XG005 for Pain Control in Subjects Undergoing Bunionectomy

Study Overview
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Brief Summary
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This study will evaluate the safety, efficacy, and PK of low dose (750 mg) and high-dose (1250 mg) XG005 oral tablets compared with placebo in subjects undergoing bunionectomy. Subjects will be confined in the clinic from check-in through 72 hours post-surgery to monitor subject safety.

Detailed Description
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This is a multi-center, randomized, double-blind, parallel-group, placebo-controlled study. Eligible subjects will be randomized in a 1:1:1 ratio to receive either 750 mg XG005, 1250 mg XG005, or placebo, twice a day, post bunionectomy surgery in domiciled clinic. Subjects and all study staff performing study assessments will be blinded to treatment allocation. Subjects will be discharged at a reasonable hour of the day after the end of the 72-hour treatment period.There will be a Follow-up Visit on Day 15.

Official Title
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A Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Safety and Efficacy of XG005 Tablets in Subjects Undergoing Bunionectomy

Conditions
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Acute Pain

Intervention / Treatment
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* Drug: XG005 tablet
* Drug: Placebo tablet


Participation Criteria
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Eligibility Criteria
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Main inclusion criteria: Scheduled to undergo unilateral first metatarsal bunionectomy Have negative urine drug screen Non-pregnant, non-lactating Main exclusion criteria: Medical condition or history that in the investigator's opinion could adversely impact the subject's participation or safety Use of disallowed medications (e.g. pain medication, CNS active drugs such as benzodiazepines, tricyclic antidepressants, Serotonin, and norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), or any other serotonergic medications, parenteral or oral corticosteroids) Antihypertensive agent or diabetic regimen at a dose that has not been stable for at least 30 days Digoxin, warfarin lithium, theophylline preparations, aminoglycosides, and all antiarrhythmics Monoamine oxidase inhibitors (MAOIs) Positive HbsAg and/or anti-HBc but negative anti-HBs HIV infection History of illicit drug use History of opioid dependence History of NSAID-induced bronchospasm or presence of nasal polyps, history of asthma or chronic rhinitis Significant history of allergic reactions or known intolerance to naproxen, pregabalin or any gabapentinoid, or to any rescue medication used in the study, or any medication used in the surgical and anesthetic protocol. Presence of severe depression as indicated by Patient Health Questionnaire (PHQ 9) total score of ≥20 or item 9 score >0 Presence of severe anxiety as indicated by General Anxiety Disorder (GAD-7) score of ≥15 Presence of history of suicidal behavior or ideation as indicated by the C-SSRS

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: high dose<br>XG005 1250 mg Q12 hours | Drug: XG005 tablet<br>* Subjects will receive XG005 prior to surgery and every 12 hours for 72 hours.<br>|
| Experimental: low dose<br>XG005 750 mg Q12 hours | Drug: XG005 tablet<br>* Subjects will receive XG005 prior to surgery and every 12 hours for 72 hours.<br>Drug: Placebo tablet<br>* Subjects will receive placebo prior to surgery and every 12 hours for 72 hours.<br>|
| Placebo Comparator: placebo<br>placebo Q12 hours | Drug: Placebo tablet<br>* Subjects will receive placebo prior to surgery and every 12 hours for 72 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Summed pain intensity from end of surgery to 48 hours post-surgery | Pain assessments via a standard 11-point NPRS at the various time points post-end of surgery | 0 to 72 hours post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total tramadol rescue medication consumption | Tramadol 50 mg, PRN | 0 to 72 hours post-surgery | 
| Time to first use of rescue medication from end of surgery | Acetaminophen 1g, PRN | 0 to 72 hours post-surgery | 
| Patient Global Assessment (PGA) at 48 hours | PGA of pain control using a 5 point scale at the following time points post-surgery | 0 to 72 hours post-surgery | 
| Cumulative Nausea (NNRS) assessment scores through 24 hours | NNRS assessment scores at various time points | 0 to 72 hours post-surgery | 
| TEAEs | First dose of study drug to 30 days after the last dose of study drug | Day 1 to Day 30 | 
| Continuous Pulse Oximetry | oxygen saturation (Sp02) will be recorded every 12 hours post-end of surgery. | 0 to 72 hours post-surgery |