Exploratory Study to Investigate the Effect of Dapagliflozin and Exenatide Combined on Body Weight (Dapalost)

This is an interventional treatment trial for Obesity focused on measuring Obesity, Dapagliflozin, Exenatide, Combination treatment, Type 2 diabetes Read More

Inclusion Criteria:

1. Provision of signed informed consent prior to any study specific procedures.
2. Female and/or male aged 18 to 70 years with body mass index (BMI) (measured as body weight (kg)/(height (m))2) 30 to 45 kg/m2.

3. Female subjects must meet all of the following criteria:

   1. Not breastfeeding
   2. Negative pregnancy test result (human chorionic gonadotropin, beta subunit [beta hCG]) at Visit 1 (Enrolment) (not applicable to hysterectomized females).

   3. 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 one of the following highly effective birth control methods during the entire duration of the study:

      • Diaphragm or partner use of condom in combination with combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

        • Oral
        • Intravaginal
        • Transdermal

      • Diaphragm or partner use of condom in combination with progestogen-only hormonal contraception associated with inhibition of ovulation:

        • Oral
        • Injectable
        • Implantable
      • Placement of an intrauterine device
      • Placement of an intrauterine hormone-releasing system
      • Bilateral tubal occlusion
      • Vasectomised partner (provided that the partner is the sole sexual partner of the female subject and that the vasectomised partner has received medical assessment of the surgical success)
      • Sexual abstinence (defined as refraining from heterosexual intercourse)
   4. Must practice appropriate birth control as stated above for 10 weeks after the last dose of study medication

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study.
2. Previous enrolment in the present study.
3. Participation in another clinical study with an Investigational Product during the last 3 months prior to Visit 1.
4. History of any clinically significant disease, disorder or condition which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
5. Previously diagnosed diabetes mellitus; or fasting P-glucose ≥7.0 mmol/L at Visit 1 confirmed by one more measurement; or P-glucose ≥11.1 mmol/L at 120 min of the oral glucose tolerance test (OGTT) at Visit 1 confirmed by one more measurement. Note: Subjects with a fasting P-glucose of ≥7.0 mmol/L at Visit 1 or ≥11.1 mmol/L at 120 min of the OGTT at Visit 1 may be offered an extra visit before Visit 2 for a second fasting P-glucose measurement. If P-glucose is still ≥7.0 mmol/L at the second measurement, the subject will be excluded.

6. Any clinically significant abnormalities in physical examination or clinical chemistry results as judged by the investigator. The following specific exclusion criteria apply to the selected Clinical Chemistry results:

   1. Creatinine clearance <60 mL/min (estimated with Cockcroft-Gault formula).
   2. Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN.
   3. Total bilirubin (TB) >2.0 mg/dL (34.2 µmol/L).
7. Positive serologic evidence of current infectious liver disease including Hepatitis B viral antibody Immunoglobulin M (IgM), Hepatitis B surface antigen and Hepatitis C virus antibody.
8. Volume depleted patients. Patients at risk for volume depletion due to co-existing conditions or concomitant medications, such as loop diuretics should have careful monitoring of their volume status.
9. Acute Coronary Syndrome (ACS) within 2 months prior to Visit 1. Hospitalization for unstable angina or acute myocardial infarction within 2 months prior to enrolment. Acute Stroke or transient ischemic attack (TIA) within two months prior to Visit 1. Less than two months post coronary artery revascularization.
10. History of gastroparesis or pancreatitis
11. History of malignancy within the last 5 years, excluding successful treatment of basal or squamous cell skin cancer.
12. Body weight loss greater than 5% within 3 months prior to Visit 1.
13. Treatment with any drug known to affect body weight within the last month, e.g. systemic glucocorticoids, antipsychotics or orlistat.
14. Multiple Endocrine Neoplasia syndrome type 2.
15. Personal or family history of medullary thyroid carcinoma.