ARX-01 Sufentanil NanoTab PCA System Effective for Management of Moderate to Severe Post-Operative Pain

AUSTIN, TXStudy data was presented at the American Pain Society's 30th Annual Scientific Meeting indicated that a noninvasive, preprogrammed method of patient-controlled analgesia (PCA) is effective in treating both major orthopedic and abdominal post-operative pain with minimal adverse events.

The ARX-01 Sufentanil NanoTab PCA System avoids the issues of medication and programming errors that occur frequently with intravenous PCA. Patients utilize ARX-01 to sublingually deliver NanoTabs, a novel small dosage form of sufentanil, with a 20-minute lockout between dosing. ARX-01 uses radiofrequency identification to uniquely match each patient to the dispensing device.

Harold Minkowitz, MD, and colleagues from Memorial Hermann Memorial City Medical Center, Houston, conducted two randomized, double-blind, placebo-controlled, dose-ranging Phase 2 studies involving knee replacement surgery or open abdominal surgery and an open-label device functionality Phase 2 study in patients undergoing knee replacement surgery to assess the system's efficacy. Primary endpoint of the double-blind studies was the summed pain intensity difference over 12 hours (SPID12), and the proportion of patients reaching study completion for the device functionality study.

In the double-blind studies, a total of 212 patients received the study drug and were included in the overall safety analysis. To assess device functionality, patients self-administered ARX-01 as needed throughout the 12 hour study period using the NanoTab PCA System with a 20 minute redosing interval.

ARX-01 15mcg was the most efficacious dose of the three dosage strengths studied (5mcg, 10mcg and 15 mcg), however, ARX-01 10mcg also showed efficacy compared to placebo in a subgroup analysis of women in the orthopedic surgery placebo-controlled study (P<0.05), as well as in the overall population in the abdominal surgery study (P<0.001). In the knee replacement surgery group, the mean (SEM) SPID12 was 2.9 (5.7), 1.3 (5.6), 12.7 (6.3) and -7.4 (5.7) in the ARX-01 5mg, 10mg, 15mg, and placebo groups, respectively. The mean difference between ARX-01 15mg and placebo was statistically significant (P=0.018). For patients who underwent abdominal surgery, the mean (SEM) SPID12 was 22.4 (3.6), 27.6 (3.5), 2.9 (3.5) for ARX-01 10mg, 15mg, and placebo groups, respectively. Mean difference between both ARX-01 groups and placebo was statistically significant (P<0.001).

Drop-out due to inadequate analgesia for ARX-01 15mcg averaged 16% in the placebo-controlled studies and 7% in the open-label knee replacement study without any rescue or adjuvant analgesic agents being allowed after the initial 30 minutes of the study. The adverse event profile of ARX-01 (15mcg; n=79) demonstrated a low incidence of somnolence (3%), oxygen desaturation (1%) and respiratory depression (0%) compared with published rates for IV PCA. The average re-dosing time was approximately 80 minutes for ARX-01 15mcg, whereas published IV PCA data indicate an average re-dosing time of 20–40 minutes.

The study authors believe these data demonstrate ARX-01 15mg administered with the NanoTab PCA System with a fixed 20 minute redosing interval is efficacious and well-tolerated and may be an optimal non-invasive PCA system for a wide range of patients.