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

Post-Operative Pain Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02992041
• Other study ID #: VVZ149-POP-P2-US002
• Status: Completed
• Phase: Phase 2
• Start date: December 27, 2016
• Est. completion date: April 26, 2018

Study information

• Verified date: August 2020
• Source: Vivozon, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: April 26, 2018
• Est. primary completion date: April 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pain, Postoperative
• Post-Operative Pain

Intervention

Drug:
• VVZ-149 Injections
IV infusion of 900 or 1100 mg of VVZ-149
• Placebo
IV infusion of 0 mg of VVZ-149

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Vivozon, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	0hr=start of PCA, 1hr and 2 hours
Secondary	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	0-2, 2-4, 4-6, 6-8, 8-10, 10-12, and 12-24 hours
Secondary	Pain Intensity (Numeric Pain Rating Scale, NRS)	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
Secondary	Global measurement of subject satisfaction with study medication	Global assessment of subject satisfaction with analgesic management using a 5-point scale (0-4)	8 and 24 hours post-initiation of PCA
Secondary	Richmond Agitation Sedation Scale (RASS)		0, 1, 2, 4, 6, 8, 10, 12, and 24 hours post-initiation of PCA
Secondary	Respiratory Depression Assessment		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
Secondary	Post-Operative Nausea and Vomiting scale (PONV)		0, 4, 8, 12, and 24 hours post-initiation of PCA