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

AstraZeneca151 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

151

Conditions

Type 1 Diabetes Mellitus

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (24)

Research Site

Aizu Wakamatsu-shi, Japan

Research Site

Chūōku, Japan

Research Site

Fukuoka, Japan

Research Site

Fukuyama-shi, Japan

Research Site

Funabashi-shi, Japan

Research Site

Hamamatsu, Japan

Research Site

Hirosaki-shi, Japan

Research Site

Ise-shi, Japan

Research Site

Kagoshima, Japan

Research Site

Koriyama-shi, Japan

...and 14 more locations

Outcomes

Primary Outcomes

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.

Time frame: From baseline to 52 weeks

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.

Time frame: From baseline to 52 weeks

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.

Time frame: From baseline to 52 weeks

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.

Time frame: From baseline to 52 weeks

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.

Time frame: From baseline to 52 weeks

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.

Time frame: From baseline to 52 weeks

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.

Time frame: From baseline to 52 weeks

Secondary Outcomes

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.