EXPAREL Dose-Response for Single-Injection Femoral Nerve Blocks

NCT01349140 | Completed Phase 1 Results FDA Drug

• 1 other identifier: EXPAREL Dose-Response
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

EXPAREL™, an investigational drug product, is a new formulation of a local anesthetic (numbing medicine) that is designed to be longer acting than the currently-available local anesthetics. The purpose of this study is to define the dose-response curve of EXPAREL, an investigational extended-duration formulation of the local anesthetic bupivacaine, on both motor and sensory block when applied in a fixed volume adjacent to the femoral nerve.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Quadriceps Femoris Muscle Strength

  A dynamometer was used to measure the force produced during a maximum voluntary isometric contraction (MVIC) in a seated position with the knees flexed at 90°. The dynamometer was placed on the anterior tibia perpendicular to the tibial crest, just proximal to the medial malleolus. Subjects were asked to take 2 seconds to come to maximum effort contracting the ipsilateral quadriceps femoris, maintain this effort for 5 seconds, and then relax. The measurements immediately before study drug administration were designated baseline, and all subsequent are expressed as a percentage of the baseline.

  Baseline until 99 hours

Secondary Outcomes (1)

• Sensory Effect

  Baseline until 99 hours

Study Arms (1)

Nerve Block

EXPERIMENTAL

The dominant side (left or right) will be randomized to one of two treatment groups: the higher or lower concentration of the local anesthetic EXPAREL. The non-dominant contralateral side will receive the other possible treatment. The volume of each and every single-injection femoral nerve block will be 30 mL (standard for femoral nerve blocks is 30-40 mL).3 Since volume will remain constant, we will vary the dose of EXPAREL by varying concentration (volume x concentration = dose). Of note, EXPAREL may be mixed with normal saline to vary the concentration. Randomization will be based on computer-generated codes. Randomization will be in blocks of two, and stratified by sex.

Drug: SKY0402

Interventions

SKY0402 DRUG

Single-injection femoral nerve block. Initial doses of SKY0402 will begin at 0 mg, and 2 mg (high) for the first subject; and 1 mg (low) and 3 mg (high) for the second subject. The next doses will be between 0-80 mg per side, determined prior to randomization of each subsequent subject. The specific subsequent doses will increase, remain the same, or decrease, determined by the P.I. in consultation with the manufacturer of SKY0402. Doses will always remain within the range of 0-80 mg per side, for a total possible dose of 0-160 mg.

Also known as: EXPAREL

Nerve Block

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• greater than or equal to 18 years old
• able and willing to have bilateral femoral nerve blocks placed and repeated motor/sensory testing for 24-120 hours (1-5 days), requiring 1-5 overnight stay(s) in the UCSD CTRI to allow dissipation of local anesthetic infusion effects to near-baseline values
• have the ability to adequately communicate with all study personnel
• willing and capable of providing written informed consent

You may not qualify if:

• daily analgesic use for over one week within the past 6 months
• opioid use within the previous 4 weeks
• any neuro-muscular deficit of either femoral nerves and/or quadriceps muscles
• body mass index \> 30 kg/m2
• current pregnancy
• incarceration
• any coagulation disorder
• uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the investigators, may interfere with study assessments or adherence
• any previous allergic reaction to fentanyl, midazolam, or an amide local anesthetic (bupivacaine is of the amide local anesthetic class)
• any previous participation in a SKY0402/EXPAREL study
• nursing mothers
• suspected or known drug or alcohol abuse within the previous year; and/or
• planning on becoming pregnant in the one month following study participation.

Sponsors & Collaborators

• University of California, San Diego: lead
• Pacira Pharmaceuticals, Inc: collaborator

Study Sites (1)

UCSD Medical Center Hillcrest

San Diego, California, 92103, United States

Location

Related Publications (3)

• Ilfeld BM, Eisenach JC, Gabriel RA. Clinical Effectiveness of Liposomal Bupivacaine Administered by Infiltration or Peripheral Nerve Block to Treat Postoperative Pain. Anesthesiology. 2021 Feb 1;134(2):283-344. doi: 10.1097/ALN.0000000000003630.

  PMID: 33372949 BACKGROUND

• Ilfeld BM, Gabriel RA, Eisenach JC. Liposomal Bupivacaine Infiltration for Knee Arthroplasty: Significant Analgesic Benefits or Just a Bunch of Fat? Anesthesiology. 2018 Oct;129(4):623-626. doi: 10.1097/ALN.0000000000002386. No abstract available.

  PMID: 30102616 BACKGROUND

• Ilfeld BM, Malhotra N, Furnish TJ, Donohue MC, Madison SJ. Liposomal bupivacaine as a single-injection peripheral nerve block: a dose-response study. Anesth Analg. 2013 Nov;117(5):1248-56. doi: 10.1213/ANE.0b013e31829cc6ae.

  PMID: 24108252 RESULT

Results Point of Contact

• Title: Brian Ilfeld, MD, MS
• Organization: University California San Diego

bilfeld@ucsd.edu

1-858-444-5949

Study Officials

• Brian M Ilfeld, MD, MS

  University California San Diego

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: DOUBLE
• Masking Details: Investigational Drug Service prepared all study medication, with each dose provided to the caregivers in a 30-mL syringe with IV line extension tubing, both wrapped in opaque tape to retain masking since the relative study drug concentration could be inferred by the opacity of the injectate. One syringe was labeled "Dominant" and the other labeled "Other." In this manner, all investigators, nursing staff, and subjects remained masked to the specific concentration/dose during all outcome measurements.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, In Residence

Model Details: Each subject is assigned two possible doses between 0-80 mg by the investigators based on previous participants' responses to various doses; and, the dominant side is then randomized to either the higher or lower dose. The response for each dose is the primary interest, and not a comparison of the left vs. the right or different dose combinations within each subject. In other words, of interest are the different doses effects on muscle strength and skin sensitivity across participants (eg., Dose A vs Dose B vs Dose C, etc).

Study Record Dates

• First Submitted: May 4, 2011
• First Posted: May 6, 2011
• Study Start: February 1, 2012
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: March 25, 2021
• Results First Posted: March 25, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)