Forrest Ringold, MD1, Harold Minkowitz, MD2, Tong-Joo Gan, MD3, Yu-kun Chiang, PhD4, Karen DiDonato, RN, MSN5, Pamela Palmer, MD, PhD5. 1Mobile Infirmary Medical Center, 2Memorial Hermann Memorial City Medical Center, 3Stony Brook University Hospital, 4Essence Sciences, Inc., 5AcelRx Pharmaceuticals
Description of Technology: The sufentanil sublingual tablet system (Zalviso™) is a non-invasive, patient-controlled analgesia (PCA) drug/device product currently under review by the U.S. FDA and European Medicines Agency for treatment of moderate to severe acute pain in a hospital setting. A second sublingual sufentanil product (30mcg tablet), dispensed using a single-dose applicator, is also in development for treatment of acute pain in a medically-supervised setting, such as Ambulatory Surgery Centers. Sufentanil appears well-suited for acute pain management when delivered sublingually as a result of its high lipid solubility, favorable therapeutic index (as suggested in animal models) and lack of active metabolites.
Objective: The primary objective of this analysis was to examine the repeat-dose safety and efficacy of sublingual sufentanil tablets (SST) when used for post-operative pain management in both a Phase 2 ambulatory surgery population (20 mcg and 30 mcg tablets) and a Phase 3 major abdominal surgery population (15 mcg tablets). Both trials were randomized and placebo-controlled with primary efficacy measures that included the time-weighted sum of pain intensity differences (SPID) to baseline over the 12 and 48-hour study periods. Safety assessments consisted of adverse events (AE), vital signs and early termination.
Results: 101 and 178 patients were randomized in the phase 2 (P2) and phase 3 (P3) studies, respectively. SST 30 mcg was superior to placebo (PBO) for SPID12 (p=0.003) in the P2 study and SST 15mcg was superior to PBO for SPID48 (p=0.001) in the P3 study. Analysis of pain relief by evaluation time point yielded statistically significant differences in favor of SST as early as 30 minutes(p<0.001) following first dose in P2 and 45 minutes (p=0.027) following first dose in P3. AE’s in general were mild to moderate in severity and similar across all treatment assignments. The most common treatment-related AEs for patients receiving SST were nausea, vomiting, dizziness and somnolence.
Conclusions: Sufentanil tablets dispensed sublingually with a handheld PCA device or by a healthcare professional using a single-dose applicator, are in development for treatment of patients with moderate-to-severe acute pain. When administered sublingually, sufentanil’s fast onset of analgesia, non-invasive route of delivery and patient satisfaction/tolerability make it a useful alternative to IM or IV dosing.
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