Pooled Phase III Safety Analysis of Sufentanil Sublingual Tablets for Short-Term Treatment of Moderate-to-Severe Acute Pain

Abstract

Aim: To evaluate the pooled safety of sufentanil sublingual tablets (SSTs) administered at 30-mcg dose equivalents over ≤72 h for moderate-to-severe acute pain management in medically supervised settings. Patients & methods: Safety data from SST 30 mcg Phase III studies were pooled with an additional patient subset from studies in which two SST 15 mcg were self-administered within 20–25 min (30-mcg dose-equivalent). Results: Analyses included 804 patients. Median (range) SST 30-mcg dosing over 24 h was 7.0 (1–15) tablets. Adverse events (AEs) were experienced by 60.5% (SST) and 61.4% (placebo) and treatment-related AEs by 43.8% (SST) and 33.5% (placebo; 10.3% difference; 95% CI: 2.0–18.6) of patients. No dose-dependent increase in oxygen desaturation was observed with SST. Conclusion: SST was well-tolerated, with most AEs considered mild or moderate in severity.

Keywords::

• acute pain
• adverse event
• analgesia
• emergency department
• opioid
• pooled safety analysis
• postoperative
• sufentanil sublingual tablet

Author contributions

All the authors analyzed and interpreted the data, drafted or revised the manuscript for important intellectual content and provided approval of the final version. Y-K Chiang was involved in the study design and carried out data analyses of the original studies included in this analysis. PP Palmer and KP DiDonato were involved in data acquisition and PP Palmer was also involved in study concept and design.

Financial & competing interests disclosure

The SST 30 mcg studies were funded by AcelRx Pharmaceuticals and were funded in part by the Clinical and Rehabilitative Medicine Research Program (CRMRP) of the US Army Medical Research and Materiel Command (USAMRMC) under contract no. W81XWH-15-C-0046 and no. W81XWH-11-1-0361. JR Miner and D Leiman are consultants to AcelRx. JR Miner, TI Melson and D Leiman received research funding from AcelRx. HS Minkowitz is a consultant for and has received research support from AcelRx, Trevana, Heron, Durect, Acacia, Avenue, Recro and Innocoll, and has also received research support from Sorrento, Semnur, Merck, SPR, Pfizer, and Sollis. YK Chiang is a paid statistical consultant for AcelRx. KP DiDonato and PP Palmer are employees and have stock ownership of AcelRx. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing and editorial assistance were provided by R Steger and P Baron (BlueMomentum, an Ashfield Company, part of UDG Healthcare plc) and funded by AcelRx Pharmaceuticals.

Ethical conduct of research

The protocols for all clinical studies used to generate data for the current analysis were approved by the corresponding Institutional Review Board for each study site and written informed consent was obtained from all patients.

Data sharing statement

The authors certify that this manuscript reports the secondary analysis of clinical trial data that have been shared with them, and that the use of this shared data is in accordance with the terms (if any) agreed upon their receipt. The source of this data is: Clinicaltrials.gov identifiers: NCT02356588, NCT02662556, NCT02447848, NCT00859313, NCT00612534, NCT00718081, NCT01539538, NCT01539642 and NCT01660763.

Additional information

Funding

The SST 30 mcg studies were funded by AcelRx Pharmaceuticals and were funded in part by the Clinical and Rehabilitative Medicine Research Program (CRMRP) of the US Army Medical Research and Materiel Command (USAMRMC) under contract no. W81XWH-15-C-0046 and no. W81XWH-11-1-0361. JR Miner and D Leiman are consultants to AcelRx. JR Miner, TI Melson and D Leiman received research funding from AcelRx. HS Minkowitz is a consultant for and has received research support from AcelRx, Trevana, Heron, Durect, Acacia, Avenue, Recro and Innocoll, and has also received research support from Sorrento, Semnur, Merck, SPR, Pfizer, and Sollis. YK Chiang is a paid statistical consultant for AcelRx. KP DiDonato and PP Palmer are employees and have stock ownership of AcelRx. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Writing and editorial assistance were provided by R Steger and P Baron (BlueMomentum, an Ashfield Company, part of UDG Healthcare plc) and funded by AcelRx Pharmaceuticals.