- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02992041
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
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.
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
Interventional
Enrollment (Actual)
69
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
-
-
Massachusetts
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Boston, Massachusetts, United States, 02115
- Brigham and Women's Hospital
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Boston, Massachusetts, United States, 02114
- Massachusetts General Hospital
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-
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 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 |
Intervention / Treatment |
---|---|
PLACEBO_COMPARATOR: Placebo
|
IV infusion of 0 mg of VVZ-149
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EXPERIMENTAL: Lower dose VVZ-149 Injections
|
IV infusion of 900 or 1100 mg of VVZ-149
Other Names:
|
EXPERIMENTAL: Higher dose VVZ-149 Injections
|
IV infusion of 900 or 1100 mg of VVZ-149
Other Names:
|
What is the study measuring?
Primary Outcome Measures
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
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)
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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
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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
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)
December 27, 2016
Primary Completion (ACTUAL)
April 1, 2018
Study Completion (ACTUAL)
April 26, 2018
Study Registration Dates
First Submitted
December 9, 2016
First Submitted That Met QC Criteria
December 9, 2016
First Posted (ESTIMATE)
December 14, 2016
Study Record Updates
Last Update Posted (ACTUAL)
August 25, 2020
Last Update Submitted That Met QC Criteria
August 18, 2020
Last Verified
August 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID 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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