A 28-week, multi-center randomized, double-blind, placebo-controlled study to evaluate the potential of Dapagliflozin plus Exenatide in combination with high-dose intensive insulin therapy compared to Placebo in obese insulin-resistant patients with Type 2 Diabetes mellitus (Proof-of-concept study)
- Conditions
- MedDRA version: 20.0Level: LLTClassification code 10045242Term: Type II diabetes mellitusSystem Organ Class: 100000004861Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]Obese insulin-resistant patients with Type 2 Diabetes mellitus (T2DM) and inadequate glycemic control (HbA1c = 8.0% and = 11.0%)
- Registration Number
- EUCTR2016-003738-25-DE
- Lead Sponsor
- niversity Medical Center Hamburg-Eppendorf
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 60
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
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 < 60 ml/min based on local laboratory results
8. Concomitant medication with loop diuretics
9. Pregnant women
10. Administration of any other antidiabetic therapy, other than insulin (see inclusion criterion no.4 and 5) and metformin with a stable total daily dose = 1500 mg or the maximum tolerated dose of metformin within 3 months prior to enrolment
11. History of, or currently have, acute or chronic pancreatitis, or have triglyceride
concentrations = 700 mg/dL (= 7.98 mmol/L) at Visit 0 (Screening).
12. 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.
13. 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.
14. 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).
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method