Obese insulin-resistant patients with Type 2 Diabetes mellitus (T2DM) and inadequate glycemic control (HbA1c = 8.0% and = 11.0%) MedDRA version: 20.0 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000004861
Conditions
Interventions
Trade Name: Bydureon
Pharmaceutical Form: Powder and solvent for suspension for injection
INN or Proposed INN: EXENATIDE
CAS Number: 141758-74-9
Concentration unit: mg milligram(s)
Concentration numbe
Sponsors
University Medical Center Hamburg-Eppendorf
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed Consent can be obtained prior to any study procedures. 2. Patient is able to read, understand and sign the Informed Consent. 3. HbA1c = 8.0% and = 11.0% based on laboratory results 4. Currently treated with a stable TDID = 80 U at least 3 months prior to enrolment 5. Patients who are receiving metformin must be on a stable total daily dose = 1500 mg or the maximum tolerated dose of metformin within 3 months prior to enrolment 6. BMI of = 30 kg/m2 at enrolment 7. Male or female and =18 and =75 years old at time of informed consent 8. For female patients: - Not breastfeeding. - Negative pregnancy test result (human chorionic gonadotropin, beta subunit [ßhCG]) at Visit 0 (Screening) and Visit 1 (randomization) -not applicable to hysterectomized and post-menopausal 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. 9. Patients who are receiving the following medications must be on a stable treatment regimen for a minimum of 2 months prior to Visit 0 (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 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Diagnosis of Type 1 Diabetes 2. History of diabetic ketoacidosis, hyperosmolar coma or corticosteroid-induced Type 2 diabetes 3. Patients with significant thyroid disease 4. Patients with history of acute or chronic pancreatitis 5. Clinically significant cardiovascular disease or procedure within 3 months prior to enrolment or expected to require coronary revascularization procedure 6. Presence of history of severe congestive heart failure (NYHA III and IV) 7. Creatinin-Clearance of 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). 15. Known history of hepatotoxicity with any medication 16. Known history of severe hepatobiliary disease. 17. Positive serological test for hepatitis B or hepatitis C. 18. Known or suspected human immunodeficiency virus (HIV) infection. 19. History of organ transplantation. 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 0 (Screening). 22. Hemoglobinopathy, hemolytic anemia, or chronic anemia (haemoglobin 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 donate blood during the study. 24. Has donated plasma within 7 days prior to first dose of study medication. 25. Any exposure to Exenatide (including BYETTA®, BYDUREON™, or exenatide suspension). 26. Any exposure to Dapagliflozin or any SGLT-2 inhibitor. 27. Has been treated, is currently being treated, or is expected to require or undergo treatment with any of the following treatment excluded medications: - Any DPP-4 inhibitor within 3 months prior to Visit 0 (Screening). - Any GLP-1 analog within 1 year prior to Visit 0 (Screening). - Systemic corticosteroids within 3 months prior to Visit 0 (Screening) by oral, intravenous, intra-articular, or intramuscular route; or potent, inhaled, or intrapulmonary (including ADVAIR®) steroids known to have a high rate of systemic absorption. For exampl
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the absolute change from baseline in HbA1c at week 28 between Dapagliflozin plus Exenatide, Placebo or Exenatide monotherapy added to high-dose intensive insulin therapy;Primary end point(s): The primary efficacy endpoint is the change in HbA1c from baseline to Week 28.;Timepoint(s) of evaluation of this end point: Week 28;Secondary Objective: -compare the absolute change from baseline in HbA1c at week 14 between Dapagliflozin plus Exenatide, Placebo or Exenatide monotherapy added to high-dose intensive insulin therapy -compare the change from baseline in total body weight at week 14 and 28 between Dapagliflozin plus Exenatide, Placebo or Exenatide monotherapy added to high-dose intensive insulin therapy - compare the change from baseline in BMI at week 14 and 28 between Dapagliflozin plus Exenatide, Placebo or Exenatide monotherapy added to high-dose intensive insulin therapy -compare the change in fasting plasma glucose (FPG) at week 14 and 28 between Dapagliflozin plus Exenatide, Placebo or Exenatide monotherapy added to high-dose intensive insulin therapy -compare the change in total daily insulin dose (TDID) at week 14 and 28 between Dapagliflozin plus Exenatide, Placebo or Exenatide monotherapy added to high-dose intensive insulin therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change in HbA1c from baseline (week 0) to week 14 - Change in total body weight from baseline (week 0) to week 14 and 28 - Change in BMI from baseline (week 0) to week 14 and 28 - Change in FPG from baseline (week 0) to week 14 and 28 -Change in TDID from baseline (week 0) to week 14 and 28 (approaching a target FPG of 100-120mg/dL/ 5.6-6.7 mmol/L) - Proportion of patients achieving HbA1c of = 7% at week 28 compared to baseline;Timepoint(s) of evaluation of this end point: - Change in HbA1c from baseline (week 0) to week 14 - Change in total body weight from baseline (week 0) to week 14 and 28 - Change in BMI from baseline (week 0) to week 14 and 28 - Change in FPG from baseline (week 0) to week 14 and 28 -Change in TDID from baseline (week 0) to week 14 and 28 (approaching a target FPG of 100-120mg/dL/ 5.6-6.7 mmol/L) - Proportion of patients achieving HbA1c of = 7% at week 28 compared to baseline | — |
Countries
Germany
Contacts
Public ContactStudy Coordinator
University Medical Center Hamburg-Eppendorf, Sektion Endokrinologie und Diabetologie
Outcome results
None listed