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Evaluate the Analgesic Efficacy and Safety of VVZ-149 Injections for Post-Operative Pain Following Colorectal Surgery

Primary Purpose

Post-Operative Pain

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

VVZ-149 Injections

Placebo

About this trial

This is an interventional treatment trial for Post-Operative Pain

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Men and women age between 18-70, inclusive.
Pain intensity (NRS) ≥4 at initial post-operative measurement in PACU.
Subjects undergoing planned laparoscopic colorectal surgery.
Ability to provide written informed consent.
Ability to understand study procedures and communicate clearly with the investigator and staff.
American Society of Anesthesiologists (ASA) risk class of I to III.

Exclusion Criteria:

< Surgical Factors >

Emergency or unplanned surgery.
Repeat operation (e.g., previous surgery within 30 days for same condition).
Cancer-related condition causing preoperative pain in site of surgery.
< Subject Characteristics >
Women with childbearing potential (Women age 18-55 must undergo pregnancy test).
Women who are pregnant or breastfeeding.
Chronic pain diagnosis (e.g., ongoing pain at baseline with NRS ≥ 4/10).
Unstable or poorly controlled psychiatric condition (e.g., untreated PTSD, anxiety, or depression) Subjects who take stable doses (same dose >30 days) of antidepressants and anti-anxiety drugs may be included.
Unstable or acute medical condition (e.g., unstable angina, congestive heart failure, renal failure, hepatic failure, AIDS).
< Drug, Alcohol, and Pharmacological Considerations >
Renal or hepatic impairment.
History of alcohol, opiate or other drug abuse or dependence within 12 months prior to Screening (TICS alcohol/drug screen will be performed at Screening).
Ongoing or recent (within 30 days prior to surgery) use of steroids, opioids, or antipsychotics.
Alcohol consumption within 24 hours of surgery.
Use of nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen within 24 hours of surgery.
Use of herbal agents or nutraceuticals (i.e., chaparral, comfrey, germander, jin bu huan, kava, pennyroyal, skullcap, St. John's wort, or valerian) within 7 days prior to surgery.
< Anesthetic and Other Exclusion Considerations >
Use of neuraxial or regional anesthesia related to the surgery.
Use of local anesthetic wound infiltration > 20 ml of 1% lidocaine
Use of ketamine, gabapentin, pregabalin, or lidocaine (>1 mg/kg) intra or peri-operatively, or within 24 hours of surgery.
Subjects with known allergies to hydromorphone.
Subjects who received another investigational drug within 30 days of scheduled surgery.
Subjects who have long PR (>200 msec) or prolonged QTc (> 450 msec) at Screening or on an EKG done immediately prior to dosing.

Sites / Locations

Massachusetts General Hospital
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

VVZ-149 Injections

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Sum of Pain Intensity Difference over 8-hours post-dose (SPID8)

SPID8 using Numerical Pain Rating Scale (NRS, 0-10) measured up to 8 hours post-dose

Secondary Outcome Measures

Difference of Opioid Consumption between Study Groups

Change of Pain Intensity (NRS)

Change of Pain Relief (PR) assessed using a 6-point categorical scale

Comparison of Global Measurement of Subject Satisfaction between Study Groups

Change of Richmond Agitation-Sedation Scale

Change of Incidence of Postoperative Nausea and Vomiting

Full Information

NCT ID

NCT02489526

First Posted

June 18, 2015

Last Updated

August 18, 2020

Sponsor

Vivozon, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02489526

Brief Title

Evaluate the Analgesic Efficacy and Safety of VVZ-149 Injections for Post-Operative Pain Following Colorectal Surgery

Official Title

A Randomized, Double-Blind, Parallel Group, Placebo-Controlled Study to Evaluate the Analgesic Efficacy and Safety of VVZ-149 Injections for Post-Operative Pain Following Laparoscopic Colorectal Surgery

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Completed

Study Start Date

September 28, 2015 (Actual)

Primary Completion Date

August 2016 (Actual)

Study Completion Date

August 15, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Vivozon, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this Phase 2 study is to evaluate the efficacy and safety of an analgesic drug candidate, VVZ-149 Injections. The study is designed as randomized, double-blind, parallel, placebo-controlled study.

Detailed Description

VVZ-149 is a dual antagonist of GlyT2 and 5HT2A. GlyT2 blockage increases inhibitory synaptic transmission by glycine in the spinal cord, resulting in a reduction of pain transmissions to the brain. 5HT2A blockage decreases descending serotonergic facilitatory modulation on pain transmission by the brain and reduces nociceptor activation in peripheral nerves, which are primary sources of pain in post-surgical pain. VVZ-149 has been shown to have comparable efficacy to morphine in well controlled (blind, complete randomization with a positive control) animal studies using rat models of post-operative pain and formalin-induced pain. The PK/PD study in animals indicates that therapeutic plasma concentration in human subjects will be 600-1,900 ng/ml. A clinical Phase 1 study performed in healthy subjects has shown no clinically significant adverse events up to a plasma concentration level of 3,261 ng/ml other than brief symptoms of mild nausea or dizziness, and mild somnolence when the plasma exposure level is more than 2,000 ng/ml.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Post-Operative Pain

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

VVZ-149 Injections

Arm Type

Experimental

Arm Title

Placebo

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

VVZ-149 Injections

Other Intervention Name(s)

Opiranserin Injections

Intervention Description

Experimental group will receive a loading dose of 1.8 mg/kg VVZ-149 intravenous infusion for 0.5 hour followed by a maintenance dose of 1.3 mg/kg/h VVZ-149 intravenous infusion for 7.5 hours.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo group will receive the corresponding amount of placebo.

