Efficacy and Safety of Dapagliflozin, Added to Therapy of Patients With Type 2 Diabetes With Inadequate Glycemic Control on Insulin

Study Overview
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Brief Summary
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This study is being carried out to see if Dapagliflozin in addition to insulin is effective and safe in treating patients with type 2 diabetes when compared to placebo (identical looking inactive treatment) in addition to insulin

Official Title
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A 24-week International, Randomized, Parallel-group, Double-blind, Placebo-controlled Phase III Study With a 80-week Extension Period to Evaluate the Efficacy and Safety of Dapagliflozin Therapy When Added to the Therapy of Patients With Type 2 Diabetes With Inadequate Glycaemic Control on Insulin

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Dapagliflozin
* Drug: Dapagliflozin
* Drug: Placebo
* Drug: Dapagliflozin
* Drug: Dapagliflozin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 Diabetes Patients with HbA1c ≥7.5% and ≤10.5% and who are on a stable insulin regimen of at least 30 IU of injectable insulin per day either without any other oral antidiabetic drug or with a stable dose of oral antidiabetic drugs Exclusion Criteria: Type 1 Diabetes Treatment with more than two additional oral antidiabetic drugs Moderate and severe renal (kidney) failure or dysfunction

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: 1<br>2.5mg | Drug: Dapagliflozin<br>* tablet oral 2.5 mg total daily dose once daily 48 weeks (= 24 week randomised treatment period + 24 week study extension period I)<br>Drug: Dapagliflozin<br>* tablet oral 2.5 total daily dose once daily 56 weeks (= 56 week study extension period II)<br>|
| Experimental: 2<br>5mg | Drug: Dapagliflozin<br>* Tablet oral 5 mg total daily dose once daily 48 weeks (= 24 week randomised treatment period + 24 week study extension period I)<br>|
| Experimental: 3<br>10mg | Drug: Dapagliflozin<br>* Tablet oral 10 mg total daily dose once daily 48 weeks (= 24 week randomised treatment period + 24 week study extension period I)<br>Drug: Dapagliflozin<br>* tablet oral 10 mg total daily dose once daily 56 weeks (= 56 week study extension period II)patients that have been treated with 5 mg during the 24 week randomised treatment period and extension I period will during extension II period switched to 10 mg<br>|
| Placebo Comparator: 4<br> | Drug: Placebo<br>* Placebo<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 | To assess the efficacy of 2.5 mg, 5 mg and 10 mg dapagliflozin compared to placebo as add-on therapy to insulin in improving glycaemic control in participants with type 2 diabetes who have inadequate glycaemic control on ≥ 30 IU injectable insulin daily for at least 8 weeks prior to enrolment, as determined by the change in HbA1c levels from baseline to Week 24, excluding data after insulin up-titration. | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change in Body Weight | To examine whether treatment with dapagliflozin in combination with insulin is superior in reducing body weight or causing less weight gain as compared to placebo added to insulin treatment after 24 weeks of treatment (LOCF), excluding data after insulin up-titration. | Baseline to Week 24 | 
| Adjusted Mean Change in Calculated Mean Daily Insulin Dose | To examine whether treatment with dapagliflozin in combination with insulin leads to a lower absolute calculated mean daily insulin dose as compared to placebo added to insulin treatment alone, from baseline to week 24, including data after insulin up-titration. | Baseline to Week 24 | 
| Proportion of Participants With Calculated Mean Daily Insulin Dose Reduction | To examine whether treatment with dapagliflozin in combination with insulin leads to higher percentage of participants with calculated mean daily insulin dose reduction from baseline to week 24 (i.e. reduction >= 10%) as compared to placebo added to insulin treatment. | Baseline to Week 24 | 
| Adjusted Mean Change in Fasting Plasma Glucose (FPG) | To examine whether treatment with dapagliflozin in combination with insulin is superior in reducing Fasting Plasma Glucose (FPG) as compared to placebo added to insulin treatment after 24 weeks of treatment, excluding data after insulin up-titration. | Baseline to Week 24 | 

 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 2 diabetes