Cebranopadol has a lower potential for abuse versus traditional C-II and C-IV opioids, such as tramadol and oxycodone, suggests new data from a phase 1 study that evaluated human abuse potential.
Findings from the oral human abuse potential study demonstrate that the likeability of cebranopadol administered orally in nondependent recreational opioid users was significantly less compared to immediate release (IR) formulations of either tramadol or oxycodone, according to a December 13, 2022, press release from Tris Pharma, Inc.
“Approximately 50 million individuals in the United States suffer from chronic pain; unfortunately, many of these patients have limited treatment options that are safe or well tolerated and live with life-impacting pain that is not well managed,” said Ketan Mehta, founder and chief executive officer of Tris Pharma, in the press statement. “These topline data reinforce the potential of cebranopadol to provide a novel alternative to traditional opioids with strong analgesic properties while also offering reduced potential for abuse and physical dependence.”
Cebranopadol is a novel, dual nociceptin/orphanin FQ peptide (NOP) receptor and μ-opioid peptide receptor agonist in development for the treatment of moderate to severe pain. The investigational therapy has been granted Fast Track Designation from the US Food & Drug Administration.
Previous clinical studies have shown that cebranopadol is efficacious in different types of pain. Also, studies have demonstrated that cebranopadol has significantly lower risks of abuse, withdrawal, physical dependence, and overdose, according to the press statement.
The single-dose, randomized, double-blind, 5-way crossover phase 1 study of 47 participants evaluated the abuse potential of 2 supratherapeutic doses of cebranopadol in adult nondependent recreational opioid users compared to placebo and oxycodone and tramadol. Eligible participants received either placebo, cebranopadol 600 μg, cebranopadol 1000 μg, tramadol IR 600 mg, or oxycodone IR 40 mg. Abuse potential was determined based on participant-reported likeability using a Visual Analog Scale following administration of cebranopadol or placebo.
Topline results show that 1 dose of cebranopadol 600 μg was similarly liked as placebo, according to Tris Pharma. Cebranopadol 600 μg and cebranopadol 1000 μg were liked significantly less than tramadol 600 mg (17.34, p<.0001 and 7.77, p=0.0077, respectively) and oxycodone 40 mg (24.43, p<.0001 and 14.86, p<.0001, respectively), according to the release.
“There is tremendous need among individuals who suffer from acute and chronic pain for improved therapies that do not carry the well-established risks inherent with traditional opioids,” said Neil Singla, MD, founder of Lotus Clinical Research, in the release. “Cebranopadol is so exciting because preliminary data suggest that it can treat pain as effectively as opioids but has much lower potential for abuse, produces significantly less respiratory depression and leads to negligible physical dependence. The results of this trial seem to definitively prove that the drug has a low potential for abuse, and if the other features of the drug are confirmed in late-stage trials, it could become the preferred option for patients who need opioid-level analgesia and allow physicians to treat their pain without significant fear of addiction or overdose.”
Overall, both supratherapeutic dosages of cebranopadol did not raise any safety concerns. The most common reported adverse event was nausea, which was greatest after the administration of tramadol 600 mg (49%) compared to either dose of cebranopadol 1000 μg (35%) and 600 μg (15%) or oxycodone (32%). The rate of vomiting after the administration of tramadol 600 mg and 1000 μg of cebranopadol was similar (31% vs 30%), and the fewest reports of vomiting were received when participants received cebranopadol 600 μg (16%). Adverse events involving the nervous system were observed most often after the administration of tramadol with fewest reported after the administration of cebranopadol or placebo, according to the release.
Tris Pharma noted it plans to share the complete results of the study in a peer-reviewed scientific forum in the near future.