AstraZeneca Adding 2 New Brilinta Studies
AstraZeneca Announces Initiation of Two Additional Global Studies with Brilinta (Ticagrelor)
SOCRATES compares ticagrelor versus aspirin for the prevention of major vascular events in patients with acute ischemic stroke or transient ischemic attack
THEMIS compares ticagrelor versus placebo for the long-term prevention of major vascular events in patients with Type 2 diabetes at high cardiovascular risk
WILMINGTON, Del., November 14, 2013--(BUSINESS WIRE)--AstraZeneca (NYSE:AZN) today announced plans to conduct two new clinical studies as part of PARTHENON, AstraZeneca’s largest clinical trial program involving over 80,000 patients. The studies are designed to build scientific understanding of BRILINTA® (ticagrelor) tablets in additional high-risk patient populations.
SOCRATES (Acute Stroke Or Transient IsChaemic Attack TReated with Aspirin or Ticagrelor and Patient OutcomES) is a global clinical trial involving 9,600 patients who have experienced an acute ischemic stroke or transient ischemic attack (TIA). Annually, 15 million people worldwide suffer a stroke of this type. Ischemic strokes occur as a result of an obstruction of a vessel supplying blood to the brain. A TIA is secondary to a temporary insufficient blood supply to parts of the brain and is often considered a warning sign that a stroke may follow.
SOCRATES is a randomized, parallel group study evaluating the efficacy of ticagrelor compared to aspirin in reducing major vascular events (composite of all-cause mortality, myocardial infarction [MI], and stroke) in patients with acute ischemic stroke (NIHSS ≤ 5) and TIA.
“The short-term stroke risk after a TIA and minor ischemic stroke is extremely high. More than 10 percent of patients have a major stroke within 90 days; and this is with aspirin. We need additional medicines in this setting and SOCRATES will tell us whether ticagrelor might be such a medicine,” said Clay Johnston, MD, PhD; Director, Clinical and Translational Science Institute, Associate Vice Chancellor of Research, University of California, San Francisco (UCSF).
Also announced today is the initiation of THEMIS (Effect of Ticagrelor on Health Outcomes in DiabEtes Mellitus Patients Intervention Study), a global clinical trial involving 17,000 patients with Type 2 diabetes at high risk of cardiovascular (CV) events. Of the 340 million people who suffer from the disease, 90 percent have type 2 diabetes and 50 percent of whom die from CV disease.
“A major goal of treating patients with diabetes is to reduce their cardiovascular risk,” said THEMIS study co-chair Deepak L. Bhatt, MD, MPH, Professor of Medicine at Harvard Medical School and Senior Physician at Brigham and Women’s Hospital.
“THEMIS will allow us to test a bold new strategy in the care of patients with diabetes who are at high risk of myocardial infarction, stroke, and cardiovascular death,” stated THEMIS study co-chair Ph. Gabriel Steg, MD, Professor of Medicine at Université Paris-Diderot and Director of the Coronary Care Unit at Hôpital Bichat.
THEMIS is an event-driven, randomized, parallel group study evaluating the efficacy of long-term treatment with ticagrelor versus placebo for the prevention of major CV events – the composite of CV death, MI or stroke – in patients with Type 2 diabetes without a history of previous MI or stroke but with documented coronary atherosclerosis.
SOCRATES and THEMIS will be monitored by Independent Data Monitoring Committees who will review the safety and efficacy of treatments in these trials. The trials will be conducted in accordance with Good Clinical Practice. Both studies will be posted on clinicaltrials.gov in the near future.
AstraZeneca is currently collaborating with over 4,000 clinical investigators in more than 30 countries as part of the PARTHENON program, and has established partnerships with a number of pre-eminent research institutions. Other studies in the PARTHENON program include PEGASUS, studying BRILINTA for secondary prevention in patients with previous myocardial infarction, and EUCLID studying patients with Peripheral Artery Disease.
PARTHENON will provide an unparalleled dataset to build scientific understanding of BRILINTA in a broad a range of atherothrombotic conditions. AstraZeneca has approved more than 100 investigator sponsored studies, which will be starting during the coming year.
BRILINTA is currently not approved for the treatment of patients with ischemic stroke, TIA,
peripheral artery disease, or for secondary prevention in patients with a history of previous myocardial infarction.
