Phase 2 Dose-Ranging Study of SKY0402 for Prolonged Postoperative Analgesia in Subject Undergoing Hemorrhoidectomy
Condition: Postoperative Pain
MeSH terms: Pain, Postoperative
Intervention: SKY0402; Bupivacaine HCl
Intervention description: SKY0402; Bupivacaine HCl
Intervention MeSH terms: Epinephrine; Bupivacaine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 100.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: hemorrhoidectomy; pain; Postoperative; analgesia

Summary:

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

Eligibility criteria:

        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.