Merck, known as MSD outside the United States and Canada, today announced that the pivotal Phase 3 RECARBRIO (imipenem 500 mg, cilastatin 500 mg, and relebactam 250 mg) RESTORE-IMI 2 trial met its primary endpoint.
The global, multicenter, randomized, non-inferiority trial investigated the efficacy and safety of Merck’s antibacterial product RECARBRIO for use in adult patients with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP).
Results from the trial showed RECARBRIO met both the primary and key secondary endpoints of statistical non-inferiority compared to piperacillin/tazobactam in Day 28 all-cause mortality and clinical response at early follow up, respectively, in the modified intent-to-treat (MITT) population. Rates of adverse events observed in the trial were similar in both groups. Merck plans to present the full data from the trial at a scientific congress in 2020.
“Additional treatment options are needed for critically ill patients with respiratory infections,” said Dr. Nicholas Kartsonis, senior vice president, clinical research, infectious diseases and vaccines, Merck Research Laboratories. “By evaluating RECARBRIO in this patient population, we have generated robust clinical evidence for its potential use in patients with hospital-acquired and ventilator-associated bacterial pneumonia. We look forward to sharing these data with the regulatory agencies.”
Relebactam (the beta lactamase inhibitor component of RECARBRIO) has received the U.S. Food and Drug Administration’s (FDA) Qualified Infectious Disease Product (QIDP) designation and Fast Track status for the treatment of hospital-acquired bacterial pneumonia/ventilator-associated bacterial pneumonia.
RECARBRIO is contraindicated in patients with a history of known severe hypersensitivity (severe systemic allergic reaction such as anaphylaxis) to any component of RECARBRIO. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams.
Central nervous system (CNS) adverse reactions, such as seizures, confusional states, and myoclonic activity, have been reported during treatment with imipenem/cilastatin, a component of RECARBRIO, especially when recommended dosages of imipenem were exceeded. These reactions have been reported most commonly in patients with CNS disorders (such as brain lesions or a history of seizures) and/or compromised renal function. Concominant use of RECARBRIO with valproic acid or divalproex sodium may increase the risk of breakthrough seizures.
Additionally, Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including imipenem/cilastatin plus relebactam and may range in severity from mild diarrhea to fatal colitis.