Cebranopadol for Acute Pain

(ALLEVIATE2 Trial)

Recruiting at 9 trial locations

Overseen By Emanuela Offidani

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Tris Pharma, Inc.

Must not be taking: Opioids, Anesthetics, NSAIDs

Disqualifiers: Allergy to opioids, NSAIDs, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 3 days

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new pain relief drug, Cebranopadol, for individuals undergoing bunion surgery. Researchers aim to evaluate Cebranopadol's effectiveness and safety compared to a placebo (a pill with no active drug) and Oxycodone IR, a common painkiller. Individuals planning a bunionectomy who can adhere to the study rules are suitable candidates. The trial excludes those with other painful conditions or allergies to certain pain medications. As a Phase 3 trial, this study serves as the final step before FDA approval, allowing participants to contribute to the potential availability of a new pain relief option.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you require analgesics for a condition unrelated to the bunion, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cebranopadol is generally safe for use. In earlier studies, patients who took cebranopadol experienced a noticeable decrease in pain levels, with no serious side effects reported.

Some individuals did experience mild side effects, such as nausea or dizziness, but these were uncommon. Researchers are testing cebranopadol to determine its effectiveness in managing sudden pain, such as after surgeries like tummy tucks and bunion removals. The safety results from these studies suggest it could be effective in similar situations. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for acute pain?

Cebranopadol is unique because it targets both the nociceptin/orphanin FQ peptide (NOP) receptor and the traditional opioid receptors, which could offer effective pain relief while potentially reducing the risk of typical opioid side effects like addiction. Unlike standard treatments such as oxycodone, which primarily engage with opioid receptors, cebranopadol's dual action might provide a more balanced pain management approach. Researchers are excited about this treatment because it could represent a new, safer class of pain relievers with less potential for abuse.

What evidence suggests that Cebranopadol could be an effective treatment for acute pain after a bunionectomy?

Research has shown that Cebranopadol reduces sudden pain after surgeries. In earlier studies, patients experienced significantly less pain after procedures like tummy tucks. Specifically, doses of 400 µg or 600 µg of Cebranopadol proved more effective than a placebo, easing pain within two hours and lasting for several hours. In this trial, participants will receive either Cebranopadol, a placebo, or Oxycodone IR to assess their effectiveness in managing acute pain, such as after bunion surgery. ^{1 2 3 4 5}

Who Is on the Research Team?

Todd M Bertoch, MD

Principal Investigator

Cenexel JBR

Are You a Good Fit for This Trial?

This trial is for individuals experiencing acute pain following a bunionectomy, which is a surgical procedure to remove bunions. Participants should meet specific health criteria set by the study's guidelines.

Inclusion Criteria

Must be able to adhere to the visit schedule, complete all study assessments and protocol requirements, including self-reported questionnaires.

I am scheduled for a specific foot surgery to correct a bunion.

Exclusion Criteria

I have no complications from surgery that could affect study results.

History of allergy or hypersensitivity to any opioid analgesics, anesthetics, ibuprofen, or other NSAIDs

My surgery and recovery followed all standard procedures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either Cebranopadol, placebo, or Oxycodone IR for 3 days to manage postoperative pain

3 days

Daily visits for medication administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cebranopadol

Trial Overview The study aims to test the effectiveness and safety of Cebranopadol in managing post-surgical pain compared with Oxycodone IR (a known painkiller) and a placebo (a substance with no therapeutic effect).

How Is the Trial Designed?

Group I: Cebranopadol Experimental Treatment 2 Interventions

once daily for 3 days

Group II: Oxycodone IR Active Control 1 Intervention

four times per day for 3 days

Group III: Placebo Placebo Group 1 Intervention

three times per day 3 days (with cebranopadol); four times per day for 3 days (placebo arm)

Who Is Running the Clinical Trial?

Tris Pharma, Inc.

Lead Sponsor

Trials

22

Recruited

4,800+

Published Research Related to This Trial

Cebranopadol, a new pain medication, showed significant analgesic effects in various mouse pain models, including acute and chronic pain, with efficacy comparable to morphine.

