Study to Evaluate Safety and Efficacy of Dapagliflozin in Patients With Type 2 Diabetes Mellitus Aged 10-24 Years

Study Overview
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Brief Summary
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A trial of patients aged 10-24 years with type 2 diabetes mellitus to evaluate the comparative efficacy and safety between dapagliflozin and Placebo.

Detailed Description
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A 24 Week, Multicenter, Randomized, Double-Blind, Parallel Group, Phase 3 Trial with a 28 Week Long Term Safety Extension Period Evaluating the Safety and Efficacy of Dapagliflozin 10 mg in T2DM Patients aged 10-24 years

Official Title
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A 24 Week, Multicenter, Randomized, Double-Blind, Parallel Group, Phase 3 Trial With a 28 Week Long Term Safety Extension Period Evaluating the Safety and Efficacy of Dapagliflozin 10 mg in T2DM Patients Aged 10-24 Years

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Dapagliflozin placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Provision of informed consent prior to any study-specific procedures Males and Females, ages 10 years of age, up to but not including 25 years of age at the time of randomization Previously diagnosed as having type 2 diabetes for at least 2 months by WHO/ADA diagnostic criteria HbA1c >= 6.5% and <= 11% obtained at screening visit Currently on diet and exercise and a stable dose of metformin (at least 1000 mg daily) for a minimum of 8 weeks, or stable dose of insulin for a minimum of 8 weeks, or a stable combination of metformin (at least 1000 mg daily) and insulin for a minimum of 8 weeks prior to screening FPG <=255 mg/dL (<= 14.2 mmol/L) obtained at screening visit Exclusion Criteria: Previous diagnosis of Type 1 diabetes Diabetes ketoacidosis (DKA) within 6 months of screening Current use of the following medications for the treatment of diabetes, or use within the specified timeframe prior to screening for the main study: Eight weeks: sulfonylureas, alpha glucosidase inhibitors, metiglinide, or injectable incretins or incretin mimetics or other antidiabetes medications not otherwise specified Sixteen weeks: thiazolidinediones Any previous history or current use of an SGLT2 inhibitor, including dapagliflozin Initiation or discontinuation of prescription or non-prescription weight loss drugs within 8 weeks of screening. Use of prescription or non-prescription weight loss drugs must be stable during the study Pregnant, positive serum pregnancy test, planning to become pregnant during the clinical trials, or breastfeeding History of unstable or rapidly progressive renal disease History of unresolved vesico-ureteral reflux Replacement or chronic systemic corticosteroid therapy, defined as any dose of systemic corticosteroid taken for > 4 weeks within 3 months prior to the Day 1 visit. Note: Topical, nasal, or inhaled corticosteroids are allowed Abnormal renal function, which is defined in subjects < 18 years of age as an estimated glomerular filtration rate (eGFR) calculated by the Schwartz Formula < 80 mL/min/1.73 m2 (1.33 mL/s), and in subjects >= 18 years as an estimated glomerular filtration rate (eGFR) calculated by the MDRD Formula < 60 mL/min/1.73 m2 (1.33 mL/s) Presence of either: antibodies to glutamic acid decarboxylase (GAD) or protein tyrosine phosphatase-like protein antibodies (IA-2) An abnormal TSH value at screening will be further evaluated for free T4. Subjects with abnormal free T4 values will be excluded Hematuria (confirmed by microscopy at screening) with no explanation as judged by the investigator up to randomization Anemia of any etiology defined as hemoglobin <=10.7 g/dL (107 g/L) for females and <= 11.3 g/dL (113 g/L) for males. Subjects who are considered to have anemia according to local guidelines should be excluded Volume-depleted subjects. Subjects at risk for volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics, should carefully monitor their volume status

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 24 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozin<br> | Drug: Dapagliflozin<br>* Dapagliflozin 10 mg tablets administered orally once daily, for the 24-week blinded treatment period. Dapagliflozin 10mg tablets administered orally once daily, for the 28-week site and subject blinded long term extension.<br>* Other names: FORXIGA;|
| Placebo Comparator: Dapagliflozin placebo<br> | Drug: Dapagliflozin placebo<br>* matching placebo tablets, administered orally once daily, for the 24-week blinded treatment period. Dapagliflozin 10mg tablets administered orally once daily,for the 28-week site and subject blinded long term extension.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Change From Baseline in Glycated Haemoglobin (HbA1c) at Week 24 |  | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 |  | Baseline to Week 24 | 
| Percentage of Participants Who Required Glycemic Rescue Medication or Permanently Discontinued Treatment Due to Lack of Glycemic Control |  | Baseline to Week 24 | 
| Percentage of Participants With Baseline Glycated Haemoglobin (HbA1c) >= 7% Who Achieved HbA1c Level < 7% at Week 24 |  | Baseline to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Dapagliflozin, Placebo, Insulin resistance, Metabolic Diseases