Dose-Escalation Study of HTX-034 Following Bunionectomy

A Phase 1b/2, Randomized, Blinded, Active-Controlled Study of Escalating Doses of HTX-034 for Postoperative Analgesia in Subjects Undergoing Unilateral, First Metatarsal Bunionectomy With Osteotomy and Internal Fixation

This was a Phase 1b/2, randomized, blinded, active-controlled study. Phase 1b evaluated escalating doses of HTX-034 compared with bupivacaine HCl. Phase 2 was a dose-expansion phase to evaluate additional subjects treated with the HTX-034 dose selected based on Phase 1b, compared with bupivacaine HCl.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain; Bunions
• Intervention / Treatment: Device: Luer lock applicator; Drug: HTX-034 low dose; Drug: HTX-034 high dose; Drug: Bupivacaine HCl

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Arizona Research Center
  • Texas
    • Bellaire, Texas, United States, 77401
      • First Surgical Hospital
    • San Antonio, Texas, United States, 78229
      • Endeavor Clinical Trials, LLC
  • Utah
    • Salt Lake City, Utah, United States, 84017
      • JBR Clinical Research

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Is medically fit to undergo an elective unilateral, first metatarsal bunionectomy with osteotomy and internal fixation under regional anesthesia; no neuraxial technique (eg, no spinal, epidural, or general anesthesia).
• Has an American Society of Anesthesiologists (ASA) 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:

• Had contralateral foot bunionectomy in the past 3 months.
• Has a planned concurrent surgical procedure.
• Has a contraindication or a known or suspected history of hypersensitivity or clinically significant idiosyncratic reaction to required study medications.
• Has a pre-existing concurrent acute or chronic painful physical/restrictive condition expected to require analgesic treatment in the postoperative period for pain.
• Has received or is taking a contraindicated or prohibited medications.
• Received an investigational product or device in a clinical trial within 30 days or within 5 elimination half lives.
• 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.
• Has a history of clinically significant cardiac abnormality such as myocardial infarction within 6 months.
• Has a history of coronary artery bypass graft surgery within 12 months.
• Has a history of known or suspected coagulopathy.
• 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 undergone 3 or more surgeries within 12 months.
• Has a known history of glucose-6-phosphate dehydrogenase deficiency.

• Has any of the following laboratory abnormalities during Screening (1 retest permitted):

