Study to Evaluate the Pharmacokinetics and Safety of EXPAREL Administered as a Pectoral Plane Block in Women Undergoing Breast Augmentation

Study Overview
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Brief Summary
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This is a pilot, open label, single center study in 30 women undergoing breast augmentation. The study will assess and collect information on pharmacokinetics and safety of EXPAREL administered as a pectoral plane block. A total of 15 subjects will be enrolled in each of the 2 cohorts.

Official Title
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A Phase 1, Pilot, Open Label, Study to Evaluate the Pharmacokinetics, and Safety, of EXPAREL Administered as Pectoral Plane Block in Women Undergoing Breast Augmentation Surgery

Conditions
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Breast Augmentation

Intervention / Treatment
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* Drug: Exparel Injectable Product
* Drug: Bupivacaine Hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged 18 or older, undergoing breast augmentation and are 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 ≥18 and ≤30 kg/m2 Exclusion Criteria: 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, NSAIDs) Documented history of long-term diabetes (≥10 years) or severe peripheral vascular disease Renal (serum creatinine level >2mg/dL [176.8 μmol/L]) or hepatic dysfunction (serum alanine or aspartame transferase > 3 times the upper limit of normal) Concurrent painful physical condition that may require analgesic treatment (such as long-term, consistent use of opioids) in the post dosing period for pain and which, in the investigator's opinion may confound the post dosing assessments 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 any psychiatric or other conditions that would constitute a contraindication to participation in the study Currently on neuroleptic agent [e.g., gabapentin, pregabalin (Lyrica), duloxetine (Cymbalta) etc.] Chronic opioid use in the last 30 days (≥30 morphine equivalents/ day)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 - EXPAREL<br>A total of 15 subjects will be enrolled in this cohort. Subjects in this cohort will receive 20mL EXPAREL (266mg) with 30mL of saline | Drug: Exparel Injectable Product<br>* bupivacaine liposome injectable suspension<br>|
| Experimental: Cohort 2 - EXPAREL<br>A total of 15 subjects will be enrolled. Subjects in this cohort will receive 20mL EXPAREL (266mg) with 30mL of 0.5% bupivacaine HCl (150mg) | Drug: Exparel Injectable Product<br>* bupivacaine liposome injectable suspension<br>Drug: Bupivacaine Hydrochloride<br>* 1.3%, 13.3 mg/mL<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic 1 (area under the plasma concentration) | Area under the plasma concentration-versus-time curve (AUC) | predose (up to 15 min before block), 15 min(±10min), 30 min(±5min), and 1(±15min), 2(±15min), 6(±30min), 10(±30min), 18(±1), 26(±1), 36(±2), 48(±2), 60(±2), 72(±3), and 96 (±3) hours from start of study drug administration | 
| Pharmacokinetic 2 (Cmax) | Maximum plasma concentration | predose (up to 15 min before block), 15 min(±10min), 30 min(±5min), and 1(±15min), 2(±15min), 6(±30min), 10(±30min), 18(±1), 26(±1), 36(±2), 48(±2), 60(±2), 72(±3), and 96 (±3) hours from start of study drug administration | 
| Pharmacokinetic 3 (half-life) | The apparent terminal elimination half-life (t1/2el) | predose (up to 15 min before block), 15 min(±10min), 30 min(±5min), and 1(±15min), 2(±15min), 6(±30min), 10(±30min), 18(±1), 26(±1), 36(±2), 48(±2), 60(±2), 72(±3), and 96 (±3) hours from start of study drug administration | 
| Pharmacokinetic 4 (apparent clearance) | Apparent Clearance (CL/F) | predose (up to 15 min before block), 15 min(±10min), 30 min(±5min), and 1(±15min), 2(±15min), 6(±30min), 10(±30min), 18(±1), 26(±1), 36(±2), 48(±2), 60(±2), 72(±3), and 96 (±3) hours from start of study drug administration | 
| Pharmacokinetic 5 (Mean residence time) | Mean residence time (MRT) | predose (up to 15 min before block), 15 min(±10min), 30 min(±5min), and 1(±15min), 2(±15min), 6(±30min), 10(±30min), 18(±1), 26(±1), 36(±2), 48(±2), 60(±2), 72(±3), and 96 (±3) hours from start of study drug administration |