Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
EXPAREL · 11 trials · 15 indications
To measure this, the Area under the curve (AUC) of the Numeric Rating Scale (NRS) for both groups will be compared. The subjects will be asked to rate their worst or average pain on a scale of 0 (no pain) - 10 (worst possible pain) on numerous time points, starting upon arrival in the Post-Anesthesia Care Unit (PACU)
• Investigate amount of post-operative opioid consumption post operatively
To compare the magnitude of the analgesic effect (NRS pain intensity scores) following a single dose injection of EXPAREL vs. bupivacaine hydrochloride (HCl) when administered as combined sciatic (in the popliteal fossa) and saphenous (in the adductor canal) nerve blocks in subjects undergoing lower extremity surgeries. Numerical Rating Scale: an 11 point scale 0=no pain, 10= the worst pain imaginable. The area under the curve (AUC) of the NRS pain intensity scores from 0 to 96 hours post-surgery comparing EXPAREL to 0.25% bupivacaine HCl
AUC of pain intensity scores at rest through 72 hours postsurgery. Participants assumed a resting position that did not exacerbate his or her postsurgical pain. Pain intensity scores were measured at baseline and 1, 2, 4, 8, 12, 24, 36, 48, 60, and 72 hours postsurgery, at first request for rescue pain medication, and on day 12 using the numeric rating scale at rest (NRS-R; 0=no pain and 10=worst possible pain).
AUC of NRS-R pain intensity scores through 72 hours. Pain intensity scores were measured on an 11-point NRS (0=no pain and 10=worst possible pain)
• Area under the plasma concentration-versus-time curve (AUClast and AUC0-inf)
Area under the concentration curve for EXPAREL
Pain intensity scores using the VAS at predose (on Day 1 prior to study drug administration); upon arrival at the post-anesthesia care unit (PACU); at 4, 8, 12, 24, 36, 48, 60, and 72 hours after the beginning of study drug administration; immediately prior to each administration of rescue pain medication; and just prior to hospital discharge
Pharmacokinetic parameters will be estimated from plasma bupivacaine measurements using non-compartmental analysis, based on the sampling schedule at predose (on Day 1 prior to study drug administration); 15 minutes, 30 minutes, 1, 2, 4, 8, 12, 24, 36, 48, 60, 72, 84, and 96 hours after the beginning of study drug administration; and on Day 7
| Arm | Type | Description |
|---|---|---|
| Admix | EXPERIMENTAL | EXPAREL admixed with 0.25% bupivacaine HCl Total volume (50 mL) will be split such that 30 mL will be administered as the sciatic nerve block (in the popliteal fossa) and 20 mL will be administered as the saphenous nerve block (in the adductor canal) |
| Reference | EXPERIMENTAL | Bupivacaine HCl arm Total volume (50 mL) will be split such that 30 mL will be administered as the sciatic nerve block (in the popliteal fossa) and 20 mL will be administered as the saphenous nerve block (in the adductor canal) |
| Blocks+Bupivacaine | ACTIVE_COMPARATOR | Use of Pecs block types I and II with bupivacaine as local anesthetic |
| Blocks+Bupivacaine+Exparel | EXPERIMENTAL | Use of Pecs block types I and II with mixture of bupivacaine and Exparel\* (\*Must include bupivacaine at lower dose to decrease intra-operative variability in pain control due to delayed onset of Exparel) |
| EXPAREL arm | EXPERIMENTAL | Subjects randomized to this treatment arm will receive 20 mL (266 mg)EXPAREL mixed with 20 mL saline |
| EXPAREL admix arm | EXPERIMENTAL | subjects randomized to this treatment arm will receive 20 mL (266 mg)EXPAREL admixed with 20 mL (50 mg) 0.25% bupivacaine HCl. |
| Bupivacaine HCl Arm | ACTIVE_COMPARATOR | subjects randomized to this treatment arm will receive 40 mL (100 mg)0.25% bupivacaine HCl. |
