Efficacy, Safety, and Pharmacokinetics of Femoral Nerve Block With EXPAREL in Total Knee Arthroplasty

NCT02713178 | Completed Phase 3 Results

• 1 other identifier: 402-C-326
• Study Type: interventional
• Target: 232
• Locations: 3 countries
• Sites: 17

Brief Summary

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study in 232 adult subjects undergoing primary unilateral TKA under general or spinal anesthesia.

Conditions

Pain

Outcome Measures

Primary Outcomes (1)

• Area Under the Curve (AUC) of Visual Analog Scale (VAS) Pain Intensity Scores Through 72 Hours

  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."

  0-72 hours

Secondary Outcomes (3)

• Total Postsurgical Opioid Consumption Through 72 Hours

  0-72 hours

• Percentage of Opioid-free Participants Through 72 Hours

  0-72 hours

• Time to First Opioid Rescue Through 72 Hours

  0-72 hours

Study Arms (3)

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.

Drug: bupivacaine liposome injectable suspension

EXPAREL 266 mg

ACTIVE COMPARATOR

Single dose of 266 mg (20 mL) EXPAREL (bupivacaine liposome injectable suspension).

Drug: bupivacaine liposome injectable suspension

Placebo

PLACEBO COMPARATOR

Normal saline (20 mL).

Drug: Placebo

Interventions

bupivacaine liposome injectable suspension DRUG

bupivacaine liposome injectable suspension 133 mg expanded with normal saline to 20 mL or 266 mg in 20 mL

Also known as: EXPAREL

EXPAREL 133 mg; EXPAREL 266 mg

Placebo DRUG

Normal saline.

Also known as: Normal saline

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, at least 18 years of age at screening.
• Scheduled to undergo primary unilateral TKA under general or spinal anesthesia.
• American Society of Anesthesiologists (ASA) physical status 1, 2, or 3.
• Female subject must be surgically sterile; or at least 2 years postmenopausal; or have a monogamous partner who is surgically sterile; or practicing double-barrier contraception; or practicing abstinence (must agree to use double-barrier contraception in the event of sexual activity); or using an insertable, injectable, transdermal, or combination oral contraceptive approved by the FDA for greater than 2 months prior to screening and commit to the use of an acceptable form of birth control for the duration of the study and for 30 days after completion of the study.
• Able to demonstrate sensory function by exhibiting sensitivity to cold, pinprick, and light touch.
• Able to provide informed consent, adhere to the study visit schedule, and complete all study assessments.

You may not qualify if:

• Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration.
• Planned concurrent surgical procedure (e.g., bilateral TKA).
• Concurrent painful physical condition that may require analgesic treatment (such as an NSAID or opioid) in the postsurgical period for pain that is not strictly related to the knee surgery and which may confound the postsurgical assessments (e.g., significant pain from other joints including the non-index knee joint, chronic neuropathic pain, concurrent or prior contralateral TKA, concurrent foot surgery).
• Previous open knee surgery on the knee being considered for TKA. Prior arthroscopy is permitted.
• History of hypersensitivity or idiosyncratic reaction to amide-type local anesthetics.
• Contraindication to any one of the following: bupivacaine, oxycodone, morphine, or hydromorphone.
• Use of any of the following medications within the times specified before surgery: long-acting opioid medication or NSAIDs (except for low-dose aspirin used for cardioprotection) within 3 days, or any opioid medication within 24 hours.
• Initiation of treatment with any of the following medications within 1 month of study drug administration 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 study drug administration.
• Current use of systemic glucocorticosteroids within 1 month of enrollment in this study.
• Use of dexmedetomidine HCl (Precedex®) within 3 days of study drug administration.
• History of impaired kidney function, poorly controlled chronic respiratory disease, rheumatoid arthritis, coagulopathy, or loss of sensation in extremities.
• Impaired kidney function (e.g., serum creatinine level \>2 mg/dL \[176.8 µmol/L\] or blood urea nitrogen level \>50 mg/dL \[17.9 mmol/L\]) or impaired liver function (e.g., serum aspartate aminotransferase \[AST\] level \>3 times the upper limit of normal \[ULN\] or serum alanine aminotransferase \[ALT\] level \>3 times the ULN.)
• Uncontrolled anxiety, psychiatric, or neurological disorder that might interfere with study assessments.
• Any chronic neuromuscular deficit effecting the peripheral nerves or muscles of the surgical extremity.
• Any chronic condition or disease that would compromise neurological or vascular assessments.

Sponsors & Collaborators

• Pacira Pharmaceuticals, Inc: lead

Study Sites (17)

Horizon Research Group, Inc

Mobile, Alabama, 36608, United States

Location

Denver Metro Orthopedics

Englewood, Colorado, 80113, United States

Location

Jackson Memorial Hospital/University of Miami

Miami, Florida, 33136, United States

Location

Pensacola Research Associates

Pensacola, Florida, 32504, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Fairview Hospital

Cleveland, Ohio, United States

Location

Indiana Regional Medical Center

Indiana, Pennsylvania, 15701, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Chan Soon-Shiong Medical Center

Windber, Pennsylvania, 15963, United States

Location

Hermann Drive Surgical Hospital

Houston, Texas, 77004, United States

Location

Westside Surgical Hospital

Houston, Texas, 77027, United States

Location

Southampton Orthopaedics Sports Medicine

Franklin, Virginia, United States

Location

Ziekenhuis Oost-Limburg

Genk, Belgium

Location

Aarhus University Hospital

Aarhus C, Denmark

Location

Regionshospital Silkeborg

Silkeborg, Denmark

Location

MeSH Terms

Conditions

Pain

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Pacira Medical Information
• Organization: Pacira Pharmaceuticals, Inc.

MedInfo@pacira.com

1-855-793-9727

Study Officials

• James B Jones, MD, PharmD

  Pacira Pharmaceuticals, Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2016
• First Posted: March 18, 2016
• Study Start: June 3, 2016
• Primary Completion: June 30, 2017
• Study Completion: June 30, 2017
• Last Updated: December 1, 2020
• Results First Posted: December 1, 2020

Record last verified: 2020-11

Locations

US (14); BE (1); DK (2)