EXPAREL Dose-Response for Single-Injection Femoral Nerve Blocks
Condition: Healthy Volunteers
Intervention: SKY0402
Intervention description: Single-injection femoral nerve block. Initial doses of SKY0402 will begin at 0 mg, and 2 mg (high) for the first subject; and 1 mg (low) and 3 mg (high) for the second subject. The next doses will be between 0-80 mg per side, determined prior to randomization of each subsequent subject. The specific subsequent doses will increase, remain the same, or decrease, determined by the P.I. in consultation with the manufacturer of SKY0402. Doses will always remain within the range of 0-80 mg per side, for a total possible dose of 0-160 mg.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: Each subject is assigned two possible doses between 0-80 mg by the investigators based on previous participants' responses to various doses; and, the dominant side is then randomized to either the higher or lower dose. The response for each dose is the primary interest, and not a comparison of the left vs. the right or different dose combinations within each subject. In other words, of interest are the different doses effects on muscle strength and skin sensitivity across participants (eg., Dose A vs Dose B vs Dose C, etc).
Masking: Double
Masking description: Investigational Drug Service prepared all study medication, with each dose provided to the caregivers in a 30-mL syringe with IV line extension tubing, both wrapped in opaque tape to retain masking since the relative study drug concentration could be inferred by the opacity of the injectate. One syringe was labeled "Dominant" and the other labeled "Other." In this manner, all investigators, nursing staff, and subjects remained masked to the specific concentration/dose during all outcome measurements.
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      EXPAREL™, an investigational drug product, is a new formulation of a local anesthetic
      (numbing medicine) that is designed to be longer acting than the currently-available local
      anesthetics. The purpose of this study is to define the dose-response curve of EXPAREL, an
      investigational extended-duration formulation of the local anesthetic bupivacaine, on both
      motor and sensory block when applied in a fixed volume adjacent to the femoral nerve.
    

Eligibility criteria:

        Inclusion Criteria:

          -  greater than or equal to 18 years old

          -  able and willing to have bilateral femoral nerve blocks placed and repeated
             motor/sensory testing for 24-120 hours (1-5 days), requiring 1-5 overnight stay(s) in
             the UCSD CTRI to allow dissipation of local anesthetic infusion effects to
             near-baseline values

          -  have the ability to adequately communicate with all study personnel

          -  willing and capable of providing written informed consent

        Exclusion Criteria:

          -  daily analgesic use for over one week within the past 6 months

          -  opioid use within the previous 4 weeks

          -  any neuro-muscular deficit of either femoral nerves and/or quadriceps muscles

          -  body mass index > 30 kg/m2

          -  current pregnancy

          -  incarceration

          -  any coagulation disorder

          -  uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the
             opinion of the investigators, may interfere with study assessments or adherence

          -  any previous allergic reaction to fentanyl, midazolam, or an amide local anesthetic
             (bupivacaine is of the amide local anesthetic class)

          -  any previous participation in a SKY0402/EXPAREL study

          -  nursing mothers

          -  suspected or known drug or alcohol abuse within the previous year; and/or

          -  planning on becoming pregnant in the one month following study participation.