  • Severe liver function impairment.
  • Severe kidney function impairment.
  • Platelet count <100,000/μL, hemoglobin <12 g/dL, or hematocrit <35%.
• 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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1b: HTX-034 Low Dose; Fixed low dose of HTX-034: 21.7 mg/4.3 mg/0.6 mg (bupivacaine/aprepitant/meloxicam doses).	Device: Luer lock applicator; Applicator for instillation; Drug: HTX-034 low dose; HTX-034 (bupivacaine/aprepitant/meloxicam) fixed dose: 21.7 mg/4.3 mg/0.6 mg
Experimental: Phase 1b: HTX-034 High Dose; Individualized high dose of HTX-034: ranging from 30.6 mg/6.1 mg/0.9 mg to 51.5 mg/10.3 mg/1.5 mg (bupivacaine/aprepitant/meloxicam doses).	Device: Luer lock applicator; Applicator for instillation; Drug: HTX-034 high dose; HTX-034 (bupivacaine/aprepitant/meloxicam) individualized dose: 30.6 mg/6.1 mg/0.9 mg to 51.5 mg/10.3 mg/1.5 mg
Experimental: Phase 2: HTX-034 Low Dose; Fixed low dose of HTX-034: 21.7 mg/4.3 mg/0.6 mg (bupivacaine/aprepitant/meloxicam doses).	Device: Luer lock applicator; Applicator for instillation; Drug: HTX-034 low dose; HTX-034 (bupivacaine/aprepitant/meloxicam) fixed dose: 21.7 mg/4.3 mg/0.6 mg
Experimental: Phase 2: HTX-034 High Dose; Individualized high dose of HTX-034: ranging from 30.6 mg/6.1 mg/0.9 mg to 51.5 mg/10.3 mg/1.5 mg (bupivacaine/aprepitant/meloxicam doses).	Device: Luer lock applicator; Applicator for instillation; Drug: HTX-034 high dose; HTX-034 (bupivacaine/aprepitant/meloxicam) individualized dose: 30.6 mg/6.1 mg/0.9 mg to 51.5 mg/10.3 mg/1.5 mg
Active Comparator: Phase 1b/2: Bupivacaine HCl; Bupivacaine HCl (without epinephrine) 0.5%: 50 mg	Drug: Bupivacaine HCl; Bupivacaine HCl 50 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of TEAEs in Phases 1b/2	The data from Phase 1b and Phase 2 were combined for each treatment group because the dose for bupivacaine HCI, HTX-034 low dose and HTX-034 high dose were the same, in both Phases, respectively. In addition, the surgical procedure, protocol assessments, and participating sites were the same in both Phases.	42 days
AUC0-72 of Pain Scores	Mean area under the curve (AUC) of the Numeric Rating Scale (NRS) of pain intensity scores with activity (windowed worst observation carried forward) through 72 hours. The NRS was an 11-point scale (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable". The data from Phase 1b and Phase 2 were combined for each treatment group because the dose for bupivacaine HCI, HTX-034 low dose and HTX-034 high dose were the same, in both Phases, respectively. In addition, the surgical procedure, protocol assessments, and participating sites were the same in both Phases.	through 72 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax for HTX-034	Maximum plasma concentration	29 days
Tmax for HTX-034	Time of maximum plasma concentration	29 days
AUClast for HTX-034	Area under the concentration-time curve from Time 0 to the time of the last quantifiable concentration	29 days
AUCinf for HTX-034	Area under the concentration-time curve from Time 0 extrapolated to infinity (Phase 1b only)	22 days
t½ of HTX-034	Apparent terminal half-life of HTX-034 (Phase 1b only)	22 days
Mean AUC of Pain Scores With Activity	Mean AUC of the Numeric Rating Scale (NRS) scores with activity (windowed worst observation carried forward). Pain intensity scores were assessed using an 11-point NRS (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable". The data from Phase 1b and Phase 2 were combined for each treatment group because the dose for bupivacaine HCI, HTX-034 low dose and HTX-034 high dose were the same, in both Phases, respectively. In addition, the surgical procedure, protocol assessments, and participating sites were the same in both Phases.	7 days
Opioid Consumption	Total postoperative opioid consumption (in IV Morphine Milligram Equivalents). The data from Phase 1b and Phase 2 were combined for each treatment group because the dose for bupivacaine HCI, HTX-034 low dose and HTX-034 high dose were the same, in both Phases, respectively. In addition, the surgical procedure, protocol assessments, and participating sites were the same in both Phases.	7 days
Proportion of Subjects Who Are Opioid-free	Proportion of subjects who took no postoperative opioids through Day 15. The data from Phase 1b and Phase 2 were combined for each treatment group because the dose for bupivacaine HCI, HTX-034 low dose and HTX-034 high dose were the same, in both Phases, respectively. In addition, the surgical procedure, protocol assessments, and participating sites were the same in both Phases.	After surgery (Day 1) through the Day 15 visit
Number of Participants With SAEs	Number and proportion of subjects with serious adverse events. The data from Phase 1b and Phase 2 were combined for each treatment group because the dose for bupivacaine HCI, HTX-034 low dose and HTX-034 high dose were the same, in both Phases, respectively. In addition, the surgical procedure, protocol assessments, and participating sites were the same in both Phases.	42 days

Collaborators and Investigators

• Sponsor: Heron Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2020
• Primary Completion (Actual): July 15, 2021
• Study Completion (Actual): July 15, 2021

Study Registration Dates

• First Submitted: May 18, 2020
• First Submitted That Met QC Criteria: May 18, 2020
• First Posted (Actual): May 21, 2020

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Analgesia; Bunionectomy
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Postoperative Complications; Pathologic Processes; Neurobehavioral Manifestations; Perceptual Disorders; Foot Deformities; Foot Deformities, Acquired; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Bunion; Pain, Postoperative; Agnosia; Organic Chemicals; Anilides; Amides; Aniline Compounds; Amines; Bupivacaine
• Other Study ID Numbers: HTX-034-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes