Date: 2014-08-06
Type of information: Clinical research agreement
Compound: levosimendan
Company: Oxygen Biotherapeutics (USA - NC) Imperial College London (UK)
Therapeutic area: Critical care - Infectious diseases
Type agreement: clinical research agreement
Action mechanism: Levosimendan is a calcium sensitizer developed for intravenous use in hospitalized patients with acutely decompensated heart failure. It was discovered and developed by Orion Pharma, Orion Corporation of Espoo Finland, and is currently approved in over 50 countries for this indication and not available in the United States. Oxygen Biotherapeutics recently acquired the North American rights to develop and commercialize levosimendan from Phyxius Pharma. The United States Food and Drug Administration (FDA) has granted Fast Track status for levosimendan for the reduction of morbidity and mortality in cardiac surgery patients at risk for developing Low Cardiac Output Syndrome (LCOS). In addition, the FDA has agreed to the Phase 3 protocol design under Special Protocol Assessment (SPA), and provided guidance that a single successful trial will be sufficient to support approval of levosimendan in this indication.
Disease: prevention of acute organ dysfunction in sepsis
Details: * On August 6, 2014, Oxygen Biotherapeutics, a specialty pharmaceutical company focused on developing and commercializing a portfolio of products for the critical care market, announced a collaboration with Imperial College London to provide supplemental funding to support the accelerated enrollment and completion of the ongoing LeoPARDS Trial (Levosimendan for the Prevention of Acute oRgan Dysfunction in Sepsis) awarded by the Efficacy and Mechanism Evaluation (EME) Programme and funded by the Medical Research Council (MRC) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnership. The LeoPARDS trial is designed to determine whether levosimendan reduces the incidence and severity of acute organ dysfunction in adult patients who have septic shock, as well as evaluate its safety profile. Given the limited treatment options that exist and the prior research data regarding the potential benefits of levosimendan in septic shock patients, the EME Programme awarded funding of the LeoPARDS trial, which will be led by Imperial College London. The LeoPARDS trial began patient enrollment in the first quarter of 2014 with significant interest and trial enrollment, but the existing funding meant several interested clinical trial sites were unable to participate. Oxygen has agreed to provide supplemental funding of $500,000 through an unrestricted grant, which will allow additional sites to enroll patients more quickly. The randomized, double-blind, placebo-controlled, multi-centre trial design is based on previously conducted small clinical trials which indicate that levosimendan may provide unique and important clinical benefits to septic shock patients through improved heart function and organ perfusion. Adults fulfilling the criteria for systemic inflammatory response syndrome due to infection, and requiring vasopressor therapy, will be eligible for inclusion in the trial. Within 24 hours of meeting these inclusion criteria, patients will be randomized in a 1:1 ratio stratified by the ICU to receive either levosimendan (0.05 to 0.2 μg.kg-1.min-1 or placebo for 24 hours in addition to standard care. The primary outcome measure is the mean Sequential Organ Failure Assessment (SOFA) score while in the ICU. Secondary outcomes include: central venous oxygen saturations and cardiac output; incidence and severity of renal failure using the Acute Kidney Injury Network criteria; duration of renal replacement therapy; serum bilirubin; time to liberation from mechanical ventilation; 28-day, hospital, 3 and 6 month survival; ICU and hospital length-of-stay; and days free from catecholamine therapy. Blood and urine samples will be collected on the day of inclusion, at 24 hours, and on days 4 and 6 post-inclusion for investigation of the mechanisms by which levosimendan might improve organ function. Eighty patients will have additional blood samples taken to measure levels of levosimendan and its active metabolites OR-1896 and OR-1855. A total of 516 patients will be recruited from approximately 25 ICUs in the United Kingdom. Oxygen is also currently preparing to initiate a Phase 3 trial in the United States during the third quarter to evaluate levosimendan in cardiac surgery patients at risk of developing low cardiac output syndrome (LCOS).
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