Bunionectomy Study for Postoperative Analgesia (EPOCH 1)

A Phase 3, Randomized, Double Blind, Saline Placebo and Active Controlled, Multicenter Study of HTX 011 Via Local Administration for Postoperative Analgesia and Decreased Opioid Use Following Unilateral Simple Bunionectomy

This is a Phase 3, randomized, double-blind, saline placebo- and active-controlled, multicenter study to evaluate the analgesic efficacy and safety of HTX 011 administered via local administration into the surgical site in subjects undergoing bunionectomy.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain
• Intervention / Treatment: Device: Luer-lock applicator; Device: Vial access device; Drug: HTX-011; Drug: Saline Placebo; Drug: Bupivacaine HCl

• Study Type: Interventional
• Enrollment (Actual): 412
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Springhill Medical Center
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Orthopaedic Specialists of North America, PLLC
    • Phoenix, Arizona, United States, 85059
      • Arizona Research Center
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC
    • Bakersfield, California, United States, 93301
      • Trovare Clinical Research, Inc.
    • Laguna Hills, California, United States, 92653
      • Alliance Research Centers
  • Maryland
    • Pasadena, Maryland, United States, 21122
      • Chesapeake Research Group, Llc
  • Texas
    • Austin, Texas, United States, 78705
      • Optimal Research , LLC
    • Houston, Texas, United States, 77004
      • Hermann Drive Surgical Hospital
    • Houston, Texas, United States, 77027
      • Westside Surgical Hospital
    • McAllen, Texas, United States, 78501
      • Futuro Clinical Trials, LLC
    • Plano, Texas, United States, 75093
      • Plano Surgical Hospital
    • San Antonio, Texas, United States, 78229
      • Endeavor Clinical Trials
  • Utah
    • Murray, Utah, United States, 84123
      • Epic Medical Research, LLC
    • Salt Lake City, Utah, United States, 84124
      • Jean Brown Research

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:

• Is scheduled to undergo a primary unilateral, distal, first metatarsal bunionectomy with osteotomy and internal fixation under regional anesthesia.
• Has an American Society of Anesthesiologists Physical Status of I, II, or III.
• Female subjects are eligible only if not pregnant, not lactating, not planning to become pregnant during the study, sterile; or using acceptable contraceptives.

Exclusion Criteria:

• Has had a contralateral foot bunionectomy in the past 3 months.
• Has a planned concurrent surgical procedure (eg, bilateral bunionectomy or collateral procedures on the surgical foot).
• Has other pre existing concurrent acute or chronic painful physical/restrictive condition expected to require analgesic treatment in the postoperative period for pain.
• Has a contraindication or a known or suspected history of hypersensitivity or clinically significant idiosyncratic reaction to required study medications.
• Has known or suspected daily use of opioids for 7 or more consecutive days within the previous 6 months.
• Has taken any NSAIDs within at least 10 days prior to the scheduled surgery.
• Has taken opioids within 24 hours prior to the scheduled surgery (3 days for long-acting).
• Has been administered bupivacaine within 5 days prior to the scheduled surgery.
• Has initiated treatment with medications within 1 month prior to study drug administration that can impact pain control.
• Has been administered systemic steroids within 5 half-lives or 10 days prior to administration of study drug.
• Has a medical condition such that, in the opinion of the Investigator, participating in the study would pose a health risk to the subject or confound the postoperative assessments.
• As per subject history and/or medical records, has active infection or is currently undergoing treatment for Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV).
• Has uncontrolled anxiety, psychiatric, or neurological disorder.
• Had a malignancy in the last year, with the exception of nonmetastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
• Has a known or suspected history of drug abuse, a positive drug screen on the day of surgery, or a recent history of alcohol abuse. Note: Subjects with a positive drug screen who are taking an allowed, prescribed medication that is known to result in a positive drug test (eg, amphetamine and dextroamphetamine for attention deficit/hyperactivity disorder, benzodiazepine for anxiety disorder) may be eligible for participation in the study. Subjects taking medical marijuana are not allowed to participate in the study.
• Received an investigational product or device in a clinical trial within 30 days or within 5 elimination half lives.
• Has undergone 3 or more surgeries within 12 months.
• Has a body mass index (BMI) >39 kg/m2.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group 1: HTX-011; HTX 011 (bupivacaine/meloxicam)	Device: Luer-lock applicator; Applicator for instillation; Device: Vial access device; Device for withdrawal of drug product; Drug: HTX-011; HTX 011 (bupivacaine/meloxicam), 60 mg/1.8 mg by instillation
Placebo Comparator: Treatment Group 2: Saline Placebo; Saline placebo	Device: Luer-lock applicator; Applicator for instillation; Drug: Saline Placebo; Saline placebo by instillation
Active Comparator: Treatment Group 3: Bupivacaine HCI; Bupivacaine HCl	Drug: Bupivacaine HCl; Bupivacaine HCl without epinephrine, 50 mg by injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Area Under the Curve (AUC) of the Numeric Rating Scale of Pain Intensity Scores With Activity (NRS-A; Windowed Worst Observation Carried Forward) for HTX-011 Compared With Saline Placebo.	Pain intensity scores are assessed using an 11-point Numeric Rating Scale (NRS) (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable". NRS scores are recorded with activity (NRS-A), seated with the plantar surface of the ball of the surgically attended foot touching the floor (no weight-bearing).	72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Saline Placebo.		72 hours
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Bupivacaine HCl.		72 hours
Mean AUC of the NRS-A Pain Intensity Scores (Windowed Worst Observation Carried Forward) for HTX 011 Compared With Bupivacaine HCl.	Pain intensity scores are assessed using an 11-point Numeric Rating Scale (NRS) (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable". NRS scores are recorded with activity (NRS-A) seated with the plantar surface of the ball of the surgically attended foot touching the floor (no weight-bearing).	72 hours
Percentage of Subjects Who Are Opioid-free for HTX-011 Compared With Bupivacaine HCl.		72 hours

Collaborators and Investigators

• Sponsor: Heron Therapeutics

Publications and helpful links

General Publications

• Yip T, Hu J, Hawn PS, Yamamoto A, Oderda G. HTX-011 effectively reduces postoperative pain intensity and opioid use in the elderly. Pain Manag. 2022 Jan;12(1):45-57. doi: 10.2217/pmt-2021-0043. Epub 2021 Jul 21.
• Viscusi E, Gimbel JS, Pollack RA, Hu J, Lee GC. HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in bunionectomy: phase III results from the randomized EPOCH 1 study. Reg Anesth Pain Med. 2019 May 21:rapm-2019-100531. doi: 10.1136/rapm-2019-100531. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2017
• Primary Completion (Actual): January 8, 2018
• Study Completion (Actual): March 13, 2018

Study Registration Dates

• First Submitted: September 25, 2017
• First Submitted That Met QC Criteria: September 25, 2017
• First Posted (Actual): September 28, 2017

Study Record Updates

• Last Update Posted (Actual): October 27, 2021
• Last Update Submitted That Met QC Criteria: September 29, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: postoperative pain; bunion; bunionectomy; bunion surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: HTX-011-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes