Efficacy and safety of HSK16149 for postoperative pain in Chinese patients after orthopedic surgery: a phase 2 randomized clinical trial

Importance: Some Chinese patients undergoing orthopedic surgery may require more effective and safer analgesics to adequately relieve moderate to severe postoperative pain. Objective: To evaluate the efficacy and safety of crisugabalin (HSK16149), a calcium channel α2δ subunit ligand oral capsule, in managing postoperative pain in Chinese patients undergoing orthopedic surgery. Methods: This Phase 2 trial was conducted from 8 March to 5 July 2023, across 20 clinical hospitals in China and employed a double-blind, randomized design, which enrolled Chinese patients scheduled for elective orthopedic surgery under general anesthesia. Patients were randomized 1:1:1:1:1 to receive HSK16149, 40 mg twice before surgery (80 mg used in total), 60 mg twice (120 mg used in total), 40 mg four times before and after surgery (160 mg used in total), 60 mg four times (240 mg used in total), and receive placebo four times before and after surgery. The primary outcome was the total morphine dose within the 24-hour postoperative period, including usage from the patient-controlled analgesia device and any additional remedial analgesia. Results: A total of 24 patients were excluded from the analysis, resulting in 235 participants randomized into the following groups: 80 mg ( n = 47), 120 mg ( n = 47), 160 mg ( n = 48), 240 mg ( n = 46), and placebo ( n = 47). Total morphine consumption within 24 hours post-surgery was significantly lower in the HSK16149 groups compared to the placebo group (Kruskal–Wallis test, P = 0.048). The means (SD) of morphine consumption were 11.00 (7.59) for the 80 mg group, 9.94 (8.15) for the 120 mg group, 10.28 (8.80) for the 160 mg group, 9.72 (10.07) for the 240 mg group, and 15.66 (12.13) for the placebo group. The P values calculated from the Wilcoxon rank sum test comparing the four HSK16149 groups to the placebo were 0.0824, 0.0239, 0.0261, and 0.0076, respectively. Conclusions: HSK16149 capsules reduced postoperative opioid consumption in Chinese patients undergoing orthopedic surgery, showing that receiving 240 mg HSK16149 was recommended and appeared to be well tolerated.