Safety of Co-Crystal of Tramadol-Celecoxib (CTC) in Patients with Acute Moderate-to-Severe Pain: Pooled Analysis of Three Phase 3 Randomized Trials.

IF 4.1 2区医学 Q1 CLINICAL NEUROLOGY

Pain and Therapy Pub Date : 2024-09-24 DOI:10.1007/s40122-024-00655-w

Eugene R Viscusi, Richard Langford, Adelaida Morte, Anna Vaqué, Jesús Cebrecos, Mariano Sust, José María Giménez-Arnau, Oscar de Leon-Casasola

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引用次数: 0

Abstract

Introduction: Multi-modal analgesia is desirable for the management of acute pain since it can provide effective pain relief at lower doses, thereby aiding tolerability. Co-crystal of tramadol-celecoxib (CTC) provides effective analgesia in models of acute pain. Co-crystallization can alter the pharmacokinetics of individual components, potentially improving tolerability. We sought to better understand the safety and tolerability of CTC in patients with acute postoperative pain.

Methods: We conducted a pooled analysis of safety data from three phase 3 randomized controlled trials in adults with acute moderate-to-severe pain following oral surgery, bunionectomy, and elective abdominal hysterectomy. We present data for CTC 200 mg twice daily (BID) and its comparators: tramadol 50 mg four times daily (QID) (one trial), tramadol 100 mg QID (two trials), celecoxib 100 mg BID (two trials), and placebo (three trials).

Results: In total, n = 551 patients received CTC 200 mg BID, n = 183 received tramadol 50 mg QID, n = 368 received tramadol 100 mg QID, n = 388 received celecoxib 100 mg BID, and n = 274 received placebo. The prevalence of adverse events (AEs) related to study drug up to 48 h was numerically lower with CTC 200 mg BID (35.9%) than with tramadol 50 mg QID (47.5%) and 100 mg QID (44.8%) but greater than with celecoxib 100 mg BID (12.4%) and placebo (20.4%). The most frequent AEs related to study drug up to 48 h were somnolence, nausea, dizziness, and vomiting, which occurred more frequently in patients receiving tramadol 100 mg QID than in those receiving CTC 200 mg BID.

Conclusion: CTC 200 mg BID appears to be better tolerated than tramadol 100 mg QID, possibly because of reduced total exposure to tramadol. This may contribute to a more favorable benefit-risk profile for CTC versus individual components, making it a promising treatment for acute pain.

Trial registration: ClinicalTrials.gov identifiers: NCT03108482, NCT02982161 (EudraCT: 2016-000592-24), NCT03062644 (EudraCT: 2016-000593-38).

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曲马多-塞来昔布共晶体（CTC）在急性中度至重度疼痛患者中的安全性：三项第三阶段随机试验的汇总分析。

导言：多模式镇痛是治疗急性疼痛的理想方法，因为它能以较低的剂量提供有效的镇痛效果，从而提高耐受性。曲马多-西来昔布（CTC）共晶体可在急性疼痛模型中提供有效镇痛。共晶体化可改变单个成分的药代动力学，从而改善耐受性。我们试图更好地了解 CTC 在急性术后疼痛患者中的安全性和耐受性：我们对三项三期随机对照试验的安全性数据进行了汇总分析，试验对象是口腔手术、拇外翻切除术和择期腹部子宫切除术后出现急性中度至重度疼痛的成人患者。我们提供了四氯化碳 200 毫克、每日两次（BID）及其对比药物的数据：曲马多 50 毫克、每日四次（QID）（一项试验）、曲马多 100 毫克、QID（两项试验）、塞来昔布 100 毫克、每日两次（两项试验）和安慰剂（三项试验）：共有 551 名患者接受了 CTC 200 毫克 BID，183 名患者接受了曲马多 50 毫克 QID，368 名患者接受了曲马多 100 毫克 QID，388 名患者接受了塞来昔布 100 毫克 BID，274 名患者接受了安慰剂。与研究药物相关的不良事件（AEs）发生率在 48 小时内，四氯化碳 200 毫克双剂量（35.9%）低于曲马多 50 毫克双剂量（47.5%）和 100 毫克双剂量（44.8%），但高于塞来昔布 100 毫克双剂量（12.4%）和安慰剂（20.4%）。48小时内最常见的与研究药物有关的不良反应是嗜睡、恶心、头晕和呕吐，接受曲马多100毫克QID治疗的患者比接受四氯化碳200毫克BID治疗的患者更常出现这些不良反应：结论：与曲马多 100 毫克 QID 相比，四氯化碳 200 毫克 BID 的耐受性似乎更好，这可能是因为曲马多的总暴露量减少了。这可能会使四氯化碳与单个成分相比具有更有利的效益-风险特征，使其成为治疗急性疼痛的一种有前途的疗法：试验注册：ClinicalTrials.gov identifiers：NCT03108482、NCT02982161（EudraCT：2016-000592-24）、NCT03062644（EudraCT：2016-000593-38）。

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来源期刊

Pain and Therapy CLINICAL NEUROLOGY-

CiteScore

6.60

自引率

5.00%

发文量

110

审稿时长

6 weeks

期刊介绍： Pain and Therapy is an international, open access, peer-reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of pain therapies and pain-related devices. Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also encouraged. Areas of focus include, but are not limited to, acute pain, cancer pain, chronic pain, headache and migraine, neuropathic pain, opioids, palliative care and pain ethics, peri- and post-operative pain as well as rheumatic pain and fibromyalgia. The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research, reviews, case reports, trial protocols, short communications such as commentaries and editorials, and letters. The journal is read by a global audience and receives submissions from around the world. Pain and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.