EXPAREL Dose-Response for Single-Injection Femoral Nerve Blocks: A Pharmacodynamics Investigation in Healthy Volunteers

Putting local anesthetic next to a nerve is a common way of decreasing the pain that patients feel after surgery. For knee surgery, the local anesthetic is placed next to the femoral nerve in the middle of the crease where the leg meets the body when bending at the hip joint. However, the local anesthetic takes away not only sensation-and therefore pain-but also motor control, leaving muscles weaker. It would greatly improve patient safety if the investigators could administer a very long-acting local anesthetic that decreased postoperative pain, but affected muscle strength only minimally. The purpose of this study is to define the dose-response curve of EXPAREL (also termed SKY0402), 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.

This investigation will be a Phase 1, prospective, double-masked, human-subjects dose-response clinical trial.

Enrollment. Subjects will be volunteers of both sexes, age 18 and older. If a volunteer meets inclusion/exclusion criteria and desires study participation, written, informed consent will be obtained. Selection for inclusion will not be based on race or socioeconomic status. The study population of interest includes men and women of all races and socioeconomic status.

Subject preparation. Following written, informed consent, subjects will be admitted to the UCSD CTRI and have demographic/morphometric data recorded (e.g., age, weight, height), a medical history recorded, and a brief physical examination. Block placement itself may occur either in the UCSD CTRI or Hillcrest Outpatient Surgical Center Post Anesthesia Care Unit (PACU: this is where regional anesthetics are administered on a regular basis for surgical patients). If the blocks are placed in the PACU, subjects will remain there for two hours and then moved (accompanied by a physician) on their gurney to the UCSD CTRI where they will spend the remainder of the study period. Women of childbearing potential will have a urine pregnancy test. Prior to dosing, baseline quadriceps strength and sensory level measurements will also be obtained. An intravenous line will be placed in an upper extremity, followed by external monitors (pulse oximeter, blood pressure, and EKG), and oxygen by nasal cannula (1-6 L/min). Sedation will be provided by a combination of one or more of the following, titrated to effect: oral valium (10 mg), intravenous fentanyl (50 mcg), and/or intravenous midazolam (1 mg). Following sterile preparation with chlorhexidine gluconate and isopropyl alcohol, and once the topical antiseptic is dry, subjects will have bilateral, single-injection, ultrasound-guided femoral nerve blocks placed using standard UC San Diego techniques as previously published by the current P.I.

Treatment Group Assignment. The dominant side (left or right) will be randomized to one of two treatment groups: the higher or lower concentration of the local anesthetic SKY0402. The non-dominant contralateral side will receive the other possible treatment. The volume of each and every single-injection femoral nerve block will be 30 mL (standard for femoral nerve blocks is 30-40 mL). Since volume will remain constant, we will vary the dose of SKY0402 by varying concentration (volume x concentration = dose). Of note, SKY0402 may be mixed with normal saline to vary the concentration. Randomization will be based on computer-generated codes. Randomization will be in blocks of two.