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.

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.

Inclusion Criteria:

1. Patient between the ages of 25 and 65 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
7. Single-side surgery patient

Exclusion Criteria:

< Surgical Factors >

1. Emergency or unplanned surgery.

2. Repeat operation

   < Subject Characteristics >

3. Women with childbearing potential, Women who are pregnant or breastfeeding.

4. Unstable or poorly controlled psychiatric condition (e.g., untreated PTSD, anxiety, or depression). Subjects who take stable doses of antidepressants and anti-anxiety drugs may be included.

5. Unstable or acute medical condition (e.g., unstable angina, congestive heart failure, renal failure, hepatic failure, AIDS).

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

   < Drug, Alcohol, and Pharmacological Considerations >

7. History of alcohol, opiate or other drug abuse or dependence within 12 months prior to Screening .

8. Ongoing or recent (within 6 hour prior to surgery) use of steroids, opioids, or antipsychotics.

9. Alcohol consumption within 24 hours of surgery.

10. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) or acetaminophen within 6 hours of surgery.

11. 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 >

12. Use of neuraxial or regional anesthesia related to the surgery.

13. Use of ketamine, gabapentin, pregabalin, or lidocaine (>1 mg/kg) intra or peri-operatively, or within 24 hours of surgery.

14. Subject with known allergies to hydromorphone.

15. Subjects who received another investigational drug within 30 days of scheduled surgery