Evaluation of Preoperative N1539 in Total Knee Arthroplasty

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Pain, Postoperative

Intervention / Treatment
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* Drug: N1539
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N1539 30 mg<br>N1539 (meloxicam injection for IV use) 30 mg every 24 hours | Drug: N1539<br>* Once Daily<br>* Other names: Intravenous meloxicam;|
| Placebo Comparator: IV Placebo<br>IV Placebo every 24 hours | Drug: Placebo<br>* Once Daily<br>* Other names: Intravenous placebo;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Total Knee Arthroplasty, Pain, Analgesia, N1539, Phase 3b, Knee Replacement