Investigational Nonopioid Beats Placebo in Phase 3 Trial: Daily Dose

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Patient Care brings primary care clinicians a lot of medical news every day—it’s easy to miss an important study. The Daily Dose provides a concise summary of one of the website's leading stories you may not have seen.

On January 29, 2025, we reported on topline results from the pivotal phase 3 ALLEVIATE-1 clinical trial evaluating cebranopadol (Tris Pharma) for the treatment of moderate-to-severe acute pain in people following abdominoplasty surgery.

The medication

Cebranopadol is an investigational therapy with potential to be a first-in-class analgesic. It targets both the nociceptin/orphanin FQ peptide (NOP) and µ-opioid peptide (MOP) receptors. The dual-NMR mechanism combines the analgesic effects of the MOP receptor with the safety characteristics of NOP receptor activation, providing “potent” pain reduction while mitigating the risk of abuse and dependence associated with traditional opioid analgesics. The mechanism of action also reduces the risk of respiratory depression and the potential for abuse.

The study

The primary objective of the multicenter, randomized, double-blind, placebo-controlled study is to assess the analgesic efficacy of cebranopadol compared with placebo for the management of moderate-to-severe acute pain following full abdominoplasty as measured by pain intensity (11-point numeric rating scale) assessments. Secondary objectives include assessing the analgesic efficacy of cebranopadol through use of rescue medication, early discontinuations and subject overall assessment of study medication.

The findings

Participants treated with cebranopadol 400 µg once daily for 44 hours following surgery experienced a least squares mean difference of 59.2 (SE 14.36; P < .001) in pain intensity, as measured by the Pain Numeric Rating Scale (NRS) Area Under the Curve (AUC4-48), satisfying the study’s primary endpoint.

Tris Pharma also reported a favorable safety profile for cebranopadol, with tolerability comparable to placebo and no serious adverse events related to the drug. The most common adverse event was nausea. The company intends to submit the full results from ALLEVIATE-1 for presentation at an upcoming medical congress.

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