Viscusi Eugene R, Skobieranda Franck, Soergel David G, Cook Emily, Burt David A, Singla Neil
Department of Anesthesiology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA,
Trevena Inc., Chesterbrook, PA, USA.
J Pain Res. 2019 Mar 11;12:927-943. doi: 10.2147/JPR.S171013. eCollection 2019.
Oliceridine is a novel G protein-biased µ-opioid receptor agonist designed to provide intravenous (IV) analgesia with a lower risk of opioid-related adverse events (ORAEs) than conventional opioids.
APOLLO-1 (NCT02815709) was a phase III, double-blind, randomized trial in patients with moderate-to-severe pain following bunionectomy. Patients received a loading dose of either placebo, oliceridine (1.5 mg), or morphine (4 mg), followed by demand doses via patient-controlled analgesia (0.1, 0.35, or 0.5 mg oliceridine, 1 mg morphine, or placebo). The primary endpoint compared the proportion of treatment responders through 48 hours for oliceridine regimens and placebo. Secondary outcomes included a composite measure of respiratory safety burden (RSB, representing the cumulative duration of respiratory safety events) and the proportion of treatment responders vs morphine.
Effective analgesia was observed for all oliceridine regimens, with responder rates of 50%, 62%, and 65.8% in the 0.1 mg, 0.35 mg, and 0.5 mg regimens, respectively (all <0.0001 vs placebo [15.2%]; 0.35 mg and 0.5 mg non-inferior to morphine). RSB showed a dose-dependent increase across oliceridine regimens (mean hours [SD]: 0.1 mg: 0.04 [0.33]; 0.35 mg: 0.28 [1.11]; 0.5 mg: 0.8 [3.33]; placebo: 0 [0]), but none were statistically different from morphine (1.1 [3.03]). Gastrointestinal adverse events also increased in a dose-dependent manner in oliceridine regimens (0.1 mg: 40.8%; 0.35 mg: 59.5%; 0.5 mg: 70.9%; placebo: 24.1%; morphine: 72.4%). The odds ratio for rescue antiemetic use was significantly lower for oliceridine regimens compared to morphine (<0.05).
Oliceridine is a novel and effective IV analgesic providing rapid analgesia for the relief of moderate-to-severe acute postoperative pain compared to placebo. Additionally, it has a favorable safety and tolerability profile with regard to respiratory and gastrointestinal adverse effects compared to morphine, and may provide a new treatment option for patients with moderate-to-severe postoperative pain where an IV opioid is required.
奥利替丁是一种新型的G蛋白偏向性μ-阿片受体激动剂，旨在提供静脉内（IV）镇痛，与传统阿片类药物相比，其阿片类药物相关不良事件（ORAEs）风险更低。
APOLLO-1（NCT02815709）是一项III期双盲随机试验，研究对象为拇囊炎切除术后中重度疼痛的患者。患者接受负荷剂量的安慰剂、奥利替丁（1.5mg）或吗啡（4mg），随后通过患者自控镇痛给予按需剂量（0.1mg、0.35mg或0.5mg奥利替丁、1mg吗啡或安慰剂）。主要终点比较了奥利替丁方案和安慰剂在48小时内治疗反应者的比例。次要结局包括呼吸安全负担的综合指标（RSB，代表呼吸安全事件的累积持续时间）以及治疗反应者与吗啡相比的比例。
所有奥利替丁方案均观察到有效镇痛，0.1mg、0.35mg和0.5mg方案的反应率分别为50%、62%和65.8%（均与安慰剂[15.2%]相比<0.0001；0.35mg和0.5mg不劣于吗啡）。RSB在奥利替丁方案中呈剂量依赖性增加（平均小时数[标准差]：0.1mg：0.04[0.33]；0.35mg：0.28[1.11]；0.5mg：0.8[3.33]；安慰剂：0[0]），但与吗啡（1.1[3.03]）相比均无统计学差异。奥利替丁方案中胃肠道不良事件也呈剂量依赖性增加（0.1mg：40.8%；0.35mg：59.5%；0.5mg：70.9%；安慰剂：24.1%；吗啡：72.4%）。与吗啡相比，奥利替丁方案使用解救性止吐药的优势比显著更低（<0.05）。
与安慰剂相比，奥利替丁是一种新型有效的静脉内镇痛药，能快速镇痛以缓解中重度急性术后疼痛。此外，与吗啡相比，它在呼吸和胃肠道不良反应方面具有良好的安全性和耐受性，对于需要静脉内使用阿片类药物的中重度术后疼痛患者可能提供一种新的治疗选择。
