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

August 18, 2020 updated by: Vivozon, Inc.

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

60

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Exclusion Criteria:

< Surgical Factors >

  1. Emergency or unplanned surgery.
  2. Repeat operation (e.g., previous surgery within 30 days for same condition).

  3. Cancer-related condition causing preoperative pain in site of surgery.

    < Subject Characteristics >

  4. Women with childbearing potential (Women age 18-55 must undergo pregnancy test).
  5. Women who are pregnant or breastfeeding.
  6. Chronic pain diagnosis (e.g., ongoing pain at baseline with NRS ≥ 4/10).
  7. 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.

  8. Unstable or acute medical condition (e.g., unstable angina, congestive heart failure, renal failure, hepatic failure, AIDS).

    < Drug, Alcohol, and Pharmacological Considerations >

  9. Renal or hepatic impairment.
  10. 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).
  11. Ongoing or recent (within 30 days prior to surgery) use of steroids, opioids, or antipsychotics.
  12. Alcohol consumption within 24 hours of surgery.
  13. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen within 24 hours of surgery.

  14. 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 >

  15. Use of neuraxial or regional anesthesia related to the surgery.
  16. Use of local anesthetic wound infiltration > 20 ml of 1% lidocaine
  17. Use of ketamine, gabapentin, pregabalin, or lidocaine (>1 mg/kg) intra or peri-operatively, or within 24 hours of surgery.
  18. Subjects with known allergies to hydromorphone.
  19. Subjects who received another investigational drug within 30 days of scheduled surgery.
  20. Subjects who have long PR (>200 msec) or prolonged QTc (> 450 msec) at Screening or on an EKG done immediately prior to dosing.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Drug: Placebo
Placebo group will receive the corresponding amount of placebo.
Experimental: VVZ-149 Injections
Drug: VVZ-149 Injections
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.
Other Names:
  • Opiranserin Injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sum of Pain Intensity Difference over 8-hours post-dose (SPID8)
Time Frame: 8 hours post-dose
SPID8 using Numerical Pain Rating Scale (NRS, 0-10) measured up to 8 hours post-dose
8 hours post-dose

Secondary Outcome Measures

Outcome Measure
Time Frame
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
0-2, 2-4, 4-6, 6-8, 8-12, 12-16, and 16-24 hours post-dose
Change of Pain Intensity (NRS)
Time Frame: 9 and 24 hours post-dose
9 and 24 hours post-dose
Change of Pain Relief (PR) assessed using a 6-point categorical scale
Time Frame: 9 and 24 hours post-dose
9 and 24 hours post-dose
Comparison of Global Measurement of Subject Satisfaction between Study Groups
Time Frame: 8 and 24 hours post-dose
8 and 24 hours post-dose
Change of Richmond Agitation-Sedation Scale
Time Frame: 9 and 24 hours post-dose
9 and 24 hours post-dose
Change of Incidence of Postoperative Nausea and Vomiting
Time Frame: 8 and 24 hours post-dose
8 and 24 hours post-dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vivozon, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 28, 2015

Primary Completion (Actual)

August 1, 2016

Study Completion (Actual)

August 15, 2016

Study Registration Dates

First Submitted

June 18, 2015

First Submitted That Met QC Criteria

June 30, 2015

First Posted (Estimate)

July 3, 2015

Study Record Updates

Last Update Posted (Actual)

August 25, 2020

Last Update Submitted That Met QC Criteria

August 18, 2020

Last Verified

March 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VVZ149-POP-P2-US001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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