CBP-0276 to Reduce Opioid Use in Adults Undergoing Major Orthopedic Surgery (CBP0276-Opd)

Proof-of-concept, Double-blind, Randomized Clinical Study to Evaluate the Safety and Efficacy of CBP-0276 at Doses of 600 mg/Day vs Placebo in Reducing Opioid Use in Pain Management in Adult Patients Undergoing Major Orthopedic Surgery

Randomized, double-blind, clinical study to evaluate the safety and efficacy of CBP-0276 at doses of 600 mg/day in reducing opioid use in pain management in adult patients undergoing major orthopedic surgery. Subjects will be allocated in 2 groups. One group will receive oxycodone (standard of care) + CBP-0276 at a dose of 600 mg, orally once daily for 28 days. A second group will receive oxycodone (standard of care) + placebo for CBP-0276, orally once daily for 28 days

Study Overview

• Status: Recruiting
• Conditions: Hip or Knee Replacement
• Intervention / Treatment: Drug: CBP-0276; Drug: Placebo for CBP-0276

Detailed Description

Randomized, Phase 2, Proof-of-concept, double-blind, parallel-group, placebo controlled clinical study to evaluate the safety and efficacy of CBP-0276 at doses of 600 mg/day in reducing opioid use in pain management in adult patients undergoing major orthopedic surgery. Subjects will be allocated in 2 groups. One group (n=40) will receive oxycodone (standard of care) + CBP-0276 at a dose of 600 mg, orally once daily for 28 days. A second group (n=40) will receive oxycodone (standard of care) + placebo for CBP-0276, orally once daily for 28 days. Primary outcome is the reduction on the number of oxycodone tablets required to controlled the moderate to severe pain management during the 28 days post-major orthopaedic surgery. Secondary and Exploratory outcomes are: A) Number of days where the use of oxycodone is required; B) Changes in quality of life according to the WHOQOL-BREF score, from baseline and at 28 days post-surgery; C) The number of oxycodone tablets required for pain management at day 15 post-surgical; D) Frequency and intensity of pain at day 28 post-surgery and at 3 months of post-surgical follow-up; E) Changes on inflamatory cytokines between baseline and end of treatment (day 28) Characteristics of the subject to be enrolled included age between 40 and 75y, male or female, BMI 18.5 to 35, under surgery of hip or knee replacement.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Pedro Gutiérrez Castrellón, MD, PhD; Phone Number: +525554198746; Email: pedro.gutierrez@elemental.org.mx
• Study Contact Backup: Name: Diana M Andrade Platas, MD; Phone Number: +525535209755; Email: diana.andrade@elemental.org.mx

Study Locations

• Mexico
  • Mexico City, Mexico, 14340
    • Recruiting
    • Innovacion y Desarrollo de Estrategias en Salud
    • Contact: Diana M Andrade Platas, MD, MSc; Phone Number: +525535209755; Email: diana.andrade@elemental.org.mx
    • Contact: Tom Jilmer Castillo, MD; Phone Number: +523324120245; Email: tom.castillo@idecsa.com.mx
    • Principal Investigator: Miguel Gonzalez Thompson, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

• Men or women
• Age between 40 and 75 years (inclusive)
• Body weight between 50 and 90 Kg
• Post-surgical patient of major orthopedic surgery, with opioid treatment (oxycodone) at discharge by treating physician
• Physical status of ASA I to III
• Be able and willing to read, understand, sign, and date the Informed
• Consent Form prior to entering the study.
• Woman of childbearing age with effective contraception, not pregnant, not on breastfeeding, not pregnancy plans during the development of the study, postmenopausal, defined by cessation of menstruation for at least 12 consecutive months and confirmed by serum FSH levels > 40 mIU/mL and estradiol < 20 pg/mL or surgically sterile (with hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) and not undergoing in vitro fertilization or other fertility treatments)
• Men agreed to use contraception or remain abstinent (when this is the subject's usual and preferred lifestyle)Be willing to complete all study visits and procedures.

Exclusion criteria:

