Pacira BioSciences, Inc. (NASDAQ: PCRX) today announced that full results its Phase 4 study of EXPAREL® (bupivacaine liposome injectable suspension) administered via transversus abdominis plane (TAP) field block in patients undergoing Cesarean section (C-section) have been published in Anesthesia and Analgesia. In this study, EXPAREL achieved its primary endpoint with a statistically significant reduction in total postsurgical opioid consumption through 72 hours. EXPAREL also achieved statistical significance for reduction in percentage of opioid-spared patients through 72 hours.

This was a multicenter, randomized, double-blind study across 13 clinical sites in the United States, in patients undergoing elective C-section and receiving spinal anesthesia and a multimodal analgesic regimen. Patients were randomized (1:1) to receive EXPAREL 266 mg plus bupivacaine HCl 50 mg or bupivacaine HCl 50 mg alone administered via TAP field block after delivery. Effectiveness was evaluated in a pre-specified modified intent-to-treat (mITT) population which met the study criteria regarding proper administration of TAP and multimodal regimen (N=136). Key findings include:

• Significant reduction in total opioid consumption with EXPAREL plus bupivacaine HCl versus bupivacaine HCl
  • 52% reduction through 72 hours, the primary endpoint of the study (least squares mean [LSM] standard error [SE], 15.5 [6.67] vs 32.0 [6.25] mg, respectively; P=0.0117)
  • 49% reduction at one week (LSM [SE], 23.3 [9.75] vs 45.8 [9.13] mg, respectively; P=0.0175)
• 41% reduction of opioid consumption at two weeks, although results did not reach statistical significance (LSM [SE], 28.2 [11.20] vs 47.8 [10.49] mg, respectively; P=0.0542)
• Significantly higher percentage of opioid-spared patients with EXPAREL versus bupivacaine HCl, defined as patients who took no more than one oxycodone 10 mg tablet (or equivalent) with no opioid-related side effects through 72 hours
  • Percentage of opioid-spared patients was 2.2 times higher in the EXPAREL group vs bupivacaine HCl group (54% vs 25%, respectively; P=0.0012)
• Optimized pain control through 72 hours, which was comparable in both groups

Patients in the EXPAREL arm of this study were administered a TAP field block with 10 mL EXPAREL admixed with 10 mL 0.25% bupivacaine HCl and 10 mL normal sterile saline injected bilaterally (for a total volume of 60 mL). Patients in the active comparator arm received a TAP field block with 10 mL 0.25% bupivacaine HCl admixed with 20 mL normal sterile saline injected bilaterally (for a total volume of 60 mL).

Research shows nearly nine in 10 mothers and mothers-to-be have concerns about taking opioids during and after childbirth, yet 51% of all C-section patients are prescribed an opioid to manage postsurgical pain.

“With C-sections being one of the most common surgeries in the United States, and data showing that one out of 300 opioid naïve women become persistent opioid users following cesarean delivery, it’s critical we evaluate our approach to postsurgical pain management,” said Ashraf Habib, MD, Chief, Division of Women’s Anesthesia and Professor of Anesthesiology at Duke University and study investigator. “The data from this Phase 4 study demonstrate that an EXPAREL-based multimodal regimen has the potential to optimize postoperative analgesia for C-section patients.”

Prior to C-section, all patients in this study received an intrathecal injection of 150 mcg preservative-free morphine for spinal injection in conjunction with single-shot spinal anesthesia using 1.4-1.6 mL bupivacaine HCl 0.75% and 15 mcg fentanyl. Following C-section, patients also received an opioid-sparing multimodal analgesic regimen which consisted of 15 mg of intravenous (IV) ketorolac, 1000 mg of IV acetaminophen at the time of skin incision closure, and scheduled oral acetaminophen and ibuprofen beginning 6 hours after skin incision closure for up to 72 hours following surgery. Rescue medication was available upon request and postsurgical opioid consumption was collected.

Safety was comparable between study groups, with 64 percent of patients in the EXPAREL group experiencing a treatment-emergent adverse event (TEAE) versus 56 percent of patients in the bupivacaine HCl group. The most common TEAEs include pruritus (itching) and nausea; serious TEAEs were rare (approximately three percent in both groups). There were no fatal TEAEs.

Earlier this year, Pacira announced positive topline results for CHOICE, a next-generation C-section trial designed to eliminate the use of spinal morphine in the EXPAREL arm. In the study, EXPAREL achieved its primary endpoint with a statistically significant reduction in total opioid consumption while maintaining pain scores through 72 hours (P≤0.001), and demonstrated statistical significance for the key secondary endpoint of a reduction in the incidence and severity of itching for 72 hours after surgery (P≤0.05).