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Pacira Announces Publication of Phase 4 Study of EXPAREL in Patients Undergoing Total Knee Replacement in The Journal of Arthroplasty
PILLAR study demonstrated a 78 percent decrease in opioid consumption and significantly better pain control with infiltration of EXPAREL plus bupivacaine versus bupivacaine alone
Ten percent of patients in the EXPAREL arm required no opioids for pain control
The study’s co-primary efficacy endpoints compared the magnitude and duration of postsurgical analgesia and associated impact on opioid consumption for 139 TKA patients randomized into two groups at 16 centers across
- Decrease in total opioid consumption by 78 percent (18.7 mg versus 84.9 mg in the bupivacaine group; P=0.0048) expressed as morphine equivalents from zero to 48 hours after surgery.
- Reduction in pain scores (180.8 versus 209.3 in the bupivacaine group; P=0.0381), measured using the area under the curve of the pain intensity scores measured on a visual analog scale from 12 to 48 hours after surgery.
Importantly, EXPAREL also achieved statistical significance for the study’s key secondary endpoints related to opioid reduction. Patients in the EXPAREL arm required 77.6 percent fewer opioids through 72 hours than those in the bupivacaine arm (20.9 mg versus 93.6 mg, respectively; P=0.0108), with 10 percent remaining opioid-free through 48 and 72 hours (compared to zero patients in the bupivacaine arm; P<0.01). Time to first opioid rescue was analyzed using logistic regression and Kaplan-Meier methods, with a significant difference between the EXPAREL group versus the bupivacaine group; P=0.0230.
EXPAREL and bupivacaine infiltrations both were well tolerated throughout the study duration. The most common treatment-emergent adverse events (TEAEs) in each group were nausea, dizziness and muscle spasms; all were mild to moderate in severity. No patients discontinued the study because of a TEAE.
“The PILLAR study provides robust evidence of the efficacy and safety of EXPAREL as an integral component of multimodal therapy to effectively control pain and substantially reduce, and in some cases completely eliminate, opioid requirements following total knee arthroplasty,” said
In order to ensure consistent results, study investigators utilized a standardized infiltration protocol designed by experienced clinicians. Key features included proper volume expansion to ensure full coverage of the nerve fibers responsible for sending pain signals to the brain, admixing with free bupivacaine to provide sufficient immediate pain relief, and a clear definition of the sites for infiltration and administration technique to ensure adequate coverage of the impacted nerve fibers.
Patients in the EXPAREL group were administered EXPAREL 266 mg/20 mL expanded to a total volume of 120 mL with 20 mL of 0.5% bupivacaine and 80 mL of saline. Patients randomized to receive bupivacaine HCl were administered 20 mL of 0.5% bupivacaine expanded to a total volume of 120 mL with 100 mL of saline. Investigators administered study drug using six 20 mL prefilled syringes.
“We are pleased to present the marketplace with confirmatory data demonstrating the significant positive impact EXPAREL can make on postsurgical recovery by sizably reducing opioid requirements while still providing superior pain control compared to bupivacaine alone,” said
Pacira and its partner in the orthopaedic and spine markets, DePuy Synthes Companies, part of the Johnson & Johnson Family of Companies, aim to raise awareness among health care professionals as well as patients of the importance of utilizing alternative options to opioids for postsurgical pain. Collaborative education and commercial efforts will emphasize best practice techniques related to the infiltration of EXPAREL in orthopaedic procedures and the positive outcomes that were obtained for TKA patients where the PILLAR protocol was employed.
The Postsurgical Infiltration With EXPAREL For Long-Lasting Analgesia In Total Knee ARthroplasty (PILLAR) study was a Phase 4 multicenter, randomized, double-blind, controlled parallel-group study conducted between
EXPAREL (bupivacaine liposome injectable suspension) is currently indicated for single-dose infiltration into the surgical site to produce postsurgical analgesia. The product combines bupivacaine with DepoFoam®, a proven product delivery technology that delivers medication over a desired period of time. EXPAREL represents the first and only multivesicular liposome local anesthetic that can be utilized in the peri- or postsurgical setting. By utilizing the DepoFoam platform, a single dose of EXPAREL delivers bupivacaine over time, providing significant reductions in cumulative pain score with up to a 45 percent decrease in opioid consumption; the clinical benefit of the opioid reduction was not demonstrated. Additional information is available at www.EXPAREL.com.
Important Safety Information
EXPAREL is contraindicated in obstetrical paracervical block anesthesia. EXPAREL has not been studied for use in patients younger than 18 years of age. Non-bupivacaine-based local anesthetics, including lidocaine, may cause an immediate release of bupivacaine from EXPAREL if administered together locally. The administration of EXPAREL may follow the administration of lidocaine after a delay of 20 minutes or more. Other formulations of bupivacaine should not be administered within 96 hours following administration of EXPAREL. Monitoring of cardiovascular and neurological status, as well as vital signs should be performed during and after injection of EXPAREL as with other local anesthetic products. Because amide-type local anesthetics, such as bupivacaine, are metabolized by the liver, EXPAREL should be used cautiously in patients with hepatic disease. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations. In clinical trials, the most common adverse reactions (incidence greater-than or equal to 10%) following EXPAREL administration were nausea, constipation, and vomiting.
Please see the full Prescribing Information for more details available at: http://www.exparel.com/hcp/pdf/EXPAREL_Prescribing_Information.pdf.
Forward Looking Statements
Any statements in this press release about our future expectations, plans, outlook and prospects, and other statements containing the words “believes,” “anticipates,” “plans,” “estimates,” “expects,” “intends,” “may” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including risks relating to: the success of our sales and manufacturing efforts in support of the commercialization of EXPAREL; the rate and degree of market acceptance of EXPAREL and our other products; the size and growth of the potential markets for EXPAREL and our ability to serve those markets; our plans to expand the use of EXPAREL to additional indications and opportunities, and the timing and success of any related clinical trials; the related timing and success of
Pacira Pharmaceuticals, Inc. Susan Mesco, (973) 451-4030 firstname.lastname@example.org Media Contact: Coyne Public Relations Alyssa Schneider, (973) 588-2270 email@example.com