Femoral Nerve Block With Liposome Bupivacaine for Postsurgical Analgesia Following Total Knee Arthroplasty

This study is currently recruiting participants.
Verified September 2013 by Pacira Pharmaceuticals, Inc
Sponsor:
Information provided by (Responsible Party):
Pacira Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT01683071
First received: September 7, 2012
Last updated: September 26, 2013
Last verified: September 2013
  Purpose

The primary objectives of Part 1 are to (1) evaluate three dose levels of liposome bupivacaine versus placebo with respect to the magnitude and duration of the analgesic effect achieved following single dose injection femoral nerve block with liposome bupivacaine, and (2) select a single therapeutic dose of liposome bupivacaine from the three dose levels to be tested in Part 2.

Part 2: The primary objective of Part 2 is to compare the magnitude and duration of the analgesic effect of single injection femoral nerve block of a single dose level of liposome bupivacaine (selected from Part 1) with placebo (preservative-free normal saline).


Condition Intervention Phase
Postoperative Pain
Drug: EXPAREL
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Dose Ranging Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Single Injection Femoral Nerve Block With Liposome Bupivacaine for Postsurgical Analgesia in Subjects Undergoing Total Knee Arthroplasty

Resource links provided by NLM:


Further study details as provided by Pacira Pharmaceuticals, Inc:

Primary Outcome Measures:
  • Postoperative pain [ Time Frame: Up to 72 hours post surgery ] [ Designated as safety issue: Yes ]
    Key measurements: (1) the area under the curve (AUC) of the numeric rating scale (NRS) at rest (NRS-R) pain intensity scores through 72 hours; (2) total postsurgical opioid consumption; (3) the time to first opioid rescue; and (4) safety data.


Estimated Enrollment: 280
Study Start Date: September 2012
Estimated Study Completion Date: February 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1
EXPAREL 67 mg
Drug: EXPAREL
EXPAREL 67 mg, 133 mg, or 266 mg
Other Name: Bupivacaine liposome injectable suspension
Active Comparator: Group 2
EXPAREL 133 mg
Drug: EXPAREL
EXPAREL 67 mg, 133 mg, or 266 mg
Other Name: Bupivacaine liposome injectable suspension
Active Comparator: Group 3
EXPAREL 266 mg
Drug: EXPAREL
EXPAREL 67 mg, 133 mg, or 266 mg
Other Name: Bupivacaine liposome injectable suspension
Placebo Comparator: Group 4
Placebo (preservative-free normal saline)
Drug: Placebo
Normal saline 20 mL
Other Name: Preservative-free normal saline.

Detailed Description:

This is a Phase 2/3, multicenter, randomized, double-blind, parallel-group, placebo-controlled, dose-ranging study in subjects undergoing primary unilateral total knee arthroplasty (TKA) under general or spinal anesthesia. Note: Bupivacaine cannot be used as the spinal anesthetic.

Part 1 During Part 1 of the study, approximately 100 subjects (25 per treatment arm) will be randomized to receive a single dose injection femoral nerve block with either one of three doses of liposome bupivacaine (67, 133, or 266 mg) or placebo in 20 mL under ultrasound guidance. Preservative-free normal saline will be added to the 67 mg and 133 mg doses of study drug to achieve a volume of 20 mL.

Part 2 In Part 2 of the study, approximately 180 subjects (randomized 1:1, resulting in approximately 90 liposome bupivacaine subjects and 90 placebo subjects) will receive a single dose injection femoral nerve block with the selected dose level of liposome bupivacaine (i.e., 67, 133, or 266 mg) or placebo in 20 mL under ultrasound guidance.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female, ≥18 years of age.
  • Scheduled to undergo primary unilateral TKA under general or spinal anesthesia.
  • American Society of Anesthesiology (ASA) Physical Status 1, 2, or 3.
  • Able to demonstrate motor function by performing a 20-meter walk, unassisted, and sensory function by exhibiting sensitivity to cold.
  • Able to provide informed consent, adhere to the study visit schedule, and complete all study assessments.

Exclusion Criteria:

  • Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration. Female subjects must be surgically sterile, at least 2 years menopausal, or using an acceptable method of birth control. If of childbearing potential, must have a documented negative pregnancy test within 24 hours before surgery.
  • Planned concurrent surgical procedure (e.g., bilateral TKA).
  • Use of any of the following medications within the times specified before surgery: long-acting opioid medication, non-steroidal anti-inflammatory drugs (NSAIDs), or aspirin (except for low-dose aspirin used for cardioprotection or acetaminophen) within 3 days, or any opioid medication within 24 hours.
  • 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 TKA 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).
  • 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, gabapentin, pregabalin (Lyrica®), or duloxetine (Cymbalta®).
  • Current use of systemic glucocorticosteroids within 1 month of enrollment in this study.
  • Body weight < 50 kg (110 pounds) or a body mass index ≥ 40 kg/m2.
  • Contraindication to morphine, hydromorphone, oxycodone, or bupivacaine.
  • 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.
  • Previous participation in a liposome bupivacaine study.
  • History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.
  • Failure to pass the urine drug screen.
  • Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the Investigator, could interfere with study assessments or compliance.
  • 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.
  • Significant medical conditions or laboratory results that, in the opinion of the Investigator, indicate an increased vulnerability to study drugs and procedures.
  • Subjects who are planned to receive Entereg® (alvimopan).
  • Subjects who will receive prophylactic antiemetics or planned postsurgical antiemetics given without regard to the subject's emesis needs.
  • Use of dexmedetomidine HCl (Precedex®) within 3 days of surgery.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01683071

  Show 30 Study Locations
Sponsors and Collaborators
Pacira Pharmaceuticals, Inc
Investigators
Study Director: Erol Onel, MD Pacira Pharmaceuticals, Inc
  More Information

No publications provided

Responsible Party: Pacira Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT01683071     History of Changes
Other Study ID Numbers: 402-C-323
Study First Received: September 7, 2012
Last Updated: September 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pacira Pharmaceuticals, Inc:
Total knee arthroplasty
Analgesia
Pain management

Additional relevant MeSH terms:
Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Signs and Symptoms
Bupivacaine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 16, 2014