| Group 1: 12 to less than 17 years, undergoing spine surgery, EXPAREL | EXPERIMENTAL | Single dose of EXPAREL 4 mg/kg (not to exceed a maximum total dose of 266 mg) via local infiltration at the end of spine surgery. |
| Group 1: 12 to less than 17 years, undergoing spine surgery, bupivacine | ACTIVE_COMPARATOR | Single dose of bupivacaine hydrochloride (HCl) 2 mg/kg (not to exceed a maximum total dose of 175 mg) via local infiltration at the end of spine surgery. |
| Group 2: 6 to less than 12 years, undergoing spine surgery, EXPAREL | EXPERIMENTAL | Single dose of EXPAREL 4 mg/kg (not to exceed a maximum total dose of 266 mg) via local infiltration at the end of spine surgery. |
| Group 2: 6 to less than 12 years, undergoing cardiac surgery, EXPAREL | EXPERIMENTAL | Single dose of EXPAREL 4 mg/kg (not to exceed a maximum total dose of 266 mg) via local infiltration at the end of cardiac surgery. |
| EXPAREL 266 mg | ACTIVE_COMPARATOR | Intercostal nerve block using single total administration of 20 mL EXPAREL (bupivacaine liposome injectable suspension) 266 mg (approximately 88 mg \[6.6 mL\] to each of three nerve segments) |
| Placebo | PLACEBO_COMPARATOR | Intercostal nerve block using single total administration of 20 mL normal saline (6.6 mL to each of three nerve segments) |
| Group 1 (30 participants) | EXPERIMENTAL | - |
| Group 2 (30 participants) | EXPERIMENTAL | - |
| (Part 1) EXPAREL 67 mg | EXPERIMENTAL | 5 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 15 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively |
| (Part 1) EXPAREL 133 mg | EXPERIMENTAL | 10 mL EXPAREL (bupivacaine liposome injectable suspension) expanded with 10 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively |
| (Part 1) EXPAREL 266 mg | EXPERIMENTAL | 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively |
| (Part 1) Placebo | PLACEBO_COMPARATOR | 20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively |
| (Part 2) EXPAREL 266 mg | EXPERIMENTAL | 20 mL EXPAREL (bupivacaine liposome injectable suspension) as single-injection femoral nerve block ≤2 h preoperatively |
| (Part 2) Placebo | PLACEBO_COMPARATOR | 20 mL normal saline as single-injection femoral nerve block ≤2 h preoperatively |
| EXPAREL | EXPERIMENTAL | A total of approximately 24 subjects (8 subjects per Part) will be enrolled. Subjects in this arm will receive EXPAREL |
| bupivacaine | ACTIVE_COMPARATOR | A total of approximately 24 subjects (8 subjects per Part) will be enrolled. Subjects in this arm will receive bupivacaine |
| Experimental: EXPAREL 4 mg/kg | EXPERIMENTAL | Single dose of EXPAREL 4 mg/kg |
| EXPAREL 266 mg/20 mL | OTHER | Eligible subjects, whose surgical incision must be at least 8 cm in length, will receive a single dose of EXPAREL (266 mg/20 mL) expanded in volume with 20-60 mL normal saline, depending on the size of the incision |
| Cohort 1 | ACTIVE_COMPARATOR | Cohort 1 will receive a single dose of EXPAREL 266 mg on Day 1. No additional dose will be given. |
| Cohort 2 | ACTIVE_COMPARATOR | Cohort 2 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 4 at 72 hours. |
| Cohort 3 | ACTIVE_COMPARATOR | Cohort 3 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 3 at 48 hours. |
| Cohort 4 | ACTIVE_COMPARATOR | Cohort 4 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 2 at 24 hours. |
| Cohort 5 | ACTIVE_COMPARATOR | Cohort 5 will receive a single dose of EXPAREL 266 mg on Day 1 followed immediately by a second dose of EXPAREL 266 mg (total of 532 mg/40 mL). |
| Name | Type | Description |
|---|---|---|
| EXPAREL | DRUG | EXPAREL (bupivacaine liposome injectable suspension) is formulated as a sterile, non-pyrogenic, white to off-white, preservative-free homogenous suspension of bupivacaine encapsulated into multivesicular liposomes (pMVL drug delivery system). For this study, EXPAREL will be provided in 20 mL (266 mg) EXPAREL single-use, clear glass vials. |
