Tris Pharma Reports Positive Topline Data from Clinical Study of Investigational Pain Therapy Cebranopadol Showing Significantly Less Potential for Abuse Versus Tramadol and Oxycodone

  -- Study evaluating human abuse potential demonstrates that the likeability of cebranopadol administered orally in nondependent recreational opioid users was significantly less as compared to immediate release (IR) formulations of either tramadol or oxycodone, suggesting a lower potential for abuse versus traditional C-II and C-IV opioids -- 

-- A first-in-class investigational analgesic uniquely designed with reduced potential for abuse, cebranopadol is a novel dual nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor agonist --

-- Cebranopadol has achieved positive phase 2b clinical study results for the treatment of moderate to severe pain; registrational phase 3 studies expected to initiate in 2023 --

MONMOUTH JUNCTION, N.J., Dec. 13, 2022 /PRNewswire/ -- Tris Pharma, Inc. (Tris), a fully integrated, innovation-driven pharmaceutical company focused on CNS disorders, today announced new clinical data from its oral human abuse potential study in patients who are nondependent recreational opioid users, which demonstrate that cebranopadol (TRN-228) possesses significantly less likeability at high doses, above the therapeutic range versus immediate release (IR) formulations of tramadol or oxycodone. These data suggest that cebranopadol has a lower potential for abuse versus both C-II and C-IV opioids.

Cebranopadol is a novel, dual nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor agonist in development for the treatment of moderate to severe pain. Multiple clinical studies have demonstrated that cebranopadol is efficacious in different types of pain. Additionally, studies have shown that cebranopadol has significantly lower risks of abuse, withdrawal, physical dependence and overdose. The investigational therapy has been granted Fast Track Designation from the U.S. Food & Drug Administration (FDA).

"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. 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," said Ketan Mehta, founder and chief executive officer of Tris Pharma. "Cebranopadol offers a compelling and truly unique mechanism of action that takes advantage of the inherent properties of the NOP receptor."

Human abuse potential studies are required prior to FDA approval in therapeutic classes with high abuse potential and are designed as phase 1 studies. The cebranopadol oral human abuse potential study was a phase 1 single-dose, randomized, double-blind, five-way crossover study of 47 participants to evaluate the abuse potential of two supratherapeutic doses of cebranopadol in adult nondependent recreational opioid users versus placebo and commonly used opioids, oxycodone, a schedule II narcotic, and tramadol, a schedule IV narcotic. Eligible participants randomly received a single dose of placebo, cebranopadol 600µg, cebranopadol 1000µg, tramadol IR 600mg, or oxycodone IR 40mg. Abuse potential was determined based on participant-reported likeability using a Visual Analog Scale (VAS) following administration of study drug or placebo. Topline results show that one 600 µg dose of cebranopadol was similarly liked as placebo. Both 600 µg and 1000 µg doses of cebranopadol were liked significantly less than tramadol 600mg (17.34, p< 0.0001 and 7.77, p=0.0077, respectively) and oxycodone 40mg (24.43, p< 0.0001 and 14.86, p< 0.0001, respectively), suggesting cebranopadol has significantly less potential for abuse compared to both schedule II and schedule IV opioids.

"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 Dr. Neil Singla of Lotus Clinical Research.  "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 600mg (49%) versus either dose of cebranopadol 1000 µg and 600 µg (35% and 15%) or oxycodone (32%). The rate of vomiting after the administration of tramadol 600 mg and 1000 µg of cebranopadol was similar, 31% versus 30%. The fewest reports of vomiting were received when participants received 600 µg of cebranopadol (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. Reports of pruritis (itchy skin) were greater after administration of oxycodone (30%) and tramadol (18%) when compared to 600 µg and 1000 µg of cebranopadol (4% and 7%).

Tris plans to share the complete results of this study in a peer-reviewed scientific forum in the near future.

Cebranopadol is a novel, centrally active dual nociceptin/orphanin FQ peptide (NOP) receptor and µ-opioid peptide (MOP) receptor agonist in development for the treatment of acute and chronic moderate to severe pain. Targeting both the NOP and MOP receptors provides additional benefits than targeting MOP alone, allowing for opioid-like efficacy with an improved safety / tolerability profile and lower likelihood of physical dependence and risk of abuse. Cebranopadol has been studied extensively for its safety and efficacy in approximately 2,000 individuals through multiple clinical trials across Europe and the United States, including in subjects with moderate to severe acute postoperative pain following bunionectomy, chronic pain due to painful diabetic polyneuropathy, chronic pain due to osteoarthritis of the knee, chronic low back pain and in subjects with cancer pain. Efficacy has been comparable to C-II opioids in both acute and chronic nociceptive pain and comparable or superior to pregabalin in neuropathic pain. Additional studies have shown cebranopadol versus traditional C-II opioids caused significantly less respiratory depression, demonstrated less abuse potential in nondependent recreational opioid users and was better tolerated with respect to some common opioid-related adverse events. In clinical trials to date, low rates of side effects associated with withdrawal and physical dependence were observed. Cebranopadol is being studied with once daily dosing and has shown no need for dose adjustment in patients with renal or hepatic impairment or with food.

Tris Pharma is a privately held, fully integrated and innovation-driven CNS company that provides a differentiated approach to target unmet medical needs, including the application of novel technologies designed to enhance patient benefits across therapeutic categories. Tris' CNS portfolio includes FDA-approved products for the treatment of Attention Deficit/Hyperactivity Disorder (ADHD) and a pipeline of treatments for pain, addiction, spasticity and narcolepsy. For more information, please visit www.trispharma.com and www.trismedical.com.

Sources

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2. Vowles KE, McEntee ML, Julnes PS, Frohe T, Ney JP, van der Goes DN. Rates of opioid misuse, abuse, and addiction in chronic pain: a systematic review and data synthesis. Pain. 2015;156(4):569-576. doi:10.1097/01.j.pain.0000460357.01998.f1.

SOURCE Tris Pharma, Inc.