Cancer‐related chronic pain: Investigation of the novel analgesic drug candidate cebranopadol in a randomized, double‐blind, noninferiority trial

Abstract Background Cancer‐related pain is a growing health problem given the increasing life expectancy of cancer patients. Opioids are commonly used to treat cancer‐related pain, but carry the risk of severe side effects, limiting their use. Cebranopadol is a first‐in‐class drug candidate, combining nociceptin/orphanin FQ peptide and opioid peptide receptor agonism. This trial examined the analgesic efficacy of cebranopadol compared with morphine prolonged release ( PR ) in patients with moderate‐to‐severe cancer‐related pain. Methods This double‐blind, parallel‐group, multiple‐dose trial was designed as noninferiority trial for efficacy of cebranopadol versus morphine PR . Planned with 524 patients, finally 126 patients were treated for up to 7 weeks (low accrual). The primary efficacy endpoint was the average amount of daily rescue medication intake (morphine immediate release) over the last 2 weeks of treatment. Results For the primary endpoint, noninferiority of cebranopadol with and superiority over morphine PR were demonstrated (Full Analysis Set: ∆[95% CI ] = −7.48 mg [−12.05, −2.92]; Per Protocol Set: ∆[95% CI ] = −4.67 mg [−9.25, −0.10]). The vast majority of patients (≥75%, either treatment) had clinically relevant pain reduction, and noninferiority on this secondary endpoint was not shown. Mostly used doses were ≤800 μg cebranopadol or ≤120 mg morphine PR daily. A total of 83.1% of patients on cebranopadol and 82.0% on morphine PR experienced treatment‐emergent adverse events. Conclusions Cebranopadol was effective, safe and well tolerated in the dose range tested (200–1,000 μg) in patients suffering from chronic moderate‐to‐severe cancer‐related pain and was superior to morphine PR on the primary endpoint. Significance Cebranopadol presents a new approach to treat cancer pain. The drug candidate was easy to titrate, safe and well tolerated, and as effective as morphine PR in patients suffering from chronic moderate‐to‐severe cancer‐related pain