Abstract ID: A48

Abstract Title: Extended-Release Liposomal Formulation of Bupivacaine for Post-Operative Pain Management after Hernia Repair Surgery

Authors: Manvelian G¹, Ardeleanu M², Rashti N³
SkyePharma Inc. San Diego CA USA¹, SkyePharma Inc. San Diego CA USA², SkyePharma Inc. San Diego CA USA³
Poster Type: Either

ABSTRACT BODY

Background and Goal of Study:
SKY0402 is a liposomal formulation of bupivacaine developed for the management of post-operative pain (POP). In this study, the safety and efficacy of SKY0402 were compared with those of a commercially-available bupivacaine HCl solution (i.e., Marcain® 0.5%, AstraZeneca), in patients undergoing inguinal hernia repair surgery.

Materials and Methods:
This is a Phase 2, double-blind study, in which 41 patients were randomized within sequential cohorts to receive either SKY0402 (175 mg in Cohort 1, 225 mg in Cohort 2) or Marcain 100 mg. The study drug was administered via surgical wound infiltration, in a 40-mL total injection volume. Supplemental use of analgesics – administered as needed after surgery – and pain scores – measured on a 0-100 mm visual analog scale (VAS) – were recorded for 96 hours post-dose. Wound healing scores (0-100 mm VAS) and adverse events (AE) were used to monitor drug safety. The study has a dose-escalation design and is currently ongoing. Preliminary data from the first two cohorts are reported below.

Results and Discussions:
1. Safety: There were no deaths in the study and no patients were discontinued because of adverse events. The incidence of local and systemic AEs (Table 1) was comparable across treatment groups and did not appear treatment- or dose-related. There was only one serious adverse event (SAE) in the study reported in the SKY0402 225-mg group, which was noted as "Post-Operative Hematoma" and required overnight hospitalization for observation. This SAE was considered ‘not related’ to the study drug and resolved in two days without other intervention. Mean wound healing scores were 86.5 (SD=15.8), 89.4 (SD=11.9), and 79.8 (SD=14.27) in the SKY0402 175-mg, SKY0402 225-mg, and Marcain 100-mg groups, respectively (where 0=worst healing and 100=best healing).
2. Efficacy: The proportion of patients requiring supplemental opioid medication for POP management was higher in the Marcain group (59%) compared with any of the SKY0402 groups (25%). Pain intensity scores at rest (VAS-R) and particularly with activity (VAS-A) were lower for the SKY0402 groups (Figure 1). To assess pain intensity with activity, patients were asked to take a deep breath and cough forcefully. Differences in VAS-A scores were statistically significant (95% confidence intervals) at 4, 8, 12, and 24 hours for SKY0402 175-mg dose and at 8, 12, and 24 hours for SKY0402 225-mg dose, compared to the Marcain group. There were no clear differences between study groups regarding the time from the end of surgery to the first administration of supplemental pain medication.

Conclusion:
These data indicate that SKY0402 has a safety profile comparable to that of commercially available bupivacaine and presents an advantage over the reference product in managing POP after inguinal hernia repair. Higher doses may be required for extended duration of action.

ATTACHED FILES

A48_C-201 S&E -Table 1(060106_1340).doc

A48_C-201 S&E -Figure 1 (with bars).doc

Reg Anesth Pain Med 2005; 30(3):A48