PK Study of EXPAREL in Subjects Undergoing Open Spinal Fusion or Reconstructive Surgery

NCT02985762 | Completed Phase 1 DMC

• 1 other identifier: 402-C-117
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

Brief Summary

The primary objective of this study is to characterize the pharmacokinetic (PK) profile of EXPAREL when administered via local wound infiltration to subjects undergoing open spinal fusion or reconstructive surgery. The secondary objectives of this study are to assess the safety, tolerability, and efficacy of EXPAREL in this surgical model.

Conditions

Spinal Fusion; Pain Management

Keywords

bupivacaine; exparel; analgesic; lumbar spine

Outcome Measures

Primary Outcomes (14)

• The area under the plasma concentration-versus-time curve from the time of administration extrapolated to infinity. The residual area from the time of the last quantifiable concentration (Ctlast) to infinity is to be calculated using the approximation

  7 days

• The VAS pain intensity scores at each assessed timepoint

  Pain intensity scores using the VAS at predose (on Day 1 prior to study drug administration); upon arrival at the post-anesthesia care unit (PACU); at 4, 8, 12, 24, 36, 48, 60, and 72 hours after the beginning of study drug administration; immediately prior to each administration of rescue pain medication; and just prior to hospital discharge

  72 hours

• Total inpatient postsurgical opioid consumption (in mg) through 72 hours or hospital discharge

  72 hours

• Time to first opioid rescue through 72 hours or hospital discharge

  72 hours

• The area under the plasma concentration-versus-time curve from the time of administration to the time of the last quantifiable concentration calculated using the log-linear trapezoidal rule

  Pharmacokinetic parameters will be estimated from plasma bupivacaine measurements using non-compartmental analysis, based on the sampling schedule at predose (on Day 1 prior to study drug administration); 15 minutes, 30 minutes, 1, 2, 4, 8, 12, 24, 36, 48, 60, 72, 84, and 96 hours after the beginning of study drug administration; and on Day 7

  7 days

• The maximum observed plasma concentration obtained directly from the experimental data without interpolation. Overall, early Cmax (occurring within 2 hours postdose) and late Cmax (occurring after 2 hours postdose) will be presented

  7 days

• The time to maximum plasma concentration (Cmax). Overall, early, and late Tmax will be presented

  7 days

• The apparent terminal elimination rate constant determined by log-linear regression of the terminal log-linear segment of the plasma concentration-versus-time curve

  7 days

• The apparent terminal elimination half-life calculated as 0.693/λz

  7 days

• Incidence of TEAEs through Day 30

  30 days

• Summary of neurological assessments (proportion of subjects who are oriented and proportion of subjects who have any of the neurological events

  30 days

• Change from baseline in ECG data closest to the median Tmax

  30 days

• Investigator assessment of the ECG (normal, abnormal - not clinically significant, abnormal - clinically significant)

  30 days

• Change from baseline in vital signs at each assessed timepoint

  30 days

Study Arms (1)

EXPAREL 266 mg/20 mL

OTHER

Eligible subjects, whose surgical incision must be at least 8 cm in length, will receive a single dose of EXPAREL (266 mg/20 mL) expanded in volume with 20-60 mL normal saline, depending on the size of the incision

Drug: EXPAREL

Interventions

EXPAREL DRUG

EXPAREL 266 mg/20 mL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• 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, 2, or 3.
• Scheduled to undergo primary, ≥3 level cervical or thoracic spine fusion or reconstruction under general anesthesia. The surgical incision must be at least 8 cm in length.
• Female subject must be surgically sterile; or at least 2 years postmenopausal; or have a monogamous partner who is surgically sterile; or practicing double-barrier contraception; or practicing abstinence (must agree to use double-barrier contraception in the event of sexual activity); or using an insertable, injectable, transdermal, or combination oral contraceptive approved by the FDA for greater than 2 months prior to screening and commit to the use of an acceptable form of birth control for the duration of the study and for 30 days after completion of the study.
• Able to provide informed consent, adhere to the study schedule, and complete all study assessments.

You may not qualify if:

• History of hypersensitivity or idiosyncratic reactions to amide-type local anesthetics or opioids.
• Contraindication to bupivacaine.
• Received bupivacaine or any other local anesthetic within 7 days of screening.
• Receiving workers' compensation.
• Currently pregnant, nursing, or planning to become pregnant during the study or within 1 month after study drug administration.
• Non-structural or acute spinal conditions (e.g., cauda equina syndrome, infection, tumor, fracture).
• Planned concurrent surgical procedure.
• Comorbidity impacting current physical function or Investigator opinion that it may impact postsurgical rehabilitation.
• Body weight \<50 kg (110 pounds) or a body mass index ≥45 kg/m2.
• History of coronary or vascular stent placed within the past 3 months (may be extended to 1 year if medically indicated per physician discretion).
• 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).
• Severely impaired renal or hepatic function (e.g., 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).
• Any neurologic or psychiatric disorder that might impact postsurgical pain or interfere with study assessments.
• Malignancy in the last 2 years, per physician discretion.
• History of misuse, abuse, or dependence on opioid analgesics, other prescription drugs, illicit drugs, or alcohol.

Sponsors & Collaborators

• Pacira Pharmaceuticals, Inc: lead

Study Sites (3)

University of Miami

Miami, Florida, 33136, United States

Location

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Agnosia

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Hassan Danesi, MD

  Pacira Pharmaceuticals, Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2016
• First Posted: December 7, 2016
• Study Start: December 1, 2016
• Primary Completion: September 1, 2017
• Study Completion: September 1, 2017
• Last Updated: April 10, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)