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
Overview
- Phase
- Phase 2
- Intervention
- VVZ-149 Injections
- Conditions
- Post-Operative Pain
- Sponsor
- Vivozon, Inc.
- Enrollment
- 60
- Locations
- 3
- Primary Endpoint
- Sum of Pain Intensity Difference over 8-hours post-dose (SPID8)
- Status
- Completed
- Last Updated
- 5 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Men and women age between 18-70, inclusive.
- •Pain intensity (NRS) ≥4 at initial post-operative measurement in PACU.
- •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.
- •\< Subject Characteristics \>
- •Women with childbearing potential (Women age 18-55 must undergo pregnancy test).
- •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 (same dose \>30 days) of antidepressants and anti-anxiety drugs may be included.
- •Unstable or acute medical condition (e.g., unstable angina, congestive heart failure, renal failure, hepatic failure, AIDS).
Arms & Interventions
VVZ-149 Injections
Intervention: VVZ-149 Injections
Placebo
Intervention: Placebo
Outcomes
Primary Outcomes
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
Secondary Outcomes
- Change of Richmond Agitation-Sedation Scale(9 and 24 hours post-dose)
- Change of Pain Intensity (NRS)(9 and 24 hours post-dose)
- Change of Pain Relief (PR) assessed using a 6-point categorical scale(9 and 24 hours post-dose)
- Comparison of Global Measurement of Subject Satisfaction between Study Groups(8 and 24 hours post-dose)
- Change of Incidence of Postoperative Nausea and Vomiting(8 and 24 hours post-dose)
- Difference of Opioid Consumption between Study Groups(0-2, 2-4, 4-6, 6-8, 8-12, 12-16, and 16-24 hours post-dose)