Bunionectomy Study for Postoperative Analgesia (EPOCH 1)

Study Overview
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Brief Summary
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This is a Phase 3, randomized, double-blind, saline placebo- and active-controlled, multicenter study to evaluate the analgesic efficacy and safety of HTX 011 administered via local administration into the surgical site in subjects undergoing bunionectomy.

Official Title
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A Phase 3, Randomized, Double Blind, Saline Placebo and Active Controlled, Multicenter Study of HTX 011 Via Local Administration for Postoperative Analgesia and Decreased Opioid Use Following Unilateral Simple Bunionectomy

Conditions
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Postoperative Pain

Intervention / Treatment
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* Drug: HTX-011
* Drug: Saline Placebo
* Drug: Bupivacaine HCl
* Device: Luer-lock applicator
* Device: Vial access device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is scheduled to undergo a primary unilateral, distal, first metatarsal bunionectomy with osteotomy and internal fixation under regional anesthesia. Has an American Society of Anesthesiologists Physical Status of I, II, or III. Female subjects are eligible only if not pregnant, not lactating, not planning to become pregnant during the study, sterile; or using acceptable contraceptives. Exclusion Criteria: Has had a contralateral foot bunionectomy in the past 3 months. Has a planned concurrent surgical procedure (eg, bilateral bunionectomy or collateral procedures on the surgical foot). Has other pre existing concurrent acute or chronic painful physical/restrictive condition expected to require analgesic treatment in the postoperative period for pain. Has a contraindication or a known or suspected history of hypersensitivity or clinically significant idiosyncratic reaction to required study medications. Has known or suspected daily use of opioids for 7 or more consecutive days within the previous 6 months. Has taken any NSAIDs within at least 10 days prior to the scheduled surgery. Has taken opioids within 24 hours prior to the scheduled surgery (3 days for long-acting). Has been administered bupivacaine within 5 days prior to the scheduled surgery. Has initiated treatment with medications within 1 month prior to study drug administration that can impact pain control. Has been administered systemic steroids within 5 half-lives or 10 days prior to administration of study drug. Has a medical condition such that, in the opinion of the Investigator, participating in the study would pose a health risk to the subject or confound the postoperative assessments. As per subject history and/or medical records, has active infection or is currently undergoing treatment for Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV). Has uncontrolled anxiety, psychiatric, or neurological disorder. 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 a known or suspected history of drug abuse, a positive drug screen on the day of surgery, or a recent history of alcohol abuse. Note: Subjects with a positive drug screen who are taking an allowed, prescribed medication that is known to result in a positive drug test (eg, amphetamine and dextroamphetamine for attention deficit/hyperactivity disorder, benzodiazepine for anxiety disorder) may be eligible for participation in the study. Subjects taking medical marijuana are not allowed to participate in the study. Received an investigational product or device in a clinical trial within 30 days or within 5 elimination half lives. Has undergone 3 or more surgeries within 12 months. Has a body mass index (BMI) >39 kg/m2.

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group 1: HTX-011<br>HTX 011 (bupivacaine/meloxicam) | Drug: HTX-011<br>* HTX 011 (bupivacaine/meloxicam), 60 mg/1.8 mg by instillation<br>Device: Luer-lock applicator<br>* Applicator for instillation<br>Device: Vial access device<br>* Device for withdrawal of drug product<br>|
| Placebo Comparator: Treatment Group 2: Saline Placebo<br>Saline placebo | Drug: Saline Placebo<br>* Saline placebo by instillation<br>Device: Luer-lock applicator<br>* Applicator for instillation<br>|
| Active Comparator: Treatment Group 3: Bupivacaine HCI<br>Bupivacaine HCl | Drug: Bupivacaine HCl<br>* Bupivacaine HCl without epinephrine, 50 mg by injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Area Under the Curve (AUC) of the Numeric Rating Scale of Pain Intensity Scores With Activity (NRS-A; Windowed Worst Observation Carried Forward) for HTX-011 Compared With Saline Placebo. | Pain intensity scores are assessed using an 11-point Numeric Rating Scale (NRS) (0-10) where 0 represents no pain and 10 represents worst pain imaginable. NRS scores are recorded with activity (NRS-A), seated with the plantar surface of the ball of the surgically attended foot touching the floor (no weight-bearing). | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean AUC of the NRS-A Pain Intensity Scores (Windowed Worst Observation Carried Forward) for HTX 011 Compared With Bupivacaine HCl. | Pain intensity scores are assessed using an 11-point Numeric Rating Scale (NRS) (0-10) where 0 represents no pain and 10 represents worst pain imaginable. NRS scores are recorded with activity (NRS-A) seated with the plantar surface of the ball of the surgically attended foot touching the floor (no weight-bearing). | 72 hours | 
| Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Saline Placebo. |  | 72 hours | 
| Percentage of Subjects Who Are Opioid-free for HTX-011 Compared With Bupivacaine HCl. |  | 72 hours | 
| Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) for HTX 011 Compared With Bupivacaine HCl. |  | 72 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bunion, bunionectomy, bunion surgery, postoperative pain