Phase IV Study With a 36-week Extension Period to Evaluate the Efficacy and Safety of Dapagliflozin Therapy When Added to the Therapy of Japanese Patients With Type 2 Diabetes With Inadequate Glycemic Control on Insulin.

Study Overview
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Brief Summary
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Japanese male and female patients with Type 2 Diabetes and aged ≥ 20 years old, with inadequate glycemic control on insulin defined as Haemoglobin A1c ≥ 7.2% and < 11% will be enrolled into the wash-out phase or directly into the lead-in phase depending on whether the patient has been receiving an Oral antidiabetic drug (including Glucagon-Like Peptide-1 agonists and excluding Thiazolidinedions) other than a Dipeptidyl Peptidase-4 inhibitor as part of the baseline treatment. Additional treatment with a concomitant Dipeptidyl Peptidase-4 inhibitor is allowed. And around 180 eligible patients in total will be randomized into the study with a 2:1 randomization scheme (i.e.120 patients into the dapagliflozin treatment group and 60 patients into the placebo treatment group. All subjects who completed a 16 weeks double-blind treatment period will shift to a 36 weeks open extension treatment period.

Official Title
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A 16-week Multicenter, Randomized, Parallel-group, Double-blind, Placebo-controlled Phase IV Study With a 36-week Extension Period to Evaluate the Efficacy and Safety of Dapagliflozin Therapy When Added to the Therapy of Japanese Patients With Type 2 Diabetes With Inadequate Glycemic Control on Insulin

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Dapagliflozin 5 mg
* Drug: Placebo tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent prior to any study specific procedures Diagnosis of Type 2 Diabetes according the criteria specified by the Japan Diabetes Society Japanese Men or women age ≥ 20 years at time of consenting. Stable (unless adjustment is required based on Fasting Plasma Glucose values) dose insulin* mono-therapy with the mean insulin [up to two types of insulin within authorized indication in Japan] dose of ≥ 0.2 IU/kg/day AND ≥ 15 IU/body/day over the past 8 weeks prior to enrolment. HbA1c ≥ 7.2% and < 11% from the blood samples collected at Visit 1 (enrolment) and Visit 3, observed from the central laboratory Exclusion Criteria: Diagnosis of Type 1 diabetes mellitus, known diagnosis of Maturity Onset Diabetes of the Young, secondary diabetes mellitus or diabetes insipidus History of diabetic ketoacidosis. Thyroid-stimulating hormone and free T4 values outside normal range, observed from the central laboratory; an abnormal Thyroid-stimulating hormone value needs to be followed up with a free T4 test. Patients with abnormal free T4 values will be excluded at Visit 1 Fasting Plasma Glucose >240 mg/dL (twice in a row) despite the permitted dose adjustment of insulin therapy during washout period and lead-in period. Recent cardiovascular events in a patient. eGFR <45 mL/min/1.73 m2 at Visit 3, observed from the central laboratory. History of unstable or rapidly progressing renal disease. History of unexplained microscopic or gross hematuria, or microscopic hematuria at Visit 1, confirmed by a follow-up sample at next scheduled visit, where according to the investigator a satisfactory evaluation of hematuria has not been conducted. Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN, observed from the central laboratory at Visit 1. Total bilirubin >2.0 mg/dL (34.2 μmol/L), observed from the central laboratory at Visit 1. Positive serologic evidence of current infectious liver disease including Hepatitis A viral antibody IgM, Hepatitis B surface antigen and Hepatitis C virus antibody, observed from the central laboratory. Haemoglobin <10 g/dL (<100 g/L) or 6.2 mmol/L for men; haemoglobin <9.0 g/dL (<90 g/L) or 5.9 mmol/L for women, observed from the central laboratory at Visit 1. History of chronic haemolytic anaemia or haemoglobinopathies (for example, sickle cell anaemia, thalassemia, sideroblastic anaemia). Mild haemolysis due to artificial heart valves or due to sickle cell trait is not an exclusion criterion except when haemoglobin levels are too low (as defined in haemoglobin criteria above). History of malignancy within the last 5 years prior to enrolment, excluding successful treatment of basal or squamous cell skin cancer.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 130 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dapagliflozin 5mg<br>dapagliflozin tablet 5mg | Drug: Dapagliflozin 5 mg<br>* Dapagliflozin, a blood glucose lowering drug. Oral dose<br>|
| Placebo Comparator: Placebo<br>dapagliflozin tablet 5mg placebo | Drug: Placebo tablet<br>* Placebo tablet. Oral dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change in HbA1c Levels | Mean change in HbA1c levels from baseline to Week 16 between dapagliflozin 5 mg versus placebo | Baseline to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting Plasma Glucose | Mean change in fasting plasma glucose from baseline to Week 16 between dapagliflozin 5 mg versus placebo | Baseline to Week 16 | 
| Total Body Weight | Mean change in total body weight from baseline to Week 16 between dapagliflozin 5 mg versus placebo | Baseline to Week 16 | 
| Total Mean Daily Insulin Dose | Mean change in calculated mean daily insulin dose from baseline to Week 16 between dapagliflozin 5 mg versus placebo | Baseline to Week 16 | 
| Proportion of Participants With Mean Daily Insulin Dose Reduction of Greater Than or Equal 10% | Proportion of participants with mean daily insulin dose reduction greater than or equal 10% from baseline to week 16 (LOCF) between dapagliflozin 5 mg versus placebo | Baseline to Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Japanese patients with type 2 diabetes with inadequate glycemic control on insulin