Investigational Acute Pain Therapy to be Evaluated in Pivotal Phase 3 Trials

Two pivotal phase 3 trials evaluating the efficacy and safety of cebranopadol for the treatment of moderate-to-severe acute pain have been initiated, Tris Pharma announced in a release.¹ The first-in-class investigational therapy is a dual-NMR agonist, as it targets the nociceptin/orphanin FQ receptor and the µ-opioid receptor. Cebranopadol has the potential to treat multiple types of pain.

Investigational Acute Pain Therapy to be Evaluated in Pivotal Phase 3 Trials / Alrandir - stock.adobe.com

ALLEVIATE-1 (NCT06545097) will enroll up to 300 patients at up to 6 sites in the US. The primary endpoint is to evaluate the analgesic efficacy of cebranopadol compared with placebo for the management of moderate-to-severe pain following full abdominoplasty. ALLEVIATE-2 (NCT06423703) will enroll up to 240 patients at up to 8 sites. The primary endpoint is to evaluate the analgesic efficacy of the therapy compared with placebo for the management of moderate-to-severe pain following bunionectomy.

READ MORE: Problematic Opioid Prescribing Among Patients with Chronic Pain

“Currently, physicians are constrained to prescribing pain medicines that either don’t effectively alleviate pain or do treat pain but often come with risk of significant side effects, misuse, addiction and overdose,” Jeffrey Gudin, MD, professor of anesthesiology, perioperative medicine and pain management at the University of Miami Miller School of Medicine, said in a release.¹ “I’ve witnessed firsthand the transformative potential of this novel pain management therapy, and the initiation of these phase 3 trials is an important step toward helping both physicians and their patients feel more confident in safely managing pain.”

Tris presented clinical data from a study on cebranopadol at the International Association for the Study of Pain’s 2024 World Congress on Pain, which was held August 5 to 9 in Amsterdam, Netherlands.² Data from the study showed the therapy produces 25% less respiratory depression compared to oxycodone at equal doses and presents a longer time to impact on respiratory parameters. Additionally, despite having a longer duration of effect, cebranopadol produces fewer respiratory adverse events over 24 hours.

In data from a human abuse potential study presented at the 2023 PAINWeek Conference, cebranopadol demonstrated a significantly lower abuse potential compared to schedule II and schedule IV opioids, with less likability, longer time to peak effect, fewer perceived good effects and more perceived bad effects than both oxycodone and tramadol.³ These findings suggest the therapy could serve as an alternative treatment option.

In August of 2023, Tris was awarded a grant worth up to $16.6 million from the NIH’s National Institute on Drug Abuse through the Helping to End Addiction Long-Term initiative. The grant, which will disperse the money over 5 years, was provided to complete preclinical through phase 2 studies evaluating cebranopadol for the treatment of opioid use disorder (OUD).⁴ The studies aim to investigate the dosage of cebranopadol needed to block withdrawal and subjective effects of opioid dependence, as well as its ability to deter the self-administration of schedule II opioids.

“There is a monumental need to improve upon available treatments for the millions of individuals who suffer from pain each day and are unable to live a normal life,” Ketan Mehta, founder and chief executive officer at Tris Pharma, said in a release.¹ “The initiation of our pivotal Phase 3 clinical trials for cebranopadol, a potentially transformational new pain therapy, is a significant step toward providing patients with a solution that is both highly effective and has a strong safety profile. We look forward to sharing the results from each study when they are available.”

READ MORE: Pain Management Resource Center

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References

1. Tris Pharma Initiates ALLEVIATE-1 and ALLEVIATE-2, Pivotal Phase 3 Trials Investigating Cebranopadol, a First-in-Class Compound with a Novel Mechanism of Action to Treat Pain. News Release. Tris Pharma. August 21, 2024. Accessed August 28, 2024. https://www.trispharma.com/tris-pharma-initiates-alleviate-1-and-alleviate-2-pivotal-phase-3-trials-investigating-cebranopadol-a-first-in-class-compound-with-a-novel-mechanism-of-action-to-treat-pain/

2. Tris Pharma Presents New Clinical Data Demonstrating Robust Safety and Efficacy of Investigational, First-in-Class Therapy Cebranopadol for Treatment of Pain. News Release. Tris Pharma. August 6, 2024. Accessed August 28, 2024. https://www.trispharma.com/tris-pharma-presents-new-clinical-data-demonstrating-robust-safety-and-efficacy-of-investigational-first-in-class-therapy-cebranopadol-for-treatment-of-pain/

3. Tris Pharma Presents Data Reinforcing Limited Abuse Potential of Investigational Pain Therapy Cebranopadol at the 2023 PAINWeek Conference. News Release. Tris Pharma. September 5, 2023. Accessed August 28, 2024. https://www.trispharma.com/tris-pharma-presents-data-reinforcing-limited-abuse-potential-of-investigational-pain-therapy-cebranopadol-at-the-2023-painweek-conference/

4. Tris Pharma Awarded Five-Year Grant of Up to $16.6M From the NIH’s National Institute on Drug Abuse to Advance Cebranopadol for the Treatment of Opioid Use Disorder. News Release. Tris Pharma. August 28, 2023. Accessed August 28, 2024. https://www.trispharma.com/tris-pharma-awarded-five-year-grant-of-up-to-16-6m-from-the-nihs-national-institute-on-drug-abuse-to-advance-cebranopadol-for-the-treatment-of-opioid-use-disorder/