Ketorolac Applied by Continuous IV Infusion for Treatment of Moderately Severe Postoperative Pain Following Bunionectomy

Inclusion Criteria:

1. Written informed consent obtained prior to any study-related procedure beingperformed.

2. Male or female subjects between 18 and <65 years of age at time of consent.

3. Body weight ≥50 kg.

4. Physical status rated as ≤2 on the American Society of Anesthesiologists (ASA)rating scale (Owens, Felts et al. 1978).

5. Scheduled to undergo primary unilateral first metatarsal bunionectomy.

6. Women must be postmenopausal, surgically sterile, abstinent, or practicing or agreeto practice an effective method of birth control if they are sexually active beforeentry, throughout the study, and for 7 days after the last dose of study drug (effective methods of birth control include prescription hormonal contraceptives,intrauterine devices, double-barrier method, and male partner sterilization). Womenof childbearing potential must have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test at screening and a negative urine pregnancy test beforesurgery.

7. Subject is willing and able to complete all study procedures including training onpain scales, follow instructions, communicate meaningfully with study personnel, andreturn for all visits as listed in the protocol.

Exclusion Criteria:

1. History of peptic ulcer disease, GI bleeding, perforation, or active peptic ulcerdisease.

2. History of asthma, urticaria, or allergic-type reactions after taking aspirin orother NSAIDs.

3. History of, or suspected or confirmed, cerebrovascular bleeding, hemorrhagicdiathesis, or incomplete hemostasis.

4. Increased risk of bleeding at the discretion of the Investigator based onprior/concomitant disease, laboratory values, medication or surgical complications.

5. Clinical laboratory values reflecting at least mild renal insufficiency as indicatedby a creatinine clearance ≤89 mL/min.

6. Risk for renal failure due to volume depletion at the discretion of theInvestigator.

7. Concomitant use of aspirin or NSAIDs.

8. History of seizure disorder or epilepsy, as suggested by the presence of any of thefollowing:

• Mild or moderate traumatic brain injury, stroke, transient ischemic attach, orbrain neoplasm within 1 year of screening.

• Severe traumatic brain injury, episode(s) of unconsciousness of more than 24hours duration, or posttraumatic amnesia of more than 24 hours duration within 15 years of screening.

9. History of alcohol or drug abuse in the Investigator's judgement based on subjecthistory and physical examination.

10. Significant chronic obstructive pulmonary disease or cor pulmonale, a substantiallydecreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratorydepression.

11. At least moderately impaired hepatic function (Child-Pugh >6), or subjects withalanine aminotransferase (ALT) or aspartate aminotransferase (AST) values greaterthan 3 times the upper limit of normal (ULN).

12. Concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within thelast 14 days.

13. The subject is not on a stable dose (at least 2 weeks prior to Screening Visit) ofmedications that may lower the seizure threshold (e.g., anti-psychotic agents) orwhich impact the serotonergic system (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclicantidepressants).

14. Evidence of significant anemia (indicated by hemoglobin concentration ≤8 g/dL).

15. Evidence of active infections that may spread to other areas of the body (e.g.,osteomyelitis, pyogenic infection of the hip, Hepatitis B or C, or other overtinfections) or a history of human immunodeficiency virus (HIV) 1 or 2.

16. History of malignancy within 2 years prior to the start of the study, with theexception of basal cell and cutaneous squamous cell carcinoma.

17. History of systemic lupus erythematosus, antiphospholipid syndrome, vasculitis,vasculopathy, or deep vein thrombosis.

18. Uncontrolled or poorly controlled post-traumatic stress disorder, generalizedanxiety disorder, depression, psychiatric, or other significant medical conditions.

19. Chronic systemic steroid therapy, excluding inhalers or a 1-time intraoperativedose, within 4 weeks before screening.

20. History of pending litigation due to pain or disability.

21. Clinically significant disease that, in the Investigator's opinion, may affectefficacy or safety assessments.

22. Employees of the Investigator or study site with direct involvement in the proposedstudy or other studies under the direction of that Investigator or study site,including family members of the employees or the Investigator.

23. Received an experimental drug or used an experimental medical device within 30 daysbefore screening or have participated in a previous study of ketorolac.

24. Contraindications to, or history of allergy or hypersensitivity to ketorolac and/ormorphine and their excipients.

25. A positive COVID-19 test (rapid antigen test) or COVID-19 related symptoms atscreening and/or at check in of Visit 2 (Surgical Period).

26. Subjects who are planning on receiving a COVID-19 vaccine during the study duration.