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 is a Phase 1b/2, randomized, blinded, active-controlled study. Phase 1b will evaluate escalating doses of HTX-034 compared with bupivacaine HCl. Phase 2 will be 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: Bunions
• Intervention / Treatment: Drug: HTX-034; Drug: HTX-034; Device: Luer lock applicator; Drug: Bupivacaine HCl

• Study Type: Interventional
• Enrollment (Actual): 73
• 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
• Genders Eligible for Study: All

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: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1b (Cohort 1); Fixed dose of HTX-034.	Drug: HTX-034; HTX-034, low dose; Drug: HTX-034; HTX-034, high dose; Device: Luer lock applicator; Applicator for instillation
Experimental: Phase 1b (Cohort 2); Individualized dose of HTX-034.	Drug: HTX-034; HTX-034, low dose; Drug: HTX-034; HTX-034, high dose; Device: Luer lock applicator; Applicator for instillation
Experimental: Phase 2 (Expansion): Low Dose; Fixed dose of HTX-034.	Drug: HTX-034; HTX-034, low dose; Drug: HTX-034; HTX-034, high dose; Device: Luer lock applicator; Applicator for instillation
Experimental: Phase 2 (Expansion): High Dose; Individualized dose of HTX-034.	Drug: HTX-034; HTX-034, low dose; Drug: HTX-034; HTX-034, high dose; Device: Luer lock applicator; Applicator for instillation
Active Comparator: Phase 1b and Phase 2; Bupivacaine HCl.	Drug: Bupivacaine HCl; Bupivacaine HCl, 50 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Treatment-emergent adverse events (TEAE's) (Phase 1B)	42 days
Mean area under the curve (AUC) of the NRS scores through 72 hours (AUC0-72) for the pooled Phase 1b and Phase 2	7 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum plasma concentration (Cmax) of HTX-034	29 days
Time of maximum plasma concentration (Tmax) of HTX-034	29 days
Area under the concentration-time curve from Time 0 to the time of the last quantitative concentration (AUClast) of HTX-034	29 days
Area under the concentration-time curve from Time 0 extrapolated to infinity (AUCinf) of HTX-034 (Phase 1B)	22 days
Apparent terminal half-life (t½) of HTX-034 (Phase 1B)	22 days
Mean AUC of the NRS pain intensity scores	7 days
Total postoperative opioid consumption (in IV Morphine Milligram Equivalents)	7 days
Proportion of subjects who are opioid-free	14 days
Incidence of serious adverse Events (SAE's)	42 days

Collaborators and Investigators

• Sponsor: Heron Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2020
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): August 3, 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): February 15, 2022
• Last Update Submitted That Met QC Criteria: January 31, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Analgesia; Bunionectomy
• 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: 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