Salt Lake City,
This is a Phase 3, randomized, double-blind, placebo-controlled study in subjects scheduled
to undergo elective bilateral third molar extraction under local anesthesia. At least one
lower mandibular third molar must involve full or partial bony impaction confirmed by visual
or radiographic evidence.
Subjects will be screened within 30 days prior to surgery.
Randomized subjects will receive a dental nerve block with lidocaine 2% with epinephrine
1:100,000 before undergoing bilateral third molar extraction under local anesthesia. In
addition to the lidocaine nerve block, the Investigator may choose to add topical benzocaine
or intraoperative nitrous oxide.
At the end of surgery, and at least 20 minutes after the lidocaine administration, blinded
study drug will be infiltrated to provide postsurgical analgesia. Subjects will be required
to remain in the research facility for 96 hours after study drug administration.
Postsurgical efficacy, safety, and pharmacokinetic (PK) assessments will be conducted.
All subjects will return for a follow-up visits on Days 7 and 10. A phone call will be made
to each subject on Day 30 for an adverse event (AE) assessment and to inquire as to whether
the subject made any unscheduled phone calls or office visits related to pain.
1. Male or female, ≥18 years of age at screening.
2. Scheduled to undergo bilateral third molar extractions (i.e., extraction of all four
third molars) under local anesthesia. At least one lower mandibular third molar must
involve full or partial bony impaction confirmed by visual or radiological evidence.
3. American Society of Anesthesiology (ASA) physical status 1, 2, or 3.
4. Female subjects must be either surgically sterile, using a medically acceptable
method of birth control, or at least 2 years postmenopausal, and must have a
documented negative pregnancy test result during screening and on Day 1 prior to
5. Able to provide informed consent, adhere to the study visit schedule, and complete
all study assessments.
1. History of hypersensitivity or idiosyncratic reaction to amide-type local anesthetics
2. Contraindication to lidocaine, epinephrine, bupivacaine, or oxycodone.
3. History of significant drug allergy (e.g., anaphylaxis or hepatotoxicity).
4. Positive test result from the urine drug screen at screening or prior to the surgical
5. Currently pregnant, nursing, or planning to become pregnant during the study or
within 1 month after study drug administration.
6. History or active psychiatric illness (including major depression, bipolar disorder,
or anxiety); Type 1 or Type 2 diabetes; severe renal or hepatic impairment;
significant cardiovascular disease (including cardiac rhythm disturbance); migraine
headaches, frequent headaches, other pain conditions, or other medical condition
that, in the opinion of the Investigator, may increase the risk of surgery or
interfere with the evaluation of the study drug.
7. History of infection requiring intravenous (IV) antibiotics within 45 days or oral
(PO) antibiotics within 30 days prior to study drug administration for reasons other
than dental prophylaxis. Subjects must be afebrile, without signs or symptoms
indicative of active infection.
8. Use of any of the following medications within the times specified before surgery:
long-acting opioid medication, nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin
(except for low-dose aspirin used for cardioprotection), or acetaminophen within 3
days, or any opioid medication within 24 hours.
9. Initiation of treatment with any of the following medications within 1 month of
EXPAREL infiltration or if the medication(s) are being given to control pain:
selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake
inhibitors (SNRIs), gabapentin, pregabalin (Lyrica®), or duloxetine (Cymbalta®). If a
subject is taking one of these medications for a reason other than pain control, he
or she must be on a stable dose for at least 1 month prior to EXPAREL administration.
10. Current use of systemic glucocorticosteroids within 1 month of enrollment in this
11. Use of any concurrent therapy that could interfere with the evaluation of efficacy or
safety, such as any drugs which in the Investigator's opinion may exert significant
analgesic properties or act synergistically with the investigational product.
12. Administration of an investigational drug within 30 days or 5 elimination half-lives
of such investigational drug, whichever is longer, prior to study drug
administration, or planned administration of another investigational product or
procedure during the subject's participation in this study.