Evaluation of Preoperative N1539 in Total Knee Arthroplasty

A Phase 3b, Randomized, Double-Blind, Placebo-Control, Multicenter, Evaluation of the Safety and Efficacy of N1539 Administered Preoperatively in Open Unilateral Total Knee Arthroplasty

The primary objective of this study is to assess the effect of preoperative administration of N1539 on opioid consumption in subjects undergoing open unilateral total knee arthroplasty compared to placebo.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative
• Intervention / Treatment: Drug: Placebo; Drug: N1539

• Study Type: Interventional
• Enrollment (Actual): 194
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Florence, Alabama, United States, 35630
      • Research Center
    • Mobile, Alabama, United States, 36608
      • Research Center
    • Sheffield, Alabama, United States, 35660
      • Research Center
  • Arizona
    • Tempe, Arizona, United States, 85284
      • Research Center
  • Florida
    • Tamarac, Florida, United States, 33321
      • Research Center
    • Vero Beach, Florida, United States, 32960
      • Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Voluntarily provide written informed consent.
• Be planned to undergo an elective, primary (no repeat arthroplasties) open unilateral total knee arthroplasty (TKA), and be expected to require IV analgesia, remain in an inpatient setting for ≥24 hours, and receive at least two doses of study drug.
• ASA physical status category 1, 2, or 3.
• Female subjects not pregnant or planning/attempting to become pregnant, not lactating; or commits to the use of an acceptable form of birth control for the duration of the study.
• Have a body mass index <40 kg/m^2

Exclusion Criteria:

• Have a known allergy or hypersensitivity to any study treatment.
• Have a history of previous TKA.
• Has plans for a concurrent surgical procedure (eg, bilateral TKA).
• Has TKA planned to be performed under general anesthesia.
• Have a history of myocardial infarction within the preceding 12 months.
• Have, as determined by the investigator or the sponsor's medical monitor, a history or clinical manifestations of significant condition that would preclude participation.
• Have active or recent (within 6 months) gastrointestinal ulceration or bleeding.
• Have a known bleeding disorder which may be worsened with the administration of an NSAID.
• Be currently receiving treatment with oral meloxicam (Mobic®) or another NSAID within 48 hours prior to surgery.
• Have previously received N1539/IV meloxicam or received any investigational product within 30 days before dosing with study medication.
• Have undergone or be expected to undergo radiation therapy, chemotherapy, or other biological therapy for cancer treatment, within 60 days prior to screening through last follow-up.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: N1539 30 mg; N1539 (meloxicam injection for IV use) 30 mg every 24 hours	Drug: N1539; Once Daily; Other Names: Intravenous meloxicam
Placebo Comparator: IV Placebo; IV Placebo every 24 hours	Drug: Placebo; Once Daily; Other Names: Intravenous placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid Use Hour 0-24	Total use of opioid analgesia, in IV morphine equivalent dose, from Hour 0 through 24.	Up to 24 Hours

Collaborators and Investigators

• Sponsor: Baudax Bio

Publications and helpful links

General Publications

• Berkowitz RD, Steinfeld R, Sah AP, Mack RJ, McCallum SW, Du W, Black LK, Freyer A, Coyle E. Safety and Efficacy of Perioperative Intravenous Meloxicam for Moderate-to-Severe Pain Management in Total Knee Arthroplasty: A Randomized Clinical Trial. Pain Med. 2021 Jun 4;22(6):1261-1271. doi: 10.1093/pm/pnab016.

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2018
• Primary Completion (Actual): May 21, 2019
• Study Completion (Actual): May 21, 2019

Study Registration Dates

• First Submitted: February 9, 2018
• First Submitted That Met QC Criteria: February 9, 2018
• First Posted (Actual): February 15, 2018

Study Record Updates

• Last Update Posted (Actual): May 25, 2023
• Last Update Submitted That Met QC Criteria: April 28, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Pain; Analgesia; Total Knee Arthroplasty; Knee Replacement; Phase 3b; N1539
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Meloxicam
• Other Study ID Numbers: REC-17-025

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: No