| 0.25% bupivacaine (HCl): 50 ml | DRUG | The reference product is 50 mL (100 mg) 0.25% bupivacaine HCl administered via a combined sciatic (in the popliteal fossa) and saphenous nerve block (in the adductor canal) |
| 0.25% bupivacaine (HCl): 30 ml | DRUG | EXPAREL admixed with 30 mL (75 mg) 0.25% bupivacaine HCl |
| Breast Reconstruction (Mammaplasty) | PROCEDURE | Breast Reconstruction (mammaplasty) surgery with implant-based tissue expander |
| Pecs blocks | DEVICE | Pectoral nerve (Pecs) blocks I and II function by blocking the pectoral, intercostal, intercostobrachial nerves, and/or long thoracic nerve. These are used primarily for breast surgeries and are gaining momentum as simple administers of local analgesics. Pecs blocks utilize ultrasound to guide injection of local analgesic. It is less invasive and more accurate than most current modes of analgesia administration. |
| Bupivacaine | DRUG | This is an anesthetic delivered during breast reconstruction surgery that will be given to participants in both arms. |
| Bupivacaine Hydrochloride | DRUG | 0.25% bupivacaine |
| 0.5% Bupivacaine HCl | DRUG | Bupivacaine HCl 2mg/kg |
| EXPAREL 266 mg | DRUG | - |
| Placebo | DRUG | - |
| Ropivacaine | DRUG | Continuous infusion of Ropivacaine via catheter, and then we follow up with patient in the recovery room with traditional common pain management. MME (milligram morphine equivalent) will be collected. |
| EXPAREL 67 mg | DRUG | 5 mL EXPAREL expanded with 15 mL normal saline as single-injection femoral nerve block prior to total knee arthroplasty |
| EXPAREL 133 mg | DRUG | 10 mL EXPAREL expanded with 10 mL normal saline as single-injection femoral nerve block prior to total knee arthroplasty |
Inclusion Criteria: * Indicated to undergo unilateral total ankle arthroplasty * American Society of Anesthesiologists (ASA) physical status 1, 2, or 3 * Able to provide informed consent, adhere to the study schedule, and complete all study assessments * Body Mass Index (BMI) ≥18 and ≤40 kg/m2 Exc...
EXPAREL is used for postoperative pain management, including in total ankle arthroplasty, spinal fusion, and posterolateral thoracotomy procedures. It is also being studied for chronic shoulder pain and in healthy volunteers. The drug is a small molecule developed by Pacira BioSciences, Inc. (PCRX) and is currently in Phase 1 clinical development.
EXPAREL is a small molecule that does not target a specific molecular target or target class. Its mechanism of action is not described in the available data. The drug is being studied for its pharmacokinetics and safety in various patient populations, including those undergoing surgical procedures for pain management.
EXPAREL is developed by Pacira BioSciences, Inc., a biopharmaceutical company traded on the stock exchange under the ticker symbol PCRX. The company is conducting clinical trials to evaluate the drug's safety and efficacy in managing postoperative pain and other conditions.
EXPAREL is in Phase 1 clinical development. While some completed trials were Phase 3, the overall development program is currently in Phase 1. The drug is investigational and has not been approved by regulatory authorities. It is being studied for postoperative pain management and other indications.
EXPAREL has been studied in several clinical trials, including NCT01802411, a Phase 3 study of intercostal nerve block in posterolateral thoracotomy patients, and NCT02985762, a Phase 1 pharmacokinetic study in spinal fusion patients. Other trials include NCT03485014 and NCT03682302, both evaluating the drug in pediatric patients for postoperative pain management.
EXPAREL is also known as liposome bupivacaine. In clinical trials, it is referred to as such, for example in the study titled 'Intercostal Nerve Block With Liposome Bupivacaine in Subjects Undergoing Posterolateral Thoracotomy.' This alternative name is used to describe the drug's formulation.