A Proof-of-concept Study Using Quantitative Sensory Threshold Analysis to Compare Two Intraoral Topical Anesthetics.

PURPOSE: CTY-5339A is an investigational topical anesthetic spray containing 14% benzocaine/2% tetracaine in a metered canister. Each spray delivers ∼0.2 mL of solution. This double-blind, randomized, crossover study compared the local anesthetic effect of CTY-5339A versus 14% benzocaine alone by using 2 quantitative sensory threshold experimental pain paradigms on the maxillary gingiva: pin prick test pain intensity (PPT PI) and heat pain threshold (HPT). METHODS: American Society of Anesthesiology Class 1 and 2 subjects (N = 50) were enrolled in this study. To qualify for the study, subjects were tested on the anterior maxillary gingiva with both PPT and HPT. Subjects had to report a PPT PI of ≥3 on a 0 to 10 numeric pain intensity scale on 1 of 2 consecutive pin pricks separated by 10 s, with at least one score ≥4. After PPT, mean HPT following 2 ramps in the same location had to be ≤ 46.5 °C, with each ramp beginning at 35 °C and an automatic cutoff of 50.6 °C. For treatment visits, subjects were randomly administered either 1 spray of CTY-5339A or 14% benzocaine to the anterior maxillary gingiva within 3 weeks of screening and then the alternative treatment 5 days to 2 weeks later. PPT PI and HPT were recorded immediately before drug application. After drug administration, PPT PI was recorded every minute through 5 min. Commencing at 5 min, PPT PI and HPT were recorded every 5 min through 60 min. For assessment of methemoglobin concentrations, venous blood (5 mL) was drawn from the antecubital fossa both before and 60 min after drug application. Oxygen saturation was recorded via pulse oximetry at baseline and every 10 min. FINDINGS: The AUCs for pain intensity difference from 0-30 and 0-60 min after PPT and HPT differences were significantly greater (P < 0.0001) for CTY-5339A compared with 14% benzocaine. Multiple time points on the time-action curves for PPT PI difference and HPT difference statistically (P < 0.05) favored CTY-5399A. Methemoglobin and oxygen saturation levels did not change compared with baseline after dosing with either treatment. IMPLICATIONS: Recommended doses of CTY-5339A provided significantly more profound and sustained local anesthesia than 14% benzocaine when applied to the maxillary gingiva. Significant changes in methemoglobin or oxygen saturation concentrations did not occur for either drug. ClinicalTrials.gov identifier: NCT03233737.

Lack of Methemoglobin Elevations After Topical Applications of Benzocaine Alone or Benzocaine Plus Tetracaine to the Oral Mucosa.

PURPOSE: This study evaluated changes in methemoglobin and oxygen saturation concentrations after the administration of recommended doses of 14% benzocaine alone or 14% benzocaine combined with 2% tetracaine. METHODS: American Society of Anesthesiology class 1 and 2 subjects (n = 40) were enrolled in this modified crossover study. Subjects were administered 0.2 mL of 14% benzocaine alone, 0.2 mL of 14% benzocaine plus 2% tetracaine, or 0.4 mL of 14% benzocaine plus 0.2% benzocaine to their cheek mucosa. Venous blood (5 mL) was drawn from the antecubital fossa before and 60 minutes after drug application for methemoglobin analyses. Oxygen saturation was also recorded via pulse oximetry at baseline and every 10 minutes through 60 minutes after drug application. FINDINGS: Methemoglobin and oxygen saturation levels did not change from baseline after the administration of benzocaine alone or when combined with tetracaine. IMPLICATIONS: Recommended doses of benzocaine or benzocaine combined with tetracaine when applied to the cheek mucosa do not induce even clinically insignificant elevations in methemoglobin levels. Metered dosing, such as that used in this study, can help avoid this overdose phenomena with these drugs. ClinicalTrials.gov identifier: NCT02908620.

Phase Four, Randomized, Double-Blinded, Controlled Trial of Phentolamine Mesylate in Two- to Five-year-old Dental Patients.

PURPOSE: The purpose of this study was to evaluate, using a randomized, double-blind methodology: (1) the safety of phentolamine mesylate (Oraverse) in accelerating the recovery of soft tissue anesthesia following the injection of two percent lidocaine plus 1:100,000 epinephrine in two- to five-year-olds; and (2) efficacy in four- to five-year-olds only. METHODS: One hundred fifty pediatric dental patients underwent routine dental restorative procedures with two percent lidocaine plus 1:100,000 epinephrine with doses based on body weight. Phentolamine mesylate or a sham injection (two to one ratio) was then administered. Subjects were monitored for safety and, in four- to five-year-olds, for efficacy during the two-hour evaluation period. RESULTS: There were no significant differences in adverse events between the phentolamine and sham injections. Compared to sham, phentolamine was not associated with nerve injury, increased analgesic use, or abnormalities of the oral cavity. Phentolamine was associated with transient decreased blood pressure in some children. In four- and five-year-olds, phentolamine induced more rapid recovery of lip anesthesia by 48 minutes (P<0.0001). CONCLUSIONS: Phentolamine was well tolerated and safe in three- to five-year-olds; in four- to five-year-olds, a statistically significant more rapid recovery of lip sensation compared to sham injections was determined.