Post-Operative PainPhase 2NCT02992041
Evaluate the Analgesic Efficacy and Safety of VVZ-149 Injections for Post-Operative Pain Following Laparoscopic Colorectomy
A Phase 2 study testing VVZ-149 Injections in people with Post-Operative Pain, run by Vivozon, Inc. at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Post-Operative Pain
- What is being tested?
- VVZ-149 Injections
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 69 participants
- Where
- 2 sitesUnited States
- Study dates
- 27 Dec 2016to 26 Apr 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- <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>
Show all 26Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
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
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.
Read the 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.
- Conditions
- Post-Operative Pain
- Being tested
- VVZ-149 Injections, Placebo
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VVZ-149 InjectionsDrug
Also called Opiranserin Injections
IV infusion of 900 or 1100 mg of VVZ-149
PlaceboDrug
IV infusion of 0 mg of VVZ-149
| Study group | Role | What they receive |
|---|---|---|
| Lower dose VVZ-149 Injections | Experimental | Not described Receives: Drug: VVZ-149 Injections |
| Higher dose VVZ-149 Injections | Experimental | Not described Receives: Drug: VVZ-149 Injections |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 0hr=start of PCA, 1hr and 2 hours
Secondary outcomes (6)
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
Measured: 0-2, 2-4, 4-6, 6-8, 8-10, 10-12, and 12-24 hours
Pain Intensity (Numeric Pain Rating Scale, NRS)
Pain Intensity (NRS at rest) measured up to 24 hours post-initiation of PCA
Measured: 0, 1, 2, 4, 6, 8, 10, 12, and 24 hours
Global measurement of subject satisfaction with study medication
Global assessment of subject satisfaction with analgesic management using a 5-point scale (0-4)
Measured: 8 and 24 hours post-initiation of PCA
Richmond Agitation Sedation Scale (RASS)
Measured: 0, 1, 2, 4, 6, 8, 10, 12, and 24 hours post-initiation of PCA
Respiratory Depression Assessment
Measured: 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)
Measured: 0, 4, 8, 12, and 24 hours post-initiation of PCA
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2016 (estimated)
- Study start27 Dec 2016
- Primary completionApr 2018
- Study completion26 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-Operative PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 69 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vivozon, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02992041
- Sponsor's protocol ID
- VVZ149-POP-P2-US002
- Status last verified
- Aug 2020
- First submitted
- 9 Dec 2016
- Last updated
- 25 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02992041
- Acronym / sponsor ID
- VVZ149-POP-P2-US002
- Conditions
- Post-Operative Pain
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 69 participants (actual)
- Lead sponsor
- Vivozon, Inc.Industry (pharma, biotech, devices)
- Study start
- 27 Dec 2016 (actual)
- Primary completion
- Apr 2018 (actual)
- Study completion
- 26 Apr 2018 (actual)
- First posted
- 14 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Lower dose VVZ-149 Injections | Experimental | Drug: VVZ-149 Injections |
| Higher dose VVZ-149 Injections | Experimental | Drug: VVZ-149 Injections |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (26 listed)
- <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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VVZ-149 InjectionsAlso: Opiranserin InjectionsIV infusion of 900 or 1100 mg of VVZ-149 | Drug | Higher dose VVZ-149 Injections, Lower dose VVZ-149 Injections |
| PlaceboIV infusion of 0 mg of VVZ-149 | Drug | Placebo |
Primary outcome
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
6 secondary outcomes
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
Pain Intensity (Numeric Pain Rating Scale, NRS)
Time frame: 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
Richmond Agitation Sedation Scale (RASS)
Time frame: 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
Post-Operative Nausea and Vomiting scale (PONV)
Time frame: 0, 4, 8, 12, and 24 hours post-initiation of PCA
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2020.
Related trials for Post-Operative Pain
RecruitingPhase 4
ESP Blocks for Posterior Spinal Fusion
Postoperative Pain
Recruiting
Effect of Cryotherapeutic and Nanotherapeutic Sodium Hypochlorite on Post-Operative Endodontic Pain.
Symptomatic Irreversible Pulpitis, Symptomatic Apical Periodontitis
RecruitingPhase 2
REctus Sheath Trial
Acute Pain, Postoperative Pain, Acute
Not yet recruiting
Effect of Pectoral Nerve Block (PECS) Using Magnesium Sulfate Added to Dexamethasone on Quality of Recovery and Chronic Post-Mastectomy Pain
Breast Cancer, Postoperative Pain
Active, not recruitingPhase 4
Effect of Dexmedetomidine on Postoperative Pain in Spinal Anesthesia for Cesarean Section at Assuit University Hospital
Cesarean Section
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing VVZ-149 Injections in people with Post-Operative Pain, run by Vivozon, Inc. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
area under the curve (AUC) of Pain Intensity (time frame: 0hr=start of PCA, 1hr and 2 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2020.