Department of Global Research and Development, Vivozon, Inc, West Windsor, New Jersey.
Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Pain Med. 2021 Sep 8;22(9):2037-2049. doi: 10.1093/pm/pnab066.
VVZ-149 is a small molecule that both inhibits the glycine transporter type 2 and the serotonin receptor 5 hydroxytryptamine 2 A. In a randomized, parallel-group, and double-blind trial (NCT02844725), we investigated the analgesic efficacy and safety of VVZ-149 Injections, which is under clinical development as a single-use injectable product for treating moderate to severe postoperative pain.
Sixty patients undergoing laparoscopic and robotic-laparoscopic gastrectomy were randomly assigned to receive a 10-hour intravenous infusion of VVZ-149 Injections or placebo, initiated approximately 1 hour before completion of surgical suturing. Major outcomes included pain intensity and opioid consumption via patient-controlled analgesia and rescue analgesia provided "as needed." The treatment efficacy of VVZ-149 was further examined in a subpopulation requiring early rescue medication, previously associated with the presence of high levels of preoperative negative affect in a prior Phase 2 study (NCT02489526).
Pain intensity was lower in the VVZ-149 (n = 30) than the placebo group (n = 29), reaching statistical significance at 4 hours post-emergence (P < .05), with a 29.5% reduction in opioid consumption for 24 hours and fewer demands for patient-controlled analgesia. In the rescued subgroup, VVZ-149 further reduced pain intensity (P < .05) with 32.6% less opioid consumption for 24 hours compared to placebo patients.
VVZ-149 demonstrated effective analgesia with reduced postoperative pain and opioid requirements. Consistent with the results from the previous Phase 2 study, patients with early rescue requirement had greater benefit from VVZ-149, supporting the hypothesis that VVZ-149 may alleviate the affective component of pain and mitigate excessive use of opioids postoperatively.
VVZ-149 是一种小分子，既能抑制甘氨酸转运蛋白 2 型，又能抑制 5-羟色胺受体 2A。在一项随机、平行分组、双盲试验（NCT02844725）中，我们研究了 VVZ-149 注射液的镇痛疗效和安全性，该药物正在开发为一种单次使用的注射产品，用于治疗中重度术后疼痛。
60 例接受腹腔镜和机器人腹腔镜胃切除术的患者被随机分配接受 VVZ-149 注射液或安慰剂静脉输注 10 小时，大约在手术缝线完成前 1 小时开始。主要结局包括通过患者自控镇痛和按需提供的解救镇痛评估的疼痛强度和阿片类药物消耗量。在一项亚人群研究中进一步检查了 VVZ-149 的治疗效果，该亚人群在先前的一项 2 期研究（NCT02489526）中与术前存在高水平负性情绪相关，需要早期解救药物。
VVZ-149 组（n=30）的疼痛强度低于安慰剂组（n=29），在术后 4 小时达到统计学意义（P<.05），24 小时内阿片类药物消耗量减少 29.5%，患者自控镇痛需求减少。在解救亚组中，与安慰剂组相比，VVZ-149 进一步降低了疼痛强度（P<.05），24 小时内阿片类药物消耗量减少 32.6%。
VVZ-149 表现出有效的镇痛作用，降低了术后疼痛和阿片类药物需求。与之前的 2 期研究结果一致，需要早期解救的患者从 VVZ-149 中获益更大，这支持了 VVZ-149 可能缓解疼痛的情感成分并减少术后阿片类药物过度使用的假设。
