The primary objective of EXSCEL will be to evaluate the effect of Bydueron, used in addition to the current usual care for glycemic control, on major macrovascular events when administered to patients with type 2 diabetes.
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Time to first confirmed CV event in the primary composite CV endpoint
Defined as the time from randomization to first confirmed CV-related death,
nonfatal MI or
nonfatal stroke.
Secondary outcome
Time to all-cause mortality
Defined as time from randomization to death due to any cause.
Time to first confirmed CV event for each component of the primary composite
endpoint
Defined as time from randomization to a confirmed CV-related death, fatal or
nonfatal MI, or
fatal or nonfatal stroke.
Time to hospitalization for acute coronary syndrome
Defined as time from randomization to a confirmed hospital admission for
unstable angina,
ST-elevation myocardial infarction or non-ST-elevation myocardial infarction.
Time to hospitalization for heart failure
Defined as time from randomization to hospital admission for congestive heart
failure
requiring treatment with increased oral or intravenous diuretics, inotropes, or
vasodilator
therapy.
Additional effectivity endpoints can be found in section 8.3 of the protocol.
Background summary
Type 2 diabetes mellitus is a leading public health issue. Often regarded as a
mild disease, it is the fourth leading cause of death in developed countries
and the number of people worldwide with diabetes is predicted to exceed 300
million by the year 2025.1 Diabetes remains the leading cause of blindness, end
stage renal disease, and lower extremity amputations and confers a two to four
times greater risk of heart disease and strokes.
Exenatide, a GLP-1 receptor agonist, has been shown in randomized clinical
trials to improve glycemic control, augment endogenous insulin secretion, to
reduce blood pressure and promote weight loss with a meta-analysis of exenatide
twice-daily (BYETTA) trials showing a trend to
lower relative risk for CV events versus pooled comparators of 0.70 (95%
confidence interval 0.38 - 1.31).
Hypotheses:
Efficacy: Bydueron, when used in addition to usual care, is superior to usual
care without Bydueron with regard to the risk of developing a confirmed event
in the primary CV composite endpoint.
Safety: Bydueron, when used in addition to usual care, is non-inferior to usual
care without Bydueron with regard to the risk of developing a confirmed event
in the primary CV composite endpoint.
Study objective
The primary objective of EXSCEL will be to evaluate the effect of Bydueron,
used in addition to the current usual care for glycemic control, on major
macrovascular events when administered to patients with type 2 diabetes.
Study design
EXSCEL is a multinational pragmatic trial that will be conducted at
approximately 800 sites worldwide. It will be run jointly by the Duke Clinical
Research Institute (DCRI) and the University of Oxford Diabetes Trials Unit
(DTU) Academic Research Organizations (AROs), in an academic collaboration with
Amylin Pharmaceuticals, LLC (Amylin), a wholly owned subsidiary of
Bristol-Myers Squibb. EXSCEL will be Co-Chaired by Professors Robert Califf
(Cardiologist) and Rury Holman (Endocrinologist) and sponsored and funded by
Amylin.
Eligible patients will have type 2 diabetes with an HbA1c *6.5% and * 10.0 % on
up to three (i.e., 0-3) oral antihyperglycemic agents (AHAs) or insulin either
alone or in combination with up to 2 (i.e., 0-2) oral AHAs. Patients enrolled
will be at a wide range of CV risk with approximately 70% having had a prior CV
event.
