Delving into the Latest Updates on Opiranserin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Vvz-149 free base

Target

5-HT2A receptor x GlyT2

Mechanism

5-HT2A receptor antagonists(Serotonin 2a (5-HT2a) receptor antagonists), GlyT2 inhibitors(Glycine transporter 2 inhibitors)

Therapeutic Areas

Nervous System Diseases

Active Indication

Acute PainPain, Postoperative

Inactive Indication

Early gastric cancer

Originator Organization

Vivozon, Inc.

Active Organization

Vivozon Pharmaceutical Co., Ltd. (Old)

Inactive Organization

Vivozon, Inc.

Drug Highest PhasePhase 3

First Approval Date-

Regulation-

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Structure

Molecular FormulaC21H34N2O5

InChIKeyJQUVQWMHZSYCRQ-UHFFFAOYSA-N

CAS Registry1441000-45-8

STUDY OBJECTIVEVVZ-149 is a small molecule that inhibits the glycine transporter type 2 and the serotonin receptor 5-hydroxytryptamine 2A. In the present study, we investigated the efficacy and safety of VVZ-149 as a single-use injectable analgesic for treating moderate to severe postoperative pain after colorectal surgery.DESIGNRandomized, parallel group, double-blind Phase 2 clinical trial (NCT02489526).SETTING3 academic institutions in the United States.PATIENTS60 patients undergoing laparoscopic colorectal surgery.INTERVENTIONSA continuous 8-h intravenous infusion of VVZ-149 Injections (n = 40) or placebo (n = 20) administered after emergence from anesthesia.MEASUREMENTSThe outcome measures included pain intensity (PI), opioid consumption via patient-controlled analgesia (PCA), and rescue dosing provided "as needed". Early rescue dosing with opioids postoperatively was associated with preoperative negative affect (anxiety, depression, and pain catastrophizing), enabling it to be used as an indirect measure of the affective component of pain. Efficacy outcomes were compared between treatment groups based on preoperative negative affect and early rescue dosing of opioids.MAIN RESULTSPostoperative PI was non-significantly lower in patients receiving VVZ-149 compared to those receiving placebo. The VVZ-149 group had a 34.2% reduction in opioid consumption for 24 h post-dose, along with fewer PCA demands. Somnolence and headache was higher in the intervention group. For patients characterized by high levels of preoperative negative affect, the VVZ-149 group experienced a significant pain reduction and 40% less opioid use compared to the placebo group.CONCLUSIONSVVZ-149 resulted in a non-significant reduction of postoperative pain during the first 8 h after surgery. Post hoc analysis indicates that VVZ-149 may benefit patients with negative affect who otherwise have higher postoperative opioid use. REGISTRATION NUMBER: www.clinicaltrials.gov, ID: NCT02489526.

08 Sep 2021·Pain MedicineQ3 · MEDICINE

Role of VVZ-149, a Novel Analgesic Molecule, in the Affective Component of Pain: Results from an Exploratory Proof-of-Concept Study of Postoperative Pain following Laparoscopic and Robotic-Laparoscopic Gastrectomy

Q3 · MEDICINE

Article

Author: Lee, Chaewon ; Nedeljkovic, Srdjan S ; Kim, Jina ; Song, Inkyung ; Bai, Sun Joon ; Lee, Sang Rim ; Cho, Sunyoung