• History of respiratory depression, severe bronchial asthma, chronic obstructive pulmonary disease, or acute and/or severe hypercepnia and cor pulmonale.
• History of gastrointestinal motility disorders (e.g., severe reflux esophagitis, gastroparesis, severe irritable bowel syndrome, active inflammatory bowel disease, and paralytic ileus).
• History of depression, seizures, and epilepsy.
• Uncontrolled hypertension: systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg confirmed by at least two measurements.
• History of allergic reactions, anaphylactic reactions, severe systemic hypersensitivity, or any allergic reaction that, in the opinion of the Principal Investigator or his /her delegate, is likely to be exacerbated by the study drug (RAP-103 and oxycodone).
• History of human immunodeficiency virus or positive HIV test result (HIV 1-2 antibodies).
• History of hepatitis C infection or positive hepatitis C virus (HCVAb) antibody screening result.
• Current hepatitis B (HBV) infection (defined as positive for HepBsAg and/or HepBcAb). Subjects with immunity to hepatitis B from prior natural infection (defined as HepBsAg negative, HepBcAb positive, and HepBsAb positive) or vaccination (defined as HepBsAg negative, HepBCAb negative, and HepBSAb positive) are eligible to participate in the study.
• Transcutaneous oxygen saturation (SpO₂) <90%.
• Patients with severe liver or kidney disease.
• Patients with immunosuppression, neoplasms, or HIV infection.
• Active substance use disorder (SUD) or within the previous 12 months, including opioid, alcohol, benzodiazepines, or any other substance with potential for abuse.
• Patients with the use of antipsychotic medications.
• Any clinical condition that makes it difficult to self-assess pain.
• Recent opioid use (14 days prior recruitment).
• Previous exposure to RAP-103 or DAPTA (T-Peptide) at any time in your life.
• Abnormal and clinically significant results at the discretion of the Principal investigator (or his/her delegate) in the laboratory tests and electrocardiogram of visit 0. Laboratory values out of range and determined to be not clinically significant at the discretion of the Principal Investigator or his/her delegate may be repeated on one occasion, the subject may be enrolled if the repeated value is within the normal range.
• Participation in any other investigational study with drugs, biologics, medical devices, or treatment with an investigational product or therapy approved for investigational use within 30 days or 5 halflives at visit 0.
• Any other condition that, in the judgment of the PI or Sponsor, determines that the subject is not suitable to participate in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CBP-0276 600mg QD; First group (n=40) will receive oxycodone (standard of care) + CBP-0276 at a dose of 600 mg, orally once daily for 28 days.	Drug: CBP-0276; Oxycodone CBP-0276 orally 600mg QD, orally once a day for 30 days
Placebo Comparator: Placebo for CBP-0276; Second group (n=40) will receive oxycodone (standard of care) + placebo for CBP-0276, orally once daily for 28 days	Drug: Placebo for CBP-0276; Oxycodone (standard of care) + placebo for CBP-0276, orally once daily for 30 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of oxycodone use	Number of oxycodone tablets required to controlled the moderate to severe pain management after hip or knee replacement.	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Oxycodone total requirements	Number of days where the use of oxycodone is required	28 days
Changes on Quality of Life	Changes in quality of life according to the WHOQOL-BREF score, from baseline and at 28 days post-surgery. This is a 26-item self-report questionnaire that assesses an individual's subjective perception of their well-being and quality of life over the previous two weeks. The raw item scores are converted into transformed domain scores on a standardized scale from 0 to 100. 0 represents the lowest possible perceived quality of life, meanwhile 100 represents the highest.	28 days
Number of oxycodone tablets required	The number of oxycodone tablets required for pain management at day 15 post-surgical	28 days
Changes on Pain Intensity	Frequency and intensity of pain evaluated by visual analoge scale (VAS) at day 28 post-surgery and at 3 months of post-surgical follow-up, where 0 is no pain and 10 is the most severy level of pain	28 days
Chnages on inflamatory cytokines	Changes on inflamatory cytokines between baseline and end of treatment (day 28)	28 days

Collaborators and Investigators

• Sponsor: Clarent Biopharma, Inc.
• Investigators: Principal Investigator: Jorge González Thompson, MD, Innovacion y Desarrollo de Estrategias en Salud SA de CV

Publications and helpful links

General Publications

• Apfelbaum JL, Chen C, Mehta SS, Gan TJ. Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg. 2003 Aug;97(2):534-540. doi: 10.1213/01.ANE.0000068822.10113.9E.
• Glare P, Aubrey KR, Myles PS. Transition from acute to chronic pain after surgery. Lancet. 2019 Apr 13;393(10180):1537-1546. doi: 10.1016/S0140-6736(19)30352-6.
• DeWire SM, Yamashita DS, Rominger DH, Liu G, Cowan CL, Graczyk TM, Chen XT, Pitis PM, Gotchev D, Yuan C, Koblish M, Lark MW, Violin JD. A G protein-biased ligand at the mu-opioid receptor is potently analgesic with reduced gastrointestinal and respiratory dysfunction compared with morphine. J Pharmacol Exp Ther. 2013 Mar;344(3):708-17. doi: 10.1124/jpet.112.201616. Epub 2013 Jan 8.
• Mattia C, Coluzzi F, Sonnino D, Anker-Moller E. Efficacy and safety of fentanyl HCl iontophoretic transdermal system compared with morphine intravenous patient-controlled analgesia for postoperative pain management for patient subgroups. Eur J Anaesthesiol. 2010 May;27(5):433-40. doi: 10.1097/EJA.0b013e3283349d82.
• Padi SSV, Shi XQ, Zhao YQ, Ruff MR, Baichoo N, Pert CB, Zhang J. Attenuation of rodent neuropathic pain by an orally active peptide, RAP-103, which potently blocks CCR2- and CCR5-mediated monocyte chemotaxis and inflammation. Pain. 2012 Jan;153(1):95-106. doi: 10.1016/j.pain.2011.09.022. Epub 2011 Oct 26.
• Noda M, Tomonaga D, Kitazono K, Yoshioka Y, Liu J, Rousseau JP, Kinkead R, Ruff MR, Pert CB. Neuropathic pain inhibitor, RAP-103, is a potent inhibitor of microglial CCL1/CCR8. Neurochem Int. 2018 Oct;119:184-189. doi: 10.1016/j.neuint.2017.12.005. Epub 2017 Dec 14.

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2026
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: June 25, 2026
• First Submitted That Met QC Criteria: July 2, 2026
• First Posted (Actual): July 7, 2026

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: July 2, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: CBP0276-PillRed2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No