Reduction of postoperative pain and opioid consumption by VVZ-149, first-in-class analgesic molecule: A confirmatory phase 3 trial of laparoscopic colectomy

초록

OBJECTIVE: VVZ-149 is a small molecule that inhibits the glycine transporter type 2 and the serotonin receptor 5-hydroxytryptamine 2&#xa0;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. METHODS: Randomized, parallel group, double-blind, Phase 3 clinical trial (Trial no. NCT05764525). METHODS: 5 tertiary referral centers in South Korea. METHODS: 284 patients undergoing laparoscopic colectomy. METHODS: A continuous 10-h intravenous infusion of VVZ-149 (n&#xa0;=&#xa0;141) or placebo (n&#xa0;=&#xa0;143) administered after emergence from anesthesia. METHODS: Pain intensity was assessed using a numeric rating scale (NRS) from the start of infusion for 48&#xa0;h. The primary efficacy measure was the Sum of Pain Intensity Difference (SPID) for the first 12&#xa0;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&#xa0;h post-dose. RESULTS: Pain relief as measured by SPID was significantly improved by 35&#xa0;% in the VVZ-149 group compared to the placebo group at 6&#xa0;h (p&#xa0;=&#xa0;0.0193) and 12&#xa0;h (p&#xa0;=&#xa0;0.0047) after the start of infusion. Significantly lower pain intensity scores were observed between 4-10&#xa0;h in the VVZ-149 group compared to the placebo group (p&#xa0;=&#xa0;0.0007), reaching mild pain (mean NRS <4) at 8&#xa0;h. VVZ-149 alleviated pain during the first 12&#xa0;h post-dose with 30.8&#xa0;% less opioid consumption and 60.2&#xa0;% fewer PCA requests when compared with placebo. A higher proportion of patients receiving VVZ-149 were rescue opioid-free during 2-6&#xa0;h (p&#xa0;=&#xa0;0.0026) and 6-12&#xa0;h (p&#xa0;=&#xa0;0.0024) compared with the placebo group. VVZ-149 administration in post-colectomy patients was generally safe and well tolerated. CONCLUSIONS: When compared to placebo, VVZ-149 infusion demonstrated a significant reduction of pain within the first 12&#xa0;h after surgery with a substantial decrease in opioid use. VVZ-149 rapidly lowers the pain intensity starting at as early as 4&#xa0;h post-dose, allowing subjects to experience mild pain levels from 8&#xa0;h through 48&#xa0;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. BACKGROUND: Trial Number NCT05764525. Copyright © 2024. Published by Elsevier Inc.

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