Phase 3 28-Week Study With 24-Week and 52-week Extension Phases to Evaluate Efficacy and Safety of Exenatide Once Weekly and Dapagliflozin Versus Exenatide and Dapagliflozin Matching Placebo

Study Overview
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Brief Summary
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Study D5553C0003 is a 28-week, randomized, double-blind, active-controlled, multicenter, Phase 3 efficacy and safety study with 24-week and 52-week extension phases of simultaneous administration of exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg once daily (QD) compared to EQW 2 mg alone and dapagliflozin 10 mg QD alone in patients with Type 2 diabetes who have inadequate glycemic control on metformin.

Official Title
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A 28-week, Multicenter, Randomized, Double-Blind, Active-Controlled, Phase 3 Study With a 24-week Extension Phase Followed by a 52-week Extension Phase to Evaluate the Efficacy and Safety of Simultaneous Administration of Exenatide Once Weekly 2 mg and Dapagliflozin Once Daily 10 mg Compared to Exenatide Once Weekly 2 mg Alone and Dapagliflozin Once Daily 10 mg Alone in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: Exantide with Dapagliflozin
* Drug: Exentide
* Drug: Dapagliflozin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Has a diagnosis of T2DM. Has HbA1c of 8.0% to 12.0%, inclusive, at Visit 1 and Visit 2. Treated with a stable dose of metformin ≥1500 mg/day for at least 2 months prior to Screening. Exclusion criteria FPG ≥280 mg/dL (15.6 mmol/L). Serum calcitonin concentration ≥40 pg/mL (≥40 ng/L) at Visit 1 (Screening) Clinically significant abnormal free T4 values or patients needing initiation or adjustment of thyroid treatment according to the investigator. Abnormal thyroid stimulating hormone (TSH) value at Screening will be further evaluated by free T4.Patients with clinically significant abnormal free T4 values will be excluded. Known active proliferative retinopathy. History of, or currently have, acute or chronic pancreatitis, or have triglyceride concentrations ≥500 mg/dL (≥5.65 mmol/L) at Visit 1 History or presence of inflammatory bowel disease or other severe GI diseases, particularly those which may impact gastric emptying, such as gastroparesis or pyloric stenosis. History of gastric bypass surgery or gastric banding surgery, or either procedure is planned during the time period of the study. Current use of gastric balloons is also excluded.

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exenatide Once Weekly 2 mg and Dapagliflozin Once Daily 10 mg<br> | Drug: Exantide with Dapagliflozin<br>* 2 mg weekly suspension injection and 10 mg Dapagliflozin<br>|
| Experimental: Exenatide Once Weekly 2 mg Alone<br> | Drug: Exentide<br>* 2 mg<br>|
| Active Comparator: Dapagliflozin Once Daily 10 mg Alone<br> | Drug: Dapagliflozin<br>* 10 mg once daily Dapagliflozin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c From Baseline to Week 28 | To compare the change from baseline to Week 28 in HbA1c between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone. | Baseline to Week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Weight From Baseline to Week 28 | To compare the change from baseline to Week 28 in body weight between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone. | Baseline to Week 28 | 
| Change in Fasting Plasma Glucose From Baseline to Week 28 | To compare the change from baseline to Week 28 in fasting plasma glucose between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone. | Baseline to Week 28 | 
| Change From Baseline to Week 28 in 2-hour Postprandial Glucose After a Standard Meal Tolerance Test | To compare the change from baseline to Week 28 in 2-hour postprandial glucose after a standard Meal Tolerance Test between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone. | Baseline to Week 28 | 
| Percentage of Patients Achieving Weight Loss ≥5.0% at Week 28 | To compare the percentage of patients achieving weight loss ≥5.0% at 28 weeks between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone. | Baseline to Week 28 | 
| Change in Fasting Plasma Glucose From Baseline to Week 2 | To compare the change from baseline to Week 2 in fasting plasma glucose between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone. | Baseline to Week 2 | 
| Percentage of Patients Achieving HbA1c <7% at Week 28 | To compare the percentage of patients achieving HbA1c <7% at 28 weeks between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone. | Baseline to Week 28 | 
| Change in Systolic Blood Pressure From Baseline to Week 28 | To compare the change from baseline to Week 28 in systolic blood pressure between exenatide once weekly (EQW) 2 mg and dapagliflozin 10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone. | Baseline to Week 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exenatide, Placebo, Diabetes Mellitus, Dapagliflozin, Diabetes medication, Treatment efficacy, Metabolism, Cardiovascular metabolic