Evaluation of EXPAREL for Prolonged Postsurgical Analgesia in Subjects Undergoing Third Molar Extraction
Condition: Dental Pain
MeSH terms: Toothache
Intervention: Bupivacaine liposome; Placebo
Intervention description: Local administration; Local administration
Intervention MeSH terms: Bupivacaine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 166.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          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 surgery.

          5. Able to provide informed consent, adhere to the study visit schedule, and complete all
             study assessments.

        Exclusion Criteria:

          1. History of hypersensitivity or idiosyncratic reaction to amide-type local anesthetics
             or opioids.

          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
             procedure.

          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
             study.

         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.