Primary Outcome Measure Information:

Title

Sum of Pain Intensity Difference over 8-hours post-dose (SPID8)

Description

SPID8 using Numerical Pain Rating Scale (NRS, 0-10) measured up to 8 hours post-dose

Time Frame

8 hours post-dose

Secondary Outcome Measure Information:

Title

Difference of Opioid Consumption between Study Groups

Time Frame

0-2, 2-4, 4-6, 6-8, 8-12, 12-16, and 16-24 hours post-dose

Title

Change of Pain Intensity (NRS)

Time Frame

9 and 24 hours post-dose

Title

Change of Pain Relief (PR) assessed using a 6-point categorical scale

Time Frame

9 and 24 hours post-dose

Title

Comparison of Global Measurement of Subject Satisfaction between Study Groups

Time Frame

8 and 24 hours post-dose

Title

Change of Richmond Agitation-Sedation Scale

Time Frame

9 and 24 hours post-dose

Title

Change of Incidence of Postoperative Nausea and Vomiting

Time Frame

8 and 24 hours post-dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Men and women age between 18-70, inclusive. Pain intensity (NRS) ≥4 at initial post-operative measurement in PACU. Subjects undergoing planned laparoscopic colorectal surgery. Ability to provide written informed consent. Ability to understand study procedures and communicate clearly with the investigator and staff. American Society of Anesthesiologists (ASA) risk class of I to III. Exclusion Criteria: < Surgical Factors > Emergency or unplanned surgery. Repeat operation (e.g., previous surgery within 30 days for same condition). Cancer-related condition causing preoperative pain in site of surgery. < Subject Characteristics > Women with childbearing potential (Women age 18-55 must undergo pregnancy test). Women who are pregnant or breastfeeding. Chronic pain diagnosis (e.g., ongoing pain at baseline with NRS ≥ 4/10). Unstable or poorly controlled psychiatric condition (e.g., untreated PTSD, anxiety, or depression) Subjects who take stable doses (same dose >30 days) of antidepressants and anti-anxiety drugs may be included. Unstable or acute medical condition (e.g., unstable angina, congestive heart failure, renal failure, hepatic failure, AIDS). < Drug, Alcohol, and Pharmacological Considerations > Renal or hepatic impairment. History of alcohol, opiate or other drug abuse or dependence within 12 months prior to Screening (TICS alcohol/drug screen will be performed at Screening). Ongoing or recent (within 30 days prior to surgery) use of steroids, opioids, or antipsychotics. Alcohol consumption within 24 hours of surgery. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen within 24 hours of surgery. Use of herbal agents or nutraceuticals (i.e., chaparral, comfrey, germander, jin bu huan, kava, pennyroyal, skullcap, St. John's wort, or valerian) within 7 days prior to surgery. < Anesthetic and Other Exclusion Considerations > Use of neuraxial or regional anesthesia related to the surgery. Use of local anesthetic wound infiltration > 20 ml of 1% lidocaine Use of ketamine, gabapentin, pregabalin, or lidocaine (>1 mg/kg) intra or peri-operatively, or within 24 hours of surgery. Subjects with known allergies to hydromorphone. Subjects who received another investigational drug within 30 days of scheduled surgery. Subjects who have long PR (>200 msec) or prolonged QTc (> 450 msec) at Screening or on an EKG done immediately prior to dosing.

Facility Information:

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Brigham and Women's Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

Beth Israel Deaconess Medical Center

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

34794108

Citation

Nedeljkovic SS, Song I, Bao X, Zeballos JL, Correll DJ, Zhang Y, Ledley JS, Bhandari A, Bai X, Lee SR, Cho S. Exploratory study of VVZ-149, a novel analgesic molecule, in the affective component of acute postoperative pain after laparoscopic colorectal surgery. J Clin Anesth. 2022 Feb;76:110576. doi: 10.1016/j.jclinane.2021.110576. Epub 2021 Nov 15.

Results Reference

derived

PubMed Identifier

33624798

Citation

Song I, Cho S, Nedeljkovic SS, Lee SR, Lee C, Kim J, Bai SJ. 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. Pain Med. 2021 Sep 8;22(9):2037-2049. doi: 10.1093/pm/pnab066.

Results Reference

derived

PubMed Identifier

28213593

Citation

Nedeljkovic SS, Correll DJ, Bao X, Zamor N, Zeballos JL, Zhang Y, Young MJ, Ledley J, Sorace J, Eng K, Hamsher CP, Maniam R, Chin JW, Tsui B, Cho S, Lee DH. Randomised, double-blind, parallel group, placebo-controlled study to evaluate the analgesic efficacy and safety of VVZ-149 injections for postoperative pain following laparoscopic colorectal surgery. BMJ Open. 2017 Feb 17;7(2):e011035. doi: 10.1136/bmjopen-2016-011035.

Results Reference

derived

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Evaluate the Analgesic Efficacy and Safety of VVZ-149 Injections for Post-Operative Pain Following Colorectal Surgery

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