Pharmacokinetics and Safety of Bupivacaine HCl Spinal Block and EXPAREL Local Infiltration in Total Knee Arthroplasty

February 11, 2021 updated by: Pacira Pharmaceuticals, Inc

Evaluation of the Pharmacokinetics and Safety of Bupivacaine HCl Spinal Block and EXPAREL Local Infiltration in Subjects Undergoing for Unilateral Total Knee Arthroplasty

This is a Phase 4, multicenter, open-label study designed to characterize the pharmacokinetic (PK) profile of total bupivacaine in approximately 15 adult subjects undergoing primary unilateral total knee arthroplasty (TKA) with bupivacaine hydrochloride (HCl) spinal nerve block (SNB) and EXPAREL local infiltration into the surgical site.

Study Overview

Status

Completed

Conditions

Detailed Description

On Day 1, following an epinephrine "wash" of the spinal block syringe, eligible subjects will receive a single 1.6 mL dose of bupivacaine HCl 7.5 mg/mL within 2 hours prior to the surgical procedure as a spinal block. EXPAREL 266 mg in 20 mL (expanded with 70 mL of preservative-free sterile normal saline to a total volume of 90 mL) will be infiltrated into the surgical site at the end of the surgery prior to wound closure. There will be no local co-administration of the two drugs.

Blood samples for bupivacaine PK analysis will be obtained from subjects at baseline (prior to bupivacaine HCl administration for nerve block), 15 minutes, 30 minutes, and 1, 2, 4, 8, 12, 24, 48, and 72 hours after the beginning of EXPAREL administration, and on Day 14.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Alabama
      • Sheffield, Alabama, United States, 35660
        • Shaols Medical Trials, Inc.
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota Medical Center - Fairview, West Bank

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Males or females ≥18 years of age.
  2. American Society of Anesthesiologists (ASA) physical status 1, 2, or 3.
  3. Scheduled to undergo spinal block in conjunction with unilateral TKA.
  4. Female subjects must be surgically sterile, at least 2 years postmenopausal, or using a medically acceptable method of birth control. Females of childbearing potential must have a documented negative blood or urine pregnancy test result within 24 hours before surgery.
  5. Able to provide informed consent, adhere to the study schedule, and complete all study assessments.

Exclusion Criteria:

  1. History of hypersensitivity or idiosyncratic reactions to amide-type local anesthetics or opioids.
  2. Contraindication to bupivacaine.
  3. Received bupivacaine or any other local anesthetic within 7 days of EXPAREL administration.
  4. Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after EXPAREL administration.
  5. Planned concurrent surgical procedure (e.g., bilateral TKA).
  6. Body weight <50 kg (110 pounds) or a body mass index ≥45 kg/m2.
  7. Received any investigational drug within 30 days prior to EXPAREL administration, and/or has planned administration of another investigational product or procedure during the subject's participation in this study.
  8. Previous participation in an EXPAREL study.
  9. Malignancy in the last 2 years, with the exception of non-metastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
  10. Current or historical evidence of any clinically significant disease or condition, especially cardiovascular or neurological conditions that, in the opinion of the Investigator, may increase the risk of surgery or complicate the subject's postsurgical course.
  11. Clinically significant medical or psychiatric disease that, in the opinion of the Investigator, would constitute a contraindication to participation in the study, or cause inability to comply with the study requirements.

    In addition, the subject will be ineligible to receive EXPAREL if he or she meets the following criteria during surgery:

  12. Any clinically significant event or condition uncovered during the surgery (e.g., excessive bleeding, acute sepsis) that might render the subject medically unstable or complicate the subject's postsurgical course.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bupivacaine SNB + EXPAREL Infiltration
Spinal block with bupivacaine HCl 7.5 mg/mL. Local infiltration of EXPAREL 266 mg.
SNB with a single 1.6 mL dose of bupivacaine HCl 7.5 mg/mL within 2 hours prior to the surgical procedure.
Other Names:
  • Bupivacaine
Local infiltration of EXPAREL 266 mg into the surgical site at the end of the surgery just prior to wound closure.
Other Names:
  • Bupivacaine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum Plasma Concentration (Cmax)
Time Frame: baseline, 15,30 min, 1,2,4,8,12,24,48,72 hours post dose, day 14
baseline, 15,30 min, 1,2,4,8,12,24,48,72 hours post dose, day 14
Time to Peak Plasma Concentration (Tmax)
Time Frame: baseline, 15,30 min, 1,2,4,8,12,24,48,72 hours post dose, day 14
baseline, 15,30 min, 1,2,4,8,12,24,48,72 hours post dose, day 14
Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Last Collection Time After Drug Administration (AUC0-last)
Time Frame: baseline, 15,30 min, 1,2,4,8,12,24,48,72 hours post dose, day 14
baseline, 15,30 min, 1,2,4,8,12,24,48,72 hours post dose, day 14
Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity After Drug Administration (AUC0-∞)
Time Frame: baseline, 15,30 min, 1,2,4,8,12,24,48,72 hours post dose, day 14
baseline, 15,30 min, 1,2,4,8,12,24,48,72 hours post dose, day 14
The Apparent Terminal Elimination Rate Constant (λz)
Time Frame: baseline, 15,30 min, 1,2,4,8,12,24,48,72 hours post dose, day 14
baseline, 15,30 min, 1,2,4,8,12,24,48,72 hours post dose, day 14
The Apparent Terminal Elimination Half-life (t1/2el)
Time Frame: baseline, 15,30 min, 1,2,4,8,12,24,48,72 hours post dose, day 14
baseline, 15,30 min, 1,2,4,8,12,24,48,72 hours post dose, day 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Jacob Hutchins, MD, University of Minnesoty

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2014

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

March 1, 2015

Study Registration Dates

First Submitted

November 3, 2014

First Submitted That Met QC Criteria

November 3, 2014

First Posted (Estimate)

November 6, 2014

Study Record Updates

Last Update Posted (Actual)

March 8, 2021

Last Update Submitted That Met QC Criteria

February 11, 2021

Last Verified

February 1, 2021

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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