Evaluation of Safety, Pharmacokinetics and Pharmacodynamics of EXPAREL® Administered Via a Single Intrathecal Injection to Healthy Volunteers

April 30, 2021 updated by: Pacira Pharmaceuticals, Inc

Phase 1, Randomized, Double-Blind, Active and Placebo Controlled, Dose Escalation Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of EXPAREL® Administered Via a Single Intrathecal Injection to Healthy Volunteers.

Primary objective: To assess the safety and tolerability of EXPAREL® administered as a single intrathecal injection in healthy volunteers

Secondary objective: To characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profile of EXPAREL® administered as a single intrathecal injection in healthy volunteers

Study Overview

Status

Terminated

Conditions

Detailed Description

This is a Phase-1, single center, randomized, double-blind, active and placebo-controlled study in approximately 40 healthy adult subjects.

On Day 1, eligible subjects will be randomized in blocks of 5, in a ratio of 3:1:1 to receive EXPAREL® or bupivacaine or placebo (saline) injection, respectively. Starting with treatment Cohort 1, healthy volunteers will be randomized to the 3 treatment arms within cohorts. Each cohort will consist of 10 subjects (6 EXPAREL®, 2 bupivacaine and 2 placebo). In each cohort, all 10 subjects in each cohort will receive cerebrospinal fluid (CSF) taps. Within the EXPAREL® arm, subjects will be randomized 2:1 with 4 subjects undergoing CSF tap and 2 subjects not undergoing CSF tap in each cohort. Subjects who are not undergoing CSF tap, will still be injected with needles without draw of CSF to prevent subject bias. Such a randomization will allow for characterization of the complete pharmacodynamics profile of the drug without risk of drug removal in the CSF. For those subjects randomized to the EXPAREL® arm - the dose of EXPAREL® will be determined by the cohort. Starting at 1 mL (13.3 mg) for Cohort 1, the volume of EXPAREL® will be increased by 1 mL in each subsequent cohort for a maximum of 4 mL (53.2 mg). The decision to proceed to the next cohort will be made following a full review of the safety, PK, and PD (sensory and motor) data from current completed cohort(s). All subjects will remain in the EPRU for 5 days after drug administration and will be discharged on Day 6. Subjects will be instructed to return for a follow up visit on Day 9. Adverse events (AEs) and serious adverse events (SAEs) will be recorded from the time of consent through 30 days after drug administration.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Healthy adult male or female volunteers ages ≥18 and ≤50 years old.
  2. American Society of Anesthesiologists (ASA) physical status 1.
  3. Able to provide informed consent, adhere to the study schedule, and complete all study assessments.

Exclusion Criteria:

  1. Allergy, hypersensitivity, intolerance, or contraindication to any of the study medications for which an alternative is not named in the protocol (eg, amide-type local anesthetics, opioids, bupivacaine, non-steroidal anti-inflammatory drugs [NSAIDs], spinal anesthesia).
  2. Impaired renal or hepatic function (eg, serum creatinine level >2 mg/dL [176.8 μmol/L], blood urea nitrogen level >50 mg/dL [17.9 mmol/L], serum aspartate aminotransferase [AST] level >1.5 times the upper limit of normal [ULN], or serum alanine aminotransferase [ALT] level >1.5 times the ULN).
  3. Subjects at an increased risk for bleeding or who have a coagulation disorder (defined as platelet count less than 80,000 × 103/mm3).
  4. 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 may confound the post dosing assessments.
  5. Women of childbearing potential must have a documented negative pregnancy test at screening and must be confirmed on the day of drug administration. If postmenopausal, must have a documented Follicle Stimulating Hormone (FSH) test confirming menopause at screening.
  6. Currently pregnant, nursing, or planning to become pregnant during the study or within 30 days after completion of the study.
  7. Positive serology test result for Human Immunodeficiency Virus (HIV), Hepatitis B virus, or Hepatitis C virus.
  8. Clinically significant abnormal ECG that in the opinion of the investigator would preclude the subject from participation in the study.
  9. Previous participation in a Pacira study.
  10. History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.
  11. 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: SEQUENTIAL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: EXPAREL®
For those subjects randomized to EXPAREL® arm - the dose of EXPAREL® will be determined by the cohort. Starting at 1mL (13.3mg) for cohort 1, the volume of EXPAREL® will be increased by 1 mL in each subsequent cohort for a maximum of 4mL (53.2mg).
Injection into the Intrathecal space.
ACTIVE_COMPARATOR: Bupivacaine
In each cohort, subjects randomized to the bupivacaine arm will receive 15mg of plain bupivacaine HCL (the equivalent of 13.3mg bupivacaine base) providing a 1:1 reference to the starting dose level chosen for EXPAREL®.
Injection into the Intrathecal space.
Other Names:
  • 0.5% Bupivacaine HCl
ACTIVE_COMPARATOR: Placebo
Subjects in the placebo arm will receive normal saline intrathecal injection
Injection into the Intrathecal space.
Other Names:
  • Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the plasma concentration-versus-time curve
Time Frame: 6-8 weeks
Pharmacokinetic endpoint
6-8 weeks
Maximum plasma concentration (Cmax) and time of Cmax (Tmax).
Time Frame: 6-8 weeks
Pharmacokinetic endpoint
6-8 weeks
The apparent terminal elimination half-life (t1/2el)
Time Frame: 6-8 weeks
Pharmacokinetic endpoint
6-8 weeks
Apparent clearance (CL/F)
Time Frame: 6-8 weeks
Pharmacokinetic endpoint
6-8 weeks
Apparent volume of distribution (Vd)
Time Frame: 6-8 weeks
Pharmacokinetic endpoint
6-8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of treatment-emergent AEs (TEAEs) through Day 9
Time Frame: 6-8 weeks
Safety endpoint
6-8 weeks
Proportion of subjects who have any of neurological events
Time Frame: 6-8 weeks
Safety endpoint
6-8 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Average time to onset of sensory block and motor block
Time Frame: 6-8 weeks
Pharmacodynamic Endpoint
6-8 weeks
Average duration of sensory block and motor block
Time Frame: 6-8 weeks
Pharmacodynamic Endpoint
6-8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Donald C Manning, MD, PhD, Pacira Pharmaceuticals, Inc

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 8, 2020

Primary Completion (ACTUAL)

December 7, 2020

Study Completion (ACTUAL)

December 7, 2020

Study Registration Dates

First Submitted

November 18, 2019

First Submitted That Met QC Criteria

November 19, 2019

First Posted (ACTUAL)

November 22, 2019

Study Record Updates

Last Update Posted (ACTUAL)

May 6, 2021

Last Update Submitted That Met QC Criteria

April 30, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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