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

Primary Purpose

Type 1 Diabetes Mellitus

Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
Dapagliflozin 5 mg
Dapagliflozin 10mg
Sponsored by
AstraZeneca
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 1 Diabetes Mellitus focused on measuring Japanese patients with type 1 diabetes with inadequate glycemic control on insulin

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

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Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

dapagliflozin 5mg + insulin

dapagliflozin 10mg + insulin

Arm Description

dapagliflozin tablet 5mg + adjustable insulin

dapagliflozin tablet 10mg + adjustable insulin

Outcomes

Primary Outcome Measures

Overall Adverse Event Summary
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.
Hypoglycemia
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.
Diabetic Ketoacidosis (DKA)
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.
Vital Signs (Heart Rate)
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.
ECGs
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.
Clinical Laboratory Measures, Urine Test Results (Any Marked Abnormality)
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.
Vital Signs (Blood Pressure)
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.

Secondary Outcome Measures

Adjusted Change From Baseline in HbA1c
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.
Adjusted Percent Change From Baseline in Total Daily Insulin Dose
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.
Adjusted Percent Change From Baseline in Body Weight
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.
Adjusted Change From Baseline in Glycoalbumin
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.
Adjusted Change From Baseline in Average Daily Glucose Measured by 6-point SMBG
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.
Adjusted Change From Baseline in Post-prandial Glucose Measured by 6-point SMBG
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.
Proportion of Subjects Achieving HbA1c Reduction of 0.5 Percent Without Severe Hypoglycemia
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
Proportion of Subjects Achieving HbA1c Reduction of 0.5 Percent
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
Proportion of Subjects Achieving HbA1c < 7.0 Percent
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
Adjusted Change From Baseline in SBP in Subjects With Baseline SBP/DBP >= 140/90 mmHg
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

Full Information

First Posted
October 20, 2015
Last Updated
January 14, 2019
Sponsor
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT02582814
Brief Title
The Safety and Efficacy of Dapagliflozin Therapy in Combination With Insulin in Japanese Subjects With T1DM
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
October 26, 2015 (Actual)
Primary Completion Date
June 15, 2017 (Actual)
Study Completion Date
June 15, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes Mellitus
Keywords
Japanese patients with type 1 diabetes with inadequate glycemic control on insulin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Masking Description
Open Label
Allocation
Randomized
Enrollment
151 (Actual)

8. Arms, Groups, and Interventions

Arm Title
dapagliflozin 5mg + insulin
Arm Type
Experimental
Arm Description
dapagliflozin tablet 5mg + adjustable insulin
Arm Title
dapagliflozin 10mg + insulin
Arm Type
Experimental
Arm Description
dapagliflozin tablet 10mg + adjustable insulin
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin 5 mg
Intervention Description
Dapagliflozin, a blood glucose lowering drug. Oral dose
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin 10mg
Intervention Description
Dapagliflozin, a blood glucose lowering drug. Oral dose
Primary Outcome Measure Information:
Title
Overall Adverse Event Summary
Description
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.
Time Frame
From baseline to 52 weeks
Title
Hypoglycemia
Description
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.
Time Frame
From baseline to 52 weeks
Title
Diabetic Ketoacidosis (DKA)
Description
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.
Time Frame
From baseline to 52 weeks
Title
Vital Signs (Heart Rate)
Description
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.
Time Frame
From baseline to 52 weeks
Title
ECGs
Description
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.
Time Frame
From baseline to 52 weeks
Title
Clinical Laboratory Measures, Urine Test Results (Any Marked Abnormality)
Description
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.
Time Frame
From baseline to 52 weeks
Title
Vital Signs (Blood Pressure)
Description
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.
Time Frame
From baseline to 52 weeks
Secondary Outcome Measure Information:
Title
Adjusted Change From Baseline in HbA1c
Description
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.
Time Frame
From baseline to 24/52 weeks
Title
Adjusted Percent Change From Baseline in Total Daily Insulin Dose
Description
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.
Time Frame
From baseline to 24/52 weeks
Title
Adjusted Percent Change From Baseline in Body Weight
Description
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.
Time Frame
From baseline to 24/52 weeks
Title
Adjusted Change From Baseline in Glycoalbumin
Description
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.
Time Frame
From baseline to 24/52 weeks
Title
Adjusted Change From Baseline in Average Daily Glucose Measured by 6-point SMBG
Description
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.
Time Frame
From baseline to 24/52 weeks
Title
Adjusted Change From Baseline in Post-prandial Glucose Measured by 6-point SMBG
Description
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.
Time Frame
From baseline to 24/52 weeks
Title
Proportion of Subjects Achieving HbA1c Reduction of 0.5 Percent Without Severe Hypoglycemia
Description
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
Time Frame
From baseline to 24/52 weeks
Title
Proportion of Subjects Achieving HbA1c Reduction of 0.5 Percent
Description
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
Time Frame
From baseline to 24/52 weeks
Title
Proportion of Subjects Achieving HbA1c < 7.0 Percent
Description
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
Time Frame
From baseline to 24/52 weeks
Title
Adjusted Change From Baseline in SBP in Subjects With Baseline SBP/DBP >= 140/90 mmHg
Description
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
Time Frame
From baseline to 24/52 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Research Site
City
Aizu Wakamatsu-shi
Country
Japan
Facility Name
Research Site
City
Chuo-ku
Country
Japan
Facility Name
Research Site
City
Fukuoka-shi
Country
Japan
Facility Name
Research Site
City
Fukuyama-shi
Country
Japan
Facility Name
Research Site
City
Funabashi-shi
Country
Japan
Facility Name
Research Site
City
Hamamatsu-shi
Country
Japan
Facility Name
Research Site
City
Hirosaki-shi
Country
Japan
Facility Name
Research Site
City
Ise-shi
Country
Japan
Facility Name
Research Site
City
Kagoshima-shi
Country
Japan
Facility Name
Research Site
City
Koriyama-shi
Country
Japan
Facility Name
Research Site
City
Kumamoto-shi
Country
Japan
Facility Name
Research Site
City
Kunitachi-shi
Country
Japan
Facility Name
Research Site
City
Minato-ku
Country
Japan
Facility Name
Research Site
City
Nagoya-shi
Country
Japan
Facility Name
Research Site
City
Oita-shi
Country
Japan
Facility Name
Research Site
City
Otsu-shi
Country
Japan
Facility Name
Research Site
City
Oyama-shi
Country
Japan
Facility Name
Research Site
City
Sapporo-shi
Country
Japan
Facility Name
Research Site
City
Sendai-shi
Country
Japan
Facility Name
Research Site
City
Shinjyuku-ku
Country
Japan
Facility Name
Research Site
City
Suita-shi
Country
Japan
Facility Name
Research Site
City
Tama-shi
Country
Japan
Facility Name
Research Site
City
Tsukuba-shi
Country
Japan
Facility Name
Research Site
City
Yokohama-shi
Country
Japan

12. IPD Sharing Statement

Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=3797&filename=D1695C00001_SAP_Redacted.pdf
Description
D1695C00001_SAP_redacted
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=3797&filename=D1695C00001_CSP_redacted.pdf
Description
D1695C00001_CSP_redacted

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

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