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

AstraZeneca

Status and phase: Completed; Phase 3

Conditions: Type 1 Diabetes Mellitus

Treatments: Drug: Dapagliflozin 10mg; Drug: Dapagliflozin 5 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT02582814

D1695C00001

Details and patient eligibility

About

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.

Enrollment: 151 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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151 participants in 2 patient groups

dapagliflozin 5mg + insulin

Experimental group

Description:

dapagliflozin tablet 5mg + adjustable insulin

Treatment:

Drug: Dapagliflozin 5 mg

dapagliflozin 10mg + insulin

Experimental group

Description:

dapagliflozin tablet 10mg + adjustable insulin

Treatment:

Drug: Dapagliflozin 10mg