A Study of Cebranopadol for the Treatment of Acute Pain After Bunionectomy (ALLEVIATE2)

A Multicenter, Randomized, Double-Blind, Placebo- and Active-Controlled Study to Evaluate the Efficacy and Safety of Cebranopadol for the Treatment of Moderate to Severe Acute Pain After Primary Unilateral Bunionectomy

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

Study Overview

• Status: Completed
• Conditions: Acute Pain
• Intervention / Treatment: Drug: Cebranopadol; Drug: Oxycodone IR; Drug: Placebo; Drug: Placebo Only

Detailed Description

This study is a Phase 3, multicenter, randomized, double-blind, placebo- and active-controlled parallel-group study to evaluate the efficacy and safety of cebranopadol in the treatment of postoperative pain following primary unilateral bunionectomy with first metatarsal osteotomy. The study will be conducted in 3 phases: Screening, Treatment, and Follow-up.

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Sheffield, Alabama, United States, 35660
      • ALLEVIATE 2 Site 001108
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • ALLEVIATE 2 Site 001106
  • Florida
    • Tampa, Florida, United States, 33613
      • ALLEVIATE 2 Site 001103
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • ALLEVIATE 2 Site 001102
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • ALLEVIATE 2 Site 001107
  • Maryland
    • Pasadena, Maryland, United States, 21122
      • ALLEVIATE 2 Site 001105
  • Texas
    • Houston, Texas, United States, 77043
      • Alleviate 2 001113
    • McAllen, Texas, United States, 78501
      • ALLEVIATE 2 Site 001104
    • San Antonio, Texas, United States, 78240
      • ALLEVIATE 2 Site 001111
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • ALLEVIATE 2 Site 001101

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria Before Surgery:

• Scheduled to undergo primary unilateral bunionectomy with first metatarsal osteotomy and internal fixation with no collateral procedures, using anesthesiologic and surgical procedures planned.
• Must be able to adhere to the visit schedule, complete all study assessments and protocol requirements, including self-reported questionnaires.

Key Exclusion Criteria Before Surgery:

• Any clinically significant disease, medical condition, or laboratory finding that in the investigator's opinion may interfere with the study procedures or data integrity, or compromise the safety of the subject.
• Secondary (i.e., unrelated to bunion) current painful condition that could confound the interpretation of efficacy, safety, or tolerability data in the study, in the opinion of the investigator.
• Subjects who require any analgesic for secondary (i.e., unrelated to bunion) painful condition that might impact the subject's ability to properly assess their postoperative pain, or that may require treatment during the Treatment Phase.
• History of allergy or hypersensitivity to any opioid analgesics, anesthetics, ibuprofen, or other NSAIDs.

Immediate Postoperative Exclusion Criteria:

• Surgical, postsurgical, or anesthetic complication that could confound the interpretation of efficacy, safety, or tolerability data in the study.
• Deviation from the surgical, postsurgical, or anesthetic protocol that could confound the interpretation of efficacy, safety, or tolerability data in the study.
• Evidence of hemodynamic instability or respiratory insufficiency.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cebranopadol; once daily for 3 days	Drug: Cebranopadol; once daily for 3 days; Other Names: TRN-228; Drug: Placebo; three times per day for 3 days
Active Comparator: Oxycodone IR; four times per day for 3 days	Drug: Oxycodone IR; four times per day for 3 days; Other Names: oxycodone immediate release
Placebo Comparator: Placebo; four times per day for 3 days	Drug: Placebo Only; four times per day for 3 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pain NRS area under the curve: cebranopadol vs. placebo	2-48 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
Proportion of subjects who require opioid rescue medication	1-7 Days
Global Assessment of Satisfaction	1-7 Days
Total oxycodone rescue consumption	1-7 Days

Other Outcome Measures

Outcome Measure	Time Frame
Incidence of Respiratory Safety Events	1-7 Days

Collaborators and Investigators

• Sponsor: Tris Pharma, Inc.
• Investigators: Principal Investigator: Todd M Bertoch, MD, Cenexel JBR

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2024
• Primary Completion (Actual): January 31, 2025
• Study Completion (Actual): January 31, 2025

Study Registration Dates

• First Submitted: May 16, 2024
• First Submitted That Met QC Criteria: May 16, 2024
• First Posted (Actual): May 21, 2024

Study Record Updates

• Last Update Posted (Actual): January 26, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Bunionectomy
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Acute Pain; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Morphine Derivatives; Codeine; Oxycodone; 6'-fluoro-4',9'-dihydro-N,N-dimethyl-4-phenylspiro(cyclohexane-1,1'(3'H)-pyrano(3,4-b)indol)-4-amine
• Other Study ID Numbers: TRN-228-302

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No