A Bioequivalence Comparison Between the Once-Daily Extended-Release Tablet and the Twice-Daily Tablet Formulations of...

Deutetrabenazine is approved for the treatment of tardive dyskinesia and chorea associated with Huntington's disease. This study compared the exposure between the once-daily (test) and twice-daily (reference) formulations of deutetrabenazine under fed conditions. Using a randomized crossover design, healthy adults (n = 262) received the 24 mg of the test formulation once daily and 12 mg of the reference formulation twice daily, each for 7 days. Plasma concentrations were collected on Days 4-6 before dose intake, and frequently for pharmacokinetic evaluation on Days 6 and 7 for determination of deutetrabenazine and active metabolites, deuterated α-dihydrotetrabenazine (α-HTBZ) and β-dihydrotetrabenazine (β-HTBZ). Geometric mean ratios (GMRs, test/reference) were computed for all analytes, and bioequivalence was tested for area under the plasma concentration-time curve over 24 hours at steady state (AUC_0-24 h,ss ) and for maximum plasma concentrations at steady state (C_max,ss ). The GMRs for AUC_0-24 h,ss were 115% for deutetrabenazine and 95% for deuterated total (α+β)-HTBZ; and the GMR for C_max,ss for deutetrabenazine was 95%. Relative bioavailability was assessed for C_max,ss of the active metabolites; the GMR was 78% for total (α+β)-HTBZ. At steady state, deutetrabenazine administered as the once-daily formulation was bioequivalent to the twice-daily formulation for both AUC and C_max, and the active metabolites were bioequivalent with regard to AUC_0-24 h,ss .