Safety and Pharmacokinetics Study of Redosing EXPAREL in Healthy Volunteers

NCT02210247 | Completed Phase 1 Results

• 1 other identifier: 402-C-113
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (5)

• 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

Study Arms (5)

Cohort 1

ACTIVE COMPARATOR

Cohort 1 will receive a single dose of EXPAREL 266 mg on Day 1. No additional dose will be given.

Drug: EXPAREL

Cohort 2

ACTIVE COMPARATOR

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

Cohort 3

ACTIVE COMPARATOR

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

Cohort 4

ACTIVE COMPARATOR

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

Cohort 5

ACTIVE COMPARATOR

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

Interventions

EXPAREL DRUG

Also known as: bupivacaine liposome injectable suspension

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pacira Pharmaceuticals, Inc: lead

Study Sites (1)

Medpace Clinical Pharmacology Unit

Cincinnati, Ohio, 45227, United States

Location

Related Publications (1)

• 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.

  PMID: 28120158 DERIVED

Results Point of Contact

• Title: Pacira Medical Information
• Organization: Pacira Pharmaceuticals Inc.

MedInfo@pacira.com

1-855-793-9727

Study Officials

• Lukasz Biernat, MD

  Medpace Clinical Pharmacology Unit

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2014
• First Posted: August 6, 2014
• Study Start: August 1, 2014
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: July 6, 2021
• Results First Posted: July 2, 2021

Record last verified: 2021-07

Locations

US (1)