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

Phase 4

Completed

• Conditions: Total Shoulder Arthroplasty; Multimodal Analgesia; Postoperative Pain
• Interventions: Drug: HTX-011; Drug: Bupivacaine Hydrochloride; Drug: Ibuprofen; Drug: Acetaminophen; Device: Luer lock applicator

• Registration Number: NCT06109415
• Lead Sponsor: Heron Therapeutics

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2021-10-20
• Primary Completion: 2022-07-18
• Study Completion: 2022-07-29
• Status Verified: 2023-10
• Study First Submitted: 2023-10-25
• Study First Submitted QC: 2023-10-25
• Last Update Submitted: 2023-10-25
• Study First Posted: 2023-10-31
• Last Update Posted: 2023-10-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

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

Exclusion Criteria

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Group 2 Cohort 1	Ibuprofen	Bupivacaine HCl + MMA regimen
Treatment Group 1 Cohort 1	Luer lock applicator	HTX-011 + multimodal analgesic (MMA) regimen
Treatment Group 2 Cohort 1	Acetaminophen	Bupivacaine HCl + MMA regimen
Treatment Group 1 Cohort 1	HTX-011	HTX-011 + multimodal analgesic (MMA) regimen
Treatment Group 2 Cohort 1	Bupivacaine Hydrochloride	Bupivacaine HCl + MMA regimen
Treatment Group 1 Cohort 1	Ibuprofen	HTX-011 + multimodal analgesic (MMA) regimen
Treatment Group 1 Cohort 1	Acetaminophen	HTX-011 + multimodal analgesic (MMA) regimen

Primary Outcome Measures

Name	Time	Method
Incidence of treatment-emergent adverse events (TEAEs).	Through Day 15

Secondary Outcome Measures

Name	Time	Method
Apparent terminal half-life (t½) 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
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 extrapolated to infinity (AUCinf) of bupivacaine and meloxicam	Through 144 hours

Trial Locations

Locations (5)

First Surgical Hospital; 🇺🇸 Bellaire, Texas, United States

Legent Orthopedic Hospital; 🇺🇸 Carrollton, Texas, United States

JBR Clinical Research; 🇺🇸 Salt Lake City, Utah, United States

Center for Orthopaedic Reconstruction and Excellence; 🇺🇸 Jenks, Oklahoma, United States

Woodland International Research Group, LLC; 🇺🇸 Little Rock, Arkansas, United States