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

August 18, 2020 updated by: Vivozon, Inc.

A Randomized, Double-Blind, Parallel Group, Placebo-Controlled Dose Finding 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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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. A clinical Phase 2 study performed in laparoscopic gastrectomy patients showed that patients who received VVZ-149 had reduced opioid consumption after surgery compared to those who received placebo, without any significant drug-related adverse events.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
69

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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, 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.
  • Surgical duration (from incision to end of closure) > 5 hours.

<Subject Characteristics>

  • Women with childbearing potential (age 18-55) must undergo blood pregnancy test at screening and then a urine pregnancy test preoperatively on day of surgery. Women with a positive pregnancy test will be excluded. Women of childbearing potential must agree to use at least one effective contraceptive method upon enrollment and for 30 days following the last dose of the investigational product.
  • 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 of antidepressants and anti-anxiety drugs, or procedure-related anti-anxiety drugs may be included.
  • Unstable or acute medical condition (e.g., unstable angina, congestive heart failure, renal failure, hepatic failure, AIDS).
  • Body weight under 55 kg.

<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 opioids or antipsychotics. However, subjects who receive procedure-related opioids (i.e., for a preoperative colonoscopy) may be included.
  • Alcohol consumption within 24 hours of surgery.
  • Use of nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen within 24 hours of surgery. Exception: use of aspirin for cardiovascular prophylaxis is acceptable.
  • 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 for males and > 470 msec for females) at Screening.

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
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
PLACEBO_COMPARATOR: Placebo
Drug: Placebo
IV infusion of 0 mg of VVZ-149
EXPERIMENTAL: Lower dose VVZ-149 Injections
Drug: VVZ-149 Injections
IV infusion of 900 or 1100 mg of VVZ-149
Other Names:
  • Opiranserin Injections
EXPERIMENTAL: Higher dose VVZ-149 Injections
Drug: VVZ-149 Injections
IV infusion of 900 or 1100 mg of VVZ-149
Other Names:
  • Opiranserin Injections

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
area under the curve (AUC) of Pain Intensity
Time Frame: 0hr=start of PCA, 1hr and 2 hours
area under the curve (AUC) of Pain Intensity using Numeric Pain Rating Scale (NRS, 0-10 at rest) measured up to 2 hours post-initiation of PCA
0hr=start of PCA, 1hr and 2 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Opioid Consumption up to 24 hours post-dosing of study drug
Time Frame: 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, and 12-24 hours
Total amount of hydromorphone (including rescue doses) consumption up to 24 hours after starting PCA
0-2, 2-4, 4-6, 6-8, 8-10, 10-12, and 12-24 hours
Pain Intensity (Numeric Pain Rating Scale, NRS)
Time Frame: 0, 1, 2, 4, 6, 8, 10, 12, and 24 hours
Pain Intensity (NRS at rest) measured up to 24 hours post-initiation of PCA
0, 1, 2, 4, 6, 8, 10, 12, and 24 hours
Global measurement of subject satisfaction with study medication
Time Frame: 8 and 24 hours post-initiation of PCA
Global assessment of subject satisfaction with analgesic management using a 5-point scale (0-4)
8 and 24 hours post-initiation of PCA
Richmond Agitation Sedation Scale (RASS)
Time Frame: 0, 1, 2, 4, 6, 8, 10, 12, and 24 hours post-initiation of PCA
0, 1, 2, 4, 6, 8, 10, 12, and 24 hours post-initiation of PCA
Respiratory Depression Assessment
Time Frame: 0, 1, 2, 4, 6, 8, 10, 12, 24 hours post-initiation of PCA and within 10 minutes prior to administering any rescue doses of hydromorphone
0, 1, 2, 4, 6, 8, 10, 12, 24 hours post-initiation of PCA and within 10 minutes prior to administering any rescue doses of hydromorphone
Post-Operative Nausea and Vomiting scale (PONV)
Time Frame: 0, 4, 8, 12, and 24 hours post-initiation of PCA
0, 4, 8, 12, and 24 hours post-initiation of PCA

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Vivozon, Inc.

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 27, 2016

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2018

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 26, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 9, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 9, 2016

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 14, 2016

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 25, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 18, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • VVZ149-POP-P2-US002

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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