The primary objective of this phase III study is to demonstrate that lixisenatide can reduce cardiovascularmorbidity and mortality (composite endpoint of cardiovascular (CV) death, non-fatal myocardialinfarction (MI), non-fatal stroke,…
ID
Source
Brief title
Condition
- Coronary artery disorders
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate cardiovascular outcomes with lixisenatide compared to placebo (time
to first occurence: cardiovascular death, non-fatal myocardial infarction,
non-fatal stroke, hospitalization for unstable angina) in type 2 diabetic
patients who experienced an acute coronary syndrome event.
Secondary outcome
To assess the effect of lixisenatide compared to placebo on:
Composite cardiovascular endpoints
* Time to the first occurrence of any of the following clinical events,
positively adjudicated by the CAC:
• Cardiovascular death.
• Non-fatal MI.
• Non-fatal stroke.
• Hospitalization for unstable angina.
• Hospitalization for heart failure.
* Time to the first occurrence of any of the following clinical events,
positively adjudicated by the CAC:
• Cardiovascular death.
• Non-fatal MI.
• Non-fatal stroke.
• Hospitalization for unstable angina.
• Hospitalization for heart failure.
• Coronary revascularization procedure
• Urinary albumin/creatinine ratio: Percent change in the urinary
albumin/creatinine ratio from baseline to Week 108 (i.e., approximately 2
years).
To assess the safety and tolerability of lixisenatide.
Background summary
In the past two decades the prevalence of type 2 diabetes has increased to
epidemic proportions worldwide; the number of subjects with type 2 diabetes is
set to rise from the current estimate of 150 million to 220 million in 2010 and
300 million in 2025. Patients with diabetes have an increased risk of
microvascular and macrovascular complications leading to decreased life
expectancy. This is mainly due to cardiovascular deaths with a risk of coronary
heart disease increased by two to fourfold in this population.
Results from large controlled trials as well as smaller studies and numerous
epidemiologic studies have demonstrated that intensive glycemic control
decreases the risk of microvascular complications. On the basis of these
findings the American Diabetes Association (ADA) and International Diabetes
Federation recommend a tight glycemic control with an HbA1c target < 7 % and <
6,5 % respectively.
Although an intensive glycemic management has also shown to have beneficial
effect of cardiovascular disease complications in type 1 diabetes, there is
still controversy whether this demonstration can also apply in patients with
type 2 diabetes. Recent individual studies conducted in type 2 diabetes have
failed to demonstrate a beneficial effect on intensive diabetes therapy on
cardiovascular disease. However, meta-analyses recently performed showed a
reduction in coronary events; effect on cardiovascular death or all-cause
mortality was less evident.
Lixisentatide belongs to the class of Glucagon-like peptide 1 (GLP-1) receptor
agonist and is being developed for the treatment of patients with type 2
diabetes.
New types of antidiabetic, such as GLP-1 receptor antagonists may achieve
physiological blood glucose-insulin response with a low risk of hypoglycemia
and may offer a valuable new therapeutic approach. These drugs reduce the blood
glucose by glucose dependent stimulation of insulin release and inhibition of
glucagons secretions, which decreases the prandial blood glucose excursions and
hepatic glucose production; they also delay gastric emptying and reduce
appetite which is associated with weight loss.
Study objective
The primary objective of this phase III study is to demonstrate that
lixisenatide can reduce cardiovascular
morbidity and mortality (composite endpoint of cardiovascular (CV) death,
non-fatal myocardial
infarction (MI), non-fatal stroke, hospitalization for unstable angina)
compared to placebo in type
2 diabetic patients who recently experienced a spontaneous, biomarker-positive
acute coronary
syndrome (ACS) event.
Study design
This will be a multicenter, multinational, double-blind, 1:1 randomized,
placebo-controlled, 2-arm parallel-group phase III study. The study will be
double-blind with regard to the active and placebo treatments. The study drug
volume (i.e. dose of active drug or matching placebo) will not be blinded.
The study will comprise 3 periods:
-A placebo run-in period of 7 days (+3 days) that will start by a screening
visit;
-A double-blind study treatment period that will include an initial 2-week
titration period. The estimated maximum duration of this double-blind study
treatment period will be approximately 250 weeks (i.e. approximately 58
months); assuming 37-month recruitment period, and a minimum of 10 months of
further follow-up for the last randomized patient.
-A post-treatment safety follow-up period of 3 days (+ 1 day), only for
patients still on study treatment at the time of the common study end date.
Intervention
Screening phase: 7 days placebo-run in
Double-blind treatment phase: maximum of 58 months treatment with lixisenatide
or placebo and minimum of 10 months treatment with lixisenatide or placebo.
Study burden and risks
Risks are related to the bloodsampling and possible adverse events from the
studymedication. The burden for the patient is the number of visits to the
research center and phone calls because of this study. Also the patient will be
asked to complete a diary and to perform self-measurements of plasma glucose.
Kampenringweg 45E
GOUDA 2803 PE
NL
Kampenringweg 45E
GOUDA 2803 PE
NL
Listed location countries
Age
Inclusion criteria
*Men and women who experienced a spontaneous ACS event (i.e., ST-segment elevation myocardial infarction [STEMI] or non-ST-segment elevation myocardial infarction [NSTEMI] or unstable angina [USA]) with the following requirements:
- a documented elevation above the normal reference range of a cardiac biomarker (Troponin or
CK-MB),
- The presentation of the event must be consistent with an acute coronary syndrome which leads to admission to an acute care facility (eg, ER, CCU, Cath Lab, hospital
- the screening visit must occur only after the patient is discharged from the acute care facility, and must take place within 180 days following the date of admission for the qualifying ACS event.
.
*Patients with history of type 2 diabetes (for patients newly diagnosed, diagnosis will be based on the WHO criteria: i.e., fasting venous plasma glucose concentration >= 7.0 mmol/L [126 mg/dL] or 2-hour post glucose load venous plasma glucose >= 11.1 mmol/L [200 mg/dL], confirmed on 2 ccasions) prior to the screening visit.
Exclusion criteria
. Type 1 diabetes mellitus or history of ketoacidosis within 6 months prior to screening.;. HbA1c <5.5 % or >11% measured at screening Visit (1 retest within a week of receipt of the result is permitted with the result of the last sample being decisive).;. Required to use incretin-based agents (eg, GLP-1 agonists or DPP-4 inhibitors) other than the study drug during the doubleblind treatment period.;. Patients who have undergone CABG surgery following the qualifying ACS event.;. Patients who have undergone PCI within 15 days prior to screening.;. Patients with planned revascularization procedure (PCI or CABG) within 90 days after screening visit.;. History of unexplained pancreatitis, chronic pancreatitis, pancreatectomy, stomach/gastric surgery, inflammatory bowel disease, personal or family history of medullary thyroid cancer (MTC), or genetic conditions that predisposes to MTC (eg, multiple endocrine neoplasia syndromes).;. Any clinically significant abnormality identified at the time of screening that in the judgment of the Investigator or any sub-Investigator would preclude safe completion of the study or constrain endpoints assessment such as major systemic diseases.
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 | EUCTR2009-012852-26-NL |
| ClinicalTrials.gov | NCT01147250 |
| CCMO | NL32257.060.10 |