The Safety and Efficacy of Dapagliflozin Therapy in Combination With Insulin in Japanese Subjects With T1DM
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 1
Intervention: Dapagliflozin 5 mg; Dapagliflozin 10mg
Intervention description: Dapagliflozin, a blood glucose lowering drug. Oral dose; Dapagliflozin, a blood glucose lowering drug. Oral dose
Intervention MeSH terms: Dapagliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Masking description: Open Label
Enrollment: 151.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Japanese patients with type 1 diabetes with inadequate glycemic control on insulin

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.
    

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