PURPOSE 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. PATIENTS AND METHODS 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. RESULTS 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 P<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 (P<0.05). CONCLUSION 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.

中文翻译：

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APOLLO-1：一项随机安慰剂和活性对照的 III 期研究，调查 oliceridine (TRV130)，一种在 μ-阿片受体上偏向 G 蛋白的配体，用于治疗拇囊炎切除术后的中度至重度急性疼痛。

目的 Oliceridine 是一种新型 G 蛋白偏向 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，阿片类药物相关不良事件 (ORAE) 的风险更低。患者和方法 APOLLO-1 (NCT02815709) 是一项 III 期、双盲、随机试验，用于治疗拇囊炎切除术后中度至重度疼痛的患者。患者接受负荷剂量的安慰剂、奥西里定（1.5 毫克）或吗啡（4 毫克），然后通过患者自控镇痛（0.1、0.35 或 0.5 毫克奥西里定、1 毫克吗啡或安慰剂）进行需求剂量。主要终点比较了 48 小时内 oliceridine 方案和安慰剂的治疗反应者比例。次要结局包括呼吸安全负担的综合测量（RSB，代表呼吸安全事件的累积持续时间）和治疗反应者与吗啡的比例。结果 所有 oliceridine 方案均观察到有效镇痛，0.1 mg、0.35 mg 和 0.5 mg 方案的反应率分别为 50%、62% 和 65.8%（与安慰剂相比，所有 P<0.0001 [15.2%]；0.35 mg 和 0.5 mg 不劣于吗啡）。RSB 在 oliceridine 方案中显示出剂量依赖性增加（平均小时数 [SD]：0.1 mg：0.04 [0.33]；0.35 mg：0.28 [1.11]；0.5 mg：0.8 [3.33]；安慰剂：0 [0]），但没有一个与吗啡有统计学差异（1.1 [3.03]）。在 oliceridine 方案中，胃肠道不良事件也以剂量依赖性方式增加（0.1 mg：40.8%；0.35 mg：59.5%；0.5 mg：70.9%；安慰剂：24.1%；吗啡：72.4%）。与吗啡相比，oliceridine 方案的抢救止吐药使用优势比显着降低（P<0.05）。结论 Oliceridine 是一种新型有效的静脉内镇痛剂，与安慰剂相比，可提供快速镇痛，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，并且可能为需要静脉注射阿片类药物的中度至重度术后疼痛患者提供新的治疗选择。