Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication EXPAREL is indicated to produce postsurgical: Local analgesia via infiltration in patients aged 6 years and older Regional analgesia via an interscalene brachial plexus nerve block in adults Regional analgesia via a sciatic nerve block in the popliteal fossa in adults Regional analgesia via an adductor canal block in adults EXPAREL contains bupivacaine, an amide local anesthetic, and is indicated to produce… FDA label
Also known as Bupivacaine liposome injectable, bupivacaine liposome injectable suspension, Liposomal bupivacaine, Bupivacaine liposome, SKY0402
Exparel · 28 trials · 26 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
The numeric rating scale pain intensity scores ranging from 0 to 10, where 0 equals no pain and 10 equals the worst possible pain, from 0 to 96 hours post-surgery. For each subject, the area under the curve was derived using the trapezoidal rule on the pain scores adjusted for opioid pain medication using the observed and imputed values. Area under the curve started with the first pain assessment obtained after surgery and use all subsequent pain assessments up to 96 hours post-surgery. Pain scores were taken at 5 interval point 0 hours, 24 hours, 48 hours, 72 hours, and 96 hours. There were also unscheduled pain scores measured before opioid consumption also included in the area under the curve calculation. The area under the curve ranged from 0 to 960. Higher scores represent a worse outcome.
The numeric rating scale pain intensity scores ranging from 0 to 10, where 0 equals no pain and 10 equals the worst possible pain, from 0 to 96 hours post-surgery. For each subject, the area under the curve was derived using the trapezoidal rule on the pain scores adjusted for opioid pain medication using the observed and imputed values. Area under the curve started with the first pain assessment obtained after surgery and use all subsequent pain assessments up to 96 hours post-surgery. Pain scores were taken at 5 interval point: 0 hours, 24 hours, 48 hours, 72 hours, and 96 hours. There were also unscheduled pain scores measured before opioid consumption also included in the area under the curve calculation. The area under the curve ranged from 0 to 960. Higher scores represent a worse outcome.
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 VAS pain intensity scores through 72 hours. Visual Analog Scale (VAS) is a pain scale. The VAS was presented as a straight 10 cm line, where 0 cm is no pain and 10 cm is the worst pain possible. Patients were asked, "How much pain are you experiencing right now? Please place a vertical mark on the line below to indicate the level of pain you are experiencing right now."
AUC of VAS pain intensity scores through 48 hours, which represents total pain experienced through 48 hours. VAS is a pain scale. The VAS was presented as a straight 10 cm line, where 0 cm is no pain and 10 cm is the worst pain possible. Patients were asked, "How much pain are you experiencing right now? Please place a vertical mark on the line below to indicate the level of pain you are experiencing right now."
AUC of NRS pain intensity scores through 48 hours. Pain intensity scores were measured on a 10-point scale (0=no pain and 10=worst possible pain)
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).
To assess pain intensity at rest (NRS-R), the subject was to assume a resting position that did not exacerbate his or her postoperative pain and respond to the following question: "On a scale of 0 to 10, where 0 = no pain and 10 = worst possible pain, how much pain are you having right now?"
The AUC of the NRS-R pain intensity scores from time 0 through 24 hours The subject was to rest for at least 5 minutes before responding to the following question, "On a scale of 0 to 10, where 0 = no pain and 10 = worst possible pain, how much pain are you having right now?"
The subject's pain intensity was assessed with activity (NRS-A), while actively flexing the involved knee from the maximum extension point to the maximum flexion point possible. The subject responded to the following question, "On a scale of 0 to 10, where 0 = no pain and 10 = worst possible pain, how much pain did you have while bending your knee?"
Postoperative opioid consumption within first five postoperative days, reported as average mg/day in morphine equivalents.
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)
Assessments of postoperative pain were conducted through 96 hours and included pain intensity at rest (NRS-R) and with activity (NRS-A). The prescribed activity was to consist of raising the arm, in full extension at the elbow and wrist, to a position parallel with the axis of the torso. Pain intensity was scored on an 11-point scale, where 0 = no pain and 10 = worst possible pain.
To assess pain intensity at rest (NRS-R), the subject was to assume a resting position that did not exacerbate his or her postoperative pain. The subject was to rest in this position for at least 5 minutes before responding to the following question: "On a scale of 0 to 10, where 0=no pain and 10=worst possible pain, how much pain are you having right now?"
The subject's pain intensity was to be assessed with activity (NRS-A), after the subject had moved himself from a supine position in bed to a sitting up position at the edge of the bed. The subject was to respond to the following question: "On a scale of 0 to 10, where 0=no pain and 10=worst possible pain, how much pain did you have while sitting up?"
