title: 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.
abstract: 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 Cmax and 42% and 70% higher AUC∞ than the solution formulation, respectively. The 2 solid-dispersion formulations provided comparable absolute ABT-102 exposures (mean ± SD AUC∞ 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 Cmax and AUC∞ 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.
authors.affiliation: Abbott Laboratories, Abbott Park, IL, USA.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Othman
authors.affiliation: Abbott Laboratories, Abbott Park, IL, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Cheskin
authors.affiliation: Abbott Laboratories, Abbott Park, IL, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Locke
authors.affiliation: Abbott Laboratories, Abbott Park, IL, USA.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Nothaft
authors.affiliation: Abbott Laboratories, Abbott Park, IL, USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Dutta
keywords: ABT‐102; bioavailability; food effect; formulation; melt‐extrusion; spray‐dried