AbstractObjectiveVVZ-149 is a small molecule that both inhibits the glycine transporter type 2 and the serotonin receptor 5 hydroxytryptamine 2 A. In a randomized, parallel-group, and double-blind trial (NCT02844725), we investigated the analgesic efficacy and safety of VVZ-149 Injections, which is under clinical development as a single-use injectable product for treating moderate to severe postoperative pain.MethodsSixty patients undergoing laparoscopic and robotic-laparoscopic gastrectomy were randomly assigned to receive a 10-hour intravenous infusion of VVZ-149 Injections or placebo, initiated approximately 1 hour before completion of surgical suturing. Major outcomes included pain intensity and opioid consumption via patient-controlled analgesia and rescue analgesia provided “as needed.” The treatment efficacy of VVZ-149 was further examined in a subpopulation requiring early rescue medication, previously associated with the presence of high levels of preoperative negative affect in a prior Phase 2 study (NCT02489526).ResultsPain intensity was lower in the VVZ-149 (n = 30) than the placebo group (n = 29), reaching statistical significance at 4 hours post-emergence (P < .05), with a 29.5% reduction in opioid consumption for 24 hours and fewer demands for patient-controlled analgesia. In the rescued subgroup, VVZ-149 further reduced pain intensity (P < .05) with 32.6% less opioid consumption for 24 hours compared to placebo patients.ConclusionsVVZ-149 demonstrated effective analgesia with reduced postoperative pain and opioid requirements. Consistent with the results from the previous Phase 2 study, patients with early rescue requirement had greater benefit from VVZ-149, supporting the hypothesis that VVZ-149 may alleviate the affective component of pain and mitigate excessive use of opioids postoperatively.

01 Jan 2018·The Journal of Clinical Pharmacology

Safety, Tolerability, and Pharmacokinetic Characteristics of a Novel Nonopioid Analgesic, VVZ‐149 Injections in Healthy Volunteers: A First‐in‐Class, First‐in‐Human Study

Article

Author: Jang, Kyungho ; Yoon, Jangsoo ; Chung, Jae‐Yong ; Lee, Sang Rim ; Cho, Sunyoung ; Yu, Kyung‐Sang ; Kim, Anhye ; Lee, SeungHwan ; Lee, Doo H. ; Oh, Jaeseong

AbstractVVZ‐149, a dual antagonist of GlyT2 and 5HT2A receptors, is an investigational analgesic with a novel mechanism of action that is currently under early‐stage clinical development as an injectable agent for the treatment of postoperative pain. Here, the safety, tolerability, and pharmacokinetics of VVZ‐149 injections in healthy male volunteers were explored in a randomized, double‐blind, single‐ and multiple‐ascending‐dose (SAD and MAD, respectively), placebo‐controlled clinical study. Subjects randomly received a 4‐hour intravenous infusion of 0.25‐8 mg/kg VVZ‐149 or placebo in the SAD study (n = 46) or a 4‐hour intravenous infusion of 4–7 mg/kg VVZ‐149 or placebo twice daily for 3 days in the MAD study (n = 20). Serial blood and urine samples were collected for the pharmacokinetic analysis of VVZ‐149 and its active metabolite (VVZ‐368). Noncompartmental and compartmental pharmacokinetic analyses were performed. Various dosing scenarios were simulated to identify the adequate dosing regimen for the subsequent trials. Plasma exposure to VVZ‐149 and VVZ‐368 showed a dose‐proportional increase. VVZ‐149 did not accumulate in the plasma, whereas the plasma concentration of VVZ‐368 increased by 1.23‐ to 2.49‐fold after the fifth and sixth doses, respectively, in the MAD trial. Among the simulated dosing regimens, a loading dose followed by a maintenance dose was found to be an optimal dosing regimen, yielding the effective concentration estimated from animal studies in rat models of neuropathic or inflammatory pain. Single‐ or multiple‐dose administration of VVZ‐149 was generally well tolerated. These results showed that 0.5–8 mg/kg VVZ‐149 exhibited linear pharmacokinetic characteristics and can be safely administered in further clinical studies.

100 Deals associated with Opiranserin

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Opiranserin	-	DB16271

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Pain, Postoperative	NDA/BLA	US	Vivozon, Inc.	23 May 2019
Early gastric cancer	NDA/BLA	KR	Vivozon, Inc.	01 Aug 2015
Pain	NDA/BLA	-	Vivozon, Inc.	01 Jul 2014
Acute Pain	Phase 3	KR	Vivozon Pharmaceutical Co., Ltd. (Old)	19 Jul 2021