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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Bupivacaine FNB | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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 | 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 | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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.
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| Name | Affiliation | Role |
|---|---|---|
| David Leiman, MD | Research Concepts, GP, LLC | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Concepts, GP, LLC | Houston | Texas | 77054 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Bupivacaine FNB + EXPAREL Infiltration | Femoral nerve block with bupivacaine hydrochloride (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. Bupivacaine FNB: 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 Infiltration: 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. |
| FG001 | Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine | Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure. Note: Seven subjects received EXPAREL mixed with bupivacaine with epinephrine. The data for these subjects are summarized as a separate arm from "Bupivacaine FNB + EXPAREL Infiltration." |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Bupivacaine FNB + EXPAREL Infiltration | FNB 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. Bupivacaine FNB: 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 Infiltration: 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | 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. | Posted | Mean | Standard Deviation | ng/mL | Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose |
|
Adverse events were to be monitored from the time the informed consent form was signed through Day 14 post-dose.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Bupivacaine FNB + EXPAREL Infiltration | FNB 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. Bupivacaine FNB: 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 Infiltration: 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pacira Medical Information | Pacira Pharmaceuticals, Inc. | 1-855-793-9727 | MedInfo@pacira.com |
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| ID | Term |
|---|---|
| D010146 | Pain |
| ID | Term |
|---|---|
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D002045 | Bupivacaine |
| ID | Term |
|---|---|
| D000813 | Anilides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D000814 | Aniline Compounds |
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|
| EXPAREL Infiltration | Drug | 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. |
|
|
| 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 | 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 | Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose |
| BG001 | Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine | Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure. Note: Seven subjects received EXPAREL mixed with bupivacaine with epinephrine. The data for these subjects are summarized as a separate arm from "Bupivacaine FNB + EXPAREL Infiltration." |
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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FNB 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.
Bupivacaine FNB: 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 Infiltration: 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.
| OG001 | Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine | Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure. Note: Seven subjects received EXPAREL mixed with bupivacaine with epinephrine. The data for these subjects are summarized as a separate arm from "Bupivacaine FNB + EXPAREL Infiltration." |
|
|
| Primary | 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 | 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. | Posted | Median | Full Range | hours | Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose |
|
|
|
| Primary | 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 | 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. | Posted | Mean | Standard Deviation | hours*ng/mL | Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose |
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| Primary | 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 | Posted | Mean | Standard Deviation | hours*ng/mL | Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose |
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| Primary | 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 | 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. | Posted | Mean | Standard Deviation | 1/hours | Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose |
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| Primary | 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 | 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. | Posted | Mean | Standard Deviation | hours | Baseline, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours, and 14 days post-dose |
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| 0 |
| 16 |
| 0 |
| 16 |
| 1 |
| 16 |
| EG001 | Bupivacaine FNB + EXPAREL Infiltration Admixed With Bupivacaine | Femoral nerve block (FNB) with bupivacaine HCl 0.5% with epinephrine 1:200,000 within 2 hours of the surgical procedure. Infiltration of EXPAREL 266 mg admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 just prior to wound closure. Bupivacaine FNB: 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 Infiltration: A single dose of EXPAREL 266 mg expanded to 60 mL with preservative-free sterile normal saline admixed with bupivacaine HCl 0.5% with epinephrine 1:200,000 infiltrated into the surgical site just prior to wound closure. | 0 | 7 | 0 | 7 | 0 | 7 |
| Hypercapnia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
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| D000588 |
| Amines |