[P3.258] Comparison of the Pharmacokinetics of USL255, an Extended-Release Topiramate, When Sprinkled Onto Soft Food or Swallowed Intact
Annie M. Clark, Bob Anders, Mark Halvorsen
Maple Grove, MN, USA
OBJECTIVE: Evaluate bioequivalence between USL255 beads sprinkled onto soft food compared with the intact USL255 capsule.
BACKGROUND: USL255 is a once-daily extended-release formulation of topiramate developed for the treatment of epilepsy. As some patients with epilepsy may have difficulty swallowing tablets or capsules, USL255 was formulated to allow the capsule to be opened and the beads sprinkled onto soft foods.
DESIGN/METHODS: Phase 1, randomized, open-label, single-dose, crossover study of 36 healthy adult subjects who received 200 mg USL255 administered as an intact capsule or sprinkled onto 1 tablespoonful of applesauce. Blood samples were collected for 14 days post-dose and pharmacokinetic parameters were calculated, including area under the plasma concentration-time curve (AUC0-∞, AUC0-t), maximum concentration (Cmax), time to Cmax (Tmax), and terminal elimination half-life (t1/2). AUC and Cmax were considered bioequivalent if the 90% confidence intervals (CI) for the ratio of geometric least-squares means (GLSM) were contained between 0.80 - 1.25. Tolerability was evaluated through adverse event (AE) monitoring, vital sign measurements, and clinical laboratory evaluations.
RESULTS: AUC and Cmax were bioequivalent between USL255 200 mg administered as an intact capsule and sprinkled onto soft food (GLSM [90% CI]: AUC0-t, 1.01 [0.97 - 1.04]; AUC0-∞, 1.02 [0.98 - 1.05]; Cmax,1.09 [1.03 - 1.14]). Median Tmax was between 10 - 14 hours and t1/2 was similar for both administration methods (81.5 hr intact; 83.6 hr sprinkled). USL255 was generally well tolerated, with similar types and numbers of AEs reported in both groups.
CONCLUSIONS: USL255 beads sprinkled onto soft food demonstrated bioequivalence for AUC and Cmax compared with the intact capsule. Therefore, USL255 can be a useful treatment option for individuals with difficulty swallowing.
Study Supported by: Upsher-Smith Laboratories, Inc.
Category - Epilepsy and Clinical Neurophysiology (EEG): Therapeutics: Medical
Tuesday, April 29, 2014 3:00 PM
P3: Poster Session III: Epilepsy and Clinical Neurophysiology: AED (3:00 PM-6:30 PM)