BRILINTA is indicated to reduce the rate of thrombotic cardiovascular (CV) events in patients with ACS (unstable angina [UA], non–ST-elevation myocardial infarction [NSTEMI], or ST-elevation myocardial infarction [STEMI]). In PLATO, BRILINTA has been shown to reduce the rate of a combined end point of CV death, myocardial infarction (MI), or stroke compared to clopidogrel. In PLATO, the difference between treatments was driven by CV death and MI with no difference in stroke. In patients treated with an artery-opening procedure known as percutaneous coronary intervention (PCI), BRILINTA reduces the rate of stent thrombosis.
BRILINTA has been studied in ACS in combination with aspirin. Maintenance doses of aspirin above 100 mg decreased the effectiveness of BRILINTA. Avoid maintenance doses of aspirin above 100 mg daily.
IMPORTANT SAFETY INFORMATION ABOUT BRILINTA (ticagrelor)
WARNING: BLEEDING RISK
•BRILINTA, like other antiplatelet agents, can cause significant, sometimes fatal, bleeding
•Do not use BRILINTA in patients with active pathological bleeding or a history of intracranial hemorrhage
•Do not start BRILINTA in patients planned to undergo urgent coronary artery bypass graft surgery (CABG). When possible, discontinue BRILINTA at least 5 days prior to any surgery
•Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, percutaneous coronary intervention (PCI), CABG, or other surgical procedures in the setting of BRILINTA
•If possible, manage bleeding without discontinuing BRILINTA. Stopping BRILINTA increases the risk of subsequent cardiovascular events
WARNING: ASPIRIN DOSE AND BRILINTA EFFECTIVENESS
•Maintenance doses of aspirin above 100 mg reduce the effectiveness of BRILINTA and should be avoided. After any initial dose, use with aspirin 75 mg - 100 mg per day
•BRILINTA is contraindicated in patients with a history of intracranial hemorrhage and active pathological bleeding such as peptic ulcer or intracranial hemorrhage. BRILINTA is contraindicated in patients with severe hepatic impairment because of a probable increase in exposure; it has not been studied in these patients. Severe hepatic impairment increases the risk of bleeding because of reduced synthesis of coagulation proteins. BRILINTA is also contraindicated in patients with hypersensitivity (e.g. angioedema) to ticagrelor or any component of the product.
WARNINGS AND PRECAUTIONS
•Moderate Hepatic Impairment: Consider the risks and benefits of treatment, noting the probable increase in exposure to ticagrelor
•Premature discontinuation increases the risk of MI, stent thrombosis, and death
•Dyspnea was reported in 14% of patients treated with BRILINTA and in 8% of patients taking clopidogrel. Dyspnea resulting from BRILINTA is self-limiting. Rule out other causes
•BRILINTA is metabolized by CYP3A4/5. Avoid use with strong CYP3A inhibitors and potent CYP3A inducers. Avoid simvastatin and lovastatin doses >40 mg
•Monitor digoxin levels with initiation of, or any change in, BRILINTA therapy
•The most commonly observed adverse reactions associated with the use of BRILINTA vs clopidogrel were Total Major Bleeding (11.6% vs 11.2%) and dyspnea (14% vs 8%)
•In clinical studies, BRILINTA has been shown to increase the occurrence of Holter-detected bradyarrhythmias. PLATO excluded patients at increased risk of bradycardic events. Consider the risks and benefits of treatment
DOSING ADMINISTRATION FOR PATIENTS WITH ACUTE CORONARY SYNDROME
BRILINTA is available in 90-mg tablets to be administered with a single 180-mg oral loading dose (two 90-mg tablets) followed by a twice daily, 90-mg maintenance dose. Following an initial loading dose of aspirin, BRILINTA should be used with a maintenance dose of 75 mg - 100 mg aspirin once daily, 81-mg aspirin dose in the US.
Please read full Prescribing Information, including Boxed WARNINGS, and Medication Guide.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/Safety/MedWatch or call 1-800-FDA-1088.
Patients can find out more information about BRILINTA at www.BRILINTAtouchpoints.com or by calling 1-888-412-7454.
AstraZeneca also offers a US patient assistance program for BRILINTA through its AZ&MeTM Prescription Savings Program. To determine eligibility, patients can visit www.AZandMe.com or call 1-800-AZandMe (292-6363).
