Placebo-Controlled Evaluation of N1539 Following Bunionectomy Surgery

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the safety of N1539 in subjects with acute moderate to severe pain following unilateral bunionectomy.

Official Title
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A Phase 2, Single-Center, Randomized, Double-Blind, Placebo-Controlled, Evaluation of the Safety, Efficacy, and Pharmacokinetics of N1539 Following Bunionectomy

Conditions
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Pain, Post-operative

Intervention / Treatment
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* Drug: N1539
* Drug: Intravenous Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily provide written informed consent. Male or female between 18 and 75 years of age, inclusive. Be scheduled to undergo a primary unilateral first metatarsal bunionectomy repair Be American Society of Anesthesiology (ASA) physical class 1 or 2. Female subject are eligible only if all the following apply: Not pregnant; Not lactating; Not planning to become pregnant during the study; Commit to the use of an acceptable form of birth control for the duration of the study through Day 30. Have a body mass index ≤35 kg/m2 Be able to understand the study procedures, comply with all study procedures, and agree to participate in the study program. Exclusion Criteria: Have a known allergy to meloxicam or any excipient of N1539, D5W, aspirin, other non-steroidal anti-inflammatory drugs (NSAIDs) or to any peri- or postoperative medications used in this study. Have a clinically significant abnormal clinical laboratory test value. Have history of or positive test results for HIV, or hepatitis B or C. Have a history or clinical manifestations of significant renal, hepatic, cardiovascular, metabolic, neurologic, psychiatric, or other condition that would preclude participation in the study. Have a history of migraine or frequent headaches, seizures, or are currently taking anticonvulsants. Have another painful physical condition that may confound the assessments of post operative pain. Have a history of syncope or other syncopal attacks. Have evidence of a clinically significant 12 lead ECG abnormality. Have a history of alcohol abuse (regularly drinks > 4 units of alcohol per day; 8 oz. beer, 3 oz. wine, 1 oz. spirits) or prescription/illicit drug abuse.. Have positive results on the urine drug screen or alcohol breath test indicative of illicit drug or alcohol abuse. Have been receiving or have received chronic opioid therapy defined as greater than 15 morphine equivalents units per day for greater than 3 out of 7 days per week over a one-month period within 12 months. Use concurrent therapy that could interfere with the evaluation of efficacy or safety, such as any drugs which in the investigator's opinion may exert significant analgesic properties or act synergistically with N1539. Unable to discontinue medications, that have not been at a stable dose for at least 14 days prior to the scheduled bunionectomy procedure, within 5 half lives of the specific prior medication (or, if half life is not known, within 48 hours) before dosing. Have utilized corticosteroids, either systemically, inhalational either intranasally or oral, or by intra-articular injection, within 14 days prior to the study. Have received any investigational product within 30 days before dosing with study medication. Be receiving warfarin, lithium, or a combination of furosemide with either an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker Be currently receiving treatment with oral meloxicam (Mobic®) Have previously received N1539 in clinical trials, or had bunionectomy in the last 3 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 30mg<br>N1539 (Intravenous meloxicam) 30mg every 24 hours for up to 3 doses. | Drug: N1539<br> <br> * Other names: Intravenous meloxicam;|
| Experimental: N1539 60mg<br>N1539 (Intravenous meloxicam) 60mg every 24 hours for up to 3 doses. | Drug: N1539<br> <br> * Other names: Intravenous meloxicam;|
| Placebo Comparator: IV Placebo<br>IV Placebo every 24 hours for up to 3 doses. | Drug: Intravenous Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Adverse Events | Number of subjects reporting treatment emergent adverse events | Through Day 30 Follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect Size of N1539 Doses Using the Summed Pain Intensity Difference Over the First 48 Hours (SPID48) | Effect size was estimated based on SPID48 derived using 2-hour windowed last observation carried forward (W2LOCF) method and an analysis of covariance (ANCOVA) model that included treatment and baseline PI score. | 48 Hours | 
| Summed Pain Intensity Difference Over the First 48 Hours (SPID48) | Pain intensity was recorded using a Numeric Pain Rating Scale (Range 0-10) where 0 equates to no pain (better), and 10 equates to the worst pain imaginable (worse). Pain intensity scores were to be recorded at the following time points: 0.25, 0.5, 0.75, 1, 2, 4, and 6 hours post Dose 1. Thereafter pain assessments were to be recorded every 2 hours until 48 hours post Dose 1. Pain intensity differences from baseline at each time point were calculated and a time weighted summed pain intensity difference (SPID) was then calculated. Time weighted SPID calculations were computed by multiplying a weight factor to each score prior to summation. The weight factor at each time point was the time elapsed since the previous observation. A smaller SPID was better. | 48 Hours | 
| Summed Pain Intensity Difference (SPID) at Other Intervals | Pain intensity was recorded using a Numeric Pain Rating Scale (Range 0-10) where 0 equates to no pain (better), and 10 equates to the worst pain imaginable (worse). Pain intensity scores were to be recorded at the following time points: 0.25, 0.5, 0.75, 1, 2, 4, and 6 hours post Dose 1. Thereafter pain assessments were to be recorded every 2 hours until 48 hours post Dose 1. Pain intensity differences from baseline at each time point were calculated and a time weighted summed pain intensity difference (SPID) was then calculated. Time weighted SPID calculations were computed by multiplying a weight factor to each score prior to summation. The weight factor at each time point was the time elapsed since the previous observation. A smaller SPID was better. | 48 Hours | 
| Number of Subjects With Use of Rescue Medication (Oral Opioids) |  | 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bunion, Bunionectomy, Pain, Analgesia, N1539