Phase 2 Dose-Ranging Study of SKY0402 for Prolonged Postoperative Analgesia in Subject Undergoing Hemorrhoidectomy

A Phase 2 Multicenter, Randomized, Double-blind, Parallel-group, Active-control, Dose-ranging Study to Evaluate the Safety and Efficacy of a Single Administration of SKY0402 for Prolonged Postoperative Analgesia in Subject Undergoing Hemorrhoidectomy

Phase 2 study to evaluate three dose levels of SKY0402 compared with 75 mg of bupivacaine HCl.

Effective postoperative pain control is a critical element in patient recovery, as the majority of patients may experience significant pain, particularly in the first few days following surgery. Appropriate postoperative pain management contributes to improved healing, faster patient mobilization, shortened hospital stays, and reduced healthcare costs.

Inclusion Criteria:

1. Male or female, 18 years of age and older at the Screening Visit.
2. Applies to female subjects only: Postmenopausal, surgically sterile, or willing to use acceptable means of contraception for at least 30 days after surgery including any of the following: hormonal contraceptives (e.g., oral, injectable, implantable starting at least 30 days before study drug administration), effective double-barrier methods (e.g., condoms with spermicide), intrauterine device, lifestyle with a personal choice of abstinence, nonheterosexual lifestyle, or a strictly monogamous relationship with a partner who has had a vasectomy.
3. Scheduled to undergo 2- or 3-column excisional hemorrhoidectomy under general anesthesia using Milligan Morgan or Ferguson-type techniques, including modified approaches with specialized instruments, such as LigaSure™ or harmonic scalpel, with a cumulative incision length of a minimum 3 cm.
4. American Society of Anesthesiology (ASA) Physical Class 1-3.
5. Able and willing to comply with all study visits and procedures.
6. Able to speak, read, and understand the language of the Informed Consent Form (ICF), study questionnaires, and other instruments used for collecting subject-reported outcomes, in order to enable accurate and appropriate responses to pain scales and other required study assessments.
7. Willing and capable of providing written informed consent.

Exclusion Criteria:

1. Pregnancy, nursing, or planning to become pregnant during the study or within one month after study drug administration.

2. Use of any of the following medications within the times specified before surgery:

   • Long-acting opioid medication within 3 days.
   • Any opioid medication within 24 hours.

3. Concurrent painful physical condition that may require analgesic treatment in the postoperative period for pain that is not surgically related and may confound the postoperative assessments (e.g., rheumatoid arthritis, chronic neuropathic pain).

4. Single-column hemorrhoidectomy or hemorrhoidectomy without an internal component.

5. Body weight less than 50 kilograms (110 pounds).

6. History of hypersensitivity or idiosyncratic reactions to amide-type local anesthetics or to opioid medication.

7. Contraindication to epinephrine, such as concurrent administration of monoamine oxidase (MAO) inhibitors or antidepressants of amitriptyline or imipramine types, conditions where the production or exacerbation of tachycardia could prove fatal (e.g., poorly controlled thyrotoxicosis or severe heart disease), or any other pathological conditions that might be aggravated by the effects of epinephrine.

8. Contraindications to any of the pain-control agents planned for postoperative use (e.g., acetaminophen [paracetamol], oxycodone, morphine, ketorolac).

9. Administration of an investigational drug within 30 days or 5 elimination half-lives of such investigational drug, whichever is longer, prior to study drug administration, or planned administration of another investigational product or procedure during the subject's participation in this study.

10. History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.

11. Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the Investigator, may interfere with study assessments or compliance.

12. Significant medical conditions or laboratory results that, in the opinion of the Investigator, indicate an increased vulnerability to study drugs and procedures, and expose the subject to an unreasonable risk as a result of participating in this clinical trial, such as: debilitating diseases, acute illnesses, hypotension, partial or complete conduction block, impaired cardiac function, untreated hypertension, advanced arteriosclerotic heart disease, cerebral vascular insufficiency, pre-existing abnormal neurological or neuromuscular disease (e.g., epilepsy, myasthenia gravis), advanced liver disease, severe renal impairment, advanced diabetes, comorbid conditions associated with an immunocompromised status, such as blood dyscrasias, HIV/AIDS, or recent chemotherapy.

    In addition, the subject will be ineligible to receive study drug if he or she meets the following criteria during surgery:

13. Any clinically significant event or condition uncovered during the surgery (e.g., excessive bleeding, acute sepsis) that might render the subject medically unstable or complicate the subject's postoperative course.

14. A cumulative incision length less than 3 cm.