A Long Term, Randomised, Double Blind, Placebo-controlled Study to Determine the Effect of Albiglutide, When Added to Standard Blood Glucose Lowering Therapies, on Major Cardiovascular Events in Patients With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 9,463
- 试验地点
- 608
- 主要终点
- Time to First Occurrence of Major Adverse Cardiovascular Events (MACE) During Cardiovascular (CV) Follow-up Time Period
研究概览
简要总结
Albiglutide is an analogue of glucagon-like peptide-1 (GLP-1), used to treat type 2 diabetes This study will test whether albiglutide affects the occurrence of major cardiovascular events such as heart attacks or strokes and other important medical outcomes in persons with type 2 diabetes, when used alone or added to other diabetes treatments.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men or women at least 40 years old. Women must be post-menopausal or using a highly effective method for avoidance of pregnancy.
- •Diagnosis of type 2 diabetes.
- •Established cardiovascular disease with at least one of the following: coronary artery disease, cerebrovascular disease, or peripheral arterial disease.
- •HbA1c >7.0% (53 mmol/mol) (based on the most recent documented laboratory measurement within 6 months).
- •Able and willing to provide informed consent.
排除标准
- •Severely reduced kidney function: eGFR <30 ml/min/1.73 m^2 (based on the last measured and documented laboratory measurement within 6 months) or renal replacement therapy.
- •Use of a GLP-1 receptor agonist at Screening.
- •Severe gastroparesis
- •History of pancreatitis or considered clinically at significant risk of developing pancreatitis during the course of the study.
- •Personal or family history of medullary carcinoma of the thyroid or subject with multiple endocrine neoplasia type 2 (MEN-2). Personal history of pancreatic neuroendocrine tumours.
- •Medical history which might limit the subject's ability to take trial treatments for the duration of the study or to otherwise complete the study.
- •Breastfeeding, pregnancy, or planning a pregnancy during the course of the study. Note: a pregnancy test will be performed on all women of child bearing potential prior to study entry.
- •Known allergy to any GLP-1 receptor agonist or excipients of albiglutide.
- •Use of another investigational product within 30 days or according to local regulations, or currently enrolled in a study of an investigational device.
- •Any other reason the investigator deems the subject to be unsuitable for the study.
研究组 & 干预措施
Albiglutide
Albiglutide once weekly by subcutaneous injection. Starting dose 30 mg may be increased to 50 mg if needed. Albiglutide will be administered in addition to standard therapy for diabetes and cardiovascular health.
干预措施: Albiglutide 30 mg (Biological)
Placebo
Placebo once weekly by subcutaneous injection. Placebo will be administered in addition to standard therapy for diabetes and cardiovascular health.
干预措施: Albiglutide matching placebo (Biological)
Albiglutide
Albiglutide once weekly by subcutaneous injection. Starting dose 30 mg may be increased to 50 mg if needed. Albiglutide will be administered in addition to standard therapy for diabetes and cardiovascular health.
干预措施: Albiglutide 50 mg (Biological)
结局指标
主要结局
Time to First Occurrence of Major Adverse Cardiovascular Events (MACE) During Cardiovascular (CV) Follow-up Time Period
时间窗: Median of 1.65 person years for CV follow-up time period
Time to MACE defined as the time to first occurrence of Cardiovascular Endpoint Committee (CEC)-adjudicated MACE (CV death, myocardial infarction \[MI\] or stroke) was analyzed using a Cox Proportional Hazards regression model with treatment group as the only covariate. The incidence rate per 100 person years (100\*number of participants with at least 1 event)/first event person-years) is presented along with 95% confidence interval. First event person-years=(cumulative total time to first event for participants who have the event+cumulative total of censored time for participants without the event)/365.25, based on the CV follow-up time period. The analysis was performed on the Intent to Treat (ITT) Population which comprised of all randomized participants excluding participants who did not provide consent.
次要结局
- Time to First Occurrence of Adjudicated Stroke(Median of 1.65 person years for CV follow-up time period)
- Time to Initiation of Insulin of More Than 3 Months Duration for Those Participants Not Treated With Insulin at Study Start(Up to 2.7 years)
- Change From Baseline in HbA1c(Baseline and Months 8 and 16)
- Time to Death(Median of 1.73 years for the Vital Status follow-up time period)
- Time to Adjudicated CV Death(Median of 1.65 person years for the CV follow-up time period)
- Change From Baseline in Body Weight(Baseline and Months 8 and 16)
- Change From Baseline in EuroQol- 5 Dimension (EQ-5D) Visual Analogue Scale (VAS) Score(Baseline and Months 8 and 16)
- Time to First Occurrence of MACE or Urgent Revascularization for Unstable Angina(Median of 1.65 person years for CV follow-up time period)
- Time to First Occurrence of a Clinically Important Microvascular Event(Up to 2.7 years)
- Change From Baseline in Treatment Related Impact Measures-Diabetes (TRIM-D) Total Score(Baseline and Months 8 and 16)
- Time to First Occurrence of Adjudicated MI(Median of 1.65 person years for CV follow-up time period)
- Time to Initiation of Prandial Insulin in Those Participants on Basal Insulin at Study Start(Up to 2.7 years)
- Time to First Occurrence of Adjudicated CV Death or Hospitalization for Heart Failure (HF)(Median of 1.65 person years for CV follow-up time period)
- Percentage of Participants Achieving Composite Metabolic Endpoint(Months 8, 16, 24 and final assessment (up to 2.7 years))
- Change From Baseline in Heart Rate(Baseline and Months 8, 16, 24 and end of study (up to 2.7 years))
- Number of Participants With Non-fatal Serious Adverse Events (SAEs)(Up to 2.7 years)
- Number of Participants With Adverse Events (AEs) Leading to Discontinuation of Investigational Product (AELD)(Up to 2.7 years)
- Change in Estimated Glomerular Filtration Rate (eGFR) Calculated Using Modification of Diet in Renal Disease (MDRD) Formula(Baseline and Months 8 and 16)
- Number of Participants With AEs of Special Interest(Up to 2.7 years)
- Change From Baseline in Blood Pressure(Baseline and Months 8,16,24 and end of study (up to 2.7 years))