Knee OsteoarthritisPhase 3NCT05139030
Phase 3 Adductor Canal Block With EXPAREL in Subjects Undergoing Primary Unilateral Total Knee Arthroplasty
A Phase 3 study testing bupivacaine liposome injectable suspension and Bupivacaine Hydrochloride in people with Knee Osteoarthritis and Pain Management, run by Pacira Pharmaceuticals, Inc at 6 sites in United States.
Trial summary
The purpose of the study is to compare magnitude of postsurgical analgesic effect in different groups following a single dose of study drug when administered via adductor canal block in subjects undergoing primary unilateral total knee arthroplasty. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Knee Osteoarthritis, Pain Management
- What is being tested?
- bupivacaine liposome injectable suspension and Bupivacaine Hydrochloride
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 167 participants
- Where
- 6 sitesUnited States
- Study dates
- 18 Jan 2022to 11 Jul 2022
- Phase
- Phase 3
- 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
- Male or female, ages 18 or older at screening.
- Indicated to undergo primary unilateral total knee arthroplasty under spinal anesthesia.
- Primary indication for TKA is degenerative osteoarthritis of the knee.
- American Society of Anesthesiologists (ASA) physical status 1, 2, or 3.
- Able to provide informed consent, adhere to the study schedule, and complete all study assessments.
- Body Mass Index (BMI) ≥18 and <40 kg/m2.
Who cannot join
- Allergy, hypersensitivity, intolerance, or contraindication to any of the study medications for which an alternative is not named in the protocol (e.g., amide-type local anesthetics, opioids, bupivacaine HCl, NSAIDs).
- Planned concurrent surgical procedure (e.g., bilateral TKA).
- Undergoing unicompartmental TKA or revision TKA.
- Concurrent painful physical condition (e.g., arthritis, fibromyalgia, cancer) that may require analgesic treatment with NSAIDs or opioids in the post dosing period for pain that is not strictly related to the knee surgery and which, in the Investigator's opinion, may confound the post dosing assessments.
- Inadequate sensory function below the knee as assessed by the Investigator.
- History of contralateral TKA within 1 year.
Show all 19Show fewer
- Previous open knee surgery on the knee being considered for TKA. Prior arthroscopy is permitted.
- History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.
- 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 an EXPAREL study.
- Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the Investigator, could interfere with study assessments or compliance.
- Currently pregnant, nursing, or planning to become pregnant during the study.
- Clinically significant medical disease that, in the opinion of the Investigator, would make participation in a clinical study inappropriate. This includes diabetic neuropathy, coagulation or bleeding disorders, severe peripheral vascular disease, renal insufficiency, hepatic dysfunction, or other conditions that would constitute a contraindication to participation in the study.
- Currently on a neuromodulating agent (e.g., gabapentin, pregabalin [Lyrica], duloxetine [Cymbalta], etc.)].
- Current use of systemic glucocorticoids within 30 days of randomization in this study.
- Use of dexmedetomidine HCl (Precedex®) or clonidine within 3 days of study drug administration.
- Any use of marijuana [including Tetrahydrocannabinol (THC) and Cannabidiol (CBD)] within 30 days prior to randomization, or planned use during the course of the study.
- Chronic opioid use (average ≥30 oral morphine equivalents/day) within 30 days prior to randomization.
- Given the coronavirus disease 2019 (COVID-19) pandemic, if there is a concern about a subject's recent or potential exposure to COVID-19, or if the subject is not medically fit/cleared for surgery due to suspected COVID-19 illness/symptoms, the subject must be excluded per Exclusion criterion #13.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
First Surgical Hospital
Bellaire, Texas, 77401
HD Research- Legent Orthopedic Hospital
Carrollton, Texas, 75006
Midwest Clinical Research Center, LLC
Dayton, Ohio, 45417
Woodland International Research Group
Little Rock, Arkansas, 72211
Lotus Clinical Research
Pasadena, California, 91105
Endeavor Clinical Trials
San Antonio, Texas, 78240
About this study
Official title: A Phase 3, Randomized, Double-Blind, Multicenter, Active-Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of EXPAREL Admixed With Bupivacaine Hydrochloric Acid (HCl) vs. Bupivacaine HCl Administered Via Adductor Canal Block for Postsurgical Analgesia in Subjects Undergoing Primary Unilateral Total Knee Arthroplasty
The purpose of the study is to compare magnitude of postsurgical analgesic effect in different groups following a single dose of study drug when administered via adductor canal block in subjects undergoing primary unilateral total knee arthroplasty.
