Valbenazine Sprinkle: An Alternative Formulation of Valbenazine for Oral Administration in Patients With Dysphagia

Valbenazine is a vesicular monoamine transporter 2 (VMAT2) inhibitor approved for the treatment of tardive dyskinesia and Huntington's chorea. Dysphagia, pill aversion, and fear of swallowing are common in patients with these conditions. A new valbenazine sprinkle capsule, to be swallowed whole or the granule contents sprinkled onto soft food, was developed and approved based on the studies presented here. Study 1 evaluated the stability of valbenazine granules in soft foods. Recovery of valbenazine granules within 2 h after addition to applesauce, pudding, and yogurt was 95.6%-100.2%, indicating acceptable stability. Study 2 was a randomized, open-label, 2-cohort, phase 1 study in healthy volunteers. Plasma concentrations of valbenazine and its active metabolite, [+]-α-dihydrotetrabenazine ([+]-α-HTBZ) were measured serially after a single dose under various conditions. Cohort 1 evaluated bioequivalence between the sprinkle capsule and the original capsule with compacted powder (reference). Pharmacokinetics of valbenazine and [+]-α-HTBZ were similar between the whole sprinkle capsule and reference. When granules were sprinkled on applesauce, a lower valbenazine C_max and AUC were observed relative to reference; all other parameters were similar. Cohort 2 evaluated food effects on valbenazine granules and found that the pharmacokinetics of valbenazine and [+]-α-HTBZ were generally similar between fed and fasted states. Overall results from both cohorts for the 90% CIs of the geometric mean ratios indicated bioequivalence between the whole sprinkle capsule or granules sprinkled on applesauce and reference, with minor exceptions. These findings support that the VMAT2 inhibitor valbenazine can be used with multiple modes of oral administration.