CBP-0276 to Reduce Opioid Use in Adults Undergoing Major Orthopedic Surgery

Официальное название

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

Обзор

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

Подробное описание

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.

Вмешательства

• Препарат CBP-0276
  Oxycodone CBP-0276 orally 600mg QD, orally once a day for 30 days
• Препарат Placebo for CBP-0276
  Oxycodone (standard of care) + placebo for CBP-0276, orally once daily for 30 days

Первичные конечные точки

• Frequency of oxycodone use [Срок оценки: 28 days]

Вторичные конечные точки (5)

• Oxycodone total requirements [Срок оценки: 28 days]
• Changes on Quality of Life [Срок оценки: 28 days]
• Number of oxycodone tablets required [Срок оценки: 28 days]
• Changes on Pain Intensity [Срок оценки: 28 days]
• Chnages on inflamatory cytokines [Срок оценки: 28 days]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Мексика · 1 центр

• Innovacion y Desarrollo de Estrategias en Salud — Mexico City

Публикации

• 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. PMID 12873949
• 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. PMID 20186064
• 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. PMID 30983589
• 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. PMID 23300227
• 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. PMID 22033364
• 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. PMID 29248693

Идентификаторы

NCT: NCT07687966 · CBP0276-PillRed2026

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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