A Multi-surgery Assessment of ZYNRELEF (HTX-011), AMAZE.

NCT06109415 | Completed Phase 4 FDA Drug FDA Device

• 1 other identifier: HTX-011-401 (Cohort 1)
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 5

Brief Summary

This is a Phase 4, randomized, blinded, active-controlled, multicohort study to evaluate HTX-011 compared with bupivacaine HCl in subjects undergoing Total Shoulder Arthroplasty (TSA) (Cohort 1).

Conditions

Postoperative Pain; Total Shoulder Arthroplasty; Multimodal Analgesia

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-emergent adverse events (TEAEs).

  Through Day 15

Secondary Outcomes (5)

• Maximum concentration (Cmax) of bupivacaine and meloxicam

  Through 144 hours

• Time of occurrence of maximum concentration (Tmax) of bupivacaine and meloxicam

  Through 144 hours

• Area under the concentration-time curve from Time 0 to the time of the last quantifiable concentration (AUClast) of bupivacaine and meloxicam

  Through 144 hours

• Area under the concentration-time curve from Time 0 extrapolated to infinity (AUCinf) of bupivacaine and meloxicam

  Through 144 hours

• Apparent terminal half-life (t½) of bupivacaine and meloxicam

  Through 144 hours

Study Arms (2)

Treatment Group 1 Cohort 1

EXPERIMENTAL

HTX-011 + multimodal analgesic (MMA) regimen

Drug: HTX-011; Drug: Ibuprofen; Drug: Acetaminophen; Device: Luer lock applicator

Treatment Group 2 Cohort 1

ACTIVE COMPARATOR

Bupivacaine HCl + MMA regimen

Drug: Bupivacaine Hydrochloride; Drug: Ibuprofen; Drug: Acetaminophen

Interventions

HTX-011 DRUG

400 mg

Treatment Group 1 Cohort 1

Bupivacaine Hydrochloride DRUG

100 mg

Treatment Group 2 Cohort 1

Ibuprofen DRUG

400 mg

Treatment Group 1 Cohort 1; Treatment Group 2 Cohort 1

Acetaminophen DRUG

1 g

Treatment Group 1 Cohort 1; Treatment Group 2 Cohort 1

Luer lock applicator DEVICE

Applicator for instillation

Treatment Group 1 Cohort 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has American Society of Anesthesiologists (ASA) Physical Status of I, II, or III.
• Is scheduled to undergo a unilateral Total Shoulder Arthroplasty.

You may not qualify if:

• Is undergoing a revision surgery.
• Has a known or suspected history of hypersensitivity or clinically significant idiosyncratic reaction to bupivacaine (or other local anesthetics), NSAIDs, acetaminophen, oxycodone, morphine, or hydromorphone.
• History of severe allergic reaction to aspirin or other NSAIDs, or known history of severe gastrointestinal adverse reactions associated with NSAID use.
• Has taken meloxicam within 10 days prior to the scheduled surgery, or any NSAID within 24 hours prior to the scheduled surgery, with the exception of subjects on low-dose (≤100 mg) daily acetylsalicylic acid for cardioprotection.
• Opioid use for most days within the last 3 months prior to Screening in the opinion of the Investigator.
• Has been administered immediate-release bupivacaine HCl within 5 days prior to the scheduled surgery, or a modified-release bupivacaine product within 14 days prior to the scheduled surgery.
• Has initiated treatment with any of the following medications within 1 month prior to study drug administration: selective serotonin reuptake inhibitors, selective norepinephrine reuptake inhibitors, gabapentin, pregabalin, duloxetine, or cyclooxygenase-2 inhibitors.
• Has been administered systemic steroids within 5 half-lives or 10 days prior to the scheduled surgery (whichever is longer).
• Has a known or suspected history of drug abuse, a positive drug screen (except for cannabinoids) on the day of surgery, or a history of alcohol abuse within the past 5 years.
• Suspected or confirmed active coronavirus disease 2019 (COVID-19) infection.
• 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, other than for diagnostic procedures (eg, colonoscopy).
• Has a body mass index (BMI) \>40 kg/m2.

Sponsors & Collaborators

• Heron Therapeutics: lead

Study Sites (5)

Woodland International Research Group, LLC

Little Rock, Arkansas, 72211, United States

Location

Center for Orthopaedic Reconstruction and Excellence

Jenks, Oklahoma, 74037, United States

Location

First Surgical Hospital

Bellaire, Texas, 77401, United States

Location

Legent Orthopedic Hospital

Carrollton, Texas, 75006, United States

Location

JBR Clinical Research

Salt Lake City, Utah, 84107, United States

Location

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Bupivacaine; Ibuprofen; Acetaminophen

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Acetanilides

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomized in a 2:1 ratio to HTX-011 or bupivacaine HCl, respectively. All subjects will receive a scheduled postoperative non opioid multimodal analgesic (MMA) regimen.

Study Record Dates

• First Submitted: October 25, 2023
• First Posted: October 31, 2023
• Study Start: October 20, 2021
• Primary Completion: July 18, 2022
• Study Completion: July 29, 2022
• Last Updated: October 31, 2023

Record last verified: 2023-10

Locations

US (5)