Problems with intravenous patient‐controlled analgesia (IV PCA) are well known, including invasive route of delivery and pump programming errors. The primary objective of this study was to evaluate patient satisfaction with a novel sublingual sufentanil PCA system (sufentanil sublingual tablet system 15 mcg with a 20‐minute lockout interval; SSTS) to IV PCA morphine sulfate 1 mg with a 6‐minute lockout interval (IV PCA MS) for the management of acute postoperative pain.

While sufentanil has good cardiac stability, a high therapeutic index, and minimal pharmacokinetic (PK) population differences, rapid redistribution from plasma and short duration of effect following IV administration limit its usefulness as an analgesic. Sufentanil’s short (6min) equilibration half-time (t½ke0) to cross the blood-brain barrier predicts a rapid onset of action even when administered sublingually. To correlate clinical data with PK predictions, data from randomized clinical trials (RCTs) with sublingual sufentanil across four product candidates, including three Phase 2 RCTs: 30mcg (acute traumatic pain); 20 to 80mcg (breakthrough cancer pain); 15mcg/200mcg triazolam (post-procedural pain and sedation) all designed for delivery via a single-dose applicator; and three Phase 2 trials (2 placebo-controlled and 1 open-label trial) and three Phase 3 RCTs using Zalviso™ (sufentanil sublingual microtablet system preprogrammed 15mcg with a 20min lockout; SSMS/15mcg) to treat postoperative pain were analyzed with respect to onset of action using time specific pain intensity and pain relief endpoints against placebo or IV PCA morphine. Across the four programs, statistically significantly better pain responses were seen with sublingual sufentanil compared to placebo or IV PCA morphine by 15 to 45min (depending on the study program). Additionally, once the pain was controlled, the interdosing interval ranged from 1-2h across the RCTs in the four development programs. For example, in the randomized active-comparator trial vs. IV PCA morphine 1mg q6min, SSMS/15mcg showed faster onset pain responses with separation between groups by 45min and statistically significant differences favoring SSMS/15mcg by 60min and continuing through the 4 hour timepoint. The novel sublingual sufentanil formulation and device designs across the four AcelRx product candidates demonstrate the rapid onset of pain response achievable with sublingual sufentanil whether administered by healthcare professionals using a single-dose applicator or self-administered by patients using the sufentanil sublingual microtablet system 15 mcg.