Status:
TERMINATED
The Potential of Dapagliflozin Plus Exenatide in Obese Insulin-resistant Patients
Lead Sponsor:
Universitätsklinikum Hamburg-Eppendorf
Collaborating Sponsors:
AstraZeneca
Conditions:
Obesity
Diabetes Mellitus, Type 2
Eligibility:
All Genders
18-75 years
Phase:
PHASE3
Brief Summary
This is a 28-week, multi-center, randomized, double-blind, placebo-controlled trial to study a potential synergistic effect of Dapagliflozin plus Exenatide once-weekly in combination with high-dose in...
Detailed Description
In this proof-of-concept study the potential of treatment with Dapagliflozin plus Exenatide added to high-dose intensive insulin therapy compared to Placebo added to high-dose intensive insulin with a...
Eligibility Criteria
Inclusion
- For inclusion in the study patients should fulfill the following key criteria:
- Informed Consent can be obtained prior to any study procedures.
- Patient is able to read, understand and sign the Informed Consent.
- HbA1c ≥ 8.0% and ≤ 11.0% based on laboratory results
- Currently treated with a stable TDID ≥ 80 U at least 3 months prior to enrolment
- 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
- BMI of ≥ 30 kg/m2 at enrolment
- Male or female and ≥18 and ≤75 years old at time of informed consent
- For female patients:
- Not breastfeeding.
- Negative pregnancy test result (human chorionic gonadotropin, beta subunit \[βhCG\]) 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.
- 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
- Exclusion Criteria:
- Diagnosis of Type 1 Diabetes
- History of diabetic ketoacidosis, hyperosmolar coma or corticosteroid-induced Type 2 diabetes
- Patients with significant thyroid disease
- Patients with history of acute or chronic pancreatitis
- Clinically significant cardiovascular disease or procedure within 3 months prior to enrolment or expected to require coronary revascularization procedure
- Presence of history of severe congestive heart failure (NYHA III and IV)
- Creatinin-Clearance of \< 60 ml/min based on local laboratory results
- Concomitant medication with loop diuretics
- Patients who, as judged by the investigator, may be at risk for dehydration or volume depletion that may affect the patient's safety (including e.g. patients with a history of Diabetes insipidus)
- Pregnant women
- 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
- History of, or currently have, acute or chronic pancreatitis, or have triglyceride concentrations ≥ 700 mg/dL (≥ 7.98 mmol/L) at Visit 0 (Screening).
- 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.
- 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).
- Known history of hepatotoxicity with any medication
- Known history of severe hepatobiliary disease.
- Positive serological test for hepatitis B or hepatitis C.
- Known or suspected human immunodeficiency virus (HIV) infection.
- History of organ transplantation.
- 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.
- Malignancy (with the exception of basal and squamous cell carcinoma of the skin) within 5 years of Visit 0 (Screening).
- 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.
- Patients with abnormal test results of hematocrit (hematocrit \> 50% for men; hematocrit \> 47% for women)
- 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.
- Has donated plasma within 7 days prior to first dose of study medication.
- Any exposure to Exenatide (including BYETTA®, BYDUREON, or exenatide suspension).
- Any exposure to Dapagliflozin or any SGLT-2 inhibitor.
- 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 examples of excluded steroids, refer to Section 7.7.
- Prescription or over-the-counter weight loss medications within 3 months prior to Visit 0 (Screening).
Exclusion
Key Trial Info
Start Date :
February 19 2018
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
August 5 2019
Estimated Enrollment :
13 Patients enrolled
Trial Details
Trial ID
NCT03419624
Start Date
February 19 2018
End Date
August 5 2019
Last Update
March 31 2020
Active Locations (4)
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1
Diabeteszentrum Oldenburg
Oldenburg, Lower Saxony, Germany, 23758
2
University Medical Center Hamburg-Eppendorf
Hamburg, Germany, 20246
3
Diabetologische Schwerpunktpraxis Harburg
Hamburg, Germany, 21073
4
Gemeinschaftspraxis für Innere Medizin und Diabetologie
Hamburg, Germany, 22607