US Department of Justice Closes Investigation into PLATO Clinical Trial

POSTED BY

Meredith Hemler

AstraZeneca today announced that it has received confirmation from the United States Department of Justice that it is closing its investigation into PLATO, a clinical trial with BRILINTA® (ticagrelor) tablets. The government is not planning any further action following the Civil Investigative Demand (CID) that AstraZeneca received in October 2013.

“We welcome the Department of Justice’s decision not to pursue further action. We have always had absolute confidence in the integrity of the PLATO trial and we are proud of the important benefit BRILINTA offers to patients around the world suffering from acute coronary syndrome. As one of AstraZeneca’s growth platforms, we remain committed to delivering the full potential of this important medicine,” said Pascal Soriot, Chief Executive Officer, AstraZeneca.

To learn more about this news, click here to read our company’s press release.

Now hear from Paul Hudson, President, AstraZeneca US, as he takes a moment to reflect on what this announcement means for the US market, healthcare providers and, most importantly, patients.

Please read full Prescribing Information, including Boxed WARNINGS, and Medication Guide for BRILINTA.

In 2011 the US Food and Drug Administration approved BRILINTA in the treatment of patients with acute coronary syndrome (ACS). BRILINTA has been approved by regulatory authorities in over 100 countries and is included in 11 major ACS management guidelines globally, including six established US guidelines. The trial manuscript from the PLATO Executive Committee was first published in the New England Journal of Medicine. Following additional rigorous peer-review, over 30 PLATO sub-analyses articles have subsequently been published. The combination of these global reviews makes the PLATO data set one of the most widely analyzed clinical trials.

BRILINTA is the first and only oral antiplatelet (OAP) U.S. Food and Drug Administration (FDA)-approved to demonstrate superior reductions in cardiovascular (CV) death vs clopidogrel in patients with ACS. BRILINTA is indicated to reduce the rate of thrombotic 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, MI, or stroke compared to clopidogrel. 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

WARNING: (A) BLEEDING RISK, (B) ASPIRIN DOSE AND BRILINTA EFFECTIVENESS

A. 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

B. 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

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.BRILINTA.com or by calling 1-888-412-7454.

AstraZeneca offers the AZ&MeTM Prescription Savings Program. To determine eligibility, patients can visit www.AZandMe.com or call 1-800-AZandMe (292-6363).

2986102 Last Updated 8/14