Clinical utility of topiramate extended-release capsules (USL255): Bioequivalence of USL255 sprinkled and intact capsule in healthy adults and an in vitro evaluation of sprinkle delivery via enteral feeding tubes

Objective: The objectives of these two studies were to determine if beads from extended-release topiramate capsules sprinkled onto soft food are bioequivalent to the intact capsule and if beads from the capsule can be passed through enteral gastrostomy (G-) and jejunostomy (J-) feeding tubes. Methods: Bioequivalence of 200-mg USL255 (Qudexy® XR [topiramate] extended-release capsules) sprinkled onto soft food (applesauce) versus the intact capsule was evaluated in a phase 1, randomized, single-dose, crossover study (N = 36). Pharmacokinetic evaluations included area under the curve (AUC), maximum plasma concentration (C_max), time to C_max (T_max), and terminal elimination half-life (t_1/2). If 90% confidence intervals (CI) of the ratio of geometric least-squares means were between 0.80 and 1.25, AUC and C_max were considered bioequivalent. In separate in vitro experiments, 100-mg USL255 beads were passed through feeding tubes using gentle syringe pressure to develop a clog-free bead-delivery method. Multiple tube sizes (14- to 18-French [Fr] tubes), dilutions (5 mg/15 mL-25 mg/15 mL), and diluents (deionized water, apple juice, Ketocal, sparkling water) were tested. Results: Area under the curve and C_max for USL255 beads sprinkled onto applesauce were bioequivalent to the intact capsule (GLSM [90% CI]: AUC_0-t 1.01 [0.97-1.04], AUC_0-∞ 1.02 [0.98-1.05]; C_max 1.09 [1.03-1.14]). Median T_max was 4 h earlier for USL255 sprinkled versus the intact capsule (10 vs 14 h; p = 0.0018), and t_1/2 was similar (84 vs 82 h, respectively). In 14-Fr G-tubes, USL255 beads diluted in Ketocal minimized bead clogging versus deionized water. Recovery of USL255 beads diluted in deionized water was nearly 100% in 16-Fr G-, 18-Fr G-, and 18-Fr J-tubes. Significance: For patients with difficulty swallowing pills, USL255 sprinkled onto applesauce offers a useful once-daily option for taking topiramate. USL255 beads were also successfully delivered in vitro through ≥. 14-Fr G- or J-tubes, with tube clogging minimized by portioning the dose and using glidant diluents for smaller tubes.