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

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

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:

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.

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.

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.

Sites / Locations

Massachusetts General Hospital
Brigham and Women's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Lower dose VVZ-149 Injections

Higher dose VVZ-149 Injections

Placebo

Arm Description

Outcomes

Primary Outcome Measures

area under the curve (AUC) of Pain Intensity

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

Secondary Outcome Measures

Opioid Consumption up to 24 hours post-dosing of study drug

Total amount of hydromorphone (including rescue doses) consumption up to 24 hours after starting PCA

Pain Intensity (Numeric Pain Rating Scale, NRS)

Pain Intensity (NRS at rest) measured up to 24 hours post-initiation of PCA

Global measurement of subject satisfaction with study medication

Global assessment of subject satisfaction with analgesic management using a 5-point scale (0-4)

Richmond Agitation Sedation Scale (RASS)

Respiratory Depression Assessment

Post-Operative Nausea and Vomiting scale (PONV)

Full Information

NCT ID

NCT02992041

First Posted

December 9, 2016

Last Updated

August 18, 2020

Sponsor

Vivozon, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02992041

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2020

Overall Recruitment Status

Completed

Study Start Date

December 27, 2016 (Actual)

Primary Completion Date

April 2018 (Actual)

Study Completion Date

April 26, 2018 (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. 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.

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

69 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Lower dose VVZ-149 Injections

Arm Type

Experimental

Arm Title

Higher dose 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

IV infusion of 900 or 1100 mg of VVZ-149

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

IV infusion of 0 mg of VVZ-149

Primary Outcome Measure Information:

Title

area under the curve (AUC) of Pain Intensity

Description

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

Time Frame

0hr=start of PCA, 1hr and 2 hours

Secondary Outcome Measure Information:

Title

Opioid Consumption up to 24 hours post-dosing of study drug

Description

Total amount of hydromorphone (including rescue doses) consumption up to 24 hours after starting PCA

Time Frame

0-2, 2-4, 4-6, 6-8, 8-10, 10-12, and 12-24 hours

Title

Pain Intensity (Numeric Pain Rating Scale, NRS)

Description

Pain Intensity (NRS at rest) measured up to 24 hours post-initiation of PCA

Time Frame

0, 1, 2, 4, 6, 8, 10, 12, and 24 hours

Title

Global measurement of subject satisfaction with study medication

Description

Global assessment of subject satisfaction with analgesic management using a 5-point scale (0-4)

Time Frame

8 and 24 hours post-initiation of PCA

Title

Richmond Agitation Sedation Scale (RASS)

Time Frame

0, 1, 2, 4, 6, 8, 10, 12, and 24 hours post-initiation of PCA

Title

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

Title

Post-Operative Nausea and Vomiting scale (PONV)

Time Frame

0, 4, 8, 12, and 24 hours post-initiation of PCA

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

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

12. IPD Sharing Statement

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

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