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EXenatide Study of Cardiovascular Event Lowering (Ongoing)



Academic Leadership

EXSCEL is managed by the Duke Clinical Research Institute and the University of Oxford Diabetes Trials Unit. The EXSCEL Executive Committee has responsibility for oversight of the trial with the majority of members being independent academics. The Operations Committee, which facilitates trial oversight at the local level, comprises academic investigators.

Sponsor

Amylin Pharmaceuticals, LLC (a wholly owned subsidiary of Bristol-Myers Squibb)

Study Phase

Phase 3b/4

Study Title

EXenatide Study of Cardiovascular Event Lowering

Study Drug

Exenatide is a receptor agonist for the human incretin Glucagon-Like Peptide-1 (GLP-1). Incretins enhance glucose-dependent insulin secretion and exhibit other antihyperglycemic actions following their release into the circulation from the gut. The GLP-1 system increases insulin secretion only in the presence of elevated plasma glucose levels, avoiding inappropriately high insulin levels during fasting. The drug also moderates peak serum glucagon levels during hyperglycemic periods following meals, but does not interfere with glucagon release in response to hypoglycemia. Secondary effects of drug administration reduces the rate of gastric emptying and decreases food intake, mitigating the potential severity of hyperglycemic events after meals.  Exenatide will be administered subcutaneously once a week in this trial.

Patient Population

Patients 18 years or older with type 2 diabetes mellitus (T2DM) and a HbA1C of ≥6.5% and ≤10.0% on up to three oral antihyperglycemic agents (AHAs) or on insulin, either alone or together with up to two AHAs, will be enrolled. Patients with any level of cardiovascular (CV) risk can be enrolled.  Recruitment will be constrained such that a certain proportion of patients will not have had a prior CV event and a defined proportion will have had a prior CV event defined as at least one of the following: myocardial infarction (MI), surgical or percutaneous (balloon and/or stent) coronary revascularization procedure, coronary angiography showing at least one stenosis ≥ 50% in a major epicardial artery or branch vessel, ischemic cerebrovascular disease including history of ischemic stroke, history of carotid arterial disease as documented by ≥50% stenosis, peripheral arterial disease as documented by intermittent claudication confirmed by ankle brachial index or the brachial pressure index of less than 0.9, amputation due to vascular disease, or history of surgical or percutaneous revascularization procedure.

Scope/Study Operations

This is a global pragmatic trial of approximately 14,000 patients conducted in approximately 800 sites in Asia, Australasia, Europe, Latin America, and North America.  The data collection and adverse event reporting will be streamlined. Recruiting sites that have a proven track record for recruiting high numbers of patients as well as sustained enrolment over time and retention of patients for the duration of the trial will be selected to participate

Study Design

This is an integrated study design with no interruption in usual care.  Exenatide/Placebo will be added to the ongoing care regimen. 

Primary Objective

To evaluate the effect of Exenatide Once Weekly used in conjunction with the current usual care for glycemic control, on major macrovascular events when administered to patients with type 2 diabetes.

Patient Follow Up Visits

Screening and Randomization can be done at the same visit. Clinic visits will be scheduled at 1 week, 2 months, 6 months, 12 months, and then every 6 months until the end of study.  All patients will receive a 90 day post-study drug phone call.  Follow-up will last for a minimum of four years.

Site Budget

Trial sites will be paid a fixed per patient fee which will cover study related expenditure including institution overheads and patient related reimbursement. Sites will be paid quarterly based on attended visits and 'clean' data which will be monitored by the Data Co-ordinating Centre. Further details will be provided should your site be eligible to participate in EXSCEL.

Site Identification

Priority will be given to sites with:

Study Timelines

First Patient randomised June 2010. The recruitment period is expected to be around 5 years and additional 2-3 years follow up may be required (total duration of up to approximately 7.5 years).