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| Routes of administration | Oral |
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| Eliminationhalf-life | ~24 hours |
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| Formula | C24H27FN2O |
| Molar mass | 378.491 g·mol−1 |
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Cebranopadol (developmental codeTRN-228 and formerlyGRT-6005) is an investigationalopioidanalgesic currently under development internationally by Tris Pharma,[1][2] a private pharmaceutical company in the United States. The drug was originally discovered and developed byGrünenthal, aGermanpharmaceutical company and was formerly developed by Park Therapeutics andDepomed (nowAssertio Terapeutics), pharmaceutical companies in theUnited States, for the treatment of a variety of different acute andchronicpain states.[3][4][5] As of June 2025,phase IIIclinical trials have been completed for acute pain with positive results.[6]
Like most opioid analgesics, cebranopadol is an agonist of theμ-opioid receptor but unlike most other opioid analgesics it also acts as an agonist of thenociceptin receptor.
Cebranopadol acts as afull agonist at two key receptors:[citation needed]
The drug also binds to other opioid receptors with lower affinity and are not believed to contribute materially to its activity:
Cebranopadol is unusual among analgesics in being a dual NOP-MOP (dual NMR) receptor agonist. While opioids like morphine, oxycodone, and fentanyl act primarily through MOP receptors with no significant NOP activity, cebranopadol activates both systems.
Cebranopadol demonstrates distinctive pharmacokinetic properties that differentiate it from other analgesic compounds. After oral administration of the immediate-release formulation, cebranopadol exhibits a single dose half-life of 24 hours and a steady state half-life ranging from 62-96 hours.[7] The time to reach maximum plasma concentration occurs 4–6 hours after oral administration, with a long half-value duration of 14–15 hours.[8] The time to reach steady state is approximately 2 weeks, with an accumulation factor of approximately 2 and low peak-trough fluctuation (70–80%).[9] Clinical studies suggest that cebranopadol's pharmacokinetics remain unaffected by hepatic or renal impairment.[10]
Cebranopadol, originally developed by Grünenthal, has undergone extensive clinical evaluation with more than 33 trials encompassing over 2,300 participants. In 2015, Depomed (which later became Assertio Therapeutics) acquired licensing rights for the United States and Canada prior to Park Therapeutics acquiring worldwide rights in 2020. Park was then acquired by Tris in 2021.
As of 2025, both Phase 3 pivotal trials (ALLEVIATE-1 and ALLEVIATE-2) for acute pain have been completed with positive results:
ALLEVIATE-1 studied Cebranopadol in patients following abdominoplasty surgery
ALLEVIATE-2 studied Cebranopadol in patients following bunionectomy surgery
Both trials demonstrated statistically significant pain reduction compared to placebo with favorable safety profiles.[citation needed]
The FDA granted Fast Track Designation to cebranopadol for chronic low back pain in 2017. Tris Pharma plans to submit their NDA to the FDA in 2025 based on the completed Phase 3 acute pain studies. The company has announced plans to conduct cebranopadol studies in multiple chronic pain indications beginning in the second half of 2025.
Cebranopadol has been awarded a five-year grant of up to $16.6 million from the National Institute of Drug Abuse (NIDA), a division of NIH, to study the drug for the treatment of opioid use disorder (OUD).