ASRA Conference Coverage

Cebranopadol Significantly Reduces Pain After Abdominoplasty

Miranda Manier, BA

Key Highlights

  • Cebranopadol 400/400 µg significantly reduced pain scores over 48 hours post-abdominoplasty compared with placebo.
  • Patients receiving cebranopadol required fewer opioid rescue medications.
  • Treatment-emergent adverse events were comparable across treatment and placebo groups.

In a multicenter, randomized, placebo-controlled phase 3 trial presented on May 1, 2025, at the 50th Annual Regional Anesthesiology and Acute Pain Medicine Meeting, cebranopadol demonstrated a statistically significant reduction in postoperative pain following abdominoplasty. Patients who received cebranopadol had lower pain scores over the first 48 hours and were less likely to require opioid rescue medication. The 400/400 µg dose met the primary endpoint, with favorable tolerability compared with placebo.

Managing acute postoperative pain presents a challenge due to the adverse effects and dependency risks associated with traditional opioids. Cebranopadol is a first-in-class analgesic that activates both the nociceptin/orphanin FQ peptide (NOP) and mu-opioid peptide (MOP) receptors. This dual mechanism is designed to provide potent analgesia while reducing the euphoria, dependence, and respiratory depression typically associated with MOP agonists. This trial aimed to evaluate the efficacy and safety of cebranopadol in patients undergoing abdominoplasty, a procedure often associated with moderate-to-severe postoperative pain.

A total of 303 patients across four United States sites were randomized to receive either cebranopadol 400/400 µg, cebranopadol 400/200 µg, or placebo. The study drug was administered 1 hour before surgery and again 24 hours later. The primary endpoint was the area under the curve (AUC) for pain intensity from 4 to 48 hours postoperatively, as measured by the Numerical Rating Scale (NRS). Rescue analgesia included IV morphine on day 1 and oral oxycodone on day 2, administered per protocol.

Cebranopadol 400/400 µg resulted in a mean AUC pain score reduction of 59.2 points compared to placebo (P < .001), representing an average hourly reduction of 1.34 points on the NRS. In contrast, the 400/200 µg dose did not achieve statistical significance (P = .183). A greater proportion of patients in the cebranopadol groups avoided opioid rescue medication compared to placebo. Adverse events occurred at similar rates across groups, with nausea being the most common. Constipation, headache, and pruritus were also reported, but without major safety concerns.

“Cebranopadol 1st 400 μg; 2nd 400 μg achieved the primary endpoint of statistically significant pain reduction over 44 hours as compared to placebo,” the authors concluded.

Reference

Singla N, Minkowitz H, Vaughn B, et al. Results of a randomized, placebo-controlled, phase 3 trial of cebranopadol for the treatment of acute pain after abdominoplasty. Presented at: 50th Annual Regional Anesthesiology and Acute Pain Medicine Meeting; May 1, 2025; Orlando, FL. https://asra.com/events-education/ra-acute-meeting