NCT02210247 - Safety and Pharmacokinetics Study of Redosing EXPAREL in Healthy Volunteers | Crick

Overview

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

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).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

60

Conditions

Healthy Volunteers

Interventions

EXPARELDRUG

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

Medpace Clinical Pharmacology Unit

Cincinnati, Ohio, United States

Outcomes

Primary Outcomes

Maximum Plasma Concentration (Cmax)

Time frame: 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)

Time frame: 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)]

Time frame: 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

Time frame: 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)

Time frame: 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