Lidocaine Hydrochloride Gel for Ocular Surface Anesthesia: Pharmacokinetic Evaluation and Randomized Placebo-Controlled Trial in China

Backgrounds: A new generic formulation of 3.5% lidocaine hydrochloride ophthalmic gel has been developed in China. This study aimed to evaluate the pharmacokinetics and effectiveness of this lidocaine hydrochloride gel for ocular surface anesthesia. Methods: In the pharmacokinetics study, the new form of 3.5% lidocaine hydrochloride gel or Akten™ 3.5% lidocaine hydrochloride gel was applied in eyes of 70 rabbits. The ocular tissues and plasma samples were collected after the application of 3.5% lidocaine hydrochloride gel or Akten lidocaine gel and analyzed using the liquid chromatography with tandem mass spectrometry (LC-MS/MS) method to determine the concentration of lidocaine. A multicenter, randomized, double-blind prospective clinical trial was conducted in Chinese adults. Two hundred twenty participants were 1:1 randomized into the sham gel group or the lidocaine hydrochloride group. The primary efficacy endpoint was defined as the percentage of subjects achieving anesthesia by 5 min. Results: The animal pharmacokinetics study showed the lidocaine level was significantly higher in the choroid at 15 min and the vitreous body at 15 and 30 min; it was lower in tears at 8 h for 3.5% lidocaine hydrochloride gel than Akten (P ≤ 0.05). Our clinical trial showed that the percentage of subjects achieving anesthesia within 5 min in the lidocaine hydrochloride gel group was significantly higher than the sham gel group (86.92%-18.18%, P < 0.0001). The incidence of adverse events was relatively low and favorable for both groups. Conclusion: This new formulation of lidocaine hydrochloride gel, with pharmacokinetics similar to Akten, may exert a sustained, effective, and safe anesthetic effect. The clinical trial for this new generic formulation of lidocaine hydrochloride has been registered with the Drug Clinical Trial Registration and Information Publicity Platform established by State Food and Drug Administration of China (Registration No. CTR20160593).