Phase 2B Upper Extremity Nerve Block Study

Study Overview
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Brief Summary
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This is a Phase 2B, randomized, assessor-blind, active- and saline placebo-controlled, multicenter study in subjects undergoing augmentation mammoplasty to evaluate the analgesic efficacy, safety, and pharmacokinetics (PK) of HTX-011 when administered via ultrasound-guided lateral and medial pectoral nerve block before surgery.

Official Title
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A Phase 2B, Randomized, Controlled Study of HTX-011 Administered Via Pectoral Nerve Block in Subjects Undergoing Upper Extremity Surgery for Augmentation Mammoplasty

Conditions
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Postoperative Pain

Intervention / Treatment
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* Drug: HTX-011
* Drug: Bupivacaine HCl without epinephrine
* Drug: Saline Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is scheduled to undergo primary bilateral submuscular augmentation mammoplasty with saline or silicone smooth implants with a volume of 300 to 500 cc, inclusive. Note: textured implants are not allowed. Has an American Society of Anesthesiologists Physical Status of I, II, or III. 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 a planned concurrent surgical procedure. Has a planned reconstructive procedure status post breast cancer therapy. 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 medication. Has known or suspected daily use of opioids for 7 or more consecutive days within the previous 6 months. Has taken NSAIDs within 10 days prior to scheduled surgery. Has been administered bupivacaine within 5 days prior to the scheduled surgery. Has been administered any local anesthetic within 72 hours prior to the scheduled surgery other than to treat an AE that occurs after signing the ICF or for pretreatment prior to a needle placement. Has initiated treatment with any of the following medications within 1 month prior to study drug administration or is taking any of these medications to control pain: selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), gabapentin, pregabalin, duloxetine, or cyclooxygenase-2 (COX-2) inhibitors. (Note: If a subject is taking one of these medications for a reason other than pain control, she must be on a stable scheduled dose [ie, not as needed] for at least 1 month prior to study drug administration.) Anxiolytics prior to surgery are permitted, if necessary. Has a medical condition that, in the opinion of the Investigator, participating in the study would pose a health risk to the subject or confound the postoperative assessments. Has a known history of Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV). Has uncontrolled anxiety, psychiatric, or neurological disorder that might interfere with study assessments Has any chronic neuromuscular deficit of either pectoral nerve function or arm/shoulder/truncal musculature. Has any chronic condition or disease that would compromise neurological or vascular assessments. Had a malignancy in the last year, with the exception of non-metastatic 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 in 12 months. Has a body mass index (BMI) >35 kg/m2.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: HTX-011<br>HTX-011 (bupivacaine/meloxicam), 60 mg/1.8 mg via nerve block. | Drug: HTX-011<br>* HTX-011 (bupivacaine/meloxicam) via nerve block or instillation.<br>|
| Experimental: Group 2: HTX-011<br>HTX-011(bupivacaine/meloxicam), 120 mg/3.6 mg via nerve block. | Drug: HTX-011<br>* HTX-011 (bupivacaine/meloxicam) via nerve block or instillation.<br>|
| Experimental: Group 3: HTX-011<br>HTX-011(bupivacaine/meloxicam), 240 mg/7.2 mg via nerve block. | Drug: HTX-011<br>* HTX-011 (bupivacaine/meloxicam) via nerve block or instillation.<br>|
| Experimental: Group 4: HTX-011<br>HTX-011 (bupivacaine/meloxicam), 400 mg/12 mg via nerve block. | Drug: HTX-011<br>* HTX-011 (bupivacaine/meloxicam) via nerve block or instillation.<br>|
| Experimental: Group 5: HTX-011<br>HTX-011 (bupivacaine/meloxicam), 400 mg/ 12 mg via instillation. | Drug: HTX-011<br>* HTX-011 (bupivacaine/meloxicam) via nerve block or instillation.<br>|
| Active Comparator: Group 6: Bupivacaine HCl<br>Bupivacaine HCl without epinephrine, 50 mg via nerve block. | Drug: Bupivacaine HCl without epinephrine<br>* Bupivacaine HCl without epinephrine, 50 mg via nerve block.<br>|
| Placebo Comparator: Group 7: Saline Placebo<br>Saline placebo via nerve block. | Drug: Saline Placebo<br>* Saline placebo via nerve block.<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), raising the hands above the head (with wrists above the crown of the head) for at least 5 seconds. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) |  | 72 Hours |