A 24-week, Single Centre, Randomized, Parallel-group, Double-blind, Placebo Controlled Phase II Study With an Optional 28-week Open-label Extension to Evaluate the Efficacy on Body Weight of Dapagliflozin 10 mg Once Daily in Combination With Exenatide 2 mg Once Weekly in Obese Non-diabetic Subjects.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Body weight (kg)
研究概览
简要总结
Obesity is a medical condition which increases the risk of other diseases, such as type 2 diabetes and cardiovascular disease. Obesity-related risk factors for the development of other metabolic diseases include unstable glucose levels and high blood pressure. Dapagliflozin and exenatide are both approved worldwide for treatment of patients with Type 2 Diabetes. Dapagliflozin works by lowering glucose levels by inhibiting the renal reabsorption of glucose and thereby promoting its urinary excretion and energy loss and thereby reduction in body fat. Exenatide exhibits many of the same glucose-lowering actions of that of a naturally occurring hormone and leads to weight loss mainly via reduced energy intake, most likely via a central effect on appetite regulation. The purpose of this exploratory study is to investigate if a combination treatment with dapagliflozin and exenatide have a synergistic effect on weight loss in non-diabetic obese subjects. Subjects will be treated for 24 weeks with either active combination treatment or placebo (non-active treatment). Neither study personnel nor subjects will know what treatment is given. All subjects completing the 24-week double-blind study and who are willing and eligible will be offered to enter a 28-week open-label extension study. All subjects entering the extension study will receive unblinded active study treatment for an additional 28 weeks. Thus the total treatment period for subjects entering the extension study will be 52 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of signed informed consent prior to any study specific procedures.
- •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/m
- •Female subjects must meet all of the following criteria:
- •Not breastfeeding
- •Negative pregnancy test result (human chorionic gonadotropin, beta subunit [beta hCG]) at Visit 1 (Enrolment) (not applicable to hysterectomized 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 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:
- •Intravaginal
- •Transdermal
- •Diaphragm or partner use of condom in combination with progestogen-only hormonal contraception associated with inhibition of ovulation:
- •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)
- •Must practice appropriate birth control as stated above for 10 weeks after the last dose of study medication
排除标准
- •Involvement in the planning and/or conduct of the study.
- •Previous enrolment in the present study.
- •Participation in another clinical study with an Investigational Product during the last 3 months prior to Visit
- •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.
- •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.
- •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:
- •Creatinine clearance <60 mL/min (estimated with Cockcroft-Gault formula).
- •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.
- •Total bilirubin (TB) >2.0 mg/dL (34.2 µmol/L).
- •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.
- •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.
- •Acute Coronary Syndrome (ACS) within 2 months prior to Visit
- •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
- •Less than two months post coronary artery revascularization.
- •History of gastroparesis or pancreatitis
- •History of malignancy within the last 5 years, excluding successful treatment of basal or squamous cell skin cancer.
- •Body weight loss greater than 5% within 3 months prior to Visit
- •Treatment with any drug known to affect body weight within the last month, e.g. systemic glucocorticoids, antipsychotics or orlistat.
- •Multiple Endocrine Neoplasia syndrome type
- •Personal or family history of medullary thyroid carcinoma.
研究组 & 干预措施
Dapagliflozin and exenatide
Dapagliflozin 10 mg film-coated tablet once daily and exenatide 2 mg once weekly injection combined treatment for 24 weeks
干预措施: Dapagliflozin (Drug)
Dapagliflozin and exenatide
Dapagliflozin 10 mg film-coated tablet once daily and exenatide 2 mg once weekly injection combined treatment for 24 weeks
干预措施: Exenatide (Drug)
Placebo
Placebo film-coated tablet once daily and placebo once weekly injection combined treatment for 24 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Body weight (kg)
时间窗: From randomization to 24 weeks
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
次要结局
- Body weight (%)(From randomization to 24 weeks)