A Phase IIb, Randomised, Parallel, Double-Blind Placebo-Controlled and Open-Label Active Comparator Study to Evaluate the Efficacy and Safety of MEDI0382 in the Treatment of Overweight and Obese Subjects With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 834
- 试验地点
- 1
- 主要终点
- Change in HbA1c
研究概览
简要总结
This study is designed to evaluate the dose range for MEDI0382 with respect to blood glucose control and weight loss effects, as well as to further explore the safety profile of MEDI0382
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)
盲法说明
The study will be conducted in a double-blind fashion for MEDI0382 and placebo. The sponsor staff, the subjects, and the Investigators involved in the treatment of subjects or in the clinical evaluation of subjects will not be aware of the treatment received. Liraglutide will be provided in an open-label active comparator arm.
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of informed consent
- •Male and female subjects aged ≥ 18 years at screening
- •Body mass index ≥ 25 kg/m2 at screening
- •HbA1c range of 7.0% to 10.5% (inclusive) at screening
- •Diagnosed with type-2 diabetes mellitus (T2DM) and treated with metformin (stable dose of ≥1500 mg/day or maximal tolerated dose) for at least 2 months prior to screening. Use of another glucose-lowering medication for up to 2 weeks in the 2 months prior to screening is acceptable
- •Women of childbearing potential (WOCBP), not breastfeeding and using appropriate birth control to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of investigational product (IP), with a negative pregnancy test within 72 hours prior to the start of IP
排除标准
- •History of, or any existing condition that, in the opinion of the Investigator, would interfere with evaluation of the IP, put the subject at risk, influence the subject's ability to participate or affect the interpretation of the results of the study and/or any subject unable or unwilling to follow study procedures
- •Any subject who has received another IP as part of a clinical study or a GLP-1 receptor agonist containing preparation within the last 30 days or 5 half lives of the drug (whichever is longer) at the time of screening
- •Severe allergy/hypersensitivity to any of the proposed study treatments or excipients
- •Symptoms of acutely decompensated blood glucose control, a history of type 1 diabetes mellitus or diabetic ketoacidosis, or if the subject has been treated with daily subcutaneous (SC) insulin for a period longer than 2 weeks within 90 days prior to screening
- •Acute or chronic pancreatitis. Subjects with serum triglyceride concentrations above 1000 mg/dL (11 mmol/L) at screening
- •Significant inflammatory bowel disease or other severe disease or surgery affecting the upper Gastrointestinal (GI) tract
- •Significant hepatic disease
- •Impaired renal function defined as estimated glomerular filtration rate (eGFR) ≤30 mL/minute/1.73m2 at screening
- •Severely uncontrolled hypertension
- •Unstable angina pectoris, myocardial infarction (MI), transient ischaemic attack (TIA), or stroke within 3 months prior to screening
- •Severe congestive heart failure
研究组 & 干预措施
MEDI0382 low dose + Metformin
Drug: MEDI0382 low dose Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
干预措施: MEDI0382 low dose (Drug)
MEDI0382 mid dose + Metformin
Drug: MEDI0382 mid dose Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
干预措施: MEDI0382 mid dose (Drug)
MEDI0382 high dose + Metformin
Drug: MEDI0382 high dose Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
干预措施: MEDI0382 high dose (Drug)
Placebo + Metformin
Drug: Placebo Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
干预措施: Placebo (Drug)
Liraglutide + Metformin
Drug: Liraglutide Drug: Metformin tablets, total daily dose of ≥1500 mg (unless only tolerated at a lower dose)
干预措施: Liraglutide (Drug)
结局指标
主要结局
Change in HbA1c
时间窗: From baseline to 14 weeks
To assess the effect of 100, 200, 300 μg of cotadutide on HbA1c versus placebo
Percent Change in Body Weight
时间窗: From baseline to 14 weeks
To assess the effect of 100, 200, 300 μg of cotadutide on body weight versus placebo
次要结局
- Change in HbA1c(from baseline to 26 weeks and 54 weeks)
- Percentage of Participants Achieving an HbA1c Target < 7.0%(after 14, 26, and 54 weeks)
- Percent Change in Body Weight(from baseline to 26 weeks and 54 weeks)
- Absolute Change in Body Weight(from baseline to 14 weeks, 26 weeks and 54 weeks)
- Percent Change in Body Weight Versus Active Comparator(from baseline to 14 weeks, 26 weeks and 54 weeks)
- Pharmacokinetic (PK) Endpoint: Trough Plasma Concentration (Cmin)(Time points at which outcome measure were assessed for plasma concentration were Weeks 1,2,6,10,14,18,22,26, and 54)
- Immunogenicity Endpoint: Overall Antidrug Antibody (ADA) Incidence (Number and Percentage of Positive Partipants)(Baseline through 54-week treatment period and 28-day follow-up)
- Absolute Change in Body Weight Versus Active Comparator(from baseline to 14 weeks, 26 weeks and 54 weeks)
- Percentage of Participants Achieving Weight Loss of ≥5% and ≥10%(after 14 weeks, 26 weeks and 54 weeks)
- Percentage of Participants Rescued or Discontinued for Lack of Glycaemic Control(at 14 weeks, 26 weeks and 54 weeks)
- Immunogenicity Endpoint: Median Titer of the Anti-Drug Antibodies (ADA) to MEDI0382 in the Positive Participants(Baseline through 54-week treatment period and 28-day follow-up)