Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of EXPAREL, EXPAREL Admixed With Bupivacaine HCl vs. Bupivacaine HCl Administered as Combined Sciatic and Saphenous Nerve Blocks for Postsurgical Analgesia in Subjects Undergoing Lower Extremity Surgeries (STRIDE)

A Phase 3, Randomized, Double Blinded, Active Controlled, Multicenter Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of EXPAREL, EXPAREL Admixed With Bupivacaine HCl vs. Bupivacaine HCl Administered as Combined Sciatic (in Popliteal Fossa) and Saphenous (in Adductor Canal) Nerve Blocks for Postsurgical Analgesia in Subjects Undergoing Lower Extremity Surgeries

This is a Phase 3, multicenter, randomized, double blinded, active controlled study in approximately 120 subjects undergoing lower extremity surgeries.

Study Overview

• Status: Completed
• Conditions: Bunion; Midfoot Fusion; Total Ankle Arthroplasty; Lower Extremity Surgery; Metatarsophalangeal Fushion; Hindfoot Fushion
• Intervention / Treatment: Drug: Exparel; Drug: Bupivacaine Hydrochloride

• Study Type: Interventional
• Enrollment (Actual): 121
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Arizona Research Center
  • California
    • Pasadena, California, United States, 91105
      • Lotus Clinical Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Chestnut Hill, Massachusetts, United States, 02467
      • Brigham and Women's Hospital
  • Texas
    • Bellaire, Texas, United States, 77401
      • HD Research, Corp

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. Healthy adult male or female volunteers ages 18 or older
2. American Society of Anesthesiologists (ASA) physical status 1, 2, or 3
3. Able to provide informed consent, adhere to the study schedule, and complete all study assessments
4. Body Mass Index (BMI) ≥18 and ≤40 kg/m2

Exclusion Criteria:

1. Allergy, hypersensitivity, intolerance, or contraindication to any of the study medications for which an alternative is not named in the protocol (e.g., amide-type local anesthetics, opioids, bupivacaine HCl, nonsteroidal anti-inflammatory drugs [NSAIDs])
2. 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, in the investigator's opinion, may confound the post dosing assessments
3. History of, suspected, or known addiction to or abuse of illicit drug(s), prescription medicine(s), or alcohol within the past 2 years
4. 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
5. Previous participation in an EXPAREL study
6. Uncontrolled anxiety, schizophrenia, or other psychiatric disorder that, in the opinion of the investigator, could interfere with study assessments or compliance
7. Currently pregnant, nursing, or planning to become pregnant during the study
8. Clinically significant medical disease that, in the opinion of the investigator, would make participation in a clinical study inappropriate. This includes diabetic neuropathy, coagulation or bleeding disorders, severe peripheral vascular disease, renal insufficiency, hepatic dysfunction or other conditions that would constitute a contraindication to participation in the study.
9. Currently on a neuromodulating agent neuroleptic agent (e.g., gabapentin, pregabalin [Lyrica], duloxetine [Cymbalta], etc.)
10. Inadequate sensory function on the foot (monofilament test)
11. Chronic opioid use within 30 days prior to randomization (average ≥30 oral morphine equivalents/day)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EXPAREL arm; Subjects randomized to this treatment arm will receive 20 mL (266 mg)EXPAREL mixed with 20 mL saline	Drug: Exparel; EXPAREL (bupivacaine liposome injectable suspension)
Experimental: EXPAREL admix arm; subjects randomized to this treatment arm will receive 20 mL (266 mg)EXPAREL admixed with 20 mL (50 mg) 0.25% bupivacaine HCl.	Drug: Exparel; EXPAREL (bupivacaine liposome injectable suspension); Drug: Bupivacaine Hydrochloride; 0.25% bupivacaine
Active Comparator: Bupivacaine HCl Arm; subjects randomized to this treatment arm will receive 40 mL (100 mg)0.25% bupivacaine HCl.	Drug: Bupivacaine Hydrochloride; 0.25% bupivacaine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Magnitude of the Analgesic Effect (NRS Pain Intensity) (AUC)	To compare the magnitude of the analgesic effect (NRS pain intensity scores) following a single dose injection of EXPAREL vs. bupivacaine hydrochloride (HCl) when administered as combined sciatic (in the popliteal fossa) and saphenous (in the adductor canal) nerve blocks in subjects undergoing lower extremity surgeries. Numerical Rating Scale: an 11 point scale 0=no pain, 10= the worst pain imaginable. The area under the curve (AUC) of the NRS pain intensity scores from 0 to 96 hours post-surgery comparing EXPAREL to 0.25% bupivacaine HCl	Post surgery - 96 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Opioid Consumption	Total Opioid Consumption in oral morphine equivalents	0 hours to 96 hours
Time to First Opioid	Time to First Opioid following a single dose of EXPAREL vs. Bupivacain HCl	Post Surgery through Day 14

Collaborators and Investigators

• Sponsor: Pacira Pharmaceuticals, Inc

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2020
• Primary Completion (Actual): April 5, 2021
• Study Completion (Actual): April 5, 2021

Study Registration Dates

• First Submitted: August 4, 2020
• First Submitted That Met QC Criteria: August 14, 2020
• First Posted (Actual): August 19, 2020

Study Record Updates

• Last Update Posted (Actual): July 18, 2022
• Last Update Submitted That Met QC Criteria: July 15, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Foot Deformities; Foot Deformities, Acquired; Bunion; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: 402-C-333

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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