Evaluate the Analgesic Efficacy and Safety of VVZ-149 Injection for Post-operative Pain Following Gastrectomy

A Randomized, Double-Blind, Parallel Group, Placebo-Controlled Stdy to Evaluate the Analgesic Efficacy and Safety of VVZ-149 Injection for Post-operative Pain Following Laparoscopic or Robotic-assisted Laparoscopic Gastrectomy

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, and placebo-controlled study.

Study Overview

• Status: Completed
• Conditions: Post-Operative Pain
• Intervention / Treatment: Drug: VVZ-149 injections; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Yonsei University Health System, Severance Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient between the ages of 25 and 70 years old
2. Male patient, in the case of female patient, postmenopausal women, or women physically incapable of childbearing
3. Subject who underwent surgery specially for the clinical study
4. Ability to provide written informed consent prior to any study procedures.
5. Ability to understand study procedures and communicate clearly with the investigator and staff.
6. Subjects with body weight under 100kg and body mass index (BMI) level lower than 35 kg/m2, inclusive

Exclusion Criteria:

< Surgical Factors >

1. Emergency or unplanned surgery.
2. Repeat operation (e.g., previous surgery within 30 days for same condition).

3. Cancer-related condition causing preoperative pain in site of surgery.

   < Subject Characteristics >

4. Women with childbearing potential, Women who are pregnant or breastfeeding.
5. Chronic pain diagnosis (e.g., ongoing pain at baseline with NRS ≥ 4/10).
6. 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.
7. Unstable or acute medical condition (e.g., unstable angina, congestive heart failure, renal failure, hepatic failure, AIDS).

8. Subjects who have long PR (>200msec) or prolonged QTc (> 450msec in male, >470msec in female) at Screening

   < Drug, Alcohol, and Pharmacological Considerations >

9. History of alcohol, opiate or other drug abuse or dependence within 12 months prior to Screening .
10. Ongoing or recent (within 30 days prior to surgery) use of steroids, opioids, or antipsychotics.
11. Alcohol consumption within 24 hours of surgery.
12. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen within 24 hours of surgery.

13. 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 >

14. Use of neuraxial or regional anesthesia related to the surgery.
15. Use of ketamine, gabapentin, pregabalin, or lidocaine (>1 mg/kg) intra or peri-operatively, or within 24 hours of surgery.
16. Subject with known allergies to hydromorphone.
17. Subjects who received another investigational drug within 30 days of scheduled surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VVZ-149 injection; VVZ-149 injections will be mixed with saline, then intravenous infusion for 10hr. The drug product will be administrated with a loading dose of 1.8 mg/kg for 0.5 hour followed by a maintenance dose of 1.3 mg/kg/h for 9.5 hours.	Drug: VVZ-149 injections; Colorless, transparent liquid in water for injection; Other Names: VVZ-149 injection
Placebo Comparator: Placebo; Placebo group will receive an water for injection the same volume and period of experimental group.	Drug: Placebo; water for injection; Other Names: water for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Pain Intensity	Change of Pain Intensity assessed on the Numerical Rating Scale (NRS) using a 10-point scale up to 24 hours	prior toPCA, at 1, 2, 4, 6, 8, 10, 24 hours post-dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Difference of Opioid Consumption between Study Groups	0-2, 2-4, 4-6, 6-8, 8-10, 10-12, 12-14, 14-16, 16-18, 18-20, 20-22, 22-24 hours post-dose
Pain Intensity Difference (PID) using Numerical Pain Rating Scale (NRS, 0-10) up to 24 hours	1, 2, 4, 6, 8, 10, 24 hours post-dose
Global measurement of patient satisfaction assessed on the questionnarie (0-5 points scale)	10, 24 hours post-dose

Collaborators and Investigators

• Sponsor: Vivozon, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2016
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: July 17, 2016
• First Submitted That Met QC Criteria: July 21, 2016
• First Posted (Estimate): July 26, 2016

Study Record Updates

• Last Update Posted (Actual): November 1, 2017
• Last Update Submitted That Met QC Criteria: October 31, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative
• Other Study ID Numbers: PT-VVZ149-05