Read the detailed description
This is a Phase 3, multicenter, randomized, double-blind, active-controlled study in approximately 160 subjects undergoing primary unilateral TKA under spinal anesthesia. The study will have 2 cohorts, enrolling in parallel.
Cohort 1 -Pharmacokinetics (PK), pharmacodynamics (PD), Efficacy, and Safety, Cohort 2 -Efficacy and Safety
An adaptive study design will be used in this study. An interim analysis to evaluate the sample size assumptions and evaluate futility will occur when a total of approximately 80 subjects (40 subjects in each arm) combined from either Cohort 1 or Cohort 2 have enrolled and provided complete assessment data for the primary efficacy outcome.
The time from study drug administration until the end of participation is Post-operative day (POD) 14 (±3 days). Therefore, subjects may participate in the study for up to 62 days.
- Conditions
- Knee Osteoarthritis, Pain Management
- Being tested
- bupivacaine liposome injectable suspension, Bupivacaine Hydrochloride
- Keywords
- EXPAREL, bupivacaine, analgesic, Adductor Canal Block, TKA, knee arthroplasty
- Medical subject headings
- Osteoarthritis, Knee, Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bupivacaine liposome injectable suspensionDrug
Also called EXPAREL
Adductor canal block with EXPAREL
Bupivacaine HydrochlorideDrug
Adductor Canal Block with bupivacaine HCl
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: EXPAREL admix arm | Experimental | subjects randomized to this treatment arm will receive 10 mL (133 mg) EXPAREL admixed with 10 mL (50 mg) 0.5% bupivacaine HCl Receives: Drug: bupivacaine liposome injectable suspension |
| Cohort 1: Bupivacaine HCl arm | Active comparator | subjects randomized to this treatment arm will receive 10 mL (50 mg) 0.5% bupivacaine HCl mixed with 10 mL normal saline Receives: Drug: Bupivacaine Hydrochloride |
| Cohort 2: EXPAREL admix arm | Experimental | subjects randomized to this treatment arm will receive 10 mL (133 mg) EXPAREL admixed with 10 mL (50 mg) 0.5% bupivacaine HCl Receives: Drug: bupivacaine liposome injectable suspension |
| Cohort 2: Bupivacaine HCl arm | Active comparator | subjects randomized to this treatment arm will receive 10 mL (50 mg) 0.5% bupivacaine HCl mixed with 10 mL normal saline Receives: Drug: Bupivacaine Hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
NRS Scores Through 96 Hours Post-surgery
The numeric rating scale pain intensity scores ranging from 0 to 10, where 0 equals no pain and 10 equals the worst possible pain, from 0 to 96 hours post-surgery. For each subject, the area under the curve was derived using the trapezoidal rule on the pain scores adjusted for opioid pain medication using the observed and imputed values. Area under the curve started with the first pain assessment obtained after surgery and use all subsequent pain assessments up to 96 hours post-surgery. Pain scores were taken at 5 interval point: 0 hours, 24 hours, 48 hours, 72 hours, and 96 hours. There were also unscheduled pain scores measured before opioid consumption also included in the area under the curve calculation. The area under the curve ranged from 0 to 960. Higher scores represent a worse outcome.
Measured: 0 to 96 hours post-surgery
Secondary outcomes (3)
Postsurgical Opioid Consumption Through 96 Hours Post-surgery
Total postsurgical opioid consumption in mg oral morphine equivalents (OMED) from 0 to 96 hours post-surgery.
