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

NCT04173611 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 402-C-121
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Keywords

Pharmacodynamics; Pharmacokinetics; Safety; Efficacy

Outcome Measures

Primary Outcomes (5)

• Area under the plasma concentration-versus-time curve

  Pharmacokinetic endpoint

  6-8 weeks

• Maximum plasma concentration (Cmax) and time of Cmax (Tmax).

  Pharmacokinetic endpoint

  6-8 weeks

• The apparent terminal elimination half-life (t1/2el)

  Pharmacokinetic endpoint

  6-8 weeks

• Apparent clearance (CL/F)

  Pharmacokinetic endpoint

  6-8 weeks

• Apparent volume of distribution (Vd)

  Pharmacokinetic endpoint

  6-8 weeks

Secondary Outcomes (2)

• Incidence of treatment-emergent AEs (TEAEs) through Day 9

  6-8 weeks

• Proportion of subjects who have any of neurological events

  6-8 weeks

Other Outcomes (2)

• Average time to onset of sensory block and motor block

  6-8 weeks

• Average duration of sensory block and motor block

  6-8 weeks

Study Arms (3)

EXPAREL®

EXPERIMENTAL

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).

Drug: EXPAREL

Bupivacaine

ACTIVE COMPARATOR

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®.

Drug: Bupivacaine Hydrochloride

Placebo

ACTIVE COMPARATOR

Subjects in the placebo arm will receive normal saline intrathecal injection

Other: Placebo

Interventions

EXPAREL DRUG

Injection into the Intrathecal space.

EXPAREL®

Bupivacaine Hydrochloride DRUG

Injection into the Intrathecal space.

Also known as: 0.5% Bupivacaine HCl

Bupivacaine

Placebo OTHER

Injection into the Intrathecal space.

Also known as: Saline

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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).
• 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).
• Subjects at an increased risk for bleeding or who have a coagulation disorder (defined as platelet count less than 80,000 × 103/mm3).
• 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.
• 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.
• Currently pregnant, nursing, or planning to become pregnant during the study or within 30 days after completion of the study.
• Positive serology test result for Human Immunodeficiency Virus (HIV), Hepatitis B virus, or Hepatitis C virus.
• Clinically significant abnormal ECG that in the opinion of the investigator would preclude the subject from participation in the study.
• Previous participation in a Pacira study.
• History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.
• 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

Sponsors & Collaborators

• Pacira Pharmaceuticals, Inc: lead

Study Sites (1)

Duke University

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Interventions

Bupivacaine; Sodium Chloride

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Donald C Manning, MD, PhD

  Pacira Pharmaceuticals, Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Each of the cohorts will be masked as to proceed to subsequent next dose escalation cohort.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The decision to proceed to each next cohort will be made following a full review of the safety, PK, and PD data from the previous completed cohort(s).

Study Record Dates

• First Submitted: November 18, 2019
• First Posted: November 22, 2019
• Study Start: June 8, 2020
• Primary Completion: December 7, 2020
• Study Completion: December 7, 2020
• Last Updated: May 6, 2021

Record last verified: 2021-04

Locations

US (1)