Sustained-release lidocaine sheet for pain following tooth extraction: A randomized, single-blind, dose-response, controlled, clinical study of efficacy and safety

BACKGROUND: We have synthesized a sustained-release lidocaine sheet (SRLS) using biodegradable polymers and previously demonstrated its safety and long-term analgesic effect in the normal mucous membrane of healthy human volunteers. OBJECTIVES: The aim of this clinical study was to evaluate the efficacy, safety, and appropriate dose of the SRLS for pain following tooth extraction. DESIGN: Randomized, single-blind, dose-response, controlled, clinical study (Phase 1/2). METHODS: The patients in this trial were enrolled between January 2014 and December 2016. A total of 99 patients were randomly divided into 5 groups as follows: the Non-administration group received the conventional extraction; the Poly Lactic-co-Glycolic Acid (PLGA) 100 mg control group received the PLGA matrix without lidocaine; the SRLS 100 mg group received a single sheet of SRLS 100 mg; the SRLS 200 mg group received double sheets of SRLS 100 mg; and the SRLS 400 mg administration group received four sheets of SRLS 100 mg. A study drug was inserted into the defect socket after the extraction, and postoperative pain intensity, satisfaction with postoperative pain relief, adverse events, and postoperative supplemental analgesic rescue use (time, dose) were investigated by patient self-report. RESULTS: In total, 94 (94.9%) patients completed the study. There were no significant differences in postoperative pain intensity, satisfaction with postoperative pain relief, and postoperative supplemental analgesic rescue use among the 5 groups. There were no serious side effects, including a plasma concentration increase of lidocaine, attributable to the SRLS. CONCLUSIONS: Administration of the SRLS at 100 mg may have clinical therapeutic potential for pain relief following tooth extraction. The safety of the SRLS for patients undergoing tooth extraction was demonstrated. TRIAL REGISTRATION: The University Hospital Medical Information Network UMIN000011945