An investigational formulation of IV meloxicam relieved pain, spared opioid usage and was well tolerated after major surgeries in patients of varied demographics and health status.
These findings come from three reports of phase 3 studies presented at the 2017 annual PAINWeek meeting.
“Because IV meloxicam is in the nonopioid class of drugs, Recro Pharma believes it will overcome many of the issues associated with commonly prescribed opioids, including respiratory depression, constipation, excessive nausea and vomiting, as well as not having addictive potential while maintaining meaningful analgesic effects for relief of pain,” said Stewart McCallum, MD, chief medical officer at Recro Pharma.
A phase 3, placebo-controlled study of the safety of IV meloxicam for moderate to severe pain after major surgery and the amount of concurrent opioid use required for breakthrough pain involved 721 patients, with 538 randomly assigned to 30 mg of IV meloxicam and 183 to placebo. The surgeries, of 1.3-hour mean duration, included orthopedic, abdominal, gynecologic and spinal procedures for which a nonsteroidal anti-inflammatory drug (NSAID) was not contraindicated.
Randall Mack, senior vice president of development at Recro Pharma, and his colleagues evaluated the safety and tolerability of meloxicam through a variety of measures, including wound healing and postoperative opioid use. With the possibility of the NSAID affecting bleeding and wound healing, the healing was assessed at multiple time points with a 10-point scale, in addition to taking measures of erythema, drainage, edema, induration and hematoma.
The analgesic efficacy of the study drug was reflected in the requirement of additional analgesia from opioids, relative to the opioid consumption by those receiving placebo. The opioid amounts were converted to an IV morphine equivalent dose from a standardized conversion table.
The study drug or placebo was administered via IV push over 15 to 30 seconds every 24 hours for up to seven doses. The majority of patients (80%) required two or three doses of the study drug during their inpatient stay. The mean time to first dose of the study drug was 1.7 hours after end of surgery.
Mr. Mack and his colleagues reported that the study drug was well tolerated, with a low incidence of serious adverse events (2.6% with IV meloxicam, 5.5% with placebo) or having to be discontinued while analgesia was still required (0.4% meloxicam, 0% placebo). Surgical wound healing was similar between study drug and placebo.
Mean opioid consumption was significantly lower in the IV meloxicam group compared with placebo in the zero- to 24-hour period (22% lower), and at zero to 48 hours (22.6% lower) and zero to 72 hours (23.7% lower). There was also a lower rate of nausea and vomiting observed in the meloxicam group, which Mr. Mack and his colleagues indicated “could have been related to the reduction in opioid use compared with placebo.”
A subset of 379 patients undergoing orthopedic surgery were examined in a separate report by Mr. Mack and his colleagues. The mean duration of surgery was 1.4 hours, and the mean time to first dose of study drug was 2.2 hours. Approximately 85% of patients received two or three doses during inpatient stay. There was a similarly low incidence of serious adverse events in this subpopulation (2.5% vs. 4.2% with placebo) and of discontinuation (0.4% vs. 0% with placebo). Opioid consumption was significantly lower by those receiving meloxicam than placebo: by 27.4% in the zero- to 24-hour period, and 26.1% at 24 to 48 hours, 26.5% at zero to 48 hours and 27.2% at zero to 72 hours.
IV Meloxicam in Patients of Advanced Age, Impaired Renal Function
The safety and tolerance of the study drug also were scrutinized in a subset of patients of advanced age with impaired renal function. Mr. Mack and his colleagues identified 119 patients ranging in age from 66 to 80 years (mean, 70.5 years), with a glomerular filtration rate of no more than 89 mL/min/1.73 m2. The patients were randomly assigned 3:1, with 88 randomly assigned to the study drug and 31 to placebo. Over 80% received two or three doses of the study drug during their inpatient stay.
Similar to the larger study cohort, few serious adverse events were associated with the study drug (2.3% with meloxicam, 12.9% with placebo). There were no instances of discontinuing the study drug while analgesia was still required. The investigators also noted that there was a low incidence of clinically meaningful changes in laboratory, vital signs and/or ECG assessments during the study, with similar measures between active drug and placebo. Wound healing also was consistent between the treatment groups.
Opioid use with meloxicam compared with those on placebo was reduced to a greater extent in this population than across the larger safety study cohort: by 41.9% in the 24- to 48-hour period, and 36.2% at zero to 48 hours and 38.2% at zero to 72 hours. Mr. Mack and his colleagues concluded, “This study supports the safety and tolerability of IV meloxicam 30 mg administered once daily for up to 7 days following major surgery in subjects older than 65 years with impaired renal function.”
Dr. McCallum indicated that the company had submitted a New Drug Application to the FDA in July. In addition to these data on safety and concurrent opioid use, the application was supported by four phase 2 trials and a phase 3 study of drug efficacy and safety after bunionectomy and abdominoplasty, with the drug having been studied for moderate to severe postsurgical pain in over 1,400 patients.