Unlike morphine, cebranopadol developed its pain-relieving effects more slowly and did not cause motor deficits, suggesting a better safety profile for treating conditions like diabetic neuropathy and cancer pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of cebranopadol, a dually acting nociceptin/orphanin FQ and opioid receptor agonist in mouse models of acute, tonic, and chemotherapy-induced neuropathic pain. Sałat, K., Furgała, A., Sałat, R.[2023]

Cebranopadol is a novel analgesic that acts on both nociceptin/orphanin FQ peptide (NOP) and opioid receptors, showing potent pain relief in various rat models with effective doses ranging from 0.5 to 5.6 µg/kg for acute and chronic pain.

Unlike traditional opioids like morphine, cebranopadol has a favorable safety profile, as it does not impair motor coordination or respiration, and it delays the development of analgesic tolerance compared to morphine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cebranopadol: a novel potent analgesic nociceptin/orphanin FQ peptide and opioid receptor agonist. Linz, K., Christoph, T., Tzschentke, TM., et al.[2023]

Cebranopadol, a new strong pain reliever, showed typical opioid-like effects, including respiratory depression, but with a significant advantage: it did not cause complete cessation of breathing (apnea) at the tested dose, unlike traditional opioids.

In a study involving 12 healthy male volunteers, cebranopadol demonstrated a half-life for respiratory depression of about 1.2 hours, suggesting a potentially safer profile for managing pain without severe respiratory risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Respiratory Effects of the Nociceptin/Orphanin FQ Peptide and Opioid Receptor Agonist, Cebranopadol, in Healthy Human Volunteers. Dahan, A., Boom, M., Sarton, E., et al.[2022]

Cebranopadol, a novel analgesic, shows promising pharmacokinetic properties with a long half-life of 62-96 hours and a time to reach maximum plasma concentration of 4-6 hours after oral administration, making it suitable for once-daily dosing.

The drug demonstrates dose proportionality across a wide range (200-1600 µg) and achieves steady state in about 2 weeks, indicating its potential effectiveness and stability for managing chronic pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Pharmacokinetic Characteristics of Cebranopadol, a Novel First-in-Class Analgesic. Kleideiter, E., Piana, C., Wang, S., et al.[2019]

Cebranopadol is a novel analgesic that works on nociceptin/orphanin FQ peptide (NOP) and opioid receptors, showing strong effectiveness in various preclinical pain models while having a better side effect profile than traditional opioids.

Phase II clinical trials have confirmed cebranopadol's efficacy and good tolerability for both acute and chronic pain, with its NOP receptor activity helping to reduce opioid-related side effects like respiratory depression and potential for abuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cebranopadol: A Novel First-in-Class Potent Analgesic Acting via NOP and Opioid Receptors. Tzschentke, TM., Linz, K., Koch, T., et al.[2023]

Citations

1. trispharma.com trispharma.com/tris-pharma-announces-positive-results-from-alleviate-1-phase-3-clinical-trial-of-cebranopadol-an-investigational-first-in-class-oral-dual-nmr-agonist-for-the-treatment-of-moderate-to-severe-acute-p/

Tris Pharma Announces Positive Results from ALLEVIATE ... Study achieved primary endpoint of statistically significant reduction in pain intensity compared to placebo following abdominoplasty ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06545097

NCT06545097 | A Study of Cebranopadol for the ... The purpose of this study is to evaluate the efficacy and safety of Cebranopadol for acute pain after a Abdominoplasty.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/29871387/

Cebranopadol: A Novel, First-in-Class, Strong Analgesic: ... Results: Cebranopadol doses of 400 µg and 600 µg were more effective in reducing postoperative acute pain compared to placebo, from 2 hours until approximately ...

4. trispharma.com trispharma.com/positive-phase-3-results-asra-2025/

Tris Pharma to Unveil Positive Phase 3 Results at ASRA ... Positive results from ALLEVIATE-1 Phase 3 pivotal trial for cebranopadol will be presented that demonstrate statistically significant pain reduction compared ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06423703

NCT06423703 | A Study of Cebranopadol for the ... The purpose of this study is to evaluate the efficacy and safety of Cebranopadol for acute pain after a bunionectomy.