SAN DIEGO, CA—Patients who received investigational, lower-dose indomethacin submicron particle capsules for acute pain following elective surgery reported effective analgesia vs. placebo, according to results of two phase 3 multicenter randomized studies presented at the 2013 ACR/ARHP Annual Meeting.

“Indomethacin is used to treat acute gouty arthritis and other acute pain conditions but, like other NSAIDs, is associated with dose-related gastrointestinal, cardiovascular, and renal complications,” reported Clarence Young, MD, Senior Vice President and Chief Medical Officer of Iroko Pharmaceuticals, LLC, Philadelphia, PA. Furthermore, “a U.S. Food and Drug Administration Public Health Advisory recommended that physicians use NSAIDs at ‘the lowest effective dose for the shortest duration consistent with individual patient treatment goals.’”

The challenge? Using existing NSAIDs at lower doses to achieve efficacy, Dr. Young noted. For that reason, “new, submicron particle NSAIDs with enhanced absorption are under investigation to evaluate efficacy at lower doses than commercially available NSAIDs.”

The studies enrolled 835 patients 18—65 years of age who were undergoing bunionectomy with osteotomy and internal fixation under regional anesthesia.

Following surgery, patients who recorded a pain intensity rating of ≥40mm on the 100mm Visual Analog Scale (VAS) received indomethacin submicron particle capsules 40mg twice or three times daily or 20mg three times daily, or placebo. One of the studies included a celecoxib 400mg loading dose followed by 200mg twice daily. Primary end point was difference in overall pain intensity measured by VAS over 48 hours.

“In Study 1, indomethacin submicron particle capsules 40mg three times daily provided significant reduction in pain intensity over 48 hours measured by overall pain intensity compared with placebo (P<0.001),” Dr. Young and colleagues noted. Indomethacin submicron particle capsules 40mg twice daily and 20mg three times daily provided significantly better analgesia vs. placebo (P=0.046 and P=0.017, respectively). “While celecoxib led to some pain control, it did not achieve statistical significance compared with placebo (P=0.103).”

In the second study, indomethacin submicron particle capsules 40mg twice daily (P=0.023) as well as three times daily (P=0.034) provided significantly better analgesia than placebo.

In both studies, adverse events were generally similar across treatment groups and included nausea, localized post-procedural edema, dizziness, and headache.

“Indomethacin submicron particle capsules are a potentially promising lower-dose option for patients with acute pain,” the investigators concluded.