A proprietary extended-release formulation of bupivacaine and meloxicam (HTX-011) reduces the intensity of pain and the use of opioids in the first days after abdominoplasty, according to a study presented here at the 2017 Annual Meeting of the American College of Surgeons (ACS).
“HTX-011 was well tolerated and significantly reduced pain and opioid use for up to 96 hours after abdominoplasty,” said David Leiman, MD, Memorial Hermann — Memorial City Medical Center, Houston, Texas, on October 23.
The early days after major surgery, including abdominoplasty, are painful. Typically the pain is treated with opioids, which has long been worrisome.
“Systemic opioids are often relied on to manage postoperative pain, increasing the risk of opioid-related adverse events and the potential for drug abuse and addiction, as well as diversion of unused opioids,” said Dr. Leiman.
The current phase 2 study (NCT02689258) was conducted in response to an unmet need for nonopioid analgesics that act for a prolonged time. HTX-011 has been designed to be released at a defined rate over an extended period. The goal of HTX-011 is postoperative pain management in various situations, including abdominoplasty.
Inclusion criteria were abdominoplasty surgery, no contraindication for local anaesthetic, American Society of Anesthesiology physical class I or II, age ≥18 years, body mass index (BMI) ≤30 kg/m2, no plans for pregnancy, and absence of lactation. A bevy of exclusion criteria included relevant allergies, painful condition that could confound pain assessment, history of migraine or frequent headache, history of seizures, current use of anticonvulsant medication, prior abdominal surgery, use of defined medications (e.g., nonsteroidal anti-inflammatory drugs, corticosteroids, sedatives, morphine, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors) within 24 hours of study-drug dosing, history/suspicion of alcohol or drug abuse, clinically significant cardiac abnormality, and history of oxygen therapy.
The efficacy endpoints assessed through 72 hours were the area under the curve (AUC) of a numeric pain intensity score, opioid use, and proportion of opioid-free patients. The safety endpoints were treatment-emergent adverse events, events that were serious, vital signs, clinical laboratory findings, and electrocardiography.
Seventy-four women (mean age, 42 years, 76% white, mean BMI, 27 kg/m2) scheduled for abdominoplasty were randomised to receive one 400-mg dose of HTX-011 (equivalent to 400 mg bupivacaine; n = 25), bupivacaine 100 mg (n = 17), or saline (n = 32). At baseline, the 3 study arms were comparable in mean age, BMI, and race.
Pain was significantly less in the patients receiving HTX-011 than in those receiving placebo during the first 24 hours after surgery (P = .0135). Pain intensity was less for the patients receiving HTX-011 than for those receiving bupivacaine during this time, but the difference was not significant (P = .0985). The same pattern was evident at 48 hours (placebo, P = .0090; bupivacaine, P = .0770). By 72 hours, the pain intensity was significantly less for patients receiving HTX-011 than for those receiving either placebo or bupivacaine (P = .0052 and .0430, respectively).
Patients receiving HTX-011 required significantly less opioid rescue medication at 24, 48, and 72 hours than those receiving placebo or bupivacaine. Frequency of opioid use in the HTX-011, bupivacaine, and placebo groups was 4.0%, 0%, and 0% at 24 hours; 20.0%, 11.8%, and12.5% at 48 hours; and 48.0%, 35.3%, and 21.9% at 72 hours. At 72 hours, patients in the treatment arm had used 26.1% fewer opioids than patients in the placebo arm.
Few adverse events occurred in the various treatment groups, and the events that did occur were similar. The most common adverse events with HTX-011 were nausea (68.0% vs 70.6% and 38% in the bupivacaine and placebo arms, respectively), constipation (28.0%, 41.2%, and 31.3%, respectively), and headache (28%, 11.8%, and 34.4%, respectively). These events were tolerable and manageable. There were no serious adverse events and no deaths.
“The differences in adverse event rates between the treatment groups were not clinically meaningful,” said Dr. Leiman.
“Taken with previous reports in herniorrhaphy and bunioectomy, these abdominoplasty data suggest that HTX-011 is well tolerated and effective across a range of surgical models with different incision sizes,” concluded Dr. Leiman, adding that “HTX-011 may represent a significant advance in postoperative pain management.”
A phase 3 study has begun to support an application for approval. In the longer term, the extended-release formulation will be evaluated for other conditions.