A Phase 1 Study to Evaluate the Bioavailability and Food Effect of 2 Solid-Dispersion Formulations of the TRPV1 Antagonist ABT-102, Relative to the Oral Solution Formulation, in Healthy Human Volunteers

ABT-102 is a selective TRPV1 antagonist designed for treatment of nociceptive pain. The objective of this study was to characterize the bioavailability and the food effect of 2 solid-dispersion (melt-extrusion [Meltrex] and spray-dried) tablet formulations of ABT-102 relative to the solution formulation used in initial clinical trials. The study followed a 2-part, single-dose (2-mg), open-label, randomized, 3-period, crossover design in 24 healthy adults, where in each study part, 1 of the 2 solid-dispersion formulations (under fasting and nonfasting conditions) was compared to the solution formulation (under nonfasting conditions). Under nonfasting conditions, the melt-extrusion and spray-dried formulations had 53% and 87% higher C-max and 42% and 70% higher AUC(infinity) than the solution formulation, respectively. The 2 solid-dispersion formulations provided comparable absolute ABT-102 exposures (mean +/- SD AUC(infinity) of 116 +/- 35 ng.h/mL [melt-extrusion] and 112 +/- 55 ng.h/mL [spray-dried]). There was no effect of food (high-fat/high-calorie breakfast) on the bioavailability of the melt-extrusion formulation with the fasting and nonfasting regimens meeting bioequivalence. Food increased C-max and AUC(infinity) central values of the spray-dried formulation by an estimated 11% and 17%, respectively. Based on the results of the study, the melt-extrusion formulation of ABT-102 was selected to replace the solution formulation for subsequent clinical development.