Primary objective: To assess the safety and tolerability of EXPAREL® administered as a single intrathecal injection in healthy volunteers Secondary objective: To characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profile of EXPAREL® administered as a single intrathecal injection in healthy volunteers
This is a Phase-1, single center, randomized, double-blind, active and placebo-controlled study in approximately 40 healthy adult subjects. On Day 1, eligible subjects will be randomized in blocks of 5, in a ratio of 3:1:1 to receive EXPAREL® or bupivacaine or placebo (saline) injection, respectively. Starting with treatment Cohort 1, healthy volunteers will be randomized to the 3 treatment arms within cohorts. Each cohort will consist of 10 subjects (6 EXPAREL®, 2 bupivacaine and 2 placebo). In each cohort, all 10 subjects in each cohort will receive cerebrospinal fluid (CSF) taps. Within the EXPAREL® arm, subjects will be randomized 2:1 with 4 subjects undergoing CSF tap and 2 subjects not undergoing CSF tap in each cohort. Subjects who are not undergoing CSF tap, will still be injected with needles without draw of CSF to prevent subject bias. Such a randomization will allow for characterization of the complete pharmacodynamics profile of the drug without risk of drug removal in the CSF. For those subjects randomized to the EXPAREL® arm - the dose of EXPAREL® will be determined by the cohort. Starting at 1 mL (13.3 mg) for Cohort 1, the volume of EXPAREL® will be increased by 1 mL in each subsequent cohort for a maximum of 4 mL (53.2 mg). The decision to proceed to the next cohort will be made following a full review of the safety, PK, and PD (sensory and motor) data from current completed cohort(s). All subjects will remain in the EPRU for 5 days after drug administration and will be discharged on Day 6. Subjects will be instructed to return for a follow up visit on Day 9. Adverse events (AEs) and serious adverse events (SAEs) will be recorded from the time of consent through 30 days after drug administration.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
20
Duke University
Durham, North Carolina, United States
Area under the plasma concentration-versus-time curve
Pharmacokinetic endpoint
Time frame: 6-8 weeks
Maximum plasma concentration (Cmax) and time of Cmax (Tmax).
Pharmacokinetic endpoint
Time frame: 6-8 weeks
The apparent terminal elimination half-life (t1/2el)
Pharmacokinetic endpoint
Time frame: 6-8 weeks
Apparent clearance (CL/F)
Pharmacokinetic endpoint
Time frame: 6-8 weeks
Apparent volume of distribution (Vd)
Pharmacokinetic endpoint
Time frame: 6-8 weeks
Incidence of treatment-emergent AEs (TEAEs) through Day 9
Safety endpoint
Time frame: 6-8 weeks
Proportion of subjects who have any of neurological events
Safety endpoint
Time frame: 6-8 weeks
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