Boehringer Ingelheim planning two new Global Clinical Trials for Pradaxa® (dabigatran etexilate) in expanded patient populations

• RE-SPECT ESUS™ will investigate the efficacy and safety of Pradaxa® (dabigatran etexilate)  for the prevention of recurrent strokes in patients who have suffered an embolic stroke of undetermined source (ESUS)
• RE-DUAL PCI ™ will investigate the efficacy and safety of Pradaxa® in patients with non-valvular atrial fibrillation who have undergone percutaneous coronary intervention (PCI) with stenting
• New clinical trials will add to Boehringer Ingelheim’s extensive RE-VOLUTION® clinical trial programme

For media outside of the US, the UK & Canada only

Ingelheim, Germany, 19 November 2013 – Boehringer Ingelheim has announced plans to initiate two large, global clinical trials of Pradaxa® (dabigatran etexilate) evaluating its efficacy and safety in stroke prevention therapy in two clinically highly relevant conditions. The RE-SPECT ESUS™ trial will investigate the efficacy and safety of Pradaxa® in patients whose first stroke was of embolic origin with unknown source (ESUS). Embolic strokes occur when a blood clot forms somewhere in the body and travels through the bloodstream to the brain.1 The RE-DUAL PCI™ trial will evaluate the efficacy and safety of Pradaxa® in patients with non-valvular atrial fibrillation (NVAF) who have undergone percutaneous coronary intervention (PCI), also known as angioplasty, with stenting.

The trials are scheduled to begin enrolment in mid-2014 and respectively, early 2015 and will form part of the extensive RE-VOLUTION® clinical trial programme for Pradaxa®, which will include 14 clinical trials involving over 55,000 patients in more than 44 countries globally when the two new trials are completed.2

Prof. Dr. Klaus
Prof. Dr. Klaus Dugi

"Pradaxa® was approved in 2010 to reduce the risk of stroke and systemic embolism in patients with atrial fibrillation, making it the first oral anticoagulant approved since warfarin was launched more than 50 years ago," said Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim "These plans for new trials reflect our confidence in the future of Pradaxa® and our belief in its potential to benefit patient populations with the greatest unmet needs. We are hopeful the results of the trials will provide greater understanding of Pradaxa®’s potential to reduce the risk of stroke and other life-threatening events for these patients."

Higher rates of morbidity and mortality are seen in patients suffering a recurrent stroke after an ESUS.3,4 There is limited knowledge and data available to guide treatment decisions regarding secondary prevention of stroke in these patients, resulting in considerable unmet need.5

The RE-SPECT ESUS™ trial (Randomized Evaluation in Secondary stroke Prevention Comparing the Thrombin inhibitor dabigatran etexilate versus ASA in Embolic Stroke of Undetermined Source) will be led by Professor Hans-Christoph Diener, Professor of Neurology and Chairman of the Department of Neurology, University of Essen, Germany. The trial aims to include 6,000 patients who had an ESUS within three months of enrolment.

Detailed plans include:

  • Evaluating Pradaxa® compared to acetylsalicylic acid 100 mg once daily (the current standard of care) for reduction of recurrent stroke. The majority of patients will receive Pradaxa® 150 mg twice daily. Patients aged 75 or older or who have moderate renal impairment (CrCl 30-50 mL/min) will receive Pradaxa® 110 mg twice daily.
  • Treatments will be given for six months to three years, and major outcomes will be assessed up to 30 days after the end of treatment.

Research shows that patients with atrial fibrillation undergoing PCI with stenting are at high risk of stroke and other major adverse cardiac events, which can be reduced by anticoagulation therapy.6 Currently, about one in every 10 patients undergoing PCI with stenting requires anticoagulant therapy to reduce their risk of stroke due to either atrial fibrillation or other conditions.7

The RE-DUAL PCI™ trial (Randomized Evaluation of Dual Therapy with Dabigatran vs. Triple Therapy Strategy with Warfarin in Patients with NVAF that have undergone PCI with Stenting) is planned to run in cooperation with Harvard Clinical Research Institute (HCRI), led by Professor Christopher Cannon, M.D., cardiologist at Brigham and Women’s Hospital in Boston and Professor of Medicine at Harvard Medical School in the US.

Detailed plans include:

  • Event-driven trial will evaluate Pradaxa® (150 mg or 110 mg twice daily) plus single antiplatelet therapy with a P2Y12 protein inhibitor, compared to the current standard of care, which includes warfarin and two antiplatelet agents, to assess key outcomes of clinically relevant bleeding and thrombotic events (defined as the combined rate of death, myocardial infarction and stroke) following PCI.