The subject's pain intensity was to be assessed with activity (NRS-A) after actively flexing the involved knee to the maximum flexion point possible. The subject was asked to respond to the following question: "On a scale of 0 to 10, where 0 = no pain and 10 = worst possible pain, how much pain did you have while bending your knee?"
The primary efficacy endpoint was the time to first use of supplemental pain medication (opioid or non-opioid) postoperatively for surgical pain.
The primary efficacy endpoint was the time to first use of supplemental pain medication (opioid or non-opioid) postoperatively for surgical wound 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) |
| Part A: EXPAREL 266 mg arm | EXPERIMENTAL | subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL mixed with 10 mL saline |
| Part A: EXPAREL 133 mg arm | EXPERIMENTAL | subjects randomized to this treatment arm will receive 10 mL (133 mg) EXPAREL mixed with 20 mL saline |
| Part A: Bupivacaine HCl arm | ACTIVE_COMPARATOR | Subjects randomized to this treatment arm will receive 20 mL (50 mg) 0.25% bupivacaine HCl mixed with 10 mL saline |
| Part B: EXPAREL 133 mg arm OR EXPAREL 266 mg arm | EXPERIMENTAL | Subjects randomized to this treatment arm will receive 20 mL (266 mg) EXPAREL mixed with 10 mL saline OR 10 mL (133 mg) EXPAREL mixed with 20 mL saline. Dose will be determined following interim analysis of Part A. |
| Part B: Bupivacaine HCl arm | ACTIVE_COMPARATOR | subjects randomized to this treatment arm will receive 20 mL (50 mg) 0.25% bupivacaine HCl mixed with 10 mL saline |
| Cohort 1: EXPAREL admix arm | EXPERIMENTAL | subjects randomized to this treatment arm will receive 10 mL (133 mg) EXPAREL admixed with 10 mL (50 mg) 0.5% bupivacaine HCl |
| Cohort 1: Bupivacaine HCl arm | ACTIVE_COMPARATOR | subjects randomized to this treatment arm will receive 10 mL (50 mg) 0.5% bupivacaine HCl mixed with 10 mL normal saline |
| Cohort 2: EXPAREL admix arm | EXPERIMENTAL | subjects randomized to this treatment arm will receive 10 mL (133 mg) EXPAREL admixed with 10 mL (50 mg) 0.5% bupivacaine HCl |
| Cohort 2: Bupivacaine HCl arm | ACTIVE_COMPARATOR | subjects randomized to this treatment arm will receive 10 mL (50 mg) 0.5% bupivacaine HCl mixed with 10 mL normal saline |
| 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 133 mg | ACTIVE_COMPARATOR | Single dose of 133 mg (10 mL) EXPAREL (bupivacaine liposome injectable suspension) expanded in volume with 10 mL of normal saline for a total volume of 20 mL. |
| EXPAREL 266 mg | ACTIVE_COMPARATOR | Single dose of 266 mg (20 mL) EXPAREL (bupivacaine liposome injectable suspension). |
| Placebo | PLACEBO_COMPARATOR | Normal saline (20 mL). |
| SKY0402 | EXPERIMENTAL | During the hemorrhoidectomy, 30cc of SKY0402 is injected into the wound. |
| Bupivacaine HCl | ACTIVE_COMPARATOR | 100 mg Bupivacaine HCl (e.g., Marcaine with epinephrine 1:200,000) is the reference-listed drug for bupivacaine and contains the same active, local anesthetic as SKY0402. A single dose of study drug was administered intraoperatively (at the end of surgery) via local infiltration. |
| Exparel | EXPERIMENTAL | The experimental medication (Exparel) will be administered per standard of care via ultrasound-guided erector spinae plane (ESP) blocks, bilaterally for sternotomy and unilaterally for mini-thoracotomy. The drug will be administered prior to cardiac surgery. The dosage will be determined by patient body weight. For this pilot project the investigators anticipate consenting 150 subjects to obtain 96 evaluable subjects; 48 Mini thoractomies (N=24 Exparel, N=24 Marcaine) 48 Open sternotomies (N=24 Exparel, N=24 Marcaine). |
| Marcaine | ACTIVE_COMPARATOR | The active comparator medication (Marcaine) will be administered per standard of care via ultrasound-guided erector spinae plane (ESP) blocks, bilaterally for sternotomy and unilaterally for mini-thoracotomy. The drug will be administered prior to cardiac surgery. The dosage will be determined by patient body weight. For this pilot project the investigators anticipate consenting 150 subjects to obtain 96 evaluable subjects; 48 Mini thoracotomies (N=24 Exparel, N=24 Marcaine) 48 Open sternotomies (N=24 Exparel, N=24 Marcaine). |
