Study in Adult Subjects Undergoing Posterolateral Thoracotomy

A Phase 1, Open-Label Study to Evaluate the Safety and Pharmacokinetics of EXPAREL When Administered for Postsurgical Analgesia in Subjects Undergoing Posterolateral Thoracotomy

Primary Objective: To characterize the pharmacokinetic (PK) profile of EXPAREL when administered as a posterior intercostal nerve block.

Secondary Objective: To assess the safety and tolerability of EXPAREL in this surgical model.

Study Overview

• Status: Terminated
• Conditions: Postoperative Pain Management
• Intervention / Treatment: Drug: EXPAREL

Detailed Description

This is a Phase 1, single-center, open-label study designed to evaluate the safety and PK profile of EXPAREL when administered as a posterior intercostal nerve block. Twenty-four adult subjects undergoing thoracotomy are planned for enrollment.

Subjects will be screened within 30 days prior to study drug administration. During the screening visit, which must take place at least 1 day prior to surgery, subjects will be assessed for past or present neurologic, cardiac, and general medical conditions that, in the opinion of the investigator, would preclude them from study participation.

Subjects will undergo their pre-planned thoracotomy procedure per the institution's standard of care. Prior to wound closure, subjects will be given either 40 mL of study drug (20 mL EXPAREL expanded with 20 mL normal saline) or 30 mL of study drug (20 mL EXPAREL expanded with 10 mL normal saline). Subjects will remain in the hospital for a minimum of 48 hours for pharmacokinetic testing and evaluation of safety.

On Day 14, the subject will complete the study via phone call in order to collect safety data.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males or females ≥18 years of age.
2. American Society of Anesthesiologists (ASA) physical status 1, 2, or 3.
3. Scheduled to undergo chest surgery using either minimally invasive (VATS or robotic-assisted surgery) or open techniques (posterolateral, lateral, or anterior thoracotomy or requiring insertion of an inter-rib spreader/retractor) for a primary thoracic non-infectious indication under general anesthesia.
4. Able to provide informed consent, adhere to the study schedule, and complete all study assessments.

Exclusion Criteria:

1. Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration. Female subjects must be surgically sterile, at least 2 years menopausal, or using an acceptable method of birth control. If of childbearing potential, the subject must have a documented negative pregnancy test within 24 hours before surgery.
2. Prior ipsilateral thoracotomy (the likely presence of adhesions will limit ability to perform a precise block guided by thoracoscopy). Note: previous VATS or robotic surgery is permissible.
3. Any planned pleurodesis as part of the surgical procedure.
4. Redo ipsilateral thoracotomy
5. Received bupivacaine or any other local anesthetic within 7 days of screening.
6. Body weight < 50 kilograms (110 pounds) or a body mass index ≥ 35 kg/m2.
7. History of hypersensitivity or idiosyncratic reactions to amide-type local anesthetics or opioids.
8. Previous participation in a liposome bupivacaine study.
9. History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years.
10. Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the investigator, could interfere with study assessments or compliance.
11. Significant medical conditions (including widely disseminated metastatic disease) or laboratory results that, in the opinion of the investigator, indicate an increased vulnerability to study drugs and procedures.
12. History of coronary or vascular stent placed within the past 3 months (may be extended to 1 year if medically indicated per physician discretion).
13. Have been treated for a deep vein thrombosis, pulmonary embolism, myocardial infarction, or ischemic stroke within the past 6 months (may be extended to 1 year if medically indicated per physician discretion).
14. Severely 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 >3 times the upper limit of normal [ULN], or serum alanine aminotransferase [ALT] level > 3 times ULN).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EXPAREL 20 + 20; 20 mL EXPAREL with 20 mL normal saline	Drug: EXPAREL; EXAPREL 266 mg in 20 mL
Experimental: EXPAREL 20 + 10; 20 mL EXPAREL with 10 mL normal saline	Drug: EXPAREL; EXAPREL 266 mg in 20 mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC of EXPAREL concentration	Area under the concentration curve for EXPAREL	0-72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events	Incidence to treatment-emergent adverse events through 14 days	0-14 days

Collaborators and Investigators

• Sponsor: Pacira Pharmaceuticals, Inc
• Investigators: Principal Investigator: David Rice, MD, MD Anderson

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2018
• Primary Completion (Actual): September 28, 2018
• Study Completion (Actual): September 28, 2018

Study Registration Dates

• First Submitted: February 5, 2018
• First Submitted That Met QC Criteria: February 8, 2018
• First Posted (Actual): February 12, 2018

Study Record Updates

• Last Update Posted (Actual): February 6, 2019
• Last Update Submitted That Met QC Criteria: February 4, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative
• Other Study ID Numbers: 402-C-118

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No