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

NCT02284386 | Completed Phase 4 Results

• 1 other identifier: 402-C-405
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Pain

Keywords

Total knee arthroplasty

Outcome Measures

Primary Outcomes (6)

• Maximum Plasma Concentration (Cmax)

  baseline, 15,30 min, 1,2,4,8,12,24,48,72 hours post dose, day 14

• Time to Peak Plasma Concentration (Tmax)

  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)

  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-∞)

  baseline, 15,30 min, 1,2,4,8,12,24,48,72 hours post dose, day 14

• The Apparent Terminal Elimination Rate Constant (λz)

  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)

  baseline, 15,30 min, 1,2,4,8,12,24,48,72 hours post dose, day 14

Study Arms (1)

Bupivacaine SNB + EXPAREL Infiltration

EXPERIMENTAL

Spinal block with bupivacaine HCl 7.5 mg/mL. Local infiltration of EXPAREL 266 mg.

Drug: Bupivacaine SNB; Drug: EXPAREL Infiltration

Interventions

Bupivacaine SNB DRUG

SNB with a single 1.6 mL dose of bupivacaine HCl 7.5 mg/mL within 2 hours prior to the surgical procedure.

Also known as: Bupivacaine

Bupivacaine SNB + EXPAREL Infiltration

EXPAREL Infiltration DRUG

Local infiltration of EXPAREL 266 mg into the surgical site at the end of the surgery just prior to wound closure.

Also known as: Bupivacaine

Bupivacaine SNB + EXPAREL Infiltration

Eligibility Criteria

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

You may qualify if:

• Males or females ≥18 years of age.
• American Society of Anesthesiologists (ASA) physical status 1, 2, or 3.
• Scheduled to undergo spinal block in conjunction with unilateral TKA.
• 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.
• Able to provide informed consent, adhere to the study schedule, and complete all study assessments.

You may not qualify if:

• History of hypersensitivity or idiosyncratic reactions to amide-type local anesthetics or opioids.
• Contraindication to bupivacaine.
• Received bupivacaine or any other local anesthetic within 7 days of EXPAREL administration.
• Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after EXPAREL administration.
• Planned concurrent surgical procedure (e.g., bilateral TKA).
• Body weight \<50 kg (110 pounds) or a body mass index ≥45 kg/m2.
• 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.
• Previous participation in an EXPAREL study.
• 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.
• 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.
• 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:
• 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.

Sponsors & Collaborators

• Pacira Pharmaceuticals, Inc: lead

Study Sites (2)

Shaols Medical Trials, Inc.

Sheffield, Alabama, 35660, United States

Location

University of Minnesota Medical Center - Fairview, West Bank

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Pain

Interventions

Bupivacaine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Results Point of Contact

• Title: James B. Jones, MD, PharmD
• Organization: Pacira

jim.jones@pacira.com

(973) 254-3560

Study Officials

• Jacob Hutchins, MD

  University of Minnesoty

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2014
• First Posted: November 6, 2014
• Study Start: December 1, 2014
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: March 8, 2021
• Results First Posted: June 28, 2016

Record last verified: 2021-02

Locations

US (2)