PainPhase 4NCT02255500

EXPAREL Infiltration in Subjects Undergoing Femoral Nerve Block With Bupivacaine HCl for Total Knee Arthroplasty

A Phase 4 study testing Bupivacaine FNB and EXPAREL Infiltration in people with Pain, run by Pacira Pharmaceuticals, Inc at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to evaluate the safety and pharmacokinetics of EXPAREL in subjects who undergo femoral nerve block with bupivacaine HCl for unilateral total knee arthroplasty (TKA). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Pain
What is being tested?: Bupivacaine FNB and EXPAREL Infiltration
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 23 participants
Where: 1 siteUnited States
Study dates: Sep 2014to Mar 2015
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Males or females ≥18 years of age.
American Society of Anesthesiologists (ASA) physical status 1, 2, or 3.
Scheduled to undergo femoral nerve 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.

Who cannot join

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.

Show all 13Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Research Concepts, GP, LLC
Houston, Texas, 77054

Other trials in United States

About this study

Official title: Evaluation of the Pharmacokinetics and Safety of Local Administration of EXPAREL in Subjects Undergoing Femoral Nerve Block With Bupivacaine HCl for Unilateral Total Knee Arthroplasty

The purpose of this study is to evaluate the safety and pharmacokinetics of EXPAREL in subjects who undergo femoral nerve block with bupivacaine HCl for unilateral total knee arthroplasty (TKA).

Read the detailed description

On Day 1, eligible subjects will receive a single 20 mL dose of bupivacaine hydrochloride (HCl) 0.5% with epinephrine 1:200,000 within 2 hours prior to the surgical procedure as an ultrasound-guided femoral nerve block (FNB). EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site prior to wound closure. There will be no local coadministration of the two drugs.

Blood samples for bupivacaine pharmacokinetic (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, 72, and 96 hours after the beginning of EXPAREL administration, and on Day 14.

Conditions: Pain
Being tested: Bupivacaine FNB, EXPAREL Infiltration
Keywords: Total knee arthroplasty
Medical subject headings: Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Bupivacaine FNBDrug
Also called Bupivacaine
A single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.
EXPAREL InfiltrationDrug
Also called Liposomal bupivacaine
A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.

Study groups in NCT02255500
Study group	Role	What they receive
Bupivacaine FNB + EXPAREL Infiltration	Experimental	Femoral nerve block with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure. Receives: Drug: Bupivacaine FNB; Drug: EXPAREL Infiltration

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Plasma Concentration (Cmax)
The maximum observed plasma concentration of a drug in the body after the drug has been administered.
Blood samples for bupivacaine pharmacokinetic (PK) analysis were to 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, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
Measured: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose
Time to Peak Plasma Concentration (Tmax)
The time to reach the maximum observed plasma concentration (Cmax)
Blood samples for bupivacaine PK analysis were to 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, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
Measured: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose
Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration After Drug Administration (AUC0-last)
Total drug exposure up to the last measurable concentration
Blood samples for bupivacaine PK analysis were to 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, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
Measured: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose
Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity After Drug Administration (AUC0-∞)
Total drug exposure, extrapolated to infinity
Blood samples for bupivacaine PK analysis were to 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, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
Measured: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose
The Apparent Terminal Elimination Rate Constant (λz)
Blood samples for bupivacaine PK analysis were to 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, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
Measured: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose
The Apparent Terminal Elimination Half-life (t1/2el)
Blood samples for bupivacaine PK analysis were to 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, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
Measured: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2014Mar 2015

First posted2 Oct 2014 (estimated)
Study startSep 2014
Primary completionMar 2015
Study completionMar 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for PainStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 23 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02255500
Sponsor's protocol ID: 402-C-406
Status last verified: Feb 2021
First submitted: 23 Sep 2014
Last updated: 8 Mar 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 8 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Evaluation of the Pharmacokinetics and Safety of Local Administration of EXPAREL in Subjects Undergoing Femoral Nerve Block With Bupivacaine HCl for Unilateral Total Knee Arthroplasty
ClinicalTrials.gov ID: NCT02255500
Acronym / sponsor ID: 402-C-406
Conditions: Pain
Keywords: Total knee arthroplasty
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 23 participants (actual)
Lead sponsor: Pacira Pharmaceuticals, IncIndustry (pharma, biotech, devices)
Study start: Sep 2014
Primary completion: Mar 2015 (actual)
Study completion: Mar 2015 (actual)
First posted: 2 Oct 2014 (estimated)
Results: Posted 24 Nov 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purpose of this study is to evaluate the safety and pharmacokinetics of EXPAREL in subjects who undergo femoral nerve block with bupivacaine HCl for unilateral total knee arthroplasty (TKA).

