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

NCT ID: NCT02844725

Last Updated: 2017-11-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2017-02-28

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, and 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.

Conditions

Post-Operative Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

VVZ-149 injections

Intervention Type: DRUG

Colorless, transparent liquid in water for injection

Placebo

Placebo group will receive an water for injection the same volume and period of experimental group.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

water for injection

Interventions

VVZ-149 injections

Colorless, transparent liquid in water for injection

Intervention Type: DRUG

Placebo

water for injection

Intervention Type: DRUG

Other Intervention Names

VVZ-149 injection; water for injection

Eligibility Criteria

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

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vivozon, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Seonjun Bae, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Yonsei University Health System, Severance Hospital

Locations

Yonsei University Health System, Severance Hospital

Seoul, , South Korea

Countries

South Korea

Other Identifiers

PT-VVZ149-05

Identifier Type: -

Identifier Source: org_study_id