Phase 2B Upper Extremity Nerve Block Study

• HTX-011 (Drug): HTX-011 (bupivacaine/meloxicam) via nerve block or instillation.
• Bupivacaine HCl without epinephrine (Drug): Bupivacaine HCl without epinephrine, 50 mg via nerve block.
• Saline Placebo (Drug): Saline placebo via nerve block.

Primary outcomes

• Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores With Activity (NRS-A) Through 24 Hours Postsurgery (AUC0-24). [24 hours]: Pain intensity is assessed using an 11-point NRS (0-10) where 0 represents "no pain" and 10 represents "worst pain imaginable" (using windowed worst observation carried forward to adjust for opioid rescue medication use). The theoretical range of AUC0-24 is 0-240. The prescribed activity for NRS-A is keeping the elbows at the side and against the body and then raising both hands in front of the abdomen with hands clasped and holding that position for at least 5 seconds.

Secondary outcomes

• Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) [72 Hours]

Sex: Female, ages: 18 Years to any

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.

Participant flow

Outcome results

• Mean Area Under the Curve (AUC) of the Numeric Rating Scale (NRS) Pain Intensity Scores With Activity (NRS-A) Through 24 Hours Postsurgery (AUC0-24). (Primary), Mean, pain intensity score*hr: Group 1: HTX-011 124.51 +/- 59.462; Group 2: HTX-011 136.17 +/- 58.598; Group 3: HTX-011 136.76 +/- 56.034; Group 4: HTX-011 116.71 +/- 52.622; Group 5: HTX-011 114.87 +/- 48.214; Group 6: Bupivacaine HCl 133.83 +/- 49.493; Group 7: Saline Placebo 151.52 +/- 46.213
• Mean Total Postoperative Opioid Consumption (in Morphine Equivalents) (Secondary), Mean, Morphine milligram equivalents (MME): Group 1: HTX-011 38.71 +/- 28.650; Group 2: HTX-011 24.39 +/- 19.878; Group 3: HTX-011 38.00 +/- 19.452; Group 4: HTX-011 28.84 +/- 22.603; Group 5: HTX-011 37.46 +/- 21.452; Group 6: Bupivacaine HCl 33.57 +/- 23.088; Group 7: Saline Placebo 36.38 +/- 23.275

Adverse events

Time frame: 28 Days.

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2017-11-15)
• Statistical Analysis Plan (PDF, 2018-01-04)