NOTES TO EDITORS
About BRILINTA® (ticagrelor) tablets
BRILINTA is an oral antiplatelet treatment for ACS. BRILINTA is a direct-acting P2Y12 receptor antagonist in a chemical class called cyclopentyltriazolopyrimidines (CPTPs). BRILINTA works by inhibiting platelet activation and has been shown to reduce the rate of thrombotic CV events, such as a heart attack or CV death, in patients with ACS.
BRILINTA is a registered trademark of the AstraZeneca group of companies.
PLATO (PLATelet inhibition and patient Outcomes) was a large (18,624 patients in 43 countries), head-to-head patient outcomes study of BRILINTA vs clopidogrel, both given in combination with aspirin and other standard therapy. The study was designed to establish whether BRILINTA (ticagrelor) could achieve a clinically meaningful reduction in cardiovascular (CV) events in acute coronary syndrome (ACS) patients, above and beyond that afforded by clopidogrel. Patients were treated for at least 6 months and up to 12 months.
PLATO demonstrated that treatment with BRILINTA led to a significantly greater reduction in the primary end point – a composite of CV death, MI (excluding silent MI), or stroke – compared to patients who received clopidogrel (9.8% vs 11.7% at 12 months; 1.9% absolute risk reduction [ARR]; 16% relative risk reduction [RRR]; 95% CI, 0.77 to 0.92; P<0.001). The difference in treatments was driven by CV death and MI with no difference in stroke. In PLATO, the absolute difference in treatment benefit vs clopidogrel was seen at 30 days and the Kaplan-Meier survival curves continued to diverge throughout the 12-month treatment period.
The PLATO study also demonstrated that treatment with BRILINTA for 12 months was associated with a 21% RRR in CV death (4% vs 5.1%; 1.1% ARR; P=0.001) and a 16% RRR in MI (excluding silent MI) compared to clopidogrel at 12 months (5.8% vs 6.9%; 1.1% ARR; P<0.005).
The primary safety end point in the PLATO study was Total Major Bleeding at 12 months (11.6% for BRILINTA and 11.2% for clopidogrel). In PLATO, non-CABG major + minor bleeding events were more common with BRILINTA vs clopidogrel (8.7% vs 7% respectively). The rate of non-CABG-related major bleeding was higher for BRILINTA (4.5%) vs clopidogrel (3.8%).
Dyspnea was reported in 14% of patients treated with BRILINTA and in 8% of patients treated with clopidogrel. Dyspnea was usually mild to moderate in intensity and often resolved during continued treatment.
* PLATO used the following bleeding severity categorization: Major Bleed–Fatal/Life-threatening. Any one of the following: fatal; intracranial; intrapericardial bleed with cardiac tamponade; hypovolemic shock or severe hypotension due to bleeding and requiring pressors or surgery; clinically overt or apparent bleeding associated with a decrease in hemoglobin (Hb) of more than 5 g/dL; transfusion of 4 or more units (whole blood or packed red blood cells [PRBCs]) for bleeding. Major Bleed–Other. Any one of the following: significantly disabling (eg, intraocular with permanent vision loss); clinically overt or apparent bleeding associated with a decrease in Hb of 3 g/dL; transfusion of 2-3 units (whole blood or PRBCs) for bleeding. Minor Bleed. Requires medical intervention to stop or treat bleeding (eg, epistaxis requiring visit to medical facility for packing). Minimal Bleed. All others (eg, bruising, bleeding gums, oozing from injection sites, etc) not requiring intervention or treatment.
About Acute Coronary Syndrome (ACS)
ACS is an umbrella term for conditions that result from insufficient blood supply to the heart muscle. These conditions include unstable angina (UA), non–ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI). The conditions are defined by ECG changes and heart muscle enzyme leakage. Non–ST-elevation acute coronary syndrome (NSTE-ACS) includes unstable angina (UA) and non–ST-elevation myocardial infarction (NSTEMI); the term is usually used before heart muscle enzymes have been analyzed.
AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialization of prescription medicines for gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide.
For more information about AstraZeneca in the US or our AZ&Me™ Prescription Savings programs, please visit: www.astrazeneca-us.com or call 1-800-AZandMe (292-6363).
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Posted: November 2013