Safety and Pharmacokinetics Study of Redosing EXPAREL in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and pharmacokinetics of redosing EXPAREL via local subcutaneous infiltration in healthy volunteers.

Detailed Description
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During Dosing Period 1, blood samples for pharmacokinetic (PK) analysis will be obtained predose (15 minutes prior to administration of EXPAREL) through 12 hours postdose (i.e., at 15 and 30 minutes, 1, 2, 4, 8, and 12 hours) for Cohort 4; through 36 hours postdose (i.e., at 15 and 30 minutes, 1, 2, 4, 8, 12, 24, and 36 hours) for Cohort 3; through 60 hours postdose (i.e., at 15 and 30 minutes, 1, 2, 4, 8, 12, 24, 36, 48, and 60 hours) for Cohort 2; and through 72 hours postdose (i.e., at 15 and 30 minutes, 1, 2, 4, 8, 12, 24, 36, 48, 60, and 72 hours) for Cohorts 1 and 5. During Dosing Period 2 (Cohorts 2, 3, and 4 only), blood samples for PK analysis will be obtained predose (15 minutes prior to administration of EXPAREL) through 72 hours postdose (i.e., at 15 and 30 minutes, 1, 2, 4, 8, 12, 24, 36, 48, 60, and 72 hours).

Official Title
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An Open-Label Cohort Study to Evaluate the Safety and Pharmacokinetics of Redosing EXPAREL Via Local Subcutaneous Infiltration in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: EXPAREL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females ≥18 years of age. American Society of Anesthesiologists (ASA) physical status 1 or 2. Female subjects must be surgically sterile, at least 2 years postmenopausal, or using a medically acceptable method of birth control. If of childbearing potential, must have a documented negative pregnancy test within 24 hours before the first study drug administration. Able to provide informed consent, adhere to the study visit schedule, and complete all study assessments. Exclusion Criteria: History of hypersensitivity or idiosyncratic reactions to amide-type local anesthetics. History of abnormal bleeding tendencies/clotting disorders. Regular use of anticoagulants (except for low dose aspirin for cardioprotection). Received any investigational drug within 30 days prior to study drug administration, and/or has planned administration of another investigational product or procedure during his/her participation in this study. Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration. Subjects with significant medical conditions or laboratory results 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. Received bupivacaine or other local anesthetic within 7 days of first study drug administration.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cohort 1<br>Cohort 1 will receive a single dose of EXPAREL 266 mg on Day 1. No additional dose will be given. | Drug: EXPAREL<br> <br> * Other names: bupivacaine liposome injectable suspension;|
| Active Comparator: Cohort 2<br>Cohort 2 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 4 at 72 hours. | Drug: EXPAREL<br> <br> * Other names: bupivacaine liposome injectable suspension;|
| Active Comparator: Cohort 3<br>Cohort 3 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 3 at 48 hours. | Drug: EXPAREL<br> <br> * Other names: bupivacaine liposome injectable suspension;|
| Active Comparator: Cohort 4<br>Cohort 4 will receive a dose of EXPAREL 266 mg on Day 1 and a second dose of EXPAREL 266 mg on Day 2 at 24 hours. | Drug: EXPAREL<br> <br> * Other names: bupivacaine liposome injectable suspension;|
| Active Comparator: Cohort 5<br>Cohort 5 will receive a single dose of EXPAREL 266 mg on Day 1 followed immediately by a second dose of EXPAREL 266 mg (total of 532 mg/40 mL). | Drug: EXPAREL<br> <br> * Other names: bupivacaine liposome injectable suspension;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) |  | Period(P)1 all cohorts (C) 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects | 
| Time to Maximum Concentration (Tmax) |  | Period(P)1 all cohorts 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects | 
| Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration [AUC(0-last)] |  | Period(P)1 all cohorts (C) 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects | 
| Apparent Terminal Elimination Half-life |  | Period(P)1 all cohorts 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects | 
| The Apparent Terminal Elimination Rate Constant (λz) |  | Period(P)1 all cohorts 15 m in pre, 15,30m, 1,2,34,8,12h postdose. C3: +24, 36 h postdose. C2: C3+48,60h postdose; C1 and C5: C2+72h postdose; P2: C2,3,4 only: 15m pre, 1,2,4,8,12,24,36,48,60,72h postdose. Final at D14- all subjects |