ZYNRELEF® for Postoperative Analgesia After Laparoscopic Sleeve Gastrectomy

Inclusion Criteria:

1. Is able to provide written informed consent.
2. Is able to adhere to the study visit schedule and complete all study assessments.
3. Is male or female or other, and ≥18 years of age at screening.
4. Is scheduled to undergo laparoscopic sleeve gastrectomy under general anesthesia
5. Has an American Society of Anesthesiologists Physical Status of I, II, or III.
6. Female subjects are eligible only if all the following apply:

• Not pregnant (female subjects of childbearing potential must have a negativeurine pregnancy test at screening and on Day 1 before surgery).
• Not lactating.
• Not planning to become pregnant during the study.
• Is surgically sterile (eg, has had a bilateral tubal ligation); or is at least 2years postmenopausal; or is in a monogamous relationship with a partner who issurgically sterile; or is practicing abstinence or agrees to use double-barriercontraception in the event of sexual activity; or is using an insertable,injectable, transdermal, or combination oral contraceptive approved by applicableregulatory authorities for greater than 2 months prior to screening and commitsto the use of an acceptable form of birth control for the duration of the studyand for 30 days after study drug administration. Note: women in only a same-sexrelationship do not need to meet this criterion.

Exclusion Criteria:

1. Has a contraindication or a known or suspected history of hypersensitivity orclinically significant idiosyncratic reaction to Ropivacaine (or other localanesthetics), meloxicam, acetaminophen, ketamine, fentanyl, hydromorphone ordexamethasone. Subjects in all cohorts must not have any contraindications to any ofthe protocol-specified drugs (Ropivacaine, bupivacaine, lidocaine, meloxicam,fentanyl, ketamine, acetaminophen, hydromorphone or dexamethasone).
2. Has been administered Ropivacaine within 5 days prior to the scheduled surgery.
3. Has been administered any local anesthetic within 72 hours prior to the scheduledsurgery, other than for pretreatment prior to a needle placement, to treat an AE thatoccurs after signing the ICF, or to decrease venous irritation (eg, caused bypropofol, in which case no more than a single administration of lidocaine 1% 20 mg IVmay be administered).
4. Has been administered systemic steroids within 5 half-lives or 10 days prior toadministration of the study drug (whichever is longer). Note that for purposes of thisexclusion criterion, inhaled, ophthalmic, and over-the-counter steroids are notconsidered systemic.
5. Has a medical condition such that, in the opinion of the Investigator, participatingin the study would pose a health risk to the subject or confound the postoperativeassessments. Conditions may include but are not limited to, any of the following:
6. History of asthma or urticarial/ allergic-type reactions after taking aspirin orNSAIDs.
7. History of clinically significant cardiac abnormality such as myocardialinfarction within 6 months prior to signing the ICF, New York Heart Associationclass III or IV, or clinically significant abnormalities of electrocardiogram (ECG) or cardiac function.
8. History of coronary artery bypass graft surgery within 12 months prior to signingthe ICF.
9. History of severe liver function impairment as defined by Child-Pugh Class C,having an aspartate aminotransferase >3 × the upper limit of normal (ULN) orhaving an alanine aminotransferase >3 × ULN.
10. History of severe kidney function impairment as defined by creatinine clearance (Cockcroft-Gault) <30 mL/min, being on dialysis, and/or having a serum creatinine >2 × ULN.
11. History of known or suspected coagulopathy or uncontrolled anticoagulation (PLTcount <100,000/μL; hemoglobin <12 g/dL; or hematocrit <35%).
12. Loss of sensation in extremities or significant peripheral neuropathy.
13. As per subject history and/or medical records, has active infection or is currentlyundergoing treatment for Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV).
14. Has uncontrolled anxiety, psychiatric, or neurological disorder that, in the opinionof the Investigator, might interfere with study assessments.
15. Had a malignancy in the last year, with the exception of nonmetastatic basal cell orsquamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
16. Has a known or suspected history of drug abuse over the last 6 months, a positive drugscreen on the day of surgery, or a recent history of alcohol abuse over the last 6months. Note: Subjects with a positive drug screen who are taking an allowed,prescribed medication that is known to result in a positive drug test (eg, amphetamineand dextroamphetamine for attention-deficit/hyperactivity disorder, benzodiazepine foranxiety disorder) may be eligible for participation in the study at the discretion ofthe Sponsor.
17. Previously participated in a ZYNRELEF® or HTX-011 study.
18. Received an investigational product or device in a clinical trial within 30 days orwithin 5 elimination half-lives (whichever is longer) prior to surgery, or is planningto take part in another clinical trial while participating in this study.
19. Has undergone 3 or more surgeries within 12 months prior to signing the InformedConsent Form, other than for diagnostic procedures (eg, colonoscopy)