the pk and pd of dapagliflozin therapy in combination with insulin in japanese subjects with t1dm

Conditions: Type 1 Diabetes Mellitus

Summary: this randomized, single-blind, 3 arm, parallel group, placebo controlled pk/pd study will enrol 30 japanese male and female patients with t1dm and age 18 to 65 years, with inadequate glycemic control on insulin defined as hba1c ≥ 7.0% and ≤ 10.0% at screening visit. lacebo-controlled design. patients will be randomized in a 1:1:1 ratio into one of the 3 single-blinded treatment arms; dapagliflozin 5 mg, dapagliflozin 10 mg or placebo. csii user are excluded.


Eligibility criteria:
inclusion criteria: * signed written informed consent subjects or their legally responsible representatives must be willing and able to give signed and dated written informed consent. * target population diagnosis of t1dm. in addition, the following criteria also needs to be met; central laboratory test of c-peptide \< 0.7 ng/ml subject re-enrolment: this study does not permit the re-enrolment of a subject who has discontinued the study as a screen failure * insulin use for at least 12 months prior to the enrolment per subject report or medical records and method of insulin administration (mdi) 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. csii users are excluded. mdi insulin administration subject must be on ≥ 3x injections per day. * gender and reproductive status japanese men and women. * hba1c eligibility criteria include: screening visit: central laboratory hba1c ≥ 7.0 % and ≤ 10.0 % (one repeat hba1c test for subjects in screening if their initial test result was an hba1c ± 0.2% of the cut off values) * bmi ≥ 20.0 kg/m², ≤ 35.0 kg/m² at visit 1 * ages 18 to 65 years, inclusive - ≥ 18 years old and \< 20 years old must have assent forms signed and dated by their parents or guardians exclusion criteria: * target disease exceptions history of t2dm in cases where the subject has a history of t2dm and has a documented history of being auto-antibody positive for gad65, tyrosine phosphatase ia-2/ia-2β, or zinc transporter 8 (znt8), or fasting c-peptide value below the lower limit of detection performed by local or central laborator, the subject will be eligible for screening * maturity onset diabetes of young (mody), pancreatic surgery, chronic pancreatitis, or other pancreatic disorders that could result in decreased β-cell capacity (eg, pancreatogenous diabetes) * any antihyperglycemic agent use, other than thiazolidinediones, or insulin, within 1 month prior to the screening visit. use of thiazolidinediones within 6 months prior to the screening visit. * history of dka requiring medical intervention (eg, emergency room visit and/or hospitalization) 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 * 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 unstable pre-proliferative and proliferative retinopathy (untreated or under treatment). * 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 ≤ 60 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

Keywords: japanese patients with type 1 diabetes with inadequate glycemic control on insulin