| 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 |
| Low-dose SKY0402 + bupivacaine HCl | ACTIVE_COMPARATOR | Marcaine with epinephrine 1:200,000 is the reference-listed drug for bupivacaine and contains the same active, local anesthetic as SKY0402 |
| Mid-dose SKY0402 + bupivacaine HCl | ACTIVE_COMPARATOR | Marcaine with epinephrine 1:200,000 is the reference-listed drug for bupivacaine and contains the same active, local anesthetic as SKY0402 |
| SKY0402 high dose | EXPERIMENTAL | SKY0402, single administration |
| SKY0402 middle dose | EXPERIMENTAL | SKY0402, single administration |
| SKY0402 low dose | EXPERIMENTAL | SKY0402, single administration |
| Bupivacaine HCl 105mg | ACTIVE_COMPARATOR | Bupivacaine HCl given during hernia repair |
| 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 |
| Moxifloxacin tablet | ACTIVE_COMPARATOR | - |
| Placebo tablet | EXPERIMENTAL | - |
| SKY0402 300mg | EXPERIMENTAL | - |
| SKY0402 450mg | EXPERIMENTAL | - |
| Placebo injection | PLACEBO_COMPARATOR | - |
| 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 liposome injectable suspension 266 mg | DRUG | Sciatic nerve block in the popliteal fossa with EXPAREL 266 mg |
| Bupivacaine HCl | DRUG | Sciatic nerve block in the popliteal fossa with Bupivacaine HCl |
| Bupivacaine liposome injectable suspension 133 mg | DRUG | Sciatic nerve block in the popliteal fossa with EXPAREL 133 mg |
| bupivacaine liposome injectable suspension | DRUG | Adductor canal block with EXPAREL |
| Bupivacaine Hydrochloride | DRUG | Adductor Canal Block with bupivacaine HCl |
| 0.5% Bupivacaine HCl | DRUG | Bupivacaine HCl 2mg/kg |
| Placebo | DRUG | Normal saline. |
| Bupivacaine liposome | DRUG | Local administration |
| EXPAREL 266 mg | DRUG | - |
| SKY0402 | DRUG | During the operation, 30cc of SKY0402 are injected into the wound. |
| 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 |
| SKY0402 + bupivacaine HCl | DRUG | Low-dose SKY0402 administered locally into one breast pocket and 75 mg bupivacaine HCl administered locally into the other breast pocket |
| Mid-dose SKY0402 + bupivacaine HCl | DRUG | Mid-dose SKY0402 administered locally into one breast pocket and 75 mg bupivacaine HCl administered locally into the other breast pocket |
| Moxifloxacin 400mg | DRUG | - |
| Placebo injection | DRUG | - |
| Placebo tablet | DRUG | - |
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 to manage postsurgical pain across a range of procedures. Its studied indications include bunionectomy, chronic shoulder pain, knee osteoarthritis, lower extremity surgery, mammaplasty, and general pain. It is also being evaluated for postsurgical analgesia in total ankle arthroplasty and cardiac surgery.
Exparel is developed by Pacira BioSciences, Inc., which trades on the Nasdaq under the ticker PCRX. The company sponsors the clinical program evaluating the drug across surgical and pain indications in the United States.
Exparel is in Phase 3 clinical development. The program includes three trials in total, with one currently active and two completed, enrolling 495 participants overall. The studies are randomized, double blind, and use active-controlled designs.
Active and recent Exparel trials include NCT07212114, a Phase 3 study of Exparel versus bupivacaine in total ankle arthroplasty, NCT06271265, a Phase 1 pharmacokinetics and safety study in cardiac surgery, and NCT06077422, a Phase 2 comparison with Marcaine ESP block for post-cardiac surgical pain. NCT05171179, a completed Phase 3 study, examined Pecs blocks with Exparel in breast reconstruction.
Yes. Exparel is also known as bupivacaine liposome injectable suspension, bupivacaine liposome injectable, and by the dose descriptions EXPAREL 67 mg and EXPAREL 266 mg. These names refer to the same product.
Exparel is a small molecule formulation of bupivacaine, a local anesthetic. It is designed to deliver bupivacaine in a liposomal form for extended postsurgical pain relief, and it is classified as a small molecule therapeutic in the musculoskeletal area.