A phase I, randomized, open-label, cross-over study of the pharmacokinetics, dermal tolerability, and safety of MRX-7EAT Etodolac-Lidocaine Topical Patch in healthy volunteers

MRX-7EAT Etodolac-Lidocaine Topical Patch (4.4% w/w) is a novel non-steroidal anti-inflammatory drug (NSAID) patch, developed by using a novel transdermal delivery system based on a proprietary ionic liquid technology. Etodolac-lidocaine is a new salt of etodolac with equimolar amounts of lidocaine. In vitro study showed that Etodolac-Lidocaine salt has higher skin permeability than free etodolac. We conducted a Phase I, randomized, open-label, cross-over study of the pharmacokinetics and safety of Etodolac-Lidocaine patch in healthy volunteers to evaluate the systemic exposure of etodolac after administration of Etodolac-Lidocaine patch compared to Etodolac-alone patch. Thirty six total subjects were planned to be enrolled with 18 subjects randomized to a treatment sequence of Etodolac-Lidocaine patch followed by Etodolac-alone patch and the other 18 subjects randomized to a sequence of Etodolac-alone patch followed by Etodolac-Lidocaine patch. At study completion, 33 subjects were enrolled and treated, with 28 subjects completing the study and 5 dropping out. The systemic exposure of etodolac was determined using the pharmacokinetic parameters of etodolac. The study result showed that the Cmax and AUC0-24 of etodolac increased by more than 6-fold after Etodolac-Lidocaine patch applications as compared with Etodolac-alone patch applications. This finding demonstrates that the inclusion of lidocaine in Etodolac-Lidocaine patch to form an ion-pair with etodolac enhanced the skin permeability to etodolac and subsequently increased the absorption of systemic exposure to etodolac through the skin by more than 6 times as compared with Etodolac- alone patch. 33.3% of subjects had at least one adverse event during Etodolac-Lidocaine patch applications and 51.5% of subjects had at least one adverse event during Etodolac-alone patch applications. All adverse events were mild to moderate. No serious adverse event or death occurred.