P-044 - (Poster #44) Results of a Randomized, Placebo-Controlled, Phase 3 Trial of Cebranopadol for the Treatment of Acute Pain After Abdominoplasty

This study evaluates the safety and efficacy of cebranopadol in managing acute post-operative pain following abdominoplasty.

Methods: A Phase 3 double-blind, randomized, placebo-controlled, multi-center study was conducted evaluating cebranopadol compared to placebo. Following ethics board approval, and informed consent, eligible participants aged 18-75 years were randomized in a 1:1:1 ratio to receive a dose of cebranopadol 400µg 1 hour prior to the abdominoplasty followed by a second 400µg dose approximately 24 hours after the first dose (400µg/400µg), 400µg/200µg, or placebo. Subjects underwent a full abdominoplasty procedure without liposuction or other collateral procedures under a standardized regimen of anesthesia. Ondansetron 4mg was administered for prophylaxis of nausea and vomiting with the possibility of a supplementary dose. Rescue medications included IV morphine for the first 24 hours following study drug administration followed by oral oxycodone thereafter. The primary efficacy endpoint was the pain numerical rating scale (NRS) area under the curve from 4 through 48 hours (AUC_4-48) of the treatment group compared to placebo. Subjects were also monitored for treatment emergent adverse events (TEAEs).

Results:

A total of 300 subjects were included in the study (400µg/400µg: n=101; 400µg/200µg: n=98; placebo: n=101). Subjects were predominantly female (98.7%) ranging in age from 22 to 68 years. Baseline characteristics were generally comparable between groups. Both cebranopadol groups demonstrated improvement in pain NRS AUC_4-48 compared to the placebo with statistically significant reductions in pain in the 400µg/400µg group (400µg/400µg: -59.2, 95%CI[-87.3, -31.1], p< 0.001; 400µg/200µg: -19.2, 95% CI[-47.7, 9.1], p=0.183).

Treatments were generally well tolerated and total TEAEs observed were similar between treatment groups (400µg/400µg: 66.3%; 400µg/200µg: 69.3%; placebo: 74.3) The most common TEAEs included nausea (400µg/400µg: 43.6%, 400µg/200µg: 45.5%, placebo:47.5%), constipation (2%, 15.8%, 12.9%), and headache (5.9%, 5.9%, 11.9%).  Similarly, serious TEAEs while not common were similar across treatment arms.

Conclusions/Implications for future research and/or clinical care: With the successful completion of the first of two Phase 3 studies, cebranopadol demonstrates promise as a first-in-class Dual-NMR Agonist, effective, and well-tolerated option for acute post-surgical pain. Cebranopadol, a novel analgesic with a unique dual mechanism of action as a nociceptin/orphanin FQ peptide (NOP) receptor and mu-opioid receptor agonist, demonstrates a more promising balance of efficacy and safety in treating moderate to severe acute pain. This study highlights cebranopadol’s potential to become a valuable new therapy for acute pain management.