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CompletedNCT03295721Updated Mar 2, 2026Results posted

Bunionectomy Study for Postoperative Analgesia (EPOCH 1)

A Phase 3 interventional study of HTX-011 and Saline Placebo in Postoperative Pain, sponsored by Heron Therapeutics. Completed at 15 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-03-02.

Sponsored by Heron Therapeutics · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
412
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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.

02

Conditions studied

  • Postoperative Pain

Keywords

  • bunion
  • bunionectomy
  • bunion surgery
  • postoperative pain
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
412 participants (actual)

Study arms

  • Experimental
    Treatment Group 1: HTX-011

    HTX 011 (bupivacaine/meloxicam)

    Drug: HTX-011 · Device: Luer-lock applicator · Device: Vial access device

  • Placebo comparator
    Treatment Group 2: Saline Placebo

    Saline placebo

    Drug: Saline Placebo · Device: Luer-lock applicator

  • Active comparator
    Treatment Group 3: Bupivacaine HCI

    Bupivacaine HCl

    Drug: Bupivacaine HCl

Interventions

  • DrugHTX-011

    HTX 011 (bupivacaine/meloxicam), 60 mg/1.8 mg by instillation

  • DrugSaline Placebo

    Saline placebo by instillation

  • DrugBupivacaine HCl

    Bupivacaine HCl without epinephrine, 50 mg by injection

  • DeviceLuer-lock applicator

    Applicator for instillation

  • DeviceVial access device

    Device for withdrawal of drug product

05

What researchers measure

Primary outcomes

  1. Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores With Activity (NRS-A) Through 72 Hours Postsurgery (AUC0-72), Compared With Saline Placebo.

    Pain intensity is assessed using an 11-point NRS (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable" (using windowed worst observation carried forward to adjust for opioid rescue medication use). The theoretical range of AUC0-72 is 0-720. The prescribed activity for NRS-A is sitting with the plantar surface of the ball of the surgically attended foot touching the floor (no weight bearing).

    Time frame: 72 hours

Secondary outcomes

  1. Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores With Activity (NRS-A) Through 72 Hours Postsurgery (AUC0-72), Compared With Bupivacaine HCl.

    Pain intensity is assessed using an 11-point NRS (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable" (using windowed worst observation carried forward to adjust for opioid rescue medication use). The theoretical range of AUC0-72 is 0-720. The prescribed activity for NRS-A is sitting with the plantar surface of the ball of the surgically attended foot touching the floor (no weight bearing).

    Time frame: 72 hours

  2. Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Saline Placebo.

    Time frame: 72 hours

  3. Percentage of Subjects Who Are Opioid-free for HTX-011 Compared With Bupivacaine HCl.

    Time frame: 72 hours

  4. Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Bupivacaine HCl.

    Time frame: 72 hours

06

Results

Posted Oct 27, 2021

Participant flow

Participant flow — Overall Study
MilestoneTreatment Group 1: HTX-011Treatment Group 2: Saline PlaceboTreatment Group 3: Bupivacaine HCI
Started157100155
Completed15499152
Not completed313
Withdrew: Adverse event100
Withdrew: Lost to follow-up111
Withdrew: Withdrawal by subject101
Withdrew: Death001

Outcome measures

PrimaryMean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores With Activity (NRS-A) Through 72 Hours Postsurgery (AUC0-72), Compared With Saline Placebo.

Pain intensity is assessed using an 11-point NRS (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable" (using windowed worst observation carried forward to adjust for opioid rescue medication use). The theoretical range of AUC0-72 is 0-720. The prescribed activity for NRS-A is sitting with the plantar surface of the ball of the surgically attended foot touching the floor (no weight bearing).

Time frame:
72 hours
Reported as:
Mean · pain intensity score*hr
Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores With Activity (NRS-A) Through 72 Hours Postsurgery (AUC0-72), Compared With Saline Placebo.
pain intensity score*hrTreatment Group 1: HTX-011Treatment Group 2: Saline Placebo
Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores With Activity (NRS-A) Through 72 Hours Postsurgery (AUC0-72), Compared With Saline Placebo.323.29 ± 182.641445.34 ± 155.792
Statistical analysis
  • Treatment Group 1: HTX-011 vs Treatment Group 2: Saline Placebo · ANOVA · p = < 0.0001 · Least squares mean difference (lsmd): -122.05 · 95% CI -163.76 to -80.34
SecondaryMean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores With Activity (NRS-A) Through 72 Hours Postsurgery (AUC0-72), Compared With Bupivacaine HCl.

