Phase 2 Bunionectomy HTX-011 Administration Study

Study Overview
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Brief Summary
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This is a Phase 2, open-label, multi-cohort study to evaluate the analgesic efficacy, safety, and pharmacokinetics (PK) of a single, individualized dose of HTX-011 administered into the surgical site as a monotherapy or with other medications to enhance analgesia in subjects undergoing unilateral simple bunionectomy.

Official Title
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A Phase 2 Open-Label Study of HTX-011 Via Individualized Dosing Administration for Postoperative Analgesia Following Unilateral Simple Bunionectomy

Conditions
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Postoperative Pain

Intervention / Treatment
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* Drug: HTX-011
* Device: Luer Lock applicator
* Device: Vial access device
* Drug: aprepitant


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. For cohort 2, acceptable contraceptives excludes hormonal contraceptives. Exclusion Criteria: Has had a contralateral foot bunionectomy in the past 3 months prior to the scheduled surgery. Has a planned concurrent surgical procedure (eg, bilateral bunionectomy or collateral procedures on the surgical foot). Has a 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 long-acting opioids within 3 days prior to the scheduled surgery. Has taken any opioids within 24 hours prior to the scheduled surgery. Has been administered bupivacaine within 5 days prior to the scheduled surgery. For Cohort 2 only, has been administered aprepitant or another NK1 receptor antagonist within 5 days prior to the scheduled surgery. Has been administered any local anesthetic within 72 hours prior to the scheduled surgery. Has initiated treatment with study 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. For Cohort 2 only, is receiving pimozide, a strong or moderate CYP3A4 inhibitor, or a strong CYP3A4 inducer. 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 at the discretion of the Sponsor. Subjects taking any marijuana (medical or recreational) are not allowed to participate in the study. Previously participated in an HTX-011 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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group 1: HTX-011<br>HTX-011 (bupivacaine/meloxicam), up to but not to exceed 60 mg/1.8 mg, via instillation. | Drug: HTX-011<br>* HTX-011 (bupivacaine/meloxicam), up to but not to exceed 60 mg/1.8 mg, via instillation.<br>Device: Luer Lock applicator<br>* Applicator for instillation.<br>Device: Vial access device<br>* Device for withdrawal of drug product.<br>|
| Experimental: Treatment Group 2: HTX-011 + Aprepitant<br>HTX-011 (bupivacaine/meloxicam), up to but not to exceed 60 mg/1.8 mg, via instillation; Aprepitant, three single doses of aprepitant will be administered orally. | Drug: HTX-011<br>* HTX-011 (bupivacaine/meloxicam), up to but not to exceed 60 mg/1.8 mg, via instillation.<br>Device: Luer Lock applicator<br>* Applicator for instillation.<br>Device: Vial access device<br>* Device for withdrawal of drug product.<br>Drug: aprepitant<br>* Aprepitant, three single doses of aprepitant will be administered orally.<br>|
| Experimental: Treatment Group 3: HTX-011 + Non-Opioid MMA Regimen<br>HTX-011 (bupivacaine/meloxicam), up to but not to exceed 60 mg/1.8 mg, via instillation and a scheduled multimodal analgesic (MMA) regimen. | Drug: HTX-011<br>* HTX-011 (bupivacaine/meloxicam), up to but not to exceed 60 mg/1.8 mg, via instillation.<br>Device: Luer Lock applicator<br>* Applicator for instillation.<br>Device: Vial access device<br>* Device for withdrawal of drug product.<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 NRS-A (Windowed Worst Observation Carried Forward) Pain Intensity Scores | 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), sitting 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 Total Postoperative Opioid Consumption (in Morphine Equivalents) Through 72 Hours |  | 72 hours | 
| Percentage of Subjects Receiving no Opioid Rescue |  | 72 hours | 
| Percentage of Subjects Receiving no Opioid Rescue | Only subjects in Cohort 3 received a scheduled, non-opioid MMA regimen following surgery. | Day 7 and Day 28 | 
| Mean Area Under the Curve (AUC) of the NRS-R (Windowed Worst Observation Carried Forward) Pain Intensity Scores | 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 measured at rest. | 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