- Cebranopadol is an investigational first-of-its kind dual NOP/MOP receptor (NMR) agonist which uses a novel approach of activating NOP and MOP receptors to work synergistically to modulate pain
- In both ALLEVIATE trials cebranopadol demonstrates significant and sustained pain reduction with a differentiated safety profile following abdominoplasty and bunionectomy
- Human abuse-potential studies showing cebranopadol is less abusable than oxycodone and tramadol, further support its potential to offer strong pain relief with an improved safety profile
MONMOUTH JUNCTION, N.J., March 06, 2026 (GLOBE NEWSWIRE) — Tris Pharma, Inc. (Tris), a commercial-stage biopharmaceutical company, today announced debut data from its Phase 3 ALLEVIATE-1 and ALLEVIATE-2 studies evaluating the safety and efficacy of cebranopadol, an investigational therapy, for the treatment of moderate-to-severe acute pain in patients following abdominoplasty and bunionectomy surgery, respectively, at the American Academy of Pain Medicine (AAPM) 2026 PainConnect annual meeting.
The debut abstract titled, “Results of ALLEVIATE-1 and ALLEVIATE-2 Phase 3 Trials of Cebranopadol, a First-in-Class, Dual NOP/MOP Receptor Agonist for the Treatment of Acute Pain After Abdominoplasty and Bunionectomy,” was presented by Dr. Todd Bertoch, MD, Chief Medical Officer of CenExel Clinical Research, and Principal Investigator on ALLEVIATE-2.
“As pain specialists, we often see how inadequately controlled acute pain can linger long after surgery or injury,” said Dr. Todd Bertoch. “If we don't get ahead of severe pain early, it can become chronic and much harder to treat. These Phase 3 results underscore the potential of cebranopadol to redefine the standard of care for acute pain management.”
Cebranopadol is an investigational, first-in-class dual nociceptin/orphanin FQ peptide (NOP) and μ-opioid peptide (MOP) receptor agonist (dual-NMR agonist). By simultaneously activating both receptors, cebranopadol is designed to provide potent analgesia while potentially mitigating many of the risks traditionally associated with preferential MOP agonists.
ALLEVIATE-1 clinical trial (NCT06545097) is a Phase 3 multicenter, randomized, double-blind, placebo-controlled study. It enrolled 303 patients undergoing abdominoplasty surgery without liposuction or other collateral procedures across four U.S. sites. Eligible participants were randomized in a 1:1:1 ratio to cebranopadol 400 ug on Days 1 and 2, cebranopadol 400 ug on Day 1 and 200 ug on Day 2 or placebo all administered once daily. The first dose was administered approximately 1 hour prior to abdominoplasty and the second dose approximately 24 hours later.
ALLEVIATE-2 clinical trial (NCT06423703) is a Phase 3 multicenter, randomized, double-blind, placebo-and active controlled study. It enrolled 242 patients undergoing unilateral bunionectomy with first metatarsal osteotomy across ten U.S. sites. Eligible participants were randomized in a 1:1:1 ratio to a cebranopadol 400 ug, oxycodone immediate release (IR) 10 mg or placebo. Cebranopadol was administered once daily on Days 1, 2, and 3; placebo was administered at 6, 12, and 18 hours to maintain blinding. Oxycodone 10 mg and placebo were administered every 6 hours.
Baseline Demographics and Allocation:
- In the abdominoplasty study, 303 participants were randomized to treatment at four sites in the U.S., and 292 (96.4%) completed the study.
- Eleven participants discontinued the study due to adverse events (AEs) (3), lost to follow-up (2), withdrawal of consent (3), and other (3).
- In the bunionectomy study, 242 participants were enrolled at 10 locations in the Unites States, and 236 (97.5%) completed the study.
- One participant was discontinued in the oxycodone group for hypersensitivity, which was considered a severe and serious AE.
- No other participants discontinued or experienced a severe or serious AE.
- Across the two trials, baseline characteristics were similar among groups. More participants in the abdominoplasty study had a history of substance abuse.
Efficacy and Safety Results
- The primary endpoints in both trials were met, demonstrating an acceptable benefit-risk profile of cebranopadol for the treatment of acute pain following abdominoplasty and bunionectomy:
- In ALLEVIATE-1, the average total pain score area under the curve (AUC 4-48) for patients dosed with 400 ug cebranopadol was significantly less than placebo (LS mean difference 59.2; SE 10.14; p<0.001).