Pain intensity is assessed using an 11-point NRS (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable" (using windowed worst observation carried forward to adjust for opioid rescue medication use). The theoretical range of AUC0-72 is 0-720. The prescribed activity for NRS-A is sitting with the plantar surface of the ball of the surgically attended foot touching the floor (no weight bearing).

Time frame:
72 hours
Reported as:
Mean · pain intensity score*hr
Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores With Activity (NRS-A) Through 72 Hours Postsurgery (AUC0-72), Compared With Bupivacaine HCl.
pain intensity score*hrTreatment Group 1: HTX-011Treatment Group 3: Bupivacaine HCI
Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores With Activity (NRS-A) Through 72 Hours Postsurgery (AUC0-72), Compared With Bupivacaine HCl.323.29 ± 182.641393.45 ± 153.756
Statistical analysis
  • Treatment Group 1: HTX-011 vs Treatment Group 3: Bupivacaine HCI · ANOVA · p = = 0.0002 · Least squares mean difference (lsmd): -70.16 · 95% CI -107.07 to -33.25
SecondaryMean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Saline Placebo.
Time frame:
72 hours
Reported as:
Mean · IV milligram morphine equivalent (MME)
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Saline Placebo.
IV milligram morphine equivalent (MME)Treatment Group 1: HTX-011Treatment Group 2: Saline Placebo
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Saline Placebo.18.80 ± 19.80130.06 ± 21.016
Statistical analysis
  • Treatment Group 1: HTX-011 vs Treatment Group 2: Saline Placebo · Wilcoxon (Mann-Whitney) · p = < 0.0001
SecondaryPercentage of Subjects Who Are Opioid-free for HTX-011 Compared With Bupivacaine HCl.
Time frame:
72 hours
Reported as:
Count of participants · Participants
Percentage of Subjects Who Are Opioid-free for HTX-011 Compared With Bupivacaine HCl.
ParticipantsTreatment Group 1: HTX-011Treatment Group 3: Bupivacaine HCI
Percentage of Subjects Who Are Opioid-free for HTX-011 Compared With Bupivacaine HCl.4517
Statistical analysis
  • Treatment Group 1: HTX-011 vs Treatment Group 3: Bupivacaine HCI · Fisher Exact · p = 0.0001 · Risk difference (rd): .177 · 95% CI .085 to .265
SecondaryMean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Bupivacaine HCl.
Time frame:
72 hours
Reported as:
Mean · IV milligram morphine equivalent (MME)
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Bupivacaine HCl.
IV milligram morphine equivalent (MME)Treatment Group 1: HTX-011Treatment Group 3: Bupivacaine HCl
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Bupivacaine HCl.18.80 ± 19.80125.09 ± 21.553
Statistical analysis
  • Treatment Group 1: HTX-011 vs Treatment Group 3: Bupivacaine HCl · Wilcoxon (Mann-Whitney) · p = = 0.0022

Adverse events

Collected over 42 days.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment Group 1: HTX-0110/157 (0%)3/157 (1.9%)111/157 (70.7%)
Treatment Group 2: Saline Placebo0/101 (0%)1/101 (1%)70/101 (69.3%)
Treatment Group 3: Bupivacaine HCl1/154 (0.6%)3/154 (1.9%)112/154 (72.7%)
Most frequent serious events
Most frequent serious events
EventTreatment Group 1: HTX-011Treatment Group 2: Saline PlaceboTreatment Group 3: Bupivacaine HCl
Deep vein thrombosis postoperativeVascular disorders0/1571/1011/154
Pulmonary embolismRespiratory, thoracic and mediastinal disorders0/1570/1011/154
Atrial fibrillationCardiac disorders0/1570/1011/154
DeathGeneral disorders0/1570/1011/154
Thoracic vertebral fractureInjury, poisoning and procedural complications1/1570/1010/154
Bile duct stoneHepatobiliary disorders1/1570/1010/154
Intestinal perforationGastrointestinal disorders1/1570/1010/154
Venous thrombosisVascular disorders1/1570/1010/154
Most frequent other events
Showing 10 of 16
Most frequent other events
EventTreatment Group 1: HTX-011Treatment Group 2: Saline PlaceboTreatment Group 3: Bupivacaine HCl
NauseaGastrointestinal disorders59/15744/10170/154
DizzinessNervous system disorders34/15718/10136/154
VomitingGastrointestinal disorders23/15719/10133/154
Incision site oedemaInjury, poisoning and procedural complications27/15713/10122/154
HeadacheNervous system disorders22/15710/10120/154
Post procedural contusionInjury, poisoning and procedural complications19/15713/10118/154
Incision site erythemaInjury, poisoning and procedural complications20/1578/10118/154
ConstipationGastrointestinal disorders9/1577/10118/154
BradycardiaCardiac disorders12/1576/10112/154
Sinus arrhythmiaCardiac disorders6/1576/10110/154

