A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of QP002 for the Treatment of Post-Operative Pain After Tension-Free Repair of Open Unilateral Inguinal Hernia.

Background: QP002 Long-acting local anaesthetic with bupivacaine and low-dose meloxicam as active ingredients for postoperative regional analgesia. The objective of the present study was to evaluate the safety, tolerability, and pharmacokinetics (PK) and pharmacodynamics (PD) of QP002 for postoperative analgesia following tension-free repair of an open unilateral inguinal hernia. Methods: This was a multicentre, randomised, double-blind, positive-controlled trial. Patients were randomly assigned to receive a single injection of QP002 (five dose groups) with 0.25% bupivacaine hydrochloride 75 mg after open unilateral tension-free repair of an inguinal hernia. Pharmacokinetic parameters were evaluated by obtaining pharmacokinetic characteristic blood samples before and 120 hours after administration, at a total of 20 sampling points. Adverse events occurring after treatment were recorded from baseline to postoperative day 27 follow-up. Results: A total of 40 patients with unilateral inguinal hernia were included in this study. In comparison to 0.25% bupivacaine hydrochloride 75 mg, the results demonstrate that QP002 was well tolerated, with no additional adverse events (AEs) observed and no instances of serious adverse events (SAEs). QP002 demonstrated prolonged absorption and clearance of bupivacaine, including a longer time to reach peak plasma concentration and a terminal elimination half-life. The peak plasma concentrations of 240 mg/7.2 mg QP002 (Cmax 250.33 ng/mL) were similar to those of 0.25% bupivacaine hydrochloride 75 mg (Cmax 258.40 ng/mL). Cumulative pain intensity scores at 24 hours postoperatively in the exercise state (NRS-A-AUC0-24) were lower in the QP002 dose groups than in the 0.25% bupivacaine hydrochloride 75 mg, with P = 0.0165 in the 320 mg/9.6 mg QP002 and P = 0.0435 in the 400 mg/12 mg QP002. Conclusion: QP002 demonstrated favorable safety profiles and exhibited distinct extended-release pharmacokinetic (PK) characteristics in single-ascending-dose administration. High doses of QP002 showed potential for postoperative incisional infiltration to control pain. Future studies will further explore its efficacy and safety in broader clinical applications.