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 Indications
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
CONTRAINDICATIONS
-
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
ADVERSE REACTIONS
-
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.
About PLATO
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.
About AstraZeneca
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).
Copyright Business Wire 2013