• Ho-Jin Lee, Ji-Yeon Sim, Inkyung Song, Srdjan S Nedeljkovic, Duk Kyung Kim, Ah-Young Oh, Seung Zhoo Yoon, Young-Jin Moon, MiHye Park, Insun Park, Jina Kim, Sang Rim Lee, Sunyoung Cho, and BahkJae-HyonJHDepartment of Anesthesiology and Pain Medicine, Seoul National University, College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address: bahkjh@snu.ac.kr..
• Department of Anesthesiology and Pain Medicine, Seoul National University, College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
• J Clin Anesth. 2024 Dec 19; 101: 111729111729.

Study ObjectiveVVZ-149 is a small molecule that inhibits the glycine transporter type 2 and the serotonin receptor 5-hydroxytryptamine 2 A. In this Phase 3 study, we investigated the efficacy and safety of VVZ-149 as a single-use injectable analgesic for treating moderate to severe postoperative pain after laparoscopic colectomy.DesignRandomized, parallel group, double-blind, Phase 3 clinical trial (Trial no. NCT05764525).Setting5 tertiary referral centers in South Korea.Patients284 patients undergoing laparoscopic colectomy.InterventionsA continuous 10-h intravenous infusion of VVZ-149 (n = 141) or placebo (n = 143) administered after emergence from anesthesia.MeasurementsPain intensity was assessed using a numeric rating scale (NRS) from the start of infusion for 48 h. The primary efficacy measure was the Sum of Pain Intensity Difference (SPID) for the first 12 h after the start of drug infusion. Other efficacy measures included SPID at other time points, opioid consumption via on-demand patient-controlled analgesia (PCA) and rescue medication, and proportion of patients who did not require rescue opioids for 48 h post-dose.Main ResultsPain relief as measured by SPID was significantly improved by 35 % in the VVZ-149 group compared to the placebo group at 6 h (p = 0.0193) and 12 h (p = 0.0047) after the start of infusion. Significantly lower pain intensity scores were observed between 4-10 h in the VVZ-149 group compared to the placebo group (p = 0.0007), reaching mild pain (mean NRS <4) at 8 h. VVZ-149 alleviated pain during the first 12 h post-dose with 30.8 % less opioid consumption and 60.2 % fewer PCA requests when compared with placebo. A higher proportion of patients receiving VVZ-149 were rescue opioid-free during 2-6 h (p = 0.0026) and 6-12 h (p = 0.0024) compared with the placebo group. VVZ-149 administration in post-colectomy patients was generally safe and well tolerated.ConclusionsWhen compared to placebo, VVZ-149 infusion demonstrated a significant reduction of pain within the first 12 h after surgery with a substantial decrease in opioid use. VVZ-149 rapidly lowers the pain intensity starting at as early as 4 h post-dose, allowing subjects to experience mild pain levels from 8 h through 48 h. Therefore, the analgesic effect of VVZ-149 was shown to effectively relieve pain and reduce opioid use for treating moderate to severe pain in the early postoperative care setting.Registration NumberTrial Number NCT05764525.Copyright © 2024. Published by Elsevier Inc.

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