28 Week Phase 3 study and 24 Week extension followed by a 52 Week extension to evaluate efficacy and safety of Exenatide once weekly and Dapagliflozin versus Exenatide and Dapagliflozin matching placebo

Phase 1

• Conditions: Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]; Diabetes Mellitus; MedDRA version: 20.0Level: HLTClassification code 10012602Term: Diabetes mellitus (incl subtypes)System Organ Class: 100000004860

• Registration Number: EUCTR2014-003503-29-SK
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-11-21
• Last Update Posted: 14 May 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 660

Inclusion Criteria

1) Is at least 18 years old at Screening; the upper age limit should be based on local metformin label restrictions.
2) Has a diagnosis of T2DM.
3) Has HbA1c of 8.0% to 12.0%, inclusive, at Visit 1 and Visit 2.
4) Treated with a stable dose of metformin =1500 mg/day for at least 2 months prior to Screening.
5) Is male, or is female and meets all the following criteria:
?-Not breastfeeding.
?-Negative pregnancy test result (human chorionic gonadotropin, beta subunit [ßhCG]) at Visit 1 (Screening) (not applicable to hysterectomized females).
?-If of childbearing potential (including perimenopausal women who have had a menstrual period within 1 year), must practice and be willing to continue to practice appropriate birth control (defined as a method which results in a low failure rate, ie, less than 1% per year, when used consistently and correctly, such as implants, injectables, hormonal contraceptives [pills, vaginal rings, or patches], some intrauterine contraceptive devices [levonorgestrel-releasing or copper-T], tubal ligation or occlusion, or a vasectomized partner) during the entire duration of the study. As applicable, all methods must be in effect prior to receiving the first dose of study medication.
?-Must practice appropriate birth control as stated above for 10 weeks after the last dose of study medication.
6) Patients who are receiving the following medications must be on a stable treatment regimen for a minimum of 2 months prior to Visit 1 (Screening):
?-Antihypertensive agents
?-Thyroid replacement therapy
?-Antidepressant agents.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 594
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 66

Exclusion Criteria

1.FPG =280 mg/dL (15.6 mmol/L).
2.Serum calcitonin concentration =40 pg/mL (=40 ng/L) at Visit 1 (Screening).
3.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.
4.Known active proliferative retinopathy.
5.History of, or currently have, acute or chronic pancreatitis, or have triglyceride concentrations =500 mg/dL (=5.65 mmol/L) at Visit 1 (Screening).
6.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.
7.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.
8.Significant hepatic disease, including, but not limited to, acute hepatitis, chronic active hepatitis, or severe hepatic insufficiency, including patients with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or total bilirubin (TB) >2 mg/dL (>34.2 µmol/L) (patients with TB >2 mg/dL [>34.2 µmol/L] and documented Gilbert’s syndrome will be allowed to participate).
9.Known history of hepatotoxicity with any medication.
10.Known history of severe hepatobiliary disease.
11.Positive serological test for hepatitis B or hepatitis C.
12.Clinically significant cardiovascular disease or procedure within 3 months of Visit 1, including but not limited to myocardial infarction, clinically significant arrhythmia, unstable angina, coronary artery bypass surgery, or angioplasty; or are expected to require coronary artery bypass surgery or angioplasty during the course of the study.
13.Presence or history of severe congestive heart failure (New York Heart Association Class IV [CCNYHA 1994]).
14.Severe uncontrolled hypertension defined as systolic blood pressure =180 mmHg and/or diastolic blood pressure =110 mmHg.
15.Creatinine clearance <60 mL/min (1 mL/s) (calculated by Cockcroft-Gault formula) or a measured serum creatinine value of =1.5 mg/dL (133 µmol/L) for male patients and =1.4 mg/dL (124 µmol/L) for female patients.
16.Congenital renal glucosuria.
17.History of unstable or rapidly progressing renal disease.
18.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 based on guidance in Section 6.3.9.
19.Known or suspected human immunodeficiency virus (HIV) infection.
20.Presence or history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN 2) OR a family history of medullary thyroid carcinoma or MEN 2.
21.Malignancy (with the exception of basal and squamous cell carcinoma of the skin) within 5 years of Visit 1 (Screening).
22.Hemoglobinopathy, hemolytic anemia, or chronic anemia (hemoglobin concentration <11.5 g/dL [115 g/L] for males, <10.5 g/dL [105 g/L] for females) or any other condition known to interfere with the HbA1c methodology.
23.Has donated blood or had a significant blood loss within 2 months of first dose of study medication or is planning to don

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the change from baseline in HbA1c at 28 weeks between EQW 2 mg and dapagliflozin<br>10 mg administered simultaneously compared to EQW 2 mg alone and dapagliflozin 10 mg alone.;Secondary Objective: To compare the effect of EQW + dapagliflozin to EQW + placebo and/or to dapagliflozin + placebo,<br>on changes in glycemic control and anthropometric measures.;Primary end point(s): The primary efficacy endpoint is the change in HbA1c. ;Timepoint(s) of evaluation of this end point: From baseline to Week 28.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary efficacy endpoints<br>• Change in total body weight from baseline to Week 28<br>• Change in FPG from baseline to Week 28<br>• Change from baseline in 2-hour PPG after standardized MTT at Week 28<br>• Proportion of patients achieving HbA1c <7.0% at Week 28<br>• Proportion of patients achieving weight loss =5.0% at Week 28<br>• Change from baseline in FPG to Week 2 (dapagliflozin+exenatide vs exenatide)<br>• Change from baseline in seated systolic BP from baseline to Week 28;Timepoint(s) of evaluation of this end point: From baseline to Week 28.