IV tramadol is a novel therapy in development in the U.S. for managing post-operative pain as an alternative to conventional narcotics.
The drug is designed to use a dual mechanism of action to block a patient’s pain signal with reduced abuse potential. This unique mechanism of action includes an opioid agonist and an inhibitor of norepinephrine and serotonin re-uptake.
In two Phase 3 trials of over 700 patients, IV tramadol demonstrated a strong safety and efficacy profile and statistically significant benefit over placebo at the 50mg dose level, achieving the study’s primary endpoints and all key secondary endpoints.
Avenue has reached agreement with the U.S. Food and Drug Administration on key elements of the Phase 3 safety study, including the primary endpoint and statistical analysis approach, for intravenous (IV) tramadol, which is in development for the treatment of acute post-operative pain in a medically supervised setting. The study will randomize post bunionectomy patients to IV tramadol or IV morphine for pain relief administered during a 48-hour post-operative period. Of note, IV tramadol demonstrated safety and efficacy in this same surgical model in a Phase 3 efficacy trial. Patients will have access to IV hydromorphone, a Schedule II opioid, for rescue of breakthrough pain. The primary endpoint is a composite of elements indicative of respiratory depression.
“Based on IV tramadol’s innovative mixed modality mechanism of action (agonism at the opioid mu receptor and reuptake inhibitor of serotonin and norepinephrine), decades of clinical experience in Europe and around the world, as well as the program’s positive data in two Phase 3 trials, we believe that IV tramadol will prove to be safe and effective in this final study and patient population,” said Alexandra MacLean, M.D., Chief Executive Officer of Avenue. “With over 100 million acute pain cases in the U.S. reported annually, patients and physicians seek an alternative pain management option with the potential to reduce the use of conventional opioids and the associated abuse potential in the post-operative setting, while effectively managing patient’s pain. We are confident that IV tramadol has the potential to overcome limitations of existing therapies and make a meaningful difference in the U.S. pain treatment landscape.”
IV tramadol has been safely used in Europe for 30 years, with approximately 370 million doses administered in Europe from 2010 to 2019.