Combination treatment with dapagliflozin and exenatide to investigate the effect of weight loss in subjects with obesity compared to placebo.

Phase 1

• Conditions: Obesity defined as body mass index (BMI) 30-45 kg/m2Obesity related metabolic disorders; MedDRA version: 18.0Level: LLTClassification code 10029885Term: Obesity, unspecifiedSystem Organ Class: 100000004861; Therapeutic area: Body processes [G] - Metabolic Phenomena [G03]

• Registration Number: EUCTR2014-003432-39-SE
• Lead Sponsor: Dept of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-09-22
• Last Update Posted: 22 May 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

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

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 <60mL/min (estimated with Cockroft-Gault formula).
b)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.
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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified