Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes

Study Overview
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Brief Summary
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The purpose of this study is to determine if adding dapagliflozin to insulin is a safe and effective therapy to improve glycemic control in patients with type 1 diabetes.

Detailed Description
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Study Classification: Safety, Efficacy and Pharmacokinetics/dynamics

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-controlled, Parallel Group, Phase 3 Study to Evaluate the Efficacy and Safety of Dapagliflozin as an Add-on to Insulin Therapy in Subjects With Type 1 Diabetes Mellitus - Study Two

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: Dapagliflozin
* Other: Placebo for dapagliflozin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Type 1 Diabetes mellitus (T1DM) Central laboratory C-peptide < 0.7 ng/ml (0.23 nmol/L) Insulin use for at least 12 months per patient reported or medical records Method of insulin administration (MDI or CSII) must have been unchanged for at least 3 months prior to screening Subjects must be on a total insulin dose of ≥ 0.3 U/kg/day for at least 3 months prior to screening If on MDI insulin administration, subject must be on ≥ 3x injections per day Screening Visit: Central laboratory HbA1c ≥ 7.7% and ≤ 11.0% Body mass index (BMI) ≥ 18.5 kg/m2 Exclusion Criteria: History of Type 2 Diabetes mellitus (T2DM) or maturity onset diabetes of the young (MODY), pancreatic surgery, or chronic pancreatitis that could result in decreased beta cell capacity Taking any non-insulin antihyperglicemic agent within 1 month prior to screening Taking GLP-1 receptor agonist within 2 months prior to screening for once weekly administration and within 1 month prior to screening for once or twice daily administration Taking metformin and/or thiazolidinediones within 2 months prior to screening History of diabetes ketoacidosis requiring medical intervention within 1 month prior to screening History of hospital admission for glycemic control (either hyperglycemia or hypoglycemia) within 1 month prior to screening Frequent episodes of severe hypoglycemia (more than one episode requiring medical assistance, emergency care), and/or glucagon therapy administered by a third-party individual within 1 month prior to screening History of Addison's disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 5 mg<br>Dapagliflozin 5 mg tablet orally, once daily for 52 weeks | Drug: Dapagliflozin<br>* Tablets<br>|
| Experimental: Dapagliflozin 10 mg<br>Dapagliflozin 10 mg tablet orally, once daily for 52 weeks | Drug: Dapagliflozin<br>* Tablets<br>|
| Placebo Comparator: Placebo<br>Placebo tablet orally, once daily for 52 weeks | Other: Placebo for dapagliflozin<br>* Tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change From Baseline in HbA1c at Week 24 | To compare the change from baseline in HbA1c between dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment | Baseline and 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Percentage Change From Baseline in Total Daily Insulin Dose at Week 24 | To compare the percent change from baseline in total daily insulin dose with dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment | Baseline and 24 weeks | 
| Adjusted Mean Percentage Change From Baseline in Body Weight at Week 24 | To compare the percentage change from baseline in body weight with dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment | Baseline and 24 weeks | 
| Adjusted Mean Change From Baseline in 24-hour Continuous Glucose Monitoring (CGM) Mean Value at Week 24 | To compare the change from baseline in mean value of 24-hour glucose readings obtained from CGM with dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment | Baseline and 24 weeks | 
| Adjusted Mean Change From Baseline in 24-hour CGM Mean Amplitude of Glycemic Excursion (MAGE) Value at Week 24 | To compare the change from baseline in mean amplitude of glucose excursions (MAGE) of 24-hour glucose readings obtained from CGM with dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment | Baseline and 24 weeks | 
| Change From Baseline in the Percent of 24-hour Glucose Readings Obtained From CGM That Falls Within the Target Range of > 70 mg/dL and <= 180 mg/dL (%) at Week 24 | To compare the change from baseline in the percent of 24-hour glucose readings obtained from CGM that falls within the target range of >70 mg/dL and <=180 mg/dL with dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin after 24 weeks of double-blinded treatment | Baseline and 24 weeks | 
| Percentage of Subjects With HbA1c Reduction From Baseline to Week 24 Last Observation Carried Forward (LOCF) >= 0.5% and Without Severe Hypoglycemia Events at Week 24 | To compare dapagliflozin 5 mg or 10 mg plus adjustable insulin versus placebo plus adjustable insulin for the proportion of subjects achieving an HbA1c reduction from baseline to Week 24 visit >=0.5% without severe hypoglycemia events | Baseline and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dapagliflozin, Efficacy, Safety, Add on to insulin, Oral Antidiabetic, Type 1 diabetes