Boehringer Ingelheim is committed to expanding scientific knowledge in stroke prevention and interventional cardiology with Pradaxa® - with an extensive and robust real-world experience of over 2 million patient years in all indications2 Pradaxa® has already established a safety and efficacy profile that delivers meaningful clinical benefits to patients.

NOTES TO EDITORS

About Pradaxa® (dabigatran etexilate)
Clinical experience of Pradaxa® (dabigatran etexilate) exceeds that of all other novel oral anticoagulants, equating to over 2 million patient-years in all licensed indications worldwide.8 Pradaxa® has already been in the market for more than 5 years and is approved in over 100 countries.8 Currently approved indications for Pradaxa® are: 9​

  • Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) and a risk factor for stroke
  • Primary prevention of venous thromboembolic events in patients undergoing elective total hip replacement surgery
  • Primary prevention of venous thromboembolic events in patients undergoing elective total knee replacement surgery

In June 2013 Boehringer Ingelheim started submitting new applications to regulatory authorities for Pradaxa® for the following indications:8

  • Treatment of acute deep vein thrombosis (DVT) and/or pulmonary embolism (PE) and prevention of related death
  • Prevention of recurrent deep vein thrombosis (DVT) and/or pulmonary embolism (PE) and related death

Important Notice: Pradaxa® is currently not approved for the acute treatment or prevention of recurrent DVT and/or PE9

Pradaxa®, a direct reversible thrombin inhibitor (DTI), was the first widely approved drug in a new generation of direct oral anticoagulants, available to target a high unmet medical need in the prevention and treatment of acute and chronic thromboembolic diseases.9,10 Potent antithrombotic effects are achieved with direct thrombin inhibitors by specifically blocking the activity of thrombin, the central enzyme in the process responsible for clot (thrombus) formation.11 In contrast to vitamin-K antagonists, which variably act via different coagulation factors, Pradaxa® provides effective, predictable and reproducible anticoagulation with a low potential for drug-drug interactions and no drug-food interactions, without the need for routine coagulation monitoring or dose adjustment.10,12

About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 140 affiliates and more than 46,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel medications of high therapeutic value for human and veterinary medicine.

Social responsibility is a central element of Boehringer Ingelheim's culture. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect, as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavours.

In 2012, Boehringer Ingelheim achieved net sales of about 14.7 billion euro. R&D expenditure in the business area Prescription Medicines corresponds to 22.5% of its net sales. For more information please visit www.boehringer-ingelheim.com

Please be advised
This release is from Boehringer Ingelheim Corporate Headquarters in Germany. Please be aware that there may be national differences between countries regarding specific medical information, including licensed uses. Please take account of this when referring to the information provided in this document. This press release is not intended for distribution within the U.S., the UK or Canada.

Related links:
www.youtube.com/cvtv

Referências

  1. National Stroke Association “Types of Stroke” Available at http://www.stroke.org/site/PageServer?pagename=TYPE Last accessed October 2013
  2. Boehringer Ingelheim. Data on file.
  3. Hankey GJ et al. Long-Term Disability After First-Ever Stroke and Related Prognostic Factors in the Perth Community Stroke Study, 1989–1990 Stroke 2002;33:1034–40
  4. Mohr JP, et al. A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke. N Engl J Me ;2001;345:1444–51
  5. Bang OY, et al. Frequency and mechanisms of stroke recurrence after cryptogenic stroke. Ann Neurol. 2003;54:227–34
  6. Ruiz-Nodar J et al. Anticoagulant and Antiplatelet Therapy Use in 426 Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention and Stent Implantation. J Am Coll Cardiol. 2008;51(8):818-825
  7. Sarafoff N, et al. Triple Therapy With Aspirin, Prasugrel, and Vitamin K Antagonists in Patients With Drug-Eluting Stent Implantation and an Indication for Oral Anticoagulation. J Am Coll Cardiol. 2013;61(20):2060–6
  8. Boehringer Ingelheim data on file.
  9. Pradaxa® European Summary of Product Characteristics 2013.
  10. Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285–95.
  11. Di Nisio M, et al. Direct thrombin inhibitors. N Engl J Med. 2005;353:1028–40.
  12. Stangier J, et al. Pharmacokinetic Profile of the Oral Direct Thrombin Inhibitor Dabagitran Etexilate in Healthy Volunteers and Patients Undergoing Total Hip Replacement. J Clin Pharmacol. 2005;45:555–63.