Pharmacokinetics and Bioequivalence of 2 Deutetrabenazine Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions

Abstract

Deutetrabenazine, a deuterated vesicular monoamine transporter 2 (VMAT2) inhibitor, is approved for the treatment of Huntington's disease (HD)-related chorea and tardive dyskinesia (TD). However, pharmacokinetics (PK) and bioequivalence (BE) evidence in the Chinese population has been lacking. This single-center, randomized, open-label, single-dose, two-formulation, four-period, fully replicated crossover study evaluated the PK, BE, and safety of test and reference deutetrabenazine 12 mg tablets under fasting and fed conditions in healthy Chinese volunteers. A total of 90 subjects were enrolled (40 fasting; 50 fed), and 88 completed the study. Plasma concentrations of deutetrabenazine and its active metabolites d6-α-dihydrotetrabenazine (d6-α-HTBZ) and d6-β-dihydrotetrabenazine (d6-β-HTBZ) were quantified using a validated liquid chromatography-tandem mass spectrometry method. BE was assessed using average bioequivalence (ABE) or reference-scaled average bioequivalence (RSABE) according to within-subject variability. Under fasting conditions, RSABE was applied for maximum plasma concentration (C_max) and met equivalence criteria (point estimate within 80%–125%, upper confidence interval bound ≤ 0); under fed conditions, as well as for all remaining PK parameters, ABE criteria were met with the 90% confidence interval within the 80%–125% range. Both formulations were well tolerated, with only mild and transient adverse events and no serious safety findings. These results demonstrate that the test and reference deutetrabenazine tablets are bioequivalent in healthy Chinese adults under both nutritional states.