Clinical trial NCT02210247: Safety and Pharmacokinetics Study of Redosing EXPAREL in Healthy Volunteers
Official title: An Open-Label Cohort Study to Evaluate the Safety and Pharmacokinetics of Redosing EXPAREL Via Local Subcutaneous Infiltration in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Pacira Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2014-08-06
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax)
timeFrame: 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
measure: Time to Maximum Concentration (Tmax)
timeFrame: 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
measure: Area Under the Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration [AUC(0-last)]
timeFrame: 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
measure: Apparent Terminal Elimination Half-life
timeFrame: 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
measure: The Apparent Terminal Elimination Rate Constant (λz)
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Medpace Clinical Pharmacology Unit
state: Ohio
Study officials:
affiliation: Medpace Clinical Pharmacology Unit
name: Lukasz Biernat, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rice D, Heil JW, Biernat L. Pharmacokinetic Profile and Tolerability of Liposomal Bupivacaine Following a Repeated Dose via Local Subcutaneous Infiltration in Healthy Volunteers. Clin Drug Investig. 2017 Mar;37(3):249-257. doi: 10.1007/s40261-017-0495-2.