Obesity defined as body mass index (BMI) 30-45 kg/m2 Obesity related metabolic disorders MedDRA version: 18.0 Level: LLT Classification code 10029885 Term: Obesity, unspecified System Organ Class: 100000004861
Conditions
Interventions
Trade Name: Forxiga 10 mg
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: DAPAGLIFLOZIN
CAS Number: 461432-26-8
Other descriptive name: DAPAGLIFLOZIN
Concentration unit: mg milligram(s)
C
Sponsors
Dept of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University
Eligibility
Sex/Gender
All
Inclusion criteria
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: a) Not breastfeeding b) Negative pregnancy test result (human chorionic gonadotropin, beta subunit [?hCG]) at Visit 1 (Enrolment) (not applicable to hysterectomized females). c) 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: i. Diaphragm or partner use of condom in combination with combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: • Oral • Intravaginal • Transdermal ii. Diaphragm or partner use of condom in combination with progestogen-only hormonal contraception associated with inhibition of ovulation: • Oral • Injectable • Implantable iii. Placement of an intrauterine device iv. Placement of an intrauterine hormone-releasing system v. Bilateral tubal occlusion vi. 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) vii. Sexual abstinence (defined as refraining from heterosexual intercourse) d) Must practice appropriate birth control as stated above for 10 weeks after the last dose of study medication 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 48 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 48
Exclusion criteria
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 IP 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) Previous or new diagnosis of diabetes mellitus. For subjects being diagnosed with diabetes at enrolment, this should be judged by an experienced diabetologist and be based on composite laboratory measures according to American Diabetes Association (ADA) guidelines. These criteria include FPG >7.0 mmol/l, 2h-PG at OGTT >11.1 mmol/l and/or HbA1c > 48 mmol/mol. Subjects with FPG =7.0 mmol/L or 2h-PG =11.1 mmol/l at Visit 1, should have a second FPG measurement on a separate day, and if diabetes diagnosis is confirmed 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: a) Creatinine clearance 3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN. c) 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 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of dapagliflozin 10 mg once daily and exenatide 2 mg once weekly in combination compared to placebo on body weight after 24 weeks of treatment in obese subjects (by measuring change in body weight (kg) from baseline to 24 weeks);Secondary Objective: Sec. Objective -Assess the efficacy of dapagliflozin 10 mg once daily and exenatide 2 mg once weekly in comb. compared to placebo on body weight after 24 w of treatment in obese subjects (by measuring change in percentage body weight from baseline to 24 w) Exploratory objectives To assess: -Proportion of subjects responding to treatment with dapagliflozin & exenatide in comb. when compared to placebo -Efficacy of a 28-w open-label period w dapagliflozin & exenatide following 24 w blinded treatment with dapagliflozin & exenatide in comb. or placebo respectively, to maintain or enhance body weight reduction -Efficacy of dapagliflozin & exenatide in comb. compared to placebo on total body fat mass, total lean body mass, percentage liver fat, visceral fat mass & subcutaneous fat mass, glucose tolerance, insulin secretion, insulin sensitivity and lipolysis regulation, blood lipid profile, blood pressure & other anthropometric measurements;Primary end point(s): Percentage change in body weight (kg) from baseline to 24 weeks ;Timepoint(s) of evaluation of this end point: End of trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoint: Change in percentage bodyweight from baseline to 24 weeks Exploratory endpoints: Proportion of subjects with at least 10% reduction in weight at 24 and proportion of subjects with at least 5% reduction in weight at 24 Change in body weight (kg and percentage) from baseline to 52 weeks Changes in -Liver fat (%) -Liver volume (l) -Total liver fat (l) -Visceral Adipose Tissue (l) -Subcutaneous Adipose Tissue (l) -Total Adipose Tissue (l) -Total lean tissue (l) -Body fat (%) and other important parameters such as insulin, glukagon and free fatty acids;Timepoint(s) of evaluation of this end point: End of trial | — |
Countries
Sweden
Contacts
Public ContactJan Eriksson
Dept of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University
Outcome results
None listed