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Bupivacaine FNB + EXPAREL Infiltration	Experimental	Drug: Bupivacaine FNB, Drug: EXPAREL InfiltrationFemoral nerve block with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg just prior to wound closure.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Males or females ≥18 years of age.
American Society of Anesthesiologists (ASA) physical status 1, 2, or 3.
Scheduled to undergo femoral nerve 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.

Key exclusion criteria (13 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Bupivacaine FNBAlso: BupivacaineA single administration of bupivacaine HCl 0.5% with epinephrine 1:200,000 in 20 mL volume will be administered within 2 hours prior to the surgical procedure as an ultrasound-guided FNB.	Drug	Bupivacaine FNB + EXPAREL Infiltration
EXPAREL InfiltrationAlso: Liposomal bupivacaineA single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline will be infiltrated into the surgical site just prior to wound closure.	Drug	Bupivacaine FNB + EXPAREL Infiltration

Primary outcome

Maximum Plasma Concentration (Cmax)
Time frame: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose
The maximum observed plasma concentration of a drug in the body after the drug has been administered. Blood samples for bupivacaine pharmacokinetic (PK) analysis were to 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, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
Time to Peak Plasma Concentration (Tmax)
Time frame: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose
The time to reach the maximum observed plasma concentration (Cmax) Blood samples for bupivacaine PK analysis were to 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, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration After Drug Administration (AUC0-last)
Time frame: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose
Total drug exposure up to the last measurable concentration Blood samples for bupivacaine PK analysis were to 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, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity After Drug Administration (AUC0-∞)
Time frame: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose
Total drug exposure, extrapolated to infinity Blood samples for bupivacaine PK analysis were to 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, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
The Apparent Terminal Elimination Rate Constant (λz)
Time frame: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose
Blood samples for bupivacaine PK analysis were to 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, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration
The Apparent Terminal Elimination Half-life (t1/2el)
Time frame: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose
Blood samples for bupivacaine PK analysis were to 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, 72, and 96 hours, and 14 days after the beginning of EXPAREL administration

Results and safety

Results posted to the registry on 24 Nov 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Bupivacaine FNB + EXPAREL Infiltration	16	15
Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine	7	7

Primary outcome: Maximum Plasma Concentration (Cmax)

Time frame: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose. Mean (Standard Deviation). Unit: ng/mL

Measure	Bupivacaine FNB + EXPAREL Infiltration n = 14	Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine n = 7
Value	499 (148)	775 (299)

Population analysed: The PK analysis set includes all subjects who received bupivacaine HCl with epinephrine and EXPAREL, provided sufficient samples to allow for calculation of the PK parameters required for analysis, and did not have significant protocol deviations that might have invalidated or biased the results.

Primary outcome: Time to Peak Plasma Concentration (Tmax)

Time frame: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose. Median (Full Range). Unit: hours

Measure	Bupivacaine FNB + EXPAREL Infiltration n = 14	Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine n = 7
Value	0.675 (0.183 to 78.0)	47.450 (0.183 to 72.9)

Primary outcome: Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration After Drug Administration (AUC0-last)

Time frame: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose. Mean (Standard Deviation). Unit: hours*ng/mL

Measure	Bupivacaine FNB + EXPAREL Infiltration n = 14	Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine n = 7
Value	28234 (10710)	46600 (16489)

Primary outcome: Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity After Drug Administration (AUC0-∞)

Time frame: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose. Mean (Standard Deviation). Unit: hours*ng/mL

Measure	Bupivacaine FNB + EXPAREL Infiltration n = 6	Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine n = 1
Value	25134 (11506)	38489 (NA)

Adverse events

Time frame: Adverse events were to be monitored from the time the informed consent form was signed through Day 14 post-dose.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Bupivacaine FNB + EXPAREL Infiltration	0 of 16 (0%)	1 of 16 (6.3%)	0 of 16
Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine	0 of 7 (0%)	0 of 7 (0%)	0 of 7

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

David Leiman, MD principal investigator

Research Concepts, GP, LLC

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Bupivacaine FNB and EXPAREL Infiltration in people with Pain, run by Pacira Pharmaceuticals, Inc at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Plasma Concentration (Cmax) (time frame: Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02255500.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Mar 2021.