Measured: 0 to 96 hours post-surgery
Time to First Opioid
Time to first opioid consumption post-surgery
Measured: 0 to 96 hours post-surgery
NRS Scores
Worst and average NRS pain intensity scores at 24h, 48h, 72h and 96h from the end of surgery Worst and average pain intensity scores on a numeric rating scale ranging from 0 to 10, where 0 equals no pain and 10 equals the worst possible pain, from 0 to 24 hours, 24 to 48 hours, 48 to 72 hours, and 72 to 96 hours. Mean scores at each timepoint are provided. The total range is 0 (no pain) to 10 (worst possible pain). Higher values on the scale represent worst outcome
Measured: 0-24hours, 24-48hours, 48-72hours, 72-96hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2021
- Study start18 Jan 2022
- Primary completion11 Jul 2022
- Study completion11 Jul 2022
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Knee OsteoarthritisStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 167 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pacira Pharmaceuticals, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gary Nevins, Study director, Pacira Pharmaceuticals, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05139030
- Sponsor's protocol ID
- 402-C-335
- Status last verified
- Oct 2024
- First submitted
- 15 Nov 2021
- Last updated
- 24 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Gadsden J, Gonzales J, Saha P. Plain language summary of a pain medication (liposomal bupivacaine) for pain relief after knee replacement surgery. Pain Manag. 2026 Feb;16(2):77-86. doi: 10.1080/17581869.2025.2592701. Epub 2025 Dec 19.
PubMed 41416686Gadsden J, Hamilton M, Schwartz G, Gonzales J, Hutchins J, Saha P, Song J, DiGiorgi M, Winston R. A Phase 3 Active-Controlled Trial of Liposomal Bupivacaine via Adductor Canal Block for Total Knee Arthroplasty. J Arthroplasty. 2025 Oct;40(10):2605-2614.e5. doi: 10.1016/j.arth.2025.07.030. Epub 2025 Jul 22.
PubMed 40701284
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-Blind, Multicenter, Active-Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of EXPAREL Admixed With Bupivacaine Hydrochloric Acid (HCl) vs. Bupivacaine HCl Administered Via Adductor Canal Block for Postsurgical Analgesia in Subjects Undergoing Primary Unilateral Total Knee Arthroplasty
- ClinicalTrials.gov ID
- NCT05139030
- Acronym / sponsor ID
- 402-C-335
- Conditions
- Knee Osteoarthritis, Pain Management
- Keywords
- EXPAREL, bupivacaine, analgesic, Adductor Canal Block, TKA, knee arthroplasty
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 167 participants (actual)
- Lead sponsor
- Pacira Pharmaceuticals, IncIndustry (pharma, biotech, devices)
- Study start
- 18 Jan 2022 (actual)
- Primary completion
- 11 Jul 2022 (actual)
- Study completion
- 11 Jul 2022 (actual)
- First posted
- 1 Dec 2021 (actual)
- Results
- Posted 24 Oct 2024
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 the study is to compare magnitude of postsurgical analgesic effect in different groups following a single dose of study drug when administered via adductor canal block in subjects undergoing primary unilateral total knee arthroplasty.
Detailed description
This is a Phase 3, multicenter, randomized, double-blind, active-controlled study in approximately 160 subjects undergoing primary unilateral TKA under spinal anesthesia. The study will have 2 cohorts, enrolling in parallel.
Cohort 1 -Pharmacokinetics (PK), pharmacodynamics (PD), Efficacy, and Safety, Cohort 2 -Efficacy and Safety
An adaptive study design will be used in this study. An interim analysis to evaluate the sample size assumptions and evaluate futility will occur when a total of approximately 80 subjects (40 subjects in each arm) combined from either Cohort 1 or Cohort 2 have enrolled and provided complete assessment data for the primary efficacy outcome.
The time from study drug administration until the end of participation is Post-operative day (POD) 14 (±3 days). Therefore, subjects may participate in the study for up to 62 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: EXPAREL admix arm | Experimental | Drug: bupivacaine liposome injectable suspensionsubjects randomized to this treatment arm will receive 10 mL (133 mg) EXPAREL admixed with 10 mL (50 mg) 0.5% bupivacaine HCl |
| Cohort 1: Bupivacaine HCl arm | Active comparator | Drug: Bupivacaine Hydrochloridesubjects randomized to this treatment arm will receive 10 mL (50 mg) 0.5% bupivacaine HCl mixed with 10 mL normal saline |
| Cohort 2: EXPAREL admix arm | Experimental | Drug: bupivacaine liposome injectable suspensionsubjects randomized to this treatment arm will receive 10 mL (133 mg) EXPAREL admixed with 10 mL (50 mg) 0.5% bupivacaine HCl |
| Cohort 2: Bupivacaine HCl arm | Active comparator | Drug: Bupivacaine Hydrochloridesubjects randomized to this treatment arm will receive 10 mL (50 mg) 0.5% bupivacaine HCl mixed with 10 mL normal saline |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female, ages 18 or older at screening.