- In ALLEVIATE-2, the average total pain score area under the curve (AUC 2-48) for patients dosed with cebranopadol was significantly less than placebo (LS mean difference 56.1; SE 13.49; p<0.001)
- Following abdominoplasty, a significantly greater proportion of patients receiving cebranopadol 400 ug required no opioid rescue medication compared with those receiving placebo (34.7% vs 9.9%; p<0.001).
- Following bunionectomy, a significantly higher proportion of patients receiving cebranopadol 400 ug required no opioid rescue medication compared with those receiving placebo (57.5% vs 28.4%; p=0.006)
- Cebranopadol was generally well tolerated and exhibited a favorable safety profile.
- Nausea was the most common AE across study groups with exception of placebo group in the bunionectomy study. Other AEs included vomiting, constipation, headache, dizziness, hypertension and pruritus.
Ketan Mehta, founder and CEO at Tris Pharma added, “Acute postoperative pain remains a significant clinical challenge, and the standard of care has serious associated risks. With our first-in-class dual NOP/MOP receptor agonist, we are taking a fundamentally new approach to pain relief, one that simultaneously targets two distinct pathways of pain modulation to deliver meaningful pain relief with a reduced risk of side effects associated with preferential MOP agonists. These data validate this mechanism of action and reinforce the potential of cebranopadol to address a critical need for safe and effective treatment options.”
About Acute Pain 
Approximately 80 million adults in the U.S. are treated for acute pain every year1,2. Acute pain can be caused by injury, invasive surgery, illness, major trauma and burns. It can last up to three months and typically resolves once the underlying cause is treated or healed. Moderate-to-severe acute pain can often only be effectively treated with opioid analgesics, which, while effective, are associated with risks including respiratory depression, tolerance, dependence, misuse, and overdose. However, undertreating severe pain in the immediate period after onset can increase the risk of a patient developing chronic pain3,4.
About Cebranopadol 
Cebranopadol is a first-in-class investigational therapy that targets two key receptors, the nociceptin/orphanin FQ peptide (NOP) and u-opioid peptide (MOP) receptors (a dual-NMR agonist), for the treatment of moderate-to-severe pain, as well as opioid use disorder (OUD). These receptors are partially homologous to each other, and they play both complementary and distinct roles to modulate pain biology pathways. Studied in over 33 clinical trials in more than 2,200 subjects, cebranopadol's profile has been well characterized in pain management studies. It has demonstrated positive clinical results in acute pain, chronic pain, and diabetic neuropathic pain with a favorable safety profile. The FDA granted Fast Track Designation to cebranopadol for chronic low back pain, and if approved, it could become the first dual-NMR pain-relief therapy with the potential to provide efficacy equivalent to selective MOP agonists such as oxycodone with less risk of misuse or physical dependence, addiction or overdose. 
Cebranopadol's novel mechanism of action has potential in treating patients with substance use disorders (SUDs). Tris plans to continue to evaluate cebranopadol's potential to help patients break the cycle of opioid addiction. 
The National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH), has awarded Tris a five-year grant of up to $16.6 million to study cebranopadol's potential to treat OUDs and SUDs. 
About Tris Pharma 
Tris Pharma is a privately held, innovation-driven biopharmaceutical company that is applying its drug development capabilities and proprietary technologies to transform the treatment of ADHD, pain, addiction and disorders of the central nervous system. Tris markets a portfolio of best-in-class ADHD products and is developing a promising pipeline of differentiated near-term drug candidates. More information is available at www.trispharma.com and on LinkedIn @TrisPharma. 
Media Contact 
Jonathan Pappas 
LifeSci Communication 
jpappas@lifescicomms.com 
Company Contact 
Cheryl Patnick 
Tris Pharma, Inc. 
cpatnick@trispharma.com
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- Banerjee S, Argaez C. Multidisciplinary Treatment Programs for Patients with Acute or Subacute Pain: A Review of Clinical Effectiveness, Cost-Effectiveness, and Guidelines [Internet]. Canadian Agency for Drugs and Technologies in Health. 2019 May 7; PMID: 31498579
- Lopez A, Menzie AM, Kenderes M, Rubin JL. A real-world database analysis of the prevalence of pain medication use in the United States. PAIN Reports. 2026 February; DOI: 10.1097/PR9.0000000000001396
- McGreevy K, Bottros MM, Raja SN. Preventing Chronic Pain following Acute Pain: Risk Factors, Preventive Strategies, and their Efficacy. European Journal of Pain Supplements. 2012 Nov 11; PMID: 22102847
- Sinatra, R. (2010). “Causes and Consequences of Inadequate Management of Acute Pain.” Pain Medicine, 11(12), 1859-1871. doi:10.1111/j.1526-4637.2010.00983.x
