Evaluation of EXPAREL for Prolonged Postsurgical Analgesia in Subjects Undergoing Third Molar Extraction

NCT ID: NCT02517905

Last Updated: 2020-12-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 166 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-31
• Study Completion Date: 2016-01-31

Brief 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.

Detailed Description

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.

Conditions

Dental Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

EXPAREL 133 mg

10 mL EXPAREL (bupivacaine liposome injectable suspension) injected into the maxilla (4 mL; 2 mL per side) and mandible (6 mL; 3 mL per side) at the end of surgery and ≥20 min after lidocaine administration

Group Type: EXPERIMENTAL

Bupivacaine liposome

Intervention Type: DRUG

Local administration

Placebo

10 mL normal saline injected into the maxilla (4 mL; 2 mL per side) and mandible (6 mL; 3 mL per side) at the end of surgery and ≥20 min after lidocaine administration

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Local administration

Interventions

Bupivacaine liposome

Local administration

Intervention Type: DRUG

Placebo

Local administration

Intervention Type: DRUG

Other Intervention Names

EXPAREL; Normal saline

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lotus Clinical Research, LLC

OTHER

Sponsor Role: collaborator

Pacira Pharmaceuticals, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jim Jones, MD, PharmD

Role: STUDY_DIRECTOR

Pacira Pharmaceuticals, Inc

Locations

Jean Brown Research

Salt Lake City, Utah, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

402-C-329

Identifier Type: -

Identifier Source: org_study_id