- Indicated to undergo primary unilateral total knee arthroplasty under spinal anesthesia.
- Primary indication for TKA is degenerative osteoarthritis of the knee.
- American Society of Anesthesiologists (ASA) physical status 1, 2, or 3.
- Able to provide informed consent, adhere to the study schedule, and complete all study assessments.
Key exclusion criteria (19 listed)
- Allergy, hypersensitivity, intolerance, or contraindication to any of the study medications for which an alternative is not named in the protocol (e.g., amide-type local anesthetics, opioids, bupivacaine HCl, NSAIDs).
- Planned concurrent surgical procedure (e.g., bilateral TKA).
- Undergoing unicompartmental TKA or revision TKA.
- Concurrent painful physical condition (e.g., arthritis, fibromyalgia, cancer) that may require analgesic treatment with NSAIDs or opioids in the post dosing period for pain that is not strictly related to the knee surgery and which, in the Investigator's opinion, may confound the post dosing assessments.
- Inadequate sensory function below the knee as assessed by the Investigator.
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 liposome injectable suspensionAlso: EXPARELAdductor canal block with EXPAREL | Drug | Cohort 1: EXPAREL admix arm, Cohort 2: EXPAREL admix arm |
| Bupivacaine HydrochlorideAdductor Canal Block with bupivacaine HCl | Drug | Cohort 1: Bupivacaine HCl arm, Cohort 2: Bupivacaine HCl arm |
Primary outcome
NRS Scores Through 96 Hours Post-surgery
Time frame: 0 to 96 hours post-surgery
The numeric rating scale pain intensity scores ranging from 0 to 10, where 0 equals no pain and 10 equals the worst possible pain, from 0 to 96 hours post-surgery. For each subject, the area under the curve was derived using the trapezoidal rule on the pain scores adjusted for opioid pain medication using the observed and imputed values. Area under the curve started with the first pain assessment obtained after surgery and use all subsequent pain assessments up to 96 hours post-surgery. Pain scores were taken at 5 interval point: 0 hours, 24 hours, 48 hours, 72 hours, and 96 hours. There were also unscheduled pain scores measured before opioid consumption also included in the area under the curve calculation. The area under the curve ranged from 0 to 960. Higher scores represent a worse outcome.
3 secondary outcomes
Postsurgical Opioid Consumption Through 96 Hours Post-surgery
Time frame: 0 to 96 hours post-surgery
Time to First Opioid
Time frame: 0 to 96 hours post-surgery
NRS Scores
Time frame: 0-24hours, 24-48hours, 48-72hours, 72-96hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41416686Gadsden J, Gonzales J, Saha P. Plain language summary of a pain medication (liposomal bupivacaine) for pain relief after knee replacement surgery. Pain Manag. 2026 Feb;16(2):77-86. doi: 10.1080/17581869.2025.2592701. Epub 2025 Dec 19.
- Derived from this study: PubMed 40701284Gadsden J, Hamilton M, Schwartz G, Gonzales J, Hutchins J, Saha P, Song J, DiGiorgi M, Winston R. A Phase 3 Active-Controlled Trial of Liposomal Bupivacaine via Adductor Canal Block for Total Knee Arthroplasty. J Arthroplasty. 2025 Oct;40(10):2605-2614.e5. doi: 10.1016/j.arth.2025.07.030. Epub 2025 Jul 22.
- Individual participant dataSharing planned: No
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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.
Gary Nevins study director
Pacira Pharmaceuticals, Inc
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing bupivacaine liposome injectable suspension and Bupivacaine Hydrochloride in people with Knee Osteoarthritis and Pain Management, run by Pacira Pharmaceuticals, Inc at 6 sites 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 6 inclusion and 19 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 24 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Oct 2024). 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?
NRS Scores Through 96 Hours Post-surgery (time frame: 0 to 96 hours post-surgery). 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 NCT05139030, which also lists 2 linked publications.
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 24 Oct 2024.