Insulin Dose
Time Frame: From baseline to 24/52 weeks
To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin therapy.
From baseline to 24/52 weeks
Adjusted Percent Change From Baseline in Body Weight
Time Frame: From baseline to 24/52 weeks
To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin therapy.
From baseline to 24/52 weeks
Adjusted Change From Baseline in Glycoalbumin
Time Frame: From baseline to 24/52 weeks
To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin therapy.
From baseline to 24/52 weeks
Adjusted Change From Baseline in Average Daily Glucose Measured by 6-point SMBG
Time Frame: From baseline to 24/52 weeks
To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin therapy.
From baseline to 24/52 weeks
Adjusted Change From Baseline in Post-prandial Glucose Measured by 6-point SMBG
Time Frame: From baseline to 24/52 weeks
To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin therapy.
From baseline to 24/52 weeks
Proportion of Subjects Achieving HbA1c Reduction of 0.5 Percent Without Severe Hypoglycemia
Time Frame: From baseline to 24/52 weeks
To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin
From baseline to 24/52 weeks
Proportion of Subjects Achieving HbA1c Reduction of 0.5 Percent
Time Frame: From baseline to 24/52 weeks
To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin
From baseline to 24/52 weeks
Proportion of Subjects Achieving HbA1c < 7.0 Percent
Time Frame: From baseline to 24/52 weeks
To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin
From baseline to 24/52 weeks
Adjusted Change From Baseline in SBP in Subjects With Baseline SBP/DBP >= 140/90 mmHg
Time Frame: From baseline to 24/52 weeks
To assess the efficacy of long-term treatment (24/52 weeks) of dapagliflozin 5mg and 10 mg in Japanese patients with T1DM inadequately controlled on insulin
From baseline to 24/52 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 26, 2015

Primary Completion (Actual)

June 15, 2017

Study Completion (Actual)

June 15, 2017

Study Registration Dates

First Submitted

October 20, 2015

First Submitted That Met QC Criteria

October 20, 2015

First Posted (Estimate)

October 21, 2015

Study Record Updates

Last Update Posted (Actual)

April 12, 2019

Last Update Submitted That Met QC Criteria

January 14, 2019

Last Verified

January 1, 2019

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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