Dose-Ranging Study for Prolonged Postoperative Analgesia in Subject Undergoing Total Knee Arthroplasty
Condition: Postoperative Pain
MeSH terms: Pain, Postoperative
Intervention: Bupivacaine HCl; SKY0402
Intervention description: 150 mg Bupivacaine HCl; 600 mg SKY0402 (study drug)
Intervention MeSH terms: Epinephrine; Bupivacaine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 138.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: pain; postoperative; total knee arthroplasty; analgesia

Summary:

      Dose-ranging study for prolonged postoperative analgesia in subjects undergoing total knee
      arthroplasty
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female, greater than or equal to 18 and less than or equal to 75 years of age
             at the Screening Visit.

          2. 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 primary unilateral total knee arthroplasty (TKA) under general
             anesthesia.

          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, 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 dosing.

          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 or concurrent surgery that may require
             analgesic treatment in the postoperative period for pain that is not strictly related
             to the surgical site administered study treatment, and which may confound the
             postoperative assessments (e.g., significant pain from other joints, chronic
             neuropathic pain, concurrent contralateral TKA, concurrent foot surgery, etc.).

          4. Body weight less than 50 kilograms (110 pounds) or morbid obesity.

          5. Contraindication to any of the pain-control agents planned for postoperative use
             (e.g., acetaminophen, morphine, oxycodone, ketorolac).

          6. 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.

          7. 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.

          8. History of, suspected, or known addiction to or abuse of illicit drug(s), prescription
             medicine(s), or alcohol within the past 2 years.

          9. Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the
             opinion of the Investigator, may interfere with study assessments or compliance.

         10. Current or historical evidence of any clinically significant disease or condition,
             especially cardiovascular or neurological conditions that, in the opinion of the
             Investigator, may increase the risk of surgery or complicate the subject's
             postoperative course.

         11. 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:

         12. Any clinically significant event or condition uncovered during surgery(e.g., excessive
             bleeding), which occurs before study drug administration, that might render the
             subject medically unstable or complicate the subject's postoperative course.