Phase 2 Bunionectomy HTX-011 Administration Study

A Phase 2 Open-Label Study of HTX-011 Via Individualized Dosing Administration for Postoperative Analgesia Following Unilateral Simple Bunionectomy

This is a Phase 2, open-label, multi-cohort study to evaluate the analgesic efficacy, safety, and pharmacokinetics (PK) of a single, individualized dose of HTX-011 administered into the surgical site as a monotherapy or with other medications to enhance analgesia in subjects undergoing unilateral simple bunionectomy.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain
• Intervention / Treatment: Device: Luer Lock applicator; Device: Vial access device; Drug: HTX-011; Drug: aprepitant

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

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Endeavor Clinical Trials, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

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. For cohort 2, acceptable contraceptives excludes hormonal contraceptives.

Exclusion Criteria:

• Has had a contralateral foot bunionectomy in the past 3 months prior to the scheduled surgery.
• Has a planned concurrent surgical procedure (eg, bilateral bunionectomy or collateral procedures on the surgical foot).
• Has a 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 long-acting opioids within 3 days prior to the scheduled surgery.
• Has taken any opioids within 24 hours prior to the scheduled surgery.
• Has been administered bupivacaine within 5 days prior to the scheduled surgery.
• For Cohort 2 only, has been administered aprepitant or another NK1 receptor antagonist within 5 days prior to the scheduled surgery.
• Has been administered any local anesthetic within 72 hours prior to the scheduled surgery.
• Has initiated treatment with study 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.
• For Cohort 2 only, is receiving pimozide, a strong or moderate CYP3A4 inhibitor, or a strong CYP3A4 inducer.
• 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 at the discretion of the Sponsor. Subjects taking any marijuana (medical or recreational) are not allowed to participate in the study.
• Previously participated in an HTX-011 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: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group 1: HTX-011; HTX-011 (bupivacaine/meloxicam), up to but not to exceed 60 mg/1.8 mg, via instillation.	Device: Luer Lock applicator; Applicator for instillation.; Device: Vial access device; Device for withdrawal of drug product.; Drug: HTX-011; HTX-011 (bupivacaine/meloxicam), up to but not to exceed 60 mg/1.8 mg, via instillation.
Experimental: Treatment Group 2: HTX-011 + Aprepitant; HTX-011 (bupivacaine/meloxicam), up to but not to exceed 60 mg/1.8 mg, via instillation; Aprepitant, three single doses of aprepitant will be administered orally.	Device: Luer Lock applicator; Applicator for instillation.; Device: Vial access device; Device for withdrawal of drug product.; Drug: HTX-011; HTX-011 (bupivacaine/meloxicam), up to but not to exceed 60 mg/1.8 mg, via instillation.; Drug: aprepitant; Aprepitant, three single doses of aprepitant will be administered orally.
Experimental: Treatment Group 3: HTX-011 + Non-Opioid MMA Regimen; HTX-011 (bupivacaine/meloxicam), up to but not to exceed 60 mg/1.8 mg, via instillation and a scheduled multimodal analgesic (MMA) regimen.	Device: Luer Lock applicator; Applicator for instillation.; Device: Vial access device; Device for withdrawal of drug product.; Drug: HTX-011; HTX-011 (bupivacaine/meloxicam), up to but not to exceed 60 mg/1.8 mg, via instillation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Area Under the Curve (AUC) of the NRS-A (Windowed Worst Observation Carried Forward) Pain Intensity Scores	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), sitting 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
Percentage of Subjects Receiving no Opioid Rescue		72 hours
Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) Through 72 Hours		72 hours
Percentage of Subjects Receiving no Opioid Rescue	Only subjects in Cohort 3 received a scheduled, non-opioid MMA regimen following surgery.	Day 7 and Day 28
Mean Area Under the Curve (AUC) of the NRS-R (Windowed Worst Observation Carried Forward) Pain Intensity Scores	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 measured at rest.	72 hours

Collaborators and Investigators

• Sponsor: Heron Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2018
• Primary Completion (Actual): January 31, 2019
• Study Completion (Actual): March 11, 2019

Study Registration Dates

• First Submitted: October 22, 2018
• First Submitted That Met QC Criteria: October 22, 2018
• First Posted (Actual): October 24, 2018

Study Record Updates

• Last Update Posted (Actual): June 26, 2023
• Last Update Submitted That Met QC Criteria: June 1, 2023
• Last Verified: June 1, 2023

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; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Antiemetics; Gastrointestinal Agents; Neurokinin-1 Receptor Antagonists; Aprepitant
• Other Study ID Numbers: HTX-011-218

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
• product manufactured in and exported from the U.S.: No