Reversal of Soft-Tissue Anesthesia by an a-adrenergic Blocker

Objective: The objective of two double-blind, randomized, multi-site, Phase, 3 pivotal studies in adults (n= 484) and a Phase 2 study of pediatric patients (n=152) was to evaluate the safety and efficacy of an alpha-adrenergic blocker (phentolamine mesylate) by testing the hypothesis that local maxillary or mandibular injections would shorten the duration of STA following routine dental and periodontal maintenance procedures. Since the duration of STA resulting from dental anesthetic solutions containing vasoconstrictors exceeds that of pulpal anesthesia, accelerated reversal may be clinically useful. Methods: Routine dental or periodontal maintenance procedures were performed under routine local anesthesia using anesthetics that contained a vasoconstrictor. After completion of the procedure, a new proprietary formulation containing phentolamine mesylate (PM) was injected into the same site(s) as the local anesthetic. The duration of soft tissue anesthesia (STA) was measured by a standardized lip tapping procedure and untoward sequelae of STA were measured by validated instruments for assessing function and patient reported outcomes. Results: The duration of STA in the lower lip was reduced by 55% (p < 0.0001) and in the upper lip by 62% (p < 0.0001) compared to the sham-injection control group. Normal lip sensation and normal function returned before the patients' perception of a return to normalcy suggesting that NV-101 treatment would not heighten the risk of self-injury. PM was well tolerated with no serious or severe adverse events (AE). No patients were discontinued due to AE. In adults 20% (mandibular) and 13% (maxilla) of PM and 16% (mandibular) and 10% (maxilla) of sham-injected patients experienced transient, treatment-related AE of mild to moderate severity. Most AE resolved within 24 hours. Conclusions: These data reveal the potential clinical utility of PM to accelerate reversal of STA and its unwanted consequences. Sponsored by Novalar Pharmaceuticals, Inc., San Diego, CA, USA