Background and Objective <p>Deutetrabenazine is approved as a treatment in adults for tardive dyskinesia and chorea associated with Huntington’s disease. A once-daily tablet (Austedo XR^® Teva) was recently approved in addition to the twice-daily tablet (Austedo^®), and studies were conducted to evaluate dosage strength proportionality and food effect of the once-daily formulation.</p> Methods <p>In a randomized cross-over study of dosage strength proportionality, healthy participants (<i>n</i> = 116) received single doses of the once-daily deutetrabenazine formulation and a power model was fitted to describe the relationship between dose and pharmacokinetic parameters (maximum observed plasma drug concentration [<i>C</i>_max], area under the plasma concentration–time curve from time 0 to 36 h [AUC_0–36h], and area under the plasma concentration–time curve from time 0 extrapolated to infinity [AUC_0–∞]). In the second cross-over study, a single 24-mg dose of the once-daily formulation was given in fasted and fed conditions to healthy participants (<i>n</i> = 84) and the effect of food was evaluated by constructing 90% confidence intervals of the geometric mean ratios for <i>C</i>_max, AUC_{0–<i>t</i>,} and AUC_0–∞.</p> Results <p>Dosage strength proportionality for the once-daily formulation was demonstrated for the dosage strengths 6 mg, 12 mg, and 24 mg; and across the approved dose range up to 48 mg for the pharmacokinetic parameters of all analytes (deutetrabenazine, and metabolites; deuterated alpha-dihydrotetrabenazine and beta-dihydrotetrabenazine), individually and as a sum). In the food effect study, the <i>C</i>_max, AUC_{0–<i>t</i>,} and AUC_0–∞ geometric mean ratios for deutetrabenazine and deuterated metabolites all fell within the 90% confidence interval of 80–125.</p> Conclusions <p>The once-daily formulation of deutetrabenazine exhibited dosage strength proportional pharmacokinetics for doses up to 48 mg and there was no observed effect of food.</p>