A Phase 3 Study to Evaluate the Safety and Efficacy of SKY0402 in Subjects Undergoing Total Knee Arthroplasty
Condition: Postoperative Pain
MeSH terms: Pain, Postoperative
Intervention: Bupivacaine HCl; SKY0402
Intervention description: 200 mg bupivacaine HCl; 600 mg SKY0402 (study drug).
Intervention MeSH terms: Bupivacaine
Phase: Phase 3
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Enrollment: 245.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Total knee arthroplasty; Pain; Analgesia

Summary:

      The primary objective is to demonstrate that SKY0402 is superior when compared to bupivacaine
      HCl in the management of postoperative pain for patients undergoing total knee arthroplasty.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female, ≥18 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 TKA under general or spinal anesthesia.

          4. American Society of Anesthesiology (ASA) Physical Classification System class 1-4.

          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, 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 being administered study drug (e.g., significant pain from other joints,
             chronic neuropathic pain, concurrent contralateral TKA, concurrent foot surgery,
             etc.), which have the potential to confound the postoperative study assessments.

          4. Body weight less than 60 kilograms (~132 pounds).

          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 ergot-type
             drugs, monoamine oxidase (MAO) inhibitors or antidepressants of triptoline 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. 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
             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 criterion 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.