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Treatment Group 1: HTX-011Treatment Group 2: Saline PlaceboTreatment Group 3: Bupivacaine HCITotal
<=18 years0000
Between 18 and 65 years13392139364
>=65 years2481648
Age, Continuous
Age, Continuous(years)Treatment Group 1: HTX-011Treatment Group 2: Saline PlaceboTreatment Group 3: Bupivacaine HCITotal
Mean48.0 ± 14.4747.3 ± 12.8345.5 ± 14.7946.9 ± 14.22
Sex: Female, Male
Sex: Female, Male(Participants)Treatment Group 1: HTX-011Treatment Group 2: Saline PlaceboTreatment Group 3: Bupivacaine HCITotal
Female13886132356
Male19142356
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Treatment Group 1: HTX-011Treatment Group 2: Saline PlaceboTreatment Group 3: Bupivacaine HCITotal
Hispanic or Latino473249128
Not Hispanic or Latino11068106284
Unknown or Not Reported0000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Treatment Group 1: HTX-011Treatment Group 2: Saline PlaceboTreatment Group 3: Bupivacaine HCITotal
American Indian or Alaska Native1023
Asian82111
Native Hawaiian or Other Pacific Islander0011
Black or African American24122258
White12386128337
More than one race1012
Unknown or Not Reported0000
Region of Enrollment
Region of Enrollment(participants)Treatment Group 1: HTX-011Treatment Group 2: Saline PlaceboTreatment Group 3: Bupivacaine HCITotal
United States157100155412
07

Study locations

15 sites
  • Springhill Medical Center
    Mobile, Alabama 36608, United States
  • Orthopaedic Specialists of North America, PLLC
    Mesa, Arizona 85206, United States
  • Arizona Research Center
    Phoenix, Arizona 85059, United States
  • Anaheim Clinical Trials, LLC
    Anaheim, California 92801, United States
  • Trovare Clinical Research, Inc.
    Bakersfield, California 93301, United States
  • Alliance Research Centers
    Laguna Hills, California 92653, United States
  • Chesapeake Research Group, LLC
    Pasadena, Maryland 21122, United States
  • Optimal Research , LLC
    Austin, Texas 78705, United States
  • Hermann Drive Surgical Hospital
    Houston, Texas 77004, United States
  • Westside Surgical Hospital
    Houston, Texas 77027, United States
  • Futuro Clinical Trials, LLC
    McAllen, Texas 78501, United States
  • Plano Surgical Hospital
    Plano, Texas 75093, United States
  • Endeavor Clinical Trials
    San Antonio, Texas 78229, United States
  • EPIC Medical Research, LLC
    Murray, Utah 84123, United States
  • Jean Brown Research
    Salt Lake City, Utah 84124, United States
08

References and documents

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. PubMed 34284613 ↗
  • 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. PubMed 31113830 ↗

Study documents

  • Study protocol · Sep 24, 2017
  • Statistical analysis plan · Oct 10, 2017

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT03295721
Lead sponsor
Heron Therapeutics
Responsible party
Sponsor
First posted
Sep 28, 2017
Start date
Oct 24, 2017
Primary completion
Jan 8, 2018
Completion
Mar 13, 2018
Results posted
Oct 27, 2021
Last update
Mar 2, 2026

Oversight

FDA-regulated drug
Yes
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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