The trial will assess the impact of Bydueron therapy upon CV outcomes in a
large population from a heterogeneous group of countries and practice
environments; patients will be enrolled in the Americas (North/South America),
Europe and Asia/Australasia. Given that this population will be at elevated CV
risk, it is anticipated that patients will see their usual care provider at
least twice per year for routine care. Trial follow up will consist of a blend
of trial visits and phone calls during the double-blind placebo-controlled
treatment period. There is no requirement to achieve glycemic equipoise between
randomized groups but all patients during the double-blind treatment period
will have their AHA regimens adjusted as deemed necessary by their usual care
provider with the addition or substitution of other AHAs, including insulin,
but excluding GLP-1 receptor agonists, to achieve appropriate individualized
glycemic goals in line with national guidelines. Adjustments in AHA medications
are permitted any time after randomization, but usual care providers will be
asked to avoid this until HbA1c levels begin to reflect the initial effect of
randomized study medication. Prior to randomization, it is anticipated that all
patients will have received counseling regarding appropriate diet and level of
physical activity as part of usual care for type 2 diabetes. Per usual care,
HbA1c values should be measured locally. An NGSP(National Glycohemoglobin
Standardization Program) certified HbA1c assay should be used if available.
Intervention
A weekly subcutaneous dose of Exenatide 2mg, or placebo administired by the
patient.
Study burden and risks
AE's, SAE's, vvital functions and laboratory safety tests are monitored to
guard the patient safety and support the evaluation fo the safetyprofile of the
drug. The burden for the patient is limited to a minimum by staying in line
with the standard care as much as possible, collaborate with the usual care
provider and limit study specific procedures.
The risks and burden for the patient are thought to be in perspective with the
treatment of the patient and the necessity to study new compounds with extra
benefits within the existing standard care.
Towne Centre Drive 9625
San Diego 92121
US
Towne Centre Drive 9625
San Diego 92121
US
Listed location countries
Age
Inclusion criteria
- Patient has type 2 diabetes mellitus;- Patient will able to see a usual care provider at least twice a year;- Patient has an HbA1c of * 6.5% and * 10.0% and is currently using one of the following treatment regimens: ;*Treatment with up to three (i.e., 0-3) oral AHAs (concomitant use of DPP-4 inhibitors is permitted). ;*Insulin therapy, either alone or in combination with up to two (ie., 0-2) oral AHAs (use of basal and prandial insulins is permitted in any combination of individual or premixed insulins);All patients should be on a stable diabetes management regimen, as assessed by the investigator, at the time of enrollment. ;- Patients with any level of CV risk. ;- Female patients must not be breast feeding and agree to use an effective method of contraception or must not otherwise be at risk of becoming pregnant.;- Patient agrees to provide permission to obtain all medical records necessary for complete data ascertainment during the follow-up period, and agrees to communication between the trial site and the usual care provider in order to facilitate routine care.;- Patient is 18 years or older at enrollment.
Exclusion criteria
- Patient has a diagnosis of type 1 diabetes mellitus, or a history of ketoacidosis.;- Patient has a history (* 2 episodes) of severe hypoglycemia within 12 months of enrollment.;- Patient has ever been treated with an approved or investigational GLP-1 receptor agonist e.g. exenatide BID, exenatide once weekly, liraglutide, lixisenatide, albiglutide, taspoglutide, or dulaglutide.;- Patient is enrolled in another experimental protocol which involves the use of an investigational drug or device, or an intervention that would interfere with the conduct of the trial.;- Patient has a planned or anticipated revascularization procedure.;- Pregnancy or planned pregnancy during the trial period.;- Patient has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance which, in the opinion of the investigator or coordinator, might pose an unacceptable risk to the patient, confound the results of the trial e.g. if patient cannot comply with requirements of the trial, or likely to interfere with the patient*s participation for the full duration of the trial.;- Patient has end-stage renal disease or an estimated glomerular filtration rate of <30 mL/min/1.73 m2.;- Patient has a history of gastroparesis.;- Personal or family history of medullary thyroid cancer or MEN2 (Multiple Endocrine Neoplasia Type 2) or calcitonin level > 40ng/L at baseline.;- Patient has previously been enrolled in EXSCEL.;- Patient has a history of pancreatitis.;- Is an employee of Amylin Pharmaceuticals LLC, Bristol-Myers Squibb Company or AstraZeneca.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-021069-63-NL |
| ClinicalTrials.gov | NCT01144338 |
| CCMO | NL47842.028.14 |